Postgraduate Ophthalmology Vol.1

Postgraduate
Ophthalmology
Postgraduate
Ophthalmology
Volume 1
Editors
Zia Chaudhuri MS DNB MNAMS FRCS Glasg
Associate Professor of Ophthalmology
Maulana Azad Medical College and Associated Hospitals
Guru Nanak Eye Center, New Delhi, India
Murugesan Vanathi MD
Associate Professor of Ophthalmology
Dr Rajendra Prasad Center for Ophthalmic Sciences
All India Institute of Medical Sciences
New Delhi, India
Foreword
P Namperumalsamy
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Publisher: Jitendar P Vij

Publishing Director: Tarun Duneja
Cover Design: Seema Dogra
Postgraduate Ophthalmology
First Edition: 2012
ISBN 978-93-5025-270-3
Printed at
Rise, awaken, seek the wise and realize.
The path is difficult to cross like the sharpened edge of the razor, so say the wise.
Adapted from a translation of the Katha-Upanishad
Dedicated to
The Almighty for His benevolence and blessings;
My parents for their unconditional affection that has guided me through every storm,
And made me live life with my head held high and an unbroken spirit;
My friends, for their trust, confidence and conviction in my abilities and dreams,
That has always made me believe in myself, when the going has been really tough!
I dedicate this work, with humility, to their constant inspiration and encouragement.
Zia Chaudhuri
The blessings of the Almighty

The selfless love of my parents—Rajeswari and (Late) Prof Dr MS Murugesan
The patient endurance and untiring support of my loving husband Ganesh and daughter Meghna
The encouragement of all others in my Family
The steadfast direction of my Friends
The unfaltering guidance of my Teachers
The abiding trust of my loving Students.
Murugesan Vanathi
Contributors
AS Karthikeyan DO DNB FRCS Glasg FNB Anamika Tandon MD FRCSEd MRCOphth
FICO MNAMS DHM Consultant Paediatric Ophthalmologist
Head, Department of Pediatric Ophthalmology University Hospitals of Coventry and Warwickshire,
Strabismus and Neuro-ophthalmology Walsgrave, Coventry
Lumbini Eye Institute United Kingdom
Shree Rana Ambika Shah Eye Hospital Anand Aggarwal MD
Rupandehi, Siddhartha Nagar Senior Resident, Cornea and Glaucoma Services
Bhairahawa, Nepal Dr Rajendra Prasad Centre for Ophthalmic Sciences
Aashima Aggarwal MS DNB All India Institute of Medical Sciences
Head, Department of Ophthalmology New Delhi, India
Primus Superspeciality Hospital Anil Kumar AS MRCOphth
New Delhi, India University of Leicester, Leicester Royal Infirmary
Senior Consultant Ophthalmologist Leicester, United Kingdom
Brahm Shakti Hospital and Research Centre
Budh Vihar, Delhi, India, and Anil N Kulkarni MS
Insight Eye Clinic, Rajouri Garden Senior Consultant
New Delhi, India Lions NAB Eye Hospital, Miraj
Maharashtra, India
Abhay R Vasavada MS FRCS Formerly: Professor and Head
Medical and Research Director Department of Ophthalmology
Raghudeep Eye Clinic and Iladevi Cataract and Government Medical College and Hospital, Miraj
IOL Research Center Maharashtra, India and
Ahmedabad, Gujarat, India Professor and Head
Abhishek Saraf MS Department of Ophthalmology, Bharati Vidyapeeth
Fellow, Cornea Services, Aravind Eye Hospital and Sangli, Maharashtra, India
Postgraduate Institute of Ophthalmology Anirban Bhaduri MS FLVPEI
Coimbatore, Tamil Nadu, India Faculty, Orbit, Oculoplasty and Ocular Oncology
Akshay G Nair MBBS Suryodaya Eye Center
Resident, Sankara Nethralaya Calcutta Medical Research Institute
A Unit of Medical Research Foundation Kolkata, West Bengal, India
Nungambakkam, Chennai Anuradha Chandra MS
Tamil Nadu, India Senior Resident, Glaucoma and Strabismus Services
Amit Batra MD Dr Rajendra Prasad Center for Ophthalmic Sciences
Resident, Department of Neurology All India Institute of Medical Sciences
Govind Ballabh Pant Superspecialty Hospital New Delhi, India
Maulana Azad Medical College Ashwin Mohan MBBS
New Delhi, India Resident, CU Shah Ophthalmic Post-Graduate Training
Amit Gupta MS DNB Centre, Sankara Nethralaya
Consultant, Pediatric Ophthalmology and Strabismus A Unit of Medical Research Foundation
LV Prasad Eye Institute Nungambakkam, Chennai
Hyderabad, Andhra Pradesh, India Tamil Nadu, India
viii Postgraduate Ophthalmology
Balasubramanya Ramamurthy MD DNB Devendra V Venkatramani MBBS

Chief Medical Officer Resident, CU Shah Ophthalmic Post-Graduate
Cornea Cataract and Refractive Surgery Training Centre, Sankara Nethralaya
Vasan Eye Care Hospital A Unit of Medical Research Foundation
Hyderabad, Andhra Pradesh, India Nungambakkam, Chennai
Formerly: Consultant, Cornea Services Tamil Nadu, India
LV Prasad Eye Institute Dinesh Shrey MD
Hyderabad Senior Resident, Pediatric Ophthalmology
Andhra Pradesh, India Oculoplasty and Ocular Oncology Services
Beula Christy PhD Dr Rajendra Prasad Center for Ophthalmic Sciences
Head and Consultant All India Institute of Medical Sciences
Dr PRK Prasad Centre for Rehabilitation of New Delhi, India
Blind and Visually Impaired Divya Jain MS DNB
LV Prasad Eye Institute, Hyderabad Senior Resident, Guru Nanak Eye Center
Andhra Pradesh, India Maulana Azad Medical College
Bharti Taneja MD New Delhi, India
Associate Professor of Anesthesiology Gangaprasad Amula DNB
Maulana Azad Medical College Fellow, Department of Paediatric Ophthalmology and
New Delhi, India Strabismus, Sankara Nethralaya
Charu Khurana MS DNB FAICO (Glaucoma) A Unit of Medical Research Foundation
Consultant, Cataract and Glaucoma Services Nungambakkam, Chennai
Center for Sight Eye Hospital Tamil Nadu, India
New Delhi, India Gaurav Kumar MS
Charuta Bapaye DO MS Senior Resident
Fellow, Department of Paediatric Ophthalmology and Dr Rajendra Prasad Center for Ophthalmic Sciences
Strabismus, Sankara Nethralaya All India Institute of Medical Sciences
A Unit of Medical Research Foundation New Delhi, India
Nungambakkam, Chennai Gaurav Sanghi MS
Tamil Nadu, India Senior Resident, Advanced Eye Centre
Chintamani Khare DNB Postgraduate Institute of Medical Education and Research
Consultant, Vitreoretinal Services Chandigarh, India
Khare Eye Hospital, Kolhapur Gauri Shah MS
Maharashtra, India Consultant, Raghudeep Eye Clinic and
Debashish Chowdhury MD DM (Neurology) Iladevi Cataract and IOL Research Center
Professor of Neurology Ahmedabad
Department of Neurology Gujarat, India
Govind Ballabh Pant Superspecialty Hospital Geeta K Vemuganti MD DNB FAMS FICP
Maulana Azad Medical College Professor and Dean of Medical Sciences
New Delhi, India School of Medical Sciences
Deepak K Bagga PGDOM BBA DROpt University of Hyderabad
Associate Optometrist Andhra Pradesh, India
Meera and LB Deshpande Centre for Formerly: Head, Ophthalmic Pathology Laboratory
Sight Enhancement and Vision Rehabilitation Centres Head, Sudhakar and Sreekant Ravi Stem Cell Biology
LV Prasad Eye Institute Laboratory, Prof Brien Holden Eye Research Centre
Hyderabad LV Prasad Eye Institute
Andhra Pradesh, India Hyderabad, Andhra Pradesh, India
Contributors ix
Geetha Krishnan Iyer DO DNB FRCS Glasg J Nirmal M Pharm

Consultant, Department of Cornea and Senior Research Fellow
Dr G Sitalakshmi Memorial Ocular Surface Clinic Department of Ocular Pharmacology
Sankara Nethralaya Dr Rajendra Prasad Centre for Ophthalmic Sciences
A Unit of Medical Research Foundation All India Institute of Medical Sciences
Nungambakkam, Chennai New Delhi, India
Tamil Nadu, India
Jameel Rizwana Hussain M Phil (Optometry) FCOVD-1
Geetha Srinivasan MS Lecturer, Elite School of Optometry
Consultant, Pediatric Ophthalmology Senior Optometrist, Sankara Nethralaya
Squint and Glaucoma Services A Unit of Medical Research Foundation
ICARE Eye Hospital and Postgraduate Institute Nungambakkam, Chennai
NOIDA, Uttar Pradesh, India Tamil Nadu, India
GVS Murthy MD MSc
Jatin N Ashar MD
Senior Lecturer, International Center for Eye Health
Fellow, Cornea Services, LV Prasad Eye Institute
London, United Kingdom and
Hyderabad, Andhra Pradesh, India
Director, South Asia Centre for Vision and Disability,
Formerly: Resident, Dr Rajendra Prasad
Centre for Ophthalmic Sciences
Formerly: Additional Professor of Community
Ophthalmology
New Delhi, India
All India Institute of Medical Sciences Jaya Chandra Das MD
New Delhi, India Director, Glaucoma Services
Harinder Singh Sethi MD DNB MNAMS FRCS Glasg Shroff Eye Center, New Delhi, India
Assistant Professor Formerly: Director-Professor of Ophthalmology and
Department of Ophthalmology In-Charge, Glaucoma Services
Vardhaman Mahavir Medical College and Guru Nanak Eye Center
Safdarjung Hospital, New Delhi, India Maulana Azad Medical College
New Delhi, India
Harsha Pagad DNB
Fellow, Department of Pediatric Ophthalmology and Jaya Gupta MS
Strabismus, Sankara Nethralaya Research Fellow, Cornea Services
A Unit of Medical Research Foundation Dr Rajendra Prasad Centre for Ophthalmic Sciences
Nungambakkam, Chennai All India Institute of Medical Sciences
Tamil Nadu, India New Delhi, India, and
Hemal J Kansagra MS Cornea Fellow, Sankara Nethralaya
Fellow, Cornea Services, Aravind Eye Hospital and A Unit of Medical Research Foundation
Postgraduate Institute of Ophthalmology Nungambakkam, Chennai
Coimbatore, Tamil Nadu, India Tamil Nadu, India
Hemlata Gupta MS DNB FAICO (Refractive Surgery) Jyotirmay Biswas MS FNAMS FICPath
Consultant, Cataract and Refractive Surgery Services Director, Department of Uveitis and Ocular Pathology
Center for Sight Eye Hospital Sankara Nethralaya
New Delhi, India A Unit of Medical Research Foundation
Nungambakkam, Chennai
Irene Gottlob MD Univ Doz FRCOphth
Tamil Nadu, India
Professor of Ophthalmology
Ophthalmology Group K Shyamsundar MS DNB SRTF
University of Leicester Lieutenant Colonel, Army Medical Corps
Leicester Royal Infirmary United Nations Hospital (MONUSCO)
Leicester, United Kingdom Congo, Africa
x Postgraduate Ophthalmology
Kalpana Narendran DO DNB Malvika Gupta DO DNB

Chief Medical Officer and Consultant Senior Resident
Pediatric Ophthalmology and Strabismus Department of Ophthalmology
Aravind Eye Hospital and Postgraduate Dr Ram Manohar Lohia Hospital, New Delhi, India
Institute of Ophthalmology, Manav Khera MS
Coimbatore, Tamil Nadu, India Fellow, LV Prasad Eye Institute
Karandeep Rishi MD Visakhapatnam, Andhra Pradesh, India
Senior Resident, Retina and Uvea Services Mangat R Dogra MS
Dr Rajendra Prasad Center for Ophthalmic Sciences Professor of Ophthalmology
All India Institute for Medical Sciences Vitreo-retina Services
New Delhi, India Advanced Eye Centre
Kirti Nath Saxena MD Postgraduate Institute of Medical Education and Research
Professor of Anesthesiology Chandigarh, India
Maulana Azad Medical College Manoj Gupta MD
New Delhi, India Senior Resident
Kirti Singh MD DNB FRCSEd Dr Rajendra Prasad Center for Ophthalmic Sciences
Professor of Ophthalmology and All India Institute of Medical Sciences
In-charge Contact Lens Clinic New Delhi, India
Guru Nanak Eye Center Manotosh Ray MD, FRCSEd
Maulana Azad Medical College Consultant, Ophthalmology
New Delhi, India Cornea, External Eye Diseases and
Kunjal Sejpal DNB FICO FMRF FRCS Glasg General Ophthalmology
Consultant, Cornea and Anterior Segment Services National University Hospital, Singapore and
LV Prasad Eye Institute, Hyderabad Instructor, Department of Ophthalmology
Andhra Pradesh, India Yong Loo Lin School of Medicine
Lingam Gopal MS FRCS DNBE FNAMS National University of Singapore
Senior Consultant, Department of Ophthalmology Singapore
National University Health System Monica Chaudhry MOpt FIACLE
1E, Kent Ridge Road Senior Consultant Optometrist
Tower Block Level 7, Singapore and Visual Aids Centre
Senior Consultant, Vitreoretinal Services New Delhi, India and
Sankara Nethralaya Faculty and Senior Consultant
A Unit of Medical Research Foundation Indira Gandhi National Open University
Nungambakkam, Chennai New Delhi, India
Tamil Nadu, India Formerly: Senior Technical Officer
Murugesan Vanathi MD Dr Rajendra Prasad Center for Ophthalmic Sciences
Associate Professor of Ophthalmology All India Institute of Medical Sciences
Cornea, Ocular Surface and Refractive Surgery Services New Delhi, India
Dr Rajendra Prasad Center for Ophthalmic Sciences Monika Nanda MS MCh
All India Institute of Medical Sciences Consultant, Pediatric Surgery
New Delhi, India Pushpanjali Crosslay Hospital, Ghaziabad
Mahipal Singh Sachdev MD Uttar Pradesh, India
Directors and Senior Consultant MR Praveen DO
Cataract, Cornea and Refractive Surgery Services Consultant, Raghudeep Eye Clinic and
Center for Sight Eye Hospital Iladevi Cataract and IOL Research Center
New Delhi, India Ahmedabad, Gujarat, India
Contributors xi
Mridula Mehta MS Parul Ichhpujani MS

Senior Research Associate Assistant Professor of Ophthalmology
Pediatric Ophthalmology Department of Ophthalmology
Oncology and Oculoplasty Services Government Medical College and Hospital
Dr Rajendra Prasad Center for Ophthalmic Sciences Chandigarh, India
All India Institute of Medical Sciences Parul Sony MD MNAMS FRCS Glasg
New Delhi, India Senior Consultant
Munish Dhawan MD Glaucoma, Cornea and Keratorefractive Surgery
Senior Resident Shroff Eye Center and Vedanta, The Medicity
Strabismus and Neuro-ophthalmology Services Gurgaon, Haryana, India
Dr Rajendra Prasad Center for Ophthalmic Sciences Pooja Magdum Bhomaj DNB
All India Institute of Medical Sciences Consultant, Glaucoma Services
New Delhi, India Shanti Saroj Nethralay and Lions NAB Hospital
Neelam Pushker MD Miraj, Maharashtra, India
Additional Professor of Ophthalmology Pradeep Venkatesh MD
Pediatric Ophthalmology Additional Professor of Ophthalmology
Oncology and Ophthalmoplasty Services Retina and Uvea Services
Dr Rajendra Prasad Center for Ophthalmic Sciences Dr Rajendra Prasad Center for Ophthalmic Sciences
All India Institute of Medical Sciences All India Institute of Medical Sciences
New Delhi, India New Delhi, India
Neeti Gupta MS Pramod K Pandey MD
Senior Resident, Department of Ophthalmology Director-Professor of Ophthalmology
Government Medical College and Hospital Strabismus Services
Chandigarh, India Guru Nanak Eye Center
Maulana Azad Medical College and
Neha Mithal MS Associated Hospitals, New Delhi, India
Senior Resident, Cornea and Glaucoma Services
Dr Rajendra Prasad Center for Ophthalmic Sciences Pranav D More MD DNB
All India Institute of Medical Sciences Resident
New Delhi, India Dr Rajendra Prasad Center for Ophthalmic Sciences
Neha Verma DNB New Delhi, India
Senior Resident, Department of Ophthalmology and Fellow, Cornea Services
Lady Hardinge Medical College Aravind Eye Hospital and Postgraduate Institute of
New Delhi, India Ophthalmology, Coimbatore, Tamil Nadu, India
Noopur Gupta MS DNB Prateek Gujar MS FMRF
Senior Research Associate, Cornea Services Fellow, Cornea and Refractive Services
Dr Rajendra Prasad Center for Ophthalmic Sciences Aravind Eye Hospital and Postgraduate
All India Institute of Medical Sciences Institute of Ophthalmology
New Delhi, India Coimbatore, Tamil Nadu, India
Parameshwar Bhat MS Preeti A Patil DNB
Fellow, Cornea Services Fellow, Department of Paediatric
Aravind Eye Hospital and Ophthalmology and Strabismus, Sankara Nethralaya
Postgraduate Institute of Ophthalmology A Unit of Medical Research Foundation
Coimbatore Nungambakkam, Chennai
Tamil Nadu, India Tamil Nadu, India
xii Postgraduate Ophthalmology
R Revathi DO MS Ramesh Murthy FRCS

Senior Consultant Director, Axis Eye Clinic
Cornea and Refractive Services Senior Consultant, Pediatric Ophthalmology
Aravind Eye Hospital and Postgraduate Strabismus, Oculoplasty and Ocular Oncology
Institute of Ophthalmology, Coimbatore Paud Road, Pune
Tamil Nadu, India Maharashtra, India
Rachna Meel MS Formerly: Consultant, Pediatric Ophthalmology
Senior Research Associate, Pediatric Ophthalmology Strabismus, Oculoplasty and Ocular Oncology
Oncology and Ophthalmoplasty Services LV Prasad Eye Institute, Hyderabad
Dr Rajendra Prasad Center for Ophthalmic Sciences Andhra Pradesh, India
All India Institute of Medical Sciences Rashmin A Gandhi FRCSEd FRCS Glasg
New Delhi, India Consultant, Department of Neuro-ophthalmology
Radhika Tandon MD FRCS FRCOphth Director, e-Learning
Professor of Ophthalmology and The Sankara Nethralaya Academy, Sankara Nethralaya
Eye Bank In-Charge, Cornea Servces A Unit of Medical Research Foundation
Dr Rajendra Prasad Center for Ophthalmic Sciences Nungambakkam, Chennai
All India Institute of Medical Sciences Tamil Nadu, India
New Delhi, India Reena Sharma MD
Rajat Chaudhary (Major) MS DNB FICO (Cornea) Senior Resident, Glaucoma and Strabismus Services
Graded Specialist (Ophthalmology) Dr Rajendra Prasad Center for Ophthalmic Sciences
Military Hospital All India Institute of Medical Sciences
Ahmedabad, Gujarat, India New Delhi, India
Rajesh Ramanjulu MD Reshmi Bhaskar MS

Resident, Dr Rajendra Prasad Centre for Ophthalmic Fellow, Department of Paediatric Ophthalmology and
Sciences, All India Institute of Medical Sciences Strabismus, Sankara Nethralaya
New Delhi, India A Unit of Medical Research Foundation
Rakhi Kusumesh MS Tamil Nadu, India
Senior Resident, Cornea and Glaucoma Services
Dr Rajendra Prasad Center for Ophthalmic Sciences Rituparna Ghoshal BOpt FLVPEI
All India Institute of Medical Sciences Lecturer, Nagar School of Optometry
New Delhi, India Nagri Municipal Eye Hospital, Ellis Bridge
Ahmedabad, Gujarat, India and
Ramanjit Sihota MD MNAMS FRCS FRCOphth Low Vision Consultant, Sankara Eye Hospital
Professor of Ophthalmology and In-Charge Anand, Gujarat, India
Glaucoma Services Formerly: Optometrist, Meera and LB Deshpande
Dr Rajendra Prasad Center for Ophthalmic Sciences Centre for Sight Enhancement
All India Institute of Medical Sciences LV Prasad Eye Institute, Hyderabad
New Delhi, India Andhra Pradesh, India
Ramesh Kekunnaya FRCS Roshmi Gupta MS FRCS Glasg
Associate Ophthalmologist, Pediatric Ophthalmology Consultant, Ophthalmic Plastics
Strabismus and Neuro-ophthalmology Services Orbital Surgery and Ocular Oncology
LV Prasad Eye Institute Vasan Eye Care
Hyderabad Bengaluru
Andhra Pradesh, India Karnataka, India
Contributors xiii
Rupesh Agrawal MMed FRCS Glasg Sanjay Kai MD

Associate Consultant Senior Resident, Cornea and Glaucoma Services
Department of Ophthalmology Dr Rajendra Prasad Center for Ophthalmic Sciences
Tan Tock Seng Hospital, Singapore All India Institute for Medical Sciences
Formerly: Fellow, Ocular Trauma, New Delhi, India
Uveitis and Comprehensive Ophthalmology
Sanjay Sharma MD
V Prasad Eye Institue, Hyderabad
Additional Professor of Radiology
Andhra Pradesh, India
S Ambika DO DNB All India Institute of Medical Sciences
Director, Department of Neuro-ophthalmology New Delhi, India
Sankara Nethralaya
Sankaranarayana P Mahesh MD
A Unit of Medical Research Foundation
Department of Ophthalmology/Immunology
George Washington University
Tamil Nadu, India
Washington DC
S Meenakshi MS USA
Director, Academics
Consultant, Department of Pediatric Santosh G Honavar MD FACS
Ophthalmology and Strabismus, Sankara Nethralaya Director, Ophthalmic and Facial Plastic Surgery
A Unit of Medical Research Foundation Orbit and Ocular Oncology
Nungambakkam, Chennai LV Prasad Eye Institute, Hyderabad
Tamil Nadu, India Andhra Pradesh, India
S Senthilkumari M Pharm PhD Sathyarekha MS

Scientist, Department of Ocular Pharmacology Fellow, Cornea Services
Aravind Medical Research Foundation Aravind Eye Hospital and Postgraduate
Aravind Eye Hospital, Madurai Institute of Ophthalmology, Coimbatore
Tamil Nadu, India Tamil Nadu, India
Formerly: Department of Ocular Pharmacology Saurabh Jain MS FRCOphth
Dr Rajendra Prasad Center for Ophthalmic Sciences Consultant Ophthalmologist
All India Institue of Medical Sciences Royal Free Hampstead NHS Trust
New Delhi, India London
S Sudharshan DOMS DNB United Kingdom
Consultant, Department of Uveitis Saurabh Sawhney DO DNB
Sankara Nethralaya Head, Department of Ophthalmology
A Unit of Medical Research Foundation Brahm Shakti Hospital and Research Center
Nungambakkam, Chennai Budh Vihar, New Delhi, India and
Tamil Nadu, India Senior Consultant Ophthalmologist
Sachin Mehta MS DNB Insight Eye Clinic, Rajouri Garden
Head, Department of Ophthalmology New Delhi, India
Om Shree Rammantra Mandir Hospital Savari T Desai DO DOMS DNB FLVPEI
Bhavnagar, Gujarat, India Consultant, Oculoplasty, Orbit
Formerly: Senior Resident, Guru Nanak Eye Center Ocular Oncology and Facial Aesthetics
Maulana Azad Medical College PD Hinduja Hospital and Medical Research Center
New Delhi, India Veer Savarkar Marg, Mahim, Mumbai
Sajani K Shah MS Maharashtra, India and
Consultant, Raghudeep Eye Clinic and Honorary Consultant, Ocular Oncology
Iladevi Cataract and IOL Research Center Tata Memorial Hospital, Mumbai
Ahmedabad, Gujarat, India Maharashtra, India
xiv Postgraduate Ophthalmology
Savitri Sharma MD FAMS Shraddha S Puranik MD

Director, Laboratory Services Resident
LVPEI Network, LV Prasad Eye Institute Dr Rajendra Prasad Center for Ophthalmic Sciences
Bhubaneswar All India Institute of Medical Sciences
Orissa, India New Delhi, India
Seema Kashyap MD Shruti Mittal MBBS
Associate Professor of Pathology Resident, CU Shah Ophthalmic Post-graduate
Department of Ocular Pathology Training Centre, Sankara Nethralaya
Dr Rajendra Prasad Center for Ophthalmic Sciences A Unit of Medical Research Foundation
All India Institute of Medical Sciences Nungambakkam, Chennai
New Delhi, India Tamil Nadu, India
Shafiq S Jafferji MBChB MMed (Ophth) FEACO FMRF Shweta S Agarwal DOMS FMRF
Consultant Ophthalmologist Associate Consultant
Vitreo Retina Surgeon Department of Cornea, Sankara Nethralaya
PCEA Kikuyu Eye Hospital and MP Shah Hospital A Unit of Medical Research Foundation
Nairobi, Kenya Nungambakkam, Chennai
Formerly: Department of Uveitis Tamil Nadu, India
Medical Research Foundation
Sankara Nethralaya Sonam Angmo Bodh MS DNB
A Unit of Medical Research Foundation Senior Resident, Guru Nanak Eye Center
Nungambakkam, Chennai Maulana Azad Medical College
Tamil Nadu, India New Delhi, India
Shah Nawaz MBBS Soundarya Lakshmi Madhira MSc

Resident Research Scholar
Dr Rajendra Prasad Center for Ophthalmic Sciences Sudhakar and Sreekant Ravi
All India Institute of Medical Sciences Stem Cell Biology Laboratory
New Delhi, India LV Prasad Eye Institute, Hyderabad
Andhra Pradesh, India
Shalini Gupta MS DNB
Senior Resident, Guru Nanak Eye Center Sowmya R MS
Maulana Azad Medical College Fellow, Department of Paediatric Ophthalmology and
New Delhi, India Strabismus, Sankara Nethralaya
Shalini Mohan MS FRCS Glasg Nungambakkam, Chennai
Assistant Professor of Ophthalmology Tamil Nadu, India
Cornea and Glaucoma Services
Ganesh Shankar Vidyarthi Memorial Medical College Sowmyalatha Maskabil MS
Kanpur, Uttar Pradesh, India Fellow, Cornea Services, Aravind Eye Hospital and
Postgraduate Institute of Ophthalmology, Coimbatore
Sharad Bhomaj MS DNB
Tamil Nadu, India
Medical Director and Senior Consultant
Vitreo-retinal Services Suhas Haldipurkar DOMS
Shanti Saroj Netralay and Lions NAB Hospital Medical Director, Laxmi Eye Institute and Laxmi
Miraj, Maharashtra, India Charitable Eye Hospital, Panvel
Maharashtra, India
Shibal Bhartiya MS
Senior Research Associate Sujata Das MS FRCS Glasg MAMS
Cornea and Glaucoma Services Head, Cornea and Anterior Segment Services
Dr Rajendra Prasad Center for Ophthalmic Sciences Medical Director, ‘Drushti Daan’ Eye Bank
All India Institute of Medical Sciences LV Prasad Eye Institute, Bhubaneswar
New Delhi, India Orissa, India
Contributors xv
Sujith Vengayil MD FRCS Glasg Sushmita Kaushik MS

Senior Resident, Cornea Services Associate Professor of Ophthalmology
Dr Rajendra Prasad Center for Ophthalmic Sciences Glaucoma Services
All India Institute of Medical Sciences Advanced Eye Centre
New Delhi, India Postgraduate Institute of Medical Education
and Research
Sumit Monga MS DNB FRCS Glasg
Chandigarh, India
Associate Consultant
Pediatric Ophthalmology Services Suyog Ughade DO
Shroff Eye Centre Resident, CU Shah Ophthalmic Post-graduate
New Delhi, India Training Centre, Sankara Nethralaya
Sumita Agarkar MS DNB
Deputy Director, Department of Paediatric
Tamil Nadu, India
Ophthalmology and Strabismus
Sankara Nethralaya Swapnali S Sharma MS
A Unit of Medical Research Foundation Fellow, Cornea and Anterior Segment
Nungambakkam, Chennai LV Prasad Eye Institute, Hyderabad and
Tamil Nadu, India Clinical Associate, LV Prasad Eye Institute
Sumita Sethi MS
Senior Research Associate, Pediatric Ophthalmology T Velpandian B Pharm MSc PhD
Oncology and Ophthalmoplasty Services Associate Professor
Dr Rajendra Prasad Center for Ophthalmic Sciences Department of Ocular Pharmacology
All India Institute of Medical Sciences Dr Rajendra Prasad Center for Ophthalmic Sciences
New Delhi, India All India Institute of Medical Sciences
New Delhi, India
Supriyo Ghose MD MAMS
Chief, Dr Rajendra Prasad Center for Ophthalmic Twinkle Khanna MD
Sciences, All India Institute for Medical Sciences Senior Resident
New Delhi, India and Dr Rajendra Prasad Center for Ophthalmic Sciences
Professor of Ophthalmology, Pediatric Ophthalmology All India Institute of Medical Sciences
Oncology and Ophthalmoplasty Services New Delhi, India
Dr Rajendra Prasad Center for Ophthalmic Sciences V Satyanarayana MD DM(Neurology)
All India Institute for Medical Sciences Founder and Chairman
New Delhi, India Head, Department of Neurology
Suresh Kumar Gupta MS Indus Hospitals, Visakhapatnam
Associate Professor of Ophthalmology Andhra Pradesh, India
Department of Ophthalmology V Subashini DO DNB
Government Medical College and Hospital Associate Consultant
Chandigarh, India Department of Neuro-ophthalmology
Sankara Nethralaya
Surinder Singh Pandav MS
Professor of Ophthalmology
Glaucoma Services
Tamil Nadu, India
Advanced Eye Centre
Postgraduate Institute of Medical Education Vaibhev Mittal DOMS
and Research Fellow, LV Prasad Eye Institute
Chandigarh, India Visakhapatnam, Andhra Pradesh, India
xvi Postgraduate Ophthalmology
Vaishali A Vasavada MS Vikas Menon DNB FLVPEI

Consultant, Raghudeep Eye Clinic and Consultant, Ophthalmic Plastic Surgery and
Iladevi Cataract and IOL Research Center Ocular Oncology
Ahmedabad, Gujarat, India Center for Sight Eye Hospital
Vandana Kohli MS New Delhi, India
Assistant Professor of Ophthalmology Viraj A Vasavada MS
Guru Nanak Eye Center Consultant, Raghudeep Eye Clinic and
Maulana Azad Medical College Iladevi Cataract and IOL Research Center
New Delhi, India Ahmedabad
Varshini Shankar DO DNB FMRF Gujarat, India
Consultant, Pediatric Ophthalmology and Strabismus Virender S Sangwan MS
Shroff ’s Charity Eye Hospital Associate Director, LV Prasad Eye Institute
New Delhi, India Head, Cornea and Anterior Segment
Vasu Kumar MS DNB Ocular Immunology and Uveitis Service
Senior Resident, Guru Nanak Eye Center LV Prasad Eye Institute
Maulana Azad Medical College Hyderabad
New Delhi, India Andhra Pradesh, India
Vijay Ananth J DO DNB Virender Sachdeva MS DNB
Consultant, Department of Neuro-ophthalmology Assistant Ophthalmologist, Pediatric Ophthalmology
Sankara Nethralaya Strabismus and Neuro-ophthalmology Services
A Unit of Medical Research Foundation LV Prasad Eye Institute
Nungambakkam, Chennai Visakhapatnam
Tamil Nadu, India Andhra Pradesh, India
Vijay Shetty MS DNB FRCS Glasg Vivek P Dave MD DNB MNAMS FRCS
Consultant, General Ophthalmology and Senior Resident
Cataract Services Laxmi Eye Institute and Dr Rajendra Prasad Center for Ophthalmic Sciences
Laxmi Charitable Eye Hospital, Panvel All India Institute of Medical Sciences
Maharashtra, India New Delhi, India
Vikas Chadha MS DNB MNAMS FRCS FRCOphth Zia Chaudhuri MS DNB MNAMS FRCS Glasg
Consultant Ophthalmologist Associate Professor of Ophthalmology
Tennent Institute of Ophthalmology Maulana Azad Medical College and
Gartnavel General and Stobhill Hospitals Associated Hospitals, Guru Nanak Eye Center
Glasgow, United Kingdom New Delhi, India
Foreword
I have great pleasure in writing this foreword for this much needed, excellent textbook for
postgraduates in ophthalmology, which will definitely serve the academic needs of not only the
residents and fellows, but will also benefit practicing ophthalmologists as a reference guide. The
text is drafted into 22 well written sections beginning with a perspective on blindness, as to why
and how one needs to study ophthalmology and what are the areas of priority. Most sections are
edited by the specialists, some of them leaders in their respective fields. Dr Zia Chaudhuri and
Dr Murugesan Vanathi have worked hard to assemble and edit the contributions of much
renowned and distinguished group of experts in each field of ophthalmology and have come out
with this excellent, unique ophthalmic text. I am happy to see that the often neglected areas like
low vision, medicolegal aspects, operating room sterilization and ocular emergencies have found
adequate space rather than a token mention, as in most other books. The inclusion of material on the much needed
awareness of the medical profession on medicolegal aspects of specialties like trauma, which can otherwise be a serious
handicap is of great relevance. At the same time, ophthalmology postgraduates and practitioners need to be well grounded
in surgical asepsis, as well as prevention and basic management of postoperative endophthalmitis to be able to practise the
specialty with confidence and safety.
In view of the accelerated rate of developments in ophthalmology at the level of both basic sciences as well as disease
management strategies, the reader not only needs an update on the latest in management, but also an understanding of the
fundamental pathological mechanisms, on which future management, particularly pharmacotherapy, is likely to be based.
I am happy to note a separate chapter on genetic aspects of ophthalmic disease, a field likely to be increasingly relevant to
clinical ophthalmologists in future. I note with satisfaction that the authors have covered their topics comprehensively from
fundamentals to the recent advances, often quoting from the most recent literature. Each section is well conceptualized
covering all aspects, namely basic techniques, investigative modules, and management methodologies inclusive of recent
advances in all arenas. I extend my hearty congratulations to all the authors for their contributions and the editors for their
commendable work in systematically compiling and editing the text ensuring completeness, comprehensiveness and quality.
I extend my best wishes to them for all success in their well-researched efforts and recommend this excellent textbook to all
those interested in the rapidly advancing specialty of ophthalmology. I have no doubt that Postgraduate Ophthalmology will be
a very valuable addition to all the libraries in medical institutions.
Dr P Namperumalsamy MS DO FAMS
(Padmashree Awardee)
Chairman Emeritus
Aravind Eye Care System
Madurai, Tamil Nadu, India
Preface
Ophthalmology has progressed by leaps and bounds with significant advancements in all subspecialties in the last decade.
With evolution of the corporate pattern of practice in almost all fields of medicine, it has now become imperative for the
general ophthalmologist to keep updated to the advancements in all the specialty fields of Ophthalmology. Ophthalmology
residents and fellows have for long-felt the need for an handy ready-reference text that fulfills the necessities of subspecialty
practice as well. With due consideration to this requirement, we have attempted to rise up to the occasion with the creation
of this well-researched text in ophthalmology, with contributions from stalwarts in the respective fields of ophthalmology,
from all over the country and abroad. We hope that the book fills in as a helpful guide to all ophthalmology students,
residents, practitioners and teachers. We are happy that our academic perseverances and services in our respective fields has
helped us to make this dynamic contribution to the world of ophthalmology.
Zia Chaudhuri
Murugesan Vanathi
Acknowledgments
We wish to acknowledge our respective institutes, Maulana Azad Medical College and Associated Hospitals (Department of
Neurosurgery, Govind Ballabh Pant Superspecialty Hospital and Guru Nanak Eye Center), New Delhi, India and Dr
Rajendra Prasad Center for Ophthalmic Sciences, All India Institute of Medical Sciences (AIIMS), New Delhi, India for the
opportunity to serve and contribute in our respective field of training, expertise and interest.
We thank all our contributors, luminaries in their fields of work, who took time out to write for this book and without
whom, this book would not have been possible.
We thank Mr Jitendar P Vij (Chairman and Managing Director) M/s Jaypee Brothers Medical Publishers (P) Ltd for
providing us a platform for presenting this work. Special thanks are due to all at M/s Jaypee Brothers Medical Publishers (P)
Ltd, especially Mr Tarun Duneja (Director-Publishing), Mr KK Raman (Production Manager), Mr Neelambar Pant and
Mr Rajesh Sharma (Production Coordinators), Mr Sunil Kumar Dogra (Production Executive); Mr Manoj Pahuja and his
team of graphic designers, including Ms Sonia Mehta, Mr Anil Kumawat and Mr Rajesh; Mr Bharat Bhushan, Mrs Yashu
Kapoor, Mr Deep Dogra, Mr Sunil Rawat and Mr Inder Jeet for the excellent typeset and Mr Gurnam Singh, Mr Balraj
Khehra, Dr Shalu Sharma, Mr Himanshu Sharma and Ms Monika Singh for acting as the final guards of control by their
meticulous copyediting. The midnight oil burnt for all in an attempt to conquer impossible deadlines!
Last but not the least, no words can express our gratitude to our families and friends, who stood by us, uncomplainingly,
as we toiled away, glued to our laptops and buried under sheets of paper!
We thank the Almighty for having guided this book over the past two and a half years, when it was no more than an
abstract conceptualization of ours, to this day when it stands out as an actual independent physical reality.
Contents
VOLUME 1
SECTION 1: COMMUNITY OPHTHALMOLOGY
GVS Murthy
1. Blindness: An International Perspective ................................................................................................... 3-17
GVS Murthy
SECTION 2: LIGHT, VISION, OPTICS AND REFRACTION

Zia Chaudhuri
2.1 Light and its Properties ............................................................................................................................ 21-29
Zia Chaudhuri
2.2 Reflection, Refraction and Geometric Optics ......................................................................................... 30-41
Zia Chaudhuri, Monica Chaudhry
2.3 Refraction of the Eye: Principles and Practice of Retinoscopy ............................................................. 42-71
Monica Chaudhry, Zia Chaudhuri
2.4 Pediatric Refraction ................................................................................................................................. 72-76
Sumit Monga, Monica Chaudhry, Zia Chaudhuri
SECTION 3: CONTACT LENS

M Vanathi
3.1 Contact Lens: Basic Concepts ................................................................................................................. 79-98
Monica Chaudhry
3.2 Contact Lens: The Clinical Spectrum .................................................................................................... 99-162
Kirti Singh
3.2.1 Essentials in Contact Lens Practice: An Overview ................................................................... 99-115
3.2.2 Special Types of Contact Lenses ............................................................................................. 115-129
3.2.3 Contact Lens Fitting in Special Situations ............................................................................... 129-153
3.2.4 Important Concerns in Contact Lens Wear ............................................................................. 153-162
SECTION 4: LOW VISION

Beula Christy
4.1 Definition and Magnitude of Low Vision ............................................................................................ 165-177
Rituparna Ghoshal
4.2 Examination of Patients with Low Vision ........................................................................................... 178-184
Deepak K Bagga
4.3 Rehabilitation of the Visually Handicapped ...................................................................................... 185-195
Beula Christy
xxiv Postgraduate Ophthalmology
SECTION 5: APPLIED BASIC SCIENCES RELATED TO OPHTHALMOLOGY

Zia Chaudhuri, M Vanathi
5.1 Genetics in Ophthalmology ................................................................................................................. 199-207
Saurabh Jain, Zia Chaudhuri
5.2 Ocular Anesthesia ................................................................................................................................. 208-217
Bharti Taneja, Kirti Nath Saxena
5.3 Ocular Microbiology ............................................................................................................................. 218-240
Savitri Sharma
5.4 Ocular Pathology .................................................................................................................................. 241-276
5.4.1 Ophthalmic Pathology for Clinicians ....................................................................................... 241-250
Geeta K Vemuganti
5.4.2 Illustrative Ocular Pathology .................................................................................................... 251-276
Seema Kashyap
5.5 Ocular and Adnexal Radiology ............................................................................................................ 277-334
5.5.1 Radiological Imaging in Ophthalmology ................................................................................ 277-290
Vandana Kohli
5.5.2 Illustrative Imaging of the Normal Orbit ............................................................................... 290-316
Vandana Kohli
5.5.3 Diagnostic Ophthalmic Ultrasonography ............................................................................... 317-329
Karandeep Rishi, Pradeep Venkatesh
5.5.4 Orbital Ultrasonography ........................................................................................................... 329-334
Sumita Sethi, Rachna Meel, Neelam Pushkar, Supriyo Ghose
5.6 Ocular Pharmacology ........................................................................................................................... 335-361
J Nirmal, S Senthilkumari, T Velpandian
SECTION 6: CORNEA AND EXTERNAL EYE DISEASES

M Vanathi
6.1 Cornea: Applied Anatomy and Functions ........................................................................................... 365-372
Rajesh Ramanjulu, Rakhi Kusumesh, M Vanathi
6.2 Evaluation of the Cornea ..................................................................................................................... 373-416
6.2.1 Specular Microscopy of the Cornea ........................................................................................ 373-378
M Vanathi, Rajesh Ramanjulu
6.2.2 Corneal Topography ................................................................................................................. 378-385
M Vanathi, Jatin N Ashar
6.2.3 Keratometry ............................................................................................................................... 385-388
Shalini Mohan, Rajesh Ramanjulu, M Vanathi
6.2.4 Pachymetry ............................................................................................................................... 389-395
Shalini Mohan
6.2.5 Corneal Esthesiometry ............................................................................................................. 396-397
M Vanathi
6.2.6 Confocal Microscopy of the Cornea ........................................................................................ 397-404
M Vanathi, Sankaranarayana P Mahesh
6.2.7 Corneal Hysteresis: Relevance in Current Clinical Practice .................................................. 405-409
Shibal Bhartiya
6.2.8 Slit Lamp Biomicroscopy Evaluation and Diagrammatic Representation ............................ 410-416
Swapnali S Sharma, Shraddha S Puranik, M Vanathi
Contents xxv
6.3 Disorders of the Pediatric Cornea ....................................................................................................... 417-429

M Vanathi, Shalini Mohan, Rakhi Kusumesh
6.4 Corneal Dystrophies ............................................................................................................................. 430-450
Jaya Gupta, Radhika Tandon
6.5 Corneal Ectasias ................................................................................................................................... 451-464
Reena Sharma, M Vanathi
6.6 Limbus Abnormalities .......................................................................................................................... 465-494
6.6.1 Diseases of the Corneal Limbus .............................................................................................. 465-481
R Revathi, Sathyarekha
6.6.2 Limbal Stem Cell Deficiency ................................................................................................... 481-494
Kunjal Sejpal, Soundarya Lakshmi Madhira, Geeta K Vemuganti, Virender S Sangwan
6.7 Infections of the Cornea and External Eye ........................................................................................ 495-562
6.7.1 Bacterial Conjunctivitis and Keratitis ...................................................................................... 495-506
R Revathi, Parameshwar Bhat, Abhishek Saraf
6.7.2 Viral Conjunctivitis and Keratitis ............................................................................................. 506-522
R Revathi, M Vanathi
6.7.3 Fungal Keratitis ......................................................................................................................... 523-533
Sujith Vengayil, M Vanathi
6.7.4 Acanthamoeba Keratitis ............................................................................................................ 534-538
R Revathi, Hemal J Kansagra
6.7.5 Microsporidial Keratitis ............................................................................................................ 538-543
Manotosh Ray
6.7.6 Contact Lens Related Keratitis ................................................................................................. 543-551
M Vanathi
6.7.7 Atypical Mycobacterial Keratitis .............................................................................................. 551-555
Sujata Das
6.7.8 Chlamydial Infections of the Eye ............................................................................................ 556-562
Gaurav Kumar, M Vanathi
6.8 Diseases of the Ocular Surface ............................................................................................................ 563-631
6.8.1 Diseases of the Conjunctiva ..................................................................................................... 563-596
M Vanathi
6.8.2 Tear Film Dysfunction—Dry Eye Disease ............................................................................. 596-608
Rakhi Kusumesh, Shweta S Agarwal, Geetha Krishnan Iyer, M Vanathi
6.8.3 Immunological Diseases of the Eye ........................................................................................ 608-631
Geetha Krishnan Iyer
6.9 Miscellaneous Conditions of the Cornea ............................................................................................ 632-639
R Revathi, Sowmyalatha Maskabil
6.10 Corneal Surgery .................................................................................................................................... 640-720
M Vanathi
6.10.1 Penetrating Keratoplasty ........................................................................................................... 640-685
6.10.1.1 Penetrating Keratoplasty: Indications and Technique .............................................. 640-650
6.10.1.2 Post Penetrating Keratoplasty Glaucoma .................................................................... 650-654
6.10.1.3 Corneal Graft Rejection ............................................................................................... 654-663
6.10.1.4 Corneal Graft Infection ................................................................................................ 663-668
6.10.1.5 High-risk Corneal Grafting ......................................................................................... 668-674
6.10.1.6 Pediatric Keratoplasty .................................................................................................. 674-682
6.10.1.7 Corneal Patch Grafts .................................................................................................... 682-683
6.10.1.8 Alternatives to Keratoplasty ......................................................................................... 683-685
xxvi Postgraduate Ophthalmology
6.10.2 Lamellar Keratoplasty ............................................................................................................... 686-699

6.10.2.1 Anterior Lamellar Keratoplasty ................................................................................... 686-694
M Vanathi
6.10.2.2 Posterior Lamellar Keratoplasty .................................................................................. 694-699
6.10.3 Ocular Surface Reconstruction with Amniotic Membrane Grafting ...................................... 700-705
M Vanathi
6.10.4 Surgical Instruments in Corneal Transplantation ................................................................... 706-710
Sankaranarayana P Mahesh
6.10.5 Keratoprosthesis ........................................................................................................................ 711-720
Noopur Gupta, Radhika Tandon
6.11 Eye Banking ........................................................................................................................................ 721-729
SECTION 7: REFRACTIVE SURGERY

M Vanathi
7.1 Incisional Keratorefractive Surgery ..................................................................................................... 733-740
7.2 Laser Refractive Surgery and Phakic IOLs ......................................................................................... 741-769
Mahipal Singh Sachdev, Charu Khurana, Hemlata Gupta
7.3 Corneal Crosslinking ............................................................................................................................ 770-775
Rakhi Kusumesh, Shah Nawaz, M Vanathi
SECTION 8: SCLERA
M Vanathi
8. Diseases of the Sclera .......................................................................................................................... 779-788
M Vanathi, Rupesh Agrawal, Sujith Vengayil, Virender S Sangwan
SECTION 9: GLAUCOMA
Jaya Chandra Das
9.1 Glaucoma: Basic Aspects and Classification ....................................................................................... 791-802
Parul Sony
9.2 Glaucoma Evaluation ........................................................................................................................... 803-844
9.2.1 Assessment of a Patient with Glaucoma .................................................................................. 803-833
Shalini Mohan
9.2.2 Evaluation and Interpretation of Visual Fields ....................................................................... 834-840
Anuradha Chandra, Reena Sharma, Shalini Mohan
9.2.3 Optic Disk Imaging in Glaucoma Suspects ............................................................................ 841-844
Sushmita Kaushik, Surinder Singh Pandav
9.3 Glaucoma: Clinical Profile .................................................................................................................... 845-885
9.3.1 Clinical Profile of Primary Glaucoma ...................................................................................... 845-854
9.3.2 Primary Angle Closure Glaucoma ........................................................................................... 854-859
Ramanjit Sihota
Contents xxvii
9.3.3 Congenital and Developmental Glaucoma: Clinical Profile ................................................... 860-869

Parul Icchpujani, Suresh Kumar Gupta, Surinder Singh Pandav
9.3.4 Secondary Glaucoma—Clinical Aspects ................................................................................. 869-885
Suresh Kumar Gupta, Parul Ichhpujani, Neeti Gupta, Surinder Singh Pandav
9.4 Management of Glaucoma ................................................................................................................... 886-949
9.4.1 Medical Management of Glaucoma ........................................................................................ 886-904
Geetha Srinivasan
9.4.2 Management of Primary Congenital Glaucoma ..................................................................... 905-910
9.4.3 Trabeculectomy and its Modifications .................................................................................... 910-936
Kirti Singh, Shalini Gupta
9.4.4 Glaucoma Drainage Devices ................................................................................................... 936-945
Jaya Chandra Das, Neha Verma
9.4.5 Recent Surgical Advances in Glaucoma ................................................................................. 945-949
9.5 Neuroprotection .................................................................................................................................... 950-953
Parul Icchpujani
SECTION 10: LENS AND ITS ANOMALIES

Abhay R Vasavada, Saurabh Sawhney
10.1 Lens: Basic Aspects .............................................................................................................................. 957-968
Aashima Aggarwal, Saurabh Sawhney
10.1.1 Embryology, Anatomy and Physiology ................................................................................... 957-961
10.1.2 Etiopathogenesis of Cataract ................................................................................................... 961-965
10.1.3 Patient Preparation and Anesthesia ......................................................................................... 965-968
10.2 Intraocular Lenses ................................................................................................................................ 969-980
Gauri Shah, Abhay R Vasavada
10.3 Intraocular Lens Power Calculation ..................................................................................................... 981-996
10.3.1 Intraocular Lens (IOL) Implant Power Calculation, Selection and Biometry ....................... 981-988
Vaishali A Vasavada, Abhay R Vasavada, Viraj A Vasavada
10.3.2 Post-refractive Surgery IOL Power Calculations ..................................................................... 988-993
M Vanathi, Manoj Gupta, Shibal Bhartiya, Saurabh Sawhney, Aashima Aggarwal
10.3.3 Analysis of Surgically Induced Astigmatism .......................................................................... 993-996
Saurabh Sawhney, Aashima Aggarwal
10.4 Cataract Surgery ................................................................................................................................. 997-1027
10.4.1 Conventional Techniques of Cataract Surgery ..................................................................... 997-1005
10.4.2 Phacoemulsification: Basics, Techniques and Instrumentation ........................................ 1005-1023
10.4.3 Micro-coaxial, Bimanual and Torsional Phacoemulsification ........................................... 1024-1027
MR Praveen, Viraj A Vasavada, Abhay R Vasavada
10.5 Phacoemulsification in Special Situations ....................................................................................... 1028-1045
Suhas S Haldipurkar, Vijay Shetty
10.5.1 Hard Cataract ........................................................................................................................ 1028-1030
10.5.2 White Cataract ....................................................................................................................... 1030-1032
10.5.3 Small Pupil Phacoemulsification .......................................................................................... 1032-1034
xxviii Postgraduate Ophthalmology
10.5.4 Phacoemulsification in Intraoperative Floppy Iris Syndrome ............................................ 1034-1035

10.5.5 Phacoemulsification in the Diabetic Patient ....................................................................... 1036-1037
10.5.6 Phacoemulsification in Posterior Polar Cataract .................................................................. 1038-1039
10.5.7 Phacoemulsification in the Subluxated Lens ...................................................................... 1040-1042
10.5.8 Phacoemulsification in Traumatic Cataract ........................................................................ 1042-1045
10.6 Phacoemulsification in Eyes with Co-existing Ocular Pathology ................................................... 1046-1051
10.7 Pediatric Lenticular Abnormalities .................................................................................................. 1052-1068
Sajani K Shah, Abhay R Vasavada
10.8 Complications of Cataract Surgery .................................................................................................. 1069-1074
SECTION 11: UVEA

Jyotirmay Biswas
11. Diseases of the Uvea ......................................................................................................................... 1077-1113
Jyotirmay Biswas, Shafiq S Jafferji, S Sudharshan
VOLUME 2
SECTION 12: RETINA AND VITREOUS
Lingam Gopal
12.1 Applied Basics of the Retina and Vitreous ...................................................................................... 1117-1134
Vasu Kumar, Sonam Angmo Bodh
12.2 Evaluation of the Retina ................................................................................................................... 1135-1141
Sonam Angmo Bodh, Vasu Kumar
12.3 Macular Function Tests .................................................................................................................... 1142-1152
12.3.1 Psychophysical and Other Clinical Macular Function Tests .............................................. 1142-1148
Vasu Kumar
12.3.2 Electrophysiological Testing in Retinal Disease ................................................................. 1149-1152
Vivek P Dave
12.4 Imaging for Retinal Disease ............................................................................................................. 1153-1169
Lingam Gopal
12.5 Dystrophy and Degenerations of the Vitreous and Retina ............................................................. 1170-1190
Lingam Gopal
12.5.1 Choroidal Dystrophy .............................................................................................................. 1170-1172
12.5.2 Hereditary Vitreoretinal Degenerations ............................................................................... 1172-1176
12.5.3 Macular Dystrophies ............................................................................................................. 1176-1179
12.5.4 Dystrophy and Abiotrophy of the Retina ............................................................................. 1180-1187
12.5.5 Peripheral Retinal Degenerations ......................................................................................... 1187-1190
12.6 Diseases of the Vitreous .................................................................................................................... 1191-1196
Lingam Gopal
12.7 Retinal Vascular Diseases ................................................................................................................. 1197-1211
Pradeep Venkatesh, Karandeep Rishi
Contents xxix
12.8 Systemic Diseases with Retinal Manifestations ............................................................................... 1212-1226

Lingam Gopal
12.9 Diseases of the Macula .................................................................................................................... 1227-1242
Lingam Gopal
12.10 Posterior Segment Ocular Trauma ................................................................................................... 1243-1254
Sharad Bhomaj
12.11 Retinal Detachment .......................................................................................................................... 1255-1275
Sharad Bhomaj, Chintamani Khare
SECTION 13: ORBIT, EYELID AND LACRIMAL SYSTEM

Santosh G Honavar
13.1 Orbit: Basic Aspects ......................................................................................................................... 1279-1290
Roshmi Gupta, Santosh G Honavar
13.1.1 Anatomy of the Orbit ............................................................................................................ 1279-1283
13.1.2 Imaging of the Orbit ............................................................................................................ 1283-1286
13.1.3 Evaluation of the Orbit ......................................................................................................... 1286-1290
13.2 Pathological Lesions of the Orbit ..................................................................................................... 1291-1320
13.2.1 Congenital and Structural Lesions of the Orbit ................................................................... 1291-1293
13.2.2 Thyroid Orbitopathy ............................................................................................................. 1293-1298
13.2.3 Cystic Lesions of the Orbit .................................................................................................... 1298-1301
13.2.4 Orbital Trauma ..................................................................................................................... 1302-1306
13.2.5 Infections of the Orbit ........................................................................................................... 1306-1312
13.2.6 Orbital Inflammations ........................................................................................................... 1312-1318
13.2.7 Vascular Lesions of the Orbit ............................................................................................... 1318-1320
13.3 Anophthalmic Socket ......................................................................................................................... 1321-1324
13.4 Orbital Surgery ................................................................................................................................. 1325-1337
13.4.1 Orbitotomy and Repair of Orbital Fracture ........................................................................ 1325-1329
13.4.2 Orbital Decompression for Thyroid Orbitopathy ................................................................ 1329-1330
13.4.3 Destructive Surgery: Enucleation, Evisceration and Exenteration ................................... 1330-1335
13.4.4 Oculoplastic Instruments and Equipment .......................................................................... 1335-1337
13.5 Eyelids: Basic Aspects ...................................................................................................................... 1338-1342
Vikas Menon
13.6 Congenital Eyelid Anomalies ........................................................................................................... 1343-1346
Vikas Menon, Monika Nanda
13.7 Benign Eyelid Lesions ..................................................................................................................... 1347-1354
Anirban Bhaduri, Vikas Menon
13.8 Structural Anomalies of the Eyelids ................................................................................................ 1355-1375
Vikas Menon
13.8.1 Ptosis .................................................................................................................................. 1355-1364
13.8.2 Eyelid Retraction .................................................................................................................. 1364-1367
13.8.3 Ectropion ............................................................................................................................... 1367-1370
13.8.4 Entropion ............................................................................................................................... 1370-1374
13.8.5 Floppy Eyelid Syndrome ...................................................................................................... 1374-1375
xxx Postgraduate Ophthalmology
13.9 Esthetic Eyelid Surgery .................................................................................................................... 1376-1381

Savari T Desai, Vikas Menon
13.10 Eyelid Reconstruction ...................................................................................................................... 1382-1388
Vikas Menon, Anirban Bhaduri
13.11 Anomalies of the Lacrimal System .................................................................................................. 1389-1398
Ramesh Murthy, Vikas Menon, Amit Gupta
13.12 Botulinum Toxin in Ophthalmology ................................................................................................ 1399-1403
Vikas Menon
SECTION 14: OCULAR ONCOLOGY

Santosh G Honavar
14.1 Basic Principles of Management of Ophthalmic Tumors ............................................................. 1407-1409
14.2 Orbital, Adnexal, Ocular Surface and Intraocular Tumors ............................................................. 1410-1449
14.2.1 Eyelid Tumors ....................................................................................................................... 1410-1415
14.2.2 Orbital Tumors ....................................................................................................................... 1415-1428
14.2.3 Tumors of the Conjunctiva and Ocular Surface ................................................................. 1428-1436
14.2.4 Intraocular Tumors ............................................................................................................... 1436-1449
SECTION 15: SYSTEMIC OPHTHALMOLOGY

Zia Chaudhuri
15.1 The Eye in Metabolic and Systemic Disorders .............................................................................. 1453-1478
Zia Chaudhuri, AS Karthikeyan
15.2 Albinism and Role of Pigment in Visual Development ................................................................. 1479-1486
Anamika Tandon
15.3 Ophthalmic Manifestations of Leukemia ........................................................................................ 1487-1493
AS Karthikeyan, Zia Chaudhuri
15.4 The Eye and Carotid Artery Disease ............................................................................................... 1494-1500
Zia Chaudhuri, Vikas Chadha
15.5 Ocular Myasthenia Gravis ................................................................................................................. 1501-1509
Akshay G Nair, Rashmin A Gandhi
15.6 The Eye in Phakomatosis .................................................................................................................. 1510-1521
Zia Chaudhuri, AS Karthikeyan
15.7 Multiple Sclerosis and the Eye ........................................................................................................ 1522-1527
Rashmin A Gandhi, Zia Chaudhuri
SECTION 16: NEURO-OPHTHALMOLOGY

Zia Chaudhuri, Rashmin A Gandhi
16.1 Neuro-ophthalmic Evaluation .......................................................................................................... 1531-1568
16.1.1 Examination Techniques in Neuro-ophthalmology ............................................................ 1531-1541
V Subashini, Rashmin A Gandhi
16.1.2 Color Vision ........................................................................................................................... 1542-1548
Dinesh Shrey, Twinkle Parmar, Supriyo Ghose
Contents xxxi
16.1.3 Cranial Nerves Evaluation from an Ophthalmologist’s Perspective ................................. 1549-1557

Debashish Chowdhury, Amit Batra
16.1.4 The Pupil ............................................................................................................................... 1558-1568
Zia Chaudhuri, Shalini Gupta
16.2 Neuroimaging in Neuro-ophthalmology ........................................................................................ 1569-1577
V Subashini, Suyog Ughade, Rashmin A Gandhi
16.3 Clinical Presentations in Neuro-ophthalmology .............................................................................. 1578-1601
16.3.1 Headache .............................................................................................................................. 1578-1583
V Satyanarayana
16.3.2 Visual Hallucinations ........................................................................................................... 1584-1588
V Satyanarayana, Zia Chaudhuri
16.3.3 Psychosomatic Disorders in Ophthalmology, Hysteria and Malingering ......................... 1589-1593
Rashmin A Gandhi, Zia Chaudhuri
16.3.4 Ocular Manifestations of Intracranial Trauma .................................................................... 1593-1601
Rajat Chaudhary, Sharad Bhomaj, Zia Chaudhuri
16.4 Electro-diagnosis in Neuro-ophthalmology ..................................................................................... 1602-1610
Devendra V Venkatramani, Rashmin A Gandhi
16.5 Anatomy of the Visual Pathway ........................................................................................................ 1611-1628
Virender Sachdeva, Ramesh Kekunnaya, Manav Khera
16.6 Optic Nerve Anomalies and Neuropathies ..................................................................................... 1629-1674
16.6.1 Congenital Optic Disk Anomalies ........................................................................................ 1629-1634
Ramesh Kekunnaya
16.6.2 Hereditary Optic Neuropathies ........................................................................................... 1635-1642
Virender Sachdeva, Ramesh Kekunnaya, Vaibhev Mittal
16.6.3 Optic Neuritis ....................................................................................................................... 1642-1648
Harinder Singh Sethi, Munish Dhawan
16.6.4 Atypical Optic Neuritis ......................................................................................................... 1648-1654
Harinder Singh Sethi, Malvika Gupta
16.6.5 Ischemic Optic Neuropathy ................................................................................................. 1654-1663
Virender Sachdeva
16.6.6 Compressive Optic Neuropathy ........................................................................................... 1663-1666
K Shyamsundar, Rashmin A Gandhi
16.6.7 Traumatic Optic Neuropathy ............................................................................................... 1666-1670
Akshay G Nair, Rashmin A Gandhi
16.6.8 Nutritional and Toxic Optic Neuropathy ............................................................................ 1670-1674
Virender Sachdeva
16.7 Optic Disk Pallor ............................................................................................................................... 1675-1684
16.7.1 Optic Atrophy ........................................................................................................................ 1675-1680
Virender Sachdeva
16.7.2 Clinical Approach to a Pale Optic Disk ............................................................................... 1680-1684
Rashmin A Gandhi, Devendra V Venkatramani, Virender Sachdeva
16.8 Optic Disk Edema ............................................................................................................................ 1685-1703
16.8.1 Papilledema ........................................................................................................................... 1685-1693
Virender Sachdeva, S Ambika
16.8.2 Swollen Optic Disk: Clinical Approach ............................................................................... 1693-1703
S Ambika, Virender Sachdeva
16.9 Principles of Ocular Motility ............................................................................................................. 1704-1711
Divya Jain, Zia Chaudhuri
xxxii Postgraduate Ophthalmology
16.10 Ocular Motility Disorders .................................................................................................................. 1712-1740

16.10.1 Ophthalmoplegia ................................................................................................................... 1712-1717
Zia Chaudhuri, Vikas Chadha, Sachin Mehta
16.10.2 Disorders of the Supranuclear Pathway ............................................................................... 1717-1728
Rashmin A Gandhi, Ashwin Mohan, Zia Chaudhuri
16.10.3 Disorders of the Infranuclear Pathway ................................................................................ 1728-1738
Vijay Ananth J, Zia Chaudhuri
16.10.4 The Orbit in Neuro-ophthalmic Disorders ......................................................................... 1738-1740
Vikas Chadha
SECTION 17: NYSTAGMUS

Zia Chaudhuri
17. Nystagmus and Other Abnormal Ocular Oscillations ................................................................... 1743-1772
Zia Chaudhuri, Jatin N Ashar
SECTION 18: PEDIATRIC OPHTHALMOLOGY

Zia Chaudhuri
18.1 Visual Functions in Children: Normal Ocular and Visual Development ..................................... 1775-1783
Sumit Monga
18.2 Pediatric Ocular Examination .......................................................................................................... 1784-1805
Sumit Monga
18.3 Amblyopia ................................................................................................................................... 1806-1814
Ramesh Murthy, Amit Gupta, Zia Chaudhuri
18.4 Ocular Embryology: Overview and Basis for Some Congenital Ocular Disorders ....................... 1815-1834
Zia Chaudhuri, Sumit Monga, Saurabh Jain
18.5 Imaging of the Eye and Orbit in Children ..................................................................................... 1835-1850
Sumita Sethi, Mridula Mehta, Sanjay Sharma, Neelam Pushker
18.6 Child Abuse, Non-accidental Injuries and the Eye ......................................................................... 1851-1862
Anamika Tandon
18.7 Craniofacial Malformations .............................................................................................................. 1863-1873
Anamika Tandon
18.8 Retinopathy of Prematurity .............................................................................................................. 1874-1887
Mangat R Dogra, Gaurav Sanghi
18.9 Benign Pediatric Ocular and Periocular Tumors ............................................................................ 1888-1902
Mridula Mehta, Sumita Sethi, Neelam Pushker, Supriyo Ghose
18.10 Intrauterine Infections and the Developing Eye ............................................................................ 1903-1909
Anamika Tandon
18.11 Ocular Clues to Pediatric Neuro-ophthalmic Diagnosis ................................................................. 1910-1928
AS Karthikeyan, Zia Chaudhuri
Contents xxxiii
SECTION 19: STRABISMUS

Zia Chaudhuri
19.1 Basics of Strabismus .......................................................................................................................... 1931-1944
Zia Chaudhuri, Divya Jain
19.1.1 Functional Anatomy and Physiology of Extraocular Muscles ............................................ 1931-1937
19.1.2 The Physiological Basis of Ocular Misalignment .............................................................. 1938-1944
19.2 Classification of Strabismus .............................................................................................................. 1945-1951
Varshini Shankar, Zia Chaudhuri
19.3 Evaluation of Strabismus ................................................................................................................. 1952-1998
19.3.1 Clinical Approach to a Patient with Strabismus .................................................................. 1952-1963
Kalpana Narendran
19.3.2 Approach to Paralytic Strabismus ........................................................................................ 1964-1972
Shruti Mittal, S Meenakshi
19.3.3 Orthoptic Evaluation and Uses of Orthoptic Instruments ................................................. 1972-1998
Jameel Rizwana Hussain
19.4 Comitant Horizontal Strabismus ...................................................................................................... 1999-2015
19.4.1 Esotropia ............................................................................................................................... 1999-2007
Preeti A Patil, Sumita Agarkar, Zia Chaudhuri
19.4.2 Exotropia ............................................................................................................................... 2007-2015
Zia Chaudhuri, Gangaprasad Amula, Sumita Agarkar
19.5 Alphabet Pattern Strabismus ............................................................................................................ 2016-2021
Varshini Shankar
19.6 Dissociated Strabismus Complex ..................................................................................................... 2022-2025
Varshini Shankar
19.7 Neurogenic Strabismus .................................................................................................................... 2026-2041
Zia Chaudhuri, Sumita Agarkar, Vikas Chadha, Gangaprasad Amula
19.8 Special Forms Of Strabismus .......................................................................................................... 2042-2060
19.8.1 Congenital Cranial Dysinnervation Disorders (CCDD) ...................................................... 2042-2047
Anil Kumar AS, Irene Gottlob
19.8.2 Management Protocols for Congenital Cranial Dysinnervation Disorders (CCDD) ......... 2048-2052
Sumita Agarkar, Charuta Bapaye, Sowmya R
19.8.3 Post Surgical Strabismus ...................................................................................................... 2052-2054
S Meenakshi, Preeti A Patil
19.8.4 Strabismus Associated with Neuro-developmental Disorders ........................................... 2054-2055
S Meenakshi, Preeti A Patil
19.8.5 Traumatic Strabismus ........................................................................................................... 2055-2060
Rajat Chaudhary, Zia Chaudhuri
19.9 Restrictive Strabismus ...................................................................................................................... 2061-2070
19.9.1 Brown’s Syndrome ................................................................................................................ 2061-2064
Sumita Agarkar, Harsha Pagad
19.9.2 Monocular Elevation Deficiency ......................................................................................... 2064-2066
Varshini Shankar
19.9.3 Strabismus in Thyroid Eye Disease .................................................................................... 2067-2070
Sumita Agarkar, Reshmi Bhaskar
xxxiv Postgraduate Ophthalmology
19.10 Myogenic Strabismus ....................................................................................................................... 2071-2077

Sumita Agarkar, Pramod K Pandey, Zia Chaudhuri
19.11 Management of Strabismus ............................................................................................................. 2078-2096
Varshini Shankar
19.12 Anterior Segment Ischemia and Vessel Sparing Procedure in Strabismus Surgery ..................... 2097-2099
Kalpana Narendran
SECTION 20: OCULAR TRAUMA

M Vanathi
20.1 Injuries of the Eye ............................................................................................................................ 2103-2123
Rupesh Agrawal, Rakhi Kusumesh, Virender S Sangwan, M Vanathi
20.2 Chemical Injuries............................................................................................................................... 2124-2131
Prateek Gujar, Geetha Krishnan Iyer
SECTION 21: LASERS IN OPHTHALMOLOGY

Pradeep Venkatesh, M Vanathi
21.1 Lasers in Cornea ............................................................................................................................... 2135-2165
21.1.1 Laser Assisted In Situ Keratomileusis (LASIK) .................................................................... 2135-2151
21.1.2 Epi-LASIK .............................................................................................................................. 2151-2153
Sujata Das, Balasubramanya Ramamurthy
21.1.3 Laser Epithelial Keratomileusis (LASEK) ........................................................................... 2154-2155
M Vanathi
21.1.4 Photorefractive Keratectomy ................................................................................................. 2156-2157
M Vanathi, Pranav D More, R Revathi
21.1.5 Phototherapeutic Keratectomy ............................................................................................. 2158-2162
M Vanathi, R Revathi
21.1.6 Femtosecond Laser in Corneal Surgery .............................................................................. 2162-2165
M Vanathi, Shibal Bhartiya, Sanjay Kai, R Revathi
21.2 Lasers in Glaucoma .......................................................................................................................... 2166-2190
21.2.1 Diode Laser Cyclophotocoagulation ..................................................................................... 2166-2171
Shalini Mohan, Neha Mithal, M Vanathi
21.2.2 Laser Trabeculoplasty ........................................................................................................... 2171-2176
Geetha Srinivasan, Neha Mithal
21.2.2.1 Selective Laser Trabeculoplasty .............................................................................. 2171-2173
21.2.2.2 Argon Laser Trabeculoplasty ................................................................................. 2174-2176
21.2.3 Laser Sclerostomy .................................................................................................................. 2177-2181
21.2.4 Laser Filtering Surgery ......................................................................................................... 2181-2183
21.2.5 Laser-assisted Deep Sclerectomy ........................................................................................ 2183-2185
21.2.6 Laser Iridotomy ..................................................................................................................... 2185-2190
Shalini Mohan, Anand Aggarwal, Neha Mithal, M Vanathi
Contents xxxv
21.3 YAG Capsulotomy .............................................................................................................................. 2191-2196

M Vanathi, Shalini Mohan
21.4 Lasers in the Posterior Segment of the Eye .................................................................................... 2197-2246
Pradeep Venkatesh, Karandeep Rishi
SECTION 22: RELEVANT CONCERNS IN OPHTHALMIC PRACTICE

Zia Chaudhuri, M Vanathi
22.1 Ethical and Medicolegal Aspects in Ophthalmology ..................................................................... 2249-2265
Anil N Kulkarni, Zia Chaudhuri
22.2 Operation Theater Asepsis ............................................................................................................... 2266-2273
Pooja Magdum Bhomaj, Divya Jain, Zia Chaudhuri
22.3 Differential Diagnosis of Ophthalmic Signs and Symptoms ......................................................... 2274-2286
Sachin Mehta
22.4 Ophthalmic Emergencies ................................................................................................................ 2287-2302
Sachin Mehta
Appendices ..................................................................................................................................... 2303-2307

Appendix 1 ..................................................................................................................................... 2303-2303
Appendix 2 ..................................................................................................................................... 2304-2307
Index ..................................................................................................................................... 2309-2339

Chapter 1
BLINDNESS: AN
INTERNATIONAL PERSPECTIVE
GVS Murthy
BACKGROUND retained till the 10th version of ICD. The recommended

classification is depicted in Table 1.1.
Every five seconds one individual in the world goes blind.
The categories of visual impairment are intended to
Blindness is egalitarian in character, affecting millions in both
correspond with the fourth digit of the numbering system
the developed countries, as well as the developing countries,
used in the international classification of diseases. In this system
though the underlying sociopathological causes may vary
the digit '9' customarily signifies the unspecified category.
widely from continent to continent.
The above categorization is primarily in terms of distant
Blindness is a global public health problem and adversely
vision. However, the field of vision should also be considered
impacts the productivity of populations. The problem is more
in defining visual impairment. With regard to the extent of
evident in the developing world where a high prevalence of
visual field loss, patients with a field of less than 10° and
blindness is further compounded by poor access to eye care
more than or equal to 5° around central fixation should be
facilities.
placed in category '3', while patients with a field less than 5°
The World Health Organization's program for prevention
around central fixation should be placed in category '4', even
of blindness was initiated in 1978 when it was believed that
if the central acuity is not impaired.
there were 28 million blind world wide.1 The estimate was
In 2008, the WHO revised the definition of blindness
later revised in 1995 to 45 million based on the global
and visual impairment to include presenting vision in place
population for 1996.2 The World Health Organization's global
of best corrected vision.5 This was done to reflect the needs
data bank recently estimated that in 2002 there were 37 million
of a significant section of the population which suffers from
blind and 161 million visually impaired persons globally.3 More
uncorrected refractive errors, which are grossly
recently, the WHO also provided estimates for uncorrected
underestimated if best corrected vision is, used.5 The revised
refractive errors. It was observed that 153 million people
categories of blindness and visual impairment are indicated
were visually impaired or blind due to uncorrected refractive
in Table 1.2.
errors.4 Combined with the earlier estimates of blindness and
The term 'low vision' (this was used in the earlier WHO
visual impairment, it is now evident that a total of 314 million
classification), has now been replaced, by the two categories,
people are visually impaired (including blindness) from all
of moderate and severe visual impairment.
causes.4
The WHO recommends that each country must define
blindness in relation to its own social and economic conditions,
Definition of Blindness
keeping the categories of visual impairment in mind.
The World Health Organization recommends a generally However, for all international comparisons, standard case
accepted definition of blindness and visual impairment as it definitions should be adhered to. The cut off point for
is felt that it was necessary to define the categories of visual international comparisons was placed at 3/60 (inability to
impairment and blindness in order to obtain comparable data count fingers at a distance of 3 meters). Thus, categories 3, 4
from different countries. This categorization is in consonance and 5 qualify as blindness, while categories 1 and 2 are labeled
with the International Classification of Diseases and has been as low vision.
4 Community Ophthalmology
Table 1.1: Categories of visual impairment and blindness

Category of visual impairment Visual acuity (with both eyes using the best possible correction)
Maximum less than Minimum equal to or better than
1 6/18 6/60
3/10 (0.3) 1/10 (0.1)
20/70 20/200
2 6/60 3/60
1/10 (0.1) 1/20 (0.5)
20/200 20/200
3 3/60 1/60
1/20 (0.50) 1/50 (0.02)
20/400 5/300 (20/1200)
4 1/60 Light perception
1/50 (0.02)
5/300
5 No light perception
9 Undetermined or unspecified
Table 1.2: Proposed revision of categories of visual impairment in ICD-10, 2008

Category of visual impairment Presenting distance visual acuity
Worse than Equal to or better than
Mild or no visual impairment 6/18
0 3/10 (0.3)
20/70
Moderate visual impairment 6/18 6/60
1 3/10 (0.3) 1/10 (0.1)
20/70 20/200
Severe visual impairment 6/60 3/60
2 1/10 (0.1) 1/20 (0.5)
20/200 20/400
Blindness 3/60 1/60*
3 1/20 (0.50) 1/50 (0.02)
20/400 5/300 (20/1200)
Blindness 1/60* Light perception
4 1/50 (0.02)
5/300 (20/1200)
5 No light perception
9 Undetermined or unspecified
*Or count fingers (CF) at 1 meter.
Reproduced with the permission of the World Health Organization (WHO) from http://www.who.int/blindness/change%20the%20definition%20of%20blindness.pdf,
2008, copyright notice, April 2011
Table 1.3: Comparison of WHO and NPCB definitions of visual impairment and blindness
WHO-ICD Classification of visual Visual acuity NPCB categorization of visual
impairment and blindness impairment and blindness
Moderate visual impairment
Category (1) < 6/18 - 6/60 in better eye Low vision
Severe visual impairment
Category (2) < 6/60 - 3/60 in better eye Economic blindness
Blindness
Category (3) < 3/60 - 1/60 in better eye Social blindness
Category (4) < 1/60 in better eye Manifest blindness
Category (5) No perception of light in better eye Absolute blindness
Blindness: An International Perspective 5
In keeping with the recommendations of the WHO, the This implies a serious handicap in education, social
National Program for Control of Blindness in India used a interaction and personality development. The inability to
different set of criteria to define blindness. The comparison count fingers at a distance of 3 meters (with the better
of the WHO and NPCB criteria is indicated in Table 1.3. eye) with best correction is used to define social blindness.
• In recent years, NPCB is not referring to manifest and For all international comparisons, this is the cut off value
absolute blindness but categorizing the same as social that is generally used. Since this level of visual impairment
blindness. curtails the day to day movement of an individual it is
also referred to as WALK VISION.
Terms Used to Define Blindness • Manifest blindness: This definition was used a few decades
• Economic blindness: This denotes the level of blindness that ago in India. A visual acuity of 1/60 in the better eye is
prevents an individual from earning his wages. The inability used for categorizing manifest blindness. This degree of
to count fingers from a distance of six meters with the disability seriously constraints the accomplishment of tasks
better eye, with the best possible correction, denotes for daily living. It also impairs mobility.
economic blindness (Fig. 1.1). If best correction is not • Absolute blindness: The inability to perceive light in any eye
provided, presenting vision (vision as a person presents denotes the stage of absolute blindness. In a significant
at an examination site, i.e. if somebody is wearing glasses, proportion, irreversible damage has already occurred.
the person is tested with glasses, otherwise testing is done • Curable blindness: This denotes that stage of blindness (which
without glasses) is considered in defining blindness. In is mostly related to a lack of an effective service delivery
India, presenting vision < 6/60 in the better eye is defined network) where the damage is reversible by prompt
as blindness, though the WHO categorizes this as severe management. Cataract is an apt example of curable
visual impairment. Since this level of visual impairment blindness.
hinders a person from earning, it is also referred to as • Preventable blindness: This denotes the loss of blindness that
WORK VISION. could have been completely prevented by institution of
• Legal blindness: This denotes the level of blindness that effective preventive or prophylactic measures.
necessitates welfare measures and legal protection. Vision Xerophthalmia, trachoma and glaucoma are prime
≤ 6/60 or 20/200 in the better eye, with correction, and/ examples of preventable blindness.
or a visual field less than 10° centrally constitutes legal • Avoidable blindness: The sum total of preventable or curable
blindness (Fig. 1.1). This definition is used in the USA blindness is often referred to as avoidable blindness. In
since 1944. If the central visual acuity is better than 6/ developing countries like India, 85 to 90 percent of all
60 or 20/200 but the field of vision is impaired to < 10 blindness is avoidable.
degrees, the individual is still labeled as blind. • Incurable blindness: This denotes the state of blindness, which
• Social blindness: This denotes the degree of disability that is beyond redemption. Absolute blindness or terminal
hampers an individual from socially interacting with the blindness denotes a similar configuration. Five to ten
family and peer groups in a satisfactory manner (Fig. 1.1). percent of blindness can be categorized as incurable.
Fig. 1.1: Commonly used definitions of blindness

Table 1.4: Global estimate of visual impairment by WHO subregion, 2002*

WHO sub-region Total population No. of blind Prevalence of No. of people Prevalence of No. of persons
(millions) people (millions) blindness (%) with low vision low vision visually impaired
(millions) (%) (millions)
Afr (D, E) 715,289 7,288 1.0 21,288 3.0 28,576
Amr (A, B, D) 852,551 2,418 0.2-0.5 13,117 1.2-2.0 15,535
Emr (B,D) 286,933 2,482 0.8-0.97 7,696 2.5-2.9 10,178
Eur (A, B1, B2, C) 877,886 2,732 0.2-0.4 1,279 1.1-1.8 15,521
Sear (B,D) 1799,358 12,558 0.6-1.0 38,108 2.0-2.4 50,665
Wpr (A, B1, B2, B3) 1681,851 9,378 0.3-0.8 31,268 1.2-1.9 40,646
World 6213,869 36,857 0.57 124,264 2.0 161,121
Afr, WHO African Region; Amr, WHO region of the Americas, Emr, WHO Eastern Mediterranean Region, Eur, WHO European Region, Sear
WHO South-East Asia Region, Wpr, WHO Western Pacific Region. (India, Nepal, Bangladesh and Pakistan are included in the sub-region
Sear D while China and Mongolia is included in Wpr B1)
*Visual impairment defined as in the ICD-10:H54 table refers to visual acuity in the better eye with best possible correction (WHO.
International classification of diseases, injuries and causes of death, tenth revision, Geneva: WHO; 1993)
Adapted with permission from the World Health Organization (All rights reserved) from Global data on visual impairment in the year
2002, Resnikoff S, et al, Bulletin of WHO 2004; 82(11): 844-51, Table 3, Copyright notice, April 2011)
Global Trends in Blindness immunization, vitamin A supplementation, improved dietaries

and improvements in environmental and personal hygiene.
In 1995, it was observed that 60 percent of all blindness was
These measures have contributed to reduce the magnitude
concentrated in India, China and countries in the African
of childhood onset blinding conditions.
continent.6 If the Eastern Mediterranean Region and other
countries in South East Asia Region were to be added, then It is anticipated that by 2025 AD, among population aged
70 percent of the global magnitude of blindness is harbored 55 years on more, blindness would increase by 4.1 times;
by these countries alone (Table 1.4).3 If the number of blind accurate projections regarding the future blindness scenario
were to be considered then this would amount to 85 percent are difficult, because of unknown variables in population
of the global burden of blindness.3 Trends in global blindness growth, life expectancy and the development of eye care
indicate that over the period 1990 to 2002, there was an services. However, if a concerted action is not initiated, the
increase of 8.5 percent in the number of people blind in the blindness load in the world will double by 2020 AD.7
developed countries. During the same period the increase in
the number of blind was 3 percent in the developing countries
(excluding India and China). In China, an increase of 3 percent
was observed while in India a decrease of 25 percent was
observed. 3 These statistics reveal that increase in life
expectancy is a major driving force for increase in blindness
magnitude but a significant proportion of the impact of
increased life expectancy can be offset by augmented eye
care services as has been the case in India.
Data on the incidence of blindness are only available
from a few countries in the developed world and using this
data, it has been extrapolated that at least 7 million people
become blind each year and the number of blind is increasing
at the rate of 1 to 2 million each year globally.6
Global trends also indicate that more than 82 percent of
all blindness is seen among those aged ≥ 50 years of age
(Fig. 1.2).3 Nutritional and infective causes of blindness have
steadily decreased over the years due to effective
implementation of primary health care strategies like Fig. 1.2: Number of blind globally (millions)
Fig. 1.3: Global causes of blindness as a percentage of total blindness (2004)

Reproduced with permission from the World Health Organization (All rights reserved) from Global magnitude of visual impairment caused
by uncorrected refractive errors in 2004, Resnikoff S, et al, Bulletin of WHO 2008; 86 (1):63-70, Fig 1, Copyright notice, April, 2011)
Global Causes of Blindness
Earlier data from WHO did not include uncorrected

refractive errors as a cause of blindness as the definition of
blindness was based on best corrected vision. With the change
of the definition by WHO to define blindness using presenting
vision, uncorrected refractive errors can now be differentiated
as an independent cause of blindness and visual impairment.
Data available from WHO for 2004 show that cataract is
responsible for 39 percent of global blindness while
uncorrected refractive errors are responsible for nearly a
fifth of all blindness (Fig. 1.3).
The major causes of blindness vary from region to region,
and are determined to a great extent by the level of
development of health services in the country, and the
economic status and lifestyles of populations (Fig. 1.4). Fig. 1.4: Determinants of blindness
Infective and nutritional causes of blindness still constitute
important entities in most developing countries, along with Four of every ten blind individuals globally are blind
cataract, while in the developed countries, age-related macular because of cataract. The estimated figures of glaucoma tend
degeneration, diabetic retinopathy, glaucoma and cataract are to be an underestimate as most surveys only measure visual
important causes of blindness (Table 1.5). acuity and do not include an assessment of the visual fields.
Table 1.5: Major causes of blindness in India

Cause ICMR (1976) % NPCB-WHO (1986) % NPCB (1999-2001) % NPCB (2006-2007) %
Cataract 55.0 80.9 62.4 77.5
Trachoma 5.0 0.39 0.3
Small pox 3.0
Other infections 18.0
Vitamin A deficiency 2.0 0.02
Injuries 1.5
Glaucoma 0.5 1.7 5.8 3.0
Uncorrected refractive errors 7.35 19.6 3.4
Aphakia 4.69 4.6
Central corneal opacification 1.52 0.9 3.6
Posterior segment 4.7 2.8
Other causes 16.0 4.25 6.5 4.8
Based on the blindness prevalence rates, countries can be merits attention because of the number of years that these
broadly categorized into the following three groups:7 children have to live in blindness.8 The proportion of avoidable
1. Countries with blindness prevalence in the general blindness among children is less than 50 percent compared
population of greater than 1 percent; in some countries, to > 80 percent among adults. Increasing life expectancy and
the prevalence may be as high as 3 to 7 percent. In these the control of preventive causes of blindness leads to a larger
countries, which are mostly in the African continent and number of people entering the 'risk age' for conditions like
Asia, trachoma, xerophthalmia, onchocerciasis, cataract and cataract, glaucoma, diabetic retinopathy and age related
ocular injuries are common. macular degeneration.
2. Countries with a blindness prevalence rate of 0.4 to 0.65 Gender: Data from all regions of the world indicate that
percent; these are countries in the intermediate stage of females have a higher prevalence of blindness and visual
development where most infective causes are under impairment compared to males.8 This could be due to a
control, but the eye-care services are not well developed. number of factors:
The critical factor responsible for high prevalence is • Higher life expectancy among females compared to males.
untreated cataract and undetected glaucoma. • Poorer awareness and access to services, especially cataract
3. Countries with blindness prevalence rate varying surgery.
between 0.15 to 0.25 percent in the general population. • Social discrimination prevalent in some countries.
These countries have advanced medical services coupled
Socioeconomic status: Ninety percent of the global blind and
with a near elimination of nutritional and infective
visually impaired live in poorer regions of the world. Proxy
conditions. Age related macular degeneration, diabetic
indicators for socioeconomic development like literacy also
retinopathy and glaucoma are the most important
indicate that the prevalence is much higher among the illiterate
conditions in this group of countries in North America,
and less literate compared to those who have attained a higher
Europe, Australasia and the rich countries in the Asia
level of literacy.
Pacific region like Japan.
A lot of evidence is available from published literature
on causes like smoking, exposure to ultraviolet radiation,
Common Risk Factors for Blindness
diabetes, use of medications like long-term steroids and body
Age: One of the strongest determinants of blindness is age. mass index (BMI) being associated with blindness. The
Increasing age is associated with a higher prevalence of attributable risk of each of these factors is difficult to state
blindness. WHO data reveals that > 80 percent of global equivocally. Therefore, it is difficult to plan any prevention
blindness is seen among those aged ≥ 50 years of age though programs or interventions based on the available evidence.
this age group globally constitutes around a fifth of the total The data on the risk factors can at best be used to prioritize
population. Though the prevalence of blindness among adults the populations that need more attention compared to the
is 10 times higher than in children, childhood blindness still others.
Table 1.6: Profile of blindness in India

Source of Data Age Group Definition % Blind
10
1921 Census All - 0.17
Bhore Committee (1984) 10 All - 0.5
Trachoma Pilot Project (1956)11 All < 2/60 in better eye 1.0
ICMR (1971-1973)12 All < 6/60 in better eye 1.3
National Sample Survey (1982)10 All < 3/60 in better eye -
WHO-NPCB survey (1986-89)13 All < 6/60 in better eye 1.49
AP Eye Diseases Survey All < 6/60 better eye + Visual field < 200 1.84%
(1998-1999)14
Rapid Assessment in 7 World Bank 50+ < 6/60 in better eye 11.84%
assisted States (1998) 15
Bharatpur (Rajasthan) Survey (1999) 16 50+ < 6/60 in better eye 12.2%
Sivaganga(Tamilnadu) Survey (1999) 17 50+ < 6/60 in better eye 6.4%
NPCB Survey in 15 States18 50+ < 6/60 in better eye 8.5%
Aravind Comprehensive Eye Survey19 40+ < 6/60 in better eye 11.4%
NPCB Rapid Assessment of Avoidable 50+ < 6/60 better eye 8.0%
Blindness (15 States) 2006-200720
Environment: The environment has been incriminated in many eye health illiteracy is a major factor leading to an accumulation
blinding conditions. The decline of blinding trachoma is directly of unoperated and inoperable cases in the community. In
related to improved environmental sanitation and personal India, cataract is common at 50 to 60 years of age, and most
hygiene practices rather than to the availability of effective of these patients could do normal work if their vision was
antibiotics. The availability of sufficient quantities of safe restored.
water and sanitary disposal of excreta and garbage, coupled
with facial hygiene practices has led to a significant decline Residence: The prevalence of blindness in general is known to
of trachoma-related blindness in India. be highest in rural and remote areas all over the world. Similar
In relation to blinding malnutrition, environmental factors trends are observed in India also. The 1986-89 WHO-NPCB
like adequacy of rainfall or adverse climatic conditions, the survey revealed a significant rural-urban differential. The rural
cropping pattern and other related factors have all exerted areas had an overall prevalence of 1.63 percent as against a
important influences. prevalence of 1.01 percent in the urban areas.
Cataract is hypothesized to be related to environmental
insults. Ultraviolet radiation, altitude, cloud cover, etc. are all The National Scenario
associated with cataract. The first systematic enumeration of blindness in India was
Ocular trauma is strongly determined by the physical undertaken in the 1921 census (Table 1.6). The decadal
factors in the environment at the workplace. national census indicated a blindness prevalence rate of 172/
Human behavior and lifestyle are closely associated with 100,000 population. Later, in 1944, the Health Survey and
blinding consequences of diabetic retinopathy, glaucoma, Development Committee under the chairmanship of Sir
cataract and ocular leprosy. In many cases, surgical phobia or Joseph Bhore estimated that the prevalence had increased to
lack of perception regarding severity of ocular conditions 500/100,000 population.10
leads to blinding consequences. Early studies have documented In 1956, a survey for enumerating the magnitude of
that less than 20 percent of patients advised cataract surgery blindness was undertaken as part of the trachoma pilot project.
actually use a surgical facility in India.9 This survey indicated that the prevalence had increased to
Though the cataract surgical services are inadequate in 1000/100,000 population.11
rural areas, it is also seen that a provided facility is not optimally The Indian Council of Medical Research undertook a
utilized on many occasions. This is mostly due to a lack of blindness survey in selected areas of the country over a
awareness regarding the benefits of surgery in cataract, or 2-year period from 1971 to 1973. By this time, the prevalence
the paucity of information on the available facilities. Thus had further increased to 1300/100,000 population.12
A comprehensive nationwide survey was undertaken under static at 1.2 million for many years. By 1992, 1.8 million
the National Program for Control of Blindness in surgeries were being performed annually in the country. The
collaboration with the World Health Organization over the initiation of the World Bank Cataract Blindness Control
period 1986-1989.13 In spite of an improved service delivery Project in 1994 led to a dramatic increase in the number of
network, the prevalence of blindness further increased to cataract surgeries reported in the country every year. By 1997,
1490/100,000 population. The period 1920-1990 has been 2.4 million surgeries were being performed and the 5 million
marked with increasing life expectancy of the Indian mark was first breached over the period April 2006-March
population. The increase in the prevalence of blindness 2007. During the last financial year (2007-2008), 5.4 million
paralleled the increase in life expectancy. cataract surgeries were performed in India.21 India has one
The prevalence of blindness in all these surveys in India of the highest cataract surgical rates in the world, next only
was based on presenting vision and not on best corrected to developed countries in Europe and North America.
vision.
An analysis of the major causes of blindness enumerated National Program for Control of Blindness
during the nationwide surveys of 1971-74 and 1986-89 reveal
Efforts for controlling blindness existed in India for a long
a changing profile over the years.13 A steady decline in the
time before our independence. These efforts were limited
infective and nutritional causes of blindness was the major
to the non-governmental organizations (NGO) and local
gains of the national efforts for control of blindness.
philanthropists, and were basically piecemeal and scattered
An analysis of trends in magnitude and causes of blindness
activities. There was no organized governmental action at the
in India over the past three decades reveals that there is a
time of independence.
significant reduction in blindness in children and that due to
Looking at the magnitude and the consequences of
nutritional and infective conditions. NPCB data show that
blindness, the Indian Council of Medical Research (ICMR)
blindness seemed to have peaked around 2000. Surveys in
undertook a trachoma control pilot project in 1956.11 At that
2001 and 2007 showed that the prevalence of blindness has
time infective causes of blindness were the predominant entity
been reducing consistently over the last decade. This seems
in the country. The success of the pilot project prompted the
to be matched by the increase in access to cataract surgery all
Government of India to launch the first organized effort for
over the country. The cataract surgical rate has increased
the control of blindness. Thus, the National Trachoma Control
dramatically over the past decade and this has had a major
Program was initiated in 1963.11 The program encompassed
impact on the prevalence of blindness in the country. The
3530 blocks in 293 districts, and covered a population of
cataract surgical rate is defined as the number of cataract
400 million.
surgeries per million population per year and is a useful
The ICMR conducted a survey during the period
indicator for monitoring the progress of a cataract blindness
1971-7412 to evaluate the magnitude of blindness in the
control program (Fig. 1.5). The total number of cataract
country. In 1975, the Central Council for Health and Family
surgeries in India was around 0.5 million in 1981 and this
increased to 1.2 million by 1987. The performance remained Welfare deliberated the trends and recommended the
launching of a comprehensive program.22 The following
strategy was recommended:
• Dissemination of information about eye care through all
media of mass communication with particular emphasis
in ocular health in children and all other vulnerable groups.
• Orientation of teachers, social workers and students to
the problem of eye health care, including nutritional
deficiencies.
• Augmentation of ophthalmic services in a manner such
that relief can be given to the community in the shortest
possible time.
• Simultaneous establishment of a permanent infrastructure
for community oriented eye health care.
Consequent to the recommendations of the Central
Fig. 1.5: Cataract surgical rates in India Council, the National Program for Control of Blindness and
Prevention of Visual Impairment was launched in 1976. The World Bank Assisted Cataract
earlier National Trachoma Control Program was merged into Blindness Control Program
the new comprehensive program. The program was later
renamed as the National Program for Control of Blindness The National Survey of Blindness and Visual Impairment
(NPCB). was conducted over a 3 year period (1986-89).13 This survey
National Program for Control of Blindness (NPCB) was revealed that the prevalence of blindness in the general
launched as a 100 percent centrally sponsored program with population was 1.49 percent and cataract was responsible for
the goal of reducing the prevalence of blindness from 1.4 80 percent of blindness. The Government of India realized
percent to 0.3 percent of population. During the period urgency to tackle the problem of cataract blindness and
1976-1989, main focus of the program was to upgrade existing approached the World Bank for additional resources.
infrastructure for eye care. This led to establishment of After numerous consultations and appraisals, a soft credit
Regional Institutes of Ophthalmology, upgradation of medical of US$ 117.8 million was agreed by IDA of the World Bank
colleges and district hospitals, development of mobile eye to control cataract blindness in India. It was first major credit
units and upgrading selected Primary Health Centers by posting agreed by the World Bank on controlling blindness. The World
ophthalmic assistants. The program did not receive high Bank assisted Cataract Blindness Control Project was thus
priority as compared to other National Health Programs. launched in 1994 to reduce the prevalence of blindness. This
Budget allocated for the program was very inadequate. seven year project was initiated in 7 States, namely Andhra
The overall objectives of the NPCB launched in 1976 Pradesh, Madhya Pradesh, Maharashtra, Orissa, Rajasthan,
were:22 Tamilnadu and Uttar Pradesh, where prevalence of blindness
• Provision of comprehensive eye care facilities at the was observed to be higher than the national average of 1.49
primary, secondary and tertiary levels of health care. percent. The project was to end on 30th June 2001 but was
• Substantial reduction in the prevalence of eye diseases in extended by one year up to 30th June 2002 to complete the
general and a reduction in the prevalence of blindness unfinished tasks.
from 1.4 to 0.3 percent by 2000 AD. The project aimed at development of a sustainable eye
All the strategies adopted under the NPCB were geared care infrastructure and systems for eye care service delivery
to meet these objectives. that would reduce the backlog of cataract blind persons and
The major component activities planned included: lay foundation for a need based and accessible eye care
• Intensification of education efforts on eye health care services to prevent and control cataract blindness in India.
through mass communication media and extension Specific objectives of the project were:
education methods. • Upgrade the quality of cataract surgery.
• Extension of eye care facilities through units, to restore • Expand coverage to underprivileged areas.
sight and to relieve eye ailments, by adopting an eye camp • Reduce the backlog of untreated cataracts to lower the
approach and by enlisting the participation of NGOs. prevalence cataract blindness by more than 50 percent
• Establishment of permanent facilities for eye health care by performing 11.03 million cataract operations.
as an integral part of the general health services at • Develop human resources and institutional capacity for
peripheral, intermediate and central levels. The peripheral eye care particularly training of ophthalmologists in extra
sector focuses on primary eye care activities at Primary capsular cataract extraction (ECCE with IOL) surgery.
Health Centers and Sub-centers, while the intermediate • Promote outreach activities/public awareness.
sector activities include development of diagnostic and • Establishment of District Blindness Control Societies
treatment facilities at district and sub-district levels. The (DBCS) in all districts.
development of sub-specialties, basic and applied research, • Create an enabling environment for involving NGOs and
and manpower development are a prerogative of the private sector in eye care delivery.
central sector. • Develop mechanisms for cost recovery to sustain the
Performance of cataract surgery was the main activity. project activities beyond the project period.
However, rate of cataract surgery was not sufficient to tackle In order to achieve the above-mentioned objectives,
huge backlog of bilaterally blind persons due to cataract. following strategies were adopted to control cataract blindness
Average annual performance was 1.1 to 1.2 million operations in the Project States:
against an estimated incidence of 2 million new cataract cases • Reduction in the backlog of bilaterally cataract blind
every year.22 persons through reach-out and reach-in approach.
• Introduction and expansion of IOL surgery through The main targets for the plan include:
training of eye surgeons, supply of equipments required • Performing more than three crore cataract surgeries of
for IOL surgery and supply of consumables. which more than 95 percent would be with an IOL
• Development of eye, care infrastructure through construction implant.
of eye wards and dedicated eye operation theaters, • Providing 15 lakh free spectacles to children under the
nonrecurring grants to NGOs to set-up or expand eye school eye screening program.
care units in underserved areas. • Collection of 2.5 lakh donated eyes.
• Improvement in quality of eye care through training of • Training 2000 eye surgeons in modern cataract surgery
personnel, supply of high quality equipments, provision and other procedures.
for maintenance of equipments and strengthening • Setting up 3000 vision centers in the country.
monitoring of quality of care and follow-up. • Develop 30 eye banks and 120 eye donation centers.
• Construction of 75 dedicated eye wards and dedicated
XI Plan Initiatives OTs in North East and other poorly served States.
For the XI five year plan period (2008-2012), the National • Development of 75 new mobile ophthalmic units for the
Program for Control of Blindness envisages the following North East and poorly served States.
strategies:23 • A total of 20 Regional Institutes of Ophthalmology to
• Decentralized implementation of the scheme through be functioning by end of the 11th plan.
District Health Societies (NPCB); Grant-in-aid for NGO institutions for performing cataract
• Reduction in the backlog of blind persons by active surgery has been revised and for the first time grants are also
screening of population above 50 years, organizing provided to cover other surgical procedures than just cataract
screening eye camps and transporting operable cases to surgery.
eye care facilities; The revised norms include:
• Involvement of voluntary organization in various eye care • Rs 1000 per pair of eyes collected for corneal transplants.
activities; • Reimbursement of Rs 750 for each surgery for cataract.
• Participation of community and panchayat raj institutions • Reimbursement of Rs 1000 for glaucoma, vitreo-retinal
in organizing services in rural areas; surgery, laser for diabetic retinopathy, childhood blindness
• Development of eye care services and improvement in and corneal transplantation.23
quality of eye care by training of personnel, supply of
high-tech ophthalmic equipments, strengthening follow-
VISION 2020
up services and regular monitoring of services;
• Screening of school age group children for identification Despite the best of efforts during the last fifty years, the
and treatment of refractive errors, with special attention burden of blindness in the world is increasing because of
in underserved areas; lack of access to eye care services, population growth and
• Public awareness about prevention and timely treatment aging. If additional resources are not urgently tapped and
of eye ailments; efforts made to control this scourge of mankind, the global
• Special focus on illiterate women in rural areas; burden of blindness can double by the year 2020.
• To make eye care comprehensive, besides cataract surgery, Avoidable blindness is blindness resulting either from
provision of assistance for other eye diseases like diabetic conditions that could have been prevented or controlled, or
retinopathy, glaucoma management, laser techniques, which can be successfully treated. Example of the former is
corneal transplantation, vitreoretinal surgery, treatment trachoma and the latter is sight restoration after cataract
of childhood blindness, etc.; surgery. Fortunately, 80 percent of the global blindness is
• Construction of dedicated eye wards and eye OTs in avoidable.
district hospitals in North-East (NE) States and few other
states as per need; VISION 2020: The right to sight is the common agenda
• Development of mobile ophthalmic units in NE States launched by the World Health Organization and a task force
and other hilly states linked with tele-ophthalmic network of International Nongovernmental Organizations to combat
and few fixed models; this gigantic problem. It is a partnership between all
• Involvement of private practitioners in sub-district, blocks international, nongovernmental and private organizations that
and village levels. collaborate with the WHO in the prevention of blindness.
VISION 2020, the Right to Sight is a global initiative to VISION 2020 will be implemented through 4 five-year
eliminate avoidable blindness. The program is a partnership plans, the first one starting in 2000. The three following phases
between the World Health Organization (WHO), and the will commence in 2005, 2010 and 2015 respectively. Priority
International Agency for Prevention of Blindness (IAPB), a is being given to advocacy, regional planning and resource
large umbrella organization for eye-care professional groups mobilization. A global plan is important for the following
and Nongovernmental Organizations (NGOs) involved in reasons:
eye-care. • Allows priorities to be defined as appropriate effective
VISION 2020 was officially launched by the WHO in and efficient strategies to be determined and then
1999. India is also a signatory to this historic development. implemented, including appropriate long-term strategies.
The WHO provides technical cooperation to member • Can be used for advocacy and resource mobilization.
countries to either launch or redefine existing national • Facilitates coordination and development of work by the
programs for control of blindness to meet the goals set out different partners involved in prevention of blindness.
in the mandate. • Encourages building new partnerships between the
involved agencies.
Goal: The aim of VISION 2020 is to eliminate avoidable • Allows evaluation of activities in order to learn from
blindness worldwide by the year 2020.24 experience.
The founding members of VISION 2020 include: The selection of the countries where VISION 2020 will
• World Health Organization be implemented is to be regionally prioritized on the basis of
• International Agency for the Prevention of Blindness the burden of blindness and available resources. Each country
• Christoffel-Blindenmission (Christian Blind Mission is preparing a plan of action for meeting the goals of Vision
International) 2020.
• Helen Keller International When VISION 2020 was launched in 1999, five conditions
• ORBIS International were identified for priority action globally. Regions or countries
The other supporting members include: were free to add other conditions which may be relevant to
• Al Noor Foundation their context. The five conditions for global action were:
• American Academy of Ophthalmology • Cataract
• Asian Foundation for the Prevention of Blindness • Refractive errors/low vision
• Canadian National Institute for the Blind • Trachoma
• Foundation Dark and Light • Onchocerciasis
• Fred Hollows Foundation • Vitamin A deficiency related and other causes of childhood
• International Center for Eye Care Education blindness.
• International Eye Foundation Available data indicated that 75 percent of the global
• Lighthouse International burden of blindness was due to these causes. Another reason
• Nadi Al Bassar for identifying these conditions was that cost effective
• Operation Eyesight Universal interventions were available for these conditions.24
• Organization pour la Prevention de la Cecite It was envisaged that if no action was taken, global
• Perkins School for the Blind blindness would double from 38 million in 1995 to 76 million
in 2020.19 Augmented activities under the aegis of VISION
• Seva Foundation
2020 would halt this process and be successful in halving the
• SIMAVI
load of blindness by 2020. It was therefore necessary to
• World Blind Union.
tackle the load of avoidable blindness as interventions existed
VISION 2020 will serve as a common platform to which could make a difference.
facilitate a focused and coordinated functioning of all the
partners in eliminating avoidable blindness by 2020. It will Objectives
further develop and strengthen the primary health/eye care The objectives of VISION 2020 are:24
approach to the problem of avoidable blindness. Broad • To raise the profile among key stake holders of the causes
regional alliances will be sought to eventually develop a global of avoidable blindness and of the solutions that will help
partnership for eye health. eliminate the problem.
• Identify and secure the necessary resources around the • Measures to overcome barriers and increase the use of
world in order to provide an increased level of activity in services.
prevention and treatment programs.
• Facilitate the planning, development and implementation Trachoma
of three elements of the VISION 2020 strategic plan by
The aim is to eliminate blindness due to trachoma. Trachoma
national programs.
remains the most common preventable cause of blindness in
Core Elements the world with an estimated 5.9 million blind, visually impaired
or at immediate risk of blindness from the disease, and a
There are three core elements of VISION 2020.24 These further 146 million cases of active trachoma in need of
are: treatment. Approximately 10.6 million adults with inturned
1. Cost effective disease control strategies. eyelashes (trichiasis/entropion) for which eyelid surgery is
2. Human resource development for eye care. needed to prevent blindness. Trachoma is common in areas
3. Infrastructure development (including appropriate of the world that are socioeconomically deprived of basic
technology). needs in housing, health, water and sanitation.
VISION 2020 strives for equity and excellence in eye The "SAFE" strategy has been developed and is being
care through development of a system which is sustainable applied in affected areas. "SAFE" is the acronym for Surgery,
and integrated into the existing health care systems of Antibiotic, Facial cleanliness, and Environmental improve-
individual countries. VISION 2020 does not mean a parallel ment. It is expected that through the use of the SAFE strategy,
system but is meant to strengthen the existing eye care systems it will be possible to eliminate trachoma as a blinding disease
in each country. by the year 2020.
Five million trichiasis surgeries will be provided between
Targets for Disease Specific Strategies 2000 and 2010. In addition, at least 60 million people with
Specific targets were set out for each of the five diseases active disease would receive treatment in the same period.
targeted for priority action.
Onchocerciasis
Cataract The aim is the elimination of blindness due to onchocerciasis.
VISION 2020 sets out to eliminate avoidable blindness due The disease is endemic in 30 countries of Africa and some
to cataract by 2020. The cataract specific targets are depicted foci in six countries of Latin America. Among these,
in Table 1.7. approximately 300,000 to 600,000 people are already blind
VISION 2020 strategies emphasize that with regard to from the disease. The recently developed and introduced
cataract surgery the following are essential: community-directed treatment with annual doses of
• High success rates in terms of restored vision and quality- ivermectin would make it possible to eliminate this blinding
of-life outcomes; disease. The disease is expected to be brought under control
• Affordable and accessible services, especially for under- by the year 2010 if present efforts in endemic countries are
served populations; successfully completed.6
Table 1.7: Global cataract prevalence targets and cataract surgical rates target 1995-2020
Year Target for CSR per Global number of cataract Target
million population surgeries (millions) No. cataract blind (millions) Prevalence cataract blindness
(%)
1995 1100 7.0 20.0 0.35
2000 2000 12.0 15.0 0.25
2010 3000 20.0 7.0 0.1
2020 4000 32.0 0 0
Adapted with permission from the World Health Organization (All rights reserved) from WHO/PBL/ 97.61 Rev 1, Global Initiative for
the elimination of avoidable blindness, Section 2, Outline of main activities within a global initiative for the elimination of avoidable
blindness, tables on Global cataract prevalence targets 1990-2020 and Global cataract surgical rates targets 1995-2020, WHO,
1997, p 10-11.
Childhood Blindness causes of low vision.6 The aim goes beyond the elimination
of blindness and also includes the provision of services for
The aim is to eliminate avoidable causes of childhood blindness.
individuals with low vision. It is estimated that there are 35
The main causes of childhood blindness are vitamin A
million people in the world who need low-vision care. Efforts
deficiency, measles, and conjunctivitis of the newborn,
will be made to make refractive services and corrective
congenital cataract and retinopathy of prematurity (ROP).
spectacles affordable and available to the majority of the
The strategy to combat childhood blindness includes
population through primary health care facilities, vision
strengthening of primary eye care programs within primary
screening in schools and low-cost production of spectacles.
health care, developing therapeutic and surgical support
The steps in the provision of refraction services and low
services to deal effectively with curable eye conditions, and
vision care include:
establishing optical and low vision services.
• Screening
Childhood blindness is considered a priority area, because
• Refraction
of the number of years of blindness that ensues. There are
• Manufacture of spectacles
an estimated 1.5 million blind children in the world, of whom
• Dispensing spectacles
1 million live in Asia and around 300,000 in Africa. The
prevalence is 0.5-1 per 1000 children aged 0 to 15 years. • Follow-up for repair of spectacles or devices and repeat
Each year, an estimated half a million children go blind, of dispensing.
whom up to 60 percent die in childhood.6 The strategies identified include:
VISION 2020 envisages the following strategy: • Create awareness and demand for refractive services
• Strengthening primary eye care programs within primary through community based services/primary eye care and
health care to eliminate preventable causes. school screening.
• Developing therapeutic and surgical support services to • Develop accessible refractive services for individuals
deal effectively with "curable" eye problems. identified with significant refractive error.
• Establishing optical and low vision services. • Ensure optical services and provide affordable spectacles
The activities include: for individuals with significant refractive errors.
• Measles immunization. • Develop and make available low vision services and
• Vitamin A supplementation. optical devices for all those in need.
• Nutrition education. • Include provision of low vision care as an integral part
• Avoidance of harmful traditional practices. of national programs for the prevention of blindness or
• Monitoring of use of oxygen in newborns. rehabilitative services for the visually disabled.
• Provide specialist training and services for management
of surgically remediable visual loss in children from Human Resources
congenital cataract, congenital glaucoma, corneal scar and
retinopathy of prematurity. The elimination of avoidable blindness needs the creation
• Develop low vision services for visually handicapped and deployment of a pool of committed and motivated
children. personnel. Therefore VISION 2020 set out targets for the
• Promote school screening programs for the diagnosis and requisite human resources for VISION 2020 on a global
management of common conditions like refractive errors level.6 Human resources would be needed at all levels of
(especially myopia) and trachoma in endemic areas. service delivery—Primary, secondary and tertiary. Primary
• Promote eye health education in schools. eye care will be integrated with Primary Health Care and no
• Ensure examination of all children admitted in blind separate primary eye care worker was envisaged.
schools by an ophthalmologist and receive medical, For ophthalmologists, a ratio of 1:250000 in Africa was
surgical, and optical or vision service to maximize potential envisaged from the present 1:500,000 level by the year 2020.
vision. The corresponding level for Asia would be 1:50000 by 2020
The control of xerophthalmia is expected to be achieved from the present level of 1:200,000.
through the Global Child Survival Program. For mid-level personnel (ophthalmic medical assistants
and ophthalmic nurses), the aim was to achieve a ratio of
Refractive Errors and Low Vision 1:100,000 from a current of 1: 400,000 in Sub Sahara Africa
The aim is to eliminate visual impairment (vision < 6/18 in by the year 2020, as compared to 1:50,000 from a current
the better eye) and blindness due to refractive errors or other level of 1:200,000 in Asia.
For refractionists, a ratio of 1: 50,000 population was During the 11th five year plan (2008-2013), the
recommended by 2020 from a current level of 1:250,000. Government of India has set out to achieve the goal of
In addition to the above categories, it was also VISION 2020 and has set out the following objectives for
recommended that a separate cadre of eye care managers/ the next five years:
hospital managers should be identified and appropriate courses • To reduce the backlog of blindness.
need to be designed to meet this need. Similarly it was • To develop comprehensive eye care facilities in all districts
proposed that equipment technicians should also be trained in the country.
to meet the needs of VISION 2020.8 • To develop human resources for providing eye care
services.
VISION 2020: NATIONAL PERSPECTIVE • To improve quality of service delivery.
• To secure participation of NGOs/private practitioners
VISION 2020 was launched by the Government of India in
in the national program.
2001. The Government of India identified the following
• To enhance community awareness of eye care.
conditions for VISION 2020 in India:25
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Table 1.8: Government of India targets for infrastructure for VISION 2020 in India
Current status Goals
2005 2010 2015 2020
Centers of excellence 5 (of varying capacity) 10 15 20 20
Training centers 50 (of reasonable standards) 75 125 150 200
Pediatric ophthalmology units in training centers 10 50 100 150 200
Low vision units in training center 10 50 100 150 200
Eye banks each attached with 20 eye donation centers 15 (of reasonable standards) 25 50 75 100
Service centers 500 750 1000 1500 2000
Vision centers at primary level 5000 10,000 15,000 20,000 20,000
Table 1.9: Proposed human resources for achieving goals of VISION 2020 in India
Category Current 2005 2010 2015 2020 Average output per annum
Ophthalmologists 10,000 13,000 17,000 21,000 25,000 1,200
Ophthalmologist technicians 8,000 12,000 25,000 40,000 60,000 4,500
Eye care managers Negligible 500 1,000 1,500 2,000 100
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908-16. 24. WHO. State of the World's sight. VISION 2020: The Right to
15. Bachani D, Murthy GVS, Gupta SK. Rapid Assessment of cataract Sight: 1999-2005. WHO Geneva, 2005.
blindness in India. Indian J Public Health 2000;44:82-9. 25. Government of India. National Plan for Vision 2020 in India.
16. Murthy GV, Gupta S, Ellwein LB, Munoz SR, Bachani D, Dada
National Program for Control of Blindness, Directorate General
VK. A population based eye survey of older adults in a rural
Health Services, Nirman Bhavan, New Delhi, 2003.
district of Rajasthan: I. Central vision impairment, blindness, and
cataract surgery. Ophthalmology 2001;108:679-85.
Chapter 2.1
LIGHT AND ITS PROPERTIES
Zia Chaudhuri
Light is fundamental to the concept of vision. It is a physical Visible light from the sun is made up of wavelengths of
attribute of the environment in which we live. It may be light from 400 to 780 nm. Each wavelength represent
defined as energy to which the eye (human or animal) is different colors of visible spectrum commonly known as
sensitive in an attempt to delineate and perceive different VIBGYOR, which is short for colors defined as violet, indigo,
objects around us. In physics, it is defined as radiation of a blue, green, yellow, orange and red. Color is determined by
wavelength that is visible to the human eye. The true nature the frequency of light. Frequency is inversely related to its
of light remains unknown but its properties have been wavelength. When there is movement of these components
extensively studied. of light at very high speed, the human brain is not able to
perceive them in their decomposed for m. Thus the
PROPERTIES OF LIGHT combination is perceived as white light. When white light is
Light is a form of electromagnetic energy. Basic physics decomposed, say with the help of prisms, the component
propagates two main theories which explain the properties colors can be made out clearly. Again, it is important to realize
of light or any other electromagnetic wave. These are: that if two prisms, equal in their powers but kept opposite to
1. The quantum form of electromagnetic energy theory: each other are placed together, the decomposed components
This theory states that light is constituted by particles of of white light, again deflect back and what comes out of the
energy called photons. combination is white light (Fig. 2.1.1). This will be discussed
2. The wave form theory: This theory states that light in a subsequent section (dispersion).
constitutes wave forms that radiate energy in concentric The electromagnetic spectrum extends much beyond the
fashion. visible range with wavelengths extending from 10-6 (cosmic
The actual property and behavior of light is believed to rays) to 1012 (radiofrequency rays). The rays in the immediate
be a complement of the above forms which is referred to as vicinity of visible light in the electromagnetic spectrum are
the wave-particle duality. This duality is a property common called ultraviolet rays (next to violet) with wavelengths between
to all electromagnetic radiations, which states that shorter the
wavelength of the radiation, greater the energy of the
individual quanta. In the case of light this refers to particles
called photons.
Optics refers to the scientific study of light and its
interaction with matter. It helps the understanding of the
true nature and behavior of light. Euclid wrote Optica in
about 300 BC, in which he demonstrated his studies on the
properties of light. Euclid postulated that light traveled in
straight lines, he described the laws of reflection and studied
them mathematically.1 Ptolemy in the 2nd century AD wrote Fig. 2.1.1: Dispersion of white light into its
about the refraction of light in his book called Optics.2 components through a prism
22 Light, Vision, Optics and Refraction
Fig. 2.1.3: Figure of a wave demonstrating the concept of wave

length and amplitude
Fig. 2.1.2: The electromagnetic spectrum
200 to 400 nm while the rays that are next to red are named wavelength of that wave (Fig. 2.1.3). Phase comprises a any
infrared rays with wavelengths between 780 to 10000 nm part of the cycle. Phase is an important concept to understand.
(Fig. 2.1.2). By convention, the infrared and ultraviolet rays If two waves of equal wavelengths are traveling in the same
are also called light though they are not visible. direction then the fraction (part) of the cycle by which one
As mentioned above, light travels in a straight line unless wave follows or leads the other defines the phase difference
it meets a surface separating two media. Light travels through between the two waves. If the phase difference between these
vacuum at a velocity of 299,792,458 meters/second or 2 waves of equal wavelength is equivalent to one complete
approximately 3 × 108 meters/second in round figures cycle (360o), then the waves are said to be “in phase”. These
(186,282 miles per second). While passing through another are termed as coherent waves. Two waves can be said to be
transparent media, there is an interaction between the light coherent only if they have the same wavelength and are in
particles (photons) and the electrons of the media, which phase with each other. If the waves are “out of phase”, then
causes the velocity of light to decrease. As the frequency of they are termed as being incoherent waves.
light remains unchanged, this implies that there is a co- The amplitude of a wave is the maximum displacement
incidental decrease in the wavelength in the new media because of a particle on either side of the wave with respect to a
of the reciprocal relation between frequency and wavelength. baseline that bisects the wave. Thus the level of the maximum
Similarly, if the surface of the new media is polished, light positive amplitude defines the peak of the wave and the
would be reflected back into the incident medium. These level of the maximum negative amplitude defines the trough
properties of light which reflect its dual nature in different of the wave (Fig. 2.1.3).
circumstances need further elaboration and comprise the study The concept of being “in phase” or “out of phase” is
of optics. fundamental to the concept of interference. The effect of
two waves of equal amplitude and wavelength moving in the
Some of these properties are: same direction is that of algebraic summation. This implies
that if the two waves of equal wavelength are in phase, the
Interference resultant wave will be a summation of the two waves
This implies the interaction of two waves of light traveling (constructive interference). If they are out of phase by half a
along the same path. When a wave of light passes through a cycle, they will completely neutralize each other, thus resulting
media, the media itself does not move. The constituent in complete annihilation of the wave (destructive interference).
particles of the media however vibrate at right angles to the Any other phase difference will result in a wave of amplitude
direction of the movement of the wave. One complete that would be the algebraic sum of the two individual waves
oscillation of the wave comprising a trough and a peak is which would be of intermediate amplitude of varying degrees
called a cycle. The distance between two symmetrical parts of (Figs 2.1.4A and B).3 This phenomenon of interference has
the wave as for example between two peaks defines the widespread applications in human optics.
Light and its Properties 23
Figs 2.1.4A and B: Demonstration of phase difference, constructive

and destructive interference: (A) The waves are completely in phase,
leading to constructive interference; (B) The waves are completely
out of phase, leading to destructive interference Fig. 2.1.6A: Scattering of light results in the sky appearing to be
blue during the day and red at dusk or dawn when light has to
travel a longer distance to reach the observer’s eyes
Fig. 2.1.5: Ray diagram explaining the scattering of light
Scattering Fig. 2.1.6B: Perception of blue color of the sky at mid-day is

dependent on the Rayleigh scattering of light
When light travels through a particulate medium and hits
these particles, the initial direction in which it was moving
may get deflected or scattered in different directions (Fig.
2.1.5). If the particles in the medium are very large, the
deflection affects all the component wavelengths of white
light. If the particles in the media are small, specific
wavelengths (those of violet, indigo and blue) may get affected
more than the other (Rayleigh Scattering).4,5 This phenomena
is called scattering of light. The scattering of specific
wavelengths corroborating to a specific color in the visible
spectrum may result in the perception of a particular color.
Rayleigh scattering is believed to be the optical basis for the
“blue” appearance of the sky (Figs 2.1.6A to C). When the
sunrays enter the atmosphere from above, they come across
millions of small particles which scatter them. As blue is the Fig. 2.1.6C: Clouds, in contrast to the blue sky appear white to gray
in color because the water droplets that make up the cloud are much
wavelength that scatters the most because the Rayleigh
larger than molecules in the air and the associated scattering from
scattering is specific for the smaller wavelengths, it is the these droplets is almost independent of wavelength in the visible
dominant color that is perceived. The same phenomenon is range
Fig. 2.1.7: Ray diagram of the onlooker looking at the sun when it is placed at the 12 O’clock position and at 6 O’clock position
responsible for the perception of the sunset being red in primary wave resulting in the production of various
color. When the sun is just above the horizon, light from the interference patterns. This interference pattern is especially
sun has to cross through a vast extent of the atmosphere. well demonstrated if the narrow opening through which the
After all the blue light has got scattered by the atmosphere, wave (in this case a light wave) passes is circular in shape.
what is left is the red light, which is why the clouds or the The circular diffraction pattern that is thus produced has a
horizon surrounding the setting sun appears to be red to the central bright zone known as the Airy Disk which is
onlooker (Fig. 2.1.7). Thus scattering can be defined as a surrounded by alternate dark and light patterns (corresponding
physical process where some forms of radiation (like light) to areas of destructive and constructive interference) (Fig.
are forced to deviate from their trajectory by the non- 2.1.8). Diffraction can account for the decrease in visual
uniformity of the medium through which they pass.6 The acuity that may be observed when the pupil is very small.
scattering of light waves when the wave hits a particle follows The interaction of the secondary waves at the pupillary edge
the laws of reflection over a surface (to be elucidated later). interferes with the direct transmission of the primary light
Scattering of light is the predominant cause of decreased vision wave into the schematic eye, thus decreasing visual acuity.
in patients with cataracts or corneal scarring. Scattered light The principles of diffraction of light through a small aperture
due to the irregularities in the ocular media comprise glare. corresponding to the wavelengths of the waves passing
through it and the subsequent interference patterns that are
Diffraction formed are the basis of the science of interferometry. It is
When a wave encounters a narrow opening which is close to important to remember that both diffraction and interference
the wavelength of the wave that is transmitting through it, refer to the bending of light from its straight path and the
the edge of the opening acts as an obstruction to the movement subsequent interaction of the primary and the secondary wave
of the primary waveform. The edge further acts as a new forms. The effects of diffraction are significant only if light
center for the propagation of secondary wave fronts. These is passing through a narrow slit or opening, not when the
secondary wave fronts are usually out of phase with the opening is very large.
as unpolarized light. If one has to select waves propagating

in only one direction and do away with the others, then it is
obvious that unpolarized light has to pass through a sieve
which transmits some waves while stopping others. As already
mentioned above, since light waves have inherent electric
fields, this property can be used to let only select waveforms
of light to propagate farther into a medium. Electric fields
are vectors, which can be resolved into components parallel
and perpendicular to the direction of the light particles. If
the medium is prepared such that it is electrically charged
along the path of the movement of the light particles, then
when unpolarized light passes through it, the electrical field
which is parallel to the movement of the particles gets
absorbed, allowing only the ones that are perpendicular to it
to pass through. Thus the light waves that come out moves
in only one direction and is called linear polarized light. The
second part that we need to realize is that the light that is
Fig. 2.1.8: Diffraction of waves through an aperture. Diffraction is coming out through this sieve or the polarizer as it may be
one of the main causes of decreased visual acuity when the pinhole called is much less than the actual quantity of light that had
aperture is very small. The increased depth of focus is neutralized
initially gone into the medium. The polarizer has already
by the “out of phase” secondary wave fronts emanating from the
aperture edges debarred all other waves but the wave in the direction it
permits to transmit. Thus the intensity of light that comes
out is much less (usually less than 50%) of the initial input.
An interesting thing to observe out here would be that if
Diffraction was first observed and carefully documented
two polarizers are taken and placed perpendicular to each
by Francesco Maria Grimaldi who coined the term diffraction
other, then what would transmit out would be complete
from the latin diffringere, which means ‘to break into pieces’,
darkness. This would be because the first polarizer would
referring to light breaking up into different directions at the
permit transmission of light in only one direction. The second
edge of the obstruction.7 His observations were published in
polarizer placed perpendicular to the direction of this
1665. This was the basis of the famous experiment by Thomas
polarized light would block this unidirectional light thus
Young in 1803, very similar to the principles of modern day
producing complete opaqueness. The second polarizer placed
interferometry, whereby by demonstrating the phenomena
in any other direction than at right angles to the first, would
of diffraction and interference, he prove that light had a
allow some light to propagate but never as much as would
waveform nature.8 He propogated the waveform theory of
propagate if the second polarizer was either not there or was
light vis-à-vis the particle theory propounded by Newton
totally parallel to the first polarizer (Figs 2.1.9A and B). The
previously. Further ratification of the wave theory of light
extent of light that transmits through the second polarizer,
based on the principles of diffraction was advanced by
often called the analyzer, is given by a mathematical formula
Christiaan Huygens and Augustin Jean Fresnel, who described
called the Malus’s law. This concept of not only creating
in details as to how light waves propagate through a media.
polarized light but to also be able to modify the amount of
These are now known mathematically as the Huygens-Fresnel
light that passes through a media with the help of two
Principle.9,10
polarizers is a very important concept in practical optics, with
widespread technological applications.
Polarization
The above was an example of polarization by absorption
Light is an electromagnetic radiation and has electrical and and transmission. Polarization can also be achieved by
magnetic fields. Light propagates as a transverse wave while reflection. The laws of reflection have been elucidated in a
transmitting forwards. However, in a beam of light, for subsequent chapter. It is important to understand that light
example, the light that is coming from the sun or from a falling upon a polished surface is reflected back and the angle
tubelight, the waves along with their inherent electrical fields of reflection is the same as the angle of incidence of the
have random directions or no polarity. This is what is termed initial incident light when compared with an imaginary
Figs 2.1.9A and B: (A) The concept of polarization demonstrates that only the rays parallel to the polarizer orientation will be transmitted; (B) If
two polarizers are placed at 90 degrees to each other, this implies that no rays of light will pass through this barrier. This is called crossed
polarization and has great optical significance. Thus the angle of the second polarizer can be changed to regulate the extent of light that will
pass through
perpendicular reference line to the surface upon which the light is incident on these surfaces from above, the reflections
incident light falls. If the surface is such that it allows are polarized in a horizontal direction. A true polaroid sunglass
transmission and absorption of light along with reflection has the filter placed in a vertical direction to prevent this
from its anterior surface, for example, glass or water, then polarized light from transmitting further. Cheap sunglasses
the minor amount of light that gets reflected is polarized. that do not obstruct this dazzle from reflected surfaces are
The extent of polarization may vary, in which case, it is called not polarized glasses, and while the wearer may feel
partially polarized rays. However, if the angle of incidence complacent, it may be dangerous to use these in high altitudes
of the light rays on glass is about 55o and that on water is for they will not prevent highly focused unidirectional linear
about 52°, the reflected light rays in these circumstances are reflected sunlight from the snow from causing macular
about 100 percent polarized. This is one of the reasons why damage, a condition known as snow blindness. Also, the relative
reflections coming out from the surface of glass, water or pupillary dilatation produced by them because of the decrease
snow are often blinding and one is not able to see beyond in luminance would ensure that more light enters the eye.
(Fig. 2.1.10). Use of polarized sunglasses, which are basically Another example of polarization by reflection seen in
polaroid filters that stop the transmission of these highly nature is the rainbow. Though the presence of the VIBGYOR
polarized reflections from reaching the eye, often do the dual in the rainbow is attributed to the prismatic decomposition
job of protecting the macula from photic damage and also of the white light (sunlight, in this case) by the raindrops,
improve visibility by doing away with the dazzle. As solar through a process known as dispersion, which will be discussed
Dispersion
Another interesting property of light is dispersion. This refers
to an interactive phenomenon between the light wave and
the medium it is passing through. While discussing the concept
of refraction, a term called the index of refraction which is
a factor constant for each media is elucidated. This factor is
an important determinant of the extent and the direction of
the bending of light that occurs when light enters or travels
through that media (discussed later). Maintaining that the
index of refraction for each media is constant, and considering
the ideal situation where the media has no irregularities which
could contribute to an inconstant index, it is a mathematical
observation that the index is dependent on the frequency
and wavelength of the incident light falling on it and
transmitting through it. Knowing that white light basically
Fig. 2.1.10: Snow blindness is caused by polarization by reflection. comprises seven inherent observable wavelengths, all
Reflection of the sun’s rays by the snow can be extremely
dangerous. Polarized glasses are recommended for high altitude corresponding to different colors, this amounts to the fact
excursions that the index of refraction of that media is different for the
different wavelengths. Mathematically, the index is higher for
shorter wavelengths (normal dispersion), which implies that
subsequently, it is important to understand that all the rays the violet component bends more than the red component.
The decomposition of white light by prisms or raindrops
that are at a tangent to the arc of the rainbow are polarized
(production of a rainbow) is an example of dispersion. If
rays. This is because of the reflection of the sunlight from
the index is higher for higher wavelengths it is termed as
within the raindrops. It is also important to emphasize here
anomalous dispersion.12
that diffuse reflection off a mirror, which is essentially from
Practical applications in optics are the presence of
the posterior metallic background of the slab of glass that is
peripheral chromatic aberrations that are often seen in higher
used for the purpose, is not polarized light.
diopteric power of spectacles. The principle of reconverting
Another method by which polarization occurs in nature
dispersed components of white light into white light again in
is through the process of scattering, which has already been
such spectacles or optical aids so as to reduce the chromatic
described above. While the infinitesimal particles in the
aberrations, is often by cementing two such media, kept in
atmosphere scatter the rays of the sun in different directions,
the positive and the negative, whose combined power adds
there is an arc in the sky for every position of the sun where
to the required power of glasses. As mentioned above, the
the reflection is occurring at 90 degrees to the direction of
dispersion that would occur at the positive surface would get
the incident ray. These rays reflecting down into the eyes of
neutralized by the cemented negative surface which would
the onlooker from this arc is 100 percent polarized light.11
again reconvert the components into white light. This is the
The principle of polarization has been extensively used
basis of achromatic spectacles, contacts lenses and intraocular
in the optics and manufacturing of optical equipments and
lenses.
the creation of light amplification by stimulated emission of
Astronomical spectroscopy is the study of the spectrum
radiation (LASER). Birefringence refers to a quality, seen in
of electromagnetic radiation, including visible light, which
liquid quartz crystals, whereby the incident unpolarized light
radiates from the stars and other heavenly objects. The optical
is broken into the fast (ordinary) and the slow (extra-ordinary)
phenomenon of dispersion in used to calculate the
ray components. When these rays are emitted, they are
composition, temperature and the distance between the
polarized, perpendicular to each other and also slow a phase
stars.13,14
difference between each other. Birefringence is said to be
due to the anisotropic nature of the liquid quartz crystals,
Absorbance
which denotes that the alignment and shape of the molecules
within the crystal is such that its properties vary depending Absorbance denotes the quantity of light that is absorbed by
upon the direction of measurement. the media on which it falls. When light interacts with another
media, it may get transmitted, absorbed or reflected. Matter rays, they are instrumental in the transmission of a single
can capture electromagnetic radiation and convert the energy beam of linear polarized light. The substance polaroid, used
of light in the form of photons to internal energy. This commonly to make sunglasses and made out of fine iodine
absorption can lead to other phenomenon whereby the energy crystals and quinine sulfate embedded in plastic, is a dichroic
that is absorbed can be used to excite electrons at a lower substance.
energy level within the medium to a higher energy level. This
Fluorescence
can be re-radiated out. This forms the basis of another
property of light called fluorescence. This is the property of a molecule denoting its capacity to
All absorbed light do not result in fluorescence. The type emit visible light after having absorbed light of a different
of excitation is dependent on the wavelength of light. wavelength. In ophthalmology, the most common example
Electrons are promoted to higher levels by visible or ultra- of this phenomenon is the emission of yellow-green light
violet rays, while infra-red rays cause vibrations in the medium. (520–530 nm) by the dye fluorescein sodium, when stimulated
Absorbance is measured by absorption spectroscopy, the by blue light (465–490 nm). The energy difference between
basis of which is that the absorption spectrum comprises the the absorbed and the emitted photons is believed to dissipate
absorption of light as a function of the wavelength absorbed. within the fluorescent material, via internal molecular
Many optical devices and sunglasses make use of this vibrations and heat.15
property of light. The name fluorescence is derived from the mineral
Dichroic substances like tourmaline are natural polarizers. calcium difluoride, which was observed to emit blue
They absorb and completely block transmission of those light fluorescent emission. The name was coined by George Gabriel
waves through them which are not aligned along their Stokes in 1852 to denote the general appearance of a solution
molecular structures. Thus by absorbing the rest of the light of sulphate of quinine and similar media.16
Table 2.1.1: Radiometry and Photometry

Radiometry Photometry
Definition Term that quantifies radiant energy in all parts Term that quantifies the visible spectrum as
of the electromagnetic (EM) spectrum. It is the defined by the response and sensitivity of
measure of optical radiation which is the EM the eye. Photometry uses the eye as the
radiation within the range of 3 × 1011 to 3 × 1016 Hz. comparison detector.
This range corresponds to the UV rays, the
visible rays and the IR rays.
Measures • Amount of light emitted from a source • Amount of visible light to which the eye
(Radiant Flux) is sensitive (Luminous Flux)
• Light Intensity emitted (Radiant Intensity) • Light intensity to which the eye is sensitive
• Amount of light falling on a surface (Irradiance) (Luminous Intensity)
• Amount of light reflected from a surface (Radiance). • Amount of light falling on a surface to
which the eye is sensitive (Illuminance)
• Amount of light reflecting from a surface to
which the eye is sensitive (Luminance).
Measurement values • Radiant Flux is measured in watts • Luminous Flux is measured in Lumens
• Radiant Intensity is measured in watts per steradian • Luminous Intensity is measured in Lumens
• Irradiance is measured in watts per square meter per steradian or candelas
• Radiance is measured in watts per steradian per • Illuminance is measured in Lumens per
square meter square meter or Lux
• Luminance is measured in Lumens per
steradian per square meter or candelas per
square meters.
Luminous Flux of one lumen per square meter
corresponds to a luminance of one apostilb.
Troland is a measure of the retinal illumination
when one candela per square meter of luminance
is viewed through a pupil of one square mm.
MEASUREMENT OF LIGHT 4. Sneep M, Ubachs W. Direct measurement of the Rayleigh scattering

cross section in various gases. J of Quantitative Spectroscopy and
The aim of this section is not to go into detailed physical Radiative Transfer 2005;92:293.
concepts regarding how light is measured. This section is meant 5. Chakraborti S. Verification of the Rayleigh scattering cross section.
to familiarize the postgraduates with certain terms related to Am J Physics 2007;75(9):824-6.
the measurement of light that they may come across. 6. Richard PO, Torres RH, Williamson S, Dyck J. Coherent light
scattering by blue feather barbs. Nature 1998;396:28-9.
The two terms that are used commonly in this context is 7. Grimaldi FM. Physico mathesis de lumine, coloribus, et iride,
radiometry and photometry.17 Table 2.1.1 provides a short aliisque annexis libri duo; Bologna, Italy: Vittorio Bonati, 1665:
relevant synopsis of the two terms. 1-11. Available on-line (in Latin) at: http://fermi.imss.fi.it/rd/
The only real difference between radiometry and bdv?/bdviewer/bid=300682# .
8. Young T. The Bakerian lecture: Experiments and calculations
photometry is that radiometry includes the entire optical relative to physical optics. Philosophical transactions of the royal
radiation spectrum, while photometry is limited to the visible society of London 1804;94:1-16 (This lecture was presented before
spectrum as defined by the response of the eye, or the spectral the Royal society on 24th November 1803).
sensitivity of the eye. The eye is very sensitive to yellow- 9. Fresnel AJ. Memoire sur la diffraction de la lumiere. Emoires de
l’Academie des Sciences 1826;5:33-475.
green light and less sensitive to light in either end of the
10. Huygens C. In: Traité de la lumiere, Chapter 1, 1690, Leiden,
spectrum. The units used in radiometry and photometry are Netherlands: Pieter van der Aa.
related by a conversion factor called the luminous efficiency 11. Halliday D, Resnick A. Polarization of light. In: Physics, 4th Ed,
of radiation, which is wavelength specific depending upon New York, John Wiley and Sons, Inc, 1992, Vol II, Chapter 48.
sensitivity of the eye to it. 12. Born M, Wolf E. In: Principles of optics. Cambridge: Cambridge
University Press 1999;14-24.
13. Lorimer DR, Kramer M. In: Handbook of pulsar astronomy, 1st
REFERENCES Ed, Vol 4 of Cambridge observing handbooks for research
astronomers. Cambridge: Cambridge University Press, 2005.
1. Shenton WF. The first English Euclid. Am Math Monthly
14. Saha MN. On a physical theory of Stellar Spectra. Proceedings of
1928;5:505-12. the Royal Society of London 1921; Series A, Vol 99, Issue 697:
2. Mark Smith A. In: Ptolemy’s theory of visual perception. An 135-53.
English translation of the optics with introduction and 15. Lakowicz JR. In: Principles of fluorescence spectroscopy, 3rd
commentary (based on Albert Lejeune’s critical Latin text of Ed, Plenum Press, New York, 2005.
1956): Transactions of the American Philosophical Society (Vol 16. Stokes GG. On the change of refrangibility of light. Philosophical
86, Part 2), Diane Publishing, Philadelphia 1996;23. Tranasactions of the Royal Society of London 1852;142:463-562.
3. Zurek WH. Decoherence and transition from quantum to classical. 17. Palmer JM, Grant BG. In: The art of radiometry; SPIE Press
Physics today 1991;44:36-44. Book 2009;184:1-9.
Chapter 2.2
REFLECTION, REFRACTION AND

GEOMETRIC OPTICS
Zia Chaudhuri, Monica Chaudhry
REFLECTION 1. The angle of incidence of the ray of light falling on the

new interface ‘i’ is equal to the angle of reflection ‘r’,
As mentioned in the previous section, when light travels in a
which is the angle whereby the reflected ray bounces back
medium, it interacts with it. Depending on the nature of the
into the first medium (Fig. 2.2.1). The angle is measured
media it travels in, it gets transmitted, absorbed or reflected.
with respect to an imaginary perpendicular line to the
Reflection is the change in direction of a wavefront at an interface
reflecting surface called the normal.
between two different media so that the wavefront returns
2. The incident ray, the normal, and the reflected ray are
into the medium from which it originated. The electromagnetic
coplanar, i.e. they all lie in the same plane.
waves, including light waves, sound waves, waves on water
3. The light paths are reversible and sometimes result in a
etc, all undergo reflection. Reflection of light is either specular
phenomenon called retroreflection.
(mirror-like) or diffuse (retaining the energy, but losing the
image) depending on the nature of the interface. There are Specular reflection forms images. Reflection from a mirror
other types of reflection like complex conjugate reflections, produces an image that is erect, virtual (cannot be captured
seismic reflections, neutron reflections etc which will not be on a screen) and laterally inverted. It lies along a perpendicular
described in this section. Reflection is an important optical to the reflecting surface and is as far behind it as the object is
concept. in front of it (Fig. 2.2.2). Another optical rule to keep in
Reflection Through a Plane Mirror

A plane mirror provides the most common model for specular
light reflection, and typically consists of a glass sheet with a
metallic coating where the reflection actually occurs. Reflection
is enhanced in metals by suppression of wave propagation
beyond their skin depths. Reflection also occurs at the surface
of transparent media, such as water or glass. It has already
been described in the previous chapter that the reflected light
from transparent media like water or glass is polarized.1
Laws of Specular Reflection

When a ray of light falls on the interface of the second
medium which is mirror-like, and bounces back into the first
medium the phenomena is called specular reflection.
The optical phenomenon for specular reflection is Fig. 2.2.1: Line diagram demonstrating the laws of
governed by the following laws, which are:1-3 specular reflection
Reflection, Refraction and Geometric Optics 31
Fig. 2.2.3: When the mirror is rotated by an angle φ, the angle of

reflection changes by 2φ
Fig. 2.2.2: The image of an object placed in front of a plane mirror is
erect, laterally inverted, virtual and of the same size. It is important to
remember that a small surface of a concave or convex mirror with a object/the distance from the mirror is an equivalent ratio,
very large radius, behaves as a plane mirror. This has practical the above formula can be extended to:
applications in optics Distance of the image
Size of the Image from the mirror
______________________ __________________________
Magnification of images = =
Size of the Object Distance of the object
mind is that when a plane mirror is rotated while light is from the mirror
incident upon its center of rotation, the reflected ray is Other types of reflection important in optics are:
deviated through an angle equal to twice the angle of rotation
of the mirror (Fig. 2.2.3). Diffuse Reflections
Specular reflection at a curved surface forms an image
When light strikes a rough or granular surface, it bounces
which may be magnified or demagnified. Curved mirrors
off in all directions due to the microscopic irregularities of
have optical power. Depending upon whether it is a concave
the interface. Thus, an ‘image’ is not formed. This is called
or a convex mirror, the images are formed which follow the
diffuse reflection (Fig. 2.2.6). The exact form of the reflection
following rules:
depends on the structure of the surface. It is important to
1. Any incident ray traveling parallel to the principal axis on
remember that in actual day to day circumstances, specular
the way to a convex or a concave mirror will reflect in
reflection is difficult to observe. Specular reflections form
such a manner that its real or virtual extension will pass
images only at the designated area. Diffuse reflections are
through the focal point.
responsible for the fact that most objects are seen.
2. Any incident ray traveling towards a convex or a convex
mirror such that its extension passes through the focal Retroreflection
point will reflect and travel parallel to the principal axis.
The structure of certain surface is such that light is returned
These two rules are used to construct ray diagrams. A ray back in the same direction from where it came. A common
diagram is a tool which is used to determine the location, example is that of seeing dew on the grass. Partial
size, orientation, and type of image formed by a mirror. retroreflection from the dew’s surface is created by both, the
refractive properties of the curved droplet’s surface and the
Reflection Through Curved Mirrors
reflective properties of the backside of the droplet.
The images formed by concave and convex mirrors are This is the same principle employed by the eyes of animals
elucidated in Figures 2.2.4A to F, and 2.2.5. The magnification to increase the amount of light available at night and thus
or minification produced by the curved mirror can be increase their sensitivity. When light is incident on this reflecting
calculated using the formula that magnification = image size/ layer in the animal’s eyes, a portion of that light is returned to
object size. By the laws of trigonometry, as the size of the the vicinity of the light source. The eyes of these animals,
Fig. 2.2.4E: When the object is at f, the image is real, inverted, of a

large size and is placed at infinity
Fig. 2.2.4A: When the object is placed at infinity, the image is formed
at the focal point of the concave mirror. It is real, inverted, and smaller
in size
Fig. 2.2.4F: When the object is placed within the focal point of the
mirror, the image is erect, large and virtual. It is important to note that
the image size varies depending upon the distance of the object from
the concave mirror
Fig. 2.2.4B: When the object is placed beyond the center of curvature
(C) of the concave mirror, the image formed is real, inverted, smaller in
size and in between the principle focal point (f) of the mirror and c
(center of curvature)
Fig. 2.2.5: When the object is placed in front of a convex mirror,

irrespective of its placement in front of the mirror, the image is smaller
in size, is virtual and erect
Fig. 2.2.4C: When the object is placed at c, the image is also placed
at c. It is of the same size, is real but is inverted
Fig. 2.2.6: Diffuse reflections
especially cats, thus glow in the dark when light is directed

Fig. 2.2.4D: When the object is placed between c and f, the image toward them. Thus the first optical elements were (and still
is real, inverted, of a large size and is beyond c are) called “cat’s eyes”. One of the main uses of retroreflectors
nowadays is on the roads. Traffic signs, road markings, road of light through a new medium whereby the incident ray of
markers, and delineators are all retroreflective and thus are light undergoes a change in its velocity due to the difference
visible when a headlight beam shines on them. The vests and in density in the second media as compared to the first is
clothing of maintenance workers have bands of retroreflective termed refraction. If the light waves intersect the boundary
materials enhancing their conspicuity. Such retroreflective of the second media at an angle, the wave’s phase velocity is
elements have also been introduced on all types of clothing altered, causing a change in direction. Its wavelength increases
for pedestrian safety. The ray diagram of a corner reflector or decreases but its frequency remains constant. A change in
is a suitable method to explain the optical physics of direction of the waves is only seen when the light rays intersect
retroreflection (Figs 2.2.7 and 2.2.8). the new surface at an angle. If a ray travels along the normal
Plane mirrors, convex and concave mirrors find (perpendicular to the boundary), the ray will change its velocity
applications in many optical instruments, the descriptions of but not its direction (Fig. 2.2.9). The optical density of the
which are beyond the scope of this section. second media thus determines both the velocity and the
direction of the oblique waves falling on it.
REFRACTION
Refraction Through a Plane Media

When light meets a polished surface separating two transparent
media, some of the light gets reflected but most of it gets
transmitted through the medium. The process of transmission
Fig. 2.2.9: When light is transmitted from one medium to another, the
rays of light deviate towards the normal when it is transmitting from a
less dense media to a denser media and vice versa. When light is
travelling from a more dense media (like glass or water) to a less
dense media (like air), and the angle of incidence of the light ray is
Fig. 2.2.7: If two plane mirrors are placed perpendicular to each other such that the angle of the refracted ray is at 90o (on the boundary of
such that the incident ray of light, when reflected, is incident upon the the intersection of the two media), this angle of incidence is called the
other mirror surface, the reflected ray from the second mirror, travels “critical angle” for that media. This angle indicates the largest angle for
back in the same direction as the initial incident ray. This is the principle which refraction can still take place. If the angle of incidence is more
of retro-reflection than the “critical angle” for that media, the refracted ray undergoes
total internal reflection and does not move out of the denser media at
all and hence the object remains “hidden” when viewed through the
intervening “less dense” media and cannot be seen by the examiner.
The critical angle for the water-air interface is about 48.6o while that
for the crown glass-air interface is about 61o. It is reiterated that this
phenomena is only possible when the refractive media is less dense
than the incident media. This has great optical significance when
extrapolated to the optical system of the eye. Light returning from the
angle of the eye is totally internally reflected within the cornea.
Additional optical systems like the goniolens (where the anterior curve
of the goniolens is such that the critical angle is not reached and
refraction is possible at the contact lens-air interface) or gonioprisms
(which have mirrors angulated appropriately such that light gets
reflected on them and leaves the eye at right angles to the contact
Fig. 2.2.8: Retroreflection from the fundus in anisometropia and lens) have to be added to the optical system of the eye to visualize
strabismus results in the classical Bruckner’s reflex these structures
The ratio of the velocities of light in the first and second situation, this implies measurement of the refractive index
media is called the relative refractive index between the of every other material with respect to that of air. The
media.1-3 refractive index, so derived (n), is unitless. Velocity is measured
The absolute refractive index of a medium “n”, is defined in its respective SI units as meters/second.
as the ratio of the velocity of the light in the medium with The history of the derivation of this interesting optical
respect to its velocity in vacuum. concept regarding waveform propagation through different
Refractive index, n = velocity of light in vacuum/velocity media starts with Ptolemy in the 2nd century AD, to Ibn Sahl
of light in the medium of Baghdad in the 10th century (who is credited with optical
diagrams suggestive of the concept of refraction and working
Snell-Descartes Law out of shapes of lenses that could be used to focus light with
The ratio of the sine of an angulated incident ray that falls no aberrations called anaclastic lens), to Willebrord Snellius
on an interface between two media to the sine of the and Rene Descartes in the 17th century, who independently
angulation of this ray as it refracts through the second media worked out the formula as mentioned above, then called the
denotes the velocity of the propagating wave in the second Law of the Sines, to Christiaan Huygens, who combined
media with respect to the first. The velocity of any physical observation with mathematics to describe the wave
electromagnetic wave, including light, in each material is nature of light (the Huygens-Fresnel principle). Thus, it is
determined by the density and the elastic modulus of that interesting to note that the discovery of the wave nature of
material. When a wave encounters an interface, this property light was an application of this mathematical principle and
of the second media causes it to either propagate faster or not vice versa. As mentioned, this law holds true for all wave
slower than what it was doing in the first media. This is what forms and has a lot of technological and industrial applications.
is optically interpreted as a change in the direction of the On transmitting from an optically less dense medium to a
wave resulting in “bending” when the initial incident ray hits denser medium, the ray of light deviates towards the normal
the new media at an angle, with respect to a mathematical while the converse is true when the ray of light traverses
constant line placed at 90o (normal) to that media. If the from a denser media to one which is optically less dense.
initial incident ray hits the interface at 90o (sine 90o is 0), Thus, in refraction through a plate of transparent media (for
there is no such “bending” observed, though the velocity of example, glass), the lateral ray of light which interacts obliquely
the propagating wave in the second media would undergo a with the glass plate and is initially deflected towards the normal
change depending on the density of the media. This implies (within the glass). However, when it emerges out into the air
that the ratio of the sines of the angles of incidence and again, the ray of light gets defected away from the normal.
refraction is a measure of the ratio of the velocity of the If the refractive index of this third media is the same as the
propagating wave in the two media which is equivalent to the initial media (in this example, air), then the angle of emergence
reciprocal of the indices of refraction of these two media. of the ray through the glass slab is equal to the initial angle
This law is called the Snell-Descartes Law and is of incidence of the same ray on the glass slab (Fig. 2.2.10).
mathematically denoted as: However, the emergent ray is laterally displaced with respect
sine i v1 n2 to the incident ray (though the direction remains the same).
______ = ____ = ____
This shift is responsible for the phenomenon of objects
sine r v2 n1 appearing to be nearer or more distant than where they are
Where sine i = The angle of incidence actually placed, when they pass from one interface to the
sine r = The angle of refraction other. For example, an object at the bottom of a bowl of
v1 = Velocity of the propagating wave in the first water appears to be closer than what it really is. Also, this
media accounts for the miscalculation that a novice swimmer often
v2 = Velocity of the propagating wave in the makes when asked to pick up a coin at the bottom of the
second media swimming pool.
n1 = Refractive index of the first media It is of importance to note that most surfaces are not
n2 = Refractive index of the second media pure reflecting or refracting surfaces. Some amount of
As mentioned, the refractive index of vacuum is taken as refraction, reflection and absorption of light takes place at
1, and the refractive index of all material is calculated on the each surface. The predominating one determines whether
basis of the above equation, taking n1 = 1. As the refractive the surface can be called a reflecting, absorptive or a refractive
index of air and vacuum is practically the same, in realistic surface (Fig. 2.2.11).
Fig. 2.2.12A: Refraction of light through a biconvex lens
Fig. 2.2.10: When light is transmitted through a denser media, it moves

towards the normal and when it transmits from a dense media to a
relatively less dense one, it moves away from the normal. If the initial
media of the incident ray and the media through which the emergent
ray emerges is the same, then the incident rays and the emergent
rays are parallel to each other
Fig. 2.2.12B: Refraction of light through a biconcave lens
Refraction Through Spherical Lenses

Spherical surfaces have uniform curvature in all the meridians.
A spherical lens has one or both of its surfaces curved on
the form of sphere. A spherical correction corrects refractive
error of the eye with a single convergent or divergent
Fig. 2.2.11: Ray diagram denoting that the incident ray of light is refractive power in all meridians.1-3
capable of simultaneous reflection and refraction. This is what normally
happens over most surfaces in different proportions and this is what
Types of Spherical Surfaces
determines the predominant property of the media as to whether it is
a reflecting media, a refracting media or a predominantly absorbing The two types of lenses can be classified as converging or
media
diverging lens. To distinguish them the relative thickness of
two parts, the center and the edges need to be compared.
The refractive index of a transparent substance is Converging lenses (convex) are thicker in the middle than they
measured when light enters the substance from a vacuum, are at the edges, while diverging lenses (concave) are thicker
but for all practical purposes it can be taken as light entering at the edges than they are in the middle (Figs 2.2.12A and B).
the substance from air. Greater the value of the refractive The types of concave and convex lenses are demonstrated
index, greater is the bending of the light. in Figures 2.2.13A to F. A lens is biconvex if both the surfaces
are convex (Fig. 2.2.12A) and biconcave if both the surfaces Refraction Through Cylindrical Lenses
are concave (Fig. 2.2.12B). However, other types of lenses
A cylindrical lens is a lens which focuses light which passes
include those where one surface is plane and the other is
through onto a line instead of onto a point, as a spherical
either convex (plano-convex) or concave (plano-concave)
lens would. The curved face or faces of a cylindrical lens are
respectively, or if both the sides are curved, but asymmetrically.
sections of a cylinder, and focus the image passing through it
These types of lenses are called meniscus lens and depending
onto a line parallel to the intersection of the surface of the
upon the predominant curvature are labeled as convex
lens and a plane tangential to it. The lens compresses the
meniscus lenses or concave meniscus lenses. These lenses
image in the direction perpendicular to this line, and leaves it
have great optical use.
unaltered in the direction parallel to it. A simple cylindrical
lens has a power only in one meridian and the other meridian
Formation of Image
perpendicular to it has no refractive power.
The image formed by the spherical lens is elucidated in the Cylindrical lenses have different curvatures in different
diagram below (Figs 2.2.14A to C). meridians. It corrects the astigmatic refractive error of the
The images formed through a convex mirror when the eye. Refraction through cylindrical lenses is demonstrated
object is placed at different positions are shown in Figures through the following ray diagram (Fig. 2.2.17).
2.2.15A to F.
The image formed by a concave lens is shown in Figure Refraction Through Prisms
2.2.16.
An ophthalmic prism is a transparent triangular wedge of
refracting material.4 The thicker portion of the wedge is the
Conjugate Foci
“base” and the thinner opposite part is called the “apex”. The
These are pairs of points, so situated that light from one angle between the non-parallel opposing surfaces of the prism,
point is focussed at the other. At these points, the positions which converge to form the apex of the prism is called the
of object and image are interchangeable. “refracting or the apical angle”. A line bisecting this angle is
called the “axis” of the prism and the straight line at the apex
at which the two faces of the prism meet is called the “edge”
of the prism. The “principal section” of a prism is a section
made by a plane perpendicular to the edge of the prism.
Generally, ophthalmic optics are related to light rays passing
through the principal sections of the prisms. The refracting
angle or apex of a prism is specified in degrees while the
angle of deviation or the refracting power of an ophthalmic
prism is always specified in prism diopters (Figs 2.2.18 and
2.2.19).
The angles of incidence and emergence through a prism
Figs 2.2.13A to F: Types of spherical lenses relate to the rays striking the first plane surface and emerging
Figs 2.2.14A to C: Images formed by a convex lens. A biconvex lens is taken as an example
Fig. 2.2.15A: If the object is at infinity, the image is formed at the

principal focus on the other side of the lens. It is real, inverted and
diminished Fig. 2.2.15E: If the object is placed at the focal point on one side,
the image is magnified, real, inverted and placed at infinity
Fig. 2.2.15B: If the object is placed just beyond the center of curvature
(c) on one side, the image formed is real, inverted and diminished. It is
formed between the focal point (f) and c on the other side
Fig. 2.2.15F: If the object is between f and optic center, the image is
formed on the same side as the object and is virtual, erect and enlarged
Fig. 2.2.15C: If the object is placed at c on one side, the image is real,
inverted and of the same size and formed at c on the other side
Fig. 2.2.16: The image in a concave lens is always formed in between

the principal focus and the optic center for all positions of the object.
It is virtual, erect and diminished in size
from the second. The total deviation is the net change in the
direction of a ray produced after refraction by both surfaces
of a prism (Fig. 2.2.18).
By the rules of trigonometry,
Fig. 2.2.15D: If the object is between f and c on one side, the image The Total deviation = Angle of Incidence + Angle of
is real, inverted, magnified, and formed beyond c on the other side Emergence – Apical Angle
One prism diopter produces an apparent linear

displacement of 1 cm of an object situated 1 meter away
(Fig. 2.2.19).
1 Prism Diopter = 1 Centrad = 0.57 Degrees
The prism Diopter represents a tangent measurement
while the degree and the centrad are units of arc measure-
ment. Thus, though for lesser degrees of deviations, the above
equation holds true most of the time, as the prism power
Fig. 2.2.17: Refraction through a surface with two radius of curvatures, increases, the corresponding values are not linear and may
results in image formation at two different foci. This intervening area
thus lose accuracy. Although the centrad may be a more
where the two images are focused is called the interval of strum and
the conoid formed is called the Strum’s Conoid. This concept is very accurate mode of measurement for high power prisms, the
important while considering the correction of astigmatism. In this area, prism diopter unit used and promoted by Prentice has found
there is a small circle within the zone where the two rays bisect each universal acceptance. The optical properties of prisms have
other. This is the area where clarity in an uncorrected astigmatic eye
largely contributed to its use in different appliances, both
is optimum and is called the circle of least confusion. At each of the
two focal points, one set of rays will be clear but not the other. ophthalmic and non-ophthalmic. It is used for performing
Breaking the Strum’s conoid and getting the two focal points to be one many diagnostic tests in ophthalmology and has many
is the paramount principle of correcting astigmatism. The circle of therapeutic applications. Some of these are enumerated in a
least confusion also defines the point where the spherical equivalent subsequent section of this chapter.
of the astigmatic lens would mathematically lie. The spherical equivalent
classically implies adding one half of the cylindrical power to the
Two things happen when light traverses through a prism:
spherical power to convert the astigmatic power into an equivalent 1. The light bends around the base.
sphere (hence the term, spherical equivalent). Though in moderate 2. The image seen through the prism is shifted towards the
astigmatism, it may provide relief, it is reiterated that the appropriate apex (Fig. 2.2.19).
correction of astigmatism is only possible when the Strum’s conoid is
broken with neutralization of the power of each of the principal axis of
In ophthalmic prescriptions, prism simply means that the
the astigmatic surface patient is not looking through the optical center. The Prentice’s
formula allows the determination of the amount of prismatic
effect created by decentration.
Prentice’s rule is:
P = d (distance from optical center in cm) × D (power
of the lens in diopters)
Fig. 2.2.18: Refraction through a prism at the position of minimum

deviation (a = Apical angle of the prism; i = angle of incidence; e =
angle of emergence; d = angle of minimum deviation) When the
incidence angle and the emergence angle are the same, the prism is
said to be in the position of minimum deviation, for a given wavelength.
Because light gets dispersed into many wavelengths, this position is
specific for the particular wavelength falling on it at that point of time.
It may not be the point of minimum deviation for other wavelengths
simultaneously. For the position of minimum deviation, the ray travels
perpendicular to the bisect of angle “a” (apical angle of the prism), and Fig. 2.2.19: Diagrammatic representation of one
the incidence and emergence angles are equal prism diopter (not to scale)
where: field in conditions like hemianopia and retinitis pigmentosa.

P = the amount of prism present at a particular point in In case of a tubular field of the extent of 5 to 15 degrees,
prism diopters; a base in prism is applied nasally and a base-out prism is
d = the distance of that point from the optical center, in applied temporally to the carrier lens to bring peripheral
cm; objects into the patient’s field of view. The patients have
D = the dioptric power of the lens. to be highly motivated for such use and have to be trained
accordingly. The patient has to be stationary while changing
Uses of Prisms in Ophthalmology fixation and has to tolerate the jump that occurs when
looking from a career lens to a zone with a prism. The
A detailed preview is outside the scope of this book but
patient has to be trained to acclimatize himself to the
some of the important uses of prisms in ophthalmology are
“Jack in the Box Phenomena” when switching to or from
elucidated.4
the prism and also to the apparent increase in the distance
• Evaluation of extent of ocular deviation and ocular
of objects as they are viewed through the prism. In
motility disturbances.
homonymous hemianopia, the vertical edge of a Fresnel
• Evaluation of the sensory state of the patient with an
prism of appropriate power is applied to each lens with
ocular motility disturbance or strabismus (Fresnel Prism
its base towards the affected field.
Trial Set).
• Management of macular dysfunction: Prisms have been
• Performance of the prism adaptation test.
advocated to improve the function in patients with macular
• Establishment of binocularity in large angle strabismus
dysfunction. The patient is first instructed to turn his head
where surgery may not be possible or may not be
to place his eyes in the position which gives him best
predictable. This is called prismotherapy. Prisms because
vision. The examiner then places an 8 PD trial prism
of their optical properties, can be used to realign the
over the eye with the better vision with the prism base in
visual axes (motor effect) and correct diplopia when
the direction of the head turn. The same procedure is
present. They can also be used to facilitate the stimulation
repeated over the eye with the poorer vision. The patient
of corresponding retinal points to assist in the development
rotates the prism over the eye with the poorer vision to
of binocular vision in a patient with fusion potential
the position of maximum comfort and binocularity.
(sensory effect).
• Management of low vision: Depending on the cause of
• Management of intractable diplopia secondary to central
low vision and the deficit it induces, prisms may be
fusion disruption. This is an extremely rare condition which
incorporated in spectacles for the amelioration of loss of
usually occurs subsequent to closed head trauma. The
binocularity and field loss that may be induced by low
diagnosis is based after aligning the patient appropriately
vision.
with the help of prisms or the major amblyoscope. A trial
• Prisms for nystagmus: Congenital nystagmus, which is
of prisms in place of occlusion is worth a try
often associated with an abnormal head posture in the
therapeutically if the patient is motivated enough. The
direction of the null point may be benefited by the use
prognosis for the regain of fusion is however poor.
of prisms. Conjugate horizontal prisms for head turn,
• Management of diplopia in conditions where the deviation
conjugate oblique prisms for head tilt, base out prisms
may fluctuate like in thyroid ophthalmopathy, or in
for blockage in convergence and prisms for improving
myasthenia gravis, strabismus following the implantation
the binocular state of a patient with latent manifest
of glaucoma drainage devices, retinal surgery, orbital
nystagmus have been used with good results. These may
surgery or residual deviations following extensive
be used preoperatively to assess the success of the
strabismus surgery.
subsequent surgery.
• Management of amblyopia: Mild or residual amblyopia,
Prisms are also extensively used in many ophthalmic
especially anisometropic amblyopia, responds well to the
instruments, the description of which is outside the scope of
use of membrane prisms over the better eye, which acts
this chapter.
as a partial occluder. The use of inverse prisms in the
treatment of moderate amblyopia associated with
Optical Aberrations
microstrabismus remains controversial.
• Management of field defects: These prisms are used to In an ideal optical system, all rays of light from a point in the
re-orient the field of vision or to displace the residual object plane would converge to the same point in the image
Fig. 2.2.20: Different types of optical aberrations
Figs 2.2.21A to F: Optical aberrations: (A) Chromatic aberration: Note that the edge of the lens acts like a prism and disperses white light into
its component colors; (B) Spherical aberration: Note again that the peripheral rays tend to converge more than the central ones; (C) Coma: An
off-axis refraction can produce a characteristic distortion called coma; (D) Astigmatism: A similar off-axis refraction when light strikes a lens
obliquely, produces distortion; (E) Pincushion effect: Classically seen with high hypermetropic correction for aphakia; (F) Barrel effect:
Classically seen with glasses with high myopic power. Both the pincushion and the barrel distortion is decreased with aspheric glasses
plane, forming a clear image. The influences which cause • Abnormal curvature of field. The focal surface is not planar
different rays to converge at different points are called but curved, in a bowl shape. This aberration is remedied
aberrations. Lenses, which have practical application in many by using a curved imaging parallel to the focal surface.
ophthalmic instruments and aids like spectacles, do not form • Astigmatism. It occurs when rays of light strike a spherical
perfect images, and there is always some degree of distortion lens obliquely or the line of sight is not parallel with the
or aberration introduced by the lens which causes the image principal axis of the lens. A toric effect is introduced
to be an imperfect replica of the object. forming a Sturm’s conoid. These images are thus distorted
Few of the main aberrations are elucidated in Figure and formed in different planes (Fig. 2.2.21D).
2.2.20. • Distortion. The image magnification is greater towards
• Chromatic aberration. The refractive index of glass and the the edges of the field or less than at its center. If the
refracting media of the normal eye varies with wavelength. lens is a minus lens, “barrel” distortion results, if the lens
This results in different focal lengths and image is a plus lens, “pincushion” distortion results, with the
magnifications for different colors of the VIBGYOR, projected image (Figs 2.2.21E and F). These are aberration
which are the components of white light, as mentioned. seen in high myopes and aphakes with their spectacle
This physiological optical principle is used for performing correction.
the duochrome test, described in another chapter of this These aberrations are important because their extra-
section (Fig. 2.2.21A). polations in the optical system of the eye are used to test
• Spherical aberration. Lenses with spherical surfaces have a different situations and conditions in ophthalmology and
shorter focal length at their periphery than at their center. corrective measures to do away with these are a major concern
It is caused by prismatic effect of peripheral lens. The in the development of spectacles and other optical
rays passing through the periphery are deviated more than instruments and appliances.2,3
the ones in the center. The rays close to lens’s edge tilt
more and come to focus closer to the lens than the one REFERENCES
that are near the optical axes (Fig. 2.2.21B). This has 1. Halliday D, Resnick A. Polarization of light. In: Physics, 4th Ed,
applications for the pinhole and the stenopic slit test, New York, John Wiley and Sons, Inc 1992;II(48).
described in another chapter of this section. 2. Elkington AR, Frank HJ, Greaney MJ. In: Clinical Optics. 3rd
Edition, Blackwell Science, London 1999;25-73.
• Coma. The various circular zones of a lens produce an
3. Peyman GA, Sanders DR, Goldberg MF, eds. Optics and
image of an off-axis point that is distorted radially into a Refraction. In: Principles and Practice of Ophthalmology; W B
comet shape known as a coma patch. Coma occurs when Saunders, Philadelphia 1987;1(14):174-93.
an object off the optical axis of the lens is imaged, where 4. Veronneau-Troutman S. Prisms in the Medical and Surgical
rays pass through the lens at an angle (Fig. 2.2.21C). Management of Strabismus. CV Mosby, St Louis, Missouri 1994.
Chapter 2.3
REFRACTION OF THE EYE: PRINCIPLES

AND PRACTICE OF RETINOSCOPY
Monica Chaudhry, Zia Chaudhuri
REFRACTION OF THE EYE with it and the effect of different procedures performed on
the optical status of the eye. Many such models, combining
Refraction is the phenomenon which makes image formation
the sciences of optics, physics, mathematics and
possible by the eye. The geometric optics of the same has
ophthalmology have been proposed in literature, the first
been discussed in the preceding section. The actual anatomy
being by Listing in 1853, but is outside the preview of the
of the eye is quite complex, but it is systemically simplified so
current chapter. Listing’s schematic eye’s refracting surface
that the optical system that is so essential for visual acuity is
had a power of 68.3 D and was situated 2.34 mm behind the
explained. Destruction, partial or complete, of the optical
schematic eye’s cornea. It had an index of refraction of 1.35,
system of the eye, results in loss of visual clarity.
a radius of curvature of 5.124 mm and a length of 20 mm.
The Eye as an Optical System Gullstrand’s number one schematic eye (1911), and the
Helmholtz-Lawrence schematic eye (1909) measured the
The eye can be considered as an optical system with a positive radius of curvature and refractive indices of the cornea and
power of about 58 to 68 D.1-3
the anterior and posterior surface of the lens, in the
It has two main refractive elements, the cornea and the accommodated and the relaxed states to formulate their
lens. The cornea bulges in the front of the eyeball, and because
models. Gullstrand’s original model (number one) comprised
its anterior surface is in contact with air, it bears most of the a mathematical representation of the eye in the
power of the eye (about 42–45 D). The eyeball has a mean
accommodated and unaccommodated states over six
length of 24 mm, and the image is formed on the inner back refracting surfaces, two of the cornea and four of the
side, where the retina is located. The aqueous humor, which
crystalline lens, with the inner core of the lens having a higher
has a refractive index of 1.336, is located in the midst of the refractive index than the peripheral part, simulating the natural
cornea and the lens. The vitreous humor has an index of
gradient of the refractive index of lens system. Though
1.337. The power of the lens is not fixed, and it can expand physiologically very accurate, Gullstrand’s model was simplified
its surface curvature and power via the ciliary muscles
by Emsley, and this popular model, combining simplicity with
surrounding it. The pupil of the eye is located 3 mm behind accuracy is commonly known as the Gullstrand’s simplified
the front vertex of the cornea. Its diameter ranges from 2 to
schematic eye model or the Gullstrand-Emsley model.
8 mm, and it is influenced by the background, illumination, Emsley’s schematic reduced eye (1952) was simpler, had a
age, drugs and health status.1,2
power of 60 D, an index of refraction of 4/3 (1.33), radius
of curvature of 50/9 (5.55 mm) and the refracting surface
Schematic Reduced Eye
was situated 1.66 mm behind the schematic eye’s cornea,
A schematic eye represents a simplified, mathematical model with anterior and posterior focal lengths of –16.67 mm
of the optical system of the eye which facilitates the (refractive index of air/power of the eye = 1/60) and +22.22
understanding of geometric optics with relation to the eye, mm (refractive index of the homogeneous media/power of
the subsequent assessment of different pathologies associated the eye = 1.33 / 60) respectively. Donder’s reduced eye model
Refraction of the Eye: Principles and Practice of Retinoscopy 43
was even more simplified with a power of 66.7 D, a radius

of curvature of 5 mm, a homogeneous index of refraction
of 4/3 and anterior and posterior focal lengths of –15 and
+20 mm, respectively, with the refracting surface situated 2
mm behind the reduced eye’s cornea. Thus, these reduced
eyes comprised a single refracting surface with one nodal
point, one principal point and one index of refraction. Though
simplifying the optical principles of geometric optics in the
eye, these however, do not conform to the actual biological
properties of the in vivo healthy eye. The Liou-Brennan
schematic eye model is a more accurate model for the human
eyes, taking into consideration the concept of a gradient
refractive index, decentered pupils and empirical measure-
ments of the in vivo eye in order to define size and parameters
such as the anterior and the posterior surface of the cornea,
Fig. 2.3.1: Representative diagram of the Emsley’s schematic eye
the lens and the axial length of the eye but requires special
softwares and complex mathematical calculations. This model
may be recommended when dealing with complex, customized
ocular models for determining the efficacy of different
procedures related to the refractive status of the in vivo human
eye as the other conventional models, by virtue of their
simplicity and homogenicity, have a tendency to over-estimate
the optical quality of the normal, emmetropic human eye.3,4
A representative diagram of Emsley’s simplified schematic
eye model and Donder’s reduced eye model are presented in
Figures 2.3.1 and 2.3.2 respectively. These diagrams have
been used to simplify and demonstrate geometric optics as
relates to the eye in this chapter and subsequent chapters in
this book.
Refractive Physiology of the Eye

Fig. 2.3.2: Representative diagram of the Donder’s reduced eye
Light rays are focused on the retina after refraction through
the cornea and lens in an emmetropic eye. The corneal
refractive power remains constant. The lens refractive power
is modifiable with accommodation and the axial length of Near Point
the eye remains constant except under certain pathological
It is the closest point which the optical system of the eye can
condition.
focus on. The near point is a valid point only because the
optical system of the eye is a dynamic system, which on the
Far Point
basis of certain anatomical and physiological configurations,
This is the farthest point that an eye can see. For an can focus on multiple points, through a process called
emmetrope, it is placed at infinity. For a 4.00D myope accommodation. Age related decrease in this configuration
without glasses, it is 25 cm in front of the eye (100 cm/4) which permits focussing at different points is responsible for
and for a 3.00D hyperope without glasses, it is 33.3 cm behind a condition called presbyopia. The near point is the sum of
the eye (100 cm/3). The location of the images is based on the power of the eye and the accommodation A patient with
the principles of geometric optics described in a previous 10.00D of accommodation and a -4.00D error without glasses
section. has a near point of 14.00D or 7.15 cm in front of the eye.
REFRACTIVE ERRORS to improve vision, by decreasing the palpebral aperture

(inducing a pin hole effect), or by increasing ocular surface
An eye that has no refractive error when viewing a distant
lubrication and wetting.
object, with the accommodation at rest is said to have
emmetropia and an eye that has a refractive error when viewing The specific refractive errors are:
a distant object, with the accommodation at rest, is said to
have ametropia. Hyperopia
Every eye grows after birth and as the eye grows, there is Commonly known as farsightedness, hyperopia or
growth of the eyeball and changes in the corneal curvature, hypermetropia is the refractive error in which the rays of
axial length, lens configuration, etc. Most children see incident light from infinity are focused behind the retina, in an
acceptably well during such growth. Changes happen unaccommodated state. The image of a distant object is
simultaneously in the eye so that the image focuses on the focused behind the retina, either because the eyeball length is
retina as the child grows up. These changes compensate for too short, or because the refractive converging power of the
each other so that the refractive power of the eye as a whole eye is too weak. Common signs and symptoms are blurring
remains within a given range. The changes in the axial length, of vision resulting in headaches, eye-strain, and/or fatigue.
refractive powers of the cornea and the crystalline lens and
Hyperopia may be associated with increased accommodation,
the relative position of these components to each other in
whereby by overacting and stimulating the process of
the growing eye so as to enable the image to focus on the
accommodation, the ciliary muscles attempt to focus the
retina as close to emmetropia as possible is called
defocused image on the retina in an attempt to see better
emmetropization. This process is a combination of the passive
(Figs 2.3.3A to C). This is possible when the extent of the
process which occurs with the normal growth of the eye.
hyperopia is mild to moderate, which can be compensated by
This mechanism also involves a visual feedback mechanism
accommodation. This may however cause severe asthenopia,
from the retinal image and subsequent adjustment of the
and in some cases, may lead to a form of strabismus called
growth of the eye to this feedback.
These changes occur in both, the spherical and the accommodative esotropia, whereby increased accommodation
astigmatic component of the eye. If at any stage, this process results in an increased convergence reflex, resulting in the
of emmetropization is disturbed, it leads to ametropia. genesis of esotropia. This condition has been described in
Following are the common refractive errors of the eye another section of this book. Another condition commonly
or conditions of ametropia: associated with uncorrected hyperopia is the early
• Hyperopia development of presbyopia. This is because of the sudden
– Without astigmatism decompensation of the latent hypermetropia and the lack of
– With astigmatism accommodative reserve because of constant overaction of
• Myopia the ciliary muscles in such patients. Any patient who presents
– Without astigmatism with early onset presbyopia or presbyopia of a power that
– With astigmatism does not commensurate with his age, should be subjected to
• Astigmatism. a cycloplegic retinoscopic evaluation to determine the exact
refractive status of his eye.
Symptoms and Signs of Refractive Errors Hyperopia can be due to:
• Eyeball being too short (Axial hyperopia).
The primary symptom of refractive errors is blurred vision • The cornea, or lens, or both, having less refractive power
for distant objects, near objects, or distortion. Sometimes, (Refractive hyperopia), which can be curvature hyperopia
the excessive ciliary muscle tone can cause headaches and or index hyperopia.
asthenopia. Occasionally, excessive staring can lead to ocular • Abnormal location of the crystalline lens posteriorly in
surface desiccation, causing eye irritation, itching, visual fatigue, the eye.
foreign body sensation and redness. Frowning and squeezing • Absence of the crystalline lens, which denotes an absence
of the eyes while reading along with excessive blinking or of a converging media in the eye. This could be rarely
rubbing are symptoms suggestive of refractive errors in congenital or more commonly be due to surgical removal.
children. These imply unconscious compensatory methods The condition is called aphakia.
Figs 2.3.3A to D: Schematic diagram of the reduced eye, demonstrating that the image is focused behind the retina in a hypermetropic eye.
By the process of accommodation, the image can be converged to the retina in an attempt to achieve better clarity of vision. Convex lenses help
in the correction of the error
• Cycloplegics uncover any latent hyperopia by preventing apparatus, then the patient may actually have no manifest
accommodation. Hence, in an eye which is hyperopic, hypermetropia, though if complete cycloplegia, with total
use of cycloplegics uncover the total extent by doing away paralysis of the accommodational apparatus is achieved,
with the dynamic refractive status of the eye. the total hypermetropia may get manifest.
• Orbital mass lesions, especially retrobulbar tumors (behind • Latent hyperopia: The hypermetropia that is masked by
the eyeball), and central serous choroidoretinopathy can the involuntary accommodative tone due to the eye
cause relative hyperopia by displacing the retina forward. attempting to attain visual clarity is termed as latent
hypermetropia. As already mentioned, this can measure
Classification of Hypermetropia upto several diopters in a child.
by Different Parameters • Total hypermetropia: This refers to the sum total of the
manifest and the latent hypermetropia.
Classification by clinical appearance
• Facultative hyperopia: This refers to hypermetropia that can
• Simple hyperopia is a normal biological variation.
be corrected or overcome by accommodation.
• Pathological hyperopia occurs due to maldevelopment of
• Absolute hyperopia: This refers to hypermetropia that is in
the eye (small eye like in microphthalmos) or ocular disease
excess of the accommodational amplitude and hence
(proptosis).
cannot be corrected by accommodation.
• Functional hyperopia occurs due to paralysis of
accommodation.
Signs and Symptoms
Classification of Hyperopia by Extent of Error The main symptom of hyperopia is blurred vision, especially
when viewing near objects. Hyperopes may have trouble
Hyperopia is often categorized by the extent of refractive focusing when performing near tasks such as reading or sewing.
error: Frequent headaches, aching eyes or eyestrain are common.
• Low hyperopia is a refractive error of +2.00 diopters (D)
or less. Management
• Moderate hyperopia is a refractive error from +2.25 to
+5.00 D. Hyperopia can be corrected with glasses using convex lenses
• High hyperopia is a refractive error of +5.25 D or more. of the required power, contact lens, or refractive surgery
(Fig. 2.3.3D).
The approach to the treatment of hyperopia is to reduce
Classification by Accommodative Status
accommodative demand and to provide clear, comfortable
This is an important functional concept: vision and normal binocularity. To achieve this, each patient’s
• Manifest hyperopia: This implies the strongest convex lens management should be customized with respect to age, degree
correction accepted by the patient for distance vision of symptoms, amount of hyperopia, state of accommodation,
clarity. As mentioned, if the patient already has clear visual acuity, and efficiency during the performance of visual
distance vision by stimulation of the accommodation tasks.1-6
Myopia malignant or progressive myopia and is associated with a

high refractive error and subnormal visual acuity after
Commonly known as near-sightedness, myopia is the
correction. This form of myopia progresses with time
refractive error in which the rays of incident light from infinity
throughout life. It leads to degenerative changes in the
are focused in front of the retina, in an unaccommodated state
retina and is characterized by marked fundus changes.
(Figs 2.3.4A and B). The anterior focusing can be a result of
It is important to realize that the hallmark of pathological
either the eyeball axis being too long, or because the refractive
myopia is the typical progressive fundus associated changes
power of the eye permits strong convergence. Myopia is the
with it and not the extent of the refractive error, though the
most common refractive error present. Distant objects remain
refractive error is usually high because of the progressive
blurred in the uncorrected state because of anterior focusing
increase in the axial length in this condition.5
of these rays in front of the retina. The far point of the eye
Based on the diopteric power of the corrective lens used,
recedes to a finite point (Fig. 2.3.4C). This condition makes
myopia is classified as:
distant objects appear out of focus and may cause headaches
• Low myopia: Myopia corrected by 3.0 DS or less
and/or eye strain.2,5,6
• Moderate myopia: Myopia corrected by lenses between
The etiology of myopia is due to:
–3.0 DS to –6.0 DS
1. The eye’s axial length may be too long, in which case it is
• High myopia: Myopia corrected with lenses greater than
called axial myopia.
–6.0 DS.
2. If there is steepening of the curvature of the cornea or
High myopia is not a synonym for pathological myopia,
the surface of the crystalline lens, it is called curvature
which is characterized by the fundus changes of posterior
myopia.
vitreous detachment (PVD), posterior staphyloma,
3. If the refractive index of the refracting surfaces of the
peripapillary atrophy, “lacquer cracks” in the Bruch’s
eye is more, say for example, lenticular sclerosis, then the
refractive status of the eye becomes myopic. In this case, membrane and choriocapillaries, Fuch’s spot in the macular
it is called refractive myopia. area and a thinned out, atrophic retina.
Other clinical entities with myopia which are usually
Classification temporary and reversible are:
• Pseudomyopia: This is the name given to a state whereby
Myopia is classified as: the myopia occurs because of an increased
• Simple: This is myopia associated with growth of the accommodative response. This is classically seen in students
eyeball. It does not progress beyond the growing years of studying for an examination.
the child, is limited to the extent that can be considered to • Induced myopia: Induced or acquired myopia is the result
be within the range of normal development and is not of exposure to various pharmaceutical agents, variation
associated with the pathological fundus changes mentioned in blood sugar levels, nuclear sclerosis of the crystalline
below. lens, or other such pathological conditions.
• Pathological: This is a degenerative condition accompanied • Nocturnal myopia: This is a specific term for myopia that
by changes in the posterior segment of the eyeball with occurs only in dim illumination, and is largely due to
lengthening of anteroposterior axis of the globe. increased accommodative response associated with low
Pathological myopia is also known as degenerative, levels of light.
Figs 2.3.4A to D: The incident rays of light come to focus in front of the retina in myopia. This could be due to a larger size of the eyeball,
whereby the retina is placed more posteriorly, or could be due to increased converging power of the refractive media of the eye. Concave lens
help in the correction of myopia
Symptoms of Myopia peripheral range of vision, especially in high refractive

errors. These differences may induce asthenopic
Myopes typically do not have “eye-strain”, “watering” of the
symptoms in patients who are shifted from one modality
eyes or headaches as often as hypermetropes do. They are
of rehabilitation to another, especially in the initial stages.
usually detected when it is discovered that they cannot execute
The treatment for nocturnal myopia is to prescribe minus
distance tasks well. When a child makes too many mistakes
power correction for night observation only. The management
while copying from the blackboard, myopia should be
for pseudomyopia involves eliminating the accommodative
suspected. A myopic person can see those objects clearly
excess responsible for the pseudomyopia. The management
that are placed closer than the far point of that eye. The far
of degenerative myopia includes correction with minus lenses
point is determined by 100 cm (1 meter)/Dioptric power of
and monitoring retinal and ocular changes. In case of induced
that eye. This implies that for a –2 D myope, the far point is
myopia, the treatment would depend upon the inducing agent
100/2 = 50 cm.5
or condition.5,6
Correction of Myopia
Astigmatism
The treatment for simple myopia is optical correction.
Astigmatism is that state of refractive error where in an
Concave lenses with the required minus power is the treatment
unaccommodated state, differences in the curvatures of the
of choice (Fig. 2.3.4D). The prognosis for correction of simple
refracting media of the eye can result in the formation of
myopia is very good. Patients can achieve better distance
images at two focal points. Depending on whether both these
vision with correction. Other options are contact lens and
images are defocused from the retina or whether one of
refractive surgery, which have been dealt in other sections of
them is focused on the retina and the other is not, the
this book. It is important to remember while managing myopia
corresponding sphere (myopic or hyperopic) can be calculated
that:
(Fig. 2.3.5). Astigmatism is an important cause of asthenopia
• Relatively adult patients with long standing undercorrected
and headache of ocular origin.
myopia of a moderate degree have hypoaccommodation
as they have never used their accommodation significantly.
Fully correcting these patients would result in signs and
symptoms of marked asthenopia as the patient would
not be able to work at near, which is something that he is
used to doing without using accommodation. The patient
also requires time to adjust to the change in the image
size of objects and increased clarity for distance objects,
which is different from the blurred, large image he is
used to. Such myopes should always be initially
undercorrected.
• However, the above does not hold true for children with
myopia who should be corrected optimally, so that the
normal emmetropic status of accommodation can
Fig. 2.3.5: Depending upon the different positions of the image upon
develop. the retina, the type of astigmatism can be defined as:
• Change from one modality of rehabilitation to another i. Both focal points beyond the retina at r1 and r2 – Compound
like for example, from spectacles to contact lens induces Hypermetropic Astigmatism
changes in the accommodation of the patient. This is ii. One focal point at r3, and the other at r1 or r2 (beyond the retina)
– Simple Hypermetropic Astigmatism
essentially because of the different physical properties iii. One focal point at r4 or r5 (in front of the retina) and the other at r1
of these rehabilitative modes. Contact lens are placed or r2 (beyond the retina) – Mixed Astigmatism. Here the position of
closer to the eye than spectacles and hence there may be r3 may co-relate with the circle of least confusion and may
a change in the image size for the appropriate myopic determine the spherical equivalent of the eye. This forms a direct
corollary of the Strum’s conoid on the optical system of the eye.
correction given for each modality. The inherent prismatic
iv. One focal point at r3, and the other at r4 or r5 (in front of the retina)
effect of the glasses that often aids in the correction of – Simple Myopic Astigmatism
phorias is also not present with contact lens. However, v. Both focal points in front of the retina at r4 and r5 – Compound
contact lens provides an increased depth of focus and Myopic Astigmatism
Classification Symptoms of astigmatism include blurring and distortion

of vertical, horizontal or diagonal lines, eyestrain, eye fatigue,
Astigmatism is defined based on the following parameters:
and headaches.
1. Regularity
Astigmatism is corrected optically with cylindrical lens. A
a. Regular astigmatism implies that the two meridians
combination of spherical and cylindrical lens (sphero-
are always at right angles (90°) to each other and lie at
cylindrical lens) is used to correct spherical errors with an
or near the 90 or 180 degree meridian. This type of
astigmatic component. Uncorrected astigmatic errors can lead
astigmatism is correctable with cylindrical lenses.
to amblyopia.
b. Irregular astigmatism implies that not only are the
principal meridians not perpendicular to each other,
on many occasions, no meridian can be made out. Anisometropia
This is especially seen in patients with scarred corneas. Anisometropia is a refractive error whereby there is significant
c. Oblique astigmatism implies that the two meridians difference in the magnitude of refractive errors between both
are at right angles to each other, but do not lie at or eyes. A difference of even 1D of hypermetropia is considered
near the 90 or 180 degree meridian. to be adequate to induce amblyopia.1,7,8 When a difference
d. Bioblique astigmatism implies that though both the of more than 3 diopters is present between both eyes, and
meridians can be made out, they are neither at right the eyes are corrected with spectacles, the difference in the
angles to each other, nor are they near the 90 or 180 image size (aniseikonia) that is produced, can lead to
degree meridian. difficulties with fusion and even suppression of one of the
Both oblique and bioblique astigmatism are very images. Children withstand aniseikonia to a greater extent
difficult to correct. than adults (as may happen after incorrect biometry for
2. If the regularity is established, the sub-categories are: cataract surgery or due to lenticular myopia subsequent to
a. ‘With the rule’ where the stronger refracting meridian progressive nuclear sclerosis). More anisometropia can be
is vertical and the horizontal meridian is weaker. In withstood with contact lens correction because contact lens
mathematical terms, this implies that the minus are placed closer to the eye with lesser image size disparity
cylinder axis is placed between 180° ± 30°. As under between both eyes.
normal circumstances, the eyelid on the superior
limbus exerts mild pressure such that the vertical
Presbyopia
meridian is steeper, any accentuation of the same
phenomena has been termed as ‘with the rule’. Presbyopia is loss of the lens’ ability to change shape to focus
b. ‘Against the rule’ astigmatism implies that the stronger on near objects due to aging. Typically, presbyopia becomes
refracting meridian is horizontal and the vertical noticeable by the time a person reaches the early or mid-40s.
meridian is weaker. In mathematical terms this implies A convex (plus) lens is used for correction when viewing
that the minus cylinder axis is placed between 90°± near objects. These lenses may be supplied as separate glasses
30°. As this state is opposite to what is physiologically or built into a lens as bifocals or multifocal lenses. Presbyopia
present in the eye, hence this type of astigmatism is is an age-related condition which can occur with or without
called ‘against the rule’. ametropia. Thus, presbyopia can be defined as age-related
It is important to note that ‘against the rule’ astigmatism, loss of ability to sustain accommodation necessary for clear
even in small quantities can cause severe asthenopia, while a near vision. As one grows old, the accommodation ability
much larger magnitude of ‘with the rule’ astigmatism can be decreases and it gets difficult to focus for near . It is a gradual
withstood by the eye. process starting at about the age of 40 in an emmetropic
The nomenclature of each of the above with the spherical patient. The complete accommodative reserve is exhausted
component in the form of compound hypermetropic, simple by the age of about 60 years. It has already been mentioned
hypermetropic, mixed, simple myopic and compound myopic that over-accommodation in moderate hyperopes may result
astigmatism defines the complete state of astigmatism in the in accommodative fatigue and premature presbyopia. It is
eye. also interesting to note that in moderate myopes of about
Thus, the appropriate description of astigmatism includes –3 D to –4 D, where the far point equals about 25 cm to 33
whether it is simple, compound, or mixed, the type of spherical cm, simple removal of the distance refractive correction results
power, its regularity and if regular, whether it is ‘with the in the patient being able to see well for near. Such patients do
rule’ or ‘against the rule’. not require to wear near-glasses. In pseudophakic patients,
accommodation is lost irrespective of age and these patients Visual acuity (VA) is defined as the ability to read a standard
require presbyopic correction. Although blurred near vision test pattern at a certain distance, usually measured in terms
signals the onset of presbyopia, the symptoms reach of a ratio to “normal” vision. 6/6 (20/20) visual acuity is
significance only when the patient’s accommodative amplitude considered “normal” vision. Visual acuity is the spatial
becomes inadequate for his or her individual needs. resolving capacity of the visual system. A concept inherent
The classical explanation of accommodative function to VA is the minimum angle of resolution of the eye, which
is given by the lens relaxation theory of Helmholtz- aids objective measurements of the capacity to see. If this
Fincham. 9-11 According to this theory, accommodative capacity cannot be objectively measured, then steps cannot
response results from ciliary muscle contraction which releases be taken to ameliorate any anomaly in it.
tension on the zonules. This relaxation of zonular tension Minimum Angle of Resolution implies that for any two
shifts the contents of the lens forward, causing the surface objects to be distinguished as separate, they must be separated
of the anterior lens to bulge. Presbyopia thus can be explained by a minimum angle of resolution of one minute of arc at
by the age-related hardening of the lens substance and an the nodal point of the eye.
associated inability of the lens to be molded by the zonules. There are various ways to measure and specify visual
Fatigue of the constantly acting accommodation apparatus is acuity. Multiple standard test patterns have been developed
another mechanism. and are in use. While a variety of test targets are used during
Presbyopia is corrected by use of simple positive spherical refraction, the most useful optical and diagnostic modality is
lenses on top of the distance prescription. This is known as the letter chart used to measure visual acuity.
reading addition or adds.12 Snellen’s Chart, designed by Hermann Snellen is the standard
When prescribing for presbyopia, the patient is allowed chart in use for 150 years since 1862. It is the commonest
to use his/her remaining accommodation. Thus, only the chart used for easy, standardized measurement of VA in clinical
minimum amount of reading add required by the patient for practice, globally. This chart is a high contrast chart containing
performing his/her near tasks is prescribed. However, the graded letter sizes, each constructed on a grid which is 5
most important consideration in determining the reading units wide and 5 units high, where the strokes on the letters
addition is the requirements of the patient, i.e. how near is are of the size of 1 unit of the grid and the width of the
the distance that they normally have to work at and what stroke equals the width of the gap. Each entire letter therefore
close work tasks do they have to perform.13,14 subtends an angle of 5 minutes of arc on the retina at this
The evaluation and management of presbyopia are distance, but in order to analyze its form completely and see
important because significant functional deficits can occur its constituent parts, it is assumed that the eye should be able
when the condition is left untreated. Undercorrected or to resolve them down to the standard limit of 1 minute (Fig.
uncorrected presbyopia can cause significant visual disability 2.3.6). Landolt’s C Chart and the tumble E charts use the
and have a negative impact on the patient’s quality of life. same principle, substituting letters for the C or the E.
Gaining an understanding of the patient’s specific vocational All letter acuity charts, including the Snellen’s Charts and
and avocational visual requirements helps in recommending the logMAR charts use the Sloan letters, designed by Louise
the treatment most appropriate for enhancing visual Sloan in 1959, which are optotypes comprising formed letters
performance. Traditional treatment options include bifocal (C, D, H, K, N, O, R, S, V and Z), and which have been
spectacles. chosen because results with them are comparable to tests
using the Landolt’s C rings (more uniform so that there is
VISUAL ACUITY standardization of recognized letter forms).
Distance visual acuity is determined first with no
Distance Visual Acuity correction and then with the patient’s habitual distance
correction. By convention, the right eye acuity is always taken
It all begins and ends with vision, the functional outcome of first followed by left eye acuity and binocular acuity.
the work of all the structures in the eye. It is necessary before Illumination level recommended for the distance and near
beginning actual refraction to measure the baseline visual vision charts is at least 12–20 foot candle (130–215 lux).
acuity. The measurement of visual acuity gives the measure Most distance VA charts are designed to be used at 6 m, but
of sharpness of vision or the ability of the eye to recognize some are specially designed to be used at a distance of 3 m.
a target in fine details.15 VA charts use characters (letters, pictures, numbers or
Fig. 2.3.6: The principle behind the standardized Snellen’s charts
Fig. 2.3.8: The tumbling E chart. The patient is required to indicate the
direction of the opening of the E. Each E subtends an angle of 5
degrees at the nodal point of the eye at the indicated distance
Snellen chart can objectively measure VA up to 6/60. If

the patient cannot determine the largest letter projected, which
indicates that the VA is less than 6/60 then, the following
steps may be followed to record the VA.
The patient is brought closer to the chart or the hand-
held charts may be brought closer to the patient. If the patient
is able to resolve the topmost letter at 4 meters, it indicates
Fig. 2.3.7: Older version of Snellen chart with non-Sloan letters. that his VA is 4/60. If the VA of the patient is poorer, the
These have gone into disuse now chart is brought closer till 1 meter. If his VA is less than 1/
60, then presence of finger counting is assessed. If finger
counting is not present, it is important to assess whether the
symbols) of different sizes. Each line in the Snellen distance
patient is able to perceive the shadow cast by the movements
VA chart is labelled as a fraction called the Snellen fraction
of the examiner’s hands in front of his eyes. If hand
(Fig. 2.3.7).
movements are not perceived, then the perception of light is
Testing Distance (meters)
Snellen fraction (VA) = _______________________________________________________ assessed. Projection of rays in different quadrants of the eye
Distance at which the size of the letter would
is an important indicator of the posterior segment status of
subtend an angle of one minute of arc at the
retina (meters) in an unaccommodated the eye in the presence of an opaque media opacity. It is
emmetrope. however important to remember that the patient can have
The numerator denotes the distance at which the patient excellent VA but the projection of rays may be inaccurate
is evaluated while the denominator denotes the distance at due to selective destruction of nerve fibers of a particular
which that letter would subtend an angle of one minute of quadrant of the eye due to either retinal or optic nerve disease
arc at the retina of an emmetropic eye without any organic like glaucoma or retinitis pigmentosa.
or functional anomaly. The problem associated with the Snellen chart is that the
Also, there are charts for illiterate persons who cannot progression of letter sizes does not represent equal
interpret letters and children (tumbling ‘E’, picture and Landolt incremental or decremental steps in terms of visual difficulty.
‘C’ Charts). As mentioned, the patient is required to tell the This deficiency is overcome by the logMAR charts. In this,
location of the opening of the C and the E in such cases (Fig. contour interaction is scaled in relation to letter size. The
2.3.8). letter size follows a logarithmic progression, in 0.1 logMAR
steps thus converting the geometric pattern of the Snellen it while the latter deals with the concept that the observer
chart to a linear one. LogMAR is an acronym for log of the can make certain spatial distinctions, whereby they can detect
Minimum Angle of Resolution (MAR) (Fig. 2.3.9). very small differences in the relative localization of different
These charts offer many advantages over Snellen’s charts. features of objects. This is also called hyperacuity.16
However, they have not become excessively popular because Although visual acuity is the most often measured
they often tend to be larger charts, the measurements may parameter of vision, it considers only one aspect of vision.
take longer time and they have to be interpreted appropriately. Other aspects, such as visual field and contrast sensitivity are
These charts are therefore not used commonly in routine equally important in defining the functional capabilities of
clinical screening set-ups but they are indispensable in a research the subject. These have been described in another section of
set-up. The key features of these charts are: this book.
• Five letters on every line (Equal letters)
• All letters have equal height and width Near Visual Acuity
• Spaces between letters are equal to one letter width
• Letters are limited to the all 10 Sloan letter set (H, V, Z, Near visual acuity measurement is used to describe the ability
D, S, N, C, K, O, R) of the eye to perceive the size and shape of an object involved
• The lines progress in 0.1 logMAR steps in near tasks, e.g. reading, and for this measurement print
• Every letter read counts as 0.02 of each line. This avoids sizes are used. The ability to read N6 size print at 33 cm (as
the use of pluses or minuses appended to the Snellen used in small newspaper advertisements) is considered normal
fraction near visual acuity.
• On a logMAR chart, the 6/6(20/20) letter has a value of The most common form of test charts are in N notation
logMAR value of 0 (as 6/6 has a Snellen fraction of 1) (Fig. 2.3.10). In this, each point is approximately 1/72nd of
• As acuity becomes worse, the value of the logMAR an inch. A test card usually starts at 6 point and increases to
increases. 36 to 48 or even 60 point. The type is usually in the standard
Other concepts useful in the assessment of distance visual Times New Roman font. The smallest letter line which an
acuity are: individual can read is written as N6. This was based on a
• Minimum visible standard newspaper font which used the Times Roman type-
• Minimum discriminable. face. This chart was thus termed as the Times New Roman
The former refers to the detection or non-detection of a Near Vision Charts as it was decided that this was the most
visual stimulus in a background by manipulation of its size in suitable font for reading-chart use.
Fig. 2.3.9: A representative diagram of logMAR visual Fig. 2.3.10: The standardized near vision chart
acuity chart using Sloan letters
Near vision charts are also available in the Reduced Snellen The Retinoscope
system. It utilizes the conventional Snellen distance VA chart The retinoscope is a small projector which emits a spot or
which is reduced such that the smallest letters in the lower streak-like image of the lamp filament itself (Fig. 2.3.11).
case subtends an angle of 5 minutes of arc at the retina at The instrument is used to illuminate the internal eye and to
one meter (12.5 minutes of arc at 40 cm) which is therefore observe and measure the rays of light as they are reflected
equivalent to a 20/50 reduced Snellen letter at 40 cm.6 by the retina.
The near test is usually read at the working distance If the projected light emitted from the retinoscope is
depending on the occupation or else at 33-40 cm. made either divergent or parallel or convergent to a point
somewhere behind the patient, the optical effect as far as the
THE PRACTICE OF RETINOSCOPY patient’s eye is concerned is the same; and this is called the
The measurement of the correct lenses required to bring the “plano-mirror” effect. If, on the other hand, the projected
images seen by the eyes into best focus is known as refraction. filament image is located somewhere between the observer’s
Retinoscopy is the chief objective method of determining eye and the patient’s eye, the retinoscope is said to have a
the refractive error of an eye. “concave-mirror” effect. The modern streak retinoscope has
It is the only way to assess the refractive error in infants, both these systems incorporated in it. Concave mirror effect
small children, illiterates, uncooperative patients, patients with is required when high refractive errors are being checked.
speech loss and patients who speak a different language. A However, when retinoscopy is performed with the concave
slit of light is projected into the eye and the motion of the mirror, it should be mentioned in the records so that a baseline
returned light is analyzed. Retinoscopy is typically used as a is established because the spherical values after assessment
starting point for subjective refractions.17 with a plane mirror and a concave mirror is different.1,2,16-18
Refraction is about identifying the far point in the eye, The original type of retinoscope called the Priestley Smith’s
locating it and neutralizing it to the pupillary plane of the retinoscope, which is still available, provides a spot light
examiner. reflected from a silvered mirror with a central aperture. It
Retinoscopy is done at an arms length from the patient,
which is anywhere between 50 to 66 cm. This is known as
the working distance and is used for convenience and accuracy.
The aim of retinoscopy is to find the lens that will stop
the retinoscopy reflex from moving. This is done by adding
lenses to make the reflex brighter, move faster, and ultimately,
stop (or neutralize) the movement. This point is known as
the end point or point of reversal. To do this the patient
must look at distant object (to prevent accommodation) and
retinoscopy must be performed as close as possible to the
patient’s visual axis.
At the end point, the patient’s eye should be focused on
the retinoscope or in other words the patient becomes relatively Fig. 2.3.11: The principles of retinoscopy. Note the mirror reflecting
myopic as compared to when he was fixating at a distant the ray of light into the eyes of the patient and the reflected light being
object.17,18 assessed by the observer, through the peephole present in the
Static Retinoscopy is used to obtain an objective measure retinoscope. Most of these peepholes incorporate a convex lens to
relax the accommodation of the observer as otherwise the retinoscopy
of the patient’s refractive state. In static retinoscopy the
values may be different. By observing the behavior of the reflex as
refractive state is determined while the patient fixates a distance mentioned above, the observer can objectively determine the refractive
object (to relax accommodation). In dynamic retinoscopy, the error of the patient’s eye. To arrive at the patient’s error of refraction,
patient fixates on an object in the plane of the retinoscope the dioptric power corresponding to the distance between the patient
thus done under accommodative state. Near point retinoscopy and the retinoscope (called the working distance) is subtracted from
the total lens power used to obtain neutralization. This method of
gives a good insight into the patient’s accommodative system. assessment is absolutely essential in those patients who are unable
However, for estimation of refractive error, static retinoscopy to provide a subjective response. This would include children,
needs to be performed.18 uncooperative patients or unconscious patients
incorporates both, a plane mirror and a concave mirror. The

plane mirror is actually a very small part of a concave mirror
with a radius of curvature of 150 cm which appears to be
plane, while the concave mirror has a radius of 25 cm. In
1901, Wolff introduced the first electric retinoscope. The
first self-illuminated retinoscopes contained a tiny lamp bulb
that shone a spot of light into the eye. Later ‘variable vergence’
models could produce the effect of the spot being reflected
by a plane mirror or less commonly, a concave mirror. The
retinoscope was invented by the ophthalmologist, Jack
Copeland. The original spot retinoscope has been refined to
the modern streak retinoscope.18
Types of Retinoscopes
The spot retinoscope: This produces the effect of a spot
being reflected by a plane mirror or, less commonly, a concave
mirror, from a light source. The classical example is the
Priestley Smith retinoscope.
Fig. 2.3.12: Reflex of light seen through a streak retinoscope
The streak retinoscope: This retinoscope incorporates a
self-illuminating source, making the instrument more flexible
and portable. It is possible to evaluate children and
uncooperative patients appropriately with this as the light
source is within the instrument itself. This light source is a 5
mm long filament that produces an image on the retina and
this reflex appears as red-orange glow with a slight shadow
around (Fig. 2.3.12).
Procedure: The retinoscope itself is a battery-charged or electric-
powered hand-held light which directs a beam of parallel or
slightly divergent beam of light into the patient’s eye (Fig.
2.3.13). The light illuminates the patient’s retina and is reflected
back causing a reflex in the patient’s pupil. The patient is
instructed to fixate at a distance target. The target chosen for
the patient to observe must be large, like, for example the 6/
60 letter on the Snellen Chart. It may be helpful to tell the
patient to relax their eyes. The patient’s right eye is evaluated
with respect to the examiner’s right eye and the patient’s left
eye is evaluated with the examiner’s left eye (Fig. 2.3.14).
The examiner, while observing the reflex in the patient’s
Fig. 2.3.13: A streak retinoscope
pupil can determine the refractive condition of the patient’s
eye by using trial lenses. The trial or corrective lenses placed
in front of the patient’s eye cause the reflected light to focus The motion of the streak of light in the patient’s eye is
or conjugate to the pupil of the examiner’s eye. The reflected either “with” or “against”. The next step is to influence the
light from the patient’s retina is known as the “fundus reflex”, direction of the motion observed by placing appropriate lenses
which is located in the plane of the patient’s pupil. To clearly in front of the patient’s eye. Thus, plus lenses are used to
see the fundus reflex, the refractionist must be within one counter any observed “with” motion and minus lenses, the
meter or less from the patient’s eye. “against” (Fig. 2.3.15).
As these lenses are added, the observer continues to watch • Neutrality: The rays converging at the focal point cause
their effect on the image motion through the retinoscope no motion. No movement implies that the patient’s myopia
“peep hole”. The goal is to “neutralize” this observed motion is equivalent to the dioptric value of the working distance.
with the lenses. At “neutrality”, a small change in the added • Against motion: The rays converge before the focal point
lens power causes prompt reversal of the direction of image and cause “against” motion. At this point, the patient’s
motion. myopia is greater than the dioptric value of the working
With no lenses in place during performing retinoscopy, distance.
there are three possible initial reflexes that may be observed Thus, the movements of “with” (hypermetropia) and
(Fig. 2.3.16): “against” (myopia) determine the possible refractive error.
• With motion: The rays converging beyond the focal point Abnormal curvature, coning, and scarring may lead to
cause “with” motion. irregular reflexes and a reflex called “scissoring”, where the
This implies that the patient is hyperopic, emmetropic or central and peripheral reflexes move against each other. These
less myopic than the dioptric value of the distance. reflexes are extremely difficult to neutralize. Also, if there
are different movements in different meridians, it implies
astigmatism.
The distance at which the refractionist observes the fundus
reflex is called the “working distance.”
The necessary lens power placed in front of the patient’s
eye in order to compensate for this distance is called the
“retinoscopy lens” or “working lens.”
Automated Refractometer
An autorefractor or automated refractor is a computer

controlled machine that is used to provide an objective
measurement of a person’s refractive error. There are different
optical principles applied for this. It is important to reiterate
that this is not an alternative to manual refraction under
difficult circumstances. In most cases of simple refractive
error, it provides accurate measurements. Some studies have
Fig. 2.3.14: The procedure of retinoscopy reported that autorefractor measurements without application
Fig. 2.3.15: Schematic diagram showing reflex as seen through the streak retinoscope during retinoscopy
Fundamentally, the principles of automated retinoscopy

are based on the optical principles mentioned below. Modern
autorefractometers use a combination of all of these principles
to arrive at a conclusion. Infrared optometers are in vogue
nowadays. They have the advantage of relaxing proximal
convergence and accommodation and are hence more
accurate.
i. Optometer principle
ii. Scheiner double pin-hole principle
iii. Meridional refractrometry simulating retinoscopy.
The Optometer Principle

This is based on the principle that if an object is placed at the
anterior focal point of a lens system whose posterior focal
point lies in a spectacle plane in front of an eye of
undetermined refractive status, the image will be formed at
the retina in an emmetropic eye. If the object is moved
anterior to the anterior focal point, the rays that will come
out from it will diverge while the converse will be true if the
Fig. 2.3.16: Ray diagrams of the genesis of the “with” and “against” object is placed posterior to the anterior focal point of a lens
reflexes during retinoscopy system. Thus the vergence of the image at the second focal
point of the lens system directly correlates with the distance
of the object with respect to the first focal point of the
of cycloplegia can result in significant overestimation of system. The measurement of this vergence gives a measure
myopia because of proximal convergence. Again, in children of the refractive status of the eye. This is the optometer
manual retinoscopy is to be preferred because the testing of principle, which forms the basis of objective auto-
the refraction of the eye of a child has to be customized as refractometers (Fig. 2.3.17).1,20
per many parameters which will be described in another chapter
in this section.1,2,17-21 The Scheiner Disk Principle
Advantages of automated refraction are that it is a simple
The Scheiner’s disk comprises a double pinhole system that
application tool that is quick, painless and very useful for
is placed in front of the pupil (Figs 2.3.18A to E). Only the
screening purposes. It can be operated by an ophthalmic
central rays from a distant object can traverse through these
technician. The patient takes a seat on the machine and places
pinholes and converge on the retina after undergoing
his chin on the chin rest. The machine evaluates one eye at a
refraction by the eye in an emmetropic state. In myopic
time and the readings are shown on the screen. Manual
patients, this convergence will occur in front of the retina
observations are not required though a manual mode is usually
and in a hypermetropic patient, behind the retina. Adjustment
present in the machine, in case the automated mode does not
of the position of the object (far point) whereby the image
show any readings. In such cases, a dilated manual retinoscopy
forms at the retina gives an objective measure of the refractive
becomes mandatory. However, as this would account for
power of that eye.1,2,21
only about a small number of patients with refractive errors,
the human effort required for assessment of refractive errors
Meridional Refractometry
by manual retinoscopy is significantly minimized by this
Simulating Retinoscopy
equipment. The basic purpose of autorefractor is therefore
to increase the speed and efficiency of the refraction process This is a modality whereby the measurement of the spherical
on a large scale screening basis. power is performed in at least three meridians in an attempt
The image quality analysis takes into consideration, the to determine the principle axis and its refractive power
clarity of the image of a picture as perceived by the patient. through an empirical mathematical formula. This measures
The picture moves in and out of focus as the machine takes astigmatic refractive errors with a great degree of accuracy.
readings to determine when the image is on the retina. The optics of this system is outside the scope of this chapter.
Fig. 2.3.17: Objective autorefractors comprise an infrared source, a fixation target and a Badal optometer. An infrared light source (around
800-900 nm) is reflected back from the deeper layers of the eye. However, the refraction of the eye to infrared rays is more hypermetropic than
that for the visible rays because they are not reflected from the same layers of the retina. This calibration is incorporated within the system of
the refractometer. Virtually all autorefractors have a Badal optometer within the measuring head. Infrared light is collimated and passes through
rectangular masks housed in a rotating drum. The light passes through a beam splitter to the optometer system. This system moves laterally to
find the optimal focus of the slit on the retina. Optimal focus is achieved when a peak signal is received from the light sensor. The polarizing
beam splitter effectively removes reflected light from the cornea whereas the slit image on the retina passes through the polarized beam splitter.
The system measures at least three meridians of the eye in order to derive the refractive power of the eye using the sine-squared function.
A variety of targets have been used for fixation ranging from less interesting ‘stars’ to pictures with peripheral blur to further relax accommodation.
All autorefractors now use the fogging technique to relax accommodation prior to objective refraction
Other essential components of a retinoscopy setup are: The sequence of inserting lenses in the slots from posterior
to anterior are:
Trial set: A typical trial set of test lenses has spheres of • Slot situated next to the eye holds a spherical lens;
every quarter of a diopter to 14 diopters and every 2 diopters • Slot in the middle holds a cylindrical lens;
to 20 diopters. Cylinders are present at a measure of every • The furthest from the eye holds a prism, Maddox rod, or
quarter of a diopter to 2 diopter and every half diopter to 6 any other accessories.
diopter in both, plus and minus lenses. It also contains prisms The adjustable parts of the frame include the temples,
upto 10 diopters, and accessories such as plano lenses, pinhole, the nose pad, the temple angle, and a scale to adjust the inter-
occluder, stenopeic slit, Maddox rod, and red and green pupillary distance (IPD). These are necessary so that the trial
glasses. lenses are well placed at standard distance from the eye and
are accurately centered.
Trial frame: It is an adjustable frame that holds trial lenses
used during retinoscopy or refraction tests on the eye. It has Cross cylinder: Jackson’s Cross Cylinder (JCC) is an important
at least three slots to incorporate the lenses, one for the tool for subjective verification of the cylindrical power and
spherical lens , one for the cylindrical lens and another one its axis (Fig. 2.3.19). It is spherocylinder combination in which
for adding prisms or for using any of the accessories the sphere is half of cylinder with an opposite sign. The
mentioned above. Sometimes an additional slot is present for commonly used cross cylinder has a –0.25D sphere with a
the near vision add. These frames are available in pediatric +0.50D cylinder incorporated in it. Cross cylinders are thus,
and adult sizes. The appropriate fit of the trial frame is combinations of two cylinders whose powers are numerically
important to assess both subjective and objective retinoscopy. equal and of opposite sign and whose axes are perpendicular
Figs 2.3.18A to E: Refraction of the eye through the Scheiner Disk Principle: (A) Position of the image of an object placed at infinity in an
emmetropic eye is at the retina; (B) Position of the image of an object placed at infinity in a myopic eye is in front of the retina and is hence not
clear; (C) Recession of the far point from infinity to a point where the image forms on the retina and is hence clear, provides a measure of the
refractive power of that eye; (D) Position of the image of an object placed at infinity in a hypermetropic eye is behind the retina and is hence
not clear; (E) Hypermetropes have a virtual far point as only converging rays can focus on the retina. Thus extrapolation of the divergence of
rays from the actual point where the rays come to focus behind the retina to the retina, again provides an objective measure of the
hypermetropia
to each other. The Jackson Cross Cylinder is usually mounted Cross cylinders are used to refine the cylindrical or the
in a ring with a handle at 45 degrees from the axis so that a spherocylindrical power and its axis.
twirl of the handle changes the cross cylinder to a second • While testing the axis, the correcting cylinder needs to be
position (Fig. 2.3.20). An example is a change from the straddled with the axis of the JCC.
retinoscopic value of +0.25DC × 90o/–0.25DC × 180o to • While refining the cylinder power, the JCC is flipped, so
–0.25DC × 90o/+0.25DC × 180o. that the dots line up with the correcting cylinder axis.
Fig. 2.3.19: Cross Cylinder
Now as the JCC is flipped, –0.50 cylinder is added or

subtracted from the retinoscopy values. The patient may Fig. 2.3.20: The handle is placed at 45o angle from the main meridian,
indicate improvement with one value. When the responses such that while keeping the cross cylinder on the temporal side of the
patient, a twirl of the hand can change the value of the cylinder being
to the JCC flip are equivocal, (equal blur on both sides of
tested
the flip) then theoretically the appropriate cylinder
correcting amount has been achieved.
The baseline for starting the procedure, is the appropriate Pinhole and stenopic slit test: This simple test is one of the
correction prescribed as per the retinoscopy finding or the backbones of subjective assessment of visual functions. The
autorefraction. The targeted visual acuity should be one line optical principle of the pinhole is based on the fact that it
above the best clarity that can be achieved. increases the depth of focus of the central single ray emanating
Procedure of JCC from an object and cuts out all peripheral rays that come to
• Checking of axis of cylinder: The principles of an obliquely focus at different points in front or behind the retina, thus
crossed cylinder are applied. A moderately strong cross- causing defocusing of a clear retinal image of the object (Fig.
cylinder, i.e. +/– 0.50 D is held before the eye so that its 2.3.21). The pinhole has a diameter of about 0.75 mm to 1
handle is in the axis of the trial cylinder axis. The visual mm in the center of a circular disk that can be placed on a
acuity is tested first with one side and then after twirling trial frame slot. Though, ideally, this diameter does not cut
the cross cylinder to the other side. If visual improvement out some of the peripheral rays, a smaller diameter would
is attained by one of the 2 faces of the cross cylinder, the decrease the visual acuity because of the optical process of
correcting cylinder is turned slightly (about 5o) in the diffraction, already described in a previous section. As the
direction of the axis of the cylinder of the same pinhole cuts out all peripheral rays causing aberration, insertion
denomination (+/-) in the JCC. The test is then repeated of the pinhole can provide us the following clinical correlations.
several times until the position of the trial cylinder is – Improvement in visual acuity: This implies the existence
found at which rotation does not give any change. of peripheral optical aberrations and the fact that the
• Checking of the power of cylinder: In order to check the decrease in vision is due to a refractive error, one of
strength of the cylinder in the trial lens, one of the two the main cause of peripheral optical aberrations.
marked cylindrical axes of the JCC is placed in the same – Neither improvement nor further decrease in visual acuity: This
direction as the axis of the cylinder in the trial frame and implies the presence of a media opacity that has
then perpendicular to it. In the former case, it enhances obstructed both, the peripheral and the central rays
the effect of the cylinder by 0.25 D, while in latter case, coming from the object. This is the reason that
it diminishes it by the same amount. If the VA is unchanged performing the pinhole test often confirms the
in either of these positions, the cylinder in the trial frame necessity for performing a cataract surgery in a patient
is correct. But, in case of improvement, the change should with media opacity in the absence of any other organic
be put into practice and repeated verification with the ocular disorders.
new combination should be continued till the point of no – Decrease in visual acuity: In cases of central retinal
change in either position is achieved. disorders like CSR (central serous retinopathy) or
Fig. 2.3.21: Ray diagram demonstrating the optical principle of the pinhole
CME (cystoid macular edema), the pinhole may Subjective Refraction

actually decrease vision because not only is the central
The procedure of retinoscopy is complete only after objective
area pathological, all peripheral rays that aided partial
refraction is followed by subjective refraction. In this
vision or even retinal eccentricity in long standing cases,
technique, the examiner is guided by the patient’s response to
is cut off. the changes in the appearance of observed targets as the
Thus, this simple out-patient procedure provides power of the lenses before the patients eye is altered. This
considerable information regarding the possible pathology determines the final power of the spectacles that is prescribed
that the patient may be having. Its simplicity and the ease of to the patient optimizing his visual needs, his occupation, age,
the interpretation of the findings implies that ophthalmic state of accommodation, facial features and any other systemic
paramedics can also perform the test with ease and refer or ocular pathology that he may be having. It is important to
correctly.1,2 note that irrespective of the excellent quality of objective
An adaptation of the pinhole is the stenopic slit. Here refraction, if the patient does not accept it, it is of no use.
instead of a circular hole, there is a slit present in the center Also, a good optician should be able to transform the
of the circular disk, which acts as an extended pinhole with a prescription to an effective and appropriate spectacle glass,
width of 0.75 to 1 mm, only permitting light rays in the axis otherwise, again, the patient will not be happy and the purpose
of the slit to enter the eye. It is thus used to determine both, of having performed the whole sequence of evaluation will
the presence of a refractive error and the principle axis in not serve any purpose.
astigmatism. Hence, when the slit lies in one principle axis of Subjective refraction may be performed by use of trial
the astigmatic eye, the other principle axis is eliminated, thus frame or by use of phoropters.
increasing the clarity of vision by breaking the Strum’s conoid. To establish a starting point, the retinoscopy finding, the
Other classical use of this optical principle is in determining evaluation of the autorefraction, and the previous power of
the axis of a possible optical iridectomy. The stenopic slit glasses are all useful guides.
determines the zone of least deformity of the cornea which
would commensurate to the best visual acuity and hence would The steps in achieving this goal are:
be the chosen area for performing the iridectomy.
Another classical use is to break the colored haloes in The First Step: Controlling Accommodation—
immature cataract due to irregular refractive index in different The Fogging Technique
parts of the lens, which differentiates it from the colored The objective is to relax accommodation which otherwise
haloes seen due to acute intraocular rise in angle closure results in acceptance of over-minus or false cylinder amounts.
glaucoma and the resultant diffuse corneal edema, where the – The spherical power is achieved.
colored haloes do not break upon rotating the stenopic slit in – The spherical correction is given by adding +1.0D
front of the eye. This is called the Fincham’s test.1,2,19 sphere or a higher lens which reduces the visual acuity
from 6/6 to 6/18 or less (provided the patient was from each other and are hence called clock dials. 1,2 The
reading 6/6 in the first case). procedure is:
– Plus power is reduced and minus power is added in • The patient is initially fogged.
0.25 steps till the patient can just read 6/6, (the best • Subsequently, fogging is discontinued and the patient asked
corrected visual acuity is achieved). to compare the sharpness of various lines in different
This is specially helpful when moderately hyperopic directions. This is to determine if there is astigmatism
powers are being corrected because over-accommodation and present.
non-acceptance of the appropriate power of glasses in the • The point of greatest contrast implies the direction of
norm in such cases and until the accommodation is relaxed the astigmatic focal line closest to the retina. If there is
by an active effort, the patient would always be happier with no such line, it is expected that the patient would not be
an undercorrected power of glasses. This may not be having significant astigmatism.
acceptable in cases of accommodative strabismus or patients • A minus cylinder is placed on the line, stated to be the
who have already presented with signs of asthenopia. In sharpest by the patient, and its power is increased in graded
children with hypermetropia and esotropia who do not accept steps till the end point is reached (which is the point when
the appropriate power of glasses, fogging with cycloplegics the all lines appear to have equal contrasts). This power
for a temporary period can be tried, under monitoring, so determines the astigmatic component of the refractive
that the child accepts the appropriate power and gets used to error and equalization of contrast implies a collapse of
it, and even upon the return of the normal ciliary tone after the Strum’s conoid. Subsequent to this, the appropriate
the effect of the cycloplegics are over, the child continues to spherical component can be determined by placing the
wear his glasses properly. sphere in the phoropter or the trial frame.
The Second Step: Astigmatic Third Step: Monocular Spherical End Point
Component of Refractive Error The rule is to prescribe the maximum plus and the least minus
Cylindrical power and axis is determined uniocularly by two power that permits the maximum acuity possible. Several
methods: techniques are used but the most common and practical is
– Jackson cross cylinder the duochrome test.
– Astigmatic fan. Duochrome or the bichrome method: It is the most useful,
JCC has been described in details in a previous section. traditional method to determine the final spherical power. It
The use of the astigmatic fan is described. utilizes the optical principle of chromatic aberration (Figs
Astigmatic fan/dial: This test is more time consuming and is 2.3.23A to I). It is a fact, as already explained in another
hence performed only when indicated. The test is performed chapter in this section that white light breaks into its seven
component colors with differing wavelengths. Thus in an
after fogging and neutralization of the cylindrical error with
emmetropic eye, the blue light comes to focus in front of the
cylinder lens of minus power is attempted (Fig. 2.3.22). Fixed
retina and the red light focuses behind. The yellow component
astigmatic dials have lines spaced at angles of 10 to 30 degrees
focuses on the retina (Fig. 2.3.23A). This has the following
implications:
• In axial myopia, with a larger eyeball, the red component
may focus on the retina (Fig. 2.3.23B)
• In a hypermetrope, with a smaller eyeball, the blue-green
component may focus on the retina (Fig. 2.3.23F).
Thus, the following situations may arise:
• An appropriately corrected myope will perceive yellow
light or no particular preference for either red or blue
light (Fig. 2.3.23C)
• An undercorrected myope will perceive red light (Fig.
2.3.23D)
• An over corrected myope will perceive blue green light
Fig. 2.3.22: An astigmatic dial/fan (Fig. 2.3.23E)
Figs 2.3.23A to I: Interpretations of the duochrome test (see text for explanations)
• An appropriately corrected hyperope will again have no difference in the power of glasses in both eyes is more than
particular red or blue green preference (Fig. 2.3.23G) 3D. A balance has to be struck between acceptable visual acuity
• An undercorrected hyperope will perceive blue green light in each eye and the binocular working of both the eyes in such
(Fig. 2.3.23H) cases. For example, if the patient is 6/6 in each eye with a
• An overcorrected hyperope will perceive red light (Fig. refractive correction of -2DS and -8DS in the right and the
2.3.23I). left eye respectively, prescribing the complete correction may
result in unacceptable aniseikonia. If -5DS is prescribed in the
Thus, this principle can be utilized to determine whether
left eye in such cases, though the patient may have acceptable
the prescribed spectacle power is under or over corrected.
The principles of fogging and astigmatic correction are image fusion, but the visual clarity may become 6/36, which is
followed. again not acceptable. Contact lens is a very valid option in such
The patient is asked to read the high contrast Snellen cases as it permits a larger range for image fusion for the
letters on a green background and a red background. appropriate refractive correction given because these are placed
Depending on the clarity of the letters in each background, much closer to the eye than spectacles. Hence, these are
the exact status of the refractive correction can be assessed considered in the appropriate management of anisometropia
and be modified as per the subjective requirements of the and also visual rehabilitation of anisometropic amblyopia after
patient. Here, it is the overall patient that we are talking about the amblyopic component is treated.1,2 It has already been
and not just the eye. What may be optimum for the eye may reiterated that children adjust to higher degrees of aniseikonia
not be acceptable for the patient. The classical example is the than adults and hence a larger disparity of spectacle power can
undercorrection of the myopia that is preferred in be prescribed for them for binocular use than in adults.
uncorrected long-standing adult myopes with decreased However, each of these management protocols is customized
accommodation as here, optimum correction for distance and requires individual care and monitoring. There are no
results in severe asthenopia for near. generalized rules here, just guidelines and principles mixing
This assessment method may be unreliable if the colored optical principles, and patient benefit.
red and green filters used are not standardized or the room
illumination is inadequate. In patients with color vision defect The Fifth Step: Near Addition
too, this assessment may be a problem. In such cases, the
After finalizing the distance power, the near addition is given
patient may not be asked to identify the background color in
over the distance power to presbyopic or pseudophakic
which he sees the letter better (that is known to the examiner)
patients. The appropriate near add is checked with the lenses
but the background situation in which he reads the letter
being inserted in the most anterior slot of the trial frame.
better gives an idea to the examiner regarding the status of
While prescribing the near add, the occupation and needs of
his subjective refractive correction for the examiner knows
the patient have to be taken into consideration. There are
whether that background is red or green.1,2,22
patients who may need a range for near vision, whereby
The Fourth Step: Binocular Equalization correction for both reading and for an intermediate work,
say on a computer, in required. This is true for librarians and
This has to be done after the best corrected lens is verified even surgeons, who require intermediate range correction
uniocularly. The binocular status then needs to be balanced. for surgical purposes without the use of any other ophthalmic
This is done by performing a rapid alternate cover test. The appliance like microscopes or loupes to aid his work.
patient continues to look at the visual acuity chart, while the Considering these needs, bifocals with a distance and a near
examiner performs the alternate cover test. The clarity and level, bifocals with an intermediate and near levels, trifocals
sharpness of the image in each eye is compared by providing with distance, intermediate and near components, progressive
the patient adequate time to pick any difference between the lens or separate use of different lenses for different types of
vision in both eyes. The spherical number can then be adjusted work (which leads to the extremely discomfiting ‘lost spectacle’
accordingly. This is similar to what a surgeon does while adjusting syndrome) are all alternatives. As already mentioned, moderate
the operating microscope binoculars. The binocular stereopsis myopes of -2DS to -4DS gain in such situations because
measures can be taken with the help of the TNO test or the they have the option of using their normal uncorrected far
Titmus fly test. In patients with anisometropia, though the point for performing near work under such circumstances,
individual clarity in each eye may be optimum, binocularly, something they have been used to all their lives. They may
there may be unacceptable aniseikonia, especially if the continue to use the distance glasses for far. Thus, there is no
situation that is better or worse than the other here. These PRESCRIPTION OF SPECTACLES
are all viable options and the patients and the examiner have
to decide what would be most appropriate in an individualized Determination of Lens Type and Power
manner.1,2
After all the efforts that go in having an appropriate
retinoscopy evaluation, the next step is to prescribe the
The Final Step: Orthoptic and
appropriate glasses, such that the optician has no problems
Binocular Vision Status
making them. It is again important to understand that the
After finalizing the power, it is mandatory to check the actual prescription may not be the ideal ophthalmic correction,
binocular visual status, especially stereopsis with the help of but what suits the patient the most, while optimizing ophthalmic
the TNO test or the Titmus fly test and rule out phorias, gains. The following points need to be kept in mind while
tropias, diplopia or suppression, so that the appropriate prescribing spectacles:
customized prescription does not result in any sensorineural
deficit or inacceptable motor problems like the decompen- Determination of Optical Center
sation of a phoria into a tropia. These have been dealt in of the Spectacle Lens
another section of this book.
It has already been mentioned in the chapter on geometric
While performing subjective refraction, it is important to optics that the optical center of a lens is a point on the principle
remember that: axis of the lens, where incident rays do not undergo any
• The testing is done in circumstances which can be deviation. For better centration of the prescribed spectacles,
considered to be the routine state in which the patient the optical center of lens should line up with the pupil. The
would be performing his everyday work. Thus, these optical center is a finite point on an ophthalmic prescription
should not be done when the pupils are under the effect lens where no prismatic effect is manifest. It should be kept
of cycloplegics or mydriatrics. These tests are very aptly in mind that in uncut lenses, the geometrical center may not
called post-mydriatic tests (PMT). The patient is called always be its optical center. Marking the optical center of the
for a re-evaluation for these parameters and comparison lens is advised before spectacle fitting. These methods are:
with the objective refraction depending on the duration
of effect of the cycloplegic used. Details regarding the Use of a cross chart: This is a very simple technique to mark
cycloplegics and mydriatrics used in ophthalmology have the optical center of a lens (Figs 2.3.24A to C). A cross is
been described in another section of this book. An marked on a plain sheet of paper and the lens is placed over
exception to this general rule is prescribing the highest it (Figs 2.3.24A and B). If the optical center of the lens is not
extent of the hypermetropic correction, subtracting only placed over the cross, it will tend to deflect (Fig. 2.3.24B).
for the distance between the patient and the examiner, in Alignment of the cross such that there is no deflection of
cases of hypermetropia with esotropia in children. In case the lines determines the optical center of the lens (Fig.
these children are evaluated after the effect of the 2.3.24C).
cycloplegic goes away, the tone of the ciliary muscles would By reflection method (using spot streak light): This has been
come back, improving vision and accentuating the extent described in a subsequent section of this chapter.
of esodeviation and the child would never accept the
spectacle power prescribed and actually required by him Use of the lensometer (focimeter): Details regarding the working
to relax the accommodation and ameliorate the of the focimeter is described in a subsequent part of this
esodeviation. The balance in such cases is very difficult section. However, it is important to stress that focimetry is
to achieve and takes time, repeated refractions and an important modality for determining the optical center of
dedication. a lens. After the instrument is calibrated, the unknown lens is
• Also, subjective testing is totally patient dependent and inserted and the mires are focused at the center of the cross
malingerers, slow responders, children or poor observers of the lensometer, by adjusting the lens. That spot on the
can provide misleading replies. In such cases, the evaluator lens where this is possible, marks the optical center of that
has to provide the best customized power of glasses lens. This is the method adopted by most opticians to mark
keeping in mind the objective refractive status of the the optical center of the lens before fitting the lens on the
patient and his needs. spectacle frame.
Figs 2.3.24A to C: The lens is placed over the cross marked on the
paper. Aligning the lens over the cross in a manner such that there is
no deflection indicates the optical center of the lens
Use of the reflection method: This is another clinical method for

determining the optical center of the lens. The lens is placed
on a table and a light source is held above it. Two images of
the light source are formed due to reflection from two surfaces
Fig. 2.3.25: The spectacle lens with the pantoscopic tilt
(anterior and posterior surface of the lens). That position
where these two reflections superimpose upon each other
mark the optical center of the lens.
Transposition of Lenses
Pantoscopic Tilt
The actual prescription of the power of glasses has to be
In normal daily life, the routine side profile of the head posture written down appropriately in the form of the sphere, the
in most adults, is a position where the head is slightly tilted cylinder and its axis. An optical prescription of a sphero-
downwards, such that the person can look downwards from cylinder can be written in two forms, as a plus cylinder and
the primary position. Thus, spectacle glasses are made such as a minus cylinder. Both imply the same number
that they are parallel to and fit this normal head position and mathematically though most of the practitioners
are made with the lower borders tilted towards the cheeks. conventionally prefer to use the minus cylinder form.1,2,23
When looking at the glasses/spectacles from the side, the Transposition of lenses implies changing one form of
frame front appear tilted outwards superiorly near the temple mathematical description of the power of sphero-cylindrical
area. This angle of the superior outwards tilt of the spectacle glasses to the other mathematical form. Thus, it indicates
frame, keeping the head straight in such a condition is called changing the minus cylinder form to the plus cylinder form
the pantoscopic angle and the tilt is known as the pantoscopic and vice versa.
tilt (Fig. 2.3.25). Pantoscopic tilt of about 8 to 10 degrees is a The procedure for performing such a transposition is:
must in all spectacle glasses.1 The advantages of this tilt are: • For the new sphere, the sphere power and the amount of
• Avoidance of all oblique astigmatism and other the cylinder is algebraically added together.
aberrations. • The sign of the cylinder amount is changed.
• Matching of the anatomic tilt of the normal human side • The axis of the cylinder is changed by 90 degrees; which
profile. means if the axis is less than 90° or equal to 90°, 90° is
• In bifocals and progressive lenses, a wide near viewing added to it and if the axis is greater than 90°, 90° is
area is provided. subtracted from it.
• While looking at both distance and near optical axis, the To understand the conversion technique, the following
lens in the frame matches with the visual axis. examples are taken:
1. Transposition of +2.0 Dsph/+4.0 Dcyl at 90° to minus

cylinder form:
Step 1. New sphere is +2.0 + (+4.0 ) = +6.0 DS
Step 2. New cylinder is +4.0 becomes - 4.0 DC
Step 3. Axis 90° becomes 180°.
Thus, the transposed form of the prescription will be
+6.0 Dsph/–4.0 Dcyl × 180°. Both these prescriptions
have similar meaning.
2. Transposition of +0.50 DS/-2.50 DC at 90o to a plus
cylinder form:
Step 1. New sphere is + 0.5 DS + (- 2.5 DC) = –2.0 DS
Step 2. New Cylinder is +2.5 DC
Step 3. New axis becomes 180°.
Thus, the transposed prescription is -2.00 DS/+2.50
DC × 180o.
While adding the sphere and the cylinder together in step
1, if the signs are the same, then the numbers get added
numerically but if the signs are different, then again they get Figs 2.3.26A to D: Designs of spectacle lens systems
added such that whichever sign, plus or minus has the greater incorporating multiple power correction
value, will comprise the final spherical number of the glasses
as seen in example 1.
It is always to be mentioned whether the glasses are for
constant use or for near use only. The near-add spectacle is
added as a bifocal, trifocal or progressive lenses to the spectacle
frame for distance or it can be a separate spectacle. Half-
read spectacle frames for only near vision are available.
Types of Spectacle Lens Designs

The types of spectacle lens is depicted in Figures 2.3.26A
to D.
• Single-vision lenses: The simplest form of spectacle or
Figs 2.3.27A to D: Types of bifocals: (A) Split bifocals: These consists
contact lens is the single-vision lens, made to a single of two different upper and lower segment of lenses; (B) Cemented
prescription to correct distance, near or intermediate bifocals: These comprise a small plus lens fused to the posterior surface
powers (Fig. 2.3.26A). of the distance correction with Canada balsam. The modern equivalent of
this is the stick on Fresnel prisms that are attached to the posterior part of
• Bifocals: Bifocal lenses (Fig. 2.3.26B) contain two optical
the lens; (C) Fused bifocals: In this case, a small button of high index
corrections with a distinct dividing line between the glass in fused to a small concavity on the anterior surface of the lens.
two parts. The upper part of the lens corrects the This has not been tried with plastic lenses, in vogue nowadays; (D) One
distance vision anomaly and the lower half corrects piece bifocals: This mold of bifocals are extensively used in making
the near vision deficit. While the earliest bifocals had bifocals from plastic lenses. The near add, with a different curve, is
carved from the same plastic lens
the near add actually abutting upon the distance
correction (Franklin lens, first used by Benjamin
Franklin), the modern bifocals have the near correction
incorporated within the distance correction. The spherical and prismatic aberrations and many patients
different types of bifocal edges and its incorporation find it extremely difficult to adjust to them. The
have also led to classifying bifocal lenses as split bifocals different bifocal designs used for different
(the Franklin lens), the fused bifocals, the cemented requirements are shown in Figures 2.3.28A to D.
bifocals and the one piece bifocal (Figs 2.3.27A to • Trifocals: These have three sections and incorporate a
D). The bifocal edge accounts for many chromatic, correction for intermediate vision. Focussing through
Fig. 2.3.29: The optics of progressive lens

Figs 2.3.28A to D: Designs of bifocal shapes: (1) D or Flat top bifocals:
These are useful when a wider range of near vision is required as
after pseudophakia. It is a popular model for bifocals nowadays; (2)
Executive bifocals: These are specific bifocals whereby the near
edge bisects the pupillary plane of the patient. These are very useful astigmatism in comparison with other lens types.
for the management of near excess esotropia with high AC / A ratio, Progressive addition lenses are expensive and take
where the extra plus add helps in the relaxation of the accomodative time for getting used to, but are the ideal solution for
convergence at near, thus doing away with the deviation, which is many presbyopes (Fig. 2.3.29).
more manifest for near than at distance; (3) Round shape (Kryptok)
bifocals: These were extremely popular bifocals at one point of time
though they have largely been replaced by the D bifocals nowadays. Measurement of Interpupillary
The Kryptok was 22 mm in diameter. A wide inner excursion of the eye Diameter (IPD)
is required to see objects at near through this design. Besides, the
prismatic jump is more severe in this type of design; (4) Ultex bifocals: It is extremely important to take into consideration the facial
These bifocals are no longer available but the design is often mentioned. profile of the patient and measure the IPD before dispensing
These bifocals have a very large diameter, placed on the posterior the spectacle frame to the patient. This is specially true in
part of the distance lens. The prismatic jump is significant with these
case high powered lenses are prescribed in unsuitable spectacle
type of bifocals though the area of near vision is relative wide
frames to children as the induced optical decentration would
decrease vision. In any case, spectacle frames for children
are subject to breakages and, tilts, all of which compromise
the centration of the lens and the consequent optimum visual
the different sections is difficult with these types of
acuity. The IPD can either be measured directly by measuring
lens, with a considerable extent of prismatic jump
the distance between the corneal reflex between the two eyes
(Fig. 2.3.26C).
with the help of a scale or by performing measurements
• Varifocal or progressive lenses: Varifocal lenses, also known
from the nasal limbus in one eye to the temporal limbus in
as progressive lenses, are used for correcting
the other eye, again with the help of a scale. The limbus to
presbyopia but unlike bifocal lenses have no visible
limbus measurement actually measures the anatomical
dividing lines between the different corrections.
configuration of the face and is more accurate. In any case,
Progressive addition lenses are designed to provide
changes in the pupillary size can result in different
distance viewing in straight-ahead gaze, a gradual
measurements of the IPD when it is measured from the
progression of power in an intermediate corridor, and
corneal reflexes only.1,2
the full addition power lower in the lens. The power
change is accomplished by increasing the curvature
Spectacle Lens Cross-Sectional Designs
of the front surface (i.e. decreasing the radius of
curvature) along the corridor toward the bottom of Figures 2.3.30A to C demonstrate the optical design of the
the lens. Progressive lenses suffer from distortion and different spectacle lens design.
The other parameters that have to be specified include

the spectacle lens designs, especially for lenses of high
refractive powers. Besides, the conventional design (Fig.
2.3.30A), whereby the exact power of the lens is incorporated,
the other common cross-sectional design types are:
– Aspheric lens: Aspheric lenses are flatter than
conventional lenses as their surfaces, though
symmetrical is not a part of a sphere. In plus lenses,
the curves flatten away from the center, so that the
lens doesn’t bulge out as much. It also does not magnify
the eye, so that the size of the eye appears more
natural. Thus aspheric lenses provide visual and
cosmetic benefits for stronger prescriptions and are
the preferred mode of correction of high ametropia
nowadays (Fig. 2.3.30B).
– Lenticular lens: The lenticular lens may be described as Figs 2.3.30A to C: Types of spectacle lens designs: (A) Conventional
small and circular, mounted on a larger diameter, thin design; (B) Aspheric design; (C) Lenticular design
planocarrier which is edged to fit into the frame. Thus
this does away with many of the peripheral aberrations
associated with high power lenses. Besides, the 3. Polarized lenses: Polarizing lenses stop the movement
peripheral thickness of the lens is markedly reduced. of the transmitted light in one plane. These lenses are
Many of the classical problems associated with aphakic made from a special polarizing film that is applied on
glasses like the pincushion distortion, and ‘Jack in the the front surface of the lens. They are beneficial for
box’ phenomena etc are done away with these glasses personnel involved in any outdoor activity especially
(Fig. 2.3.30C). those who work on snow or near the sea.
4. Ultraviolet lenses: Lenses, especially CR 39 plastic lenses
Tints, Coatings and Other Features absorb UV light shorter than 370 nm and act as UV
As a final point in the prescription, it is also required that the filters. These are highly protective in areas where there
evaluator writes down whether any special tints, or coatings is higher concentration of UV rays like the snow-
are required for the glasses. Some of these special types of capped mountains. Mountaineers should ideally wear
lenses are: both polarized and UV protected sun-glasses.
1. Tinted lenses: Tinted lenses modify the profile of the 5. Scratch coatings: It is recommended that to protect plastic
light that passes through it, the mechanisms of which lenses from normal everyday wear and tear, a coating
is absorption of specific wavelengths or the reflection solution containing tri- and tetra-acrylates in a butanol
of the same. Most plastic lenses are tinted by a process solvent is spin-coated onto the surface of a plastic
of immersion in a dye which percolates into the lens lens.
material. Alternatively, absorptive or reflective coatings 6. Anti-reflective coating: When light passes through
can be applied over the lens surface. spectacles, some light rays are reflected by the front
2. Photochromic lenses: Photochromatic lenses automatically and back surface of the lens to produce spurious or
adjusts for the amount of light present in the ‘ghost images’ and ‘loss of light’. Anti-reflecting
background and changes from light to dark as one coatings (ARC) are superficially applied coats which
goes out in the sunlight. When glass photochromics decrease the amount of reflections from the lens
were used the process introduced silver halide crystals surfaces. AR coatings work on the principle of optical
into the glass mix. With plastic photochromics, the interference, and visual acuity, contrast sensitivity and
process deposited the photochromic coat onto the clarity are enhanced by them.
lens surface or in wafers within the substrate. Most plastic lenses with scratch resistant coatings
Photochromic lenses with UV protection lenses and AR coatings are also given an aquaphobic coating
decrease glare and filter out harmful ultraviolet light. intended to make cleaning easier.
THE MAKING OF SPECTACLES and semi-rimless frames, children’s eyeglasses and safety
23 eyeglasses. A major disadvantage is the presence of high degree
The important steps are:
of chromatic aberrations, inherently present.
Lens Material
Trivex
Glass (Traditional)
It is the latest super-impact-resistant lens introduced in 2001,
The traditional material for making spectacles is glass, which which is presumed to be optically better than polycarbonate.
is a mixture of silicates and metallic oxides. The glass mainly Both trivex and polycarbonate have inherent UV protective
used for manufacture of ophthalmic lenses is crown glass properties.
with refractive index of 1.523. While manufacturing, all the
ingredients are mixed and placed in a dome shaped silica Frame Material
crucible with an opening to allow for stirring. The mixture is Spectacle frame materials fall into 2 main categories, metals
then raised to a temperature of approximately 900oC, kept and plastics.
steady for 2 to 3 days, when the mass liquefies. The procedure Frame materials must be light, strong, adjustable but retain
of gassing and stirring is continued until all bubbles are their shape well. They should be flexible enough to hold a
remassed. With cooling, the glass tends to split into pieces of lens, inert both to external agents and body fluids, and be
varying size, which are re-heated, pressed into slabs of the cosmetically attractive.
required thickness and examined for striae, bubbles and other
faults. Annealing allows the glass to cool very slowly over Plastics
several days, thus preventing the outer portion of slab from Some of the material used in plastic frames are:
cooling before the inner. This is important to increase the a. Cellulose acetate: It is light, strong, stable at normal
durability of the glass formed and strengthen it. The two temperatures and is relatively inert.
opposite surfaces of glass are polished and forged out in b. Cellulose nitrate: Cellulose nitrate is similar to cellulose
discs of reduced thickness known as blanks, which are further acetate. It catches fire at a temperature very slightly above
processed to inculcate curvature and power for the the temperature required to adjust it and hence has been
manufacture of ophthalmic lenses. banned in many countries. Though when originally worked
upon, it is clear, it takes on a dark yellow hue subsequently
High-index Lenses and becomes brittle with age.
Increasing the refractive index of glass reduces the volume c. Cellulose propionate/cellulose acetate-propionate: These materials
of the lens, hence making it thinner. In minus lenses, it reduces are similar to cellulose acetate but are stronger and more
edge thickness and in plus lenses, it reduces central thickness. flexible.
The lenses with higher index are known as high-index lenses. d. Cellulose acetate butyrate (CAB): It is a thermoplastic polymer
Availability of high-index materials and aspheric designs mean occasionally used to make safety spectacles. Some of the
that lenses are thinner, lighter and better looking than the plastic side tips of metal frames may also be made from
traditional lens types. High index lenses are available in 1.60, it.
1.66, 1.67, 1.70, 1.74, 1.8 and 1.9 refractive indexes. e. Polymethylmethacrylate (PMMA): It is tougher than cellulose
acetate. This material is almost obsolete as a frame material
Plastic at present.
Plastic lenses are generally made from allyl diglycol carbonate f. Epoxy (or epoxide) resins: These frames are made by a
(CR 39). Plastic lenses have less refractive index than glass process of polymerization of the epoxide resin, in a
and the specific gravity is more than glass. For the same process akin to vacuum molding. Frames are colored by
refractive correction, plastic lenses are thus half the weight surface dyeing. Epoxy frames are translucent and have
of glass besides being highly impact-resistant. However, plastic been claimed to be hypoallergenic. They have been
lenses get scratches more easily and do not protect the eye extensively used to make motorcycle goggles and ski
from UV rays unless properly tinted. masks.
g. Polyamides: These materials have been used to make
Polycarbonate sunglasses, sports spectacles, safety spectacles and
This material is up to 20 percent thinner and 25 percent temporary aphakic spectacles. They are strong, with a
lighter than plastic. It is highly impact-resistant, ideal for drilled soft surface, and are flexible.
h. Polycarbonate: Similar to the lens material, its use as a frame aligned with a standard optical lens and a rotatable target
material is uncommon, other than for sports and safety illuminated by a light source. It measures the focal length of
spectacles. a lens and converts it into diopters on a circular number line
called a power drum.
Metals
Some of the metal frame materials are:
1. Alloys: These are commonly used to make spectacle frames.
Amongst these are German silver (copper-nickel-zinc),
Blanka-Z (copper-nickel-zinc-tin), nickel-manganese and
nickel silver alloys. Nickel silver comprises 12 to 25 percent
nickel, the rest being copper. Bronze (copper-tin alloy) is
rarely used as a frame material
2. Stainless steel: It is a relatively uncommon material for
spectacle frames, although its use is increasing, mainly
because it does not oxidize.
3. Titanium: This is an excellent frame material which is light,
strong, inert and hypoallergenic but relatively expensive.
ASSESSMENT OF LENS POWER

It is extremely important to assess the lens power of a given
spectacle lens. There are different modalities by which this
can be done. These are:
Clinical
This is rough modality for determining the type of lens in
spectacles. The method is diagrammatically represented in
Figures 2.3.31A to E. Figs 2.3.31A to E: Method for determining the type of lens in the
Instead of the image of the tubelight, the same test can spectacle frame: (A) and (B) Placing the lens well away from the
be performed on a cross drawn on a sheet on plain paper, as eyes, and observing the image of a tubelight through the same, if the
already explained in the section on determining the optical tubelight image appears magnified and moves away from the direction
of the movement of the lens, it implies that it is a convex lens. The
center of the lens (Figs 2.3.24A to C). magnification gives an idea about the magnitude of the hypermetropia,
with larger magnification implying a higher power. The power can be
Focimeter neutralized by concave lenses from the trial set. That power of
concave lens that totally neutralizes the movement of the image of the
Focimeter, also called the lensometer, refractionometer, tubelight in the opposite direction upon movement of the lens on one
vertometer or the ultimeter, is used to measure the vertex side, along with equalization of the image size, gives an approximate
power and optical centration of the spectacle lens inserted idea about the diopteric power of the lens in the spectacle. This test
can be easily performed in an outpatients’ clinic; (C) If upon moving the
into it. The lensometer is based on the principle that the lens over the tubelight, there is minification of the image and the
image of a target which is usually a ring of illuminated dots is movement of the tubelight image is in the same direction as the
focused by a standard lens when seen through a telescope. A movement of the lens, it indicates that the lens being tested is a
lens of unknown power when inserted into optical system concave lens. Neutralization of the power with a convex lens will
provide the approximate power of the lens; (D) If upon moving the lens
changes the position of target. The exercise required to bring over the tubelight, distortion of the image is observed, and the direction
the target again into focus measures the strength of the of the tubelight image is not in line with the movement of the lens, then
unknown lens. In order to see the target clearly, the power it indicates an astigmatic error. The lens may be rotated till the tubelight
knob is rotated so that it moves to result in emergence of image aligns itself in the same direction as the lens. This provides an
approximation of the axis of the astigmatic lens; (E) If upon placing the
parallel rays. The amount of knob rotated denotes the strength
lens over the tubelight, there is constant displacement of the image of
of the unknown lens which can then be read directly from the tubelight in any direction, it is indicative of a prism incorporated in
scale. Thus, it is essentially a centered telescopic optical system the spectacle lens
Optical Principle of Lensometer Procedure for the Manual Assessment

of the Spectacle Power with the
The image of the target is seen through a telescope and is Help of a Lensometer
focused by a standard lens. The unknown lens is inserted into
1. The lensometer is turned on and the observer’s eye is
the system and the target is focused once again. The change
appropriately focused. Conventionally, the right eye is
in position of the target gives the measure of the diopteric
evaluated first.
strength of the unknown lens (Fig. 2.3.32).
2. The power drum and axis wheel is used to get the lines
The target is a cross hair, with the thin, closely spaced
sharp and a crisp axis is delineated. Both the lenses should
lines representing the sphere component of lens power and rest evenly against the table.
the thicker, widely spaced lines representing the cylinder power 3. The power drum is rotated such that one set of lines
(Fig. 2.3.33). The lensmeter actually does not read the come into focus. This is especially true if one is evaluating
prescription of a lens, but rather the powers of the lens in a cylinder. Then the drum is rotated such that the other
each meridian. In the case of a spherical lens, all the lines of set of lines comes into focus. This indicates the other axis
the target focus at the same time, while in the case of a of a cylinder. The difference between the two readings
sphero-cylinder lens, the lines focus separately at different gives a measure of the cylindrical power. In the case of a
power drum readings. sphere, both sets get focused simultaneously.
4. In the case of bifocal segments, the distance power is
measured first followed by the near addition.
Types of Focimeters
1. Projection focimeter: In this optical system, the practitioner
does not have to peer into the instrument. The image is
projected on a screen.
2. Conventional focimeter: This refers to the manually handled
focimeters, which have been conventionally used for this
Fig. 2.3.32: Optical principle of the lensometer. A clear image of the

target C is focused by a standard lens and is seen through the telescope
t. The target c comes into focus only when it coincides with focal point
f1 of the standard lens. The ray f1h passing through the focal point f1
of the standard lens is refracted parallel to the axis f1f2 and meet the
telescope at t in the aperture e and is seen through the eyepiece. This
is the zero position. The lens whose diopteric strength is to be
determined is inserted at d to make the whole a co-axial homocentric
system of lenses. The back surface of the combination faces the
standard lens. The homocentric system will now have the focal point
at f2 and the target c will be focused at the aperture e if c coincides
with f2. The excursion of the target is calibrated and the reading of the
excursion gives the diopteric strength. The position of f2 varies
accordingly whether the used lens is concave or convex. In concave
lenses the shift from f1 is away from the standard lens and in convex Fig. 2.3.33: The mires are focused while performing focimetry. The
lenses the shift from the f1 is towards the standard lens. zone (1), (2), (3) and (4) are marking out the different zones
purpose, the description of which has been provided in 2. Peyman GA, Sanders DR, Goldberg MF (Eds). Optics and
details above. refraction. In: Principles and practice of ophthalmology; Vol 1;
Chapter 4; WB Saunders, Philadelphia 1987;194-221.
3. Automatic focimeter: The system is similar to the manual
3. Emsley HH. Aberrations of the reduced schematic eye with an
focimeters but does not require manual handling. The elliptical refracting surface. In: Visual Optics, Hatton Press Ltd,
optical principle used here is that when a light ray passes London, 1952.
through a lens, it gets deflected depending on the prismatic 4. Liou HL, Brennan. Anatomically accurate, finite model eye for
power and the position of the optical center of the lens. optical modeling. J Opt Soc Am A Opt Image Sci Vis 1997;14(8):
1684-95.
In the automated focimeter, 4 such beams of light are
5. Curtin BJ. In: The myopias: basic science and clinical management.
passed through the lens to be tested and the deflection of Harper and Row, Philadelphia 1985;237-435.
the beam in each case is useful for the calculation of the 6. Grosvenor T. Management of anomalies of refraction and binocular
diopteric power of the lens based on an empirical formula. vision. In: Primary care optimetry, 5th edition, Butterworth
Heinemann Elsevier, St Louis 2007; Chapter 12; 251-440.
Geneva Lens Measure 7. Menon V, Chaudhuri Z, Saxena R, et al. Classification of
amblyopia. Indian J Ophthalmol 2006;54(3):212.
Many opticians used the Geneva lens measure (also known 8. Menon V, Chaudhuri Z, Saxena R, et al. Profile of amblyopia in a
as a ‘spherometer’), a hand-held device like a pocket watch hospital referral practice. Indian J Ophthalmol 2005;53(4):227–
34.
with a prong to press against the lens, offsetting a pointer
9. Duke Elder S. Ophthalmic optics and refraction. In: System of
that is read against a round scale (Fig. 2.3.34). The radius of Ophthalmology, Vol V, Duke Elder S, Ed. CV Mosby, St Louis,
curvature of the lens is measured and the reading is directly 1970;451-86.
converted into diopter on the instrument scale. As the 10. Fincham EF. The mechanism of accommodation. Br J Ophthalmol
prescription of a lens depends upon the shape of both the 1937; VIII (suppl): 1-80.
11. Hermans E, Dubbelman M, van der Heijde R, Heethaar R. The
front and the back surfaces more than one measurement is
shape of the human lens nucleus with accommodation. J Vis
usually required. The principle used is based on the sagittal 2007;7(10):16.1-10.
depth formula whereby the height of the instrument that 12. Patorgis CJ. Presbyopia. In: Diagnosis and management in vision
gives the correct measure while pressing upon the lens care. Amos JF, Ed. Butterworth Heinemann 1987;203-38.
provides the diopteric measure of the power of the lens (Fig. 13. Milder B, Rubin ML. The fine art of prescribing glasses without
making a spectacle of yourself, 2nd Ed. Triad, Gainsville, Florida
2.3.34).
1991;52-3.
The Geneva lens measure is mainly used to: 14. Wagstaff DF. The objective measurement of the amplitude of
1. Verify the correct prescription in a pair of eyeglasses; accommodation. Part VII. Optician 1966;151:431.
2. Properly orient and mark uncut lenses; and 15. Westheimer G. Visual Acuity. In: Adler’s physiology of the eye,
3. Confirm the correct mounting of lenses in spectacle 9th Ed. Hart WM, Jr, Ed. CV Mosby, St Louis, Chapter 17;531-
frames. 47.
16. Westheimer G. The spatial sense of the eye. Proctor Lecture.
This can also verify the power of contact lenses, if a Invest Ophthalmol Vis Sci 1979;18:893.
special lens support is used. 17. Corboy JM. Basic Concepts. In: The retinoscopy book: an
introductory manual for eye care, 5th Edition Slack Incorporated,
REFERENCES New Jersey 2003;25-35.
18. Duke Elder S, Abrams D. Retinoscopy. In: System of
1. Elkington AR, Frank HJ, Greaney MJ. Optics of ametropia. In: Ophthalmology, Vol V, Duke Elder S. Ed, CV Mosby, St Louis,
Clinical optics. 3rd Edition, Blackwell Science, London 1999;99- 1970;390.
151. 19. Benjamin W. In: Borish’s clinical refraction. Butterworth
Heinemann Elsevier 2006; Philadelphia, 2006.
20. Teel DF, Copland RJ, Jacobs RJ, et al. Design and validation of an
infrared Badal optometer for laser speckle. Optom Vis Sci 2008;
85(9):834-42.
21. Jiang BC. Steady state of accommodation during observation of
a Scheiner image. Am J Optom Physiol Opt 1988;65(10):809-13.
22. Kruger PB, Mathews S, Aggarwala KR, Sanchez N. Chromatic
aberration and ocular focus: Fincham revisted. Vis Res 1993;
33(10):1397-411.
23. Fowler C, Petre KL. Astigmatic lens forms, Chapter 3, In: Spectacle
lenses: theory and practice. Reed Educational and Professional
Fig. 2.3.34: The Geneva lens measure Publishing Ltd, Butterworth Heinemann, 2001, Oxford, p. 34.
Chapter 2.4
PEDIATRIC REFRACTION
Sumit Monga, Monica Chaudhry, Zia Chaudhuri
To start with, the serious responsibility of the practitioner Some of these important concepts regarding pediatric
towards correctly prescribing the appropriate refractive retinoscopy are:
correction to a child has to be understood. A child will live • Infant eyes are normally hyperopic1
with the benefits and also the side effects of the prescription • Accommodation is very strong in children which reduces
all through his life. This chapter deals with this special situation. rapidly with age
The problems peculiar to performing refraction in children • Eyes that become myopic usually continue to grow
are: throughout childhood, hence resulting in an increase in
• Subjective refraction is difficult to perform and hence the myopia
objective data has to be as accurate as possible • Binocular alignment and stereopsis develop by about 4
• Objective post-refraction assessment is difficult and often months of age
one has to depend upon the retinoscopy findings only • 50 percent of children are astigmatic by 1 diopter or
• It is difficult to assess visual acuity more.
• The extent and degree of accommodation varies and hence
cycloplegic retinoscopy is a must The concept of emmetropization has been elaborated in
• Associated strabismus and binocular dysfunction may be the section on pediatric ophthalmology. It is important to
present reiterate that:
• The change in the refractive status in infants and toddlers • It is a process by which the refractive power of the anterior
is very fast and hence constant monitoring is required, segment of the eye reduces its power proportionate to
otherwise the prescribed power may become redundant. the increase in the axial length of the eye
The basics and interpretations of pediatric refraction • At birth, the refractive error in the eyes can vary between
depends upon knowledge of the growing eye and its –2D to +4D but by about 2 years of age, the tendency is
anatomical and functional parameters. These have been dealt to hover as close to being emmetropic as possible in most
in another section of this book. The age of the child, the cases.
existing refractive error and its magnitude, the association In the process of emmetropization, it has been studied
with other structural and functional ocular abnormalities like that spectacle correction that removes blur entirely may result
strabismus and amblyopia, all make a impact while finally in higher refractive error by stopping emmetropization. Hence,
deciding the customized management. The history given by it is still a matter of controversy whether the full correction,
parents related to abnormal signs like rubbing of eyes, especially hypermetropic be given to infants. However, if
excessive blinking, and closing of one eye should never be there is an associated esodeviation, the full hyperopic
ignored. It is important to remember that refractive errors correction has to be given irrespective of age.1-4 Simple
may not only be associated with amblyopia but may be guideline charts to prescribe for patients with pediatric
amblyogenic also. To decide whether the complete correction hyperopia are presented in Figures 2.4.1 to 2.4.4. An overview
is to be given or not has to be customized to the patient, of the prescription protocols in children with myopia is
taking into consideration all objective parameters. elaborated in Figures 2.4.5 and 2.4.6.5
Pediatric Refraction 73
Fig. 2.4.4: Prescription in conditions with and without amblyopia can

be different. In older children, low errors need to be prescribed if the
child has asthenopic symptoms only
Fig. 2.4.1: General algorithm for prescribing glasses

in children with hyperopia
VA = Visual acuity; BV = Binocular vision
Fig. 2.4.2: In case pediatric hyperopia is present with esotropia, Fig. 2.4.5: A generalized overview of prescribing myopic glasses in
complete correction, subtracting only for the working distance has to children is presented. In older children it is important to prescribe
be prescribed irrespective of age completely, as otherwise the reduced visual acuity may hamper
performance. There is an average increase of about 0.5 diopter of
myopia every year, especially in the growing years of the child. A
regular vision assessment once a year at least every year is must
one can start with under correction, monitor and increase

gradually, after observing the subjective acceptance of the
child. Parents should be counseled in such cases and
encouraged to become observant monitoring guides.1-3,6,7
The general guideline for prescribing glasses in children
Fig. 2.4.3: An overall guideline while prescribing with astigmatism is presented in Figures 2.4.7 and 2.4.8.
for hypermetropia in children is presented In a child with anisometropia, the entire correction should
be prescribed, for equal accommodative demand. Axial
myopes tolerate full corrections without diplopia. Children,
In a child with astigmatism, correction of astigmatism is in general tolerate higher extent of anisometropia than adults.
required in infants and toddlers only if the cylinder is more Contact lenses are useful in the reduction of aniseikonia, if
than 2 Diopters. In older children, however, the full correction any.3,6-9 Figure 2.4.9 provides general guidelines for the
needs to be prescribed. In younger children with high cylinders, prescription of glasses in children with anisometropia.
Fig. 2.4.6: If the optical development is complete or if there is any

other associated functional or structural disorders, the complete
correction should be prescribed. It is important to correct the myopia
completely in childhood so as to make the patient have emmetropic
status of accommodation with corrected glasses. In case myopia is
kept undercorrected or uncorrected till adulthood, the patient would
have asthenopia if the optimal distance correction is given because
by then the accommodational apparatus would have gone into disuse
Fig. 2.4.8: General guidelines for prescribing astigmatic glasses in

children. The child should be scheduled for a regular follow-up for
temporal monitoring
Fig. 2.4.7: While astigmatism need not be fully corrected in a child

where the optical system development is not yet complete, in older
children with full optical system development, full correction is an
absolute must. Uncorrected astigmatism can cause severe asthenopia
and may also cause amblyopia
In children with bilateral aphakia, (contact lens is the mode

of visual rehabilitation in unilateral aphakia), aphakic glasses
of the appropriate power should be prescribed immediately.
Though a near add (as there is no accommodation in an
aphake) is not prescribed, given the difficulties of making a
child wear such heavy glasses, an overplus lens of about
1.5D to 2D above the retinoscopy to aid near vision is
indicated to prevent amblyopia. In any case, secondary
intraocular implantation should be planned at the earliest. Fig. 2.4.9: General guidelines for prescribing
Current day protocols of standards of management for glasses for pediatric anisometropia
pediatric cataract indicate that at present, aphakic
rehabilitation can only be considered to be a temporizing
measure before the child is made pseudophakic. Repeated Procedure of Retinoscopy
retinoscopy and contact lens prescription are the ideal modes in Small Children
of visual rehabilitation till such an eventuality. Primary Retinoscopy in a toddler is really an art. As it has to be
pseudophakia should be preferred in older children.10 performed appropriately, a lot of effort has to be made initially
Pediatric Refraction 75
to establish a rapport with the child. It is of use to note that cycloplegic used should be mentioned along with the
most children co-operate for objective retinoscopy very well. prescription. This is not only to aid appropriate prescription,
It is upto the examiner to make the child comfortable and but on most occasions, these children undergo repeated
hold his interest. The child should preferably be taken up for retinoscopy. Thus mentioning the cycloplegic used, ensures
retinoscopy after feeds because that is the time when the that subsequent retinoscopy is also done under similar
child is usually playful. After appropriate cycloplegia as circumstances, so that a baseline is established.
indicated, the child should be sitting on his parent’s lap as this There is no definite criterion for selection of the
is the situation when the child feels most secure and capable cycloplegic to be used. The rule is to choose the drug which
of dealing with unusual circumstances. The evaluation has to relaxes accommodation for that age, such that there is no
be rapid as fixation may be for short fleeting intervals. It is a fluctuation of retinoscopic findings. As accommodation is
good idea to establish whether the initial movement of the very strong at birth, the recommended drugs are atropine
reflex is “with” or “against” and then use a higher spherical (the ointment form is preferred as it is less toxic),
lens of the type that is indicated to observe whether the cyclopentolate or homatropine. Tropicamide is too mild a
reflexes reverse or not. If in an adult, an increment of 0.5D cycloplegic to cause complete cycloplegia in young children
would be tested at one time, in a child an increment of 1D to and hence its use may result in erroneous data. Phenylnephrine
2D can be used. This helps determine the intervals where a should be used with caution as its systemic toxicity is high.
close retinoscopy would be indicated. For example if there is However, tropicamide and phenylnephrine in combination,
‘with’ movement, a concave lens of –1D can be used in very low concentration is used to dilate the pupils of
subsequently. In case there is a reversal of movement, it children with ROP. Care should be taken to monitor signs
indicates that the values would be between 0 to –1D and a and symptoms of toxicity of the cycloplegics used in children.
closer evaluation in this interval can be performed. If, The preferred dosages of the cycloplegics used are given
however, the movement is still a “with” movement, one can in Table 2.4.1.
go forth to –2D and perform the same step again. This makes The prescription is derived after subtracting for the
the evaluation faster. The same is repeated for the other axis working distance and the cycloplegic used. 1D is subtracted
in the same eye and then for the other eye. for atropine, and 0.5D for homatropine and cyclopentolate
Some other points to note are that children are not very drops. Small cylindrical values can be ignored. Autorefraction
comfortable with a trial frame. The evaluator should hold may be performed under cycloplegia with the help of hand
the lens with which the testing is being done in his other hand held auto-refractometer. Pediatric autorefractometers are
while evaluating. available.
Again, whenever there is a shift from one eye to the other,
the examiner is expected to move and not vice versa. Spectacle Prescription in Children
The child should be humored under all circumstances if Children are not small adults. Besides physical and
accurate results are to be expected. psychological differences, there are also differences in the
If the child has neurodevelopmental disorders, though activity level. For example, it is very difficult to make a child
the child may not actively co-operate, in most cases he would fixate for retinoscopy or to make him wear glasses. Wear and
be too lethargic to resist retinoscopy. tear of spectacles is very high. Even if a child has worn
If the child is still not co-operative, then retinoscopy can glasses, it may not be serving its purpose if the child peeps
be performed under sedation or under anesthesia. Peripheral above or below the frame.
screening of the fundus under most circumstances requires Thus optometric concerns for an appropriate fit of
examination under anesthesia (EUA). spectacles should consider the following:
Other pre-requisites are dark room with pupils dilated • Proper frame selection
under the effect of an appropriate cycloplegic, which are: • Proper adjustable nose-pad that fits well
– Atropine 1 percent ointment • Rimless (or semi-rimless) frames are not to be used
– Homatropine 2 percent drops • Optical centration of spectacle lenses is important
– Cyclopentolate 1 percent drops especially for higher refractive errors and patients with
– Tropicamide 0.5 percent drops. strabismus (half-eyes spectacles are to be avoided in
Cycloplegia is most important in children. Incomplete children)
cycloplegia results in reduced reliability of results and that • The facial profile should be given importance for both
may be detrimental to the management of the child. The functional and cosmetic reasons
Table 2.4.1: Cycloplegics used in pediatric refraction

Drug Percentage Dosage Duration of
cycloplegic effect Use
Atropine ointment 1 percent Three times a day for 3 days 2 weeks In all infants and toddlers,
before refraction especially with strabismus,
(eso deviation)
Cyclopentolate drops 0.5 percent in children 2 hours before retinoscopy; 4 days Preschool children upto
less than 1 year and then 4–5 instillations every age of 7 years
in a 1 percent combination 15 minutes before evaluation
thereafter
Homatropine drops 2 percent 1 hour before retinoscopy, 7 days Older children
3 instillations every 15 minutes
before evaluation
• Ensuring that there are elastic head bands/comfort cables/ to understand the importance of the refractive error
curved spectacles rods that fit the ear and do not slip, correction and occlusion therapy for amblyopia. Follow-up is
and maintain the spectacles in place over the eyes. a must and compliance is important. It is important to
Spectacle material for frames and lenses are: remember that refractive errors play a role in the etiology of
A. Spectacle Frames: many forms of strabismus and optical modulation of
1. Plastic frames: These are durable, flexible, resilient strabismus by appropriate refractive prescriptions is one of
to low impact and bumping but are sensitive to the most important therapeutic tools available for the
temperature. Cellulose acetate is the preferred management of the same. This has been covered in another
material. Some of the other material that is used are section of this book.
propionate, polyamide, carbon fiber, graphite, optyl
plastic and nylon. REFERENCES
2. Metal frames: These are strong but inflexible and 1. Hopkisson B, Arnold P, Billingham B, et al. Can retinoscopy be
should preferably not be used in active children as used to screen infants for amblyopia? A longitudinal study of
injuries may occur. refraction in the first year of life. Eye 1992;6:607-9.
B. Lens Material: 2. Ong E, Grice K, Held R, Thorn F, Gwiazda J. Effects of spectacle
1. Plastic lenses of CR39, polycarbonate (safest) and intervention on the progression of myopia in children. Optom
Vis Sci 1999;76(6):363–9.
cellulose acetate with scratch resistant coatings are
3. Farbrother JE. Spectacle prescribing in childhood: a survey of
preferred. hospital optometrists. Br J Ophthalmol 2008; 92 (3):392-5. Epub
2. Glass lenses are heavier and more fragile and are to 2008 Jan 22.
be avoided except when executive bifocals are 4. Lyons SA, Jones LA, Walline JJ, et al. A survey of clinical prescribing
prescribed as executive bifocals are not made in plastic. philosophies for hyperopia. Optom Vis Sci 2004;81(1):233-7.
A larger flat top D bifocal made in plastic may 5. Irinarren R, Cortinez MF, Chiappe JP. Age of first prescription
substitute a short executive bifocal if made and final myopia refractive error. Ophthalmic Epidemiology
2009;16(2):84-9.
appropriately. 6. Harvey EM, Miller JM, Dobson V, Clifford CE. Prescribing eyeglass
In short, selecting the material carefully and assessing the correction for astigmatism in infancy and early childhood: a survey
of AAPOS members. J AAPOS 2005;9(2):189-91.
appropriate fit of the spectacle would go a long way in the 7. Robaei D, Rose K, Kifley A, Mitchell P. Patterns of spectacle use
appropriate execution of the prescription. It is important to in young Australian school children: Findings from a population
be sensitive to the child’s needs, emphasize the positive, use based study. J AAPOS 2005;9(6):579-83.
sympathy judiciously and reward achievement in order to get 8. Kivlin JD, Flynn JT. Therapy of anisometropic amblyopia. JPOS
good results. Children are very perceptive to adult role models, 1982;18(5):47-56.
especially parents. Getting the parent to wear a spectacle glass 9. Reiter C, Leising D, Madsen EM. Survey of German clinical
prescribing philosophies for hyperopia. Optom Vis Sci
goes a long way in making the child use it regularly. Teaching
2007;84(2):131-6.
eye care to the child and his parents is important. After a 10. Burton BJ, Fernando AI, Odufuwa TO, Vogt U. Contact lens
while, contact lenses may be considered, if indicated. prescribing in a specialist medical contact lens clinic based in ab
Vision screening and binocular function tests should always NHS hospital: An audit of changing practice. Eye Contact Lens
be carried out on follow-up visits. Parents have to be educated 2004;30(2):87-9.
Chapter 3.1
CONTACT LENS: BASIC CONCEPTS
Monica Chaudhry
Contact lenses (CLs) are used primarily to neutralize refractive the amount of oxygen transmissibility levels needed with the
errors as an alternative to vision correction by spectacles or contact lens on the eye, for safe contact lens wear:4,5
refractive surgery. The first plastic corneal contact lens, made
of PMMA (polymethyl methacrylate) was introduced in 1947 For safe wear Dk/L
by Kelvin Touhy. In 1949, the first “corneal” lenses were Safe daily wear 24.1 + 2.7 × 10–9
developed. PMMA corneal lenses became the first contact Safe extended wear 87.0 + 3.3 × 10 –9
lenses through the 1960s. The major disadvantage of PMMA
lenses was that no oxygen was transmitted through the lens to where oxygen transmissibility is denoted by Dk/L. (Dk is oxygen
the cornea, which caused a number of adverse clinical effects. permeability and L is lens thickness in centimeters).
By the end of the 1970s, and through the 1980s and 1990s, a Transmissibility may thus decrease as the lens thickness
range of oxygen-permeable rigid materials (“RGP”) were increases. Dk/L is expressed as Barrer/cm.5
developed to overcome this problem. Modern soft contact
lenses were invented by the Czech chemist Otto Wichterle CONTACT LENS MATERIALS
and his assistant Drahoslav Lím1 which was the principal
breakthrough in soft lenses made of HEMA material. In 1999, Contact lenses can be mainly classified as gas permeable and
an important development was the launch of the first silicone nongas permeable. Nongas permeable lenses are commonly
hydrogels in the market, which has extremely high oxygen known as hard (PMMA) lenses. Gas permeable lenses have
permeability and compatability of soft lenses. been further divided into rigid (RGP) and soft (Hydrogel)
lenses. Today, gas-permeable lenses account for about 98
CORNEA, OXYGEN AND CONTACT LENS percent of rigid lens prescriptions; PMMA is rarely used
anymore for contact lenses.
Oxygenation of anterior cornea underneath a contact lens is
brought about by diffusion of atmospheric oxygen through
Hydrogels: Soft Contact Lenses
the contact lens and the influx of oxygenated tear fluid
underneath the contact lens as a result of blinking. The tear Hydrogels are made of soft, flexible plastics that allow oxygen
pump 2 supplies about 14 to 20 percent tear exchange to pass through to the cornea. Hydroxyethyl methacrylate
underneath a RGP lens whereas a soft lens exchanges tears (HEMA) is a stable, clear, nontoxic, nonallergic, and optically
from 1 to 5 percent only. The tear pump supplies oxygen and clear material. Soft contact lenses are easier to adjust and are
nutrients to the cornea and also removes waste products like more comfortable than RGP lenses due to which they can be
carbon dioxide, lactic acid and dead epithelial cells. However, worn on occasional basis also.
the tear pump alone is insufficient to provide adequate amounts HEMA and vinyl pyrrolidone (VP) are monomers
of oxygen required by the cornea. Hence, the contact lens commonly used in the formulation of soft contact lens
must allow oxygen to pass through it to maintain the normal materials. Nonproprietary (generic) names identify specific
physiology of the cornea.3 Studies have been done to calculate contact lens materials composed of various polymers,
80 Contact Lens
monomers and macromers. Manufacturers use these generic a. Silicone acrylate are the first successful RGP lenses. It is
materials to make their own brands and designs of contact composed of copolymers with “silicon” for oxygen
lenses, which they give trade (proprietary) names, e.g. permeability, methylmethacrylate for stability, wetting
polymacon is the generic name of the original HEMA material. agents (methacrylic acid, HEMA), and cross-linking agents
Hydrogel lenses’ oxygen permeability results from the for stability. The oxygen permeability of rigid lenses was
water content (k). Because the highest practical water content improved by copolymerization of methyl methacrylate with
for any material is about 80 percent, maximum permeability is certain siloxane ( Si – O –Si), alkyl (–CH2 – CH2 – CH2– )
approximately 40 Dk. Manufacturers typically add components and methacrylate (CH2=C–COO– ) monomers, e.g. Boston
such as methacrylic acid (MAA) and vinyl pyrolidone to methyl II, IV, Ablerta II, III, Menicon O2, and polycon II.
methacrylate (MMA) or hydroxy ethyl methacrylate (HEMA) b. Fluoro-silicone acrylate: Fluorine is combined with the other
(38% water) to increase water content and oxygen permeability ingredients of silicone acrylate to enhance wettability and
while ethylene glycol dimethacrylate (EGDMA) adds stability increase Dk, e.g. Fluorperm, Fluorex, Quantum II, Alberta
and elasticity but decreases water content. Because various and Equalens.
hydrogel polymers can greatly differ in chemical and physical
properties, they may react differently to changes in pH, Advantages of Rigid Contact Lenses
osmolarity, temperature and the components of the various
lens care products on the market. • Durability
• Resistant to deposits
Silicone Hydrogel Contact Lenses • Better quality of vision. It corrects regular and irregular
Newer soft lens materials are called silicone-hydrogels as they astigmatism better than soft lenses
have silicone content which provides more oxygen to the eye. • Low costs
This makes it highly oxygen permeable. The benefits to wearers • Suitable for patients with dry eye and corneal irregularities
include comfort and convenience. • Better oxygen permeability than soft lenses
In 1986, US Food and Drug Administration (FDA) • Can be modified in clinical settings to some extent.
classified hydrogel contact lenses into 4 groups:
Group I Nonionic, low water content Disadvantages of Rigid Contact Lenses
Group II Nonionic, high water content • Not suitable for occasional wearers
Group III Ionic, low water content
• Less comfortable than soft lenses
Group IV Ionic, high water content
• Difficulty in achieving ‘on eye’ stability.
Where:Low water = Less than 50 percent water content
High water = More than 50 percent water content
CLASSIFICATION
Ionic material = Contains a net negative charge on the
surface On Basis of Wear Time
Nonionic = Have no net surface charge.
• Daily wear: Lenses which are removed prior to sleeping.
Rigid Contact Lenses • Extended wear: Lenses which can be worn during sleep.
(Rigid Gas Permeable Lenses or RGP) Extended wear contact lenses are available for overnight
Rigid contact lenses have been available for a much longer or continuous wear ranging from one to six nights or up to
period than soft contact lenses, although many improvements 30 days. Lenses that can be worn for up to a month conti-
have been made over this time in allowing more oxygen to nuously are called “Continuous wear” (CW) contact lenses. Newer
pass through the rigid material. They are smaller (average materials, such as silicone hydrogels, allow for longer wear
diameter 9 to 10 mm) than the soft lenses and take longer to periods of up to 30 consecutive nights.
get used to initially, due to their rigid structure but regular Extended lens wearers may have an increased risk for
wearers find them comfortable. corneal infections, corneal ulcers and allergic or giant papillary
conjunctivitis. Corneal neovascularization has also been
Types of RGP Materials reported as common complication of extended lens wear,
There are two most commonly used RGP materials these days: though this does not appear to be a problem with silicone
a. Silicone acrylate hydrogel extended wear. The most common complication of
b. Fluoro-silicone acrylate. extended lens use is conjunctivitis, usually GPC.
Contact Lens: Basic Concepts 81
On Basis of Frequency of Replacement

• Daily disposable: They are single use lenses, which are
disposed of after every use. Single use lenses are also useful
for people who use contacts occasionally.
• Frequent replacement program (FRP): Some soft contact lenses
like monthly disposable lenses are referred to as
“disposable” by contact lens sellers, but actually, they are
for frequent/planned replacement. The majority of soft
contact lens wearers are prescribed some type of frequent
replacement schedule. Commonly, contact lenses are Fig. 3.1.2: Cast molding process
prescribed to be disposed of on a two-week or monthly
basis.6
• Conventional or annual lenses: These are very common in button which is placed in a diamond-tool lathe and rotated
developing countries and are disposed of after the useful at a very high speed. The polymer is cut as per the
life of the lens. Usually this is scheduled to be changed specifications required and a precise lens surface is then
every year. polished. A hydrogel lens is hydrated and inspected. Lenses
• Rigid gas permeable lenses: They are very durable and may last can be of custom designs for an individual patient by this
for more than a year without the need for replacement. process but it has the disadvantage that it is time consuming
They are also recommended to be changed every year. The and labor intensive process.
higher the Dk of the RGP material the earlier it may need c. Molded: In this process, the liquid polymer is poured in the
to be replaced. concave mold. The convex mold is then clamped over the
concave mold. The polymer is then cured by ultraviolet
MANUFACTURING OF CONTACT LENSES radiation. The dry state of the lens is then removed and
hydrated. It is fast and less labor intensive, cost-effective
Contact lenses are broadly produced by three methods:
process by which high volumes can be produced
a. Spin-cast lenses: A spin cast lens is a soft contact lens
(Fig. 3.1.2).
manufactured by whirling liquid polymer in a revolving
mold at high speed. It is then curreted with UV and finally
CONTACT LENS TERMINOLOGY
hydrated. Lenses can be produced in large quantities by
this method and they can also be easily reproduced The parameters specified in a contact lenses prescription
(Fig. 3.1.1). (Fig. 3.1.3) may include:7
b. Lathe cut: A lathe turned contact lens is cut and polished • Base curve radius (BC or Back optic zone radius, BOZR): This is
on a CNC lathe. Both RGP and soft lenses can be made the back curve of the contact lens, which contours the
by this process. The process begins with a pre-formed front surface of the eye. To achieve a proper fit the base
Fig. 3.1.1: Spin casting process Fig. 3.1.3: Description of contact lens terminology
82 Contact Lens
curve of the contact lens should be aligned with the

curvature of the cornea. Base curve is expressed in mm
(millimeters) or diopters.
• Diameter (total diameter–TD or overall diameter–OD): It is the
length of the lens across its widest diameter. It is specified
in millimeters. A soft lens is usually 12 to 15 mm and a
rigid lens is of 8 to 10 mm diameter.
• Power: The ability of the lens to converge (+ lenses) or Fig. 3.1.5: Edge lift
diverge (– lenses) the light rays, in other words the dioptric
power of the contact lens. This can be spherical, cylindrical
or reading addition in diopters. – Bicurve: Lens with two posterior curves, base curve
• Peripheral curve (PC): The peripheral curve is the curve and the peripheral curve.
surrounding the base curve on the posterior surface of – Tricurve: Lens with three posterior curves, base curve,
the lens. If there is more than one peripheral curve then peripheral curve and one intermediate curve.
the inner curves are called secondary or intermediate curves (IC).
OPTICS OF THE CONTACT LENS
• Optic zone (OZ): The central optic portion, which carries
AND THE FLUID LENS
the base curve of the lens, is called the optic zone. It is the
central region of a CL that has a prescribed optical effect Fluid lens is the representative tear film lens formed between
and is measured in mm. the anterior surface of the cornea and the posterior surface
• Center thickness (CT): It is the distance in mm from the front of the contact lens. If the base curve of a contact lens is
surface to back surface of a lens, measured at the geometric selected steeper than K, then a positive tear lens is formed
center of a lens. A plus power lens will have greater center between cornea and the lens (Fig. 3.1.6). Whereas, if the base
thickness than a minus power lens of the same power. It curve of a contact lens is flatter than K, then a negative tear
is measured with a thickness gauge in mm. lens is formed (Fig. 3.1.6). In other words, when base curve is
• Sagittal depth (Sag): Sagittal depth is the distance between a chosen steeper than the flattest corneal meridian, a plus lacrimal
superficial plane over which the contact lens is placed lens is formed and it has to be compensated with induction
and the center of the optical zone diameter of minus power in contact lens.8
(Fig. 3.1.4). Rule of thumb: The tear lens power is 0.05 mm which is equal
• Axial edge lift (AEL): It is the distance between a point on to 0.25D. This means that if the lens is steeper by
the back surface of a lens at a specified diameter and 0.05 mm, –0.25D of power should be added to the contact
continuation of the back central optic zone, measured lens or else if it is flatter by 0.05 mm, +0.25D of power should
parallel to the lens axis (Fig. 3.1.5). be added to the contact lens.
• Radial edge lift (REL): It is the distance between a point on
the back surface of a lens at a specified diameter and the
continuation of the back central optic zone, measured along
a radius of curvature of the latter (Fig. 3.1.5).
• Lens designs:
– Monocut lens: A contact lens having single anterior
curve.
– Monocurve: Single posterior curve.
Fig. 3.1.4: Sagittal depth Fig. 3.1.6: Positive and negative tear film
As the posterior surface of spherical contact lens is segment of the eye and abnormalities of the ocular and
spherical, the lacrimal lens neutralizes the regular as well as lid surfaces should be done to rule out any contraindication.
irregular astigmatism of the anterior surface of the cornea • Keratometry: As baseline quantification of corneal curvature.
and gives an impact on the spherical component of the • Horizontal visible iris diameter (HVID): Corneal diameter is
refractive error of the eye. measured in mm by the normal PD rule. The HVID must
be at least 2 mm more than the TD of the lens to be fitted
Convergence demand in contact lenses is more in myopes with
in case of soft lenses.
CL wear and less in hyperopes with CL wear compared to
• Tear film assessment: Schirmer, phenol red thread, inferior
spectacles.
tear prism height and tear quality (NIBUT and BUT) to
Accommodative demand in contact lens is less with hyperopes in quantify and assess the quality of the tears before fitting is
case of contact lenses compared to spectacles. important as dry eyes are one of the major causes of
contact lens discontinuance. The lenses become
The magnification is reduced with contact lenses in plus powers
uncomfortable, lens surfaces dehydrate and corneal staining
compared to spectacles as they are close to the corneal plane
can result.
and the minus powers have lesser minification of image with
• Pupil diameter: It is measured in normal room illumination
contact lenses.
with a mm ruler.
PRE-FITTING EXAMINATION • Palpebral aperture: The distance between the lid margins with
the patient looking straight ahead is measured using a mm
Preliminary evaluation is very important for giving the prac- ruler.
titioner a feel for patient suitability. A comprehensive examina- • Lid position: One should record the position of the lid
tion is done to rule out any of the following contraindications: margins with respect to the limbus. This information can
• Inflammation or disease of the anterior segment. be helpful in selecting the diameter of a RGP lens.
• Any systemic disease which may be complicated by contact • Corneal topography: Is useful in determining the shape of
lens wear, such as diabetes, epilepsy, mental incompetency, the cornea and will prove helpful in fitting RGP lenses
pregnancy, chronic allergies, chronic antihistamine and diagnosing conditions such as keratoconus and other
use, etc. corneal distortions.
• Poor hygiene.
• Lack of motivation. TRIAL LENS SELECTION
• Work environment should not be dry, dusty, dirty or Selection of the lens is done for either a hydrogel or a RGP
unsanitary.
lens. A hydrogel is selected for initial comfort, occasional wear
• Poor tear quality or quantity.
and for patients in dusty environments. RGP lenses are good
Record basic history to evaluate the needs to decide a suitable in masking of cornea toricity and corneal distortion, is durable
lens: and can be made in custom parameters.
• Nature of presenting problem and chief complaint Lens selection is mostly done on the basis of keratometry
• Visual, ocular and general health history and patient’s spectacle prescription (Table 3.1.1).
• Family history Selection on the modality of the wear is also done on the
• Medication usage and medication allergies basis of the number of wearing hours required. Shorter the
• Vocational and vision requirements. replacement, the better it is for the eye.
Water content and ionicity of the lens material is also
Prefit Measurements selected before the trial fitting is done.
• Visual acuity (distant and near): Unaided and with glasses Hydrogels can be further classified as:
and the best corrected VA. • Low water content lens: When the water content is
• Refraction: An accurate refraction is required to determine less than 50 percent.
the type of lens to fit, to assess the power to order in the • High water content: When the water content is greater
lens and will also be a baseline finding to a later refraction than 50 percent water.
at a follow-up visit. Increasing the water content, increases oxygen permeability
• Ocular health assessment by slit lamp examination: Evaluation and decreases durability. A low water content lens is the lens
of anterior segment and tear layer, evaluation of posterior of choice in dry eyes also.
84 Contact Lens
Table 3.1.1: Selection of trial lens

K reading Spectacle prescription Type of lens selected
Near spherical Near spherical spectacle prescription Soft or rigid lens
Astigmatic cornea Astigmatism (over 0.50D or 0.75D of cylinder) Toric soft or RGP
Astigmatic cornea Spectacle cylinder matches or nearly matches Spherical rigid lens or toric soft lens
the corneal toricity
Astigmatic cornea Spectacle cylinder does not match the corneal toricity A toric soft lens
Significant corneal astigmatism Little or no spectacle cylinder A spherical soft lens
Highly toric cornea High cylinder Toric (bitoric) rigid lens
Initial Trial Lens Parameters Selection 45D range and a flat BC for K less than 41D. Some
manufacturers assign sag or vault based fitting.
The first trial lens should be chosen using the basis of the
following criteria:
CONTACT LENS FITTING
• Power: It should be as close as possible to the patients’
prescription, and compensate for the back vertex power Diagnostic Fit Method
to cornea level if the spectacle prescription is greater than
Predicted lens parameters are selected as discussed above and
+ 4D. It should be equal to the spherical equivalent for
trial lenses are tried on the patient to verify that predicted lens
patients with low amounts of spectacle cylinder.
parameters are the lens parameters to dispense.
• Total diameter: It must be larger than the HVID by 2.0 mm
to allow for full corneal coverage in case of soft lenses Fitting Steps in Hydrogel Lenses
and less than the HVID by 2 mm for RGP lenses. Soft
lenses are generally available in 13.5 to 15 mm diameters • The patient’s lenses are inserted and the lens allowed to
and RGP lens diameter ranges between 8 to 10 mm. settle for 5 to 10 minutes.
• Base curve: If a choice of base curve is available, the • The positioning, coverage and movement of the lens is
manufacturer’s guidelines for which lens to try first should assessed (Figs 3.1.7 and 3.1.8): These fitting characteristics
be followed. This should be done without regard to should be assessed using a slit lamp biomicroscope, with
K-readings. Usually they are 4 to 5D flatter than the flatter low magnification and diffuse illumination.
K. Disposable lenses are typically available in 2 to 4 BC i. The lens should be centered in all position of gaze.
and in such cases the manufacturers’ steepest BC is ii. There should be complete corneal coverage extending
selected, if K greater than 45D, a middle BC for 41 to on the sclera for a minimum of 1.0 mm in all directions.
Figs 3.1.7A and B: A well centered soft lens with complete coverage
the lens may be decentered inferiorly. It may show

edge lift inferiorly and will slide inferiorly upon
upgaze.
• Push-up test: The most useful criterion for assessing dynamic
soft lens fit is the push-up test. The lens is dislodged
vertically by gently pushing upwards on the lower eyelid
margin against the lower edge of the contact lens, and
then releasing the lid. The measure is to see how easily the
lens is displaced (resistance to decentration) and then how
quickly it returns to its central position. A percentage
grading scale is often used to record this measure of
tightness with 50 percent being optimal, where the lens
shows smooth movement and prompt recovery; zero
Fig. 3.1.8: A decentered flat soft lens
percent is too loose where the lens is held in the eye by lid
tension only (and would fall from the cornea if the lower
iii. Movements of 0.5 to 1 mm in straight ahead gaze is lid is removed), and 100 percent represents no movement
ideal (0.50 mm movement is ideal in most modern thin or a bound lens.
lens designs): • Over-keratometry aids in the determination of the fit:
– If the fit is tight there is little to no movement, – Steep fit: Clear mire immediately after a blink which
conjunctival drag. The push-up test will show then becomes distorted and blurry
tightness more than 60 percent. – Flat fit: Mire distortion which becomes more distorted
– If the lens is too loose, there will be greater than on blink
1 mm movement, moving partially off the cornea, • The patient comfort is assessed (Table 3.1.2).
Table 3.1.2: Assessment of soft contact lens fit

Fit assessment Ideal Unacceptable fit Possible cause Trouble shooting
Comfort Comfortable Continual discomfort Poor centration Tighten lens or change design
Discomfort worse on blinking Loose lens
Edge stand-off
Vision Clear, stable vision Blurred vision Incorrect power Reconfirm power
Variable vision, after blinking Loose lens Tighten fit—decrease BC/
increase OD
Variable over-refraction Loose lens
Centration Full corneal coverage • Greater than 2 mm Lens too large Reduce total diameter
conjunctival overlap
(1–2 mm overlap) • Corneal exposure Too small lens Increase total diameter
• Poor centration
Centered in all
position of gaze
Edge alignment Regular alignment Edge stand-off Loose lens Tighten lens
to conjunctiva
Conjunctival indentation Tight lens Loosen lens
Post-blink 0.2 to 0.4 mm Less than 0.2 mm Tight lens Loosen lens, try different
movement movement design
(primary gaze More than 0.4 mm Loose lens Tighten lens, try different
movement) design
See comfort
Push-up test Smooth recovery Resistance to movement Tight lens Loosen lens
from push-up
Excessive movement and Loose lens Tighten lens
erratic recovery
86 Contact Lens
Altering the Fit Parameters required in ordering lens:

• Base curve (BOZR)
Lens fit can be affected by two key variables—lens parameters
and ocular features. The main lens parameter that is considered • Diameter (TD)
to have an effect on lens fit is the BOZR, with an increase in • Power (BVP—vertex corrected)
radius leading to an increase in lens movement and vice versa. • Replacement frequency—monthly disposable, quarterly,
A change in the TD of the lens can affect dynamic fit in daily disposable
addition to centration. With an increase in diameter, the sag • Modality—Daily wear/Extended wear, etc.
of a lens increases, hence tightens the fit, and a smaller lens For example: 8.8/14.0/–3.75/monthly disposable/
has the opposite effect. Peripheral lens design has also been daily wear.
shown to have a effect on lens fit. Changing a patient to a
different lens design with the same BOZR and TD may not Soft Toric Contact Lens Fitting Outline
fit in the same way. The manufacturing method and the material Toric hydrogel lenses are indicated for patients with astigmatic
composition also affect the fitting characteristics. Ocular spectacle prescription usually > 0.5 diopters. A soft lens is
features that can affect lens fitting characteristics includes the indicated where there is rigid lens intolerance or when the
ocular sag. The position of the corneal apex, where a decentered patient has unsatisfactory visual acuity with spherical lenses
apex means the lens will decenter (this can be overcome with due to uncorrected astigmatism. They are specifically indicated
a larger diameter lens). Excessive lid pressure, which can cause
when there is difference in corneal and ocular astigmatism.9
a lens to ride high, or show excessive movement.
Spherical lenses have the same power all around the lens,
Table 3.1.2 summarizes the assessments that are made
so it doesn’t matter if the lens rotates on the eye. Toric lenses
during soft lens fitting, their possible causes and remedies.
have two different powers in the lens, so they must remain in
After finalizing the fit, determine the visual acuity and do
over-refraction. position for best visual acuity. These lenses are stabilized in
the eye by the following methods:
Over-refraction • Prism ballast
• Back surface toric
The power of the contact lens should preferably be calculated
• Double slab-off
by doing over-refraction (refracting over the trial contact lens).
• Periblast
The final power is the algebraic addition of the trial lens added
• Truncation
to make the patient achieve the best corrected visual acuity.
• Any combination of the above.
The over refraction should always be within 4 diopters. It is
usually carried out with a trial frame and trial lenses. The idea Prism ballast: This technique is most commonly used by the
is not only to verify the visual acuity and the lens power with manufacturers to stabilize toric lenses (Fig. 3.1.9). There is a 1
the contact lenses in place but also to identify any residual to 1.5 diopter prism at the inferior base. The prism acts as a
refractive error. weight and prevents rotation. These lenses are specified by
The final lens power in the spherical lens fitting is a marks which are used in assessing the orientation of the lens.10
spherical power. So the additional lens power should always Different manufacturers give different form of markings.
be spherical power. If there is significant cylindrical acceptance
over the diagnostic lens and the vision is not acceptable by
spherical equivalent then a toric lens fitting is required.
Example:
Power of trial contact lens on the eye = – 3 .0
Over-refraction = – 0.75
Final lens power to be ordered = – 3.75
The dispensing should be out of the inventory. When an
adequate fit is not achievable with one manufacturer’s lens,
an alternative with different parameters may be considered.
The lens vial specifications should be verified prior to
dispensing. Fig. 3.1.9: Prism ballast design
This calculation is done in following steps:

• The spectacle prescription is written in the cross cylinder
form (at the two principle meridians).
• The back vertex is compensated for.
• The prescription is re-written in the sphero-cylinder form.
For example: A toric soft lens prescription: 8.6/14.2/–3.75/
–2.25 × 10°/SL/66 toric monthly disposable/daily wear lens.
Spherical Rigid Contact

Lenses Fitting Outline
RGP lenses are lenses of choice because of better vision and
optical quality specially in cases of irregular astigmatism, in
borderline dry eyes and have long term benefits due to better
oxygen transmissibility to the cornea. Fitting of such lenses is
Fig. 3.1.10: A toric lens showing rotation to the left purely done on trial lens methodology.
Selecting the RGP Trial Lens

Fitting Summary of Toric Lenses
After performing the preliminary examination, a suitable
• The spherical, cylindrical or spherocylindrical refraction is
RGP lens is selected based on measurements and inserted
performed. The spectacle power prescription is converted
into the eye.13
to ocular prescription by compensating for the vertex
distance. Diameter selection: The HVID gives an initial clue as to the
• The appropriate lens is selected as close as possible to the overall lens diameter, usually approximately 2 mm less than
spectacle power and axis. The base curve is also selected the HVID. A total diameter of about 9.0 mm is a good
as done for spherical lenses. starting point. Steeper base curves need smaller diameters
and flatter corneas fit better with larger diameters. A narrow
• The lens fit is checked and the base curve finalized. The
palpebral aperture needs a small lens diameter, e.g. 8.50 to
base curve should not be changed after axis finalization.
9.00 mm; A patient with a wide palpebral aperture is more
• Orientation of the axis and stability should be checked
likely to need a larger lens diameter, e.g. 10.00 to 10.50 mm.
(Fig. 3.1.10). This helps the upper lid to grasp the lens edge to prevent
• The axis rotation should be compensated. the lens from riding low.
Axis compensation is done in the final ordering based
on the rotation assessed by a simple rule called the LARS Base curve selection: This begins with the measured corneal
rule (Left add right subtract). This is assessed commonly by curvature values. The first choice lens usually has a back optic
using a slit lamp and aligning the slit beam with the zone radius of curvature (BOZR) nearest to the flattest
keratometry ‘K’ reading. When the corneal astigmatism is
orientation marks. To identify the lens rotation, one needs
approximately 1.50D, for the fitting of a traditional tricurve
to observe the markings on the lens.11,12
design, a lens BOZR of 0.05 to 0.10 mm steeper than the
If the lens shows rotation to the left of the observer by
flattest keratometry reading should be chosen. The more
10°, the final prescription of the contact lens is 10° added to
spherical the Ks, the more likelihood of the optimum RGP
the spectacle prescription. For example:
CL BZOR being slightly flatter or the same as the flat K. The
If the spectacle prescription is –3.0 DS/–1.25 DC × 10°
more astigmatic the Ks, the more likely it is that the appropriate
and the trial lens shows rotation of 10° to the left, the final
base curve will be close to the mean K.
contact lens power will be –3.0 DS/–1.25 DC × 20°. If the
same lens is rotated to the right then the final ordered lens Power: The power of the trial lens should be as far as possible
power would become –3.0 DS/–1.25 DC × 180°. The final within ± 4.0 Dsph of the spectacle power.
lens shows the same degree of rotation when placed on the An assessment and note of the lens fit and performance
same eye. is made (Fig. 3.1.11). The practitioner needs skill in successful
The power of the spherical and cylindrical lens is calculated RGP lens fitting. Thirty minutes or more for more accurate
from the spectacle prescription. reassessment of the fit and comfort is allowed.
88 Contact Lens
Fig. 3.1.11: Assessment of dynamic fit: Fig. 3.1.12: Ideal RGP fit
(Centering, coverage, movement)
The rigid lens fitting is evaluated in two ways: A good fit shows (Fig. 3.1.12):
a. Static: With the lens in stationary position, the fluorescein • Shows satisfactory lens centration
pattern with central alignment, mid peripheral minimal • Aligns with the flattest corneal meridian
clearance and adequate pooling in the peripheral curves is • Moves freely giving a good tear flow beneath the lens
evaluated. • Covers the pupil but slight vertical or lateral positioning is
b. Dynamic: Dynamic fitting evaluation evaluates movement acceptable
of the lens with blinks and further judges the tear exchange • It is more comfortable after the tolerance trial
under it with the fluorescein dye. The centration and the • An alignment type fluorescein pattern that has uniform
coverage are also evaluated. tear film behind the lens in the central region, a mid-
Sodium fluorescein dye is usually used to fit a RGP base peripheral mild bearing and a peripheral edge pool of
curve, show alignment with the corneal surface, position the 0.26 mm to 0.35 mm is ideal.
CL under the upper lid or cause it to ride within the palpebral
A flat fit (Fig. 3.1.13):
aperture to enhance tolerance. The posterior peripheral curve
• It bears heavily on the central cornea
system is custom designed to lift the edge of the CL gently
• It moves very freely
off the corneal surface.
Rigid Lens Fit Assessment

The lens fit is assessed after a drop of fluorescein is instilled,
the patient blinks several times and the fluorescein pattern
observed using the Burton lamp or the slitlamp with the cobalt
blue filter. The lens centration, movement and fit should be
noted during the primary position of gaze and on eye version
movements. An ideal rigid lens moves 1 to 1.5 mm vertically
with each blink. This movement should also be smooth
indicating an alignment fit.
The following are the 3 areas of observation which define
an ideal alignment fit, steep or flat fit on the eye.
• Central
• Mid-peripheral
• Edge width with clearance Fig. 3.1.13: A flat fit
the plus power. Over-refract to determine the best sphere

power.
The final order of an RGP lens includes:
• BC
• Power
• OD
• OZ
• IC/width
• PC/width
• Tint
• Material.
DISPENSING OF CONTACT LENSES
Fig. 3.1.14: A steep fitting lens While dispensing, the practitioner should assess the following
on a routine to confirm the performance of the lens:
• It decenters markedly Step 1: Evaluate lens performance by evaluating the following
• It usually gives unstable vision after lens insertion:
• It is very uncomfortable • Record visual acuity with lenses uniocularly and binocularly.
• A central blue area of apical touch and absence of
Do overrefraction and check for any deficiencies or any
fluorescein indicates a flat fit. A flat fit usually shows a
residual astigmatism.
broad green edge band of lens clearance >0.4 mm.
• Check fitting, movement, centering, and coverage for soft
To improve a flat fitting, a steeper curve lens with smaller
lenses and check static and dynamic fitting for RGP lenses.
BOZR, or a larger BOZD is chosen.
• Assure that the parameters are correct and the surface
A steep fit (Fig. 3.1.14): quality is proper.
• It shows central pooling surrounded by a ring of touch
which restricts tear flow and interferes with corneal Step 2: Educate the patient on lens care procedures
metabolism This is also the time when the patient should be given
• It usually centers well instructions on insertion/removal and care of the lenses.
• It shows less movement with the blink. The movement is Provide the patient with written instructions.
rather static and sluggish even when the lens is pushed
• It is initially comfortable on the eye as it causes little lid Insertion Technique for Soft
sensation and Rigid Lenses
• The appearance of central green tear pooling beneath the
lens, sometimes is seen with trapped bubbles under the • Wash the hands thoroughly with soap and dry.
lens, blue heavy touch of the lens at the mid-peripheral • Place the lens on the tip of the index finger. Make sure the
transition region, and minimal lens edge clearance lens is right side out and inspect lens for damage or
< 0.25 mm. deposits.
To alter the fit, to achieve alignment is done by either altering • Look up, and retract the lower lid with the middle finger
the base curve, diameter or the edge curvature and width. and while looking upward, gently apply the lens to the
• To alter a steep fit — flatten base curve or reduce diameter cornea of eye.
• To alter a flat fit — steepen base curve or increase diameter. • Remove the finger and then slowly release the lid. Release
Once the base curve, diameter, peripheral curves are the lower lid first and then the upper.
decided the next step is over refraction. Final changes in BC • Close the eye and gently massage the lids.
will directly affect the optical power of the CL/eye system • Cover the other eye and focus it to make the correct
and will require direct optical power compensation based on centration.
the fluid lens between the lens and the cornea. For a steep • Repeat the same procedure to the next eye.
lens, add minus and for a flat fitting lens, compensate by adding • Remove the lens for cleaning and sterilizing.
90 Contact Lens
Soft Lens Removal Technique debris. After washing, a lint free towel should be used to dry
hands.
• Look up securing the upper lid with the left hand and the
• Cleaning: Cleaners mostly contain a surfactant, viscosity
lower lid with the right hand.
agent, chelating agent, buffer and preservative.
• Using the index finger, of right hand slide the lens down Lenses are cleaned with the cleaning solution because
and out on to the sclera. this removes the protein deposits as well as other debris
• Once the lens is on to the sclera, use the thumb and index that build up on lenses. Daily cleaner is used to clean lenses
finger to pinch the lens off the eye. on a daily basis. A few drops of the cleaner are applied to
the lens while it rests in the palm of the hand. Then the
Rigid Lenses Removal Technique contact lens is rubbed for about 20 seconds with a fingertip
This is slightly different from the soft lens technique. In this: (depending on the cleaner’s directions) on each side. The
• Look downward, open the lids wide so that the edge of lenses should be cleaned after removal every night.
the lid will engage the edge of the lens. • Rinsing: Saline solutions are the rinsing agents in contact
• Draw the lid tight by a lateral pull of the index finger and lens care solutions. The next step is to rinse off the cleaning
blink. solution from the lenses with saline or multipurpose
• The lid should dislodge the lens slowly. solutions. This is also important because this washes off
• Cup the other hand under the eye to catch the lens. the loosened debris. Water should never be used for rinsing
lenses.
Scissors Technique • Soaking and disinfection: To disinfect the lenses, the container
should be filled with fresh soaking solution every night.
Another technique suggested by some practitioners is the This is the disinfecting solution and it kills the micro-
Scissors Technique of removal. organisms that could be growing on the lens.15
• Hold the upper lid by the index finger and the lower by The commonly used antimicrobial agents in contact
middle finger. lens solutions are:
• Apply lateral traction to the lids and squeeze the lens off – Biguanides, e.g. polyaminopropyl biguinamide,
by a scissors motion. polyhexidine
– Polyquad
Normal Adaptation Symptoms – Sorbic acid
It is common for the patient to have mild symptoms with soft – Benzalkonium chloride
lenses and significant ones with RGP wearers in the initial – Chlorhexidine
days. They may include mild redness, tearing, lid irritation, – Quaternary ammonium and
difficulty in looking up, occasional blurring or disturbance of – Thiomersal.
vision, excessive blinking, headache and lens displacement. Multipurpose solution is the most popular cleaning, rinsing
and soaking solution for contact lenses.
LENS CARE AND MAINTENANCE The use of water to clean contact lenses may lead to lens
While daily disposable lenses require no cleaning, other types contamination and has been known in some cases to cause
require regular cleaning and disinfecting in order to retain clear irreparable harm to the eye. The tips of the containers for
vision and prevent discomfort and infections by various micro- these solutions should not touch any surface, and the container
organisms including bacteria, fungi, and acanthamoeba that should be kept closed when not in use.16
form a biofilm on the lens surface.
Optional Systems of Maintenance
Contact Lens Care Regimen: Daily Steps
Hydrogen Peroxide Solution
Lens care and maintenance procedure really have 3 steps
(cleaning, rinsing, disinfecting and storing the lenses).14 Hydrogen peroxide is a very effective disinfectant for a wide
Following are the basic steps followed in routine for range of bacteria and viruses. An oxidative reaction occurs
maintenance of contact lenses. whereby the hydrogen peroxide molecule breaks down into
Before insertion or removal of contact lenses, hands should free radicals, which disrupts the cell wall of the micro-
be washed thoroughly so that they are free of dirt, germs and organisms. This free radical further breaks into water and
oxygen. Neutralization compounds like catalytic disk of day. The patient should be able to “see good”, “feel good”
platinum, sodium pyruvate, sodium thiosulphate or catalase and “look good”.
is used to convert peroxide into water and oxygen. It is used • Compliance on usage of solutions should be checked. Lens
for disinfecting the lenses, and are available as ‘two-step’ or handling, insertion and removal, use of solution and its
‘one-step’ systems. They are specially indicated for patients steps in usage and the hygiene, should be instructed orally
who have preservative sensitivity. They also perform better in and in the written format.
disinfection compared to multipurpose solutions. They are • Visual acuity should be assessed. Over-refraction should
strongly recommended for silicone hydrogel lens materials.17 be done and any deficiency calls for power adjustments.
• Slit lamp evaluation with lenses starting with examination
Enzymatic Cleaner for surface integrity, deposits, lens surface and edges should
This is used for cleaning protein deposits off lenses. They be done. The lens fitting should be reviewed.
form a part of cleaners by breaking down of proteins and are • Slit lamp evaluation upon lens removal should be done
advised usually weekly. Emphasis is now on regular and edema (striae, microcysts, polymegathism) and
replacement of hydrogels, so that this system is not popular neovascularization should be looked for. The lid should
now. The three main components of enzyme tablets used are be everted and the upper tarsal conjunctiva examined for
papdine, pancreatin or subtilisin. contact lens induced papillary conjunctivitis.
• Fluorescein evaluation should be done. The corneal
Procedure of enzyme treatment: The lens are cleaned prior to
integrity should be checked by staining the cornea with
enzyme treatment. One tablet of enzyme is soaked in 5 ml of
the fluorescein dye and looking for any aberrations and
soaking solution for 15 minutes to 4 hours (as per manufacturer
staining on the cornea.
guidelines). The lens is removed and cleaned well again.
Resoaking, in fresh solution, may be needed in some type of • Dryness is the most common complaint with soft lenses.
tablets.
COMPLICATIONS OF CONTACT LENS WEAR
Lubricating Drops Complications associated with contact lenses range from mild
Lubricating drops need to be added to improve wettability to severe and occur with all types of contact lens wear. Other
and prevent the lens from drying in the eye. Certain artificial complications include lens deposition, allergic conjunctivitis,
tear substitutes or tear supplement drops used can bind with giant papillary conjunctivitis, peripheral infiltrates, microbial
the soft lens material and cause problems. keratitis, and neovascularization.18
Compliance is a major issue with the use of contact lenses As such, lenses do not cause any complications.19 They
because patient noncompliance often leads to contamination usually happen because of:
of the lens, storage case, or both. Therefore, the patient or • Mechanical reasons: When the lens fitting is not proper or
guardian should be trained in lens care, maintenance, and the quality of the lens may be poor.
handling. An appropriate follow-up care under professional • Physiological reasons: When the oxygen requirement of the
supervision should be stressed. cornea is physiologically compromised, thus leading to
hypoxic reactions of the cornea
Follow-up Examination • Environmental reasons
Contact lenses are medical devices, relatively safe, yet not free • Noncompliance: When it happens due to the neglect of the
from complications. Most complications of CLs could be patient in following proper care and maintenance
prevented if the patient has regular follow-up. instructions, ignoring symptoms, over wearing of lenses,
Routine follow-ups in case of daily wear lenses are at sharing of lenses and solutions, etc. Patient related factors,
1 week, 1 month, 3 months, 6 months and every 6 months such as alteration of the recommended wearing or
thereafter and in case of extended wear are at 24 hours, replacement schedules and noncompliance with
3 days, 1 week, 2 weeks, 1 month, 3 months and every 3 months recommended contact lens care regimens for economic
thereafter. reasons, convenience, contribute to contact lens-related
On the follow-up visit: complications.20
• Any problems/complaints should be identified. Complications may require discontinuation of contact
• The patient should be successfully wearing the CL for 12 lenses, topical therapy, and changes in contact lens wearing
to 14 hours everyday with good vision, throughout the schedules, materials, and care solutions.6 To avoid serious
92 Contact Lens
complications, patients should be reminded to remove their by deposits or any mechanical interaction between lid and
contact lenses as soon as ocular irritation occurs, and to call lens. The condition progresses from mild to severe stage, if
their eye care practitioner immediately, if symptoms persist. the predisposing factor is not removed. GPC is one of the
The majority of complications encountered with daily CL major reasons for lens dropouts. Its incidence reduces
wear are manageable by discontinuing the use of the CLs. remarkably if the lenses are replaced frequently.
Extending CL wear through one or more sleep cycles appears The preservatives in the solutions can cause immediate
to increase both the prevalence and severity of all allergic reactions or delayed hypersensitivity reactions. The
complications. patient develops an inflammatory reaction and sensitivity to
Noninfectious contact lens complications include: solutions. One has to shift the patient to unpreserved unit
• Sterile corneal infiltrates dose solutions, peroxide system or to one day disposable lenses
• Corneal epithelial problems in such cases.
• Mechanical corneal abrasion Epithelial or subepithelial corneal staining can be of various
• Hypoxic reactions types and typically diagnostic of several complications. It
• Toxic and/or immune reactions should be routine to instill fluorescein in the eye and examine
• Superior limbic keratoconjunctivitis for any corneal staining, superficial punctate keratitis, 3 and 9
• Giant papillary conjunctivitis o’clock staining, arcuate defects or dry eye. They occur because
• Endothelial complications. of some mechanical trauma to the eye. With an abrasion on
One of the uncommon but serious complications of the eye the patient is at risk to microbes that can penetrate the
contact lens is corneal ulcer.21 It is thought that hypoxia or cornea easily. The management includes discontinuation of wear
mechanical irritation leads to reduction in ability of the eye to till the abrasion heals and the cause is treated.
resist invading organism. The most important organisms
leading to serious infections are Pseudomonas aeruginosa and Ocular Response to Contact Lens
Acanthamoeba. The infection can be passed on from patient’s Wear Due to Hypoxia
contaminated hands, lens case, solution or through an
If the critical levels of oxygen required by the cornea to
improperly disinfected lens. The patient and the practitioner
maintain its functional and structural integrity are not available,
plays a very important role in the prevention of ulcer. One
the following changes may be seen in contact lens wearers.
can reduce such sight threatening complications if the patient
Contact lens wear can cause a change in corneal physiology,
is made aware of the warning signs, does not sleep with the
which can lead to epithelial, stromal, and endothelial compro-
lenses and follows proper hygiene and compliance. Corneal
ulcer needs immediate medical intervention. mise.
Another commonly seen complication with conventional • Effect on epithelium: Hypoxia leads to formation of micro-
soft lenses is contact lens induced papillary conjunctivitis22 (CLPC) cysts, epithelial thinning, epithelial injury like abrasions and
(Fig. 3.1.15). This is an inflammatory response that is induced reduction in epithelial adhesion due to decrease in
hemidesmosomes synthesis. Epithelial and subepithelial
infiltrates are commonly seen in such situations.
• Effect on stroma: The hypoxia leads to corneal edema seen
as striae and folds, stromal thinning and corneal
neovascularization.
• Effect on endothelium: Effects are seen as polymegathism and
endothelial blebs.
SPECIALIZED USES OF CONTACT LENSES
Bandage Contact Lenses

Soft lenses are often used in the treatment and management
of nonrefractive disorders of the eye. A bandage contact lens
protects an injured or diseased cornea from constant rubbing
of blinking eyelids, thereby allowing it to heal. They are used
Fig. 3.1.15: Contact lens induced papillary conjunctivitis in the treatment of conditions including bullous keratopathy,
dry eyes, corneal ulcers and erosion, keratitis, corneal edema, Tinted contact lenses have a dye incorporated into the
descemetocele, corneal ectasis, Mooren’s ulcer, anterior corneal lens material which is safe and compatible with ocular tissues.
dystrophy, and neurotrophic keratitis. Bandage lenses provide This dye gives the lens a particular hue or tint, depending on
protection to healing of the cornea, so that a hydrophilic, thick, the color of the dye used. Some tinted contact lenses can be
low water content lens, which allows oxygen to permeate results used to subtly alter the natural color of the eye, while others
in enhancement of stromal vascularization to prevent further can be used to completely change the color of the eye.
melting. Postoperative use of bandage contact lenses is There are three types of tinted contact lenses:
beneficial in treating surgical conditions of the cornea and 1. Visibility tinted contact lenses do not change the eye color.
ocular surface. They also reduce subepithelial scars and haze 2. Color enhancement contact lenses enhance the color of the
by shielding the bare underlying stroma from persistent trauma iris. Color enhancement lenses allow light to pass
by the eyelid. With the new silicone hydrogel lenses, incidence through the tinted portion of the lens.
of vascularization and infection is much less than that in the 3. Opaque contact lenses are also referred to as “eye color
case of low Dk lenses used in extended and overnight wear. changing” contact lenses. Opaque contact lenses allow
The use of disposable lenses was most effective in conditions people with dark eyes to have a completely different
requiring short-term lens use where one to two lens applica- eye color.
tions is sufficient to allow healing, making disposable lenses a The fitting of cosmetic lenses is the same as for soft contact
very convenient and cost-effective alternative to conventional lenses. As with any other contact lens, patients should be
therapeutic bandage contact lenses.23 educated regarding proper handling and disinfection care.
Orthokeratology (Ortho-K) Prosthetic Contact Lenses
Orthokeratology is a lens fitting procedure that uses specially Prosthetic contact lenses (Figs 3.1.16A and B) provide an
designed rigid gas permeable contact lenses to change the important therapeutic tool in the treatment of diseased and
curvature of the cornea to temporarily improve the eye’s ability disfigured eyes. Iris painted contact lenses are good cosmetic
to focus on objects. This procedure is primarily used for the prosthesis for disfigured or blind eyes for which no evisceration
correction of myopia. Overnight Ortho-K lenses are the most or enucleation is indicated. These contact lenses mask flaws
common type of lens used. The vision correction effect is and improve the appearance of an eye disfigured from a birth
temporary. defect, trauma, or eye disease. Other eye conditions and
accompanying disfigurement that may benefit from use of a
prosthetic contact lens include aniridia, albinism, diplopia,
Cosmetic Contact Lenses
nystagmus and amblyopia. Occlusive contact lens are used to
Colored contact lenses have found a niche in the consumer provide occlusion therapy in amblyopia.
marketplace. Some contact lenses do not correct vision and Prosthetic lenses used in such cases are hydrogels with
are intended solely to change appearance. two main designs:
Figs 3.1.16A and B: A scarred cornea fitted with prosthetic lens

94 Contact Lens
1. Iris painted, center clear

2. Iris painted, center black/opaque.
In a non-seeing eye, one has the choice of using a clear
pupil or a black opaque pupil CL. If there is nothing to hide
in the pupil area, then iris painted, center clear lens design is
used.
Fitting a prosthetic lens is much like fitting a regular soft
contact lens with a few extra considerations like achieving a
cosmetic match in eye color with the other eye. Several
companies manufacture “stock” prosthetic soft lenses, which Fig. 3.1.17: Simultaneous vision lenses
have some set parameters and iris color choices. The opaque
stock prosthetic contact lenses are usually designed to be
Bifocal contacts lenses (Fig. 3.1.19) have two prescriptions
replaced annually. When fitting hand-painted lenses for
for the same lens. The availability of disposable lenses as trial
therapeutic or cosmetic application, it is important to precisely
lenses has made the fitting of these lenses easy. The fitting
measure the iris diameter in the horizontal and vertical
procedure is the same as for soft lenses. The pupil size plays
dimensions, pupil sizes in the normal room illumination, and
an important role in the fitting bifocal CLs. One needs to
to document iris details.
understand the design and the need of the patient to achieve
Dry Eye and Contact Lens success in fitting presbyopes.
Contact lens intolerance is often a consequence of dry eye. Contact Lenses and Keratoconus
Dryness is the primary reason why people permanently
discontinue contact lens wear. Approximately four out of five Contact lenses remain a popular treatment for keratoconus,
lens wearers report symptomatic dryness during some portion with sight restoration being good in this group with lenses.
of their wearing schedule. The successful management of the keratoconus patient with
There are ways for contact lens wearers to combat dry contact lenses requires a corneal topography as the disease
eyes and feel comfortable in their lenses for longer periods of affects the cornea far beyond the range of the keratometer.
wearing time. Possible remedies of contact lens related dryness Topography is quantitatively viewed to identify the size, shape,
include use of contact lens lubricating drops, soaking lenses and location of the apex, i.e. the steepest area of the cornea.
during the day or switching to either disposable lenses or a Because of the varying peripheral corneal topographies
different lens material like silicone hydrogel with wetting agents found in advanced keratoconus, no single lens design or fitting
within the lens matrix. philosophy consistently results in an optimal fit. Various
options are available for fitting keratoconus. Some of the fitting
Bifocal/Multifocal Contact Lens philosophies are as follows:
With contact lenses on the eye there is an option to correct Rigid gas permeable contact lenses are the simplest fitting
near vision with spectacles over CL. choice and are often able to achieve success in mild cases of
Three main types of contact lens are used for presbyopic keratoconus. A diagnostic lens is selected with base curve radius
correction:24 equal to the dioptric curvature at the corneal apex. The lens is
a. Monovision correction involves using single-vision lenses with placed on the eye and its position and relationship to the cornea
near prescription on one eye and distance prescription on evaluated with fluorescein.
the other.25 Modified monovision uses a single-vision lens An optimum lens-to-cornea fitting relationship is accomp-
on one eye and a multifocal/bifocal lens on the other. lished when we achieve a “three point touch” (Fig. 3.1.18).
b. Alternating/Translating vision lenses are so named because the • The base curve radius should provide minimal clearance
pupil alternates between the two powers, as one’s gaze shifts across the 3 mm corneal apex.
upward or downward. • The mid-periphery of the lens should touch the mid-
c. Simultaneous vision lenses (Fig. 3.1.17) require the eye to be peripheral cornea at 3 and 9 o’clock to prevent nasal/
looking through both distance and near powers at the same temporal lens decentration.
time. Simultaneous vision lenses are available as, the Aspheric lens designs are sometimes necessary in cases of
concentric ring designs and the aspheric designs with moderate and advancing keratoconus. These designs take into
center-near or center-distance optics. account the cone shape of the cornea caused by keratoconus.
with irregular astigmatism or those who had discomfort and

decentration with traditional GP lens designs.
In certain cases, traditional spherical and aspherical GP
lens designs may not provide the desired centration, optics, or
comfort required by the patient. In these situations, the patient
may benefit from a large diameter (13.5 to 16.0 mm) semi-
scleral lens. Semiscleral lenses have proven to be extremely
beneficial for patients with highly irregular and/or asymmetric
keratoconic corneas.
Regular soft lenses are unlikely to compensate for the
refractive error associated with keratoconus, but new soft lens
designs specially designed for irregular corneas with complex
optics can be used in some patients. Toric soft contact lenses have
been successfully used in the early stages of keratoconus.
Fig. 3.1.18: Three-point-touch pattern in keratoconus fit Scleral lenses are found to be extremely useful in the
management of keratoconus when all other options fail.
Because scleral lenses rest on the sclera, they do not depend
The Soper lens has been designed with a very steep central
on precise alignment on the corneal surface. Therefore, even
posterior base curve to accommodate the protrusion of the
highly irregular corneal topography can be fitted with some
cornea. The peripheral curves are much flatter. It gives excellent
kind of scleral lens. They are almost never dislodged because
results in moderate and advanced keratoconus patients,
they fit under the eyelids and the lid sensation is minimal.
especially those with nipple cones.
They are dimensionally stable, robust and not subject to much
The Rose K RGP lens is probably the most widely fitted deterioration.27,28
keratoconus lens worldwide and achieves an 85 percent first- Over-refraction is an integral part of diagnostic fitting.
fit success. Its flexible lens design works well in an early to All keratoconus contact lenses should be ordered in a moderate
advanced keratoconus patients. Complex lens geometry, to high Dk rigid gas permeable material to avoid epithelial
combined with the enhanced material benefits of Boston hypoxia and corneal erosion during the long wearing schedule
ES™, makes the Rose K lens function with a good fit, of keratoconus patients.
enhancing patient comfort and visual acuity.
Refractive Surgery and Contact Lens
Piggyback contact lenses are occasionally used to correct
keratoconus. In piggy back lenses, a rigid gas permeable contact Contact lenses may provide the only option for restoration of
lens is placed on top of soft contact lens to help maintain the vision in patients with bad results after refractive surgery.
shape and improve visual acuity further. Early piggyback Indications for fitting included the correction of residual
systems consisted of thick, low Dk, soft lenses in combination ametropia, anisometropia, and regular and irregular
with low Dk silicone/acrylate rigid lenses. It was not surprising astigmatism. Usually such patients are not psychologically
that this combination frequently resulted in corneal hypoxia prepared to wear contact lenses which is why they had opted
and neovascularization, which limited its usefulness. However, for refractive surgery in the first place.
with the recent introduction of high Dk silicone hydrogel The fitting procedure involves anterior segment assessment
lenses and stable high Dk GP materials, these complications and measurement of ocular parameters including corneal
are less. Once the appropriate soft lens fit has been determined, topography. It is recommended to wait for three months post-
the rigid lens can be removed and K readings can be obtained treatment to allow the corneal topography to stabilize before
over the central portion of the soft lens. A diagnostic GP lens commencing fitting. Good oxygen transmission, surface
with a base curve radius equal to flat K is then inserted and wettability and appropriate lens design are important concerns.
the base curve is adjusted until an appropriate lens-to-lens The options available for fitting contact lenses after
fitting relationship is established over this soft lens.26 refractive surgery (Figs 3.1.19A to C) are:
Another modified option is the hybrid lens. This lens • Soft lenses: Daily disposable or frequent replacement of soft
incorporates a high Dk rigid center and a soft lens skirt. It is silicone hydrogels lens modalities are viable options for
recommended in patients with keratoconus especially those most post-refractive surgery cornea. However, traditional
96 Contact Lens
soft contact lens designs often provide less than optimal

visual acuity. A soft lens draped over the cornea gives good
comfort and lens centration. However, it is less effective
in correcting irregular astigmatism. It may lead to variable
visual acuity after radial keratotomy (RK) or over wide
laser ablation zones.
• Soft toric lenses: It is common to find astigmatism after
refractive surgery. Toric soft contact lenses may be
appropriate. Fitting them is done by trial method and is
not empirical. Significant astigmatism may make it difficult
to stabilize these CLs on these corneas.
• Rigid gas permeable (RGP) lenses: These could support and
protect the cornea, provided there is a corrective tear lens
between the lens and the new corneal contour, and help to
Fig. 3.1.19A: Post LASIK eye fitted with Rose K lens stabilize visual acuity. Often a RGP lens of large diameter
(10 mm) is required to bridge over the contours of the central
corneal region and assist lens centration. Central K readings
can be taken as the starting point for fitting but are usually
misleading and the lens may behave differently on each
cornea. The BC of the trial lens selected is 0.1 mm steeper
than the mean keratometry reading. The fit is assessed with
fluorescein, for good coverage of pupil, centering and
adequate movement (0.5-1.5 mm). Decentered ablation
frequently results in loss of best corrected visual acuity,
monocular diplopia and ghost distance images. When the
central area is relatively flat and the peripheral cornea is
steep, the conventional multicurve RGP design may
be unsuccessful. A reverse geometry lens (peripheral steep and
center flat) is made to fit such corneas.
• Hybrid combinations: A combination of RGP lens with soft
skirt lens is useful in some cases of decentered zones, highly
Fig. 3.1.19B: An unstable normal design
RGP— CL on a post RK eye irregular corneal topographical profiles, and for highly
sensitive eyes. Piggy back option gives the comfort of soft
lens and vision quality of rigid lens.
• Scleral lenses: Improvement in designs have made it easy to
fit an irregular corneal surface by scleral lenses.
These lenses are supported almost entirely by the sclera
and generally center well.
Despite the continuing success of refractive surgery,
contact lenses are still required after surgery in some patients
with postoperative regression or astigmatism to optimize their
postoperative vision. Rigid gas permeable contact lenses with
high oxygen transmissibility are generally selected. Scleral lenses
are extremely useful. Ordinary soft lenses are less useful
because they do not correct severe corneal irregularities. With
all types of lenses, central vaulting with excess tear pooling
can occur due to central corneal flattening in myopic
corrections. Thus, in a number of post-LASIK cases for which
Fig. 3.1.19C: A soft CL on a post RK eye soft contact lenses offer limited visual benefits, GP lenses come
Fig. 3.1.20: Lenticular design of aphakic RGP lens
to play an important role in achieving optimal quality and

quantity of vision. The wide array of GPs available includes
standard spherical, keratoconic, custom multicurve, and reverse
geometry lenses.
Aphakia and Contact Lens

Since the advent of cataract surgery, due to improved
intraocular lens designs and surgical techniques, adults are
rarely fitted with contact lenses for aphakia. Aphakic contact Fig. 3.1.21A: A patient with advanced keratoconus
lenses are indicated in monocular aphakia in children.29 New
materials, better lens designs, and improved contact lens care
solutions, have made aphakic contact lens fitting more
successful. Children and adults can be fitted with either
hydrophilic or rigid gas permeable lenses (Fig. 3.1.20).
Scleral Lenses
Scleral lens is a large type of contact lens (> 18 mm diameter)
that rests on the sclera and creates a tear-filled vault over the
cornea.30
Advances in lens design have made scleral rigid gas-
permeable lenses a practical option for an increasing number
and variety of patients with corneal disease like:
• Irregular or abnormal corneal topography:
– High astigmatism Fig. 3.1.21B: Same eye fitted with scleral lens with good visual
– Keratoconus or other primary corneal ectasia (Figs recovery to delay corneal graft surgery. The lens in place shows
3.1.21A and B) the tear film behind the lens which is stained with fluorescein
– Corneal transplant
– Traumatized eye – Prevention of tear film evaporation with poor lid
– Chemical and burn injuries closure or lid absence
– Post-refractive surgery – Corneal protection against trichiasis or lid margin
– Aniridia keratinization
– Microphthalmos. – Preventing mucus filaments adhering to the cornea
– Neurotrophic keratitis – Ptosis.
– Pellucid degeneration Clinicians who treat patients with ocular surface disease
• High refractive errors: should be aware of scleral rigid gas-permeable lenses as a
– High powers leading to centration difficulties with therapeutic option for their patients.
high-power corneal lenses The new generation of scleral lenses are made from a highly
– Intolerance to corneal or hydrogel lens wear in myopia permeable oxygen polymer and allow sufficient oxygen
or hypermetropia. transmission through the required thickness of scleral lenses.
• Therapeutic applications: The cushion of fluid beneath the lens also provides oxygen
– Serious dry eye conditions such as Stevens-Johnson to the cornea, allowing the eye to heal.
syndrome, Sjögren’s syndrome and cicatrizing Scleral lenses were first made with rigid gas permeable
pemphigoid materials in 1983. The introduction of RGP materials enabled
98 Contact Lens
a major shift away from traditional fitting methods.31 Before 11. Slonim CB. Ophthalmology Clinics of North America. In: Clarence
the introduction of rigid gas permeable materials, scleral lenses H Russell (Ed). The correction of astigmatism with soft contact
lenses 2003;16(Issue 3):353-8.
were only considered for the most advanced pathological eye
12. Ames KS, Erickson P, Medici L. Factors influencing hydrogel toric
conditions, but now they are prescribed for many conditions lens rotation. International Contact Lens Clinic 1989;16 (Issue 7):
for with corneal lens in tolerance as an alternative. However, 221-5.
they are labor intensive to produce compared to most other 13. Jackson J, Wolsley CJ. Rigid gas permeable contact lenses. Contact
lens types and some patients are conscious of the feeling of Lens and Anterior Eye 2009;32:204-6.
bulk. 14. Rakow PL. Current contact lens care systems. Ophthalmology
Clinics of North America 2003;16(Issue 3):415-32.
Scleral lenses are available in the following four main
15. Rosenthal RA, Stein JM, McAnally CL, Schlech BA. A comparative
diameter ranges and named according to their size: study of microbiologic effectiveness of chemical disinfectants and
a. Corneoscleral – 12.9-13.5 mm peroxide-neutralizer systems. CLAO J 1995;21:99-110.
b. Semiscleral – 13.6-14.9 mm 16. Wilson LA, Sawant AD, Simmons RB, Ahearn DG. Microbial
c. Miniscleral – 15.0-18.0 mm contamination of contact lens storage cases and solutions. Am J
d. Scleral – 18.1 mm and above Ophthalmol 1990;110:193-8.
17. Holden B. A report card on hydrogen peroxide for contact lens
These lenses can replace the need for corneal transplant
disinfection. CLAO J 1990;16:S61-S64.
surgery which has potential for serious complications, long 18. McMonnies CW. Contact-lens induced corneal vascularization. Int
healing period and uncertain visual outcome. When corneal Contact Lens Clin 1983;10:12.
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to utilize residual vision. Ophthalmology Clinics of North America 2003;16(Issue 3):471-
In some cases, sealed sclerals are unsatisfactory and so a 84.
20. Stretton S, Jalbert I, Sweeney DF. Corneal hypoxia secondary to
corneal impression moulding is needed to produce a shell that
contact lenses: the effect of high-Dk lenses. Ophthalmology Clinics
fits the irregular cornea. of North America 2003;(16(Issue 3):327-40.
21. Clemons CS, Cohen EJ, Arentsen JJ, et al. Pseudomonas ulcers
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Ophthalmol Vis Sci 1984;25:1161-7. 26. Richard G. Lembach Use of contact lenses for management of
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Chapter 3.2
CONTACT LENS:
THE CLINICAL SPECTRUM
Kirti Singh
3.2.1 Essentials in Contact Lens Practice:

An Overview
CONTACT LENS: APPLIED ANATOMY Limbal Area
AND PHYSIOLOGY
Limbal epithelium differs from bulbar conjunctiva in absence
Cornea is the principal optical surface of the eye accounting of goblet cells, presence of melanocytes, blood vessels and
for two-thirds of the eye’s refractive power. It is a meniscus lymphatic vessels. Vascular supply is by superficial marginal
lens with an average front apical radius of 7.8 mm, back apical arteries (of anterior ciliary arteries origin) which include
radius of 6.5 mm, a refractive index of 1.376 and a power of terminal arteries forming the peripheral arcades and recurrent
43.27D. Its prolate curvature flattens towards the periphery arteries forming the peripheral arcades. Peripheral arcades pass
and its toricity is manifest by an increased difference in the through palisades of Vogt to supply the perilimbal conjunctiva.
radii of curvature of the principal meridians. The optically Episcleral venous plexus lies deeper to the palisades.
non-homogeneous cornea is composed of 78 percent water,
15 percent collagen, 5 percent other proteins, 1 percent Tear Film
glycosaminoglycans (GAGs) and 1 percent salts. Epithelial Tears constitute a lacrimal river at lid margin and lacrimal lake
cellular turnover, or the time required for basal cells to migrate at the middle canthus. Tear turnover rate is approximately 16
anteriorly to become surface cells, is approximately seven days. percent per minute. Mucin layer of tear film hugs the cornea
Stroma comprising 90 percent of corneal thickness is and makes the hydrophobic epithelium hydrophilic. Thinning
composed almost entirely of collagenous lamellae whose of tears leaves an oil and mucin admixture which does not
turnover time is 12 months. ‘wet’ the epithelium leading to a break-up of the tear film.
For the purpose of visual acuity, corneal epithelial tear During lid blinking, the upward lid movement draws aqueous
film interface is the most important optical surface. To maintain component over the cornea followed by spreading of lipid
its integrity and function, continuous migration and layer over the surface. Orbicularis oculi muscle contracture
transformation of limbal stem cell along with surface during lid closure creates a scissor-like lid movement towards
desquamation is essential. Contact lens wear impacts this the nose and distends the upper part of the lacrimal sac, and
homeostatic control and causes reduced surface epithelial cell both actions propel and draw tears towards the medial canthus.
shedding, prolonged basal cell retention and decreased During blinking, the globe moves up and in towards the nose
epithelial proliferation. This causes a stagnant epithelial layer as well as backwards. This movement is echoed by a well-
and a thinner central corneal epithelium.1 fitted contact lens. Rigid gas permeable (RGP) lenses on
100 Contact Lens
account of this movement allow for 15 percent tear exchange hypoxia by developing hypoesthesia with an actual decrease
with each blink while soft lenses (SCL) with their limited in corneal nerve endings. This phase is called as adaptation.4
movement allow only for a 1 percent exchange.
Energy Utilization
Corneal Permeability and
Cornea utilizes energy by both aerobic and anaerobic pathways,
Oxygen Requirement
the end products being pyruvic acid and lactic acid (anaerobic)
Corneal epithelium has low permeability to water and lactic or carbon dioxide and water (aerobic). Glucose requirement
acid. Oxygen required by cornea is derived from oxygen is 38 to 90 micrograms/hour of which 40 to 66 percent is
dissolved in tear film and partly from palpebral/limbal required by the epithelium. Aqueous humor contributes to 90
vasculature (especially in closed eye circumstances). Additional percent of epithelial glucose supply with the rest being sourced
sources are atmospheric oxygen (20.9% oxygen or 155 mm from the limbal vasculature or the tear film. When oxygen
Hg partial pressure) for corneal epithelium and aqueous humor levels are normal, glycogen is stored in the two surface layers
(7.4% oxygen or 55 mm Hg partial pressure) for corneal of epithelial cells. In hypoxic conditions ATP production by
endothelium. That the endothelium is partly dependent on glycolytic pathway increases, thereby increasing lactate
atmospheric oxygen is evident by Zantos’ blebs (transient production by 40 to 140 percent. Lactic acid is not metabolized
endothelial changes) in closed eye condition.2 The cornea is by the cornea, thus it diffuses into the aqueous humor.
highly permeable to carbon dioxide with Dk value for CO2 Accumulation of lactic acid creates increased osmotic pressure
being seven times of oxygen. This helps the cornea resist pH resulting in osmotically driven epithelial and stromal edema.
and metabolic changes. In open eye conditions, carbon dioxide This hypoxic edema alters optical properties of corneal
diffuses out through tears but in closed-eye conditions it exits epithelium manifesting as Sattler’s veil which leads to haloes
via aqueous humor. The amount of carbon dioxide that and light scattering. In closed eye conditions hypoxia induces
diffuses freely from the cornea for every 5 µl O2/cm2 cornea/ 3 to 4 percent corneal swelling. Lower tear osmolarity, increased
hour consumed is 21 µl CO2/cm2 cornea/hour. Contact lenses temperature and humidity compound the corneal edema. In
act as a barrier to both oxygen influx and carbon dioxide efflux. open eye conditions the cornea recovers due to tear
An oxygen partial pressure of 75 mm Hg is essential to evaporation and tear hypertonicity induced osmotic
prevent hypoxic corneal edema. Contact lens material and wear deturgescence. Initial contact lens wear causes reflex tearing
must be able to deliver this critical amount of oxygen. Rate of of hypotonic tears and decreased tear osmolality with
oxygen exchange is related to oxygen permeability of polymer subsequent corneal swelling by 2 to 4 percent. Adaptation
(Dk) value and inversely related to lens thickness Dk/ L. For process to pre-lens value occurs within a week.
soft hydrogel lens, the Dk value is proportional to water
content whereas for RGP lenses, Dk is proportional to Corneal Topography
silicone/ fluorine content. Conventional daily wear lenses with Asphericity is the degree of peripheral flattening or steepening
Dk 40 can cause corneal swelling of 12 percent with overnight from apical radius of curvature and is expressed as eccentricity
wear. A lens must have oxygen transmissibility of 125 or more (e) or the shape factor (p). For a circle the asphericity value is
to prevent corneal edema after overnight wear.3 e = 0 while cornea is an ellipsoid with e values between 0.41 to
Hypoxia induced accumulation of lactic acid and carbon 0.58, average: 0.47.5 Based on asphericity, the cornea may be
dioxide decreases pH and causes hypoxic endothelial damage divided into three regions:
which manifests as epithelial edema or microcysts, stromal a. Central corneal cap is of 4 mm diameter and is decentered
folds, corneal neovascularization, endothelial polymegathism nasally by 0.2 to 0.6 mm and superiorly by 0.2 mm.
or blebs with accompanying symptoms of pain, watering and Keratometer does not measure exact geometric center,
photophobia. This is known as overwear syndrome. Vertical striae instead it reads 1.2 to 1.8 mm to each side.
start to occur once cornea thickens by 6 percent, whereas b. Mid-peripheral region of greater flattening. The mid-
posterior folds occur once corneal thickness increases by 10 peripheral non-alignment with monocurve rigid lenses
percent. Hypoxia also increases bacterial binding to corneal bears testimony to this curvature variation between central
epithelial cells by up-regulating Pseudomonas aeruginosa and peripheral regions.
receptors.1 A healthy cornea adjusts to the initial lens induced c. Peripheral region has a positive asphericity.
Contact Lens: The Clinical Spectrum 101
Corneal Repair
Re-epithelialization occurs by sliding or migration in about
seven days, after which laying down of basement membrane
starts with hemidesmosomal attachment to Bowman’s layer.
A cell-surface glycoprotein fibronectin, released by regenerating
epithelium helps in cell adhesion. Regeneration is almost
complete by six weeks.
ANTERIOR SEGMENT CONDITIONS

AFFECTING CONTACT LENS FITTING
Contact lenses (CL) intimately move in conjunction with

cornea under the eyelid. Ocular surface disorders need to be
treated before prescribing a contact lens. Some conditions
contraindicate CL wear whereas others need to be treated
before prescribing CL. The structures which need to be
assessed before CL fit are:
• Eyelids: Both upper and lower lid positions in relation to Fig. 3.2.1.1: Aphakia with scleral thinning
limbus and asymmetry between two eyes must be
documented. Lids need to checked for erythema, dryness, • Tear break up time: This detects ‘dry spots’ indicative of
eczema, oily discharge, puncta position, eyelash position. tear thinning and exposure of the underlying corneal
Any swelling, growth or infection of lids needs to be noted epithelium. Fluorescein stained tear film is observed for
and treated. Adequate lid tonus has to be assessed by the occurrence of post-blink random appearance of dry spots
snap back test. A good tone ensures stability of a RGP with a cobalt blue light. Time elapsed between last blink
lens. Use of eye cosmetics like ‘kajal’, eyeliner and mascara to appearance of dry spot of < 10 seconds indicates tear
must be documented and would need specific instructions film instability.
as to their safe and correct usage with the CL on. • Tear prism height: This tests tear meniscus along the lower
• Conjunctiva: Palpebral, bulbar and limbal conjunctiva need lid margin. Normally convex, it has a height of 0.3 to 0.5
to be inspected for any redness, roughness, or swelling. mm. Movement of debris in the lacrimal river is assessed
Upper lid needs to be everted and both tarsal area and under diffuse illumination.
junctional palpebral conjunctiva inspected. Concretions • Rose Bengal staining: This determines presence of devitalized
and papillary hyperplasia must be treated otherwise they epithelial and conjunctival cells which take up the stain
cause foreign body sensations with CL use, more so with and confirms dry eye.
soft CL.
• Cornea: Clarity, regularity and corneal reflex must be RELATIVE CONTRAINDICATIONS
checked. Position of opacities and vascularization, if any, TO CONTACT LENS FIT
must be noted and documented. Limbal area must be
Active Infection in and around Lids
carefully evaluated and the junction graded.
• Sclera: Scleral thinning, ectasia, staphyloma, inflammation Blepharitis
and episcleritis need to be evaluated. Scleromalacia cases Inflammation of lid margins of either squamous (seborrheic)
as in rheumatoid arthritis, bad aphakia or glaucoma can or ulcerative type has to be treated before prescribing CL.
only be fitted with special lenses (Fig. 3.2.1.1). Symptoms of burning and stickiness of eyelids, more in
• Iris: The color, architecture, partial loss (large peripheral morning are corroborated by cr usts on lid margins
iridectomy), growth, pigmentation would determine the (Fig. 3.2.1.2).
type and diameter of the CL.
• Tear film status: This has to be reviewed in detail since fit, Hordeolum Externum/Hordeolum Internum,
optical performance of CL as well as patient tolerance Dacrocystitis/Canaliculitis/Dacroadenitis
and comfort depends on an adequate tear film. This is Any active focus of infection in or around the lids is a
more relevant in extremes of age. contraindication for continued CL wear. The lenses need to
102 Contact Lens
Fig. 3.2.1.2: Blepharitis in soft CL wear Fig. 3.2.1.5: Meibomitis
Fig. 3.2.1.3: Multiple hordeolum internum Fig. 3.2.1.6: Meibomitis with hordeolum externum
meibomian orifices. If untreated, this would cause intolerance

to lens wear, blurring of vision and red eye (Figs 3.2.1.5 and
3.2.1.6).
Trichiasis
In turning of eyelashes, a common accompaniment of
entropion can cause corneal abrasions and exacerbate infection
in conjunction with CL usage (Fig. 3.2.1.7).
Conjunctivitis or Conjunctival Masses

Elevated pinguecula at the limbus may affect contact lens fit.
Fig. 3.2.1.4: Resolving dacrocystitis
Pterygium may cause displacement and intolerance of the lens
(Figs 3.2.1.8 and 3.2.1.9).
be discontinued and the condition treated before re-institution
of CL (Figs 3.2.1.3 and 3.2.1.4). Giant Papillary Conjunctivitis (GPC)
Meibomitis Cobblestone-like nodules of the palpebral conjunctiva occur

due to irritation brought about by mechanical effect of lens,
Usually concomitant to blepharitis it causes an oily tear film deposits on lens or by care solutions (Fig. 3.2.1.10). Small
which can spoil a SCL and cause deposit on a RGP lens. To papillae are normal but giant ones are due to immunological
corroborate the diagnosis, secretions can be expressed from reaction to lens deposits.
Fig. 3.2.1.10: Early giant papillary conjunctivitis
Fig. 3.2.1.7: Trichiasis in a RGP lens wearer
Fig. 3.2.1.11: Band-shaped keratopathy
Band-shaped Keratopathy
Fig. 3.2.1.8: Phlycten

Associated with rheumatoid arthritis, dry eyes or degenerated
globes, it makes lens fit difficult. Commonly encountered in
aphakia with juvenile rheumatoid arthritis it requires a little
flatter fit of lens and frequent use of preservative free
lubricants over CL wear (Fig. 3.2.1.11). The use of RGP lens
is not possible with such cases.
Trachomatous Eye
Often associated with Herbert’s pits, dry eyes and corneal
opacities. Use of lenses in such eye needs to be monitored
more frequently as dry eye exacerbates lens deposits and blurs
vision in addition to lens intolerance (Fig. 3.2.1.12).
Dry Eyes
Often seen in elderly age group and those with prior ocular
Fig. 3.2.1.9: Pinguecula causing fitting problems with SCL wear surgery like aphakia these patients require specialized fits,
104 Contact Lens
understood as that would determine the type and methodology

of lens prescribed.
Accommodation depletion: Myopes using lenses need to use more
accommodation leading to increased convergence demands.
This leads to asthenopic symptoms when myopes switch to
lenses from spectacles. In addition presbyopia is not as retarded
as would be with the spectacled myope.
Residual astigmatism: With rigid gas permeable lenses (RGP)
the newly created corneal optical surface has identical spherical
curvature to base curve of CL regardless of actual corneal
topography, thus irregular and regular corneal astigmatism are
neutralized. Soft lens on the other hand, moulds to the cornea
Fig. 3.2.1.12: Trachoma with irregular lid margin, and transmits the patient’s refractive astigmatism. Residual
Herbert’s pits and pannus astigmatism is the term used to denote the lenticular
astigmatism which is unmasked after contact lens corrects the
corneal astigmatism.
Tear lens: Refractive index of the tear fluid almost equals cornea.
Thus the fluid tear lens created between the posterior surface
of the lens and the cornea creates a spherical lens. A steep
fitting CL creates a plus fluid lens, and flat fit creates a minus
tear lens. The power of this tear lens amounts to 0.2D for
every 0.05 mm radius of curvature difference between base
curve of lens and flat K of the cornea. This has been explained
in the previous chapter.
CONTACT LENS FITTING PHILOSOPHY
Fitting Methodology
• History: The patients activities, educational and occupa-
tional needs, hobbies and family background should be
noted. Relevant drug history with special reference to oral
Fig. 3.2.1.13: Aphakia with drying of CL contraceptives, antihistaminics, immune suppressives and
topical medications like anti-glaucoma drugs should also
be noted. Diabetes, pregnancy, prior ocular surgery or past
lens materials and care. Figure demonstrates deposits and
history of any significant ocular event should be recorded.
drying and deposits on lens in an aphakic with dry eyes
• Examination: This includes binocular vision, refraction and
(Fig. 3.2.1.13).
visual acuity, ocular motility, pupillary reflex tests, and intra-
ocular pressure measurement.
INDICATIONS OF CONTACT LENSES
• Specific contact lens related tests: These include slit lamp
• Optical: Refractive errors including irregular astigmatism biomicroscopy, keratometry, corneal topography, details
and aphakia, both monocular and binocular. of trial lenses used and final lenses to be prescribed.
• Therapeutic: In albinism, aniridia, keratoconus, nystagmus. • Follow-up information: Tests that need to be conducted during
As a bandage lens for non-healing erosions, and for pain the follow-up and aftercare visits are recorded.
relief in bullous keratopathy.
• Cosmetic: As a prosthetic lens in non-seeing eye or for Parameters Evaluated
concealing disfiguring scars in the seeing eye. • Visual acuity must be recorded under both high and low
To understand fitting philosophies, a brief description of contrast conditions. Spectacle refraction dictates the trial
certain optical phenomenon with contact lenses needs to be lens to be selected.
Fig. 3.2.1.14: Everted lid reveals early papillary hyperplasia Fig. 3.2.1.15: Use of Burton lamp to evaluate CL fit in a child. The
which would exacerbate with CL wear device gives a magnified view and has cobalt blue filter incorporated
in it
• Palpebral aperture and lid characteristics like no lid position, jump, ghosting especially with use of lenticular lenses (high
tone and margin position need to be noted as normal lid refractive errors) may be seen.
aperture size and position will influence fit and diameter • A key requirement in fitting patients with RGP lenses is a
of CL especially RGP. Lid tone is graded on eversion as large trial set. This makes it possible to fit a lens that is
loose, average or tight. close to the final design required for their eye.
• Conjunctiva (bulbar, limbal and palpebral areas) need to be
evaluated. The everted upper lid is divided into upper, Conventional Devices for Examination
central, lower, nasal and temporal junctional tarsal area.
Abnormal findings of erythema, papillae, follicles, pannus • Torch light exam for gross observation
or concretions in any of these areas are to be noted and • Burton lamp allows for simultaneous magnification and
documented (Fig. 3.2.1.14). illumination. It also has cobalt blue light for fluorescein
• Cornea with special reference to limbus, size, transparency examination (Fig. 3.2.1.15).
and topography is noted. • Oblique illumination with penlight held at the temporal canthus
• Iris with reference to horizontal visible iris diameter
can be performed.
(HVID) and vertical visible iris diameter (VVID) is noted.
• Magnification devices such as direct ophthalmoscope, hand-
For RGP lens, total diameter would be 2.3 to 2.5 mm less
held magnifying glass, +10D trial case lens are used.
than HVID. For measurement an interpupillary distance
measuring rule (PD rule) is used avoiding parallax. Ophthalmoscope can be used to observe conjunctiva,
• Tear film is assessed by the tear break-up time (BUT). Tear cornea and limbus by starting with a high plus power and
prism height (tear film along the lower lid margin) and adjusting the observation distance until a clear view is
Schirmer test may also provide an evaluation of tear status. obtained. It is a very useful method to assess lens fit in a
• Skin of eyelids is evaluated for any dryness, erythema, young child when a portable slit lamp is not available.
swelling or scaling. They would require treatment before • Slit-lamp biomicroscopy with variable magnification, controlled
commencing with CL wear. illumination, cobalt filters and measuring graticules make
• Pupil diameter is measured in both standard room it the best device for examination.
illumination (approximately 200 lux) and low illumination • Corneal topography with placido disk, photokeratoscope,
(< 100 lux). This needs to be done to determine the keratometer, and computer-assisted topographic analysis
appropriate optic zone diameter. If the optical zone is too are based on optical reflection principle (Figs 3.2.1.16A
small, significant visual disturbance like blurring, image and B). Corneal reflections viewed by a central magnifying
106 Contact Lens
Figs 3.2.1.16A and B: (A) Corneal topography setup (B) Optical reflection principle
lens confirm to various patterns. An elliptical pattern

denotes astigmatism, asymmetric keratoconus whereas
corneal scars reveal a distorted picture. The patients need
to blink before capturing the image as poor tear film
causes a disrupted or defocused image.
• Keratometer is used to measure corneal surface curvature in
the central 3 mm using the Scheiner disc doubling principle.
Illuminated object mires are reflected from the front
surface of the cornea which acts as a convex mirror. The
keratometer measures apparent image height of the
reflected image (Purkinje Image 1) formed by the cornea
of an object of known linear size. It determines power
Fig. 3.2.1.16C: Corneal topography showing keratoconus
and location of steepest meridian and the meridian 90o
away based on the assumption that the cornea is sphero-
cylindrical. Errors in measurement arise from eye
corneal surface, analogous to K values of a keratometer.
movements, unsteady fixation and defocused mire images.
A corneal map is generated which represents the entire
Averaging measurements of three readings minimize errors
corneal curvature changes that can affect contact lens fit
due to eye movements. Error due to proximal accommo-
(Fig. 3.2.1.16C). Measurement is done in millimeter radius
dation can be avoided by asking the patient to keep both
(mm).
eyes open, while the examiner focuses the eyepiece from
Corneal curvature steepens for the first few hours of hard
plus to minus. At all times the eyepiece graticule crosshairs
CL wear subsequent to which the CL fit changes. Extent of
must be in sharp focus. Alignment errors in aspheric cornea
these changes depends on daily wearing time and the number
and measurement of corneal curvature away from the area
of years that the lenses has been worn.6 Soft CL wear on the
of the optic cap can increase the image height and,
other hand causes nominal curvature changes.
therefore radius measure. Periodic calibration of the
keratometer needs to be performed with spherical steel or SOFT CONTACT LENS FITTING
glass balls of known radii. PHILOSOPHY
• Topographic analysis systems generate a simulated keratometry
value (Sim K) which is the power and location of the Indications for Soft Lenses
steepest and the flattest meridians from a reconstructed • Spherical refractive errors with astigmatism of < 0.75 Dcyl.
• High refractive errors including aphakia where RGP lenses A trial lens is selected from the manufacturer’s fitting guide
are difficult to fit and center. based on the flat K value to which is added 0.8 to 0.9 mm for
• Significant corneal astigmatism with RGP intolerance. less flexible lens materials (thicker, low water) and 0.3 to 0.6
Soft contact lens are highly acceptable to the patient due to mm for flexible materials (thinner, high water). A lens of
the stable vision, minimal physiological disturbance, rapid nearest BOZR is selected from the trial set. The common
adaptation and comfort it provides. From the practitioner’s point range covered in most stock trial sets is BOZR 7.90 to 9.30
of view they are technically very easy lenses to fit. For them to mm. The trial lens is placed on the patient’s eye and fitting
mould to the corneal and scleral contours appropriately, these behavior is reviewed after 5 to 10 minutes of wear. For higher
lenses are larger than the cornea with a BOZR flatter than the water content and high power lenses which take longer to
cornea. A good fit ensures complete corneal coverage in all equilibrate due to their greater water volume, the fit must be
gazes. reassessed later at least after 15 to 60 minutes of wear.
Fitting of a Soft Contact Lens Parameters to be Evaluated while
Sagittal height, total diameter: Back optic zone radius (BOZR) of Assessing SCL Fit
soft lenses is usually fitted flatter than the cornea to achieve a • Centration in primary gaze up to 0.75 mm decentration is
normal fit. A successful fit requires the inner sagittal height of acceptable
lens to be greater than that of the anterior eye.7 Thus to tighten • Position and movement on blink in primary position,
the fit, lens height needs to be made greater than that of the vertical and lateral gazes. A decentration of up to 1.5 mm
anterior eye. Decreasing the BOZR steepens the lens fit and is acceptable. Excessive lag indicates flat fit whereas no
increasing the BOZR loosens the fit proportional to increase lag or decentration implies a steep fit.
or decrease in sagittal height respectively. In addition, the type • Lens movement depends on type (convex, concave, high
and make of the lens would also determine the fit. Thick lenses or low power, lenticulated or full aperture), lens thickness,
interact more with the lids and move more during blinking, lens material and back surface design (aspheric, monocurve,
thus are more prone to decentration. Thin lenses or those with bicurve). Lid tone also contributes in that a tight lid reduces
thin edges react less with the lids, move less with blinking and movement in primary gaze and leads to upriding of a lens.
thereby center better. Higher water content (more oxygen • Lens lag is the delay of lens in the following eye movements
permeable) lenses are more fragile versus more rigid and durable and must be assessed in supraversions and lateral versions
low water content materials. A lens with less rigidity hugs the (Fig. 3.2.1.17).
eye, creates a thin post-lens tear film and increases viscous drag • Lower lid push-up test is performed to unsettle the lens and
on lens resulting in minimal lens movement. Manufacturing speed of lens resettling is observed in primary gaze. After
technology also determines the rigidity since spin-cast lenses
are less rigid, more elastic than lathe-cut. Sagittal height of the
anterior part of eye is influenced by corneal asphericity, diameter,
central corneal curvature and limbal scleral curvature.8 This
additional effect of corneal diameter and asphericity on sagittal
height, and therefore lens fit, clarifies why keratometry alone is
never a reliable indicator of lens fit.
Increasing the lens diameter would tighten and steepen
the lens fit by increasing sagittal height whereas a decrease in
diameter will flatten the fit. To retain the same fit, the BOZR
needs to be increased subsequent to increase in overall
diameter. For a diameter increase of 0.5 mm, BOZR needs to
be increased by 0.3 mm to retain the similar fitting profile.
Back surface design determines ‘on-eye’ behavior of a lens.
With similar power and overall diameter lenses of different
series would exhibit dissimilar behavior. Different materials,
peripheral curves, radii, widths, and thicknesses of different
lens series compound the potential performance differences
between lenses of different makes. Thus, one must order lens Fig. 3.2.1.17: Lens lag. In aniridia, the optic zone of the aphakic
of the same series that has been used for the trial. lens is lagging during upward movement of eyeball
108 Contact Lens
Fig. 3.2.1.18A: Excessive lens excursion denotes a flat fit Fig. 3.2.1.18B: A lens unwilling to return to primary position
denotes a flat fit
Fig. 3.2.1.19A: Tight fit. Note the conjunctival Fig. 3.2.1.19B: Tight fit manifesting with corneal edema
indentation at the lens edge after few hours of lens wear
easing the lid manipulation, a well-fitted lens should rapidly lens edge, an apparent ‘step’ in blood vessel caliber which
recenter on the cornea. A tight lens is difficult to displace, coincides with lens edge. If missed, such a fit causes
and equally sluggish to recenter whereas a very tight lens chronic hypoxia with subsequent corneal edema and
would not recenter at all.9 Excessive lens movement and sterile inflammation (Figs 3.2.1.19A and B). A slightly
lens unwilling to return to primary position implies a flat tight fit may be acceptable with high water content or
lens (Figs 3.2.1.18A and B). ultra-thin lenses since tear exchange any way does not
• Immobility of lens despite lower lid push-up, conjunctival contribute significantly to oxygen permeability under a
indentation at lens edge and blood vessel crimping in soft lens. ‘On-eye’ dehydration tightens fit especially for
peri-limbal vessels under lens periphery indicate a steep higher water content lenses. Thus, fit must always be
fit. The latter manifests as blanching of vessels under evaluated after 30 min to 1 hour after wear.
limbal ‘scuffing’ due to mechanical pressure of a steep

back peripheral design point to a tight fit.
• Visual acuity provides a clue to the fit. Clear vision
immediately after a blink points to a steep fit whereas
blurred vision after a blink points to a flat fit. A steep lens
attains an irregular aspheric shape when standing off from
the cornea and a blink forces it to conform to central
cornea thereby transiently clearing vision. Excessive
decentration with a flat fit causes visual fluctuations and/
or corneal exposure.
Power Calculation and Prescription

Lens power can be calculated by extrapolating spectacle
refraction by means of vertex correction (special charts
provided). The preferred method is by performing over
refraction over SCL in situ and subsequently performing
Fig. 3.2.1.20: Edge buckling in a flat lens
subjective testing with the help of trial lenses from the
refraction set.
In case of residual astigmatism, the wearer may opt for
• Edge buckling or folding indicates either a flat lens or an reduced acuity as acceptable for ‘social’ wear. For fine visual
inside out lens. Edge curling, stand-off or wrinkling acuity in case of astigmatism, soft toric lens is preferred. The
indicates a loose fit (Fig. 3.2.1.20). Edge lift and bubbles 4:1 rule states that for a spherical component 4 times greater
under the periphery corroborate a flat fit. than cylinder component and vision with best sphere
• Corneal coverage in all gazes must be maintained and correction is quite acceptable. This rule, however, does not
limbal compression must be avoided (Fig. 3.2.1.21). apply when cylinder magnitude is more than 1.50D.
Incomplete corneal coverage causes corneal exposure,
dessication and tear film thinning due to meniscus effect Some Relevant Facts
at the lens edge. Conjunctival indentation, limbal or peri- A soft lens material’s ionicity and water content defines
propensity to accumulate protein deposits on its surfaces.
Based on these parameters soft lenses are classified as:
Group I: Low water content, non-ionic; Group II: High water
content, non-ionic; Group III: Low water content, ionic; and
Group IV: High water content, ionic.
Soft lenses can absorb preservatives from the care system
due to their water content. These preservatives can be
concentrated inside the lens material and leach out on the
ocular surface once they exceed saturation point of the
material. This proves to be very detrimental to ocular health
and is a factor in inciting immune reactions from the lid.
Tints in a soft lens are defined according to the purpose
they serve, namely handling, color enhancing, cosmetic or
opaque. Handling tints are light encompassing the entire
diameter or limited to iris diameter. Enhancing tints are
transparent tints aimed at altering the native natural color of
patient’s eye. Choice of color and intensity must take into
account occupational and safety factors. An iris diameter tint,
Fig. 3.2.1.21: No blood vessels crimping at limbus denotes a good especially in a darker shade, may affect color perception
fit. This must be noted after at least 15 to 30 minute of lens wear adversely, a fact which is being used in color deficient patients.
110 Contact Lens
Cosmetic or opaque tints are designed to give a natural depth mesopic pupil size causes refraction by the optic zone, first
to the apparent iris color. curve junction and lens periphery simultaneously resulting in
ghosting and decreased image contrast.11 An increase in BOZD
RIGID GAS PERMEABLE LENS increases lens sag with resultant increase in tear lens thickness
FITTING PHILOSOPHY (TLT) and a tight fit. A small BOZD translates into better
lens movement and increased decentration. Thus BOZD, TD
Indications of RGP Lens and edge widths have to be altered in synchronization. For a
• Regular astigmatism > 1.0 to 1.5 Dcyl constant TD, increase in BOZD reduces the edge clearance.
• Irregular astigmatism as in keratoconus, healed keratitis, For each 0.05 mm increase in BOZR, the BOZD must be
pellucid degeneration increased by 0.7 mm to maintain the same sagittal relationship
• Post-keratoplasty/refractive surgery astigmatism. and the central TLT constant at 22 microns.12
Advantages over SCL Back Vertex Power (BVP) Compensation

for BOZR Changes
• Crisper vision due to better optics
• Less incidence of allergies and deposits If the BOZR is increased (flattened) by 0.05 mm, as the tear
• Creates a liquid tear lens between posterior lens surface lens power will increase by –0.25D. In cases of corneal
and anterior surface of cornea, which corrects most of astigmatism of > 1.50D a 0.05 mm decrease in BOZR is
corneal astigmatism warranted for each 0.50D increase in corneal astigmatism.
• Good tear exchange helps in maintaining corneal physiology
Lens Center Thickness
and reduces chances of debris build up and infection
• Can be modified and polished An inverse relationship exists between oxygen permeability
• Easier maintenance and has a longer life span. and lens thickness, otherwise known by the ratio Dk/t or
oxygen transmissibility. Oxygen transmission can be increased
Relevant RGP Lens Parameters by reducing center thickness (tc). However, it is limited by
lens durability and handling.
Center of Gravity (C of G)
Anterior placement of C of G subjects the lens to a greater Edge Profile
rotational movement induced by gravity and causes excessive Lens edge determines comfort, vision, tear meniscus and
lens excursions. In addition by enhancing lid interaction it can physiological changes like 3 and 9 o’clock staining. An anteriorly
destabilize the lens if carried too far. This is the cause of poor rounded, thinner, smoother edge decreases lid interaction and
fit seen with small lenses. A larger diameter plus lens places thus enhances comfort. A thick edge influences lens-lid
the C of G posteriorly, and lenticulation of the lens shifts it a interaction especially vertical centration, often causing the lens
little anterior. Affected by lens diameter and center thickness, to ride lower if the lens is made thicker (due to the upper lid
the effect of lens diameter predominates. A diameter change pushing the lens down) or higher (when the upper lid carries
of 0.1 mm produces a seven times greater effect on C of G the lens). Where thickness changes to edge profile result from
than a 0.01 mm change in lens center thickness. This effect is decreasing the TD, resultant reduction in tear meniscus makes
enhanced in plus lenses. Thinning of a lens leads to an inward lens removal difficult. Too thin an edge makes the lens less
shift of the center of gravity which translates into improved durable and more friable.
lens stability. This is limited by the fact that reduction in
thickness to < 0.16 mm causes lens deformation and flexure Back Mid-periphery
with concomitant fluctuation of vision.10
Since, the cornea flattens paracentrally, lens periphery must
have progressively flatter curves than BOZR. This may be
Total Diameter/Overall Diameter (TD/OD)
achieved by progressively flat blended spherical curves or by a
and Edge Width
continuous aspheric curve. Back mid periphery of lens
Alteration in TD requires commensurate changes in back optic determines stability of fit, tear exchange and is the ill-defined
zone diameter (BOZD) to ensure adequate edge clearance for contact zone in steep fit or the lack of contact when the BOZR
tear exchange. Injudicious reduction of BOZD to smaller than is flatter than the cornea. It is visualized as a 360 degree band
Fig. 3.2.1.22A: Back mid-periphery Fig. 3.2.1.22B: Steep back mid-periphery causing
visualized as band of clearance arcuate indentation on cornea
of contact adjacent to central pooling of fluorescein in a steep

fit and a circular band of clearance in a flat fit (Figs 3.2.1.22A
and B). It can cause a paracentral corneal shape or arcuate
indentation due to localized bearing which is exacerbated with
a steep fit. The brightness of the fluorescein pool is
proportional to the extent of clearance.
Back Surface Periphery/Edge

Peripheral curves are ground on posterior lens surface to allow
the lens to fit better on the aspheric cornea. These curves
help to circulate tears and inadequate edge clearance can cause
corneal indentation noted after lens removal. Normal blinking
causes bubble formation due to tear exchange which resolves
spontaneously. Inadequate edge clearance may cause
entrapment of bubbles (dimple veiling) and thinning of corneal
tear film adjacent to the lens edge, which ultimately causes
epithelial surface desiccation (Fig. 3.2.1.23). Excessive edge Fig. 3.2.1.23: Dimple veiling
clearance on the other hand can cause poor centration, where
the lens usually decenters superiorly due to alterations in surface
tension forces. Excessive clearance also increases likelihood bridging over corneal epithelium by lids while resting on lens
of upper lid ejecting the lens from the eye during a blink. and the 3 and 9 o’clock corneal periphery, causing tear film
Changes in peripheral curve width have greater impact on axial thinning and epithelial desiccation. Insufficient lens movement
edge clearance compared to changes in peripheral curve radius. and sometimes insufficient edge lift or lens adherence also
Three and nine o’clock staining is a phenomenon due to contribute. Reducing the center and edge thickness, smoothen-
excessive lens edge thickness or excessive edge clearance ing the edge, blinking exercises and re-using lubricating drops
wherein stand-off of the lens edge results in inadequate are some modalities used to treat this condition.
112 Contact Lens
Front Peripheral Radius

Increasing the front optical zone diameter results in narrowing
of the front peripheral width (FPW). For a thick lens edge,
this creates a minus carrier, possibly causing the lens to ride
high with the upper lid (lid attachment). Increasing the junction
thickness of the lens enables the lens to position in a central
or slightly higher corneal location. Minimizing the junction
thickness or thinning edge profile improves comfort, minimizes
upper lid interaction but positions the lens lower down.
Front Surface Design Edge Thickness

The edge thickness depends on the BVP, lens design, material
properties and manufacturing process. For a given RGP lens
design, as the minus BVP increases, the unfinished edge
thickness also increases. An edge thickness of about 0.12 mm
is optimal for comfort and lens durability.
Fig. 3.2.1.24: Washing out of fluorescein dye
The trial set for RGP fitting must have two diameters for due to excessive tearing
each back vertex power (BVP). Diameters of 9.2 and 9.60
mm are sufficient to fit the majority of patients. Back optic
whose diameter is 2 mm smaller than HVID is chosen as
zone radius must range from 7.00 to 8.40 mm in 0.1 mm steps
the first trial lens. High back vertex power lenses of
and 7.60 to 8.00 mm in 0.05 mm steps.
> 8.0 D have to be made larger than average to allow for
adequate lenticulation of the front peripheral design. Back
Fitting of a RGP Lens
optic zone diameter needs to be large enough to cover the
The BOZR chosen is +/– 0.10 mm of flat K value. In cases of pupil in photopic and mesopic illumination, and must be
astigmatism of more than 3 Dcyl difference between two princi- larger than mesopic pupil by 1 mm.
pal meridians, 1/3rd of difference between corneal radii is added • Lid position in primary gaze places lower lid margin in
to the flat K to get final K. (Example: In astigmatism of 43D opposition to limbus at the 6 o’clock visible iris position
at 180 degrees and 49D at 90 degrees, K = flat K (43) + 1/3 of and upper lid margin crosses the visible iris at 10 and
6 (49-43) = 43 =2 = 45 is final K of trial lens). 2 o’clock. This position gives an interpalpebral aperture
After lens application wearer is asked to close eyes for of 9.5 mm. In case of smaller palpebral aperture lens TD
5 to 10 seconds, to minimize risk of lens dislocation due to needs to be reduced. For loose and flaccid lids a larger
excessive blinking. Reflex tearing always follows lens total diameter lens would center better.
application and must be allowed to abate before assessing • Blink induced movement during down sweep of the upper lid
fluorescein pattern and dynamic lens fitting characteristics. results in the lens gets pulled up due to Bells phenomenon.
Excessive tearing results in quick ‘wash-out’ of fluorescein Subsequently, up sweep of the lid causes the lens to drop
with resultant misleading dark pattern (Fig. 3.2.1.24). It also down and then recenter in the post-blink period
causes excessive lens movement and gives misleading results (Figs 3.2.1.25A and B). Lens movement is difficult to
quantify due to speed of lid excursion and extent of lid
on dynamic fitting.
coverage. Thus, post-blink recentration of lens is measured
Parameters and Techniques in by assessing the highest point on the cornea reached by
Evaluating RGP Lens Fit the inferior edge of the lens. Then the extent of excursion
made by the lens to regain its pre-blink position is assessed.
• Corneal size also determines lens total diameter. For Normal post-blink movement can be till 3.0 mm. A 1 to
horizontal vertical iris diameter (HVID) of <11.00 mm, 2 mm vertical smooth movement across the corneal
both BOZD and TD would need to be decreased to ensure surface with and following each blink is aimed for as it
best static as well as dynamic fit. Usually, an RGP lens provides stable vision with adequate tear exchange.
Fig. 3.2.1.25A: Lens in process of dropping down after lid blink Fig. 3.2.1.25B: Lens drops down a little later after blink
• Lid attachment fit results in the lens maintaining a high riding

position between blinks.
• Post-blink lens speed is graded as slow, average or fast and
as vertical or oblique (temporal-nasal). A near vertical
direction after blink is ideal. Lens rotation around the apex,
either nasal, temporal, oblique or diagonal, must be
documented.
Methods of Assessment
• Dynamic fitting assessment method: Fitting is assessed13 after a
10 to 15 minute adaptation period. The fit is observed in
primary gaze, extreme gazes, and on blinking. Lens lag is
measured horizontally and vertically in mm and lens
stability is assessed post-blink. Patient comfort is the best
guide of lid sensation.
• Static fitting assessment (Fluorescein application): Fluorescein
dye is used to understand the relationship between the
Fig. 3.2.1.26: Lens rotation around apex of a scarred cornea
lens back surface and corneal front surface (by evaluating
lens clearance or contact on cornea). With blinking,
• In central corneal touch fit, the CL is likely to rotate about fluorescein is spread across the eye by the lid and tear
the corneal apex from the superior to the inferior position film movement. The fluorescein pattern should correlate
(Fig. 3.2.1.26). As the central radius of curvature of the with dynamic fitting characteristics. Static assessment is
lens is flatter than the corneal apex, the path of least independent of lid action and thus assesses different lens
resistance for the lens to move is around the apex. This designs and assesses changes in lens fitting over time.
may be either on the nasal or the temporal side. With Three zones that are assessed are central, mid-peripheral
increase in corneal toricity, lens stability and movements and peripheral. Fit is denoted as steep (pooling), flat
become more erratic. In tight fits, small rocking (touch), and width of pooling or touch zone assessed
movement occurs around the flatter meridian. along horizontal meridian.
114 Contact Lens
clearance, a narrow edge width or tight periphery. A steep

lens hugs the cornea and impedes tear flow and lens movement
to less than 1.0 mm because of increased viscous drag.
Flat fit is diagnosed on static assessment as limited zone of
central corneal touch. When the BOZR is made longer (flatter),
the central back surface of the lens rests against relatively
steeper central cornea. This manifests as apical touch with
excess fluorescein in mid-periphery and peripheral zone
(Figs 3.2.1.28A and B). During dynamic assessment a loose
fit lens displays excessive excursion of > 0.5 mm, resulting in
high or lateral riding position. High-riding occurs due to upper
lid forces acting on the lens. When the upper lid is unable to
hold the lens, it typically falls slowly to an inferior location on
Fig. 3.2.1.27: Steep fit on static assessment. Note the central the cornea. Thus, the resting position of the lens is inconsistent
pool with peripheral touch and the lens may rotate around the corneal apex on either
nasal or temporal side, as it returns to a low resting position
on the cornea.
Steep or tight fit is diagnosed as apical pool of fluorescein Once tearing has settled and lens fit has stabilized, the
stained tear film indicating excessive central clearance power is finalized by performing over refraction (perform-
(Fig. 3.2.1.27). Degree of clearance increases with shortening ing retinoscopy over the lens in situ) to determine BVP.
of BOZR resulting in a heavy mid-periphery contact. This Initially, after the RGP fit, foreign body sensation is
high pressure contact results5 in warpage (deformation) of experienced by all patients. Adaptation occurs within few
corneal topography. Peripheral zone shows reduced edge days to weeks.
Figs 3.2.1.28A and B: Flat fit on static assessment. Note the central touch and fluorescein in the mid-periphery and peripheral zone
REFERENCES 3. Holden BA, Mertz GW. Critical oxygen level to avoid corneal edema
for daily and extended wear contact lenses. Invest Ophthalmol Vis
1. Cavangh HD. The effects of low and hyper DK contact lenses on Sci 1984;25:1161-7.
corneal epithelial homeostasis. Ophthalmology Clinics of North 4. Millodot M. Effect of long time wear of hard contact lens on
America 2003;16:311-25. corneal sensitivity. Arch Ophthalmol 1978;96:1225-7.
2. Zantos SG, Holden BA. Ocular changes associated with 5. Guillon M, Lydon DP. Tear layer thickness characteristics of rigid
continuous wear of contact lenses. Aust J Optom 1978;61:418- gas permeable lenses. Am J Optom Physiol Opt. 1986;63(7):527-
26. 35.
6. Rengstorff RH. Refractive changes after wearing contact lenses. 10. Cornish R, Sulaiman S. Do thinner rigid gas permeable contact
In: Phillips A, Stone J (Eds). Contact lenses. A textbook for practi- lenses provide superior initial comfort? Optom Vis Sci.
tioner and student. 3rd edn. Jaypee Brothers, New Delhi 1994;741. 1996;73:139-43.
7. Gasson A. Soft hydrogel lens fitting. In: Phillips A, Stone J (Eds). 11. Philips AJ. Rigid gas permeable and hard corneal lens fiting. In :
Phillips A, Stone J (Eds). Contact lenses. A textbook for practitioner
Contact lenses. A textbook for practitioner and student. 3rd edn.
and student. 3rd edn. Jaypee Brothers, New Delhi 1994;372.
Jaypee Brothers, New Delhi 1994;412.
12. Atkinson TCO. A re appraisal of the concept of fitting rigid hard
8. Garner LF. Sagittal height of the anterior eye and contact lens lenses by the tear layer and edge clearance technique. J Br Contact
fitting. Am J Optom Physiol Opt. 1982;59:301-5. lens Assistant 1984;7:106-10.
9. Young G. Evaluation of soft contact lens fitting characteristics. 13. van der Worp E, de Brabander J, Swarbrick HA, Hendrikse F.
Optom Vis Sci 1996;73:247-54. Evaluation of signs and symptoms in 3- and 9-o’clock staining.
Optom Vis Sci 2009;86:260-5.
3.2.2 Special Types of Contact Lenses
EXTENDED WEAR LENSES • RGP lenses: New materials like Menicon Z RGP lenses have
also been evaluated for EW but are not so freely
Extended wear (EW) lenses are most useful in pediatric
available.9,10
aphakes, followed by the elderly with compromised ocular
surfaces. The fears associated and substantiated with EW use
Indications of EW
are primarily two-fold; increase in microbial keratitis and sequel
to lens induced hypoxia.1,2 Hypoxia induced by EW lens • Pediatric aphakia
increases corneal binding of bacteria and alters the commensal • Occupational issues
microbial flora with an increase in gram negative organisms. The frequent complications associated with EW use make
Subsequent risk of microbial keratitis especially by Pseudomonas it an unsafe option in most patients. EW contact lenses may
aeruginosa increases as IgA specific for P. aeruginosa is reduced.3,4 also be used with considerable success even in young children.
The practice of EW wear although much safer now than
in the past, is still not very widely practiced due to the above Complications Associated with EW
mentioned drawbacks.5 • Corneal infections11-13
Types • Discomfort, dry and red eyes
• Noninfectious complications like contact lens induced
• Soft lenses : acute red eye (CLARE), giant papillary conjunctivitis,
– High water content with 70 to 80 percent water have peripheral corneal infiltrates, superior epithelial arcuate
high oxygen transmissibility but are more fragile and lesions (SEAL) are subsequent to mechanical and immune
deposit prone. mediated results of EW wear.
– Low water content with 38 to 45 percent water content • Lens overwear with consequent hypoxia, corneal edema,
are very thin lenses with inherent handling difficulties. neovascularization and corneal endothelial cell polymega-
– Medium water content with 48 to 69 percent water thism.13
content, balance the oxygen permeability with good
handling properties.3
THERAPEUTIC CONTACT LENSES
Extended wear lenses are now being made of silicone
hydrogel material like lotrafilcon A, B or galyfilcon Silicone Therapeutic contact lenses or ‘bandage’ lenses are lenses worn
hydrogel material has excellent oxygen transmission and for therapeutic reasons such as wound stabilization and as an
results in minimal corneal insult during extended wear.4,6 aid to epithelial healing. The preferred lenses are hydrogels
Silicone hydrogels are currently the most popular EW with larger diameter since they ensure complete corneal
lenses.5,7,8 coverage in all gazes.
116 Contact Lens
Indications
• Recurrent corneal erosions: These occur in basement
membrane/Bowman’s layer dystrophies, post-abrasive
trauma and in metaherpetic keratitis. Diabetics undergoing
intraocular surgery often develop a chronic epitheliopathy.
Bandage lenses in such conditions aid healing and allow
normal epithelial resurfacing.14,15 They need to be worn
for a longer time, sometimes even for 4 to 5 months to
allow epithelial hemidesmosomes to reform and re-
establish links with the defective basement membrane.16
• Filamentary keratitis and bullous keratopathy: Aberrant
epithelial turnover in filamentary keratitis causes mucous
filaments to be formed over focal corneal micro-erosions.
These filaments cause pain by stimulating corneal nerves.
During blinking the filaments deform the epithelium Fig. 3.2.2.1: Bandage lens over a corneal perforation sealed with
adjacent to the attached filament site and thus stimulate tissue glue. The lens shows a flat fit
sensory nerves. Bandage lenses provide pain relief by
shielding the filaments from the blinking action of lids scar formation by protecting the denuded stroma from
and decrease filament formation by reducing sites of abrasive action of lids, thus allowing cellular adhesion and
epithelial desquamation. 17 In pseudophakic bullous tissue relationships to develop normally.
keratopathy recurrent pain caused by rupture of bullae is • As a barrage to flatten over filtering blebs after trabeculectomy:
relieved by the bandage lens. It is also used post-stromal In cases of hypotony and shallow anterior chamber post-
puncture in these cases. glaucoma filtering surgery oversized bandage lenses maybe
• Neuroparalytic keratitis and exposure keratopathy: Corneal tried as a temporary measure to tamponade aqueous
desiccation maybe treated by bandage lenses. However, filtration through an overfiltering bleb.
hydrogel lenses succumb to the effects of exposure and • Entropion /Trichiasis: A bandage contact lens may be used
consequent dehydration, thus require very frequent to protect the cornea till the primary cause is resolved.
lubrication. A lateral tarsorrhaphy would be a better option • Protection from lid sutures: Surgery involving full-thickness
albeit more disfiguring. suturing of the eyelid, e.g. lid biopsy and lid laceration
• Stromal melt: This may occur in cases of chronic non-healing repair often leaves suture material in apposition to the
epithelial defect or peripheral ulcerative keratopathy. cornea. Subsequent corneal irritation, abrasion and
Bandage lenses treat the persistent epithelial defects and infection can be prevented by bandage contact lens until
may help prevent the initiation of the melt. However, once suture removal is done.
a melt has started, bandage lenses are not sufficient on • To deliver ophthalmic drugs on the ocular surface.
their own to arrest the collagenase activity. A thicker less
The lenses must be replaced within a month or earlier if
oxygen permeable lens maybe used as an adjunct in
breaks or chips are noted. The patient needs to be evaluated
peripheral melts to promote vascularization which may
fortnightly for assessment of healing and to rule out
arrest further melt.17
occurrence of neovascularization or corneal infiltration.
• Corneal perforations: Bandage lenses may be used to ‘seal’
Silicone-hydrogel material therapeutic lenses, due to their
small corneal perforations. After use of tissue glue or
higher oxygen permeability can be worn for longer periods,
suturing, patient comfort is enhanced by the bandage lens
decreasing the need for frequent lens replacement.19 Topical
smoothing over the rough surface of the suture or glue
lubricants must be used frequently along with broad spectrum
(Fig. 3.2.2.1). They are also useful to seal micro leaks after
antibiotics over these lenses in situ.
penetrating keratoplasty.18
• Keratoconus: It is used after planned after planned surgical
Mechanisms of Action
debridement of epithelium in post- refractive surgery or
after C3R treatment for keratoconus. In addition to • Pain relief from exposed nerve endings in corneal abrasions
providing comfort, bandage lenses decrease sub-epithelial and bullous keratopathy.
• Mechanical protection of cornea in trichiasis and in 25 mm diameter and at least one fenestration needs to be
cicatrizing ocular surface diseases. incorporated to facilitate tear exchange.22
• Epithelial defect healing by protecting migrated and/or
newly formed cells from abrasive action of lids during Fitting Parameters
blinking.
• Adequate movement: The fit must not be too loose otherwise
• Maintenance of ocular surface hydration by preventing
the excessive movement causes mechanical abrading of
tear evaporation and providing a moisture reservoir in dry
the corneal epithelium. Alternatively, a tight lens with
eye.
minimal movement will cause discomfort, a red-eye
• Action as vehicle for drug delivery thereby allowing
inflammatory response to cellular debris and corneal
prolonged drug delivery at a lower dosage rate.
metabolic waste trapped under the lens. Such compromised
eyes become vulnerable to infection.
Precautions
• Patient comfort: Comfort of patient has to be checked after
• High water lenses must be used as they have better Dk values 30 to 60 minutes of wear. After-care visits should be
to reduce risk of corneal edema and neovascularization.18 conducted as with normal EW patients.
• Tear stagnation under the lenses decreases the flushing • Corneal vascularization: Mild corneal vascularization is an
and cleansing action of blinking, thus broad spectrum expected corollary of long-term, low oxygen transmissi-
antibiotic drops and lubricants need to be used over the bility lens wear, especially in an already compromised
lenses. These drops should be preservative free otherwise cornea. An encroachment of upto 1 to 1.5 mm from limbus
preservatives bind to the lens and cause corneal toxicity. may be acceptable. Neovascularization can be discouraged
• Gels and ointments should not be used as they smear the by optimizing oxygen transmission and assuring free lens
lens surfaces and cause vision blur. movement without either conjunctival or vascular limbal
• Bandage lens should not be fitted on an eye with active impingement.
infection unless it is to be worn for drug delivery or to • Lens deposits: These develop rapidly in compromised eyes
promote healing as an adjunct to medical treatment. with a challenged lacrimal system. A lens with deposits
• In persistent epithelial defects as in hypoesthesic corneas, has reduced wettability and induces immunological
e.g. post-herpetic or neuroparalytic keratitis, the patients problems.
should be monitored frequently as warning sign of pain is • Steal phenomenon: The hydrophilic polymer of hydrogel
deficient. lenses absorbs moisture from the ocular surface and
• The lenses need to be replaced within a month or earlier exacerbates dry eye. Consequently, the lenses can dehydrate
if spoilage is seen. significantly on the eye and are more vulnerable to deposits.
Materials used are hydrogel, siloxane hydrogels, siloxane Higher the water content, more is it affected by
elastomers, collagen, and RGP polymers. Hydrogel lenses were dehydration. Sometimes a lower water content lens presents
the lenses of choice because their large diameter ‘bandages’ a greater barrier to lens dehydration and possibly better
the cornea and their soft, supple nature enhances comfort. bandaging effect, inspite of having lower oxygen
They dehydrate on the eye and draw water from an edematous transmissibility.
cornea. This water movement can challenge an eye that is
already dry. The relatively low oxygen permeability (Dk) may TORIC LENSES
induce corneal edema, unless the lens is made sufficiently thin.
Often, a mid-water content (approximately 50 to 60% water) Over the past decades soft toric lenses have undergone
disposable hydrogel lens is a more feasible choice. Currently continuous improvements which have led to an increase in
bandage lenses are being made from silicone hydrogel material the proportion of these lenses being fitted.23-26 These soft
for their better oxygen transmission. The available materials lenses are used to treat cylindrical refractive error of more
are balafilcon A and lotrafilcon A. Alternatively, very thin than 0.75D. The cylinder which is incorporated in the lens
membrane type lenses made of crofilcon A maybe used.20 needs to be aligned to the cylindrical axis of eye which it
Use of disposable soft lenses is also a good option and is attempts to correct. ‘On-eye’ lens dynamics and stabilization
more economical.21 are influenced by gravity, lid pressure, tear fluid forces and
Scleral lenses are most durable, inert and optically efficient thickness differentials due to lens design and base vertex power.
as therapeutic lenses. Their dimension needs to be at least Toric lenses need to maintain their correct meridional
118 Contact Lens
orientation under all reasonable circumstances and eye by pre-lens tear film viscosity moves the lens in the same
positions. However, in the interests of eye physiology the lens direction as itself. This action is opposed by post-lens tear
must also move on the eye. Thus the whole art of toric fitting film.
is to balance these two aspects of stability and movement. • Blinking effect: During normal blinking, the upper lid
forcefully pushes against the superior lens edge and creates
Some Optical Terms Relevant to a rotational force thereby pushing lens medially and
Understanding the Toric Lens Fit inferiorly (clockwise for left, counterclockwise for right
• Corneal astigmatism is usually applied to anterior surface eye).28
astigmatism. True corneal astigmatism should take into • Gravity: This affects toric lens position and thus vision.
account the refractive effects of the posterior cornea as Reading while lying down or reclining and turning on one
well as any refractive index anomalies in the cornea as a side to watch television would influence vision while
whole. Current instrumentation does not easily measure wearing a toric lens.29
posterior corneal curvature. A RGP lens corrects corneal • Hydrostatic force of tear film: Inadequate tear film increases
astigmatism better than a soft lens. the hydrostatic force on lens. The larger volume of inferior
• Lenticular astigmatism is due to meridional differences in the tear film coupled with smaller superior tear film creates a
refractive power, intralenticular differences in refractive greater hydrostatic force acting on superior lens margin
index, or differing surface flattening rates of the various culminating in its torsional rotation.
lens layers. Since the lens is surrounded by aqueous whose • Lens parameters: Excessive prism incorporation adds to the
refractive index 1.336 is marginally different from the lens weight of lens which causes down-riding of lens.
(1.386-1.406), any lenticular contribution to astigmatism Insufficient prism decreases the lens weight, makes the
is usually minimal.27 A tilted and/or decentered crystalline lens more mobile and is less able to resist rotation with
lens, however, does induce significant astigmatism. Soft each blink.
lenses are able to correct lenticular astigmatism better than Toric manufacturing involves incorporation of certain
a RGP lens by moulding to the eye. designs which neutralize the above mentioned destabilizing
• Internal astigmatism is due to optical aberrations at the retinal action of lid and other factors on the lens. These stabilization
level. designs are:
• Total astigmatism is the combination of corneal, lenticular – Prism ballast: Increasing inferior lens thickness creates a
and internal astigmatism. base down prism inferiorly with consequent increase in
• Residual astigmatism is another term for internal or lenticular the inferior lens mass. Gravity aids this bottom heavy lens
astigmatism. in orienting itself according to weight distribution. The
• Lens flexure occurs when a lens is subjected to lid pressure, upper lid acts on thickness differences to orient the lens.
blinking and capillary attraction. A lens of sufficient Usually a base down prism of 1 to 1.5 Δ (prism diopters)
thickness withstands these forces, however in physio- is used. The inherent problems with this design are induced
logically desirable thicknesses, some conformance is vertical prismatic imbalance, increased inferior lid sensitivity
inevitable. Flexure depends on physical properties of lens and hypoxia to inferior cornea due to increased inferior
material, thickness and fitting relationship (amount of lens thickness.30,31
corneal toricity). Lens flexure usually induces a plus cylinder – Truncation: Part of inferior lens is physically removed along
whose axis aligns with the flattest corneal meridian. a 0.5 to 1.5 mm long chord at 6 o’clock position.32 This
• Tear lens is applicable to RGP lenses. This post-lens tear can cause inferior lid margin irritation and limbal
film neutralizes 90 percent of corneal astigmatism in cases neovascularization.
of low to moderate astigmatism. This tear lens is absent – Peri-ballast: This involves a minus carrier design wherein
in soft contact lenses since they conform to the corneal the superior carrier is slabbed-off or chamfered to reduce
curvature. This is one of the reasons why RGP lenses are thickness. It allows the lens periphery to position
able to correct more astigmatism than a soft lens. comfortably under the lids and limits the prism to an area
outside the optic zone.
Forces Acting on a Toric Lens – Thin zones/Dynamic stabilization or double slab off design: In
Which Affects Vision this design, thin zones are placed in the superior and
• Lid: Static and dynamic lid forces hold contact lenses inferior portion of lens thereby reducing peripheral lens
‘captive’ in the interpalpebral space. Lid movement aided thickness. This thinning makes such a lens very lid
dependent. Both lids press against the thinned out once mislocated, whereas a flat fit lens shows excessive
peripheral parts and decrease lens torque. The thin edges movement, poor centration, unstable orientation and patient
contribute to increased comfort. This design is not suitable discomfort.35
for patients with loose floppy lids. For evaluating fit, the lens needs to be screened after a
– Chamfering: The lens edges are slabbed off on the anterior 20 minute resting period on the eye. The lens markings are
surface and the lens mass is effectively reduced. evaluated and amount of rotation (degrees) and degree of
– Back surface torics: This design incorporates both prism rotation (left or right) is noted. The rotation direction is always
ballast and thin zones. The fit is aligned to corneal to be noted from the fitter’s perspective (clockwise rotation is
curvature so that the vertical lens movement during recorded as left and counterclockwise as right) (Fig. 3.2.2.2).
blinking is minimized. The marking point is at 6 o’ clock position, thus clockwise
would be to practitioner’s left. One clock hour of rotation
Fitting Principles equals 30 degrees. Rotation is assessed by clock hours of
torsion. The acronym used to remember is LARS (Left Add,
For high refractive errors with small corneal astigmatism, the
Right Subtract). This compensates for any rotation of
spherical equivalent is calculated and a spherical soft lens is
diagnostic lens determined from the observer’s point of view
used to mask the astigmatism. The 4:1 rule is applied wherein
looking at the 6 o'clock position of lens. If rotation is to the
if a corneal cylinder is less than 25 percent of the spherical
left (clockwise) the amount of trial lens rotation needs to be
component, then cylindrical correction maybe left
added to cylinder axis of spectacles (not the cylinder axis seen
uncorrected.33 A relatively thicker soft lens (center thickness
on trial lens). If however the rotation occurs to the right
being more relevant) enhances the masking effect. For higher
(counterclockwise) the amount of rotation is to be subtracted
cylindrical errors torics are preferred. They are usually
from the cylinder axis of spectacles. In the example given in
manufactured in plus cylinder and are best suited to treat
Figure 3.2.2.3, the toric lens rotates 10 degree to the left while
cylindrical errors of 1- 3D.23,34
on the eye. If the spectacle refraction is –4 DS/–3.0 DC axis
It needs to be remembered that for toric lenses, upper lid
180 degrees then the final axis to be ordered is 180 ADD
forces are more significant than lower lid forces. Due to the
10 degrees as left rotation occurred. So final lens axis is –3
scissoring lid action seen during blinking, torics usually rotate
DC axis 190 degrees.
nasally by 10 degrees. However, in some situations the lower
After stabilization, an over refraction is performed using
lid may override the upper lid force depending on lid position,
only spherical lenses and spherical power determined by over
tightness, and amount of lateral movement.35,36
refraction is added to the spherical power of trial lens with
Lens markings engraved on the lens help the fitter evaluate
adequate compensation for vertex distance. On an average, a
and quantify in situ lens rotation. These laser markings which
toric soft contact lenses will tend to rotate nasally by about 5
are placed at certain positions of the lens, either 6 o’clock or
to 10° (nasal rotation is rotation towards the nose with respect
3 and 9 o’clock, are visible on the slit lamp. In case of grouped
markings, the standard difference between two marks is by
convention 30 degrees. These markings serve as ‘on eye’ ruler
to evaluate rotation and position of lens. They do not denote
the axis of the toric lens.
A trial lens set comprising many cylinders in many axis is
used. The common axis of 180 and 90 degrees should be
covered in powers ranging from +3 Ds to –3 Ds. Of these
trial lenses, one confirming as near as possible to the wearer’s
spectacle correction should be placed in the wearer’s eye. An
‘on eye’ stabilization time of 15 to 20 minutes is mandatory
before the lens fit can be assessed for centration, stability and
movement. Stabilization designs cease to be effective in
orienting the lens to the cylindrical axis in steep or flat fit. A
well-fitted lens displays full corneal coverage, good centration
Fig. 3.2.2.2: The 3 marking lines are placed inferiorly with the central
and movement and is quick to return to axis once mislocated.37
one at 6 o’clock position. The arrow in red indicates counter-
A tight fit is diagnosed by good centration, initial comfort clockwise rotation or right from fitter’s perspective. The difference
with little or no movement, coupled with a slow return to axis between two marking lines is 30 degrees or one clock hour
120 Contact Lens
beyond limbus, they usually have a diameter of 23 to 25 mm.

Such lenses may be preformed or pressed from a molded cast
of the patient’s eye. The older lenses were fraught with the
problems of poor tolerance, reduced wearing time and corneal
edema (Sattler’s veil). Fenestration of the earlier PMMA lenses
solved the problem to a certain extent but with the advent of
silicone elastomers material like the current Boston lens, these
lenses can be successfully worn without causing corneal
damage. These custom-designed, fluid-ventilated, rigid gas-
permeable scleral lenses retain a pool of oxygenated artificial
tears over the corneal surface and help in restoring vision in
many incapacitating and blinding ocular surface and refractive
disorders.40-42
Indications
• In irregular ocular surface on which conventional lenses fail
to center like keratoglobus, advanced keratoconus, pellucid
degeneration and post-keratoplasty corneas.43-45
• To protect the anterior segment with a complete corneal-
Fig. 3.2.2.3: The 3 marking lines are placed inferiorly with the central clearance.46
one at 6 o’clock position. The arrow in red indicates counter-
clockwise rotation or right from fitter’s perspective
• Ocular surface disorders with disrupted distorted corneas and
lid deformity, e.g. severe dry eyes, Stevens-Johnsons
to the inferior aspect or base of the lens).37 Actual magnitude syndrome, post-chemical burns and corneal anesthesia
and direction of rotation depends on lid anatomy (tight lids, syndromes.22,40-42,45,47-49 Therapeutic benefits of these lenses
loose lids), lid location and palpebral aperture size. are provided by the oxygenated precorneal fluid compart-
ment they create over the corneal epithelium. This fluid,
Complications Seen with Toric Lenses at neutral pressure, protects the epithelial surface from the
desiccating effects of the environment, blink generated
• Fluctuating vision due to blink-induced lens movement friction and avoids the shearing forces generated during
causing vertical lens movement and rotation.38 This is more the blink-induced movement of soft lenses. Thus, this lens
troublesome in cases of high astigmatism.39 With higher is able to provide stable vision over distorted corneas while
astigmatism, fluctuating vision, poorer centration and lens simultaneously allowing for corneal healing.41,42,50,51
rocking on the flatter meridian increases. • Occupational and recreational uses include sports like
• The thicker toric lenses versus thinner spherical lenses swimming and skiing as they are difficult to dislodge.
cause increased lens awareness, 3 and 9 o’clock staining • For cosmesis in scarred shrunken blind eyes.
and reduced oxygen permeability. These large lenses are easy to handle and maintain, which
• Corneal edema particularly in the inferior 1/3 of the lens makes them ideal for use in elderly patients with poor vision
due to decreased oxygen transmissibility as a result of and poor manual dexterity as in arthritis and hand tremors.
added lens thickness.35 Their main drawbacks are the specialized training required to
• Corneal vascularization, in usually inferior and superior fit them, their cost and the lack of easy availability.
areas.
• Scleral or conjunctival indentation. Advantages
• Inadequate tear exchange due to limitation in the amount
• Their scleral bearing makes them independent of corneal
of movement.
alignment, thus making them useful in fitting irregular
corneas.
SCLERAL LENSES
• Dimensionally stable and robust lenses.
Historically scleral lenses made of blown glass were the first • Minimize lid sensation as dimensions exceed lid margins.
contact lenses to be created. Defined as large diameter lens • Are almost never dislodged out of eye.
with scleral bearing surface and optic zone clearance extending • High range of powers is possible.
Disadvantages lens is unimportant but excessive rotation must be

corrected.
• Some amount of corneal edema occurs
• High cost and lack of easy availability
Complications or Problems Associated
• Unilateral fit causes a pseudo-proptosis appearance
with Scleral Lens Wear
• Fenestrations cause air bubbles leading to visual blur,
localized desiccation of cornea and settling back of lens. • Bubbles or froth indicate improper placement, inadequate
size of fenestration or excessive apical clearance.
Fitting Philosophies • Sometimes a clicking sound is caused by the bubble passing
through the fenestration.
These lenses are fabricated by the following techniques:
• Photophobia occurs due to over-correction, inadequate
• Integrated fitting for preformed scleral lenses with known
tear exchange or insufficient limbal clearance with resultant
optic, limbal, transition and haptic zone parameters is
hypoxia.
similar to conventional lenses.
• Insufficient tear exchange or inadequate limbal clearance
• Impression lenses are made after taking an impression
also cause lens intolerance and vision blur after lens
mould from the patient’s eye.
removal.
• Computer generated lenses are fabricated from over-sized
• Mucus deposition is common and occurs due to corneal
buttons.45 Acceptable fits are either flush to the eye contour
bearing due to rough edges of lens coupled with inadequate
or a semi-sealed fit. The latter incorporate modifications
tear exchange.
in the haptic area like grooves, furrows or channels to allow
• Decentered/non-aligned optics or a large bubble can cause
for tear exchange or are ventilated with fenestrations to
monocular diplopia.
allow air entry.52 For stability, the lens diameter should be
• On removal of a tight lens, the conjunctiva may show signs
kept as large as possible with a wide inferior scleral portion
of a ‘lens imprint’ or so-called conjunctival indentation.53
to prevent the lens from dropping. A well-fitted scleral
These lenses are difficult to fit but once the art has been
lens is fitted a little flatter than alignment with a flat edge
mastered they can often serve to avert a keratoplasty and provide
zone to allow for tear exchange. The BOZR thus should
adequate vision for many years as evidenced from an exhaustive
be flatter than the average K by at least 1 mm to keep
study on 875 eyes over a 18-year period by Rosenthal et al.41,42
contact with the cornea to a minimum, with an apical
clearance of 0.2 to 0.3 mm. Limbal zone should be 2 to 3
PRESBYOPIC CONTACT LENSES
mm wide with a clearance of 0.1 to 0.2 mm. The central
corneal zone vaults over the cornea and limbus. A scleral The aging population highlights the need to provide effective
flange prevents excessive pressure/bearing at the limbus. near vision options for contact lens wearers developing
Compression needs to be evaluated by local blood vessel presbyopia and for emmetropes developing presbyopia. A
blanching and should be avoided at all cost. Fenestrations recent survey estimates that fewer than 40 percent of contact
(reserved for older PMMA lenses) need to be 1 mm wide lens wearers over 45 years of age were prescribed contact
and are placed in the interpalpebral/limbal zone to allow lens presbyopic correction.54 The stronger need for this
for air entry during eye movements. The lens is fitted after modality by older females is a manifestation of their stronger
being filled with saline which serves as oxygenated desire for the cosmetic benefits of contact lens wear.55
precorneal fluid compartment. This saline may need to be However, the main deterrent is that lenses that correct
replaced after a time interval. presbyopia compromise visual performance to some extent
An ideal fluorescein pattern should reveal an even by reducing stereo-acuity and contrast sensitivity and also by
clearance over the cornea starting 1 to 2 mm peripheral to causing fluctuating vision or image jump.56-58
the limbus. Absence of limbal clearance indicates limbal The other problem faced by bifocal lens wearers is
tightness and needs to be rectified. A bubble if present, is disruption in binocular balance so there is a tendency for
mostly sausage shaped, and overlies the corneo-scleral unsuccessful monovision wearers to exhibit esophoria for
junction. It should not be located in the nasal or inferior distance. The patient thus must have realistic expectations and
position since that interferes with near vision. A large the fitter should have knowledge of the visual demands of
bubble indicates excessive corneal clearance and prevents the patients before fitting a presbyopic lens.56, 59
the lens from centring. Lens centration is checked by To understand the problems associated with lens wear in
assessing areas of corneal touch. Slight rotation of the the presbyopic age it is important to understand the changes
122 Contact Lens
which occur during the normal physiological process of wearers. This may translate into problems during driving.56
aging. Strong ocular dominance and visual tasks which require a
smooth shift of gaze between objects reduces success rates.
Age-Related Corneal Changes Monovision adversely affects contrast sensitivity (almost
20% loss), stereopsis, and quality of vision by causing
• Reduced nerve elements in the cornea and eyelids decreases
ghosting.56, 58 This may lead to problems in night driving
corneal sensitivity. This is coupled with increased visibility
and during the need for a third focal length, for example
of corneal nerves.
with computer screens at intermediate distances. The
• Pinguecula and pterygium at limbal area along with
additional loss of stereopsis makes it imperative to take
peripheral thinning.
the patient’s occupational needs into account before pres-
• Increasing ‘against the rule’ (ATR) astigmatism as the
cribing monovision as a presbyopic correction modality.
vertical cornea flattens with increasing age.
It disrupts binocular status by influencing spatial
• Endothelial cell loss, decreased cell density with concomi-
localization and may cause disorientation or imbalance.
tant decreased endothelial pump activity may increase
Small pupils can facilitate binocular suppression by
hydration and decrease corneal transparency.
reducing the differential blur of two ocular images. Thus
• Increased permeability of limbal vasculature allows leakage
this modality is not advisable in those with a high visual
of low-density lipoproteins into cornea.
demand or those with an existing binocular vision prob-
• Increase in refractive index due to altered hydration.
lem.56,60 However, near high and low contrast visual acuities
Fitting Philosophies are better with monovision than bifocal lens wearers.62
• Simultaneous vision: Light entering each eye emanates from Technique: Commonly dominant eye or the least myopic eye is
distant, intermediate and near objects. With the lens in situ corrected for distance. Dominance needs to be established by
the image of the distant object is focused on the retina by sighting tests, e.g. Dolman Card. The patient is asked to hold
the distance zone of the contact lens over which is super- a special sighting card with both hands, and view a letter on
imposed a blurred image of near objects, focused by the the Snellen chart through a central hole keeping both eyes
lens’s near zone. At near, this situation is reversed. Such open. The eye used for sighting is the dominant eye. However,
lenses are symmetrical about the geometric center. They now it is being realized that dominance is not fixed parameter
cause reduction in vision quality due to effect of but rather a fluid, adaptive, phenomenon. The wearer’s
superimposed, out-of-focus images from all other distances occupational needs need to be assessed along with dominance
imaged by all optical zones of the lens on the retina.58,60 checking.56 The near lens is inserted first and removed last as
• Alternating vision: This provides either distance or near this enables the patient better vision for handling their distance
vision (i.e. alternate between the distances) by changing lens. Usage of handling tints maximizes the presbyope’s chance
the lens position on the eye. Such lenses “translate’ as the of seeing the lens against light backgrounds, e.g. lens case and
wearer’s direction of gaze changes from straight ahead to palm of the hand.
down gaze for near. Excessive or insufficient lens Enhanced monovision refers to a single vision lens in one eye
movement results in disturbed vision, e.g. inadequate (usually the dominant eye) and a bifocal lens in the other,
translation causes only part of each lens zone occupying usually biased towards near vision.
the pupil area. This technique requires correct orientation
Modified monovision refers to a bifocal contact lens in each eye
of lens at all times, and this is ensured by prism ballasting
with one lens tailored to provide ‘better’ distance vision (usually
or a truncation.61
the dominant eye) and the other lens providing ‘better’ near
• Monovision: In this technique one eye usually the dominant
vision. Eventually as monovision patients grow older they
eye is corrected for distance and the other eye is fitted for
require a higher reading add, leading to loss of intermediate
near vision. If the visual needs of the patient require near
vision. They then require multifocal correction.
vision, then the dominant eye is corrected for near. The
wearer has to select the ‘better’ image or ability to actively
Patient Selection and Pre-screening
suppress the blurred image (sensory inhibition). The ability
to suppress is also determined by contrast in visual stimuli, • Age: Most patients are older, so systemic and ocular
e.g. blur from defocused, small, bright stimuli against a conditions should be taken into account before fitting
dark background is difficult to ignore by monovision presbyopic lenses. History of dry eye syndrome, thyroid
disorders, diabetes, hand tremors, use of medications like Patients wearing CN lenses often complain of variable
antihistaminics, decongestants, hormone replacement vision during the day. In sunlight, distance vision is reduced
therapy and diabetes must be taken.63 as less of distance zone is in front of the miosed pupil, whereas
• Pupil size: Light induced variations in pupil size influence in twilight near vision gets impaired since both distance and
vision drastically so light levels at work and home need to near zones rest over the dilated pupil. Sunglasses must be
be accounted for. Distance contrast sensitivity at photopic prescribed during outdoor activities for such patients. Such
and mesopic light is reduced with both monovision and lenses perform better at near if the lens translates on the eye
bifocal lens wear, more so with the former.60 A lens with with the patient looking downward to read. Patients wearing
an extended depth of focus may provide the answer.64 CD lenses complain of flare around headlights while night
• Distance at which most work is done: This differs according to driving since the pupil dilates into the near zone of the lens
the visual needs of the wearer, e.g. computer usage, file causing ghosting.
work, reading, and work at arm’s length (intermediate For RGP concentric bifocals the need of a larger central
distance). Frequency of changes from near to far viewing distance zone increases the chance of bubble formation
distances is more relevant for translating designs. (because of increased sagittal height of the local post-lens
• Visual acuity: Reduced acuity for distance assumes tear film). Optimum centration and minimum movement with
importance during driving. As per licensing rules a distant blinking should be aimed at while fitting this lens. To achieve
visual acuity of 20/40 (6/12) in the better eye is mandatory, this, a larger, steeper and thinner lens needs to be prescribed.
thus occupational requirements must be discussed with
these patients.57,65 Visual quality with a bifocal can also Translating/Alternating Design
degrade depending on pre-existing ocular aberrations.66
• Screening for monovision: Patients needing fine detailed vision Translating is when the lens has two distinct segments or
with depth perception like surgeons, watchmakers, jewelers annular concentric design. The inferiorly positioned reading
and those who drive a lot during night would be very segment maintains its position with the help of prism ballasting
unhappy with monovision quality. Amblyopic people also or truncation. Such lenses are gaze dependent and are fitted
are not good candidates for monovision. in the low riding position to enhance reading in the traditional
downward reading gaze. Annular concentric design on the
Lens Designs other hand incorporates the reading segment circumferentially
and is more suited for near acuity in primary gaze, e.g. computer
Concentric Bifocal, Multifocal
users. However, they are riddled with problems of flare,
These are lenses in which light from far, near, and all ghosting and poor intermediate vision. The Acuvue bifocal
intermediate distances enters the eye simultaneously. These (Vistakon) has five concentric zones which distribute light
lenses need no special lens orientation or movement and as more evenly. This pupil intelligent lens consists of central
long as the lens covers the pupil, good vision occurs. However, distance zone surrounded by an annular near ring, second
these lenses lead to diminished contrast as multiple images of distance ring, then second near and third distance ring in the
varying focus quality are simultaneously imaged on the retina. periphery. This minimizes flare and haloes in dim illumi-
Alterations in pupil size effects quality of vision as small pupils nation.63 Like monovision here too the dominant eye can be
‘convert’ simultaneous vision lenses to single vision lenses fit for distance and the non-dominant for near, but unlike
(since only the center zone fills the eye’s reduced pupil). Pupil monovision binocularity and stereopsis are retained since both
dependency is reduced by using alternate concentric zones eyes remain corrected for both distance and near.
for D and N (pupil-intelligent diffractive lens).
Bi-concentric simultaneous vision bifocals are solid (i.e. Diffractive Design
one-piece) and incorporate either a back or front surface ‘near’
segment. Mostly near segment is on the front surface as this These lenses achieve good optical quality regardless of the
provides more predictable fitting and increased comfort. The pupil size. Conventional concentric bifocal designs encompass
lens’ central zone may be intended for either distance (Center two lens powers within the pupil and, as the pupil size alters,
Distance, CD) or near (Centre Near, CN). Most CN lenses the relative contribution of each component to the final retinal
have central zone diameters of < 3 mm. However, it must be image varies. With a diffractive lens, the entire ‘optical’ zone
changed depending on the pupil diameter measured in reduced directs light to its two focal points independent of pupil size.
illumination. Such lenses are better for patients with moderate adds, small
124 Contact Lens
to medium pupil sizes, and good tolerance of reduced contrast. • A recent study highlighted a very relevant fact. While
Vision loss occurs due to distance and near images being performing computerized automatic perimetry on patients
superimposed causing reduction in contrast. Incident light is wearing presbyopic contact lens reduced differential light
split between both distance and near images with forty percent sensitivity leading to reduction in global sensitivities (GS)
light going to each distance and near images. Twenty percent of the central visual field, was seen, more so with bifocal
is lost to higher order diffractive images, scatter, reflection contact lenses.67 This can have an implication in testing
and absorption. This reduction in image contrast is more for for comorbidities like glaucoma occurring in this age group.
near61 and is compounded by any uncorrected astigmatism.
Patients with > 0.75D cylinder are not likely to be successful PROSTHETIC AND TINTED LENSES
with a diffractive lens. Also some degree of flare in low levels
of illumination may also be reported. Most wearers do not Prosthetic Lenses
adapt to ghost images and visual performance does not Prosthetic lenses, specially designed to match the other eye as
improve with further wear. closely as possible are used both for sighted and non-sighted
eyes to improve their cosmetic appearance. Some disfiguring
Aspheric Lenses Maybe Progressive eye conditions lead to a loss of self-esteem and social ostracism
or Digressive of the patient. Prosthetic lenses help in returning these patients
Progressive addition lens (PAL) has a central distance vision to the social fabric. These lenses can be—rigid, soft, corneal
with progressive increase in plus power in the periphery. or scleral. For rigid lenses, the iris is hand-painted to the desired
Digressive have near central with gradual increase in minus color and laminated with a clear plastic overlay. For soft contact
power in the periphery. These lenses provide stable vision in lenses, colors and shades can be custom-ordered from the
the intermediate range and are very useful for computer users. laboratory.
Optimum centration is critical as the central optical zone is
2 mm or less, thus small amounts of decentration cause Indications
ghosting. Digressive lens users experience a three dimensional
• Corneal opacities: For masking scarred corneas, a lens with
effect while reading with letters standing off the book, and
complain of delay in changing focus from distance to near. clear pupil area is needed for seeing eyes, whereas a lens
These effects show adaptation with time.63 with opaque pupil is ordered for the blind eye. If the
opacity is large then an opaque iris with black pupil is
Contact Lens with Spectacle Overcorrection needed (Figs 3.2.2.4A, B and 3.2.2.5A, B).68
• Aniridia: In aniridia the function of a contact lens is to
Half eye granny/professorial lenses maybe prescribed over supply an iris on the contact lens which matches the good
distance focus lenses. Myopes used to wearing minus lenses eye and to provide a pupil approximately the same size as
may become uncomfortable with plus lenses and have to adapt that of the good eye. Providing an opaque iris will reduce
to using head movements to do near tasks while wearing such the photophobia (Fig. 3.2.2.6).
glasses.63 • Irregular pupils: These can be enlarged, small or decentered.
Some practical tips: Complaints of photophobia and associated squint is
• The lens should be allowed to settle in the eye for 20 to 30 redressed with a clear pupil opaque lens.
minutes before evaluating fit. • Malignancy: Disfiguring malignancy like melanoma or
• For pupil dependent lenses, the pupil should be measured retinoblastoma.
in different lighting conditions simulating work environ- • Cataracts: Hypermature/traumatic with no vision
ment of the patient. (Figs 3.2.2.7A and B).
• Monocular and binocular distance vision should be • Large squints: A large squint maybe concealed with an opaque
checked to demonstrate acceptable vision for tasks like soft corneal or scleral lens. These are usually cases where
driving. surgical intervention has failed or is not advised. The scleral
• Near vision is tested at different distances according to lens has an opaque scleral portion and a painted iris and
occupational or visual needs like score cards of music, pupil are positioned to give the appearance of a straight
medicine bottles, prescriptions and maps. eye. In paralytic squint, a cosmetic lens may relieve diplopia.
• Best visual acuity is achieved after 1 to 2 weeks of wear • Heterochromia: A translucent tinted lens is used over the
after the brain has adapted to simultaneous vision.63 lighter colored eye.
A B
Figs 3.2.2.4A and B: A scarred eye (pre- and post-prosthetic lens fitting)
Note that the exotropia is more manifest after the prosthetic lens fitting
A B
Figs 3.2.2.5A and B: Another case of pre- and post-prosthetic lens fitting
• Buphthalmos: These large globes have associated larger

vertical palpebral aperture. An opaque lens with a white
scleral portion, painted iris portion of normal diameter
with a black pupil is used. The wide vertical aperture
imparts an appearance of ‘surprise’. Incomplete blinking
can lead to dehydration of lens which needs treatment
with lubricants. A flat, very large diameter (15-16 mm)
lens would need to be used.
• Albinos: The lenses relieve the disabling photophobia by
reducing light transmission through the unpigmented iris
and aids comfort. Visual improvement does not occur.
• Iris colobomas: Such patients use tinted glasses and do not
look straight at people. Use of opaque lenses with clear
pupils has tremendous positive impact on the personality
Fig. 3.2.2.6: A tinted aphakic lens on an aniridia patient after
cataract surgery for dislocated lens of such patients.
126 Contact Lens
A B
Figs 3.2.2.7A and B: Masking of a blind eye with cataract using a prosthetic lens
• Microphthalmos: In case of large discrepancy between two depth of the anterior chamber is retained, they ensure
globes, a thicker lens increases the volume in addition to better cosmesis.70
masking the disfigured globe. In cases where the difference Normally, soft prosthetic lenses do not correct astigmatism.
in globe size is not too great an opaque or translucent lens Opaque lenses with clear pupil also cause loss of peripheral
with outer tinted portion equal to the horizontal visible vision. The wearer must be forewarned of field loss associated
iris diameter (HVID) of the good eye suffices. with such lenses.
• Alternative to evisceration or enucleation for unsightly eyes: 69 The optimum prosthetic pupil diameter is difficult to
They need to be color matched with the healthy eye by determine because it does not respond to varying illumination
using a pre-made set or by ordering custom-painted contact as the normal pupil does. A pupil diameter appropriate to
lenses. Light colored irides are more difficult to match than high illumination environment like 3.5 mm is preferred as it is
dark brown eyes. this condition that other people are more likely to notice the
patient’s eye.
Types of Lenses Used Socket changes may occur during follow-up and adjust-
ments to lens size or shape maybe necessary. For protection
• Scleral: Scleral lenses are used when the affected eye is safety glasses (preferably with polycarbonate or other suitable
extremely disfigured and not amenable to conventional plastic lenses) are advisable especially for active children.
soft lens or corneal lens fit. The lenses are very durable, Spectacles also make the prosthetic lens less noticeable. It has
extremely stable on the eye, have a long life and are easy to been suggested that the lens over the prosthetic lens be made
maintain. Its thickness can be varied, so a sunken globe 1.00 D more minus (or less plus) than the good eye so there is
can be made to appear fuller using a thicker lens. The slightly less magnification or more minification.
expense and poor availability are the only drawbacks. Fluid-
ventilated, gas-permeable Boston scleral lens has been used In Color Vision Deficient Patients
to correct astigmatism and improve vision in scarred eyes.41 For some patients with color vision defects, the use of an
• Corneal lenses: These lenses are used for seeing eyes with appropriate tinted contact lens can assist discrimination of
regular or irregular astigmatism. These hand-painted lenses colored objects. This discrimination is achieved by inducing a
are the same size as HVID. Normal lenses have a thickness brightness difference between the colors confused by the color
of 0.75 to 1 mm with a possible increase till 3 mm. defective observer. A red-tinted contact lens, e.g. X-Chrom lens
• Soft opaque lenses: These lenses are used to enhance an in one eye has been proposed for patients with a red-green
existing color and not to change a color dramatically. deficiency, i.e. an anomalous trichromacy or dichromacy. The
• Soft translucent tinted lenses: These are hydrogel lens which X-Chrom lens can be made of both PMMA or hefilcon material.
have been dyed with a single color. Cheaper to produce Blurred vision and reduced stereopsis complicate its wear.71
than multicolor opaque lenses, such lenses enhance color Achromats can also benefit from wearing a red-tinted soft
or change a light iris to a darker shade. Since, the natural lens in each eye. Such a lens increases the achromat’s ability to
discriminate objects from one another by brightening the red- Contact Lenses for up to 30 Days Continuous Wear in the United
colored objects while darkening the blue or green colored objects States. Eye Contact Lens 2010 Aug 10. [Epub ahead of print].
10. Saltarelli DP. Hyper oxygen-permeable rigid contact lenses as an
but is not very beneficial in natural environmental conditions.71
alternative for the treatment of pediatric aphakia. Eye Contact
Lens 2008;34:84-93.
For Amblyopia
11. Keay L, Stapleton F. Development and evaluation of evidence-
Occlusion therapy is the cornerstone of amblyopia. However, based guidelines on contact lens-related microbial keratitis. Cont
it is easier said than practiced as children resent and resist the Lens Anterior Eye 2008;31:3-12. Epub 2007 Nov 26.
placement of a occluding patch or frosted glass over their 12. Chalmers RL, McNally JJ, Schein OD, Katz J, Tielsch JM, Alfonso
E, et al. Risk factors for corneal infiltrates with continuous wear
seeing eye. In such situations when conventional patching fails
of contact lenses. Optom Vis Sci 2007;84:573-9.
another way to penalizing the better eye is using an opaque/ 13. Epstein RJ, Fernandes A, Stulting RD, Wright JD, Tigges MH,
dark contact to replace occlusion.72 In these cases it is advisable Gammon JA. Extended-wear contact lens correction of aphakia
to make the iris portion larger than the HVID of the fellow in infant primates. Corneal studies. Ophthalmology 1986;93(12):
eye, otherwise movement of the lens allows chinks of light 1495-501.
into the occluded eye. A soft lens with a complete opaque iris 14. Kuckelkorn R, Bertram B, Redbrake C, Reim M. Therapeutic
hydrophilic bandage lenses after perforating keratoplasty in severe
and pupil are employed. Such a lens is more comfortable than
eye chemical burns. Klin Monbl Augenheilkd 1995;207(2):95-101.
the adhesive patch on the skin and is also difficult to dislodge 15. Rosenthal P, Cotter JM, Baum J. Treatment of persistent corneal
accidentally or remove intentionally, thereby improving the epithelial defect with extended wear of a fluid-ventilated gas-
level of compliance. Another option is using a non-tinted soft permeable scleral contact lens. Am J Ophthalmol 2000;130(1):33-
lens in a relatively high plus power as a reasonably effective 41.
occlusive effect with less effort and at a lower cost. Such an 16. Foulks GN. The management of recurrent corneal erosions.
Seminal Ophthalmol 1991;6:114-21.
approach to “occlusion” uses defocus for its effect while
17. Foulks GN, Harvey T, Sunder Raj CV. Therapeutic contact lenses:
retaining light perception and some degree of peripheral vision the role of high Dk lenses. Ophthalmic Clinics North America
during the treatment periods. 2003;16:455-61.
18. Arora R, Gupta S, Taneja M, Raina UK, Mehta DK. Disposable
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Zloty P, et al. Over-the-counter decorative contact lenses: Cosmetic Jul 2.
3.2.3 Contact Lens Fitting in Special Situations
DRY EYES AND THE CONTACT LENS

Contact lens wearers are subject to an increased risk of dry eye
syndrome (DES) and the factors responsible are increased tear
evaporation, reduced blinking and altered ocular surface
environment.1-3 Incomplete blinking contributes to the lid wiper
epitheliopathy causing excessive evaporation. This leads to lens
surface drying and formation of lens deposits. An incomplete
blink doubles the inter blink interval and tear evaporation time
for inferior cornea or contact lens. Inadequate aqueous, mucous
and lipid distribution, as well as tear thinning over the exposed
ocular or contact lens surface further increases the rate and
significance of tear break-up and evaporation following an
incomplete blink. Increased tear osmolarity that is associated
with accelerated tear evaporation contributes to tissue changes Fig. 3.2.3.1: A soft hydrogel after 6 months of wear in a bank
and symptoms. This dryness increases with the duration of employee involved in excessive computer work. Note the dry spots
lens wear which may partly be explained by decrease in the appearing on lens surface immediately after a blink
number of functional meibomian glands.4,5
The oxygen permeability of conventional hydrogel lenses • Patient related: Blink efficiency and rate, wearing time, work
is proportional to their water content and inversely profile relating to intentness of visual tasks and age.
proportional to their central thickness. Dehydration of lens Reduced blinking characteristic of people engaged in near
alters the hydration profile of soft lens. This altered hydration or distance visual tasks requiring concentration decreases
changes the lens parameters and subsequently its fitting, visual blink rate, increases tear evaporation by widening exposed
performance and patient comfort. In conditions where ocular surface area. Thus dryness is exacerbated after such
blinking is restricted due to concentrated visual work, such as tasks, e.g. after intense reading.6-9
visual display terminal work, reading and driving, visual • Computer usage in cramped, poorly ventilated environ-
performance is further compromised due to excessive ment causes decreased blinking and lens dehydration.7
evaporation.6 Dry spots may be seen on the lens in a soft • Tear related: Pre-existing dry eye due to poor tear quality
contact lens wearer with poor blinking practices (Fig. 3.2.3.1). and quantity. A higher water content lens may be
detrimental in an eye predisposed to dry eye condition
Factors Contributing to
since the “steal phenomenon” draws water out of the high
“On Eye Drying” of Lenses
water content lens. In addition, they further compromise
• Environment related: Temperature, humidity, and wind the tear film.10 This, in turn, causes greater lens adherence,
speed.7 reduced oxygen transmissibility, and reduced tear exchange
130 Contact Lens
as demonstrated by the Contact Lens and Dry Eye Study

(CLADES) study.11
Sometimes changing the lens type to silicone hydrogels
like hioxifilcon A or omafilcon A material or using a lower
water content lenses may help.12,13
Treatment involves improving blink efficiency with
concomitant lubricant drop instillation. Ocular discomfort and
dryness are amongst the most common reasons for contact
lens dissatisfaction and discontinuation. Thus, symptoms of
dry eye must be treated with utmost urgency and care.14
CONTACT LENS FITTING IN

KERATOCONUS Fig. 3.2.3.2: Corneal topography of a keratoconus patient
depicting a nipple cone with inferior decentration
Keratoconus is a condition with non-inflammatory ectasia of
the cornea, seen during adolescent period. It has been found
to occur more frequently and at an earlier age in patients of
Asian origin.15,16 It causes visual loss due to regular astigmatism
in early stages, which is correctable by spectacles. In moderate
and advanced stages, it causes profound visual loss due to
irregular astigmatism and requires contact lens for visual
rehabilitation.17,18 A good contact lens fit not only gives stable
and comfortable vision to these young people but also averts
the need for keratoplasty.19 Lenses are often required after
keratoplasty to correct the residual astigmatism. Afflicted
adolescents are often involved in intensive rigorous study and
deciding professional careers, thus a well-fitting lens at this
crucial time of their life helps in shaping these young
Fig. 3.2.3.3: Corneal topography of a keratoconus patient
individuals life and personality.20-23
depicting a centrally located nipple cone
Keratoconus cases may present with three main types of
cones which determine CL fit:
• Nipple cones which have a small diameter and a short radius
of curvature. These cones are located centrally or para-
centrally and often have an infero-nasal decentration
(Figs 3.2.3.2 and 3.2.3.3).
• Oval/sagging cones have a larger base diameter and are often
located in inferotemporal quadrant.
• Globus cones are less common and involve almost 2/3rd of
cornea.
The latter two types are more difficult to fit with CL.
Corneal topography reveals asymmetric, bowtie patterns
with skewed radial axes (Srax) accompanied commonly with
inferior steepening (Fig. 3.2.3.2).
Rigid gas permeable are the lenses of choice as they
neutralize the irregular astigmatism with new, regular, ‘anterior’ Fig. 3.2.3.4: Note the inferiorly decentered lens in a case of
optical surface, however they must be centered without advanced keratoconus post healed hydrops
traumatizing the apex of cone.24 Lenses always gravitate to
the steeper part of cornea which is most often in the inferior and are prone to decentration (Figs 3.2.3.4 and 3.2.3.5).
part, thus these inferiorly positioning lenses cause discomfort Specially designed lenses align to the flatter superior cornea,
demonstrate feather apical touch, mid-peripheral bearing with

sufficient edge lift and clearance (0.5- 0.7 mm).27 Usually three
to four back curves are necessary to conform to the rapid
flattening of the cornea in the mid-periphery and the periphery.
To prevent seal-off and lens adherence, outer peripheral curves
of the conus lenses are made flatter and wider. Lens movement
is evaluated with blinking movements and should be
approximately 1 mm with each blink.
The three different fitting philosophies are:
a. Apical bearing/touch: In this, (Figs 3.2.3.6A and B) the
lens bears heavily against the apex of the cone, thus is
more liable to cause corneal scarring.28 Flat fitting
lenses cause bearing, resulting in abrasions, epithelial
breakdown and lens intolerance. However this fitting
Fig. 3.2.3.5: Fluorescein fit in an inferior positioned lens depicting

excessive central cone bearing, insufficient edge clearance. Such
a fit is unacceptable
redistribute pressure over peripheral cornea and prevent cone

compression. Such designs incorporate a rapidly flattening
periphery, with central steep curvature lenses, e.g. Rose K
lenses.
Fitting Principles and Philosophies

In moderate to advanced conus where keratometry may not
be feasible, video topography provides Sim K values, and helps
in selecting the base curve of the first trial lens.25,26 The trial
A
lens is preferably chosen from a diagnostic keratoconic trial
set in the same material as final lens. The keratoconic set comes
in base curves of 5.5 to 7.0 or till 7.65 as per CLEK guide-
lines, powers of -3D and -6D with overall diameters ranging
from 8.7 mm to 9.6 mm. A suitable starting point is to choose
a lens with a BOZR that approximates the midpoint of the apical
keratometric or topography values. The CLEK nomogram dictates
using 2 diopters flatter than K (K= flattest axis) for 45.0 to
50.0 Diopters, 3 diopters flatter than K for 50-55 D, and 4
diopters flatter than K for 55-60 diopters.26 First trial lens
diameter should be kept small, a suitable starting point is
8.70 mm OD. In cases where it is more desirable to fit a lens
with a smaller TD and BOZD, it is appropriate to start with a
BOZR 0.2 mm steeper than the mean keratometry (or
videokeratoscopy) reading. Round nipple cones require
diameters of 8.5 to 9.0 mm whereas oval cones require larger B
diameter lenses ranging from 9.2 to 9.7 mm. Fitting is then Figs 3.2.3.6A and B: Fluorescein fit demonstrating apical touch
assessed with fluorescein pattern. An ideal pattern should in central and superior area
132 Contact Lens
visual axis, as a result of which the pupil is only partly

covered by optic zone transition leading to poor vision.
The small diameter can also contribute to glare and/
or monocular diplopia, especially at night when the
pupil dilates. The plus tear lens resulting from an apical
clearance fit necessitates a more minus contact lens
back vertex power (BVP) and greater junction
thicknesses at the edge of the optic zone which causes
more discomfort. A lens-to-cornea adherence or
peripheral ‘seal-off ’ resulting in a stagnant post-lens
tear film must be avoided by monitoring the fluorescein
pattern.
c. Three-point touch: In this the lens rests lightly against the
cone apex and is supported on the nasal and temporal
corneal zones by the mid-periphery of its back surface
(Fig. 3.2.3.9). The prototype is the Rose K lens. Thus
Fig. 3.2.3.7: Fluorescein pattern depicting apical clearance over
the inferior nipple cone lens weight is distributed over a larger area, ‘divided
support’. An apical contact area of 2 to 3 mm (minimal
feather touch) is surrounded by intermediate clearance
zone (paracentral fluorescein ring), mid-peripheral
contact annulus, and edge clearance at periphery (bull’s
eye pattern). This fit gives rise to stable vision, comfort
and increased lens tolerance and is the preferred fit.
The degree of edge lift achieved with an RGP lens on a
keratoconic cornea is almost as important as determining the
central curve. When the peripheral curves are too steep, lens
movement is restricted and there is an inadequate tear reservoir.
This leads to tight fit, lens adherence and discomfort.30 On
the other hand, flat peripheral curves result in excessive edge
lift with resultant excessive lens movement and repeated lens
Fig. 3.2.3.8: The small diameter lens with apical clearance

centers well on the eye
yields good vision, possibly due to corneal reshaping

(regularizing) and/or masking of irregular astigmatism.
b. Apical clearance: Here the lens back surface vaults (clears)
the cone apex (Figs 3.2.3.7 and 3.2.3.8). Lens support
is redirected to the paracentral cornea, thus risk of
apical scarring is reduced. Some reports state that this
fitting may accelerate progression of the ectasia.29 This
fit often results in variable vision due to uncorrected
corneal astigmatism. The lens used has steep back optic
zone radius (BOZR), small back optic zone diameter
(BOZD) and small total diameter (TD). These small
lenses center on the cone, which is often not on the Fig. 3.2.3.9: Three-point touch in a nipple cone (Ideal fit)
Special Lenses for Keratoconus

• Multicurve spherical lenses: These have central spherical steep
curve in the optical center followed by multiple progres-
sively flatter curves in non-optical periphery. An aspheric
lens on the other hand has a continuous posterior radius
of curvature defined by geometric shape rather than conti-
nuation of progressively flatter spherical base curves.24
• Rose K lenses: These lenses, designed by Paul Rose have a
small posterior optic zone and three peripheral lens
clearances to help minimize superior corneal
impingement.32-34 Three types of fitting sets are provided
for keratoconus; K2 series (which has an aspheric back
surface with aberration free curves in front of lens), IC
set and PK set. The base curve in K2 set ranges from 5.1
to 7.6 and they work best for nipple and large oval cones.
Fig. 3.2.3.10: Axial edge lift from 2 to 6 o'clock position causes The set is provided in a standard edge lift design which is
excessive lens excursion and displacement adequate for 70 percent cases. After assessing the peripheral
fit, the fitter can order for a 20 percent increased or 10
percent decreased edge lift design. The optimum
dislodgement along with lid irritation. The ophthalmologist
fluorescein band at the periphery is 0.6 to 0.8 mm wide.
must ensure adequate lens movement with each blink to
Due to unequal corneal flattening, the edge lift may be
prevent lens adherence and/or 3 and 9 o’clock staining.
different in the nasal and the temporal horizontal
Adequate tear exchange is a must to maintain corneal
meridians. The lens is recommended to be fitted in the
homeostasis. If peripheral curves are too steep, lens movement following steps:
is restricted leading to lens adherence. Conversely, flat steep
– Evaluate for central fit: For a mean K of 7.1 or flatter,
peripheral curves cause excessive edge lift, excessive lens first trial lens selected is 0.2 steeper than average. For
movement, displaced lenses and lid irritation (Fig. 3.2.3.10).
a mean K between 6.0 to 7.0, the trial lens is based on
an average K. For steeper corneas with an average K
Relevant Facts to Contact Lens
of 5.9 or steeper, the trial lens selected is 0.4 flatter
Fitting in Keratoconus
than the average K. The strategy is to fit the CL steeper
• Lid: Many patients have associated atopy with lid and then modify based on fluorescein pattern. Apical
thickening, blepharitis, misdirected lashes which need to staining needs to be avoided to prevent scarring. If
be treated. Lax lids would require large diameter lenses apical staining is seen, a lens with steeper BC is fitted.
whereas tight lids mandate small diameter lenses to avoid Fitting must always be checked with the patient looking
lid awareness. straight ahead.
• Cone type and presence of hydrops: Nipple round cones are – Evaluate peripheral fit/edge lift: Trial is done with standard
easiest to fit and oval cones are more prone to develop edge lift. In case of tight fit, an increased edge lift has to
corneal hydrops. Subsequent scarring after resolved attack be ordered. Edge lift increments come in 0.1 steps, with
of hydrops may flatten the apex and make contact lens a maximum increase of 1.3. A tight lens digs into cornea
fitting easier. and causes lens intolerance. Peripheral fit is the single
• Lens material: RGP material should have high oxygen most important factor for comfortable RGP lens fit.
transmissibility (Dk/t of 60 -100+) with proven shape – Assess lens diameter: The commonest diameter used is
stability and show minimal flexure or warpage. Most of 8.7 mm (range 7.8-10.4 mm). The diameter is chosen
contact lenses used for keratoconus have high minus so that the upper lid margin and lens edge just touch.
powers with thin center and thick edges. Larger diameters are preferred for steeper cones, larger
• Ocular lubricants: Concomitant use of tear supplements palpebral aperture and for pellucid marginal degene-
greatly enhances comfort with contact lens in keratoconus ration to ensure centration and stability. As diameter
patients.31 of the lens increases the base curve flattens.
134 Contact Lens
– Evaluate location of lens: This is controlled by overall piece lens, is not a bonding of two disparate materials
diameter and edge lift. Low riding lenses settling into a lens but has properties of differing phases of the
beyond the limbus would cause discomfort and ghost same lens material.38 The lens movement must be to the
images. The modification required is to increase the tune of 0.2 mm, assessed by exerting manual pressure over
OD, increase edge lift or flatten the BC. the lid. It must be evaluated after 2 to 3 weeks of wear to
– Assess lens movement: A 1-2 mm movement with each rule out a peripheral seal off. Prototype lens is the SoftPerm
blink is ideal and necessary for tear exchange. The lens (based on the historical Saturn and Saturn II hybrid
after moving during blinking should return to its lenses).39 The low Dk material results in poor oxygen
original position of rest. Limited movement causes transmissibility, endothelial cell loss, handling difficulties,
peripheral corneal drying and staining. Flatter, smaller edge pucker, a tendency to tear or split at soft-rigid junction,
lenses and those with increased edge lift undergo more and high replacement costs.40
movement. • Aspheric lenses: These are recommended for those patients
– Bubbles under lens: If bubbles are seen, the lens needs to who develop staining, recurrent erosions with multicurve
have flatter BC, increased EL or decrease in overall lenses. They can be fitted slightly steeper than conventional
diameter. lenses without changing the sagittal depth of the lens.
• Soper lens: This is a bicurve lens design with steep optical • Scleral lens: These large (13.5 mm TD) lenses may be the
portion and second flatter curve. The carrier width is only option in advanced keratoconus especially for inferior
2 mm. decentered cones, where corneal lenses of any reasonable
• McGuire design: This incorporates central step curve with diameter would not provide positional stability, e.g. RGP
four additional progressively flatter peripheral curves.35 EpiCon LC, Boston lens.41,42
These multicurve lens designs fit round nipple cones • Toric lenses: Toric soft CL may be tried in RGP intolerant
patients. They provide adequate visual correction in the
very well. However, all these lenses need a separate trial
early stages of keratoconus. Toric siloxane hydrogel and
inventory set and the final fit must be evaluated by
reverse geometry lenses have also been used.43
fluorescein pattern.
Contact lens fitting in keratoconus is time consuming but
• Piggyback lenses: This system uses two separate lenses, a large
can provide adequate visual rehabilitation in almost 70 to 90
diameter (upto 16 mm), soft lenses with an anterior RGP
percent of patients. 44,45 Often with maximum effort,
of smallest vault.36,37 Some systems have built in recessed
suboptimal vision and comfort are achieved. Patient motivation
compartment into the anterior surface of the soft lens into
is thus mandatory to achieve compliance.46 The lens is still
which the RGP lens tucks in. Edge lift and air bubble
required after corneal surgery or reshaping with C3R
capturing is prevented by choosing a RGP with a small vault. technology to maintain visual clarity or achieve binocular
The carrier soft lens is either ultra-thin which drapes over balance.47 This information when given to patients help them
the cone or a high plus lens which provides more bulk/ make realistic decisions regarding keratoplasty and motivates
rigidity to hold the RGP lens. A siloxane hydrogel them to adapt to lens wear. A functional end point needs to
combination is the best option. With piggyback lenses, be reached where comfort is finely balanced with the visual
centration and comfort are ensured but at the cost of needs of the patient.
intersurface deposits, corneal neovascularization, cleaning
difficulties with expense and inconvenience of double lens Complications
systems. The SCL is fitted first and its adequate movement • Fluctuating vision occurs due to decentration of lens, lens
is assessed. Subsequently keratometry needs to be done with flexure or warpage, progression of the conus and
the SCL in situ. The high Dk RGP lens is fitted over the soft occurrence of presbyopia.
lens. It should center well and move independently. Fit must • Corneal staining at the apex of cone is common.
be evaluated with high molecular weight fluorescein (normal Examination of keratoconus patients should be done after
sodium fluorescein will stain SCL). If lens binding occurs, asking the patient to report after 6 to 8 hours of wear so
the wearing time decreases. The lens BC then needs to be that the fitter can assess the extent of corneal impingement.
flattened or edge lift increased. Excessive or symptomatic staining requires re-edging with
• Hybrid lens: This has a rigid 6 mm central optical portion.20 increased peripheral blending.
The large diameter skirt provides good centration whereas • Lens adhesion is commonly seen in inferior cones with
central RGP portion provides clarity of vision. This one low riding lenses which demonstrate limbal compression
with minimal injection. The remedy is to refit them with Time of Fitting
steeper, smaller lenses which are anchored by the upper
Normally lenses are fitted after sufficient time has been allowed
lid.
for healing and after suture removal which is usually 1 year or
• Ocular surface changes manifesting as decrease in goblet
more after graft.50 After removal of the continuous suture,
cell densities and tear break up time have been documented
refraction and keratometry is repeated till stability is achieved,
after many years of CL wear.48
following which lens fitting can be commenced. Only in some
• Accelerated corneal endothelial cell loss has been
situations like pediatric aphakia, lens fitting is done before suture
documented in keratoconus patients wearing contact
removal to prevent the development of amblyopia. However,
lenses, more with soft lens wear than RGP lenses.40,49
this must be attempted only if stringent follow-up can be ensured
so as to pick up any graft infection or rejection, both of which
CONTACT LENS FITTING IN
can occur when a lens is placed over corneal sutures. Ongoing
POST-KERATOPLASTY EYES
host graft junction healing may necessitate a lens change, thus
Despite improved success rate for clear corneal grafts after the patient must be warned that frequent change of lens is to
penetrating keratoplasty, induced surgical astigmatism due to a be expected in the initial 1 to 2 years post graft.
significant curvature change at the donor-host junction is the
commonest bug bear causing visual impairment. This Types of Lenses
astigmatism depends on suturing technique, uniformity of suture Lenses with high oxygen permeability only should be fitted.
tension and graft size. Normal donor host discrepancy is 0.5 The different types of lenses which have been successfully
mm, where donor graft is cut 0.5 mm larger than the recipient. fitted on post-graft patients are the following:
A larger than 0.5 mm difference graft placed into a small bed • RGP lens: They are the preferred because of superior
results in steeper corneal graft topography (since donor tissue optics in cases of irregular astigmatism exceeding 3 to
steepens to reduce the ‘skirt’ diameter in order to match the 4 D, which is the common scenario in post-keratoplasty
trephine size used on the host). In addition eccentric positioning cases and because they disturb corneal physiology the
of graft contributes to irregular astigmatism. least.51-53 For larger grafts, small diameter lenses with
steep base curves can be used. However, for smaller
Indications for Contact Lens grafts, a larger RGP lens with the BOZD extending
• Irregular surgical astigmatism is due to uneven wound across both the host and donor corneas might prove to
healing at graft host interface, unequal suture tension, be more suitable. Sometimes, very large diameter lens
scarring either preexisting or as a sequel of graft. only are able to center adequately (Figs 3.2.3.11A and
• Anisometropia—spherical and astigmatic.50 B).47,54,55 Peripheral curves of these multicurve lenses
• Aphakia or high myopia. need to be custom made.52,55
Figs 3.2.3.11A and B: (A) A larger diameter 9.6 mm RGP lens over a graft. Note the adequate edge clearance;
(B) The topographic picture depicting irregular astigmatism
136 Contact Lens
The trial lens is selected on flat K if astigmatism is less pulled up by the upper lid. The remedy is to fit a larger or
than 5 D, using a minimum diameter of 9.0 mm. For astig- steeper lens which would also rectify any inferior edge standoff.
matism greater than 5 D, base curve of trial lens should be A lens with poor movement needs to be substituted with a
steeper than flat K, using a minimum 8.5-9.0 m diameter.56 flatter/smaller lens. Reduced corneal sensitivity makes pain
• Hydrogel or silicone hydrogel lens: These lenses are indicated in an unreliable watchdog in graft fits, thus more frequent follow
special situations like post keratoglobus graft, RGP ups are warranted.
instability/intolerance.57 If a lens must be fitted with Trial RGP lens assessment evaluates both static and
sutures in situ, then a thin soft lens may be the best option dynamic fitting and fluorescein pattern. This would disclose
as it will drape over the raised graft-host junction and not areas of excessive clearance or bearing in the irregular cornea.
cause excessive rubbing or discomfort. A slightly thicker Bearing pressure on the peripheral cornea is the key factor to
soft lens may provide a more stable fitting and better visual achieve a successful fit. Ideally, there should be adequate
performance. However, the low oxygen transmissibility of bearing along the horizontal corneal meridian to provide lens
conventional hydrogel contact lenses can result in corneal stability. With the rule astigmatism is generally easier to fit than
edema and peripheral corneal vascularization. The growth against the rule or oblique astigmatism. The well-fitting lens
of blood vessels into the graft can precipitate a rejection should move at least 2 to 3 mm post blink and must center well.
episode. Siloxane hydrogels by virtue of their relative Since graft host topography influences lens fitting
rigidity provide a stable fit and have excellent oxygen dramatically, knowledge of some common types of topo-
transmission, but they can cause elevated bearing pressures graphy is essential.
on a proud graft host junction. a. Proud graft topography: A proud graft is more likely in grafted
• Extended wear soft contact lenses: These are used mainly for keratoconus where host cornea thickness is less than the
aphakics who have undergone keratoplasty. A 3 monthly donor button. The raised step at the host-graft interface
follow-up is warranted to check for any corneal neo- causes an RGP lens to ski off the graft when displaced by
vascularization, graft rejection and microbial keratitis.58 the lid during a blink (Fig. 3.2.3.12A). To circumvent this,
Grafted patients have depressed corneal sensitivity for large diameter lenses can be used (Fig. 3.2.3.12B).
some time. Thus, the warning symptom of pain in b. Flat or sunken graft: This is seen when the graft and the
infective keratitis maybe muted for such patients. Piggyback recipient bed are of the same size. An RGP lens vaults the
contact lens combination is a risky proposition since the area of the graft and result in bubble formation if excessive
combined thickness of soft-RGP lens combo causes pooling is present (Fig. 3.2.3.13). Lens fenestration would
reduced oxygen transmissibility. allow trapped air egress from the post-lens tear film.
• Rose K lenses and reverse geometry lenses: These lenses center c. Plateau graft topography: In this situation reverse geometry
much better than the conventional RGP lenses, however design works better as a spherical lens design result in
cost is a limiting factor. The post-keratoplasty set of Rose significant apical and peripheral edge clearance.
K lenses is used in such situations.59 d. Tilted graft topography: Tilt occurs due to variations in the
• Scleral lenses: Often used as the last resort, they ensure stable host or graft margin thickness or to variations in the suture
‘on-eye’ fitting providing optimum centration and good depth between graft and host. A large RGP lens in this
vision. In addition the lenses are durable, easy to handle case causes a localized gutter over the recessed graft region
and maintain. Cost and availability are the major limiting and may produce persistent bubbles in this region.
factor.60
Problems
Fitting Philosophies and Modifications • Corneal neovascularization (Fig. 3.2.3.14).62
• Transitory punctate epithelial keratitis.58
Corneal topography is a very useful tool as it locates the high • Suture infiltrates and graft infection.
point of graft host junction, which can be used as the fulcrum • Graft rejection or failure especially once an inflammatory
to hold lens in position.61 Keratometry is often an unreliable episode is triggered. Treatment is with temporary cessation
guide in these distorted corneas. of contact lens wear and refitting with higher Dk lens.
Lens decentration is a common phenomenon in graft fits. • Monocular diplopia and flare for decentered grafts since
The common cause is a proud graft (steeper and protruding the RGP lens tends to position on the decentered graft
from host cornea). One treatable cause of a proud graft is zone. These cases maybe benefitted by a piggyback lens
tight sutures.62 Decentered lenses ride high as they get easily system.
Fig. 3.2.3.14: Note the neovascularization at 11 o'clock position,

beneath the lens on a post graft patient
• Large RGP lenses often have handling difficulties and give

rise to inadequate lens movement or bubbles near the graft
junction (excessive pooling under the lens in this region),
which maybe treated with fenestrations.
• Fluctuating vision due to lens decentration.
• Lens intolerance.
B
Figs 3.2.3.12A and B: (A) Lens gets ejected out of the eye after Special Considerations
blink in a case with proud graft junction; (B) Solution is to use a
• Presence of blood vessels near graft interface prior to
large diameter lens
fitting a lens should be ruled out.
• Only lenses which supply maximum oxygen should be used
to minimize the risk of graft vascularization.
• Heavy bearing on the graft-host interface should be
minimized,
• Only high oxygen transmissibility RGP materials must be
used.
Follow-up is done fortnightly for a month, then 3
monthly followed by yearly check ups. The regimen is tighter
for children. Topical steroid and anti-glaucoma medications
can be continued provided they are not used when a soft
lens is in situ. Lenses become tighter and move less with
time.54
CONTACT LENS FITTING IN APHAKIA

Aphakic spectacles with their inherent optical effects of
differences in image size, magnification and prismatic effects
Fig. 3.2.3.13: Air bubbles trapped beneath a RGP do not allow them to be a viable option in unilateral aphakia.
lens over a flat host graft junction The placement of a plus (convex) lens positioned anterior to
138 Contact Lens
illnesses such as diabetes or arthritis and loss of manual

dexterity make lens maintenance arduous.
• Loss of filtering effect of crystalline lens exposes the retina
to ultraviolet radiation.
• Children often develop exotropia after advent of
monocular aphakia as binocularity is interrupted, however
with visual rehabilitation of aphakia it often resolves on
its own under the incentive of diplopia.
CONTACT LENSES FOR CHILDREN

Contact lens aided visual correction of aphakic children and
infants permits a more normal development of vision, 15
Fig. 3.2.3.15: Heavy convex glasses in a child percent wider field of view and better motor and perceptual
with bilateral aphakia skills compared with spectacles. Contact lens rehabilitation
of the aphakic child enables retention of binocularity albeit
less than that with the use of intraocular lens implantation.66,67
the crystalline lens position and cornea creates a Galilean In the very young, spectacle wear may be difficult due to
telescope, thus leading to magnification of images. With contact absence of a prominent nose bridge and propensity of the
lens rehabilitation this magnification is minimal (5-7%), whereas child to break/discard glasses. To prevent amblyopia, contact
for spectacles it is 25 to 35 percent. The image disparity between lenses are fitted early on in the post-surgical period (within a
two eyes with monocular aphakic spectacles causes peripheral fortnight to a month), provided there is no significant ocular
aberrations like pincushion effect (where the magnification inflammation64,68,69 (Fig. 3.2.3.16).
increases from lens center to edge), prismatic effects ( jack-in-
the-box effect due to base in prism effect of high plus lenses). Facts about Pediatric Eye
In addition aphakic spectacles cause a 30 percent restriction of • Axial length of infant eyeball is 17 mm versus 24 mm in
visual fields leading to a ring scotoma. In monocular aphakia, adult.
the aniseikonia problems with binocular fusion usually result in • Corneal diameter at birth is 10.0 mm and by 1 year it
diplopia. The weight of high plus spectacles on the bridge of reaches the adult size of 11.6 mm.
the nose (even in lightweight, high index materials) is another • Corneal radius at birth is around 7.0 mm and gradually
hindrance (Fig. 3.2.3.15). Contact lenses overcome these flattens to the adult size of 7.86 mm by 10 years.
problems and achieve aphakic correction especially in a pediatric
and monocular aphakia.63,64
Physiological Alterations in the Aphakic

Eye Relevant to Contact Lens Fitting
• Reduced epithelial oxygen uptake and consumption due
to denervation induced reduction in metabolic activity.
• Decreased corneal sensitivity—ensures faster adaptation
to CL wear, however warning symptoms of pain due to
infective keratitis may be delayed.
• Reduced endothelial cell density.65
• Lower corneal edema response to contact lens since oxygen
availability is increased due to absence of crystalline lens,
as well as corneal denervation which reduces the
epithelium’s oxygen consumption.
• Elderly aphakes have a lower corneal basal metabolic rate,
decreased tear production, lax upper lid tone and senile Fig. 3.2.3.16: An aphakic soft lens in a child with megalocornea
ptosis. Concomitant degenerative conditions, systemic and operated cataract
• Newborn refractive error is moderately hyperopic with

slight astigmatic component.
• Accordingly, the lens total diameter, base vertex power and
radius of curvature must be altered to maintain optimum
lens-cornea fitting relationship.
• Small palpebral aperture with tight lids makes insertion
of CL difficult in a child. Incessant crying and straining
worsen the problem. Manually trying to open lids by force
causes lid eversion. Thus it is better to wait until the child
is asleep, or use a pacifier while inserting lenses.
• Infants have higher tear aqueous component which aids
in tolerating a contact lens.
Indications for Pediatric Contact Lenses

• Aphakia especially uniocular.64,67 A
• High myopía/ hypermetropia and unilateral ametropia. In high
myopia, lenses provide a larger field and more normal
image size than spectacles and in hypermetropia accommo-
dative and convergence demand is less than with spectacles.
In high minus power lenses, the lens may ride high due to
the upper lid grasping the thicker lens edge, i.e. lid
attachment. In such cases, a larger lens diameter may be
required to ensure adequate pupil coverage.
• Anisometropia: Contact lens visual rehabilitation needs to
be combined with occlusion therapy to treat amblyopia.
Sometimes special tinted lenses may be used as an
alternative method of occlusion.
• High astigmatism may be corrected with lenses to minimize
risk of meridional amblyopia.
• Irregular astigmatism, e.g. post-traumatic corneal scarring.
B
• Special conditions like albinism, dislocated lenses,70 aphakia
with penetrating keratoplasty.71 Figs 3.2.3.17A and B: Aphakic hydrogel lens in post-trauma and
post-congenital cataract surgery cases
Types of Lenses Used

changes rapidly over the first two years of life. Hydrogels
• Soft Hydrogels: These lenses are easy to fit, have better have a tendency to dehydrate on the eye and aggravate
tolerability and are the preferred modality in aphakics with dry-eye by causing “steal phenomenon” (absorb water from
low astigmatism or failed RGP lens wearers. High water tears to maintain their shape). They also get discolored
content (70-80%) lenses are used as they translate into with the use of topical medications. Risk of corneal
better oxygen transmission since infants sleep or are decompensation and neovascularization is significant
subjected to closed eye condition for most of the day. An especially in a previously compromised cornea as in post-
ultraviolet blocker also needs to be incorporated in these vitrectomy eyes and glaucoma associated with aphakia.
lenses. They are fitted on the average K reading and are Lubricating drops need to be used with these lenses in situ,
2 mm larger than horizontal visible iris diameter as they often get stuck-on after a period of napping.
(Figs 3.2.3.17A and B).72 Such lenses are fragile, deposit • Silicone elastomer: They are made of a copolymer of silicone
damage prone and require frequent replacement. combined with conventional hydrogel monomers
Meticulous cleaning is essential to decrease risk of infection (balafilcon A., lotrafilcon A). These lenses are treated in
and frequent dioptric changes are required as power gas plasma reactive chamber to create an ultrathin 25 μ
140 Contact Lens
thick coating, which makes the hydrophobic lens

biocompatible. These durable, easily handled lenses are
ideal for an infant and have high oxygen permeability (340
× 10–11 cm2 ml O2/sec. ml mm Hg) and relatively small
overall diameter of 11.5 mm.68,73 These lenses are more
rigid, easier to handle and more difficult to be rubbed out
of the eye. The surface coating of the inherent hydrophobic
material makes them prone to deposit formation, scratches
and damage to the coating resulting in loss of lens wettability
and intolerance. They may adhere to the cornea so they
are fitted 0.40 to 0.60 mm flatter than the K to create an
edge lift and to reduce the risk of “sucked on” lens
syndrome.72,73 The fit is evaluated by movements and the
Fig. 3.2.3.19: A well-centered RGP lens on an aphakic child.

Note the good followability of lens on up-gaze
digital push up test (Figs 3.2.3.18A and B). It is important

to evaluate the fit after 1 hour of wear since the lens
tightens in situ on the eye. Lens removal can be difficult
due to greater capillary attraction between the eye and
silicone. These lenses need to be replaced every 3 to 6
months, are expensive and not easily available.
• RGP: The clarity of vision is better with this lens and by
allowing adequate tear exchange it results in a better
physiological environment for cornea, e.g. Menicon Z
material.74-76 The advantage of good oxygen transmission
A is negated by the weight of the high plus lens which makes
it uncomfortable for the patient. The lens often rides
low, causes lid irritation and is more easily dislodged from
the eye. These lenses are a fit steeper than the flattest K
(Fig. 3.2.3.19).74,75 They are easy to handle and have less
propensity for causing infective keratitis or protein
adherence. They are best suited for traumatic aphakes
with corneal scars and high corneal astigmatism and
corneal distortion (Figs 3.2.3.20A and B). Fitting of lenses
in larger diameters of 9.4 to 9.8 mm helps to improve
centration.
• Extended wear lenses: They are an option in pediatric or
geriatric aphake if there are problems with lens handling,
insertion and removal of soft lenses. Wearing schedule
must be monitored to ensure that after 6 consecutive
nights of lens wear, lenses are thoroughly cleaned and
B disinfected during 1 night of no-lens wear. These lenses
are to be used with considerable caution, with disposable
Figs 3.2.3.18A and B: On up-gaze or with push-up the lens is
displaced and remains decentered on primary gaze lenses, frequently replaceable lenses being a safer option.
diameter (9.0-10.5 mm) is often resorted to. Materials used

are siloxane acrylate or fluoro-siloxane-acrylate. A UV light
blocker addition must be incorporated into the material to
compensate for the loss of crystalline lens filter.
Fitting and Follow-up Protocol

• Refraction for children is done under strong cycloplegics
except for aphakics. In aphakic children, due to lack of
accommodative mechanism pure mydriatics suffice for
refraction.
• Corneal curvature is measured by hand-held keratometers.
Central corneal curvature of infants is usually steep ranging
from 47-50 D (7.18-6.75 mm) in the first 1 to 2 months.
By 3 to 4 years of age, the cornea flattens to 43.0-44.0 D
(7.85-7.67 mm), except in cases of retinopathy of
prematurity, where the value remains steep.
• Corneal diameter is measured by HVID with a hand-held
rule. Soft hydrogel lenses are fitted 2 to 2.5 mm larger
than HVID.
• The child is soothed with pacifier or feeding bottle. For
infants or toddlers, one to two people (parents) hold the
child’s arms and shoulders down, while the fitter pulls the
lids apart and inserts the lens. Small children may be
wrapped in a towel or blanket.
• Over-refraction: The trial lenses need to be kept close to
the child’s eye to minimize the risk of prescribing an
incorrect contact lens BVP due to the high plus prescrip-
tion involved. Back vertex power comes into effect more
for high powers. Compensation for the vertex distance is
a must while ordering the lens. The following table gives
Figs 3.2.3.20A and B: RGP lens in post-traumatic aphakia with an approximate estimation of the base curve and back
peripheral and central corneal scarring vertex power required as per the age of the infant.
RGP Lens Design and Fitting Age (months) BOZR (mm) BVP (D)
6 weeks 4.5 +34.00 D
Aphakic RGP lenses are fabricated in lenticular designs with a 0-6 7.5 +29
peripheral carrier zone and are not single-cut. This promotes 7-17 7.7/7.9 +26
a central positioning of the lens. Such a design reduces central 18-28 7.9 +23
lens thickness with subsequent increase in Dk/t value. 29-34 7.9/8.1 +18
Increased peripheral thickness encourages lid holding and
causes the lens to ride high enough so that the optic zone • Power range of infant corrected for distance is usually
centers over the pupil. Peripheral axial edge clearance is between +20.0 to + 35.0 D. Children need to be corrected
fabricated from 90 to 120 μm. Lenses are fitted with slight for near point needs as the infant’s world is the near world.
apical clearance to ensure stability and a slight 1 to 1.5 mm Thus, the lens should be over-corrected by +2.00 to +3.00
movement with blinking is aimed for. A thinner lens, minus D.73 As the child grows, it may be altered to favor distance
carrier, larger diameter design, all serve to place the center of vision with addition of bifocals for reading, which may
gravity posteriorly and prevent the lens from dropping to the also incorporate any astigmatic correction. A set of spare
inferior lid margin. However, if the lens still rides low a larger lenses must be available with the parents at all times.
142 Contact Lens
To ensure continuous visual stimulation, a pair of back up

spectacles should be prescribed.
• The rapid decrease in refractive correction over the first
two years of life necessitates a refractive change every 3
months for the first year and then at 6 months for the
next few years.69,77 The power reduces from +34D after
birth to +18D at 2 years. Refraction needs to be performed
frequently to pick up the refractive change. Amblyopia
therapy needs to be coupled with use of occlusion and/or
penalization especially in unilateral aphakia as this is the
major determinant for final visual outcome.64,66 Patching
may be tried with opaque black tinted contact lenses, opaque
pupil lenses, or over-plus lenses in the good eye.
• As the child grows overcorrection is reduced and patient
encouraged to wear a distance corrected lens with bifocal A
spectacles for near work.72
Parental Instructions
• Parents should initially be supervised during the initial
contact lens insertion. Young infants are better handled
when asleep. The learning curve is difficult but once this
has been surmounted most parents are very comfortable
with the use of contact lenses for their children.78 Older
children can be taught to handle and care for their own
B
lenses. Lens removal is simpler than insertion. For RGP
Figs 3.2.3.21A and B: Note development of deposits (A) and
lens, the child’s eyelids are moved to break the ‘suction’
strabismus (B) in children wearing aphakic lenses
(overcoming the negative pressure generated under a lens
during its removal) and the lens is lifted out with the aid
Complications and Problems
of lids. For soft lenses a pinch method is used to extricate
the lens. Removal of silicone lenses is difficult as they • Potential for corneal abrasion and infection
tighten ‘on eye’. Using pressure of lid margin against edge • Lens handling difficulty, lens loss
of lens, air is introduced underneath the lifted edge and • Costs incurred in frequent lens change and follow up73
the suction is broken. • Discharge, eye rubbing, increased crying must be reported
• For long periods of sleep, the mother should be instructed by parents
to remove the lens. Thus silicone elastomers or extended • Dull lens surface – indicating deposits
wear hydrogels remain a more feasible option in infants. • Vascularization of the cornea
• A meticulous follow-up schedule is mapped out and written • Pupil irregularities
instructions provided regarding lens care. First follow-up • Amblyopia is the biggest problem and its therapy is the
is after the first week and then at monthly or three monthly cornerstone of successful visual rehabilitation77
visits. At each visit, evaluation is done of the lens fitting • Development of strabismus.
and any adverse effects on ocular physiology are ruled out. Successful contact lens wear can improve both vision and
The practitioner must check list all essential features like the quality of life of the pediatric patient but requires
deposits, breakages, corneal clarity, IOP, fundus exam, commitment and team effort. Fitting pediatric contact lenses
development of strabismus (Figs 3.2.3.21A and B) at each requires building a bond between the parents, child and doctor.
follow-up visit. Proper education of both parents and children on the useful-
• Lens loss or breakages are common. Coupled with frequent ness of lenses is required. A detailed warning of problems
power change in the first year of life, the parents must be which may occur, a strong social support network and adequate
told to expect 4-5 lens change per year.79 financial aid are important factors for families learning to cope
with lens wear.80 Holding combined sessions with parents of Indications for Contact Lens
successful pediatric aphakic patients on contact lens wear, helps
• As a bandage lens for corneal protection immediately after
to motivate and teach new lens wearers since the initial learning the refractive surgery.
period can be very frustrating. • For residual anisometropia.
CONTACT LENS FITTING IN POST • For post-surgical regression of the manifest refractive error.
CORNEAL REFRACTIVE SURGERY • For under or over-corrections.84
• Eccentric/decentered ablations results in a large dioptric
Refractive surgery like RK, PRK or LASIK alters the normal shift across the central pupil zone and causes reduction in
prolate cornea (steep centrally) into an oblate cornea (flatter vision, glare, halos, monocular diplopia, decreased contrast
centrally). This creates an elbow at the transition of the flat sensitivity and irregular astigmatism.
center with the steep periphery. Thus, it is often difficult to • Corneal scarring/ectasia.31,85
center conventional lenses designed for fit on an oblate cornea • Paracentral steep island is a well-circumscribed area of
(Fig. 3.2.3.22).81 In addition, the healed RK incisions are more greater refractive power, with power variations of up to
susceptible to erosions, infiltrations and neovascularization. >20.00 D in the pupil zone.
Since the amount of induced corneal flattening is directly • Irregular ATR astigmatism with inferior corneal steepening
proportional to the amount of myopia corrected, fitting is resembling pellucid marginal degeneration and significant
more difficult in higher refractive errors corrected. In addition irregular corneal topography as a consequence of flap
the hyperopic shift over time experienced with radial dislocation, are an indication.
keratotomy patients compounds to the refractive add to be
prescribed.82 Post-corneal refractive surgery patients referred Types of Lenses
for contact lens fit are disillusioned with the visual outcome • RGP lenses are the lenses of choice as they provide a
of a surgery which was supposed to relieve them of their smooth, regular, artificial anterior surface for the eye that
dependence on spectacles. Although visual function may be masks the irregularities that exist at every incision86-88
improved by a contact lens, patient motivation is poor as they (Fig. 3.2.3.23). The lens vaults over the flattened central
are being asked to adopt a form of vision correction they zone and provides stable vision along with correction of
chose to discard previously. They have unrealistic expectations. irregular astigmatism which is often greater than 0.75 to
Lens fitting in such patients is challenging but frustrating. It 1.0 DC.85 It may also reduce the flare that may result from
should never be undertaken until the incisions have fully healed corneal incisions. Fluctuations in vision occur in these
and topography has stabilized.83 patients due to changes in the corneal shape that occur
Fig. 3.2.3.22: Corneal topography depicting the flatt center and

steeper periphery post RK surgery Fig. 3.2.3.23: Post RK with an astigmatism of –7.0 Dc
144 Contact Lens
over the course of a day. The tear lens that present under
the RGP lenses can mask these changes, at least partially,
and result in more stable vision, i.e. little diurnal variation.
Such lenses are resistant to flexure, have high oxygen
permeability and good tear exchange.
• Siloxane hydrogel lenses/hydrogel lenses drape over the
contours of post refractive surgery corneas but correct
little or none of the astigmatism present. They are only
useful in simple over or under corrections.88,89 In addition,
they have a propensity to induce corneal edema with
resultant corneal vascularization along the RK incisions
thereby limiting their use in this condition.
• Piggyback lens system base lens must be a silicone
hydrogel. Choosing a standard HEMA lens would give
rise to the problem of neovascularization.83 After allowing
Fig. 3.2.3.24: Decentered RGP lens over a post LASIK eye
for a settling time, a fresh keratometry reading is taken
over the soft lens, the flat K of which decides the base
curve of the RGP lens to be placed anteriorly. This system The RGP lens is fitted using superior alignment technique
is a last resort since tremendous problems are faced in the where the lens is positioned high and moves in concurrence
care and performance of two different lens systems. with the upper lid. The base curve is calculated on preoperative
• Reverse geometry lenses designed with steeper secondary flat K values. If preoperative values are not available, then to
curves confirm to the altered corneal topography post postoperative K value, the amount of surgical correction is
refractive surgery. The secondary or reverse curve is designed added or a base curve which is 2.5D steeper to postoperative
to be 2 to 4 diopters steeper than the central base curve. K value is chosen as the initial trial lens. Subsequent
The fit of such a lens is better but care must be taken to modifications are made on fluorescein staining pattern. Due
ensure that adequate tear exchange occurs at the elbow which to the cornea’s flat central zone, a standard RGP lens will
is where the reverse curve bears upon the cornea.90,91 usually result in significant apical clearance, and a large pool
• Cosmetic artificial pupil soft lens made of high diffusion of fluorescein being observed centrally with a zone of mid-
coefficient material may be an option in cases with eccentric peripheral bearing. Large diameters, in the range of 9.5 to 10
ablation patterns.92,93 mm with large optic zone are chosen. Small optic zones may be
needed to avoid excessive fluorescein pooling. Fit is modified
Fitting Philosophies to ensure no central bubble entrapment or steep fit as that would
lead to epithelial desiccation. A good fit should show apical
Lens fitting should be deferred till at least 6 months or more clearing and mild corneal touch at the elbow (mid-periphery)
have elapsed to allow for topographic stabilization and for to allow for complete tear exchange. Multicurve lenses with
corneal hypoesthesia to recover. Corneal topography is used peripheral curves customized to enhance tear interchange are
to delineate the degree of central corneal flattening, transition the best choice.95
to the peripheral cornea which, in turn, dictates the design The gap between flat central cornea and contact lens creates
and fit of the contact lens.94 a positive tear lens which needs to be compensated by adding
After radial (RK), central cornea flattens relatively to a minus power to the final lens prescription. Thus over-refraction
steep and irregular mid-periphery. The transition zone forms should be the guide to final lens power, a simple mathematical
an ‘elbow’ or bend spanning the flatter center and the steeper transposition is never reliable for these corneas.83 Frequent
periphery. In addition the corneal apex can be displaced use of ocular lubricants is needed during the initial adaptation
significantly towards the corneal mid-periphery, this new period.31
location then becomes the steepest region of the cornea.
Because an RGP lens has the tendency to center over this Complications
steeper region, significant decentration can occur. Post PRK/ • Epithelial staining occurs due to the friction/rubbing/
LASIK the corneal topography is more predictable than after bearing effect of the lens back surface on proud areas of
RK surgery (Fig. 3.2.3.24). the cornea.
• The disturbed epithelial basement membrane in post

refractive surgery corneas may result in recurrent corneal
erosions with CL wear.
• Vascularization of post-RK cornea which follows the
incision lines is seen with use of conventional hydrogel
lenses.
• Glare, haloes, and double vision (diplopia).
• Dry eyes.
• Reduced night vision due to irregular astigmatism, non-
uniform corneal refractive indices, decentration of ablated
zone or mismatch between pupil and optical zone.
CONTACT LENS FITTING

IN CORNEAL OPACITIES
Ocular trauma or healed keratitis constitutes a large chunk of
patients presenting with diminished vision. Contact lenses are A
used to rehabilitate those cases with corneal scars who have
astigmatism (regular and irregular), aphakia or superficial
corneal opacities.96 Rigid gas permeable contact lens with high
permeability index are the preferred modality. However, soft
lenses may be useful in the correction of aphakia97 (Fig.
3.2.3.25). The fit must be modified to ensure adequate tear
exchange. The site of the corneal scar is often depressed and
causes fluorescein pooling due to lens vaulting over the opacity.
If paracentral, this lends itself to adequate centration but if
extensive, as in limbus to limbus scar, it often causes excessive
decentration and epithelial desiccation (Figs 3.2.3.26 and
3.2.3.27). A large overall diameter of 9.6 to 10 mm range is
chosen and high oxygen permeable fluorosilicate material is
to be used (Fig. 3.2.3.28).
B
Figs 3.2.3.26A and B: A long corneal scar causes fluorescein
pooling over the scar site and lens decentration
Contact lenses offer good vision in nebular and nebulo-

macular corneal opacities.98,99 In developing countries where
the waiting period for corneal grafting is long, this modality
offers a viable means of visual rehabilitation for many patients
suffering from visually disabling corneal opacities. Very often
significant improvement in vision is achieved so that a graft is
no longer felt necessary. Contrast sensitivity and mesopic vision
however do not improve to the same extent as visual acuity.98
ORTHOKERATOLOGY
This procedure employs programmed application of specially
Fig. 3.2.3.25: Soft lens in an eye with traumatic aphakia designed contact lenses which reshape the cornea to
with large full thickness corneo iridic scar temporarily reduce or modify myopia. The early lenses were
146 Contact Lens
Fig. 3.2.3.29: Reverse geometry lens
centration (Fig. 3.2.3.29).106 This 5 curve reverse geometry

lens is made of a very high Dk material (> 85), e.g. Boston
XO, which allows sufficient oxygen transmission during
overnight lens wear and prevents corneal hypoxia.
Fig. 3.2.3.27: A mildly decentered RGP lens over a paracentral
maculoleucomatous corneal opacity Principle of Orthokeratology
The central flat base curve exerts a positive pressure on the
central corneal epithelium. This works on the tear film
meniscus, which hydraulically redistributes epithelial cells under
the lens from the center towards the periphery. As a
consequence of this, the central corneal epithelium is thinned
out. The steeper secondary curve, creates an annular tear pool
which by virtue of negative pressure leads to mid peripheral
corneal epithelial and stromal thickening (Fig. 3.2.3.30).107-110
A 20 µ reduction in corneal epithelial thickness has been
documented over a three month period of ortho K wear.111
The end result is a reduction in corneal convexity and sagittal
corneal height, which effectively reduces myopic error. Age
plays a direct role in this corneal shaping as this response has
been noted to be rapid in children and young adults but reduced
and delayed in older people.110
Reverse Geometry Design

Fig. 3.2.3.28: Large diameter RGP lens centers well over a
• Central back optic zone radius (BOZR): Radius of curvature
dense corneal scar
of this zone is calculated as the flat K, minus the desired
amount of correction minus the compression factor of
conventionally flat-fitting, rigid contact lenses and induced 0.75D.
significant with-the-rule corneal toricity due to decentra- • Reverse curve or 2nd curve: The steep reverse curve aligns
tion.100,101 With the advent of reverse-geometry designs made back surface of the lens with cornea.
of high Dk material in late 1980, orthokeratology has • Alignment curve or 3rd and 4th curve: This 1.0 to 1.5 mm wide
re-established itself as a safe, viable procedure to correct bearing zone is made flatter than the reverse curve, thereby
myopia.102-105 Reverse-geometry lenses are fitted with base closely aligning the peripheral cornea. This curve helps in
curve flatter than the central corneal curvature. The flat base centering the lens and enhancing the orthokeratology
curve applies pressure to the central treatment zone, achieving effect.
sphericalization of the prolate cornea resulting in reduction • Peripheral curve: This aids lens lift, ensures adequate tear
of myopia. A steeper secondary curve is ground to aid exchange and helps in removal of lens (Fig. 3.2.3.30).
Fig. 3.2.3.30: Reverse geometry lens with bullseye fluorescein pattern
Orthokeratology is useful in the following situations: lens insertion, centration is checked based on the fluorescein
• Age: It is used to correct myopic refractive error in pattern. Centration is critical to achieve the ortho-K effect.
adolescents to young adults. Decentered lenses not only fail to produce the desired myopia
• It successfully corrects myopia in the range of –1.00D to reduction, but also distort the cornea. A good fluorescein
–6.00D pattern is a bull’s eye pattern, with a central zone of light
• It can correct cylindrical errors of –2.00D or less, with- touch of 3.5 to 4.0 mm in diameter, a midperipheral ring of
the-rule corneal astigmatism or < –0.75D against-the-rule fluorescein pooling, or ‘tear reservoir’, under the steeper
astigmatism. secondary curve and a peripheral circular band of alignment
• It works best for corneal curvatures in the range of 40.00D tapering to the edge lift (Fig. 3.2.3.30). A well-fitting lens should
(8.44 mm) to 45.50D (7.42 mm). move approximately 1 mm with blinking. The lenses are
• Refractive endpoint is typically reached with these lenses removed after 1 hour of trial wearing in the office and the
after 7 to 10 days of wear, with overnight 7 to 8 hours patient’s visual acuity before and after lens wearing is assessed.
lens-wearing protocol.102,107 Variation of Effect on the Basis
of Eccentricity “e”
Fitting Technique
An “e” value close to zero implies a spherical shape and hence,
Corneal topography is performed to determine corneal size, a more spherical cornea. Higher “e” value implies rapid corneal
flat-K value and eccentricity. Flat-K value determines radius flattening towards the periphery, thus the potential to flatten
of curvature for center. Radius of curvature for periphery central corneal curvature is greater. In low eccentricity values
also needs to be assessed by adapting corneal eccentricity with or oblate corneas the effect of Ortho K is reduced.
flat-K value. Corneal eccentricity “e” is defined as the rate at Table 3.2.3.1 gives the trial lens dimensions selected according
which the cornea flattens from the central area to the peripheral to eccentricity values.
area. Corneal size determines which part of the cornea comes The following figures depict certain illustrative examples
in contact with the alignment curve. Normal corneal size of of the Ortho K fit (Figs 3.2.3.31 to 3.2.3.33):
over 11.6 mm requires a 10.6 mm diagnostic/inventory lens. • Good centration: Fluorescein fit and topography picture.
Subsequently an initial lens is selected from the trial kit based A well-centered lens exhibits quick lens movement and
on the adjusted flat K. Flat K is adjusted with eccentricity “e” base curve zone touch of 4-6 mm. The reverse curve zone
as per the table provided. For eccentricity values ranging (green colored ring) is of equal width and the alignment
between 0.46 to 0.54, flat K value need not be adjusted. After zone (black part) is of equal width.
148 Contact Lens
Table 3.2.3.1: Trial lens dimensions in accordance to eccentricity values

Eccentricity value Trial lens Flat K adjustment Power adjustment required
0.30-0.39 0.50-0.75D steeper than flat K 43.50 (7.76) –43.75 (7.72) –3.50 to –3.75D
0.40-0.45 0.00-0.25D steeper than flat K 43.00 (7.85) –43.25 (7.80) –3.00 to –3.25D
0.46-0.54 On Flat K 43.00D (7.85 mm) –3.00D
0.55-0.60 0.25-0.50D flatter than flat K 42.75 (7.90) –42.50 (7.94) –2.75 to –2.50D
Figs 3.2.3.32A and B: Topography and staining pattern in

B steep fit Ortho K lens
Figs 3.2.3.31A and B: Fluorescein pattern in a post-fit topography

in a good fit. Note the central flattening on topography and there is a thick ring or air bubble at the reverse curve
zone. The alignment zone is broad.
• Poor centration (flat fit) fluorescein fit and topography picture:
• Poor centration (Steep Fit) fluorescein fit and topography picture: The movement of a flat lens is excessive and the base
A steep lens moves slightly, less than 1 mm and often rides curve zone is wide (> 5 mm). The reverse curve zone has
low. The base curve zone touch area is narrow (< 4 mm), an irregular width and the alignment zone is narrow.
A B
Figs 3.2.3.33A and B: Topography and staining pattern in flat fit Ortho K lens
Fig. 3.2.3.34: Sequential topography changes in a patient with Ortho K lens wear
150 Contact Lens
The following example highlights the technique of fitting: associated with soft contact lens wear. Vestn Oftalmol
A 21-year-old female with –3.50D myopia has keratometry 2010;126(3):31-4.
2. Guillon M, Maissa C. Contact lens wear affects tear film
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7.61-3.5 DS BC/–3.5 DS/10.6 mm. After lens insertion 4. Martin R, Sanchez I, de la Rosa C, de Juan V, Rodriguez G, de Paz
I, Zalama M. Differences in the daily symptoms associated with
fluorescein pattern is evaluated for lens centering, alignment, the silicone hydrogel contact lens wear. Eye Contact Lens
movement, tear meniscus size and shape. If the lens adheres/ 2010;36(1):49-53.
or air bubbles are noted in the reverse curve zone, then the 5. Arita R, Itoh K, Inoue K, Kuchiba A, Yamaguchi T, Amano S.
central bearing needs to be changed and fit made steeper. Contact lens wear is associated with decrease of meibomian glands.
Ortho K effect is evaluated after removing the lens following Ophthalmology 2009;116 (3):379-84. Epub 2009 Jan 22.
6. Toda I, Yoshida A, Sakai C, Hori-Komai Y, Tsubota K. Visual
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8. González-Méijome JM, Parafita MA, Yebra-Pimentel E, Almeida
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74. Saltarelli DP. Hyper oxygen-permeable rigid contact lenses as an
94. Szczotka LB, Aronsky M. Contact lenses after LASIK. J Am Optom
alternative for the treatment of pediatric aphakia. Eye Contact Assoc 1998;69(12):775-84.
Lens 2008;34(2):84-93. 95. Choi HJ, Kim MK, Lee JL. Optimization of contact lens fitting in
75. McQuaid K, Young T. Rigid gas permeable contact lenses changes keratectasia patients after laser in situ keratomileusis. J Cataract
in the aphakic infant. CLAO 1998;24(1):36-40. Refract Surg 2004;30(5):1057-66.
76. Amos CF, Lambert SR, Ward MA. Rigid gas permeable contact 96. Smiddy WE, Hamburg TR, Kracher GP, Gottsch JD, Stark WJ.
lens correction of aphakia following congenital cataract removal Contact lenses for visual rehabilitation after corneal laceration
during infancy. J Pediatr Ophthalmol Strabismus 1992;29(4):243- repair. Ophthalmology 1989;96(3):293-8.
5. 97. Netto AL, Lui AC, Lui GA. Visual rehabilitation with contact lenses
77. Moore BD. Changes in the aphakic refraction of children with after ocular trauma. Arq Bras Oftalmol 2008;71(6 Suppl):23-31.
unilateral congenital cataracts. J Pediatr Ophthalmol Strabismus 98. Titiyal JS, Das A, Dada VK, Tandon R, Ray M, Vajpayee RB. Visual
1989;26(6):290-5. performance of rigid gas permeable contact lenses in patients with
78. Ma JJ, Morad Y, Mau E, Brent HP, Barclay R, Levin AV. Contact corneal opacity. CLAO J 2001;27(3):163-5.
lenses for the treatment of pediatric cataracts. Ophthalmology 99. Grünauer-Kloevekorn C, Habermann A, Wilhelm F, Duncker GI,
2003;110(2):299-305. Hammer T. Contact lens fitting as a possibility for visual
rehabilitation in patients after open globe injuries. Klin Monbl 114. Cheung SW, Cho P, Chui WS, Woo GC. Refractive error and visual
Augenheilkd 2004;221(8):652-7. acuity changes in orthokeratology patients. Optom Vis Sci 2007;
100. Kerns RL. Research in orthokeratology. Part VIII: results, 84(5):410-6.
conclusions and discussion of techniques. J Am Optom Assoc 115. Walline JJ, Rah MJ, Jones LA. The Children’s Overnight
1978;49:308-14. Orthokeratology Investigation (COOKI) pilot study. Optom Vis
101. Binder PS, May CH, Grant SC. An evaluation of orthokeratology. Sci 2004;81(6):407-13.
Ophthalmology 1980;87:729-44.
116. Rah MJ, Jackson JM, Jones LA, Marsden HJ, Bailey MD, Barr JT.
102. Nichols JJ, Marsich MM, Nguyen M, et al. Overnight ortho-
Overnight orthokeratology: preliminary results of the Lenses and
keratology. Optom Vis Sci 2000;77:252-9.
Overnight Orthokeratology (LOOK) study. Optom Vis Sci 2002;
103. Swarbrick HA, Alharbi A. Overnight orthokeratology induces
central corneal epithelial thinning. Invest Ophthalmol Vis Sci 79(9):598-605.
2001;42:S597. 117. Van Meter WS, Musch DC, Jacobs DS, Kaufman SC, Reinhart WJ,
104. Mountford J. An analysis of the changes in corneal shape and Udell IJ. Safety of overnight orthokeratology for myopia: a report
refractive error induced by accelerated orthokeratology. ICLC by the American Academy of Ophthalmology. Ophthalmology
1997;24:128-44. 2008;115(12):2301-13.e1. Epub 2008 Sep 20.
105. Lui W-O, Edwards MH. Orthokeratology in low myopia. Part 1: 118. Hiraoka T, Okamoto C, Ishii Y, Kakita T, Okamoto F, Oshika T.
efficacy and predictability. Cont Lens Anterior Eye 2000;23:77-89. Time course of changes in ocular higher-order aberrations and
106. Wlodyga RJ, Bryla C. Corneal molding: the easy way. Contact Lens contrast sensitivity after overnight orthokeratology. Invest
Spectrum 1989;4:58-65. Ophthalmol Vis Sci 2008;49(10):4314-20. Epub 2008 May 23.
107. Swarbrick HA. Orthokeratology (corneal refractive therapy): what 119. Hiraoka T, Okamoto F, Kaji Y, Oshika T, Hiraoka T, Okamoto C,
is it and how does it work? Eye Contact Lens 2004;30(4):181-5; et al. Recovery of corneal irregular astigmatism, ocular higher-
discussion 205-6. order aberrations, and contrast sensitivity after discontinuation of
108. Alharbi A, Swarbrick HA. The effects of overnight orthokeratology overnight orthokeratology. Br J Ophthalmol 2008.
lens wear on corneal thickness. Invest Ophthalmol Vis Sci
120. Yang X, Zhong X, Gong X, Zeng J. Topographical evaluation of
2003;44(6):2518-23.
the decentration of orthokeratology lenses. Yan Ke Xue Bao 2005;
109. Walline JJ, Holden BA, Bullimore MA, et al. The current state of
corneal reshaping. Eye Contact Lens 2005;31(5):209-14. 21(3):132-5,195.
110. Jayakumar J, Swarbrick HA. The effect of age on short-term 121. Watt KG, Swarbrick HA. Trends in microbial keratitis associated
orthokeratology. Optom Vis Sci 2005;82(6):505-11. with orthokeratology. Eye Contact Lens 2007;33(6 Pt 2):373-7;
111. Soni PS, Nguyen TT, Bonanno JA. Overnight orthokeratology: discussion 382.
visual and corneal changes. Eye Contact Lens 2003;29(3):137-45. 122. Shehadeh-Masha’our R, Segev F, Barequet IS, Ton Y, Garzozi HJ.
112. Chan B, Cho P, Cheung SW. Orthokeratology practice in children Orthokeratology associated microbial keratitis. Eur J Ophthalmol
in a university clinic in Hong Kong. Clin Exp Optom 2008;91(5): 2009;19(1):133-6.
453-60. Epub 2008 Mar 18. 123. Van Meter WS, Musch DC, Jacobs DS, Kaufman SC, Reinhart WJ,
113. Johnson KL, Carney LG, Mountford JA, Collins MJ, Cluff S, Udell IJ. Safety of overnight orthokeratology for myopia: a report
Collins PK. Visual performance after overnight orthokeratology. by the American Academy of Ophthalmology. Ophthalmology
Cont Lens Anterior Eye 2007;30(1):29-36. Epub 2007 Jan 9. 2008;115(12):2301-2313.e1. Epub 2008 Sep 20.
3.2.4 Important Concerns

in Contact Lens Wear
COMPLICATIONS OF CONTACT LENS WEAR developed countries. 1 Soft lenses are more notorious for
Contact lenses compromise the eye by inhibiting tear film causing severe complications.2 Daily disposable soft lenses are
cleansing action, by compromising epithelial barrier function associated with significantly less complications. People
and by introducing more micro-organisms. However, the suffering from allergic conjunctivitis, atopy, dry eyes, and
overall rate of complications is quite low at six percent in blepharitis are more prone for lens induced complications.
154 Contact Lens
anterior corneal surface and manifest as corneal ‘dry spots’.

If less than 10 in number, they require no treatment, for
larger numbers replacement with high Dk lens is necessary.
• Stromal edema: Chronic wearing of lens causes depletion
of stromal keratocytes with subsequent stromal thinning.
• Endothelium: Initial response is transient blebs and poly-
megathism due to hypoxia induced acidic shift. This is
partly driven by ethnicity, since few studies have reported
a more vivid response in Asians.5
• Neovascularization at limbus: Both deep and superficial
neovascularization occurs due to chronic hypoxia subse-
quent to lens wear. Superficial vessels encroaching less than
1.5 mm into the corneal periphery are acceptable and must
be monitored. However deep vessels and/or vessels
A extending beyond 2 mm need to be treated by refitting
with higher Dk lens. After being refitted with a high Dk
lens, the vessels do not regress but instead become
converted into ghost vessels.6
• Myopic creep: This is the refractive change towards
increase in myopia to the tune of 0.5D over a 6-month
period. This change is said to be reversible after shifting
to high Dk wear lenses, thus giving credence to a hypoxic
etiology.
Treatment involves discontinuation of tight lens, lubricants
and low dose steroid-antibiotic combination. Subsequently,
the patient needs to be fitted with a flatter fit, modifying the
poor fit and/or high Dk lens.
Inflammatory Adverse Effects

B These are seen more often with continuous-wear high Dk value
Figs 3.2.4.1A and B: Lens overwear showing red eye and lenses. The patient experiences discomfort, lens intolerance
superficial punctate keratopathy and impaired vision.
• Contact lens induced peripheral ulcer (CLPU): These sterile,
small (< 1.5 mm), subepithelial and anterior stromal ulcers
Adverse Effects Related to Corneal Hypoxia
occur due to an immune response mounted by eye to lens
Acute hypoxia due to lens overwear or tight lens is manifested material or solutions. Inflammatory cells migrate from the
by pain, lacrimation, blurred vision, photophobia and limbal vasculature in response to hypoxia induced by
intolerance to lens. The eye is congested and diffuse corneal extended wear lens. The condition must be differentiated
epithelial staining is seen (Figs 3.2.4.1A and B). from its infective ulcers which are more symptomatic, larger
Chronic hypoxia manifests as microcysts, stromal edema, in size and have accompanying anterior chamber reaction.
endothelial changes and neovascularization at limbus. Staphylococcus species have been sometimes cultured from
• Corneal stria: These occur due to buckling of the Descemet’s these infiltrates. Treatment includes discontinuation of
membrane and endothelium. They signify corneal edema lens, use of broad spectrum topical antibiotic like
of more than five to eight percent.3,4 fluoroquinolones followed by low dose steroids after 24
• Microcysts: These asymptomatic small (15-50 μm) irregularly hours. The infiltrates respond rapidly, but the patient
shaped inclusions occur after a lag period of 1 to 3 months should be refitted with daily wear lenses.
of lens wear. These higher refractive index inclusions, occur • Superior arcuate epithelial lesions (SEAL): Superior limbic
in the basal layers of epithelium and are detected by keratoconjunctivitis in limbal/paralimbal area between 10
retroillumination. Microcysts can break through the to 2 o’clock positions occurs due to mechanical chaffing
of limbal vasculature by lens edge during blinking

movements. It is aggravated by tight fit, poor wettability
and use of thiomersal cleaning solutions. Treatment
consists of discontinuation of lens and use of lubricant
drops. The patient is then refitted with a new lens and the
cleaning solution is altered. Sometimes disposable lenses
may be required if the condition persists.
• Contact lens induced red eye (CLARE): This is an acute red
eye with corneal infiltration seen with extended wear (EW)
lens usage. Toxins from bacteria present in EW lenses cause
peripheral stromal infiltrates, conjunctival injection and
anterior chamber reaction. The condition resolves
completely on discontinuation of the lens and may recur
on reintroduction of another EW lens.
• Giant papillary conjunctivitis (GPC)/Contact lens induced Fig. 3.2.4.3: Fluorescein staining of active giant papillary
papillary conjunctivitis (CLPC): Tarsal conjunctival hyperemia, conjunctivitis seen in Figure 3.2.4.1
loss of vascular pattern and enlarged papillae of
> 0.3 mm size is seen on eversion of the upper lid (Figs immune response to lens deposits whereas localized GPC
3.2.4.2A and B). Patient reports with ocular discomfort, is primarily due to mechanical trauma with faulty lens edge
gritty sensation, itching, foreign body sensation, mucoid design or poorly fitted lenses. Active GPC stains with
discharge and lens intolerance. Diffuse GPC is due to an fluorescein (Fig. 3.2.4.3). Treatment involves discontinua-
tion of the lens, use of topical mast cell stabilizer,
olopatidine and lubricants. Rarely a short course of low
potency steroids may be needed. After the inflammation
has subsided, the patient is refitted with disposable lenses
or RGP lenses.
Mechanical Adverse Effects

• Deposits: These may be organic, inorganic or mixed. Tear
related deposits arise from lysozyme, lipids, albumin,
mucin, immunoglobulins (A, G and E), lactoferrin,
A
fibronectin and calcium. Lysozyme deposits on lens once
the tears evaporate and subsequently mucin adheres and a
build up starts. Non-tear related deposits from environ-
ment are rust, kajal, mascara, perfume, mercurial or tobacco
residues (Fig. 3.2.4.4). Extended wear, aphakia, high water
content lens, ionic lenses, poor hygiene, dry eyes, and
improper blinking increase deposit incidence.
– Protein deposits appear as flat, film-like protein or jelly
bumps (mulberry spots, barnacles). Jelly bumps appear
as a clump of raised translucent mulberry-like deposits,
typically in the inferior, exposed part (Fig. 3.2.4.5).
Lipids, proteins and calcium salts are involved.
Discomfort caused by protruding deposits leads to
cessation of lens wear. They lead to CLPC or GPC
and even lens flexure. Removal is impossible because
A
B their base is within the lens matrix. Forced removal
Figs 3.2.4.2A and B: Diffuse giant papillary conjunctivitis in a creates a pit in the lens which acts as a seed for rapid
soft lens wearer re-growth. Thus lens needs to be replaced.
156 Contact Lens
Fig. 3.2.4.4: Contact lens with deposits Fig. 3.2.4.5: Jelly bump protein deposits
Figs 3.2.4.6A and B: Inorganic and filamentous deposits
– Lipid deposits appear as greasy, smooth and shiny frequently seen with aphakic lenses, incomplete
adherent films. A fingerprint like incomplete film is blinking and dry eyes. Removal of leaves pits on the
characteristic. Patients with oily tears, thick lipid layer, lens surface. Thus, lens replacement is a better solution.
chronic blepharoconjunctivitis and meibominitis, Non-phosphate buffered saline must be used to store
exposed to environmental pollution are prone to it. the new lenses.
Regular cleaning of lens with alcohol-based surfactant – Filamentous or film like deposits (Fig. 3.2.4.6B) may harbor
cleaners, use of water-based cosmetics/skin bacteria or fungi.
preparations and frequent replacements of lens are Deposits reduce surface wetting, impair vision and
some measures that prevent lipid build up. comfort. Allergic reactions are more frequent once the
– Inorganic films/salts appear as white crystalline specks lens is infested with deposits. Proper cleaning and rubbing
on the surface and in the lens matrix (Fig. 3.2.4.6A). of lens with surfactant solutions and occasional use of
They develop rapidly within days/weeks and occur due enzymatic cleaners can prevent this problem.
to calcium carbonate or phosphate precipitating out • Inadequate blinking: Incomplete or reduced blinking causes
of tears. Once covered by a protein film, their rough drying of CL (Fig. 3.2.4.7). This is more common with
surfaces become smoother. These deposits are those working on computers, living in dry or air
curve with subsequent tightening of lens. The symptoms

of photophobia, blurred vision and discomfort occur after
few hours of lens fit, thus the patient must be examined
after he has been wearing the lens for some hours.
Circumcorneal congestion, arcuate corneal staining in
peripheral cornea, minimal lens movements, epithelial
infiltrates, and kinking of blood vessels under lens edge is
evident. Rarely anterior chamber inflammatory reaction may
be seen in severe cases. Treatment includes discontinuation
of lens, cycloplegic antibiotic combination, and refitting the
patient with higher Dk, flatter lens after few weeks.
Contact Lens Related Keratitis

Microbial keratitis is potentially blinding condition7-9 which
Fig. 3.2.4.7: Incomplete blinking causes lens drying is fortunately infrequent if proper hygiene and lens care
is practiced. (This has been elucidated in the section on Contact Lens
Keratitis.)
Lens Spoilage
Lens spoilage occurs due to aging and deposits. Poor wetting
causes ocular irritation and increases inflammatory and allergic
lid reactions. It is important to replace the lenses periodically
(one-year interval for soft CL (SCL) and 2-year interval for
RGP). Periodic edging and polishing of RGP-CL and
ultrasonic cleaning of SCL must be part of the instructions
imparted to patient at the time of CL dispensing.
Warpage of lens denotes change in base curve from the
initial parameters which subsequently lead to poor fitting of
lens. Chips or cracks in lens are more common with soft lenses
and cause ocular irritation and may induce corneal abrasions
Fig. 3.2.4.8: Dellen formation next to a flat fitting RGP lens or infections (Fig. 3.2.4.9). The patient presents with blurred
vision, discomfort, tearing or red eye.
conditioned environment. Reduced tear exchange as a
consequence of incomplete blinking, causes uneven tear CONTACT LENS CARE REGIMENS
distribution over the lens, poor CL fit which translates
Maintenance of the prescribed contact lens influences the
into “3 and 9 o'clock” staining with RGP lenses. Other causes
success of lens wear, patients’ satisfaction, tolerance and
are trauma from lens edge, small overall diameter and
minimizes complications. Lenses interfere with tear flow,
excessive edge lift. The cornea shows punctate staining,
impede washing of foreign bodies and contaminants, and
epithelial erosions, neovascularization and dellen formation
thereby favor growth of commensal organisms. Thus cleaning
(Fig. 3.2.4.8). Treatment involves use of lubricants,
and disinfecting of the lens is important to prevent visually
modification of CL fit and educating patient on proper
threatening corneal infections. Multipurpose solutions
blinking. Superficial punctuate keratitis is caused by dry
combine activities of cleaning, rinsing, disinfecting solutions
eye and exacerbated by mechanical injury, tight lens, lens
and are commonly used nowadays.10
overwear, and solution preservative toxicity. Lubricants and
topical antibiotics are instituted along with lens
Lens Care Protocol
discontinuation.
• Tight lens syndrome: This is seen in high water content hydrogel • Hand washing is to be done with fragrance free soap. Lenses
lens, which on desiccation causes steepening of the base are then placed in the palm of the hand and rubbed with
158 Contact Lens
A B
Figs 3.2.4.9A and B: Chipped edge and scratches on a soft and RGP lens respectively
the forefinger for 15 to 20 seconds using a to and fro and intolerance, diminished wearing time, burning, stinging,
lateral rolling action, utilizing 2 to 3 drops of cleaning dryness, conjunctival hyperemia and corneal toxicity.
solution.11 Mechanical rubbing and rinsing the lens after • Hydrogen peroxide (3%): A highly reactive oxidizing agent
removal from the eye reduces debris, proteins, microbes which produces reactive free oxygen radicals. This is a very
and enhances the efficacy of the cleaning solution’s effective antimicrobial agent and it acts very rapidly
surfactant. Of the two, rinsing is the most critical step.12,13 (10-20 minute soaking times). It decomposes into non-
• Cleaning solution removes loosely bound cell debris, mucus, toxic water and oxygen after neutralization. It is very
lipid, protein, dust, cosmetics and micro-organisms. The compatible with lenses as it reversibly alters the water
surfactant component emulsifies and dissolves lipid content and polymers of the lens.16 Neutralization is
globules. Hypertonic property of the solution extracts necessary prior to lens insertion since hydrogen peroxide
soluble contaminants from a soft lens. Additions of is toxic. It is marketed as one-step or two-step packs.
polymeric beads helps in removing deposits. – One-Step Peroxide Systems performs disinfection and
• Rinsing solution consists of preserved, unpreserved saline neutralization. It uses a platinum disc catalyst or catalase
with buffering agents to maintain pH of 7.2-5 (of tears). tablets which cause rapid or slow neutralization
Home-made saline is not used as it is a source of contami- respectively.17 Oxygen generated during the reaction
nation.14,15 escapes through specially designed vented lens cases.
• Disinfecting solution serve to deactivate potentially pathogenic Platinum disc efficacy decreases over time due to
organisms (bacteria, fungi, viruses, amoeba) and maintain contamination. However, poorer the catalyst
lens hydration. Disinfectants reduce the microbial level to performance, greater is efficacy of disinfection, since
a safer level. neutralization occurs slowly. Lenses need to be placed
in lens baskets prior to pouring the hydrogen peroxide
Soft Lens Disinfection into the case.
– In two-step systems, neutralization is performed as a
Thermal: Heat in the range of 70 to 80°C deactivates living
separate step. A bicarbonate buffer alters the pH to
lens contaminants. Heat disinfection is highly effective against
where peroxide is less stable and decomposes slowly
all microbes including spores and Acanthamoeba cysts. It requires
into water and oxygen. The lenses need to be stored
a time of 20 to 30 minutes. However, this is incompatible
overnight in the peroxide.
with high water content lenses and it discolors/ages lenses by
Some studies have more comfortable wear with this
denaturing protein.
disinfecting system.18
Chemical: Hydrogen peroxide, chlorine, thimerosal, benzal- • Thiomersal (0.001-0.004%): A mercurial antibacterial and
konium chloride or chlorhexidine are used as oxidants. These antifungal, its mercury ions form covalent bonds with the
compounds can lead to sensitivity which manifests as lens sulphydryl groups of bacterial cell enzymes or proteins
and incapacitate them. It is cytotoxic to corneal epithelium disinfection and before insertion to remove residual
and shows a reduction in effect when combined with chemicals.22
EDTA/chlorhexidine and is incompatible with benzyl
alkonium chloride. As it is decomposed by light, the Factors Affecting Efficacy of Disinfectants
solutions should be stored in light-proof containers.
• D-Value (Death-Rate Kinetics): The D-value of a solution
• Chlorhexidine gluconate (0.001-0.006%): A biguanide
defines its antimicrobial ability. It is the time required for
antimicrobial, it gets adsorbed on the siloxane acrylates
the substance or method to decrease the number of
and protein deposits. This can cause ocular irritation and
organisms by one log unit or time to kill 90 percent of
corneal toxicity.19 It is effective against both trophozoite
organisms originally present. It determines time required
and cyst forms of Acanthamoeba.20
for disinfection. A longer time indicates slower killing rate
• Mercurials: These have significant antifungal action and
but not necessarily a lower anti-microbial efficacy.
chlorhexidine has a superior antibacterial action, thus the
• Exposure period: The kill rates determine soaking time.
combination of the two compounds makes a good
• Biofilm (polysaccharide slime) formed by Serratia marcescens,
disinfection system.
• Benzalkonium chloride (BAK 0.002-0.01%): A surface active Pseudomonas, Staphylococcus epidermis and S. aureus act as a
cationic surfactant, it disrupts cell membrane integrity. It protective biofilm enveloping the organism and prevent
is normally used in conjunction with a wetting and chelating penetration of disinfectants.
agent to increase its effectiveness. In concentration greater Multipurpose CL Solution
than 0.005 percent it is toxic to the cornea.
• Benzyl/Isopropyl alcohol: It is not effective against spores of These isotonic solutions contain surfactant along with
Clostridium botulinum, C. tetani and Bacillus subtilis and antimicrobial agent which serves as a preservative, and prevents
against Pseudomonas aeruginosa in low concentrations. It is contamination of the solution after opening. They also contain
unsuitable for soft contact lenses and is relatively non- non-ionic or ionic charged amphoteric compounds, chelating
sensitizing. agents like EDTA along with viscosity-enhancing agents.
• EDTA: It disrupts cell growth by chelation of calcium, Polyhexamethylene biguanide 0.0001 percent or polyamino-
and magnesium from cell walls of gram-negative propyl biguanide 0.0001 percent are the disinfectants. Abrasive
organisms. It potentiates the action of quarternary polyamide polymeric beads for mechanical cleaning may be
ammonium compounds against gram-negative organism incorporated. They use acetate/borate/bicarbonate/citrate/
but is an insufficient preservative on its own. phosphate buffer to prevent stinging or discomfort on lens
• DYMED (0.00005-0.0015 percent polyaminopropyl insertion and maintain pH of the solution. Lenses stored in
biguanide PAPB): A member of the biguanide family, it solution outside the normal pH alter their parameters leading
selectively binds with phospholipids in cell walls and causes to deranged fit, comfort and vision.23 A decrease in pH
membrane damage and has amoebicidal properties.21 decreases water content and causes lenses to tighten on the
• POLYQUAD (0.001-0.005%): A high molecular weight eye. Extremely acid/basic solutions cause brittleness,
quarternary ammonium compound, it is used with a citrate discoloration and spoilage of lens. Maintaining the pH is very
buffer. It is marketed as Opti-Free, Opti-Free Express, relevant as preservative action is pH dependent and for ocular
Opti-One and Opti-Soak (Alcon). comfort pH should range between 6.6 to 7.8.
• Chlorine systems (Polydichlorosulphamoyl benzoic acid): They are
supplied as a blister packed anhydrous effervescent tablets RGP Lens Disinfection
of either stabilized halane (sodium dichloroisocyanurate The oxygen permeable siloxane material is essentially
Softab™) or halazone poly (dichlorosulphamoyl benzoic hydrophobic and thus more prone to deposits. Surface drying
acid Aerotab™). A tablet dissolved in 10 ml unpreserved exacerbates this problem. This aspect of RGP lens dictates
sterile saline makes a disinfecting solution with a pH of 5.5- different care regimens.
7.5. Tablets hydrolyze to produce hypochlorous acid which, • Solutions used for RGP disinfection need to combine
in turn, dissociates into hydrogen and hypochlorite ions. elements of enhancing lens wettability to negate the
This produces chlorine concentrations of 4-8 ppm, and hydrophobicity of the siloxane material. Disinfecting/
requires lens soaking time of 30 minutes to 4 hours. Lenses soaking solutions for RGP lenses can be classified as
must be rinsed thoroughly with sterile saline before multipurpose since they soak, wet and disinfect.
160 Contact Lens
• Only chemical systems should be used to disinfect RGP Trial Lens Care
lenses as thermal disinfection can cause lens warpage.
RGP lens: Trial set lenses may be stored in the dry to avoid
Peroxide system is not preferred as it lacks any significant replacing storage vial solutions regularly. Dry storage is
wetting function.24 convenient because there are no solutions requiring regular
• Deposits are a major issue with RGP lens wear. They need replacement, a necessary step if microbial growth is to be
to be mechanically removed by rubbing with a surfactant prevented. Further, dry storage removes all potential media
cleaner. Alcohol-based surfactant cleaners are preferred for microbial growth provided the lenses and cases are truly
for extensive deposits. During lens rubbing, a 10 seconds clean and dry. However, lenses that are ‘dry’ stored may not
minimum rub followed by a saline rinse is advisable. Rolling wet as well during the trial fitting. The lenses need to be cleaned
finger movements from left to right ensures cleaning of with alcohol-based cleaner immediately after use and placed
the lens periphery. 25 Surface polishing and edging or ‘concave-up’ in a flat, clean container to prevent lens sucking
resurfacing needs to be performed annually or once onto the floor. If wet storage is done, then the solution needs
scratches/deposits form on the lens as an alternative to to be changed on a monthly basis. The fitter must remember
replacement. Micro-organisms cannot readily attach to to clean, rinse and disinfectant lenses every time (CRADLE
RGP lens surfaces. However, deposits lend themselves to acronym).
microbial attachment. Soft CL always need to be stored wet. The solution must
be discarded after each use and the case refilled with fresh
Conditioning/Wetting/Soaking Solutions solution. Heat or peroxide disinfection is done periodically.
RGP lenses need to be stored in solutions, since drying alters
lens parameters like flattening of BOZR. These solutions Methods Used to Disinfect Trial Sets
comprise antimicrobial agents, wetting agents, viscosity- • Heater/stirrer units with/without oxidizing agents like 6/9
enhancing agent and buffer systems. Solution toxicity is percent H2O2.
uncommon as preservatives are not normally absorbed by the • Microwaves: A 2.5 GHz unit at 500 watts warrants a
RGP lenses. 5 minutes exposure and can handle a large number of
lenses simultaneously. Vented lens containers need to be
Protein Cleaning
used to allow escape of steam generated by boiling saline.
This is used for soft CL and RGP lenses to loosen tightly Sealed cases would rupture. As with any heat disinfection,
bound protein deposits by cleaving peptide bonds. Prior to lens longevity is reduced.
protein removal, the lenses should be cleaned and rinsed. • Standing waves: Vertically oriented high energy waves
Protein treatment is usually done weekly or at a frequency generated by a vibrating plate cause low-frequency agitation
proportional to rate of patient protein deposition. Lenses need of a lens vial and dislodges contaminants.
to be soaked in the remover for 15 minutes to 2 hours. • Ultrasound: High frequency 15 to 20 kHz waves create
Examples are papain, subtilisin, pancreatin and lipase which intense agitation of small bubbles at the lens surface and
attack the lysozyme, albumins and immunoglobulins deposits cleans by cavitation effect, e.g. Sonasept ultrasonic cleaner.
whereas pronase and amylase target mucin deposits. After It destroys cell walls of microbial contaminants and is more
deproteinization the lens needs to be cleaned and rinsed to effective for low water content soft lenses. It is not useful
remove loosened deposits. The more effective Subtilisin A for high water content SCL or RGP due to reduced
and B are formulated for use with peroxide and chemical effectiveness of the acoustic interface between saline and
systems respectively. high water content lens.
• Ultraviolet: Ozone produced by the ultraviolet emitting
Lubricant Drops discharge tube kills microbes by breaking bonds and cross
Used primarily for RGP lens, these rewetting solutions promote links between nucleic acids. It is effective in disinfecting
both SCLs and RGPs.26,27
comfort, reduce friction between lids and lens, and overcome
dryness. Composed of saline, polyvinyl alcohol (wetting agent)
Storage of Lenses
and methylcellulose (viscosity enhancer), they are useful during
lens adaptation and under situations of increased drying of Lenses must be stored in a clean case using fresh disinfecting
lens. solution each time. Each morning the case is rinsed and dried
after the lens is removed from it. In the evening, prior to or preserved). Disinfection is done with heat, cold chemical,
placement of lens it must be refilled with fresh solution. Soiled oxidative or multi-purpose systems. Deproteinization is
lens case leads to microbial contamination, lens discoloration required at a lower frequency. For monthly replacement lenses,
and intolerance.28 Biofilm or glycocalyx formation on the it can safely be omitted.
surface of contact lens storage cases can harbor Pseudomonas
Conventional (lenses replaced >6 months – yearly): Protein removal
aeruginosa and Serratia marcescens.
has to be incorporated in addition to frequently replacement
lens regime. Heat/thimerosal/chlorhexidine-based disinfection
Case Care
is not recommended.
The lens cases should be scrubbed regularly with a dedicated
toothbrush with oil free soaps or detergents and subsequently Instructions Given to Patients
rinsed with hot water, rubbed dry with clean, dry tissue/cloth.
• Hands must be washed prior to handling lenses.
This rub and rinse regimen has to be followed meticulously.
• Each side of each lens should be rubbed for 10 to 15
Rubbing disrupts the biofilm which forms on the case, the
seconds using a surfactant cleaner. The rubbing step is
hot water of > 70°C temperature kills Acanthamoeba, and drying
always followed by a rinsing step. The former dislodges
the case prevents colonization by most micro-organisms. The
lens contaminants while the rinsing step removes the
case must be replaced at frequent intervals (monthly when a
displaced contaminants as well as any residual lens cleaner.
new case is supplied with each bottle of disinfecting solution)
• Each lens should be rinsed thoroughly in normal saline.
to reduce the risk of contamination/biofilm build-up. Vented
• Disinfection should be done in a fresh disinfecting solution
storage cases are not recommended.
in a clean storage case. Spare storage cases should be kept.
Two-step hydrogen peroxide systems provide better long-
• Solution types and brands should not be mixed.
term storage alternative since the lenses can be stored in a 3
• The case must be thoroughly cleaned and dried once a
percent hydrogen peroxide solution between lens uses.
week.
Solutions must not be used after expiry date or after long
• A written instruction sheet with illustrations helps in
time of initial opening. Any used solution must be discarded.
clarifying these steps. Inspection of the cases by the treating
For semi- tropical countries like India every 10°C increase in
physician is advisable. This reduces non-compliance with
temperature doubles the rate of chemical reactions. Thus
care regimens which is one of the major contributing
solutions stored in warmer environments would require the
factors of lens related complications.29
expiry date to be brought forward.
REFERENCES
Lens Discoloration
1. Suchecki JK, Donshik P, Ehlers WH. Contact lens complications.
Pigment deposits, cosmetics, nicotine (cigarette smokers), iron Ophthalmic Clinics of North America 2003;471-48412.
(rust), mercurial deposits (thiomersal), and phenylephrine can 2. Forister JF, Forister EF, Yeung KK, Ye P, Chung MY, Tsui A,
produce black, gray or brown discoloration. It may be removed Weissman BA. Prevalence of contact lens-related complications:
with an oxidizing agent (sodium perborate, hydrogen peroxide UCLA contact lens study. Eye Contact Lens 2009;35(4):176-80.
with or without heat). Use of tetracyclines can cause a yellow 3. Brooks AM, Grant G, Westmore R, Robertson IF. Deep corneal
color discoloration and use of henna (Mehndi) an orange one. stromal opacities with contact lenses. Aust N Z J Ophthalmol
Concomitant use of eye drops over the soft CL should be 1986;14(3):243-9.
avoided. 4. Remeijer L, van Rij G, Beekhuis WH, Polak BC, van Nes J. Deep
corneal stromal opacities in long-term contact lens wear.
Cleaning Depends on Lens Wear Schedules Ophthalmology 1990;97(3):281-5.
5. Hamano H, Jacob J, Senft C, et al. Differences in contact lens
Daily disposables: As evident such a lens does not require any induced response in the cornea of Asian and non Asian subjects.
cleaning. Weekly or biweekly disposables can be managed CLAO J 2002;28:101-4.
adequately with multipurpose solutions. Protein removal is 6. Wong AL, Weissman BA, Mondino BJ. Bilateral corneal
not necessary. Re-wetting drops may be used for rinsing neovascularization and opacification associated with unmonitored
disposable lens prior to insertion. contact lens wear. Am J Ophthalmol 2003;136(5):957-8.
7. Szczotka-Flynn L, Ahmadian R, Diaz M. A re-evaluation of the
Frequently replaced lenses (1–6 months): Cleaning is done with a risk of microbial keratitis from overnight contact lens wear
multi-purpose solution or a surfactant cleaner followed by compared with other life risks. Eye Contact Lens 2009;35(2):
rinsing with a multi-purpose/saline solution (unit-dose, aerosol 69-75.
162 Contact Lens
8. Petroutsos G, Paschides CA, Kitsos G, Drosos AA, Psilas K. Sterile 19. Tripathi BJ, Tripathi RC, Kolli SP. Cytotoxicity of ophthalmic
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J Fr Ophthalmol 1992;15(2):106-11. 1993;9(3 and 4):361-75.
9. Preechawat P, Ratananikom U, Lerdvitayasakul R, Kunavisarut S. 20. Seal DV, Hay J, Kirkness CM. Chlorhexidine or polyhexamethylene
Contact lens-related microbial keratitis. J Med Assoc Thai biguanide for acanthamoeba keratitis. Lancet 1995;345(8942):136.
2007;90(4):737-43. 21. Stapleton F, Harmis N, Deshpande R, Tran D. Preliminary studies
10. Efron N, Morgan PB. Soft contact lens care regimens in the UK. on the amoebicidal efficacy of contact lens disinfection systems.
Cont Lens Anterior Eye 2008;31(6):283-4. Epub 2008 Nov 5. Aust N Z J Ophthalmol 1998;26 (Suppl 1):S44-6.
11. Shih KL, Hu J, Sibley MJ. The microbial benefit of cleaning and 22. Rosenthal RA, Henry CL, Schlech BA. Contribution of regimen
rinsing contact lenses. ICLC 1985;12(4):235-42. steps to disinfection of hydrophilic contact lenses. Cont Lens
12. Heaselgrave W, Lonnen J, Kilvington S, Santodomingo-Rubido J, Anterior Eye 2004;27(3):149-56.
Mori O. The disinfection efficacy of MeniCare soft multipurpose 23. Dalton K, Subbaraman LN, Rogers R, Jones L. Physical properties
solution against Acanthamoeba and viruses using stand-alone of soft contact lens solutions. Optom Vis Sci 2008;85(2):122-8.
biocidal and regimen testing. Eye Contact Lens 2010;36(2):90-5. 24. Boltz RL, Leach NE, Piccolo MG, Peltzer B. The effect of repeated
13. Pucker AD, Nichols JJ. Impact of a rinse step on protein removal disinfection of rigid gas permeable lens materials using 3 percent
from silicone hydrogel contact lenses. Optom Vis Sci 2009;86(8): hydrogen peroxide. ICLC 1993;20(11 and 12):215-21.
943-7. 25. Butcko V, McMahon TT, Joslin CE, Jones L. Microbial keratitis
14. Forister JF, Forister EF, Yeung KK, Ye P, Chung MY, Tsui A, et al. and the role of rub and rinsing. Eye Contact Lens 2007;33(6 Pt 2):
Prevalence of contact lens-related complications: UCLA contact 421-3; discussion 424-5.
lens study. Eye Contact Lens 2009;35(4):176-80. 26. Harris MG, Fluss L, Lem A, Leong H. Ultraviolet disinfection of
15. Donzis PB, Mondino BJ, Weissman BA, Bruckner DA. Microbial contact lenses. Optom Vis Sci 1993;70(10):839-42.
contamination of contact lens care systems. Am J Ophthalmol 27. Choate W, Fontana F, Potter J, Schachet J, Shaw R, Soulsby M,
1987;104(4):325-33. White E. Evaluation of the Puri Lens contact lens care system: an
16. Young G, Garofalo R, Harmer O, Peters S. The effect of soft automatic care system incorporating UV disinfection and
contact lens care products on lens modulus. Cont Lens Anterior hydrodynamic shear cleaning. CLAO J 2000;26(3):134-40.
Eye 2010;33(5):210-4. Epub 2010 Jul 31. 28. Larkin DFP, Kilvington S, Easty DL. Contamination of contact
17. Ngo W, Heynen M, Joyce E, Jones L. Impact of protein and lipid lens storage cases by Acanthamoeba and bacteria. Br J Ophthalmol
on neutralization times of hydrogen peroxide care regimens. Eye 1990;74:133-5.
Contact Lens 2009;35(6):282-6. 29. Donshik PC, Ehlers WH, Anderson LD, Suchecki JK. Strategies
18. Keir N, Woods CA, Dumbleton K, Jones L. Clinical performance to better engage, educate, and empower patient compliance and safe
of different care systems with silicone hydrogel lenses. Cont Lens lens wear: compliance: what we know, what we do not know, and
Anterior Eye 2010;33(4):189-95. Epub 2010 Mar 3. what we need to know. Eye Contact Lens 2007;33(6 Pt 2):430-3.
Chapter 4.1
DEFINITION AND MAGNITUDE

OF LOW VISION
Rituparna Ghoshal
DEFINITION So, based on this definition, only a person with no

perception of light is considered as blind.
The World Health Organization publishes a classification of
known diseases and injuries called the International Statistical MAGNITUDE
Classification of Diseases and Related Health Problems or Based on the current estimate2 (using ICD-10 definition of
ICD-10. Visual disturbances and blindness is classified as low vision and blindness and world population in 2002)
H53-54.9. worldwide, there are 161 million people with visual
Low vision was traditionally defined (ICD-10, H54, 9)1 impairment; out of which 37 million are blind and rest 124
as visual acuity of <6/18 but equal to or better than 3/60 or million are people with low vision. 90 percent of the people
a corresponding visual field of <20° in the better eye with with visual impairment live in developing countries. In the
best possible correction (ICD-10 visual impairment categories same study, it was estimated that 6.7 million people in India
are blind. Extrapolating 1:3.7 ratio of blindness and low vision,
1 and 2), whereas blindness was defined as visual acuity of
the national estimate of people with low vision is
< 3/60, or a corresponding visual field loss to less than 10°
approximately 24.79 million.
in the better eye with best possible correction (ICD-10 visual Another study5 estimated 10.6 million people in India
impairment categories 3, 4 and 5).2 Visual impairment includes with low vision, using revised criteria of low vision (1992).
both low vision and blindness. The huge difference in the estimated results is found between
However, studies3 have shown that the persons labeled the two studies because of the difference in methodology
blind, based on the above definition, may have sufficient and definition used in the two studies. The global causes of
visual potential to perform some of the activities of daily blindness as a percentage of total blindness are elaborated in
living. So 'low vision' was redefined4 in the Bangkok meeting Table 4.1.1 as:2
of World Health Organization in the year 1992, and the Table 4.1.1: Causes of blindness/excluding
following definition was suggested. refractive error
“A person with low vision (LV) is one who has impairment Causes of global blindness Percentages
of visual functioning even after treatment and/or standard Cataract 47.8
refractive correction, and has a visual acuity of <6/18 to Glaucoma 12.3
Age related macular degeneration 8.7
light perception or a visual field loss of <10° from point of
Corneal opacities 5.1
fixation in the better eye, but who uses, or is potentially able Diabetic Retinopathy 4.8
to use, vision for the planning and/or execution of task.” Childhood blindness 3.9
The major advantages of the present definition are: Trachoma 3.6
1. Component of functional vision is included in this Onchocerciasis 0.8
Others 13
definition; and
(Adapted with the permission of the World Health Organization from Global data on
2. The range of visual acuity is enlarged from <6/18 to visual impairment in the year 2002, Resnikoff S, et al. Bulletin of World Health
light perception. Organization 2004;82(11): 844–51; Table 4; copyright notice March 2011)
166 Low Vision
CHILDHOOD BLINDNESS FUNCTIONAL IMPLICATIONS AND

2 MANAGEMENT OF DIFFERENT
Global childhood blindness was estimated as 1.4 million using
CONDITIONS CAUSING LOW VISION
the following definition:
• Child = Age of <15 years Low vision does not impact every person in same way. There
• Blindness = BCVA of <3/60 or visual field of <10° are many conditions leading to the vision loss. Understanding
from point of fixation. the specific ocular conditions helps one to understand the
Causes of childhood blindness are very different from visual impairments and functional difficulties of the affected
the causes of blindness in adults and vary according to the individual better. Thereby, it helps in the management of the
region and socioeconomic development.6-9 In developing specific disorders. Vision loss can be categorized into three
countries, major causes of blindness10 are corneal scarring types:12
due to vitamin A deficiency, measles, harmful traditional eye a. Overall blurred vision
remedies, congenital rubella, ophthalmic neonatorum, etc. b. Central field loss
Table 4.1.2 elucidates the causes, distribution and magnitude c. Peripheral field loss.
of blindness in India. In middle-income and affluent countries, Each of them shall be discussed in detail.
the causes are retinopathy of prematurity, retinal dystrophies
and congenital anomalies. Uncorrected refractive error, Overall Blurred Vision
cataract and glaucoma cause visual impairment in all regions.
Table 4.1.3 elucidates some causes of vision loss Overall blurred vision is the decreased ability to perceive a
Representative fundus pictures of some of these conditions clear view of objects, but there is no association of field loss.
in each of these categories are shown in Figures 4.1.1, 4.1.2 In this category of vision loss, visual functions like visual
and 4.1.3. acuity (both distance and near), and contrast sensitivity are
Table 4.1.2: Causes of blindness in children. Blindness defined as presenting visual acuity <6/60 in the better eye
No (%) of blind children
Causes of blindness
APEDS RESC All
Refractive error 2 (40) 2 (28.6) 4 (33.3)

Retinal 0 2 (28.6) 2 (16.7)
Corneal opacity 1 (20) 1 (14.3) 2 (16.7)
Congenital eye anomaly 1 (20) 1 (14.3) 2 (16.7)
Amblyopia 1 (20) 1 (14.3) 2 (16.7)
Total 5 (100) 7 (100) 12 (100)
APEDS = Andhra Pradesh Eye Disease Study; RESC = Refractive Error Study in Children; and All = both the studies combined
(Reproduced from Childhood blindness in India, Dandona R, Dandona L, British Journal of Ophthalmology 2003, Volume 87(3), page
263–5, copyright notice February 2011 with permission from BMJ Publishing Group Ltd.)
Table 4.1.3: Causes of different categories of vision loss

Overall blurred vision Central field loss Peripheral field loss
1. Keratoconus 1. Age related macular degeneration (AMD) 1. Retinitis pigmentosa (Fig. 4.1.3)
2. Microphthalmos 2. Heredomacular degeneration (HMD) (Fig. 4.1.2) 2. Glaucoma
3. Corneal degeneration 3. Macular hole 3. Retinopathy of prematurity
4. Failed corneal graft 4. Myopic macular degeneration 4. Lebers congenital amaurosis
5. Congenital cataract 5. Diabetic maculopathy 5. Optic atrophy
6. Amblyopia 6. Lasered diabetic retinopathy
7. Aniridia 7. Lesions in the optic nerve pathway
8. Albinism (Fig. 4.1.1)
9. Corneal Scar
10. Vitreous Hemorrhage
11. Nystagmus
Definition and Magnitude of Low Vision 167
Fig. 4.1.4A: Scene as perceived by a normally sighted person
Fig. 4.1.1: Albinotic fundus
Fig. 4.1.4B: Overall blurred vision
Fig. 4.1.2: Fundus picture demonstrating impaired. Due to these impairments, the person's ability to
heredomacular degeneration perform certain tasks are hampered.13-15 The visual scene
perceived by a normal person and a person having blurring
of vision is demonstrated in Figures 4.1.4A and B. The
functional implications of overall blurred vision are elaborated
in Table 4.1.4.
Management of Overall Field Loss
Low Vision Rehabilitation (LVR) service maximizes the residual
vision to provide the individual with practical adaptation for
their daily living activities. Thereby it increases the level of
independence. Trained professionals in hospitals, vision
rehabilitation organizations, and private optometric and
ophthalmic practices provide comprehensive low vision
services.
Management of overall blurred vision is discussed in the
following steps:
• Counseling: The first and foremost step of vision
Fig. 4.1.3: Fundus picture demonstrating retinitis pigmentosa rehabilitation services is to explain the present status and
168 Low Vision
Table 4.1.4: Functional implications of

overall blurred vision
Impairments of different Impacts on daily living activities
visual functions
1. Decrease in a. Difficulty in face recognition,
distance vision reading road signs, bus numbers
b. Difficulty in copying from board
c. Difficulty in orientation and mobility
2. Decrease in near vision a. Difficulty in literary task like reading
and writing
b. Difficulty in self-care like grooming
c. Difficulty in using computers
3. Impaired contrast a. Bumping into objects
sensitivity b. Difficulty in seeing time in watch
c. Difficulty in currency identification
d. Difficulty in mobility in dim light
e. Difficulty in reading poor contrast Fig. 4.1.5A: Central relative scotoma
materials
4. Glare a. Discomfort in sunlight (squeezing
eyes)
b. Difficulty in bright light (e.g. car
lights)
prognosis of the ocular condition to the patient and his/

her family members.
• Assessment of different visual functions: Then, a thorough
assessment of different visual functions is carried out to
understand the difficulties and needs of the individual
with visual impairment (Different steps of a Low Vision
Examination will be discussed in next chapter).
• Magnification: Magnification can be provided by means
Fig. 4.1.5B: Central absolute scotoma
of either optical or nonoptical or electronic devices. Some
of the optical devices that are used to enhance visual
performance are telescope (for distance and intermediate),
• Rehabilitation services: Details of additional rehabilitation
spectacle magnifier, stand magnifier and handheld
services including training in use of LVDs, home
magnifier (for near). Magnifiers should be prescribed after
management, training in daily living skills, orientation and
determining the required magnification.16
mobility, functional vision assessments, early interventions,
Some of the nonoptical devices such as large print
educational guidance and vocational guidance is discussed
books, large dial clock and large print dictionary are used
in the subsequent chapters.
to achieve relative size magnification. In case of moderate
to severe impairments, electronic devices such as CCTVs
Central Field Loss
are helpful in accomplishing higher magnification.
• Contrast enhancing measures: Contrast can be enhanced by In this category of vision loss, the ability to perceive objects
either using nonoptical devices (such as Typoscopes) or or people in the direct line of vision is affected. In central
by environmental modifications such as incorporating field loss, different visual functions affected are visual fields,
extra lighting. distance and near visual acuity and contrast sensitivity. Figures
• Glare comfort devices: Patient with albinism and aniridia often 4.1.5A and B demonstrate the possible quality of vision in
complain of glare. In these conditions, nonoptical devices patients with central relative scotoma and central absolute
such as tinted lenses and visors, filters, and peaked caps scotoma respectively. The functional implications of central
are useful as glare comfort measures. field loss are elaborated in Table 4.1.5.
Table 4.1.5: Functional implications of central field loss

visual functions
1. Visual field defect in the a. Not talking directly to people
form of central scotoma b. Lack of eye contact
(Partial perceptions c. Missing letters or words in
of objects) between while reading
2. Decrease in a. Difficulty in face recognition
distance vision b. Difficulty in reading road signs
c. Difficulty in copying from board
d. Difficulty in orientation and mobility
3. Decrease in near vision a. Difficulty in reading and writing
b. Difficulty in grooming
c. Difficulty in using computers Fig. 4.1.6A: Reading distance at 33 cm
d. Difficulty in signing
e. Difficulty in different daily living
skills (preparing food, cutting
vegetables)
4. Poor color vision a. Inability to identify the color of the
object
b. Uncoordinated clothing
c. Difficulty in sorting fruits and
vegetables
sensitivity b. Seeing time in watch
c. Currency identification
e. Difficulty in reading poor contrast
materials
6. Glare a. Discomfort in sunlight (squeezing
eyes)
b. Difficulty in bright light (e.g. car
lights) Fig. 4.1.6B: Reading distance 33 cm
Management of Central Field Loss • Magnification: Magnification is another important component

in the management of CFL because it enlarges the size of
Management of overall blurred vision is discussed in the the objects thereby scotoma appears smaller compared to
following steps: the object. Even close reading distance (relative distance
• Eccentric viewing training: One of the most important aspects magnification) is helpful to avoid central scotoma while
of providing LVR services to people with central field reading. Figure 4.1.6A demonstrates the difficulties faced
loss (CFL) involves eccentric viewing training. Apart from while reading at 33 cm in a patient with central scotoma
explaining the ocular condition, the individual should be and the relative improvement in the ability to read when
motivated to use his or her unaffected part of the retina there is magnification of the letters in the reading lines
by means of eccentric viewing technique. This requires (Fig. 4.1.6B). As the extent of the scotoma remains the same,
development of new preferred retinal locus (PRL) that magnification helps in the letters going beyond the extent of
can be used as the "new fovea". Various techniques in the scotoma. Different types of LVDs in the management
eccentric viewing training17 are as follows: of overall field loss have already been discussed.
– Teaching awareness of the scotoma • Contrast enhancing measures: Illuminated magnifiers (such
– Teaching off-foveal viewing as illuminated stand and handheld magnifiers) are useful
– Moving reading material instead of moving the head as most of the conditions are associated with impaired
– Using image relocation method with help of prisms contrast sensitivity. Other contrast enhancing measures
(by placing apex of the prism towards the PRL).18,19 are overhead reading lamp, typoscope, etc.
170 Low Vision
• Glare comfort devices: As described earlier, different tinted • Magnification: Higher the magnification, lesser the visual
glasses, filters, peaked cap, etc. are of use to control glare. field. In advanced peripheral field loss, there is poor
response to higher magnifications. Sometimes, only lower
Peripheral Field Loss magnification is suitable for patients with peripheral field
loss. Various options regarding available LVDs are already
The ability to perceive people or objects to the sides is affected
discussed in the management of overall blurred vision.
in this category of vision loss. Diseases causing peripheral
Different measures to enhance contrast remain similar
field loss even cause partial blurring of vision.
to that of the management of the overall blurred vision.
Different visual functions affected in peripheral field loss
Condition causing PFL rarely cause glare except diseases
are visual field, contrast sensitivity, and in some conditions
like glaucoma, lasered diabetic retinopathy, etc.
even visual acuity (Table 4.1.6). Figure 4.1.7 demonstrates
the visual acuity in patient with peripheral visual loss. Conclusions
Management of Peripheral Field Loss Visual impairment has several impacts on the individual's
Management of peripheral field loss is discussed below: quality of life in different aspects21 that can be significantly
• Different field expanders: Various visual field enhancing improved by providing a comprehensive low vision
measures such as prisms20 (usually helpful in cases of rehabilitation service.22,23
hemianopic defects), mirrors (can be attached to the
LOW VISION DEVICES
spectacles) and reverse telescope and minus lenses (minifies
objects resulting in increased visual field) can be tried, A low vision device (LVD) can be anything that enables the
considering the limitations of each. individual to improve his/her visual performance. There are
• Training in orientation and mobility: A person with peripheral
field loss experiences more difficulty in orientations and
mobility as compared to other two categories of vision
loss. Methods of safe navigation are sighted guide, mobility
using cane, guide dogs, etc. Figure 4.1.8 demonstrates a
mobility cane which aids safe navigation.
Table 4.1.6: Functional implications of

peripheral field loss
visual functions
1. Peripheral field loss a. Difficulty in mobility and orientation
b. Unusual head movements
c. Bumping into objects
Fig. 4.1.7: Vision with peripheral visual loss.
2. Partial blurred vision a. Difficulty in reading and writing
b. Difficulty in recognizing details like
facial features and facial
expressions
c. Difficulty in reading road signs
d. Difficulty in orientation and mobility
e. Difficulty in driving
f . Difficulty in grooming
g. Difficulty in using computers
h. Difficulty in signing
sensitivity b. Seeing time in watch
c. Currency identification
e. Difficulty in reading poor contrast
materials
4. Decreased night vision a. Difficulty in mobility at night
Fig. 4.1.8: Mobility cane
basically three categories of LVDs: optical devices, non-optical

devices and electronic devices.24 Each category shall be
discussed briefly.
Optical Devices
Optical LVDs incorporate lenses resulting in optical
magnification. Telescope is the only optical LVD for
intermediate and distance use. For near, there are mainly
three types of optical LVDs: spectacle magnifier, stand
magnifier, and hand-held magnifier.
Telescope
Telescope (Fig. 4.1.9) is an afocal system used to magnify Fig. 4.1.9: Telescopes of different magnifications
distance objects. It basically provides angular magnification.
There are two types of telescopes, Galilean and Keplerian.
Telescope consists of two elements, one objective (always a
positive lens) and one eyepiece (either a positive or a negative
lens). Here, the secondary focal point of the objective should
coincide with the primary focal point of the eyepiece and
either an erect virtual magnified image (in Galilean telescope)
or an inverted real magnified image (in Keplerian telescope)
is formed. 2X to 20X magnification is available in different
forms of telescope. The optical ray diagrams of the telescopes
are demonstrated in Figures 4.1.10 and 4.1.11.
It provides variable working distances (distance,
Fig. 4.1.10: Optics of a Keplerian telescope
intermediate, near). It can be a monocular or a binocular
device. It can be spectacle-mounted (can be used for
prolonged viewing and therefore hands are free for writing,
etc.) or hand-held (can be used for short-term tasks such as
spot viewing).
Advantages:
• Telescope allows a student to copy from the board in
classroom.
• It also helps in identifying street signs, addresses, traffic
signals.
• It is useful for spot viewing such as reading bus/train
schedule, etc.
• It is available in various forms and different
Fig. 4.1.11: Optics of a Galilean telescope
magnifications.
Disadvantages:
• Restricted field of view. Principle of relative distance magnification is used here.
• Not an aid of choice for patients with restricted fields. Higher the power, shorter the working distances. For high-
• Restricted light gathering properties. powered spectacle, reading material is kept close to the eye,
• More training time is required. thereby providing relative distance magnification. Figure 4.1.13
demonstrates the optical principle of spectacle magnification.
Spectacle Magnifier (SM) Spectacle magnifiers are available from +5.00D to
Spectacle magnifier (Fig. 4.1.12) is a spectacle mounted high +24.00D either as a full field magnifier or as a half eyed
convex lens. spectacle magnifiers.
172 Low Vision
Fig. 4.1.12: Spectacle magnifier with base-in prisms Fig. 4.1.14: Non-illuminated stand magnifier
Fig. 4.1.13: Optics of spectacle magnifier Fig. 4.1.15: Optics of stand magnifier
Advantages: of the lens. This results into a virtual, erect and magnified
• Better cosmesis. image. The optics of the stand magnifier is presented in Figure
• Larger field of view. 4.1.15.
• Binocularity in low magnification. Stand magnifier can be self-illuminated or non-illuminated
• Useful for prolonged reading. (Fig. 4.1.16) ranging up to +76 diopter in different forms.
Most of the stand magnifiers require some amount of
Disadvantages:
accommodation or near addition.
• Close working distance.
• Decreased illumination. Advantages:
• Limited range of magnification. • Fixed focus.
• Inconvenient for spot reading. • May have its own light source.
Stand Magnifier • Useful for spot reading as these are portable and handy.
• High range of magnification (+8.00D – +76.00D).
A stand magnifier (Fig. 4.1.14) is a convex lens mounted at a
fixed distance from the reading material. Disadvantages:
Here, both angular magnification and relative distance • Reduced working distance.
magnification is used. Height of the stand is always shorter • Restricted field of view.
than the focal length of the lens used in the stand magnifier. • Poor posture, unless a reading stand is introduced.
Thereby the reading material is kept within the focal length • Requires flat surface to keep the material.
Fig. 4.1.18: Optics of Hand-held magnifier

Fig. 4.1.16: Different types of stand magnifiers (The one on the left
is an illuminated one, rest are non-illuminated ones)
Fig. 4.1.19: Different types of hand-held and pocket magnifier
Fig. 4.1.17: Hand-held magnifier

Advantages:
• Normal reading distance.
• Good range of magnification.
• Wide field of view in low powered magnifiers with large
Hand-held Magnifier diameter.
A hand-held magnifier is a convex lens that is held by means • Easily available, portable and inexpensive.
of a handle at various distances from the reading plane (Fig.
Disadvantages:
4.1.17).
• Slow and uncomfortable for prolonged reading.
Optics of hand-held magnifier is the same as spectacle
• Must be held at correct distance from the reading material
magnifiers, if the reading material is kept at the focal point
to obtain maximum power.
of the magnifier. However, when the reading material is kept
• Not suitable for patients with tremors and arthritis.
within the focal length of the magnifier, it follows the optics
• Requires more training.
of a stand magnifier. Figure 4.1.18 demonstrates the optics
of hand-held magnifiers.
Electronic Low Vision Devices
Hand-held magnifiers are also grouped into two types
—illuminated and non-illuminated (Fig. 4.1.19) available in These are electronic optical systems that make the object
different forms upto +58.00D. It is always recommended to appear larger. The principle of projection magnification is
use magnifiers over spectacle correction. used here.
174 Low Vision
Electronic low vision devices can be categorized into two Nonoptical Devices
types:
Nonoptical devices are supplementary devices that do not
A. Closed Circuit Television (CCTV)
use any optical lens. We can group the commonly used non-
B. Head Mounted System (HMS)
optical devices under the following seven categories:
Closed Circuit Television (CCTV) A. Relative size and larger assistive devices;
CCTV consists of two major components, camera and a B. Glare and contrast control devices;
monitor. In some of the designs, moveable reading platform C. Posture and comfort maintenance devices;
is also used. Figures 4.1.20A and B demonstrate different D. Orientation and mobility techniques and devices;
types of CCTV. E. Sensory substitution device; and
Higher magnification (up to 70X) can be achieved by F. Medical management and life skill devices.
CCTV. Binocularity is possible even with high magnification Relative Size and Larger Assistive Device
levels. But CCTVs are expensive and needs more training
Large print materials are the best example for relative size
and practice to use, compared to optical LVDs.
magnification. Figure 4.1.21 demonstrates large print books.
Head Mounted Systems
Glare Control Device
There are two types of head mounted systems (HMS), Low
Conditions like glaucoma, albinism, rod cone mono-
Vision Enhancement System and V-max. The details regarding
chromatism produce glare. Use of different tinted glasses,
these are outside the scope of this chapter.
filters, and visors provide great comfort in these situations.
Figure 4.1.22 demonstrates different types of filters used in
different clinical conditions.
Contrast Enhancing Devices
Contrast plays an important role in enhancing the functional
vision of a person. Some nonoptical devices to enhance
contrast sensitivity are mentioned below:
• Overhead reading lamp;
• Felt-tip, black ink pen and bold line paper;
• Filters;
• Typoscope (Letter writer) (Fig. 4.1.23);
• Flash light.
Posture and Comfort Maintenance Device
Fig. 4.1.20A: Camera-Mouse CCTV
Most of the optical devices require closer reading distance.
A reading stand will allow the person to have a comfortable
body posture while reading for prolonged time at a close
Fig. 4.1.20B: Portable CCTV Fig. 4.1.21 Large print books

Fig. 4.1.25: Pre-set insulin syringe
Fig. 4.1.22: Filters
Fig. 4.1.26: Notex
Fig. 4.1.23: Letter writer (Typoscope)

working distance. Figure 4.1.24 demonstrates an appropriate
comfort maintenance device.
Orientation and Mobility Device
Mobility cane is the most commonly and widely used device.
Mobility canes are cost-effective and easily available. It comes
in foldable and unfoldable models (Fig. 4.1.9).
Sensory Substitution Devices
When vision is affected, the loss is compensated using other
residual senses. Some of the sensory substitution devices are
audio books, and Braille.
Medical Management and Life Skill Devices
• Pre-set insulin syringe: This is the most useful device for
Fig. 4.1.24: Reading stand patients with diabetes mellitus (Fig. 4.1.25) and low vision.
176 Low Vision
• Talking clock and watch: These are readily available in the

market at low cost. Both have raised buttons with speech
output option.
REFERENCES
1. WHO. International Statistical classification of diseases, injuries
and causes of death, tenth revision, 1993.
2. Resnikoff S, Pascolini D, Etya'ale D, et al. Global data on visual
impairment in the year 2002. Bull World Health Organ
2004;82(11):844-51.
3. Silver J, Gilbert CE, Spoerer P, Foster A. Low vision in east
African blind school students: Need for optical low vision services.
Br J Ophthalmol 1995;79(9):814-20.
4. WHO. The management of Low Vision in children. Report of
WHO Consultation: Bangkok 1992.
5. Dandona R, Dandona L, Srinivas M, et al. Planning low vision
services in India : A population-based perspective. Ophthalmology
Fig. 4.1.27: Needle threader
2002;109(10):1871-8.
6. Dandona L, Dandona R, Naduvilath TJ, et al. Is current eye-care-
policy focus almost exclusively on cataract adequate to deal with
blindness in India? Lancet 1998;351(9112):1312-6.
7. WHO. Preventing blindness in children: Report of WHO/IAPB
scientific meeting. World Health Organization, Programme for
the Prevention of Blindness and Deafness, and International
Agency for Prevention of Blindness, 2000.
8. Gilbert CE, Anderton L, Dandona L, Foster A. Prevalence of
visual impairment in children: A review of available data.
Ophthalmic Epidemiol 1999;6(1):73-82.
9. Gilbert C. Changing challenges in the control of blindness in
children. Eye 2007;21(10):1338-43.
10. Gilbert C, Awan H. Blindness in children. BMJ 2003;327(7418):
760-1.
11. Dandona R, Dandona L. Childhood blindness in India: A population
based perspective. Br J Ophthalmol 2003;87(3):263-5.
12. The Lighthouse Ophthalmology Resident Training Manual: A New
Look at Low Vision Care: Lighthouse International, 2000.
13. Rudberg MA, Furner SE, Dunn JE, Cassel CK. The relationship
of visual and hearing impairments to disability: An analysis using
the longitudinal study of aging. J Gerontol 1993;48(6):M261-5.
14. Salive ME, Guralnik J, Glynn RJ, et al. Association of visual
Fig. 4.1.28: Color identifier
impairment with mobility and physical function. J Am Geriatr
Soc 1994;42(3):287-92.
15. Laitinen A, Sainio P, Koskinen S, et al. The association between
The patient feels the pre-set level notes and knows how visual acuity and functional limitations: Findings from a nationally
much to inject even if he is not able to see the markings. representative population sur vey. Ophthalmic Epidemiol
• Notex: It is a scientifically accepted device for currency 2007;14(6):333-42.
identification (Fig. 4.1.26). 16. Lovie-Kitchin JE, Whittaker SG. Prescribing near magnification
• Needle threader: It helps in easy threading. Even a person for low vision patients. Clin Exp Optom 1999;82(6):214-24.
17. O'Connell WF. Eccentric viewing, remidiation and management
with visual impairment can pass time meaningfully
of low vision: Mosby, 1996.
(Fig. 4.1.27). 18. Verezen CA, Volker-Dieben HJ, Hoyng CB. Eccentric viewing
• Color identifier: Color identifier is helpful for those who spectacles in everyday life, for the optimum use of residual
cannot differentiate colors due to their vision problem. functional retinal areas, in patients with age-related macular
Color identifier is a tactual identifier (Fig. 4.1.28). degeneration. Optom Vis Sci 1996;73(6):413-7.
19. Rosenberg R, Faye E, Fischer M, Budick D. Role of prism 22. McCabe P, Nason F, Turco PD, et al. Evaluating the effectiveness
relocation in improving visual performance of patients with of a vision rehabilitation intervention using an objective and
macular dysfunction. Optom Vis Sci 1989;66(11):747-50. subjective measure of functional performance. Ophthalmic
20. Perlin RR, Dziadul J. Fresnel prisms for field enhancement of Epidemiology 2000;7:259-70.
patients with constricted or hemianopic visual fields. J Am Optom 23. Vijayakumar V, John RK, Datta D, et al. Quality of life after
Assoc 1991;62(1):58-64. community-based rehabilitation for blind persons in a rural popu-
21. O'Connor P, Keeffe J. Focus on Low Vision: Centre for Eye lation of South India. Indian J Ophthalmol 2004;52(4):331-5.
Research Australia, 2007. 24. Brilliannt RL. Essentials of low vision practice, Butterworth-
Heinemann, Boston, 1999.
Chapter 4.2
EXAMINATION OF PATIENTS
WITH LOW VISION
Deepak K Bagga
The main objective in examining patients with low vision is to – Appearance: Fatigued appearance indicates systemic
identify those who might benefit from low vision rehabilitation disorder and depression resulting from recent vision
programs, evaluate their functional needs, and needs for loss or impact of other psychosocial factors. Soiled
assistive devices and training. clothing or missing buttons indicate difficulty in daily
living skills. Sunglasses worn inside the examination
STRUCTURED EXAMINATION room indicates severe photophobia/glare.
In the absence of an appropriate evaluation of visual – Mobility: While escorting the patient from the waiting
functions, the choice of rehabilitation options depends room to the examination room, the tentative gait,
primarily on trial and error with different devices and postural stiffness, maintenance of close proximity to
interventions, which may frustrate the patients.1 The base of walls or handrails and reliance on tactile information
current evaluation of visually impaired patients was laid down by holding onto an individual or trailing a wall should
by Dr William Feinbloom in 1935.2 The first four elements be looked for. These are indicators of advanced visual
(A-D) of the structured examination is briefly discussed in field loss.
the subsequent section. • Assessment of functional needs: The assessment starts
with a comprehensive history which reveals:
Elements of Structured Examination i. How has the vision impairment impacted the person's
• Review of medical records. daily activities?
• Observation. ii. What does the patient do or want to do?
• Assessment of functional need. The components of history include:
• Assessment of abilities and limitation of visual system. – Ocular history
• Calculating magnification. – Medical history
• Selection and trial of appropriate assistive devices. – History of previous vision rehabilitation care
• Review of medical records: Reviewing of previous – Specific literary requirements (textbook, a devotional
medical and surgical records of the patient serve as a book, the newspaper or mail)1
guide to the starting point for examination of visual acuity, – Other near and intermediate visual abilities and needs
and refraction. (writing, sewing, cooking, viewing the computer, a
• Observation: calculator screen or a watch)
– Postural Abnormality: Usually the head turn or tilt is – Distance vision tasks (recognizing faces from distance,
noticed towards the direction of visual field loss.3 reading bus numbers)
Increased head and eye movement for distance – Basic and instrumental activities of daily living (routine
indicates advanced visual field loss, whereas head turn housekeeping duties like cleaning, paying bills, laundry,
while reading may indicate scotomas in the central self-help skills and home making, etc.)
visual field. – Independent travel ability and needs
Examination of Patients with Low Vision 179
– Photophobia, glare, and lighting requirements

– Social history (about family, interactions and support
and emotional status)
– Educational concerns (mode and model of education,
academic performance, copying from chalkboard,
visual environment in the classroom, sitting position,
and access to computer technology adapted for visual
impairment, closed circuit magnification, audio
textbooks or a personal reader/note taker in the
school)
– Employment issues (status of employment, type of
work/nature of job, visual requirements for the job,
visual environment and lighting)
– Recreational concerns (problem in watching television).
Thus, at the completion of the case history, the examiner
has an idea of the patient's aspirations and goals, whether or
not they are reasonable, the patient's reaction to the vision
loss, and determines how much time to spend with the patient.
To be precise, the examiner can sense what can and cannot
be covered during the first visit, without fatiguing the patient.
• Assessment of capabilities and limitation of the visual system:
Following the comprehensive history, visual functions and
visual systems are examined. The tests and techniques
Fig. 4.2.1: Bailey-Lovie chart No. 4 (National Research
are tailored to suit each patient's visual impairment.4 Institute of Australia)
ELEMENTS OF CLINICAL EXAMINATION

• Visual acuity (distance and near)
• Refraction
• Contrast sensitivity
• Color vision test
• Visual field assessment
• Glare test
• Ocular motility and binocular vision assessment
• Ocular health examination.
Visual Acuity (VA)
Distance Visual Acuity

The ideal chart for recording visual acuity should have high
contrast, geometric progression of size difference between lines
and proportional spacing of optotypes. It should maintain a
consistent number of letters in each row and should allow
testing at non-standard testing distances of 4 meters or closer.5
The logMAR (Minimum Angle of Resolution) test charts fulfill
these requirements. Some of the frequently used charts are: Fig. 4.2.2: Lighthouse distance visual acuity chart (Sloan letters)
• Bailey-Lovie logMAR letter chart (Fig. 4.2.1)
• Lighthouse distance visual acuity charts (Sloan letters) • Feinbloom chart (Fig. 4.2.3)
(Fig. 4.2.2) • Lea Symbols chart (Precision vision) (Fig. 4.2.4)
180 Low Vision
Fig. 4.2.3: Distance test chart for the partially sighted

(By William Feinbloom)
Monocular as well as binocular visual acuity is recorded

using age appropriate test chart.6 Visual acuity test begins
from a reduced test distance of 4 meter. Patients' with macular
degeneration are encouraged to view eccentrically while
recording visual acuity. When the top line cannot be seen
from 4 meter, the test distance is reduced to 2 meter or 1
meter and then to 0.5 meter till the patient is able to read a Fig. 4.2.4: Lea Symbols (developed by Lea Hyvarinen, MD)
couple of letters or lines. The visual acuity is then recorded
as the smallest line seen (e.g. 0.5/24, which means that a for comparisons this can be converted and documented as
person with normal vision can see this letter from a distance 6/288 or 20/960). Table 4.2.1 provides the distance VA
of 24 meter, which is seen by the eye under test at 0.5 meter; conversion chart for this purpose. When visual acuity falls
Table 4.2.1 Distance VA conversion chart

Test distance 0.5 1 1.5 2 2.5 3
Letter size meter feet meter feet meter f eet meter f eet meter f eet meter feet
38 456 1520 228 760 152 506.7 114 380 91.2 304 76 253.3
30 360 1200 180 600 120 400 90 300 72 240 60 200.0
24 288 960 144 480 96 320 72 240 57.6 192 48 160.0
19 228 760 114 380 76 253.3 57 190 45.6 152 38 126.7
15 180 600 90 300 60 200 45 150 36 120 30 100.0
12 144 480 72 240 48 160 36 120 28.8 96 24 80.0
9.5 114 380 57 190 38 126.7 28.5 95 22.8 76 19 63.3
7.5 90 300 45 150 30 100 22.5 75 18 60 15 50.0
6 72 240 36 120 24 80 18 60 14.4 48 12 40.0
4.8 57.6 192 28.8 96 19.2 64 14.4 48 11.52 38.4 9.6 32.0
3.8 45.6 152 22.8 76 15.2 50.7 11.4 38 9.12 30.4 7.6 25.3
3 36 120 18 60 12 40 9 30 7.2 24 6 20.0
2.4 28.8 96 14.4 48 9.6 32 7.2 24 5.76 19.2 4.8 16.0
1.9 22.8 76 11.4 38 7.6 25.3 5.7 19 4.56 15.2 3.8 12.7
To use this chart:

X-axis Test distance (in meter)
Y-axis Letter size (in meter)
Example: if patient reads 24 letter size at 0.5 meter, the VA is recorded as 0.5/24, or 6/288 or 20/960
Similarly if patient reads 2/30, using conversion table we know it is equal to 6/90 or 20/300
VA: Visual Acuity
below that which can be recorded on standard chart at 0.5

meters, the examiner proceeds to test for projection of rays
and perception of light (PL). Distance VA checked with a
multiple pinhole may indicate existing refractive error.
Near Visual Acuity
Graded continuous text materials provide comparatively
precise measure of reading ability than single optotypes
measure. Some of the commercially available test charts are
Bailey-Lovie word reading chart (Fig. 4.2.5),7 Lighthouse
"NUMBER" card, Lighthouse near visual acuity test chart
(Modified ETDRS with Sloan letters), LEA symbols,
Logarithmic near visual acuity chart "2000" chart "2" (for
testing at 40 cm) (Fig. 4.2.6). Fig. 4.2.5: Bailey-Lovie word reading chart (National Vision
Recording of binocular near acuity is performed by Research Institute of Australia)
asking the patients to read the smallest line of words using
appropriate reading correction (if needed). If the patients is
a prepresbyope or a child, he/she is encouraged to hold the
NV chart close to their face (as close as possible). Patients are
re-assured that reading at close distance is not harmful to their
eyes. Attention is paid to the preferred level of illumination.
Refraction
In routine eye care, the emphasis lies on attention to the
medical and surgical aspects of the eye condition and in the
process, correction of ametropia may be ignored. However,
it is important to correct refractive error, as the patient may
appreciate a subjective improvement in functional ability with
glasses and the performance with assistive devices may also
improve with glasses.
Objective Refraction
Fig. 4.2.6: Logarithmic near visual acuity chart "2000" chart "2"
Preferably retinoscopy is performed with a wide aperture
(For testing at 40 cm)
trial lens, using an adjustable trial frame. A large fixation target
is given. In cases of nystagmus or unique head posture, loose
lenses or lens racks and the techniques that allow for eccentric accommodation cannot be relaxed for manifest refraction
(by fogging), refraction under cycloplegia is considered.
viewing are employed. While observing through the peephole
of the retinoscope, examiner moves close to the eye until Phoropter is not recommended for refraction of visually
impaired patients because the reflex is comparatively poor
either a 'with' or 'against' movement is clearly visible (Radical
retinoscopy).8 This is essentially useful in high myopia or those (due to multiple lenses). Maintaining a stable vertex distance
and eccentric viewing is difficult with the phoropter and
with small pupils. It is important to note that shorter the
working distance, the smaller the zone of neutrality, thus incorporation of other special trial filters, doublet microscopes
and telescopes is not possible.
chances of error is high. To find a reflex that may not be
apparent when refracting along the visual axis moving off Keratometry is a very useful procedure for estimating
the axis is helpful. In case of high astigmatism, each meridian astigmatic error in cases where good retinoscopy findings
can be neutralized independently. In case of media cannot be obtained because of poor or irregular/scissors
irregularities, opacities and miotic pupils6 retinoscopy is reflex. In case of latent nystagmus, it is performed without
repeated under mydriasis. In cases where amplitude of occlusion of the other eye.
accommodation is high (especially children) and
182 Low Vision
Subjective Refraction • Low contrast flip chart with Lea SYMBOLS (Developed
Subjective refraction is generally performed using an adjustable by Lea Hyvarinen).14
trial frame and wide-aperture loose lenses. Trial frame should
fit well so that refraction can be performed as close as possible
to the patient's normal vertex distance, allowing the eccentric
viewing positions. Trial lens clips can also be used over the
patient's habitual glasses. In case keratometry and retinoscopy
are not possible, power of the current spectacle prescription
can be taken as the starting point for subjective refinement.
Refraction should be performed at a distance where the
patient can read multiple optotypes on a line. If refracting at
a distance closer than 4 m, refraction should be corrected
for the object distance. For example, when refracting at 1 m,
the patient accepts 1.00D more plus than the true refractive
error, so –1.00D should be added to the refraction for distance
correction.
Bracketing is a useful technique for subjective refraction.
The strength of bracketing lenses depends on 'Just Noticeable
Difference' (JND). JND is the amount of spherical lens
change at which a change in clarity or blur is first noticed.
JND (for working distance 6 m) = Snellen Acuity
Denominator/30
Example: For presenting acuity of 6/60, the JND will be 2D
(denotes width of the bracket) and bracketing lenses ± 1.00D.
As the patient accepts the lenses, improvement in VA is Fig. 4.2.7: Pelli-Robson contrast sensitivity chart
recorded and smaller bracket lenses are used. To refine the
astigmatic correction, the choice of Jackson Cross Cylinder
(JCC) depends on the patient's JND after the spherical
refraction. Usually JCC of ±1.00 D, ± 0.75 D and ± 0.50 D
lenses are used.
Contrast Sensitivity
Contrast sensitivity (CS) is the ability to detect objects at low
contrast and is a better predictor of real world functioning.
This measure has been shown to relate visual functioning
and activities of daily living more closely than visual acuity
measured with high contrast tests.9 It is an important test to
help in the prescription of adaptive devices, so that lighting
and other nonoptical devices can be considered. Further in
determining the need of a higher than predicted add, need
of occlusion is based on impairment (Structured low vision
examination, Lighthouse International). The commercially
available test charts are:
• Pelli-Robson chart (Fig. 4.2.7)10
• Mars letter contrast sensitivity chart11-13
• Hiding Heidi low contrast "FACE" test (Developed by Fig. 4.2.8: Hiding Heidi low contrast "FACE" test
Lea Hyvarinen) (Fig. 4.2.8) (Developed by Lea Hyvarinen, MD)
Glare Test
The Brightness Acuity Tester (BAT) is used to subjectively
determine the effect of a glare on visual performance.17,18
The alternative objective method to observe glare is by taking
the patient outside the clinic in the bright sun and look for
squeezing of lids, movements of head downwards, use of
hand as visor, mobility (comfort, speed, any use of tactile
Fig. 4.2.9: Farnsworth D-15 color test kit clue, bumping into object). The effect of filters to relieve
glare is subsequently tried.19,20
Low Contrast Visual Acuity Charts (LCVA)
Ocular Motility and Binocular
Contrast sensitivity can be indirectly measured by using low Vision Testing
contrast visual acuity charts. Low-contrast letter charts have
several advantages including sensitivity to detect sub-clinical Presence or absence of binocularity helps decide the
appropriate assistive devices. Patients with tunnel vision may
vision loss, speed, low cost and familiarity of test procedure.15
experience a breakdown in binocular vision. Available Stereo-
In this chart, the letter size varies and contrast is fixed. Low
tests are Stereo fly test, Reindeer test, etc.
contrast charts are usually printed at 10 percent, 5 percent,
2.5 percent and 1.2 percent contrast.
Ocular Health Examination
Color Vision Test External examination (with torch light), slit-lamp bio-
microscopy, tonometry, direct and indirect ophthalmoscopy
Color vision test indicates the level of difficulty a patient are performed as a routine. This is important to ensure that
may have in performing tasks that require processing of there are no treatable lesions that may require medical
color information such as that used in activities of daily living intervention or referral to other specialist.
(i.e. matching cloths, coloring, recognizing traffic signals, etc.).
Most commonly used color vision tests include Ishihara Low Vision Care Providers
(Pseudo-isochromatic color plates), and Farnsworth
dichotomous test (D-15) color arrangement tests (Fig. 4.2.9). Low vision clinicians (optometrists/ophthalmologists) play an
important role in the management of patients with mild to
Visual Fields Assessment moderate vision loss. However, patients with progressive vision
loss, with severe visual impairment and/or additional
It helps in understanding the abilities of the patient to perform disabilities require comprehensive rehabilitation care by a
day-to-day activities, indicates the expected response to multidisciplinary team.
various rehabilitative approaches and whether the patient is Primary role of optometrists/ophthalmologists is
eligible (legal blindness) to avail support services. assessment of patients with low vision, prescribing low vision
Peripheral visual fields may be tested by confrontation, devices (LVDs), training in use of LVDs, dispensing LVDs,
manual perimeters and automated perimeters. If the purpose patient education and follow-ups. However the rehabilitation
of visual fields (VF) testing is not to determine legal blindness, professionals offer a wide range of services which is beyond
confrontation or standard tangent screen testing may provide the expertise of low vision clinicians. Rehabilitation
needed useful information. Advanced peripheral field professionals, counselors, mobility instructors, special
constriction signals a need for orientation and mobility training educators, social workers, and occupational therapists are the
or educational/vocational modifications.16 other key members of the multidisciplinary team.
Amsler grid is the most commonly used test for evaluating
the integrity of the central visual field. Some patients have The author and editors have no financial interest in any procedures or products
smaller scotomas when observing the grid binocularly than mentioned in this chapter.
they have with each eye alone, whereas other patients may
have larger scotomas binocularly. This information helps in REFERENCES
making the choice of assistive devices (monocular vs. 1. Whittaker SG, Lovie-Kitchin J. Visual requirements for reading.
binocular) for the individual. Optom Vis Sci 1993;70:54-65.
184 Low Vision
2. Feinbloom W. Introduction to the principles and practice of sub- 12. Haymes SA, Roberts KF, Cruess AF, et al. The letter contrast
normal vision correction. The Journal of the American Optometric sensitivity test: clinical evaluation of a new design. Invest
Association 1935;VI:3-18. Ophthalmol Vis Sci 2006;47:2739-45.
3. Zagora E. Observations on Compensatory Adjustments in One- 13. Dougherty BE, Flom RE, Bullimore MA. An evaluation of the Mars
Eyed Persons. Br J Ophthalmol 1959;43:596-601. Letter Contrast Sensitivity Test. Optom Vis Sci 2005;82:970-5.
4. Markowitz SN. Principles of modern low vision rehabilitation. 14. Leat SJ, Wegmann D. Clinical testing of contrast sensitivity in
Can J Ophthalmol 2006;41:289-312. children: age-related norms and validity. Optom Vis Sci
5. Bailey IL, Lovie-Kitchin JE. New design principles for visual 2004;81:245-54.
acuity letter charts. American Journal of Optometry and 15. Regan D, Neima D. Low-contrast letter charts in early diabetic
Physiological Optics 1976;53. retinopathy, ocular hypertension, glaucoma, and Parkinson's
6. Rubin GS, Munoz B, Bandeen-Roche K, West SK. Monocular disease. Br J Ophthalmol 1984;68:885-9.
versus binocular visual acuity as measures of vision impairment 16. Ellen E. Freeman BM, Gary Rubin, and Sheila K West. Visual
and predictors of visual disability. Invest Ophthalmol Vis Sci field loss increases the risk of falls in older adults: The Salisbury
2000;41:3327-34. Eye Evaluation. Investigative Ophthalmology and Visual Science
7. Bailey IL, Lovie-JE. The design and use of a new near-vision 2007;48:4445-50.
chart. American Journal of Optometry and Physiological Optics 17. Elliott DB, Bullimore MA. Assessing the reliability, discriminative
1980;57:378-87. ability, and validity of disability glare tests. Invest Ophthalmol
8. Grosvenor TP. In: Primary Care Optometry. 5th edn. Elsevier Vis Sci 1993;34:108-19.
Health Sciences 2006;200. 18. Smith PW, Pratzer KA, Webster N, Fenton J, Bonham RD. A
9. Owsley C, Sloane ME. Contrast sensitivity, acuity, and the per- clinical comparison of two methods of glare testing. Ophthalmic
ception of 'real-world' targets. Br J Ophthalmol 1987;71:791-6. Surg 1987;18:680-2.
10. Pelli DG, Robson JG, Wilkins AJ. The Design of a new letter 19. Eperjesi F, Fowler CW, Evans BJ. Do tinted lenses or filters
chart for measuring contrast sensitivity. Clinic Vision Sci improve visual performance in low vision? A review of the
1988;2:187-99. literature. Ophthalmic Physiol Opt 2002;22:68-77.
11. Thayaparan K, Crossland MD, Rubin GS. Clinical assessment of 20. de Fez MD, Luque MJ, Viqueira V. Enhancement of contrast
two new contrast sensitivity charts. Br J Ophthalmol 2007;91:749- sensitivity and losses of chromatic discrimination with tinted
52. lenses. Optom Vis Sci 2002;79:590-7.
Chapter 4.3
REHABILITATION OF THE
VISUALLY HANDICAPPED
Beula Christy
"Rehabilitation involves the combined and coordinated use of medical, system offers education and services including medical,
social, educational and vocational measures for training or retraining academic, extra-curricular, social, vocational courses,
the individual at the highest possible level of functional ability" — placement and follow-up. The residential school is designed,
International Labor Organization (ILO).1 equipped and staffed specifically to meet the needs of the
Rehabilitation signifies restoration of any individual to visually impaired children.
previous, probable or possible activities, which that person
may perform despite visual impairment after certain training, Integrated Education
retraining, and other tangible or intangible inputs. In the general
Integrated education refers to the measures taken to provide
sense, rehabilitation encompasses:
educational resources within the ordinary educational system
• Medical rehabilitation, i.e. cure of the curable disability
for those children who need them. The aim of integration is
and lessening the disability to the extent possible
to avoid or reduce restrictions on any aspects of a child's
• Educational rehabilitation
development which might result from segregated education.
• Complete social integration
This system provides equal educational opportunities and
• Economic rehabilitation to the extent possible for the
experiences to children with disabilities, with the assistance
working age group
of a trained specialist teacher, in the least restrictive
• Providing all the available concessions, benefits, guidance
environment such as a regular school.
and counseling.
The approach to rehabilitation is highly individualized and
Inclusive Education
personalized. The nature of the rehabilitation program
depends on the severity of the disability, and its onset, in In inclusive education all the children learn together, as far as
childhood, youth, adulthood or old age. possible, regardless of any difficulties or differences they
may have. It is teamwork in the school, with the class teacher
EDUCATIONAL REHABILITATION playing the major role and being provided with the following
support services:
Visually challenged children require special forms of education
• Supply of special teaching aids and materials
that provide facilities which is otherwise not possible in the
• Availability of assistance by the parents, volunteers or
ordinary educational provisions. The three important models
older students
of special education are: (1) Residential schools 1,2 (2)
• Modification or adaptation of the physical environment,
Integrated education1,2 and (3) Inclusive education.3
curriculum, timetable and evaluation procedures as per
the specific needs of the child
Residential Schools
• Provision of in-service training to upgrade his/her
In this system of education, the visually impaired children knowledge and skills
are usually provided with free boarding and lodging. This • Appropriate services of guidance and counseling.
186 Low Vision
SPECIAL EDUCATIONAL dealing with the study needs of the visually impaired students.
DEVICES FOR THE BLIND Rather, each student needs to be considered individually, and
this necessitates individual discussion and negotiation. A child
The following educational devices are in use for the children
with visual impairment (Fig. 4.3.1):1 may need a single medium or a combination of media.4
• Braille duplicators and writers: For example, Brailler, and • Regular print: Most children will improve their reading of
Thermoform machine are useful in making Braille regular print at closer distance under good lighting. As
matters. reading from closer distance does not harm vision, it
• Writing devices: Braille slates, Taylor postcard frame, pocket should be encouraged. Children with visual impairment
Braille frame and the Braille paper. should be encouraged to sit by an open veranda/window
• Talking books and tape recorders: The material recorded on to take advantage of natural illumination. Provision of
cassettes has emerged to be a popular mode of imparting an overhead reading lamp enhances contrast in the print
education. and helps increase the reading speed.
• Reading machines: Kurzweil reading machine, which reads • Large print: Large format print enables a visually impaired
typeset or typewritten text and turns it into speech is a person to read conveniently. Non-availability of ready-
very useful mode. made large format print could be tackled in the following
• Assistive software: JAWS screen reading software, MAGIC ways: (a) Enlarge the regular text to a comfortable reading
screen reading and magnifying software, Braille window, size for the child by making a good quality photocopy.
Index Braille, Braille'n Speak, etc. are softwares that can (b) Re-type or scan the text and make large size printouts
be used with personal computers. if there is access to a computer. (c) Have volunteers
• Mathematical devices: Taylor arithmetic frame, abacus, talking (student, family members, and social workers) prepare
calculator, spur wheel, etc. helps in learning mathematics. large size handwritten materials (Fig. 4.3.2).
• Geography devices: Sensory quill and raised maps help in • Low vision devices: Optical and nonoptical devices could be
learning geography. of great use to children with visual impairment in tackling
• Science devices: Three dimensional, raised charts help in most classroom problems. Visually impaired children might
learning human physiology, zoology, and botany. benefit greatly by the use of the simple monocular
telescope for board work and stand magnifier for reading
SUPPORTIVE LEARNING MEDIA text. Bold lined notebooks and dark lead pens and pencils
FOR THE EDUCATION OF enhance contrast and help improve writing skills (Figs
A VISUALLY IMPAIRED 4.3.3 and 4.3.4).
All students are unique, and each child's visual problem is • Audio books: Audio books are books that are recorded on
different. Therefore, there can be no standard templates for cassette tapes for those who are unable to read regular
Fig. 4.3.1: Special educational devices Fig. 4.3.2: Large print books
Rehabilitation of the Visually Handicapped 187
printed materials. Audio books are a proven learning tool • Braille: For children whose eyesight prevents them from
for children with severe visual impairment (Fig. 4.3.5). reading and writing print, Braille is the route to literacy.
• Assistive technology: Assistive technology, computer literacy Braille helps children with residual vision to read for longer
and information access are important to everyone in periods of time without experiencing eye fatigue and strain
society, the visually impaired not excluded. Information during the non-availability of magnifiers, scanners, audio
that would otherwise be inaccessible or requires manual books and computers. When children have eye conditions
processing to become accessible can be automatically that may worsen over time, learning Braille early gives
transformed into formats better suited for the visually them more options. Hence, it is better to teach Braille to
impaired. Assistive technologies are becoming the main a student with low vision who might need it in few years
stream, thus increasing the opportunities in terms of (Fig. 4.3.7).
employment and education (Fig. 4.3.6).
Fig. 4.3.3: Use of telescopes Fig. 4.3.4: Use of magnifying devices like stand magnifier
Fig. 4.3.5: Use of audio books Fig. 4.3.6: Use of assistive technology
188 Low Vision
Fig. 4.3.7: Use of Braille Fig. 4.3.8: Economic rehabilitation (Case 1)
HELPFUL GUIDELINES IN DECIDING • Reading rates and accuracy: Can the child read with good
THE LEARNING MEDIA4 speed and accuracy (95% at least) with the medium
These are:4 selected? Is there any measurable growth in reading rates,
• Age of the child: Is the child mentally ready to understand vocabulary and comprehension with the suggested mode?
the concept of a specific device? Has the child developed • Visual fatigue: The optimal-sized print for a primary
the motor skills to manipulate a suggested device? Is the learning medium is the size that a student can read for an
suggested device appropriate to use for the age of the extended period of time, without experiencing fatigue.
child? (e.g.: A four-year-old child might have difficulty in Can the print size chosen for primary learning medium
manipulating devices such as telescope and computer allow the student to demonstrate consistency of
software). performance throughout the day? Can the student rely
• Support from the family: Will/does the child receive any upon this medium to meet all his educational visual
educational support from the family? Are the family demands?
members willing to provide support to continue the use
of the specifically selected mode? (e.g. The practicality ECONOMIC REHABILITATION
of preparing large print materials, audio cassettes). Economic rehabilitation includes any trade; economic activity
• Residual vision of the child: Can the child read at the same or profession which enables an individual to make any tangible
speed using the devices without getting tired? The priority- or intangible contribution; any monetary or non-monetary
reading mode whether print, Braille or a combination of service support to the family or community in the organized
both can be decided depending on the residual vision. as well as the unorganized sector (Figs 4.3.8 and 4.3.9).1,2
• Stability of vision: Is there any risk of further deterioration The main economic rehabilitation categories include:
of vision? Will the vision be stable both during the day • Traditional rural crafts and activities (e.g. weaving)
and the night? (e.g. a child with retinitis pigmentosa is • Small businesses and petty shops (e.g. provisional stores)
more likely to lose residual vision. Hence, it is safer to • Small cooperatives (e.g. local cigar making)
introduce Braille/audio cassettes as a secondary mode • Agriculture and horticulture (e.g. farming)
early). • Technical and professional activities (e.g. lawyers, teachers)
• Economic status of the family: Can the family afford to • Dairy and animal husbandry (e.g. cattle rearing).
purchase the suggested device? (e.g. if the child's visual
requirement demands a closed circuit television to read SOCIAL REHABILITATION
print, will the family be able to afford it?).
• Visual need of the child: Does the device help the child to The component of social rehabilitation includes skills training
read the required print size for his/her grade level more for independent mobility, communication skill and activities
easily? of daily living.
Fig. 4.3.9: Economic rehabilitation (Case 2)
Mobility is the art of moving from one place to another

independently, safely and gracefully. Orientation is the science
of using all other senses by a person to become aware of
his/her surroundings, places and things, both movable and
immovable, in relation to his/her own position.1,2
IMPORTANCE OF ORIENTATION
AND MOBILITY Fig. 4.3.10: Assistive training with cane
Enhances independence: As being able to travel freely is very
important for a sense of independence, it is an important
prerequisite for integration into the community and working
life.
Safety of the individual: It enhances the safety of the individual
and his fellow men.
Self-image: It is essential for correcting gait and postural defects.
It is not just overcoming the practical difficulties, but also a
step towards developing and maintaining one's own self-image.
Leads to comprehensive rehabilitation: It is a step towards
comprehensive rehabilitation, self-confidence and also
liberation from solitude. It also helps in changing public
attitudes towards blindness.
Mobility Techniques
There are four mobility techniques currently available to the
blind (Figs 4.3.10 and 4.3.11).
a. The use of a sighted guide;
b. The use of a cane;
c. The use of an electronic aid; and
d. The use of a guide dog. Fig. 4.3.11: Sighted guide technique
190 Low Vision
Only the first two are generally used in India. The use of Services for Multi-handicapped Children
a guide dog and the use of an electronic aid is not very
• Parental counseling and guidance: Explaining the prognosis of
practical and also are not cost-effective in developing countries.
the condition and preparing the parents to accept reality.
• Assessment of additional disabilities: Ruling out additional
SERVICES FOR CHILDREN WITH
disabilities (motor, speech and cognitive impairment).
MULTI-HANDICAPS
• Individualized intensive training: Special skills in areas
Multi-handicapped refers to a condition where a person has such as orientation, mobility, and daily living, skills, to
more than one disability, in combination with the vision loss. enhance functional independence.
Early intervention is required for children of ages between • Training to the parents: Training on selection of
birth and five years, who are at risk of developmental delay educational and play materials, safety measures and
in the form of absence of age specific developmental environmental modifications required for children with
behavior and the multi-handicapped. Early intervention can additional disabilities.
make a major difference to the development of a child who • Functional education: Functional literacy in reading,
may not be able to communicate visual problems verbally. writing and arithmetic skills.
Early intervention aims to provide remedial or preventive • Adaptive devices and materials: Arrangements to access
services to reduce the effects of the condition (Figs 4.3.12 devices required for training the child.
and 4.3.13).5-9 • Multi-sensorial training: Training in vision stimulation,
speech therapy and physiotherapy.
Vision Stimulation
Children born with impaired vision do not know how they
are expected to see the world.7
Vision is a learned and developed skill that requires
stimulation and experience as the children must learn to use
their vision in learning to walk and talk. The visual system
interacts with the muscles of the body to develop reaching,
crawling, grabbing and walking movements. Without patterned
stimulation, these areas of the brain do not develop the ability
to process visual information. As vision requires stimulation,
problems that occur in the eye or in the visual areas of the
Fig. 4.3.12: Training of multi-handicapped children (Case 1) brain can affect the child's vision. Examples of these problems
include eye diseases, such as congenital cataracts, retinopathy
of pre-maturity, ocular albinism, optic nerve and retinal
disease, neurological abnormalities of the visual pathways
and visual centers of the brain. Vision stimulation helps in
improving the child's eyesight, eye movement skills, eye
teaming, focusing, depth perception, color vision, peripheral
vision, visual perception and processing, and the ability to
integrate all of this information with other senses (Figs 4.3.14
to 4.3.16).
VISION STIMULATION MATERIALS

Vision stimulation materials include pen light, color lamp, shiny
and glittering papers such as silver foil papers, decorative
materials, glow balls, gift wrappers, contrast checker boards,
Fig. 4.3.13: Training of multi-handicapped children (Case 2) charts, fluorescent toys, and stickers (Fig. 4.3.17).
Fig. 4.3.14: "Be active" box. This child is made to lie inside this Fig. 4.3.15: Vision stimulation with contrast checkerboards
small enclosure and exposed to visual stimulation made possible by
the over hanging toys
Fig. 4.3.16: Vision stimulation with striped stimulus Fig. 4.3.17: Vision stimulation material
Points to Remember CONSIDERATIONS FOR

• Stimulation activities with any source of light (torch, lamp, CHILDREN WITH LOW VISION
etc.) should not be continued for more than five minutes IN MAINSTREAM EDUCATION
in case of any previous history of convulsions in the
child as it can further aggravate the problem. According to UNICEF’s report on the status of disability in
• The child should not be made tired by over stimulation. India there were around 30 million children suffering from
• Vision stimulation should be integrated with other sensory some form of disability.10 The sixth All-India Educational
stimulation. Survey (NCERT, 1998) reports that of India's 200 million
• The child should be positioned such that he uses the best school-aged children (6–14 years), 20 million require special
part of the visual field. needs education. 11 While the national average of gross
192 Low Vision
enrollment in school is over 90 percent, less than five percent Environmental Considerations
of children with disabilities are in school. The majority of
Environmental factors include color, contrast, time, space,
these children remain outside mainstream education. Despite
and illumination. These can be easily manipulated in enhancing
the efforts taken by the National Policy on Education for
visual functioning. The type of modification required for
‘Education for all’, a proportion of children with disabilities
each factor may vary according to the child’s individual needs.
including visual problem are not included in the school.12
Some children may depend on color cues, while others need
Equal opportunity for education is possible through the present
good contrast in printed or graphic materials. Most children
global concept of inclusive education program, where a blind
need good lighting though and a few may need minimal
child attends the same school as their sighted siblings and the
same class where they get education with the same teacher illumination in order to see optimally. Some children need
who is competent and able to provide resource assistance to extra time when using vision for functional tasks, and others
the children. While comparing the models of education, may find visual concentration easier when pictures, words,
inclusive model is the only viable option to include more or numbers are spaced well apart. The teacher can make
number of visually challenged children in educational suggestions for visual comfort and efficiency, based on each
institutions. Children in special schools were seen as child’s individual visual needs.
geographically and socially segregated from their peers, and
the initial movement to integrate these students in mainstream Contrast
schools (‘integration’) shifted to one where the whole school • It should be ensured that the blackboard is painted
was encouraged to become more adaptable and inclusive in frequently to enhance contrast. As far as possible color
its day-to-day educational practices for all students (‘inclusive boards and color chalks should be avoided and white
education’).
chalks on blackboard should be used.
Below are the strategies that provide an opportunity for
• Paper with bold lines and enlarged spaces and black felt
the visually impaired student to make complete use of his/
tipped pens increase contrast for a student when writing.
her range of residual vision and thus participate fully in
• Contrast should be considered when producing materials
classroom activities.
for a student. Better contrast around pictures and symbols
Teaching Strategies should be created.
Some of these strategies are: Lighting

• While writing on the board, the contents should also be • It should be ensured that lighting conditions are
read out slowly and loudly appropriate for the student’s vision impairment.
• Large print maps, hung at eye level, should be used • A desk lamp should be used to increase the contrast on
• The time limit on achievement tests should be waived the work surface. Additional lighting may be required.
• Completion of most reading and writing tasks in the morning
• Additional lights in areas where the student moves, such
should be encouraged as the child may be less tired
as stairs, covered walkways, and toilets should be
• Suitable intervals between sessions should be allowed
considered.
• White or yellow chalk on a clean black chalkboard should
be used to increase contrast Glare
• Visual clutter on the chalkboard should be reduced
• Young students can focus at short distances, so concern • The student’s sensitiveness to glare should be assessed.
about the short reading distance should not be there • A student should not be positioned such that he/she faces
• Signs of vision fatigue such as red or watering eyes, rubbing a light source (natural or artificial).
eyes and/or headaches should be watched for. Rest breaks • The light source should not be placed behind the examiner.
should be allowed • Sunglasses and a peaked cap for the student may be
• Time for the student to explore materials at a close distance considered particularly when outside in the playground.
should be allowed • Glare in the classroom should be reduced with blinds,
• Verbal rewards and praise should be used as the student curtains, and posters. Windows producing glare should be
cannot see a smile or nod of the head covered.
• It should be ensured that all relevant staff are aware of • Computer screens should be placed to minimize glare. A
the student's vision impairment and the related implications. black background on the screen can be used.
• Time should be allowed for the student to adjust to • Color deficient students should be taught the color of
different lighting levels when moving between outdoors common objects. Example: when asked to color a map,
and indoors. they will know to use the blue for river, brown for
mountains, etc.
Seating • The boundaries in a map should be marked with dark
bold lines to maximize contrast. The boundaries may be
• A seating position in the front row of the class, with
differentiated using different patterns. Example: A double
centering the blackboard should be provided.
line may be drawn for the country border and a single
• The classroom environment should be kept static. This
line for the state border.
helps the student with orientation to the classroom.
• The student should be alerted to any changes in the room
LOW VISION INTERVENTION
layout.
FOR THE ELDERLY
• A slanting desk should be used to balance head and eye
posture. Growing old can be a dynamic life process in which meaningful
new roles and goals are identified, anticipated or expanded,
Time but old age can also be a condition of isolation, resignation,
bewilderment, regression and loss of health, status and
• Additional time should be allowed to investigate a visual
dignity.13 When visual impairment is compounded with old
stimulus.
age, the problem appears insoluble. The incapacity to make a
• Additional time should be permitted to complete the set
psychological adjustment to vision impairment seems greater
work. Extra time to write an examination is legally
than the ability to accept most other losses. Many elderly
permissible.
people with vision loss refuse to avail themselves of the wide
variety of services that are available and do not continue
Size of Text Material Font
with programs to which they have been introduced.13 From
• Large print text materials should be provided as far as a psychodynamic standpoint, it may be said that some elderly
possible. people are in a masochistic situation in which they feel that
• The size of the print that the student requires to access they must be miserable to be happy. Adjustment to vision
information should be considered. loss is affected by a number of factors such as the degree of
loss, the speed of onset, the medical prognosis, the age at
GUIDELINES TO HELP A CHILD which it occurs, any preconceived ideas the person holds
WITH COLOR DEFICIENCY about blindness, other health factors, social circumstances
Color blindness is the reduced ability to distinguish between and immediate life-style, personality and previous capacity to
certain colors or wavelengths of light. To see colors properly, handle other losses.13
light sensitive photoreceptor cells, called cones, are needed in The common psychological problems faced by elderly
the retina of the eye. There are three types of color receptors are depression, fear, frustration, lack of interest, low self-
in the eye, red, green and blue. Color blindness results from esteem, suspicion, anger, and emotional stress.13
a lack of one or more of the types of color receptors. Most Failure to recognize and respond to the psychological
color perception defects are for red or green or both. Yellow- problems may lead to frustration when trying to provide
blue is the second most common form, but it is extremely rehabilitation services to this population. A successful
rare. It is also possible to have the color receptors missing rehabilitation of an elderly visually impaired person depends
entirely, which would result in black and white vision. upon the relationship built between the professionals and the
• A picture with words or symbols should be labeled when client. The professionals should be sensitive enough to
the response requires color recognition. understand and respect the feelings of the client. The vocal
• Coloring materials such as crayons, colored pencils, and tone, posture and gesture of the counselor help to gain the
pens should be labeled with the name of the corresponding confidence of the other person. Most elderly visually impaired
color. people often respond more readily to good professional
• Color chalk should be avoided. White chalk on the board services and therapeutic procedures than do most other age
to maximize contrast should be used. groups. The older person when treated properly is thankful
• A classmate may be assigned to help color deficient and appreciative and is glad that the helping professional has
students when assignments require color recognition. come into their life.
194 Low Vision
Table 4.3.1: Visual impairment categories

Category Better eye Worst eye Percentage impairment
0 6/9 – 6/18 6/24 – 6/36 20%
I 6/18 – 6/36 6/60 – Nil 40%
II 6/60 – 4/60 or 3/60 – Nil 75%
Field of Vision 10°–20°
III 3/60 – 1/60 or FC 1 ft. – Nil 100%
Field of Vision 10°
IV FC at 1 ft. to Nil Field of Vision 100%
Or Field of Vision 10° 10°
One-eyed person 6/6 FC 1 ft. to Nil 30%
FC stands for Finger Counting
• Categories II, III and IV are considered blind
• Category I is considered partially blind
• Category 0 is considered partially sighted.
Source: Ministry of Welfare Publication 'Uniform Definitions of the Physically Handicapped2
Visual Impairment Categories • Orientation and mobility instructors: Orientation and mobility
with Corrections instructors teach the techniques of indoor and outdoor
The definition of visual impairment adopted by the Ministry safe navigation such as sighted guide, mobility cane,
of Welfare Government of India vide Notification No. guide dog and electronic aid that is appropriate for an
4–2/83–HW. III dated 6 August, 1986 classifies visual individual.
impairment into six categories as given in the Table 4.3.1. • Physiotherapist: He/she assesses the physical condition of
patients to diagnose problems and plan appropriate
MEMBERS OF LOW VISION TEAM treatment using a range of techniques to strengthen and
stretch muscles and joints to improve movement damaged
Comprehensive low vision rehabilitation intervention requires by injury or diseases.
the services from interdisciplinary team13-15 members as low • Clinical psychologist: He/she assists in understanding the
vision patients require additional support and resources for level of functioning ability in areas such as intelligence
meeting their educational needs, social skills training, and
(IQ), emotional (EQ), and social (SQ) aspects.
psychological counseling to improve their independent living
• Social worker: He/she helps with a particular crisis and/or
besides the optometry care for low vision devices. The
day-to-day problems with family, school, work, financial
members of the team include:
concerns, and government programs.
• Low vision consultant: Optometrists/low vision clinicians who
• Speech therapist: He/she evaluates and treats communi-
can assess ocular status, evaluate visual functioning,
cation disorders.
prescribe low vision devices (e.g. optical, nonoptical,
• Audiologist: He/she helps in identification, assessment and
electronic), and coordinate other forms of care to
improve the functioning of the patient's impaired visual management disorders of the auditory, balance, and other
system. neural systems. Audiologists select, fit, and dispense
• Rehabilitation consultant: Rehabilitation managers/ amplification systems such as hearing aids and related
counselors, who can provide psychological counseling to devices.
improve the person’s ability to cope with vision loss, • Occupational therapist: A therapist who evaluates fine motor
conduct individualized needs assessment and plan for and eye-hand coordination skills of a person and assists
rehabilitation intervention. in improving the hand strength and using the arms and
• Special educator: Specially trained resource teacher who can hands to develop and restore the person's ability to
guide on various educational needs such as training in accomplish activities of daily living (eating, dressing,
using educational devices such as Braille, Taylor frame, bathing) and necessary occupational tasks.
etc. preparation of specialized educational materials, and The author and editors have no financial interest in any procedures or product
recommendations for classroom modifications. mentioned in this chapter.
REFERENCES 7. Fellowship Manual, LV Prasad Eye Institute, Hyderabad 2002.

8. Smith W. Developmental milestones in children—A parent's guide
1. Punani B, Rawal N. Manual-Community Based Rehabilitation, (www.medic8.com)
Royal Danish Embassy 1996;45-134. 9. Developmental delays—A pediatrician's guide to your children's
2. Punani B, Rawal N. Visual Impairment Hand Book, Published by health and safety (www.keepkidshealthy.com)
Harish M. Panchal (BPA), 2000;339-421. 10. The United Nations Children's Fund (UNICEF) Document 2003.
3. Fernadez G, Koenig. C, Mani MNG, Sian T. See with the Blind, 11. NCERT. Sixth All-India Educational Survey. National Council
Christoffel Blindenmission 1999. of Educational Research and Training, New Delhi 1998.
4. Christy B. Teaching-learning materials for school-teachers to assist 12. MHRD. National Policy on Education. Ministry of Human
children with low vision, Project report conducted in LV Prasad Resource Development, New Delhi 1992.
Eye Institute (LVPEI), Hyderabad supported by International 13. Randoll T Jose. Understanding Low Vision 1997;43-55.
Council for Education of People with Visual Impairment (ICEVI), 14. American Optometric Association. Position statement on the role
West Asia Region 2000. of optometry in low vision. J Am Optom Assoc 1995;66:15.
5. Chen C. Essential Elements in Early Intervention. American 15. Kathleen EF, Roy GC, et al. Optometric clinical practice guideline;
Foundation for the Blind, NY 1999. care of the patient with low vision. American Optometric
6. Ferral KA. Reach out and Teach. American Foundation for the Association (AOA): 243 n. Lindbergh Blvd., St. Louis, MO
Blind, NY 1986. 2001;63141-7881.
Chapter 5.1
GENETICS IN OPHTHALMOLOGY
Saurabh Jain, Zia Chaudhuri
GENETIC BASIS OF OCULAR DISEASE composed of four different nucleotide bases, adenine (A), thymine
(T), cytosine (C) and guanine (G). These purine (A and G) and
A better understanding of the role of genes in ophthalmic
pyrimidine (C and T) bases combine in a specific manner (A
disease has been gained with improvement in gene testing
always with T and C always with G) and align to form the double
technologies and mapping of the human genome. A vast
helix DNA first described by Watson and Crick.2
number of genes underlying monogenic ocular disorders have
Transferring genetic information from DNA into protein
been isolated and studied enabling genetic counseling of the
involves a multi-step process that includes several types of
patient and non-affected family members.
ribonucleic acid or RNA. To summarize, DNA codes for RNA
In addition to the inherited causes of childhood blindness,
and RNA code for proteins. This route of transferring
it is now known that genetic factors contribute to the blinding
information from DNA to proteins is known as the “central
effect of adult onset disorders like glaucoma, age related
dogma” of molecular genetics. Mutations or structural
macular degeneration (AMD) and diabetic retinopathy. A
alterations in the genes or genetic material produce mutant
working knowledge of genetics is therefore important for every
RNA, which produces mutant protein and leads to external
practicing ophthalmologist.
manifestation of disease or the ‘phenotype’.3 These mutations
Basics of Genetics can be inherited or acquired as de novo changes. The various
patterns of inheritance are discussed below.
Genetics is the study of biologically inherited traits that include
the effect of environment. Genes are transmitted between PATTERNS OF INHERITANCE
generations and are located on specific loci in chromosomes.
The chromosomes exist in the nuclei of all cells as well as in The patterns of inheritance in genetic disease may be divided
the mitochondria in the cytoplasm. Human beings have 46 into single-gene, chromosomal, and complex or multifactorial
chromosomes (23 pairs) with 22 pairs classified as autosomes disorders.
and one pair classified as sex chromosomes. The sex
Single-Gene Disorders
chromosomes are the 23rd chromosome pair and differ
according to gender as females have two X chromosomes These are caused by a mutation or in a single gene, which
(X,X) and males have an X and Y chromosome (X,Y).1 may be on one (heterozygous) or both (homozygous)
During conception, humans receive matched pairs of chromosomes in the pair. Single-gene disorders are usually
chromosomes or one chromosome from each parent that carry recognized in childhood, with less than ten percent
the genomic complement of the offspring. Mitochondrial manifesting after puberty. 1 Simple Mendelian laws of
DNA is transmitted maternally only. inheritance govern the diseases caused by inheritance of
The human genome consists of the total number of genes single genes and these may be autosomal recessive, autosomal
carried by a person. Genes are the building blocks of life and are dominant, X-linked recessive, and X-linked dominant,
made up of deoxyribonucleic acid (DNA). The DNA, in turn, is discussed further below.
200 Applied Basic Sciences Related to Ophthalmology
Mendelian Inheritance Patterns autosomes need to have the same gene defect to produce
symptoms. The affected individuals inherit one faulty gene
Gregor Mendel identified the principles of heredity (Mendel’s
from each parent who are carriers of the condition. When
laws of inheritance) through his study of garden peas and
both parents carry a recessive gene the chance of inheritance
their offspring. He noted that heredity units or genes were
of the disorder is 1 in 4 and 2/3rds of unaffected siblings run
either recessive or dominant.
the risk of being carriers (Fig. 5.1.2).
There is usually no strong family history of the disease
Autosomal Dominant Inheritance
but affected individuals may be found in previous generations
This mode of inheritance leads to expression of the phenotype on closer questioning. Consanguinity increases the risk of
with the gene in a heterozygous stage or when it is present on inheritance of these disorders.
only one of the pair of chromosomes. These patients usually Examples include oculocutaneous albinism, Leber's
have a strong family history of the disorder. Half of the congenital amaurosis and achromatopsia.
offspring can inherit the disorder with one affected parent.
Autosomal dominant pedigrees show two or more X-linked Recessive Disorders
generations affected with a 50:50 ratio of affected and
unaffected persons (of either sex) per sibship (Fig. 5.1.1). The disease is carried on the X sex chromosome and usually
Examples of conditions inherited in this manner include only the males are affected with the females acting as carriers
Rieger’s disease, autosomal dominant congenital cataracts, (Fig. 5.1.3). However, it is important to reiterate that due to
Stickler’s disease, retinitis pigmentosa and Best’s disease. variable expressivity of the affected gene on the X chromo-
However not everyone who inherits a gene mutation some, if an affected male has an offspring with a carried female,
develops the disorder. Two terms in this context must be sometimes females may be affected. In such a case, the
discussed here. condition often resembles the inheritance pattern seen in the
extremely rare X-linked dominant diseases. Again, if an
Expressivity: This relates to the degree of expression of a affected male has an offspring with a genetically normal female,
disease. Individuals with the same mutation can manifest the female offspring of this union are going to be carriers of
variability in the severity of the disease signs and symptoms, the affected gene. The male offspring of such an union are
e.g. Marfan’s syndrome. going to be largely unaffected. This implies that there is no
Penetrance: This is an all or none phenomenon that refers to father to son transmission of the disease. Examples of X-
the presence or complete absence of phenotype in carriers. linked recessive include megalocornea, Noorie’s disease,
Therefore genes with reduced penetrance may display no congenital stationary night blindness, color blindness and
symptoms in gene carriers whereas genes with reduced retinitis pigmentosa.
expressivity display milder symptoms.
Both of these can modify the presentation of the disease. X-linked Dominant Disorders
This uncommon inheritance pattern can affect both males
Autosomal Recessive Inheritance
and females but is usually lethal in the former. If both the
In this pattern of inheritance the phenotype is manifested parents are affected, all the female offspring of such an union
only in the homozygous state, i.e. both of the pair of would be affected, though to varying degrees depending upon
Fig. 5.1.1: Autosomal dominant inheritance family tree (the Fig. 5.1.2: Autosomal recessive inheritance family tree (the affected
affected person is marked in red) person is marked in red, while the carriers are marked in pink)
Genetics in Ophthalmology 201
Y chromosome). Hence, there is no father to son transmis-

sion of the disease in X-linked inheritance patterns.
Mitochondrial Inheritance
Mitochondria are cellular organelles with a distinctive circular
genome. Abnormalities in the mitochondrial DNA are
maternally inherited as cells get all their mitochondria
exclusively from the ovum. Examples of mitochondrial
inheritance patterns include Leber’s hereditary optic
neuropathy (LHON) and Kearne Sayre’s syndrome.
Fig. 5.1.3: X-linked recessive inheritance family tree (the affected
Mitochondrial disorders can affect almost all organ systems
person is marked in red, while the carriers are marked in pink)
but the cells and organs that have the highest energy
consumption are most severely affected, e.g. the brain, skeletal
and cardiac muscle (mitochondrial encephalomyopathies).
Over 270 inherited mitochondrial disorders have been
described with widespread heterogeneity in clinical
presentation. Some mitochondrial disorders, e.g. Leber
hereditary optic neuropathy affects a single organ but the
majority causes multiple organ involvement with prominent
neurological abnormalities and muscle disease.
The neurological abnormalities include loss of vision and
hearing, migraine, seizures and focal neurological deficits.
Muscle disease may present with weakness, exercise intolerance,
rhabdomyolysis, a fibromyalgia-like picture, and abnormal
Fig. 5.1.4: X-linked dominant inheritance family tree EMG. Extraocular muscles are especially susceptible as they
(the affected person is marked in red) have a high proportion of type 1 (oxidative) fibers. Thus, ptosis
and ophthalmoplegia are very common in mitochondrio-
the expressivity of the gene (Fig. 5.1.4). Male offsprings have pathies.
a chance of being spared. In case, the father is affected, again
the only offspring that may be spared is a male offspring. Chromosomal Disorders
However, if the mother is affected and the father is normal,
there is a chance that along with a male offspring, a female Chromosomal disorders result from an abnormal chromosome
offspring may also be normal. It is important to reiterate number or structural rearrangement. Aneuploidy is caused by
that if the male or the female offspring is normal, their an error in cell division in which a sperm or egg has too many
children will not be carriers of the affected gene. An example or too few chromosomes. Most persons with aneuploidy have
of this rare genetic pattern of inheritance is incontinentia monosomy or trisomy. An example of monosomy is Turner
pigmenti. syndrome (45, X) and the most common type of trisomy is
The major difference between the X-linked recessive trisomy 21 or Down’s syndrome (47, XX or 47, XY).
disorder and the X-linked dominant disorder is the Chromosomal disorders can result from nondisjunction,
expressivity of the affected X chromosome in a female deletions, or translocations.
patient. In X-linked recessive disorders, both the
Complex Disorders
chromosomes need to be affected (similar to autosomal
recessive disorders) for the female to be affected while in Complex or multifactorial disorders occur when the interaction
X-linked dominant disorders, the presence of one affected of small gene alterations and environmental factors, result in
sex chromosome is adequate for the disease to be manifest . a disorder or the increased susceptibility to one. The pattern
Males are affected in both types of inheritance patterns if of inheritance is a complex or multifactorial pattern that does
they harbor the affected X chromosome. Males do not not follow the Mendelian pattern of inheritance.4 Examples
transmit the X chromosome to their sons (they transmit the of complex disorders are Alzheimer’s disease, autism, cleft lip
resolved using classic cytogenetic techniques. Fluorescent

probes are used to detect the presence or absence of specific
DNA sequences by binding to only those parts of the
chromosome with which they show a high degree of sequence
similarity. Fluorescence microscopy can be used to find out
where the fluorescent probe bind to the chromosomes. The
correlation between the PAX 6 gene affected in aniridia and
the Wilms’ tumor suppressor gene was discovered by this
technique by Crolla et al.4
Restriction Fragment Length

Polymorphism (RFLP)
This was one of the earlier techniques used to map the human
Fig. 5.1.5: Karyotype spread analysis of Edward’s syndrome
genome and localize genes for detection of genetic disorders.
Restriction enzymes are used to detect and cleave DNA
wherever specific short sequences occur and these resultant
and palate, neural tube defects, schizophrenia, and Type 1 strands are separated by agarose gel electrophoresis using
diabetes. Southern blotting. Complementary DNA probes are then used
to bind to specific DNA strands and RFLP is said to occur
PROCEDURES/TECHNIQUES when there is a difference in the length of the same strand
FOR GENETIC TESTING between individuals. Insertions, deletions, translocations and
With improvements in technology the human genome has inversions can all lead to RFLP. This technique has now
been mapped in considerable detail and more genes are being become largely obsolete as it requires a large quantity of DNA
discovered everyday. There are many techniques used to isolate and the various steps involved can take upto a month to
candidate genes but only the commonly used ones are detailed complete.5
below.
Single Strand Conformation
Polymorphism (SSCP)
Karyotyping Analysis
It is difficult to detect changes in single nucleotides using RFLP
During mitosis, chromosomes can be visualized micro- as the mobility of double-stranded DNA in gel electrophoresis
scopically after staining with an agent such as Giemsa is dependent on strand size and length but is relatively
(G-banding). Each chromosome has a characteristic banding independent of the particular nucleotide sequence. However,
pattern, consisting of alternating light and dark bands. This when this DNA is converted to single strands, the mobility is
direct or microscopic analysis of the structure of the noticeably affected by very small changes in sequence. After
chromosomes to detect chromosomal rearrangement is called denaturation single stranded DNA undergoes a three-
karyotyping. Abnormalities that can be detected by this dimensional folding and may assume a unique conformational
technique range from aneuploidy to more subtle abnormalities, state based on its DNA sequence. Single-strand conformation
such as partial deletion or duplication of chromosomes, polymorphism analysis uses this quality of single-stranded
insertions, and translocations. Even at its highest resolution, DNA to detect DNA polymorphisms, or sequence variations.
karyotyping only provides a broad overview of the genetic SSCP analysis offers an inexpensive, convenient, and
landscape; each chromosomal band represents large segments sensitive method for determining genetic variation.6 The
(megabases) of DNA and multiple genes. Disorders that have procedure used during SSCP consists of digestion of genomic
been discovered by this technique include Down’s syndrome DNA with restriction endonucleases, electrophoresis on a
or trisomy 21, Edward’s syndrome or trisomy 18 (Fig. 5.1.5) neutral polyacrylamide gel and hybridization with either DNA
and Turner’s syndrome (monosomy of X chromosome). fragments or more clearly with RNA copies synthesized on
each strand as probes.7 SSCP was initially a way to discover
Fluorescein in situ Hybridization (FISH)
new DNA polymorphisms apart from DNA sequencing, but
This is a cytogenetic technique used to detect and localize is now being supplanted by sequencing techniques due to
specific DNA sequences on chromosomes too small to be greater efficiency and accuracy.
Linkage Analysis Chorionic villus sampling: Chorionic villus sampling (CVS) is a

diagnostic procedure performed during pregnancy to diagnose
Linkage analysis is the technique typically used to determine
chromosome abnormalities. It is usually performed in the first
the genetic location of a disease gene and is useful especially
trimester of pregnancy as an outpatient procedure. A thin
when there are no other indicators for the position of the
needle or catheter is guided through the abdomen or vagina
gene such as coinherited disorders, cytogenetic abnormality
to obtain a sample of the placental tissue depending on the
or good candidate genes.
placental position. This can diagnose 99 percent of fetal
The goal of linkage analysis is to identify a DNA sequence
anomalies but unlike amniocentesis cannot provide
of known location that is inherited by all affected family
information about neural tube defects.
members, and is not inherited by any of the unaffected family
members. Once this sequence of DNA is found, the diseased Amniocentesis: Amniocentesis is performed on amniotic fluid
gene location can be estimated. Determining the location of usually between 16 and 18 weeks of pregnancy (second
the disease gene is the first step toward identifying the gene trimester). A thin needle is inserted through the abdomen
itself. This technique of DNA sequence analysis to identify under ultrasound guidance into the amniotic sac, and a small
mutations can be quite time-consuming and costly, especially amount of amniotic fluid is removed for genetic analysis.
if a disease can be caused by mutations in any one of a number Traditional amniocentesis increases the risk of miscarriage by
of genes (e.g. retinitis pigmentosa or Leber congenital approximately 0.5 percent (1/200).
amaurosis).8
GENETIC ASSOCIATION
A recent example of linkage analysis to identify a gene
OF OCULAR DISEASE
responsible for disease was in identifying the mutation on the
FRMD 7 gene responsible for X-linked congenital idiopathic Cornea
nystagmus (CIN). The researchers knew that the mutant gene The mode of inheritance and clinical features of different
was present on X chromosome between q26 and q27, a ocular disorders are enumerated in Table 5.1.1.
segment containing 12 million base pairs. They identified 16 A wide variety of corneal disorders are determined by
families with affected members and screened their DNA for inheritance including abnormalities of corneal shape, size,
genetic markers (fixed DNA sequences of known location clarity or integrity.
that are present in everyone). The markers present close to Normal mean corneal diameter is 10 mm at birth, reaching
the affected gene are likely to be cosegregated or inherited 11.7 mm at two years. Microcornea is a diameter less than 10
together unlike those far away from it as they are separated mm and megalocornea >13 mm.
during recombination of chromosomes. By identifying these
linked genetic markers and comparing these between affected Cataract
and unaffected people, they confirmed and refined the locus Congenital infantile cataract has a prevalence of 1 to 3 per
NYS1 at Xq26-27. After refining the locus to the minimum 10,000 live births and upto a third of these are inherited in an
possible interval, they sequenced all the exons and splice autosomal dominant manner. Therefore, examination of
junctions of all the genes in the region which led to the siblings and parents of these children is useful in making the
discovery of the novel gene called FRMD7, mutations in which diagnosis. Variable expressivity and reduced penetrance is
cause X-linked congenital idiopathic nystagmus (CIN).9 common leading to a diverse clinical phenotype. These can be
isolated or can occur in association with a large number of
Prenatal Genetic Testing metabolic diseases and genetic syndromes. Isolated congenital
cataracts tend to be highly penetrant Mendelian traits, with
Prenatal genetic testing generally refers to tests that are done autosomal dominant more common than autosomal recessive
during pregnancy to either screen for or diagnose a birth cataracts. Mutations in genes coding for crystallins, beaded
defect. These can be screening tests, e.g. maternal serum filaments and connexins have been largely implicated, as these
screening for alpha fetoprotein (AFP) that identifies are the structural components of the human lens. In contrast
pregnancies at increased risk for open neural tube defects, to congenital cataracts, mapping and identification of genes
Down’s syndrome and trisomy 18. Other prenatal tests are for age-related cataract is still in its infancy due to a large
diagnostic and can diagnose certain fetal disorders with a number of potential genes, the multiple chromosomal regions
high degree of accuracy, e.g. amniocentesis and chorionic possibly involved and the relatively low likelihood that each
villus sampling. one is significant.10
Table 5.1.1: The mode of inheritance and clinical features of different ocular disorders
Genetic disorder Mode of inheritance Clinical features
Cornea plana Autosomal dominant (AD) Extreme hypermetropia,
and autosomal recessive (AR) Hazy limbus with arcus juvenilis, stromal opacities.
Meesman dystrophy AD Epithelial corneal dystrophy with multiple intraepithelial cysts.
Granular dystrophy AD Gray discrete anterior stromal opacities with clear intervening stroma.
May be classic or atypical which has fewer deposits.
Lattice dystrophy type I AD Gray linear and fine deposits of amyloid protein in central cornea.
Lattice dystrophy type II AD Corneal lattice dystrophy and cranial neuropathy.
(Meretoja's syndrome)
Lattice dystrophy type III AR Coarser lattice that traverses limbus to limbus.
Macular dystrophy AR Diffuse corneal stromal clouding and reduction of corneal thickness.
Deposition of glycosaminoglycans that does not spare the limbus.
Fuch’s endothelial dystrophy Sporadic, AD Focal guttata of the Descemet’s membrane leading to endothelial
decompensation.
Primary congenital glaucoma AR Due to abnormal development of the drainage angle with no other
ocular anomalies. Usually bilateral.
Juvenile primary open AD Early onset open angle glaucoma with high pressures and normal
angle glaucoma anterior segments. Patients are usually teenagers, myopic and require
filtration surgery.
Primary open Complex inheritance patterns Multifactorial disorder characterized by optic neuropathy, progressive
angle glaucoma but AD common disc cupping and field loss.
Aniridia AD Partial or complete absence of iris tissue associated with stem
Sporadic (WT1 gene that cell abnormalities, developmental glaucoma and cataracts.
underlies Wilms’ tumor)
PAX 6 gene
Anterior segment AD Heterogeneous disorders of anterior segment development including
mesenchymal dysgenesis AR (less common) Peter’s and Axenfield-Rieger’s anomalies.
PITX3; FOXC1 genes affected
Achromatopsia AR A form of rod monochromatism with absence of functioning cones.
Blue cone monochromatism X-linked recessive Only functional rods and short wave (blue) cones leading to severely
reduced central vision, photophobia and abnormal color discrimination
with nystagmus.
Stargardt’s disease AR Early onset macular degeneration with progressive loss of central
AD (less common) vision. Posterior pole exhibits round, linear or disciform lesions.
Vitelliform macular dystrophy AD Round, yellow vitelliform lesions at the macula whch may progress to
the vitteluruptive stage leading to loss of central vision.
Grossly reduced EOG with normal ERG.
Choroideremia X-linked recessive Visual field constriction and night blindness with large scalloped lesions
through which choroidal vessels can be seen.
Lebers congenital amaurosis AR Group of early onset retinal dystrophies associated with photophobia,
eye poking, nystagmus, sluggish or paradoxical pupillary reactions
and high hypermetropia but normal fundi.
ERG non-detectable by 3 months of age.
Retinitis pigmentosa AD (20–25%) Abnormalities of the RPE or photoreceptors characterized by night
AR (15–30%) blindness, constriction of the peripheral fields and loss of central
X-linked RP (10–23%) vision.
Fundoscopy reveals perivascular pigment deposition in the mid
peripheral region with vascular attenuation and optic disc pallor.
Progressive bilateral photoreceptor dysfunction with reduced amplitude
ERG's.
Contd...
Contd...
Genetic disorder Mode of inheritance Clinical features
Familial exudative AD, AR Abnormal peripheral retinal vascularization and organized vitreoretinal
vitreoretinopathy X-linked membranes causing macular dragging and retinal detachments.
Incontinentia pigmenti X-linked dominant Presents in females with defects of peripheral retinal vascularization,
leukocoria, erythematous blistering rash, hypodontia and seizures.
Norrie’s disease X-linked recessive Disease of male infants, females are carriers.
Abnormal vascularization and congenital detachment of the retina. A
third of the affected, have hearing defects.
Stickler's syndrome AD Early onset high myopia with ‘empty’ vitreous, paravascular lattice
degeneration and retinal detachments in childhood. Associated with
orofacial abnormalities, hearing loss and arthropathy.
Dominant optic atrophy AD Gradual onset optic atrophy with visual deterioration through childhood.
Lebers hereditary optic Mutations in mitochondrial Acute or subacute painless visual loss in mid-life. Disc swelling and
neuropathy DNA inherited exclusively peripapillary telangiectasia in acute phase with optic atrophy and
from the mother centrocecal scotoma in latter stages.
Oculocutaneous albinism AR Disruption in normal melanogenesis leading to ocular, skin and hair
(OCA) hypopigmentation.
Ocular albinism X-linked recessive Boys have ocular signs similar to OCA but no hair or skin signs.
Females are asymptomatic but can reveal iris transillumination and a
mud splattered fundus.
Neurofibromatosis AD Type 1 presents with Lisch nodules, café au lait spots, neurofibromas
17q11 (Type 1) and optic nerve gliomas.
22q12 (Type 2) Type 2 is associated with bilateral cataracts, epiretinal membranes,
hamartomas of the retina and RPE and vestibular schwannomas.
Retinoblastoma AD Childhood malignancy (1-4 years) derived from retinal cells. Presents
Sporadic (mutations in the commonly as leukocoria and strabismus but can also mimic uveitis,
tumor suppressor gene RB1) glaucoma and orbital cellulitis.
Congenital fibrosis of the AD (CFEOM 1) Non-progressive restrictive ophthalmoplegia with bilateral ptosis.
extraocular muscles (CFEOM) AR (CFEOM 2)
Blepharophimosis, ptosis and AD Horizontal shortening of the palpebral aperture with ptosis,
epicanthus inversus (BPES) Loss of function of the telecanthus and epicanthus.
Forkhead transcription Type1: BPES with female infertility
factor (FOXL2) Type II: Isolated BPES
X-linked idiopathic X-linked inheritance Horizontal, conjugate, gaze-dependent nystagmus with onset in the
infantile nystagmus of the FRMD7 gene first six months of life. Binocular vision and color vision are normal
and visual acuity is typically better than 6/12. The eyes are structurally
normal and electrodiagnostic testing does not reveal any abnormalities.
Glaucoma have been identified that participates in the metabolism of

Glaucoma can be inherited as a Mendelian autosomal-dominant many compounds, including 17β-estradiol.12
or autosomal-recessive trait, or as a complex multifactorial trait.11
Anterior Segment Dysgenesis Syndromes
Primary Congenital Glaucoma (Axenfield-Reiger, Nail-patella, Aniridia)
This arises from abnormality in development of the anterior The genes responsible for these disorders participate in the
segment and outflow pathways leading to high intraocular development of the periocular mesenchyme, which includes
pressure. Congenital glaucoma can be inherited as an neural crest and cranial paraxial mesoderm-derived cells. These
autosomal-recessive trait and is prevalent in countries where developmental disorders are all inherited as autosomal-
consanguinity is common. Using consanguineous pedigrees dominant traits, and are caused by mutations in the PITX2
from Saudi Arabia and Turkey, defects in the CYP1B1 gene gene and FOXC1 gene.13
Patients with defects in both of these genes may also have (DRS), congenital ptosis and horizontal gaze palsies. Most of
associated systemic defects involving the teeth, facial bones, these are inherited and the techniques described above have
heart, and umbilicus. Abnormalities in the PAX6 gene can been utilized to identify the chromosomal locations of the
cause aniridia, as well as a spectrum of iris abnormalities related identified genes. These now include three CFEOM loci
to glaucoma. Nail-patella syndrome is a systemic (FEOM1-3), two Duane loci (DRRS, DURS3), and one ptosis
developmental disease associated with glaucoma caused by locus (PTOS1) and HGPPS (Horizontal gaze palsy with
defects in LMX1B. progressive scoliosis) disease genes.17
Adult Onset POAG Nystagmus

As mentioned in earlier section in this chapter, linkage analysis
Adult-onset glaucoma often occurs in multiple family members
has been used to identify a gene responsible for X-linked
(familial aggregation) but does not usually follow a clear
congenital nystagmus at the locus NYS1 at Xq26-27. This gene
Mendelian inheritance pattern, suggesting multiple risk factors
has been called the FRMD7 gene.9
and/or environmental factors.
Table 5.1.2 elaborates some of the affected gene sequences
Defects in MYOC coding for myocilin are found in three
in congenital ocular disease.
to five percent of patients with adult-onset POAG. Mutations
in the Q368X gene, which results in a truncated polypeptide, GENETIC COUNSELING
is more frequently found in patients with adult-onset POAG
This is a communication process that deals with the human
than in patients with early-onset POAG. Recently, DNA
problems associated with the occurrence or risk of occurrence
sequence changes have been identified in the WDR36 gene,
of a genetic disorder in a family. This should impart the
located within the chromosomal region defined as GLC1G.
necessary information about the condition that affects them
Although the function of the protein product is unknown
as well as its implications for family planning. An accurate
and the role of the protein in glaucoma remains to be
three generation pedigree is essential to underpin this process.
confirmed, prior studies suggest that it may participate in
This process integrates the following:
immune responses. Mutations in the WDR36 gene are not an
• Interpretation of family and medical histories to assess
independent cause of glaucoma but may modify the severity
the chance of disease occurrence or recurrence
of the disease in an affected person.14
• Education about inheritance, testing, management,
prevention, resources and research
Age-related Macular Degeneration
• Counseling to promote informed choices and adaptation
Age-related maculopathy (ARM) is a complex disorder in to the risk or condition.18
which multiple genetic variants contribute to the risk of
developing the disease. In addition, external factors, such as Table 5.1.2: Genes affected in congenital
ocular genetic disorders
diet and smoking, also contribute to disease susceptibility.
There is no evidence to suggest that familial ARM is any Disorder Gene affected
different than sporadic ARM. The genes implicated in the Crouzon/Apert FGFR2
causation of ARM include the complement factor H (CFH) Treacher Collins TCOF1
gene and the HTRA1 (a serine protease gene). However, based Marfan syndrome FBN1
on the concordance of case-control and family-based Ataxia telangiectasia ATM
Oculocutaneous albinism Type 1 TYR
association studies, the contribution of genetics seems to be
Oculocutaneous albinism Type 2 OCA 2
comparable for those with and without family histories of the
Alagile syndrome JAG 1, NOTCH 2
disease.15,16 Stickler syndrome COL9A1, COL11A1, COL11A2
Cataract PAX6, BMP 4, 7
Congenital Cranial
Aniridia PAX6, WT
Dysinnervation Syndromes
Peters anomaly PAX6, PITX3, CYP1B1
These are a group of disorders characterized by incomitant Microphthalmos PAX6
strabismus secondary to maldevelopment of cranial nerve and Chediak-Hegashi syndrome LYST
motor nuclei rather than primary extraocular muscle Retinitis pigmentosa CRB1
abnormalities. Examples include congenital fibrosis of the Blepharophimosis syndrome FOXL2X
extraocular muscles (CFEOM), Duanes retraction syndrome X-linked retinoschisis XLRS1
There are various issues that become important during 7. Orita M, et al. Detection of Polymorphisms of Human DNA by
genetic counseling. Patients and their families should be made Gel Electrophoresis as SSCPs. Proceedings of the National
Academy of Sciences of the United States of America; 1989,
aware of the possibility to uncover nonpaternity and adoption
(86):2766-70.
in cases of linkage analysis or DNA testing involving several 8. Blan D, Brooks BP. Molecular Diagnosis and Genetic Counseling
family members. The process of determining the transmission in Ophthalmology. Arch Ophthalmol 2007;125(2):196-203.
of the ‘faulty’ gene may invoke feelings of guilt and despair in 9. Tarpey P, Thomas S, Sarvananthan N, et al. Mutations in FRMD7, a
the carrier parent or family member. Non-affected family newly identified member of the FERM family, cause X-linked
idiopathic congenital nystagmus. Nat Genet 2006;38(11):1242-4.
members may also be identified during the process of linkage
10. Shiels A, Hejtmancik JF. Genetic origins of cataract. Arch
analysis which can have an impact on their employment and Ophthalmol 2007;125:165-73.
insurance status. Adoption and paternity issue may similarly 11. Wiggs JL. Genetic etiologies of glaucoma. Arch Ophthalmol
be uncovered during the process. These eventualities must be 2007;125:30-7.
discussed before commencement and post-test counseling 12. Sena DF, Finzi S, Rodgers K, Del Bono E, Haines JL, Wiggs JL.
offered to all who need it. Founder mutations of CYP1B1 gene in patients with congenital
glaucoma from the United States and Brazil. J Med Genet
2004;41:e6.
REFERENCES 13. Nishimura DY, Searby CC, Alward WL, et al. A spectrum of
FOXC1 mutations suggests gene dosage as a mechanism for
1. Nussbaum RL, McInnes RR, Willard HF. Thompson and developmental defects of the anterior chamber of the eye. Am J
Thompson genetics in medicine. Revised reprint, 6th edn. Hum Genet 2001;68:364-72.
Philadelphia: WB Saunders; 2004. 14. Nemesure B, Jiao X, He Q, et al. Barbados Family Study Group. A
2. Watson JD, Crick FH. Molecular structure of nucleic acids: A genome-wide scan for primary open-angle glaucoma (POAG):
structure for deoxyribose nucleic acid. Nature 1953;171(4356): 737- the Barbados Family Study of Open-Angle Glaucoma. Hum Genet
8. 2003;112:600-9.
3. Hartl DL, Jones EW. Genetics: analysis of genes and genomes. 15. Gorin MB. A clinician's view of the molecular genetics of age-
6th edn. Sudbury MA ed: Jones and Bartlett; 2004. related maculopathy. Arch Ophthalmol 2007;125:21-9.
4. Crolla JA, van Heyningen V. Frequent chromosome aberrations 16. Postel EA, Agarwal A, Schmidt S, et al. Comparing age-related
revealed by molecular cytogenetic studies in patients with aniridia. macular degeneration phenotype in probands from singleton and
Am J Hum Genet 2002;71:1138-49. multiplex families. Am J Ophthalmol 2005;139:820-5.
5. Saiki RK, et al. “Enzymatic amplification of beta-globin genomic 17. Engle E. The genetics of strabismus: Duane, Moebius, and fibrosis
sequences and restriction site analysis for diagnosis of sickle cell syndromes. In: Genetic diseases of the eye: a textbook and atlas
anemia.” Science 230 (4732):1350-4. Traboulsi E (Ed). 477-512 (Oxford University Press, New York,
6. Sunnucks P, et al. SSCP Is Not So Difficult: The Application and 1998).
Utility of Single-Stranded Conformation Polymorphism in 18. Resta R, Biesecker BB, Bennett RL, et al. A new definition of
Evolutionary Biology and Molecular Ecology. Molecular Ecology; genetic counseling: National society of genetic counselors’ task
2000;(9):1699-710. force report. J Genet Couns 2006;15:77-83.
Chapter 5.2
OCULAR ANESTHESIA
Bharti Taneja, Kirti Nath Saxena
Ocular surgery involves patients of all age groups and presents PREOPERATIVE ANESTHETIC
several anesthetic challenges that are unique to ocular CONSIDERATIONS IN AN
anesthesia. These include intraoperative maintenance of OPHTHALMIC PATIENT
intraocular pressure, prevention and management of the
The success of any procedure depends on proper preoperative
oculocardiac reflex, prevention of intraocular gas expansion, screening, patient selection, and preparation for anesthesia.
as well as the need to deal with comorbid conditions and Although the general principles of preoperative evaluation
congenital syndromes associated with many ophthalmologic and medication are standard, specific considerations are
disorders. Apart from the special anesthetic considerations, important for ophthalmic surgery and anesthesia.
the neonate and pediatric patients have a risk of associated
congenital anomalies, while the geriatric patient may have co- Patient Profile
existing serious medical problems such as cardiorespiratory
disorders, diabetes, arthritis, etc.1 Another consideration is Choice of anesthesia depends on age of the patient and
the need for absolute immobility of the patient intra- associated comorbidities to a large extent. For example;
operatively. A closed claims analysis by Gild and colleagues2 children are usually uncooperative and require general
revealed that 30 percent of eye injury claims associated with anesthesia (GA) while older patients can be managed with
anesthesia was characterized by patient movement during regional blocks of the eye provided there are no comorbidities.
ophthalmic surgery. However, patients with chronic spontaneous cough,
Despite the anesthetic considerations involved, ocular orthopnea, parkinsonism, senile tremor, or claustrophobia
surgery has a lower morbidity and mortality since it is may be very difficult to manage with regional anesthesia and
associated with minimal blood loss, low intraoperative stress general anesthesia is usually required. This would be equally
true for highly uncooperative patients and mentally challenged
response and mild to nil postoperative pain.3
patients.
The role of the anesthesiologist in ocular anesthesia is to
provide general anesthesia (GA), administer regional
Intraocular Pressure and Anesthesia
anesthesia (RA) or eye blocks for surgeries to be performed
under local anesthesia and to provide monitored anesthesia Control of intraocular pressure (IOP) before, during, and
care (MAC) for high-risk patient being operated under RA after the procedure is essential for the success of
with sedation. Most of the patients are posted as day care ophthalmologic surgery. Maintenance of normal intraocular
surgery and a thorough understanding of the above mentioned pressure (12–20 mm Hg) is the result of interplay of many
potential problems is essential to favorably influence surgical physiological factors. In cases of traumatic rupture or during
outcome.3 certain surgical procedures where the globe is open, the
Ocular Anesthesia 209
intraocular pressure approaches the atmospheric pressure. INTRAOCULAR GAS EXPANSION

In such a situation, any further rise in IOP can lead to The ophthalmologist often injects intravitreal air or sulphur
extrusion of vitreous through the wound which is a serious hexafluoride during vitreous and retinal detachment surgery.
complication and can permanently worsen vision. Thus, This helps to flatten a detached retina and allows anatomically
maintenance of intraoperative IOP is a serious concern for correct healing. The administration of the highly diffusible
the anesthesiologist.4 The factors that affect IOP4,5 include: Nitrous Oxide (N2O) results in the rapid increase in the size
• Drugs: Most anesthetic drugs either lower or have no effect of the injected gas bubble. The injected gas bubble can
on intraocular pressure. Inhalational agents as well as most increase up to three times its original size8 which causes IOP
intravenous (IV) anesthetics decrease intraocular pressure to increase from 14 to 30 mm Hg. On the other hand,
in proportion to the depth of anesthesia. Ketamine, is the discontinuation of nitrous oxide leads to rapid reabsorption
only intravenous induction agent that usually raises arterial of N2O and both the bubble size and the IOP decreases
blood pressure and does not relax the extraocular muscles. (29–12 mm Hg),9 sometimes precipitating another retinal
With the exception of succinylcholine, muscle relaxants detachment.
used have no effect on the IOP. The prolonged This may be prevented by discontinuing nitrous oxide at
contracture of extraocular muscles caused by the IV least 15 min prior to the injection of air or sulfur hexafluoride.
administration of depolarizing muscle relaxant Nitrous oxide should be avoided until the bubble is absorbed
(5 days after air and 10 days after sulfur hexafluoride
succinylcholine increases the intraocular pressure by 5
injection).
to 10 mm Hg for five to ten minutes.6 The resulting
increase in intraocular pressure has the following OCULOCARDIAC REFLEX
consequences:
A major anesthetic concern is the prevention and management
– Risk of extrusion of ocular contents through an open
of the oculocardiac reflex (OCR). Traction on the extraocular
surgical or traumatic wound
muscles, pain or pressure on the eyeball can evoke a trigeminal-
– False high readings of intraocular pressure recorded vagal reflex response that is manifested by a wide variety of
during examinations under anesthesia in glaucoma cardiac dysrhythmias ranging from bradycardia, ventricular
patients ectopics, hypotension, ventricular fibrillation to sometimes
– Abnormal forced duction test for 20 min. even cardiac arrest. In the awake patients, the oculocardiac
In view of the above mentioned problems, the use of reflex may also be associated with somnolence and nausea.
succinylcholine is restricted in ophthalmologic surgery and Although more commonly encountered during strabismus
limited to full stomach patients for emergency surgery. surgery and in pediatric patients, it can be evoked in all age
• Hypercarbia: Presence of hypercarbia can lead to increased groups and during a variety of ocular procedures, including
IOP and optimal ventilation of the patient with avoidance cataract extraction, enucleation and retinal detachment repair.
of hypercarbia is desirable. It can occur at the time of injection for retrobulbar block
and sometimes can occur even during non-ophthalmic surgery
• Effect of arterial blood pressure: Sudden rises in arterial blood
if pressure is placed on the eyeball. Presence of hypercarbia
pressure may produce a small, transient rise while the
significantly increase the incidence of OCR during strabismus
pressures have to be well below 90 mm Hg before any
surgery.10
reduction in IOP occurs
• Venous pressure changes: Rise in the central venous pressure Reflex Pathway
following coughing, obstructed airway, intermittent positive
This reflex consists of a trigeminal afferent and a vagal
pressure ventilation (IPPV), vomiting, straining or any efferent pathway. The afferent pathway follows the long and
factor that impedes free venous return such as head low short ciliary nerves to the ciliary ganglion and then to the
position or ligature will immediately increase the IOP. Gasserian ganglion along the ophthalmic division of the
• Intubation and laryngeal mask airway: IOP will also increase trigeminal nerve. These afferent pathways terminate in the
in response to the stimulus of laryngoscopy and main trigeminal sensory nucleus in the floor of the fourth
endotracheal intubation. Insertion of a laryngeal mask ventricle. The efferent impulse are carried in the vagal cardiac
airway (LMA) after propofol induction has been shown depressor nerve and cause negative inotropic effects and
to have minimal effect on IOP.7 conduction disorders.
The reported incidence of OCR varies from 32 to 90 anesthetic implications and it is imperative that associated
percent depending on the intensity of observation and the congenital disorders are ruled out or diagnosed correctly
definition of arrhythmias. Transient cardiac arrest may occur before taking up any patient for surgery (Table 5.2.2).
as frequently as 1 in 2200 strabismus surgeries.10
GENERAL ANESTHESIA FOR
Preventing the OCR OPHTHALMOLOGIC SURGERY
• Intramuscular atropine or glycopyrrolate prior to surgery The choice between general and local anesthesia should be
• Gentle manipulation of the extraocular muscles made jointly by the patient, anesthesiologist, and surgeon.
• Control of ventilation to maintain normocapnia Some patients refuse to consider local anesthesia due to fear
• Retrobulbar blockade (controversial since this can also of being awake during a surgical procedure or the recollection
elicit the oculocardiac reflex) of pain during prior regional techniques. Although there is
• Deep inhalational anesthesia. no conclusive evidence that any one form of anesthesia is
safer, local anesthesia seems to be less stressful. The specific
Management of the Oculocardiac Reflex indications for GA are as follows:
• The surgeon should be informed and requested to Indications

immediately stop the surgical stimulation until the heart
rate increases Patient Indications
• Oxygenation, normocarbia and depth of anesthesia should • General anesthesia is indicated in children and
be ensured uncooperative patients, as even small head movements
• Administration of intravenous atropine (0.007 mg/kg)11 can be greatly magnified under the operating microscope
• In refractory cases, local anesthetic infiltration of the and can prove disastrous.
rectus muscle is an option. • Patients with movement disorders, such as Huntingtons
chorea, senile tremors, parkinsonian head tremor.
SYSTEMIC EFFECTS OF • Patients suffering from claustrophobia.
OPHTHALMIC DRUGS • Patients with co-morbid conditions.
The rate of absorption of drugs administered topically in the • Patient refusal for RA.
eye varies at a rate intermediate between absorption following
Surgical Indications
intravenous and subcutaneous injection. The toxic effects of
these drugs is of particular concern in children and the elderly. • Vitreoretinal surgery by virtue of the long duration
Ophthalmic drugs that have significant systemic effects are involved are often preferred under GA
outlined in Table 5.2.1. • Oculoplastic surgery especially involving autologous graft
• Ocular trauma
Table 5.2.1: Systemic side effects of ophthalmic drugs • Orbital decompression and tumors.
Drug Systemic effect Patients opting for general anesthesia are usually either in
Acetazolamide Diuresis, hypokalemic metabolic acidosis the pediatric age group or elderly with comorbid conditions.
Atropine Central anticholinergic syndrome They may also be extremely apprehensive if there is risk of
Cyclopentolate Disorientation, psychosis, convulsions permanent eye damage.
Epinephrine Hypertension, bradycardia, tachycardia,
headache Preoperative Preparation
Phenylephrine Hypertension, tachycardia, dysrhythmias
• Every effort must be made to help the patient understand
Timolol Bradycardia, asthma, congestive heart failure
the procedure
• Individualized premedication can be helpful in lessening
CONGENITAL SYNDROMES
anxiety and enhancing amnesia
INVOLVING EYE PATHOLOGY
• Hearing aids and dentures should be left in place
A significant number of pediatric patients may have an ocular • Patient's usual medication regimens should not be
problem which may be one of the manifestations of a multi- interrupted. Therapy for asthma, hypertension, angina,
system congenital disorder. Sometimes, this may have serious congestive heart failure, or diabetes should be continued.
Table 5.2.2: Anesthesia in systemic syndromes with ocular manifestations

Congenital disorder Ocular manifestation Anesthetic implication Anesthetic management
Homocystinuria • Lens subluxation • Thromboembolic complications • Pretreatment with acetylsalicylic
• Glaucoma • Hyperinsulinemia acid and dipyridamole
• Hypoglycemic convulsions • Adequate hydration
• Maintenance of arterial BP
• Peripheral vasodilation
• Early ambulation
Marfan's syndrome • Lens subluxation • Cardiac valvular defects • Cardiorespiratory complications
• Retinal detachment • Thoracic aneurysms,
• Kyphoscoliosis
Down’s syndrome • Strabismus • Hypotonia • Cardiorespiratory complications
• Cataracts • Cardiac valvular defects • Careful titration of anesthetic drugs
• Hypothyroidism • Difficult intubation
• Macroglossia • Neurological problems
• Seizures
• Atlantoaxial instability
Sturge-Weber syndrome • Secondary glaucoma • Angioma of the cerebral cortex • Risk of seizures
and lower airway • Airway bleeding
Sickle cell disease • Retinitis proliferans • Sickle cell crisis • Avoidance of dehydration,
and Thalassemia • Vitreous hemorrhage • Anemia acidosis, hypoxia, infection,
• Retinal detachment venous stasis, and hypothermia
Crouzon's disease, • Myopia • Craniofacial abnormalities • Difficult intubation
Alport's syndrome, • Detached retinas
Goldenhar syndrome • Exophthalmos
• Glaucoma
The Goals for General Anesthesia for Maintenance

Ocular Surgery Include
All standard and vigilant monitoring is essential, especially
• Smooth induction with maintenance of anesthesia because the patient is at risk of life-threatening arrhythmias
• Low IOP with minimal to nil fluctuations caused by the oculocardiac reflex. The pulse oximetry and
• Careful monitoring with prompt management of OCR capnography monitoring are important since the anesthesio-
• Airway control with adequate oxygenation logist is away from the patient's airway. Even though the
• Immobility of the patient surgical requirement and stress response is considerably less
in an ocular surgery, adequate depth has to be maintained
• Smooth and uneventful extubation
since the slightest of movements can lead to disastrous
• Minimal postoperative nausea and vomiting
consequences. Postoperative nausea and vomiting (PONV)
• Clear headed recovery to facilitate early discharge.
is a common postoperative problem especially after squint
surgery and can be detrimental to the surgical outcome if
Induction not dealt with promptly. Low to normal IOP should be
maintained in the intraoperative period. This can be
Smooth induction with control of IOP is the key to successful
accomplished by ensuring an adequate depth of anesthesia,
induction in ocular anesthesia. All induction agents with the
hyperventilation, lowering of systemic arterial blood pressure
exception of ketamine, lower the IOP. Laryngoscopy and and slight head up positioning of the patient. The extubation
endotracheal intubation evoke a rise in IOP that can be should be smooth without any straining and coughing. The
attenuated by prior administration of intravenous lidocaine pain following ocular surgery is rarely severe and small doses
(1.5 mg/kg) or an opioid (Fentanyl 2–3 µg/kg). The use of of narcotics or NSAIDs usually suffice. Amongst the more
succinylcholine is avoided as it causes postoperative myalgias painful procedures are scleral buckling procedures,
and can increase the intraoperative IOP. Succinylcholine enucleation, and ruptured-globe repair. Severe postoperative
administration increases the IOP rapidly by 6 to 12 mm Hg pain may signal intraocular hypertension, corneal abrasion,
and this rise in IOP persists for up to ten minutes. or other surgical complications.
LOCAL ANESTHESIA FOR The advantages notwithstanding, equipment and personnel

OCULAR SURGERY required to treat the complications of local anesthesia and to
induce general anesthesia must be readily available. Proper
Traditionally, majority of ocular surgeries are performed under
patient selection, thorough preoperative evaluation, adequate
local anesthesia. These blocks provide good surgical conditions
sedation and monitoring are essential even for a patient posted
with a high success rate. The complications of GA are avoided
under RA. The contraindications to local anesthesia include:
and the interactions with concurrent drug therapy and co-
• Age below 15 years
morbid conditions are minimal. Many ophthalmic procedures,
• Bleeding disorders
such as cataract extraction, corneal transplants,
• Known allergy to local anesthetic drugs
trabeculectomy, lid surgery, and even vitrectomy or repair of
• Psychotic or uncooperative patient
a detached retina, can be performed safely in an outpatient
• Patient refusal
setting with regional anesthesia and mild sedation.
• Patients with chronic spontaneous cough, shortness of
The advantages of local anesthesia are manifold and
breath while lying flat, parkinsonian head tremor,
include:
Alzheimer's disease, or claustrophobia.
• Continuation of analgesia in the postoperative period
• Respiratory and cardiovascular stability Preoperative sedation with a benzodiazepine and
• Excellent muscle relaxation explanation of the technique to the patient helps in reducing
• No interference with the airway anxiety, ensures amnesia for the block, decreases the
• Decreased metabolic and neuroendocrine stress response discomfort of the injection and helps achieve patient co-
to surgery operation to a great extent. The patient must be calm,
• More cost effective; low cost of anesthesia in terms of cooperative, and aware during the operation. The reflexes
drugs, equipment and manpower should not be obtunded and the airway should not be
• Need for less intensive postoperative care and ideal for obstructed.
day care surgery
• Allows early discharge and ambulation. Prerequisites
Certain prerequisites and precautions are essential before
Drugs used as Local Anesthetic application of regional anesthesia. These include:
The commonly used local anesthetic (LA) solution12 is a • Resuscitation drugs and equipment should be available
combination of equal parts of the faster acting, shorter and ready for use
duration two percent lidocaine and slower onset, longer • Intravenous line in situ is essential
duration 0.5 percent bupivacaine. An alternative solution for • Needle length should not more than 31 mm
procedures lasting less than one hour is a combination of • Aspiration should be done before injecting the drug
two percent lignocaine and two percent prilocaine.13 Additives • Slow deposition of the local anesthetic solution is essential
that have been used successfully include epinephrine 5 µg/ • The total permissible dose of 7 mg/kg of lignocaine with
ml and hyaluronidase (3–7 U/ml). Addition of epinephrine adrenaline and 4 mg/kg of lignocaine without adrenaline
may reduce bleeding and prolong the anesthesia. Hyaluroni- should not be exceeded
dase, a hydrolyzer of connective tissue polysaccharides, is • The concentration of adrenaline is ideally 1:2,00,000. It
frequently added to enhance the retrobulbar spread of the should not exceed more than 1:1,00,000
local anesthetic. The newer LA drugs ropivacaine and levo- • Patient monitoring and observation after injection of local
bupivacaine14,15 have been tried and show effective analgesia anesthetic is essential.
with reduced toxicity and lower motor blockade but were
Monitoring
associated with a longer duration of action. Residual diplopia
lasting 24 hours has been reported and requires padding of Standard monitoring for regional anesthesia during ophthalmic
the eye till the residual effect of LA wears off. Some workers surgery includes observation of heart rate, arterial blood
prefer to use sodium bicarbonate as an additive. Sodium pressure, the electrocardiogram (ECG), and the pulse
bicarbonate by virtue of changing the pH to an alkaline one, oximeter. A facemask delivering an air-oxygen mixture at a
results in a greater fraction of the LA in being the unionized, total flow rate of at least 10 L/min should be used to
active form leading to a faster onset of action. supplement oxygen and prevent accumulation of carbon
dioxide under the drapes surrounding the face. These drapes

should be tented away from the patient to prevent
claustrophobia and to permit free flow of air.
Equipment
• Intravenous cannula in situ
• Two percent lidocaine and 0.5 percent bupivacaine
• Hyaluronidase/epinephrine
• 25G; <31 mm needle
• Gauge swab
• Orbital compression balloon.
Preparation of Drug Solution

Commercial preparations of hyaluronidase contain 1500 IU/
ml. To prepare a 50 IU/ml solution, 1 ml of 1500 IU/ml Fig. 5.2.1: Demonstration of the different locations of regional
hyaluronidase is added to 29 ml of 2 percent lidocaine. blocks in ophthalmology
The LA solution used for the block is constituted by adding
4-4.5 ml of 2 percent lidocaine along with 4-4.5 ml of 0.5
percent bupivacaine and 1 ml of hyaluronidase (50 IU/ml).
The final preparation will now contain 1 percent lidocaine,
0.25 percent bupivacaine and 5 IU/ml hyaluronidase
Regional Blocks for the Eye

• Retrobulbar (Intraconal) block involves injection of local
anesthetic agent into the part of the orbital cavity behind
the globe1 (Fig. 5.2.1).
• Peribulbar (Extraconal) block refers to the placement of
needle tip outside the muscle cone2 (Fig. 5.2.1). Fig. 5.2.2: Technique of retrobulbar block
• Sub-Tenon block refers to the injection of local anesthetic
agent beneath the Tenon capsule. This block is also known
as parabulbar block, pinpoint anesthesia and medial the conal space just behind the globe (Fig. 5.2.2).
episcleral block3 (Fig. 5.2.1). Occasionally, a ‘pop’ may be felt as the needle tip passes
into the muscle cone.
Retrobulbar Block
• After careful aspiration, 2 to 4 ml of local anesthetic
Technique: agent is injected.
• The patient is instructed to look straight ahead in the • The globe is continuously observed for any rise in IOP
primary gaze position. and proptosis during the needle placement and injection
• Needle approach is through the infratemporal region, of the drug.
either from the conjunctiva or from the eyelid. • A reliable sign of successful block is onset of ptosis with
• Topical LA eye drops may be used whenever the injection of the LA.
conjunctival approach is chosen in order to minimize the Although mostly successful, sometimes there is sparing
pain of injection. of the orbicularis oculi and the superior oblique muscle. This
• A 25G, <3.1 cm needle is inserted close to the lateral can be remedied by supplemental block to the orbicularis
canthus tangential/away from the globe, below it and along oculi by medial peribulbar injection. Due to a high complication
the floor of the orbit. rate and with the introduction of the technically simpler and
• On crossing the equator as gauged by axial length of the safer peribulbar block the retrobulbar block is rarely used in
globe, the needle is directed upwards and inwards to enter clinical practice.
Peribulbar Block Tenon space from where it diffuses into the retrobulbar space.
It avoids the blind use of sharp needles and thus, has minimal
As compared to the retrobulbar block, peribulbar is safer.16
risk of serious complications.18 This is of particular advantage
There is no penetration of the cone formed by the extraocular
in patients on anticoagulants as well as in patients with longer
muscles as a result of which there is decreased risk of injury
axial length of the eye.
to the optic nerve and artery as well as less pain on injection.
However, the onset of action is slower, an increased likelihood Technique
of ecchymosis and a higher incidence supplementary injection • Topical LA drops is instilled in the eye to be blocked
in 5 to 24 percent of patients is present.17 • An eye speculum is applied or an assistant retracts the
Technique lower eyelid
• The patient is instructed to look straight ahead in the • This patient is asked to look upwards and outwards to
primary gaze position expose the inferonasal quadrant
• Topical LA drops/subconjunctival injections are instilled • Five percent povidone iodine eye drop is instilled before
injection to minimize pain dissection
• The conjunctiva is grasped with non-toothed forceps
• Needle approach is through the infratemporal region in
• A small button hole incision is made with blunt-tipped
the subconjunctival fornix close to the lateral canthus,
scissors about 5 to 10 mm from the limbus in the
about 2 mm from the sclera
inferonasal portion of the conjunctiva and Tenon's capsule
• A 25 G, 2.5 cm needle is inserted away from and then
• A blunt plastic cannula is passed to the posterior pole of
below the globe
the eye following the contour of the globe, deep to the
• Once in the extraconal space, the needle direction is not
Tenon’s fascia and extends past the equator
changed (not directed upward and inward) but directed
• Three to five ml of LA solution is instilled
along the orbital floor
• The block is assessed for akinesia after five minutes.
• Needle depth should not be further than the equator of
the globe as measured by the axial length of the eye
• 5 ml of the LA is injected Facial Nerve Block
• A rise in the orbital pressure with injection of the LA is Squeezing or squinting of the eyelids during surgery is a
watched for. troublesome feature and hinders the placement of the eye
speculum. This is mediated by the orbicularis oculi muscle
Medial Peribulbar Block
which is innervated by the facial nerve. Various techniques
Use is limited to situations where supplementation of an of facial nerve block19 have been postulated but the preferred
inadequate retrobulbar or peribulbar block is required. It is techniques amongst them include the van Lint, Atkinson, and
sometimes preferred as a primary anesthesia injection the O’Brien technique.
technique in patient with longer axial length of the eye.
Commonly Used Facial Nerve Blocks
Technique
• The patient is instructed to look straight ahead in the • O’Brien technique: This method blocks all the branches
primary gaze position of the facial nerve. This is an intraparotid injection and
• A 25G, 2.5 cm needle is inserted between the medial blocks the facial nerve as it passes over the condyle of
canthus and caruncle the mandible.
• Needle is directed backwards and parallel to the medial Technique: Needle is inserted just anterior to the tragus of
wall of the orbit the ear, just above the condyloid process of the mandible.
• At a depth of about 1.5 to 2 cm, 3 to 5 ml of solution is Disadvantage: Frequent blockade of only the upper portion
injected of the peripheral facial nerve.
• Sometimes at this point, a loss of resistance is felt as the • Nadbath/Rehman technique (modified O’Brien
needle pierces the medial check ligament. block): Injection just inferior to the earlobe.
Technique: Injection is given at the dorsal rim of the
Sub-Tenon Block mandible near the tragus of the ear. Five millimeter of
Sub-Tenon block is a painless, safe and reliable technique of the anesthetic solution injected at a maximal depth of
RA. A blunt probe is used to instill LA solution into the sub- 1.7 cm.
Advantage: Better orbicularis akinesia due to blockade of Limitations

the upper and lower portions of the peripheral facial nerve.
• Lack of eye akinesia
• van Lint technique: Infiltration anesthesia at the temporal
• Treatment of uncomplicated cataracts only
orbital margin, aiming at the short zygomatic branches
• Not appropriate for posterior chamber surgery (e.g. retinal
of the facial nerve.
detachment repair with a buckle).
Technique: The needle is inserted 1 cm lateral to the lateral
orbital rim at the crossing of lines drawn parallel to the
Drugs Used
lower and temporal rim of the orbit. The needle is directed
horizontally across the lower lid and LA injected as the Local anesthetic eye drops used for topical eye anesthesia
needle is withdrawn. Without withdrawing the needle fully, include 0.5 to 0.75 percent bupivacaine, 4 percent lidocaine,
the needle is directed superiorly along the lateral orbital 0.5 percent proparacaine, and tetracaine. Proparacaine is the
rim and again injected as the needle is withdrawn. 2 to 4 least irritating on application.20 Recently, oxybuprocaine 0.4
ml of LA solution is injected. percent has also been used. Topical instillations may be
Disadvantage: Lower lid swelling, hematoma, poor repeated at five minutes intervals till the desired result.
orbicularis akinesia.
• The Atkinson block: Subcutaneous injection at the Indications
midpoint of a line between the lower edge of the zygoma • Eye examination (to relieve any discomfort)
and the temporomandibular joint. 2 to 5 ml of the • Tonometry and gonioscopy
anesthetic solution is injected subcutaneously along this • Removal of corneal and conjunctival foreign body
line in both directions towards the zygoma and the • Laser procedures
temporomandibular joint. • Phacoemulsification.
• The lid block: 2 to 5 ml of the anesthetic solution is
injected in the lids, 0.5 cm below (lower lid) and 1 cm Contraindications
above (upper lid) the middle of the lateral canthus.
• Hypersensitivity to LA
Topical Instillations • Penetrating injury.
With the advent of small incision procedures such as Complications of Use of Local Anesthetic
phacoemulsification for cataract surgery, the need for akinesia
is minimal and the surgery can be easily performed using Systemic Toxicity
topical LA drops alone. The sensory nerve supply to the
An overdose or accidental IV injection of the LA solution or
cornea is through the long ciliary nerves. The terminal nerve
the vasoconstrictor can lead to serious consequences. The
endings are superficial and topically applied local anesthetics
local anesthetic toxicity manifests as predominantly CNS and
are easily absorbed through the conjunctival membrane
CVS side effects with the CNS toxicity manifesting earlier
resulting in topical anesthesia.
than the CVS toxicity. The CNS manifestations include perioral
tingling, numbness, confusion, tinnitus, diplopia, disorientation,
Prerequisites
seizures and coma. CVS toxicity manifests as bradycardia
• Careful selection of patients who are cooperative, and resistant to atropine, hypotension, arrhythmias and
communicative. cardiovascular collapse.
• Gentle surgical technique and fast surgeon. Rarely, allergic/anaphylactic reaction are seen with LA.
Advantages Retrobulbar Hemorrhage

• Avoidance of any needle related complication like This is one of the most dreaded complication of eye blocks
hemorrhage, brainstem anesthesia, optic nerve damage, with an incidence of 1 in 700 retrobulbar blocks.21 A high
or perforation of the globe. index of suspicion should be maintained for early diagnosis
• No need of any eye padding and the signs suggestive of a retrobulbar hemorrhage in the
• Rapid recovery of sight form of increasing proptosis, tight eyelids, peri/
• No troublesome side effects such as diplopia in the post- subconjunctival hemorrhage and sudden rise in IOP should
operative period. be noted.
Management Central Spread of LA

• Planned surgery should be postponed
The optic nerve sheath is a dural cuff communicating with
• Urgent orbital decompression can be planned
the intracranial cavity. Deposition of LA into the optic nerve
• Gentle pressure can be given to the eyeball for 20 to 30
sheath leads to central spread causing drowsiness, ipsilateral
minutes.
or contralateral loss of vision, convulsions, respiratory or
Retrobulbar hemorrhage is less frequently seen with
CVS collapse. The central spread of the LA is often delayed
peribulbar or sub-Tenon blocks and can be avoided by:
with the symptoms manifesting in the postoperative period,
• Use of fine-gauge needles (25–30 gauge)
thus the need for continued monitoring for prompt detection
• Lateral inferotemporal approach (less vascular)
and management.
• Avoiding deep needle placement (less than 31 mm)
• Pressure to the eye for one minute after injection.
External Ocular Muscle Palsy
Direct Trauma/Globe Penetration The muscles most commonly involved are the medial rectus
or Perforation and the inferior oblique muscles. The palsy is self-limiting
due to local spread of the another agents and the muscles
Incorrect needle insertion can lead to needle entering through
usually recover without treatment. Sometimes, the effect may
the globe (penetration) or passing right through it (perforation).
last longer if there is injury to the muscle while injecting. The
It presents as severe pain, sudden loss of vision and hypotonia
palsy may manifest as diplopia or ptosis depending on the
of the globe (Fig. 5.2.3).
muscle involved.
Myopic eyes and eyes with previous retinal detachment
surgery are at greater risk. Thus, careful needle insertion with
Other Minor Complications
preoperative knowledge of the axial length is desirable.
Failure of the block, corneal abrasion, chemosis, and
Optic Nerve Damage conjunctival hemorrhage are other complications seen.
Optic nerve damage may be due to either direct trauma or Optimal anesthetic management is the keystone for the
instillation/injection into the optic nerve sheath. Sometimes success of ocular surgery. The choice of anesthesia should
sudden rise in pressure due to retrobulbar hemorrhage may be made in consultation with the patient, surgeon and
also lead to optic nerve damage. Use of high concentrations anesthesiologist. Although both regional and general anesthesia
of certain LA such as prilocaine may be neurotoxic. is safe, RA is the preferred anesthesia for ocular surgery.
Ocular surgery has lower morbidity and mortality since it
Amaurosis causes low intraoperative stress response, minimal blood
loss and almost nil postoperative pain.
A temporary loss of vision follows spread of LA to the optic
nerve with retrobulbar block. This condition requires REFERENCES
reassurance to the patient and the vision recovers as the block
1. Desai P, Reidy A, Minassian DC. Profile of patients presenting
wears off. for cataract surgery in the UK: National data collection. Br J
Ophthalmol 1999; 83:893-6.
2. Gild WM, Posner KL, Caplan RA, et al. Eye injuries associated
with anesthesia. Anesthesiology 1992;76:204.
3. Donlon JV Jr. Anesthesia for ophthalmic surgery. In: Barash P
(Ed): ASA Refresher Course Lectures, vol 16. Philadelphia, JB
Lippincott, 1988, p 81.
4. Cunningham AJ, Barry P. Intraocular pressure-physiology and
implications for anaesthetic management. Can J Anaesth
1986;33:195.
5. Murphy DF. Anesthesia and intraocular pressure. Anesth Analg
1985;64:520.
6. Vachon C, Warner D, Bacon D. Succinylcholine and the open
globe. Anesthesiology 2003;99:220-3.
Fig. 5.2.3: Globe perforation, intravascular injection and optic 7. Lamb K, James MF, Janicki PK. The laryngeal mask airway for
nerve damage due to incorrect needle insertion intra-ocular surgery: effects on IOP. Br J Anaesth 1992;69:143-7.
8. Stinson T, Donlon JV. Interaction of intraocular sulfur hexafluoride 15. Huha T, Ala-Koko Ti, Salomaki T, Alahuhta S. Clinical efficacy
and nitrous oxide. Anesthesiology 1982;56:49. and pharmacokinetics of 1 percent ropivacaine and 0.75 percent
9. Wolf GL, Capuano C, Hartung J. Nitrous oxide increases IOP bupivaciane in peribulbar anesthesia for cataract surgery.
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1983;59:547. 16. Davis DB, Mandel MR. Efficacy and complication rate of 16,224
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or glycopyrrolate for prevention of oculocardiac reflex in children 12000 cataract extraction and intraocular lens implantation
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Chapter 5.3
OCULAR MICROBIOLOGY
Savitri Sharma
The external ocular surface acquires microbial flora at birth Considerable progress has been made in the diagnosis of
while the inner portions of the eye remain sterile. Some of viral infections using molecular methods. The current
the commensals may become resident flora in the conjunctiva emphasis is on rapid diagnosis of infections using molecular
and lids such as Staphylococcus epidermidis, other species of tools.
Staphylococcus including S. aureus, Propionibacterium acnes In a limited space, this chapter outlines the common
and different species of Corynebacterium. On the other hand, infections of the anterior and posterior segment of the eye
any microorganism can form a transient flora in the eye. followed by laboratory diagnosis.
Several protective mechanisms protect the eye against this
onslaught of microorganisms. PATHOGENESIS
• Mechanical protection of the lids and blinking reflex.
Bacterial Infections
• Triple-layered tear film containing outer oily layer from
the meibomian glands, an aqueous layer from the lacrimal The balance between the number and virulence of the
glands and inner mucus derived from goblet cells in the invading bacteria and the strength of the immune system
conjunctiva. determines whether or not an infection will occur. The
• Antimicrobial action of the tear fluid rendered by IgA, organism must be able to adhere to the ocular surface, multiply,
lysozyme, lactoferrin, complement, IgG, etc. colonize and evade the host defence system (mechanical
Despite the protective mechanisms, any organism removal and immune system) to invade the tissues. While the
(bacteria, fungi, viruses, parasites) can cause an eye infection eukaryotic organisms of the third kingdom of living things,
under special situation. Infection is facilitated by break in Protista, are fungi, protozoa and algae, the prokaryotic
superficial epithelium due to trauma, contact lens wear or organisms are the bacteria. Newer techniques such as
other causes. While the anterior segment is infected by direct deoxyribonucleic acid (DNA) typing and sequencing
invasion from the anterior route, blood borne infections may demonstrate great heterogeneity (guanine + cytosine content
reach the posterior segment of the eye. Local as well as from 25–75%) of bacteria within their groups. This variation
systemic immunity play significant roles in the pathogenesis in DNA sequences in bacteria is now being used clinically to
of an infection. Virulence of the organisms is an equally develop diagnostic techniques.
important factor that determines the outcome of invasion Bacterial morpholog y, their growth conditions,
by an organism. classification and identification details can be found in excellent
Clinical features combined with timely and appropriate microbiology books1 and these details are not in the scope
microbiological investigations aid in specific diagnosis of the of this chapter. Identification of bacteria is a laborious time-
infection and in specific treatment. Antibiotic susceptibility consuming exercise involving testing for their morphology,
tests provide trend of susceptibility of organisms to a cultural morphology, biochemical and antigenic variations.
spectrum of antibiotics. Recent trends suggest development Automated rapid methods such as Vitek or Analytical Profile
of resistance by bacteria to various common antibiotics. Index (API, bioMerieux, France) have made it easier to identify
Ocular Microbiology 219
bacterial genus and species with high accuracy and minimum The normal conjunctiva contains all immunologic
effort. Recent trends have also seen a shift from conventional components including cells. Apart from immunoglobulins and
identification methods to molecular methods.2 Bacteria complement system, there are several other factors such as
commonly associated with ocular infections are shown in fibronectin, C-reactive protein, lysozyme, and transferrin, that
Table 5.3.1. Bacteria produce a variety of eye infections such play an important role in defence against bacteria. Lysozymes
as blepharitis, canaliculitis, dacryocystitis, conjunctivitis, act as muramidase and cleave the glycosidic bond of the N-
keratitis, scleritis, endophthalmitis, preseptal and orbital acetylmuramic acid residues in the bacterial cell wall. Tears
cellulitis. They can also be associated with indirect phenomena usually contain IgA, IgG and IgE. Secretary IgA along with
such as syphilitic interstitial keratitis and mycobacterial complement is usually bacteriolytic. Complement activation
phlyctenulosis. Important attributes of organisms causing leads to lysis of bacteria, production of inflammatory
ocular infections include virulence, invasiveness, numbers mediators, opsonization and antibody mediated immune
entering the host tissues and the site of entry. Collagenases responses. The primary cells found at the site of bacterial
(Clostridium perfringens), coagulase (Staphylococcus), infection of the cornea have been shown to be polymorph-
hyaluronidases (Streptococcus), hemolysins and leukocidines onuclear cells.3 During phagocytosis they release prostaglandins
(Streptococcus, Clostridium, gram-negative bacilli), proteases which in turn increases vascular permeability. Antibody
(Neisseria, Streptococcus), etc. are some of the extracellular synthesis normally occurs in lacrimal gland but some
enzymes that are important in the initiation and spread of antibodies are synthesized in mucosal immune system.4
infection through tissues. Lipases and esterases are important Antibodies, especially surface IgA, prevent bacterial adhesion
bacterial enzymes produced by staphylococci and to epithelial cells.5 Antibodies also neutralize the exotoxins
propionibacteria associated with blepharitis. released by some bacteria.
Several characteristics of the host also determine the
Fungal Infections
effect of bacterial virulence factors and development of
disease. Age, use of drugs, contact lens use, trauma, surgery, Normal bacterial commensals of the anterior surface of the
etc. may influence the effect of virulence factors. Risk factors eye, along with other protective mechanisms of the eye, are
also include presence of dry eye states, chronic nasolacrimal not favorable for the growth of most opportunistic fungi.
duct obstruction and previous ocular disease. Tissue injury Alteration of the normal flora with systemic or topical
results from direct action of bacteria, their toxins, as well as corticosteroids or antibiotics may, however, allow colonization
from bacteria induced inflammation. Immunopathologic and growth of fungi. Normal body temperature is also
activities include recruitment of polymorphonuclear cells, inimical to growth of fungi. Of all fungal infections the most
macrophages and lymphocytes. Mediators of inflammation common is keratomycosis, probably due to lower temperature
such as histamine, tumor necrosis factor, cytokines, of the cornea and susceptibility to trauma. Breach of corneal
leukotrienes and prostaglandins, play important roles in epithelium is a predisposing factor for keratomycosis. In
interaction with the bacteria and their removal or proliferation. addition, surgical procedures such as cataract surgery,
keratoplasty and radial keratotomy may introduce fungi into
Table 5.3.1: Bacterial genera and species commonly the eye through contaminated transplant tissue or irrigating
associated with ocular infection solutions. 6 Fungal endophthalmitis associated with lens
Gram-positive cocci Gram-negative cocci implantation and contaminated irrigating solutions have been
Staphylococcus aureus Neisseria reported.7 The role of local antibodies and complement in
Coagulase negative staphylococci Branhamella the protection of the eye against fungi is not well defined.
Streptococcus pneumoniae Moraxella
Alpha hemolytic streptococci Kingella The polysaccharide in fungal cell wall can activate complement
Beta hemolytic streptococci Acinetobacter and IgA can protect against fungal infection, especially
Gram-positive bacilli Gram-negative bacilli infection by yeast-like fungi, but the extent of protection
Bacillus cereus Escherichia offered to the eye by these methods, against fungal infections,
Propionibacterium acnes Klebsiella is not clear. Clinical experience and elegant studies,8 have
Listeria monocytogenes Enterobacter
Actinomyces Serratia demonstrated worsening of fungal infection with topical and
Nocardia asteroides Proteus systemic corticosteroids and this suggests importance of
Clostridium perfringens Pseudomonas immunity (local and systemic) in protection of the eye. Ocular
Haemophilus
fungal infection is often associated with systemic
Figs 5.3.1A to D: Paraffin sections of the cornea from patients with fungal keratitis showing: (A) Suppurative inflammation in the corneal
stroma, with the breach in the Descemets membrane (DM). The fungal filaments can be seen as unstained hollow filaments (*) along the DM (H
& E, ×400); (B) Granulomatous inflammation (arrow) the anterior chamber (H & E, x100); (C) The distribution of fungal filaments could be either
like a carpet like growth on the surface (GMS, x400); (D) or in the deep stroma along the Descemets membrane (GMS, x400). (Courtesy: Dr
Geeta K Vemuganti, LVPEI, Hyderabad)
immunosuppression. Chemotherapy induced neutropenia may elaborate proteases, phospholipases and mycotoxins that may
lead to fungal infection of retina and choroid through blood cause destruction of the ocular tissues.
stream. With high dose inoculation fungi such as Candida and
Aspergillus species have been reported to invade the retina Viral Infections
even with normal granulocyte blood count.9,10 Cell mediated
immunity (CMI) is a well characterized protection against Viruses are obligate intracellular infectious units that are small
fungal infections. Cryptococcus neoformans infection of the orbit (10–400 nm) and consist of a nucleic acid genome, a protein
or chorioretina is more common in patients with CMI capsid coat and may or may not have a lipid/glycoprotein
deficiency such as acquired immunodeficiency syndrome envelope. They lack independent means of metabolism.
(AIDS) and those on heavy dose of steroids. International committee on taxonomy has classified virus
Fungus tends to spread in tissue planes as in groups based on their morphology, physical properties, nucleic
keratomycosis. The host response to fungal infection is acute acid type and strandedness, physical state of the genome,
suppurative inflammation, chronic inflammation or proteins expressed, antigenic properties, serologic cross-
granulomatous inflammation, depending on the fungal species reactivity as well as biological effects of infection. Table 5.3.2
and tissue location (Figs 5.3.1A to D). Fungi may actively presents the classification of viruses affecting the eye.11
Table 5.3.2: Viruses affecting the human eye

Virus Family Nucleic acid Target structure of the eye
Herpes simplex virus, type 1 (HHV1) Herpesviridae dsDNA Eyelid, Conjunctiva, Cornea, Trabecular
meshwork, Uvea, Retina
Herpes simplex virus, type 2 (HHV2) Herpesviridae dsDNA Eyelid, Conjunctiva, Cornea, Trabecular
Varicella zoster virus (HHV3) Herpesviridae dsDNA Eyelid, Conjunctiva, Cornea, Trabecular
Epstein-Barr virus (HHV4) Herpesviridae dsDNA Lacrimal gland, Conjunctiva, Uvea, Retina,
Optic nerve
Human cytomegalovirus (HHV5) Herpesviridae dsDNA Retina, Optic nerve
Human herpes virus 6 (HHV6) Herpesviridae dsDNA Retina
Human herpes virus 7 (HHV7) Herpesviridae dsDNA Not known
Human herpes virus 8 (HHV8) Herpesviridae dsDNA Conjunctiva
Adenovirus Adenoviridae dsDNA Conjunctiva, Cornea
HPV Papovaviridae dsDNA Eyelid, Conjunctiva, Cornea
Smallpox (variola) virus Poxviridae dsDNA Eyelid, Conjunctiva, Cornea, Uvea,
Optic nerve
Vaccinia virus Poxviridae dsDNA Eyelid, Conjunctiva, Cornea
Molluscum contagiosum virus Poxviridae dsDNA Eyelid, Conjunctiva, Cornea
Orf virus Enterovirus(es) (includes Poxviridae dsDNA Eyelid, Conjunctiva, Cornea
Poliovirus), Coxsackievirus, Picornaviridae
Echovirus, Enterovirus)
Rhinovirus Picoraviridae ssRNA(+) Conjunctiva
Rubella virus Togaviridae ssRNA(+) Cornea, Uvea, Lens, Trabecular meshwork,
Retina, Globe
Alphavirus/Flavivirus Togaviridae ssRNA(+) Conjunctiva
Influenza virus Orthomyxo-viridae ssRNA(-) Lacrimal gland, Conjunctiva, Episclera,
Cornea, Uvea, Retina, Optic nerve, Cranial
nerves
Human coronavirus Coronaviridae ssRNA(+) Conjunctiva
Newcastle disease virus Paramyxoviridae ssRNA(-) Conjunctiva, Cornea
Parainfluenzavirus Paramyxoviridae ssRNA(-) Conjunctiva
Respiratory syncitial virus Paramyxoviridae ssRNA(-) Conjunctiva
Mumps virus Paramyxoviridae ssRNA (-) Lacrimal gland, Conjunctiva, Sclera,
Cornea, Uvea, Optic nerve, Cranial nerves
Measles (rubeola) virus Paramyxoviridae ssRNA (-) Conjunctiva, Cornea, Uvea, Retina, Optic
nerve, Cranial nerves
Rift Valley fever virus Bunyaviridae ssRNA (-) Retina
Human immuno-deficiency virus Retroviridae ssRNA (+) Lacrimal gland, Retina
Specific receptors (protein, lipid, glycoprotein or Ocular infection by viruses usually follows direct contact
carbohydrate) on target cells have been shown to determine with virus. Some of the examples include contact with infected
virus tropism for specific cell types. These receptors bind to secretions during birth (herpes simplex virus, human papilloma
a ligand present on either the viral capsid or envelope. The virus), contact with contaminated fomites (adenovirus), or
virus ligand-host cell receptor interaction is essential for airborne particles (rhinovirus). Contiguous spread of viral
adsorption of the virus to the cell surface, the first step in infection from adnexa to trigeminal nerve fibers typically
viral infection. The binding of the virus to a cell surface occurs in herpes simplex virus infections.
component subverts the natural function of that cellular Virus infections may be suppressed by neutrophils, natural
molecule. In lytic viral infections, virus replication diverts killer cells, B lymphocyte-derived antibodies, and effector T
cellular protein production machinery for the synthesis of lymphocytes. Unlike B and T lymphocytes, natural killer cells
viral proteins. The synthesis of viral encoded proteins is can act without antigenic specificity or immunologic memory.
essential for the viral infection of the cell. Thus the replicative Additionally, activated natural killer cells attack cells with
cycle of most viruses can be divided into six stages of reduced MHC class 1 expression to counter viral evasion of
attachment, penetration, uncoating, replication, assembly and MHC class 1 presentation. In the eye, chemokine expression
release.11 by infected host cells induce rapid migration of leukocytes
into virus infected tissues, but may serve to increase local host include Trichuris trichiura, Ascaris lumbricoides, Ancylostoma
tissue damage and lead to reduced vision.12 Virus specific duodenale and Necator americanus.
antibodies can neutralize free virus in blood and mucosal
surfaces. They also mediate cell death of infected cells through Protozoa Affecting the Eye
complement mediated killing and by antibody dependent cell
mediated cytotoxicity. CD 8+ cytotoxic T lymphocytes (CTLs) Toxoplasmosis caused by Toxoplasma gondii is associated with
recognize viral epitopes in the context of MHC class 1 acute focal choroiditis, papillitis, papilloedema, vitritis, and
molecules expressed on the surface of virus infected cells. recurrent retinitis. Granulomatous anterior uveitis is sometimes
All nucleated cells express class 1 molecules, therefore, any seen. In immunocompetent host, the infection may be self-
virus infected cell may be a target for CTLs. limiting while choroiditis may lead to severe necrotizing form
Certain viruses produce homolog of human proteins that in immunocompromised patients.14
can influence host immunity. Epstein-Barr virus encodes a Acanthamoeba is a free living ubiquitous protozoa and an
homolog of human IL-10 and its expression inhibits interferon important cause of microbial keratitis. It exists in nature as a
γ production and T cell immunity resulting in enhanced dormant cyst, which under favorable conditions turns into
survival of virus infected cells.13 Viruses have also been active trophozoite. Though a breach in corneal epithelium
incriminated in autoimmune diseases and molecular mimicry can hasten the adhesion and penetration by Acanthamoeba it
has been suggested to cause immune-mediated damage at has been shown to attack intact Chinese hamster cornea in
distant sites. vitro. 15 One mechanism of Acanthamoeba adhesion to the
While some viruses cause self-limiting disease others can corneal surface involves interaction between the mannose
persist (latent infection) indefinitely. During latency, limited binding protein of the amoebae and mannose glycoprotein
viral gene expression occurs and the immune system response receptor of corneal epithelium.16 Following adhesion, the
to the few gene products of the latent virus is absent or organism requires cellular elements (keratocytes) of the cornea
altered. Latent viral infection usually occurs in cell types that for its sustenance. Trophozoites of Acanthamoeba penetrate
do not allow lytic infection by the virus, for example, herpes the tissues with the help of several enzymes (ribonuclease,
simplex virus and neurons, Epstein-Barr virus and B phosphatase, protease, glucosidase, etc.) as well as by
lymphocytes, and human papilloma virus (HPV) and basal phagocytosis. The inflammatory response is usually acute with
skin epithelial cells. Persistent infections intermittently produce varying degrees of fibroblastic response and necrosis. Apart
infectious virus particles in tears, mucosa and skin. Persistent from phagocytic activity, the loss of keratocytes is also
viral infection may lead to malignant transformation (HPV attributed to apoptosis.17
induced squamous cell carcinoma). Ocular manifestations in malaria include retinal
hemorrhage or exudates, usually in cerebral malaria and
Parasitic Infections indicate a poor prognosis. Retinopathy after chloroquine
Parasitic infections of the eye may be a manifestation of treatment has also been reported. Other rare findings in malaria
generalized systemic disease or a localized phenomenon. While include malarial amaurosis, optic neuritis, oculomotor paralysis,
protozoa are eukaryotic unicellular organisms belonging to and cortical blindness.
the kingdom protista, the helminths are eukaryotic multicellular Ocular manifestations of mucocutaneous leishmaniasis
organisms placed in the kingdom animalia. include granular or nodular conjunctivitis, interstitial keratitis,
Parasitic infections may originate from large number of nodular keratitis with heavy pannus formation, and ulcerative
sources; contaminated water and soil being the commonest. keratitis. Cutaneous leishmaniasis generally involves eyelids,
Other sources include fresh water fishes, crabs, undercooked/ most often on the external corner. Eyelid lesions are usually
raw beef or pork, blood sucking insects, housefly, pet animals, ulcerative, with occasional spread to conjunctiva and lacrimal
etc. In most cases, the definitive host is the mammalian host ducts.
in which either the most developed form of the parasite Microsporidia are obligate intracellular parasites belonging
occurs or the sexual reproduction of the parasite takes place. to the phylum Microspora. Multiple genera are involved in a
Some of the parasites may have no intermediate host. wide range of clinical diseases. The most common infection
Protozoa with no intermediate host in their life cycle include involves the gastrointestinal tract and others include
Acanthamoeba, microsporidia, Giardia and Entamoeba. The encephalitis, sinusitis, myositis, ocular infections and
helminths that may affect the eye and have no intermediate disseminated infection. Two forms of microsporidial infection
of the cornea have been described, stromal or interstitial reaction to the migrating worm. Degenerating or dead worm
keratitis in the immunocompetent and superficial keratoconj- may induce more severe reaction than the living parasite.
unctivitis seen in the immunosuppressed or the immuno- Dirofilariasis is caused by Dirofilaria immitis, D. tenuis,
competent.18 In a suitable host, the polar tubule of the D. repens, D. ursi or D. subdermata. Primarily seen in dogs,
microsporidial spore is extruded. Contact of the end of the the disease has been reported in humans from almost all
tubule with a host cell membrane allows the spore to transfer parts of the world. It is transmitted by mosquitoes of genera
its contents (sporoplasm) to initiate infection within the new Aedes, Anopheles and Culex. Ocular form of dirofilariasis is
host cell. The earliest developmental stage is meront which less common than pulmonary and subcutaneous forms. Eyelids
divides by binary fission and the resultant daughter cells are are commonly involved followed by orbit, subconjunctival
often seen in pairs.18 tissue and intraocular tissues. The larvae inoculated by
mosquitoes migrate and mature in the subcutaneous tissues.
Helminths Affecting the Eye The differential diagnosis is usually cyst, dermoid, abscess,
or inflammatory pseudotumor. A single parasite may be
Toxocariasis is caused by dog ascarid, Toxocara canis and less
present in the center of a lesion showing eosinophilic or
frequently by Toxocara cati, the cat ascarid. Infection of man
necrotizing granuloma.
by these organisms leads to persistent larval migration in
Bancroftian filariasis is caused by Wuchereria bancrofti
various viscera (Visceral larva migrans) including the eye (Ocular
and brugian filariasis by either Brugia malayi or Brugia timori.
larva migrans). The latter is usually seen in older children and
The adult worms live in lymphatic systems and the infection
young adults and may manifest as unilateral, solitary painless
is transmitted by mosquitoes. The ocular manifestations may
lesion located posteriorly close to optic nerve and disk. In
be caused by either the adult worms or microfilariae.
most cases, the retina is involved while lesions have been
Thelaziasis is caused by Thelazia callipaeda or T.
seen on the iris. Histologically, the lesion is composed of
granulomata with necrotic centers and fragments of larvae californiensis and is seen in dogs, cats, rabbits and many other
in the granulomata. animals.19 In man only the eye is involved. The mode of
Onchocerciasis caused by the nematode Onchocerca volvulus infection is not known although flies (family Muscidae) are
is a devastating parasitic infection of the eye. It is widely speculated to transmit the disease. It is believed that the flies
distributed across the African continent and South America. ingest the embryonated eg gs and after a period of
The female Simulium fly is the intermediate host and vector development the infective larvae may pass from the proboscis
ingests the microfilariae on biting an infected person during a of a fly feeding on or around the eyes. The adult worms are
blood meal. The larvae then transform into infective forms creamy-white, filaria-like nematodes (males: 4.5–13 mm × 0.25–
that may enter a new host when the simulid takes another 0.75 mm; females: 6.2–17 mm × 0.3–0.85 mm). The oral end
blood meal. The larvae migrate in the body for approximately has a round chitinoid capsule, an inner circle of six sessile
one year before they settle in a nodule, which is most papillae, and a pair of amphids. The male shows a distinctly
frequently subcutaneous. Here, the male and female mate curved posterior end.
and produce numerous microfilariae that migrate to various The differences between T. callipaeda and T. californiensis
parts of the body. Ocular manifestations of onchocerciasis are:
include punctate keratitis surrounding dead microfilariae, • The vulva of callipaeda is anterior to the esophagointestinal
sclerosing keratitis, anterior uveitis with secondary cataract junction, while that of californiensis is posterior.
and glaucoma, chorioretinitits, and papillitis with severe • Callipaeda has eight to ten pairs of precloacal papillae,
constriction of the visual fields. while californiensis has six to seven pairs.
Loiasis is caused by Loa loa and is transmitted by Cysticercosis is caused by larvae of tape worms Taenia
mangrove flies of genus Chrysops. It is endemic in Central solium or Taenia saginata, the larvae of the former being
and West Africa. The clinical disease mainly results from the called Cysticercus cellulosae and that of latter Cysticercus bovis.
migration of the adult worms in the subcutaneous tissues In taeniasis, man is the definitive host, the adult tape worms
called Calabar or "fugitive" swelling. The worms may migrate residing in the intestine. In cysticercosis, man acts as the
across the bulbar conjunctiva. Loa loa induced retinopathy, intermediate host. Most commonly the infection is contracted
uveitis, and migration of the worm in the eye lid, the vitreous by ingesting eggs in contaminated food or water. It can occur
and the anterior chamber have been documented. The in patients with taeniasis, either by fecal-oral autoinfection or
pathogenesis of loiasis involves mechanical injury or allergic by reverse peristalsis of proglottids into the stomach.
Ocular involvement is very common in cysticercosis (13– trauma.21 Mycobacterial infection is rare. Fungi may be
46%) and it is the most common helminthic ocular infection involved in diabetic patients and immunocompromised or
in man. Posterior segment of the eye is involved in more debilitated patients. Fungi belonging to various genera such
than 70 percent of reported ocular cases. In subcutaneous as Aspergillus, Mucor, Rhizopus, Sporothrix, Bipolaris, etc. have
cysticercosis, the lesions are numerous, firm, elastic, round, been reported. Hydatid cyst (Echinocccus granulosus) and
painless nodules or papules which may become caseated or Cysticercus cellulosae may cause proptosis with cellulitis.
calcified. Cysticercosis of the extraocular muscles is not Oppurtunistic infections by Toxoplasma gondii and Pneumocystis
uncommon.20 carinii have also been reported. Diagnostic studies include
Hydatid disease is caused by larval stage of the tapeworm white blood cell count and differential cell count, culture of
Echinococcus granulosus. Adult worms live in the small intestine blood, periorbital tissue, pus, and fluids from sinus drainage,
of the definitive host, a dog, and man acts as the intermediate orbital CT scan, ultrasonography, and sinus X-ray.
host carrying the larval tapeworm or hydatid cyst. Hydatid The urgency of treatment cannot be overstated, as a delay
disease is contracted by ingesting the eggs of Echinococcus may cause irreversible visual loss. Immediate treatment
species in contaminated food or water or by the inadvertent consists of high dose of intravenous antibiotics. Parenteral
swallowing of matter contaminated by the feces of an infected
animal. The hexacanth embryos, called oncospheres, hatch
in the duodenum, penetrate the intestinal wall, gain access to
the portal vein, may pass through the hepatic circulation and
spread to the lungs or other organs of the intermediate host.
A hydatid cyst may persist in the body of an infected
intermediate host for many years. The ocular form comprises
about 1 percent of all published cases of hydatid disease.
Almost all reported cases of ocular echinococcosis show orbital
involvement and the most common symptom is proptosis.
Painless restriction of ocular movement may occur. The cyst
may erode the orbital wall and thus invade the cranial cavity.
Ocular complications include neurokeratitis, phthisis bulbi, Fig. 5.3.2: Clinical photograph of a 16-year-old female child shows
optic neuritis, and optic atrophy. periorbital edema and hyperemia of the left eye. The lateral displacement
of the eye ball and motility limitation are due to medial subperiosteal
INFECTIONS OF THE ORBIT, LIDS abscess and surrounding orbital cellulitis (Courtesy: Dr. Suryasnata
Rath, LVPEI-Bhubaneswar).
AND LACRIMAL SYSTEM
Orbital Cellulitis
Table 5.3.3: Causes of orbital infection
This condition is commonly seen in children (Fig. 5.3.2). It is
Preexisting orbital disease
a retroseptal infection of the extraocular orbital contents
presenting with pain, lid edema, proptosis and diplopia. The • Occult malignancy
infection may spread to the eye or the cranial cavity. Serious • Orbital dermoid
complications include subperiosteal abscess with displacement Contiguous spread from neighboring structures
of the globe or cavernous sinus thrombosis with delayed • Nasal and sinus disease
treatment leading to blindness or death. Table 5.3.3 lists some • Sinus or lacrimal sac mucocele
of the etiological factors associated with orbital infection. • Orbital fracture
The organisms associated with orbital cellulitis are derived • Preseptal cellulitis
from the sinuses and may consist of aerobic and anaerobic • Facial necrotizing fascitis
bacteria. Streptococcus pneumoniae, Staphylococcus aureus and Direct injury
Haemophilus influenzae are the commonest organisms causing • Penetrating orbital or sinus injury
orbital cellulitis. Botryomycosis, a chronic bacterial • Surgery for eyelid
granulomatous disease of skin and subcutaneous tissue caused Hematogenous spread
by an encapsulated variety of Staphylococcus, may involve the • Dental infection
orbit. Polymicrobial orbital cellulitis may result following • Subacute bacterial endocarditis
cefuroxime and metronidazole covering both aerobic and the lid is a rare condition resembling necrotizing fascitis and
anaerobic organisms may be given initially until culture results is induced by the bite of the black African widow spider
are known. Most cases respond to medical treatment. A Lactodectus geometricus.
subperiosteal collection of pus that does not respond to
antibiotics requires surgical drainage. Blepharitis
Preseptal Cellulitis Inflammation of the lid margin may be anterior or posterior,

the former involving the lash line and the latter meibomian
This condition may resemble orbital cellulitis, however glands. Both the conditions may be associated with skin
presence of normal ocular motility and absence of global diseases such as dermatitis (seborrhoeic or atopic) and rosacea.
inflammation helps to differentiate them. Magnetic resonance The anterior blepharitis with lash collarettes, crusting, lid
imaging (MRI) also helps to differentiate the conditions. The ulceration and folliculitis is usually associated with S. aureus.
causative organisms are similar to that of orbital cellulitis, However, S. aureus can also be a normal flora of the lids in 6
Haemophilus influenzae being the commonest in young to 15 percent people. Lid margin culture may be positive for
children and augmentin or cefuroxime are the drugs of choice. S. aureus in 70 percent of cases with atopic dermatitis. In an
Infections with Streptococci or Staphylococci may be treated ulcerative subgroup, especially associated with steroid use,
with intravenous benzylpenicillin or clindamycin or Candida spp. may be grown in culture from lid margins. In
vancomycin. Trauma due to human or animal bite have been acute blepharitis, beads of pus and an ulcerated margin may
reported to be caused by anaerobic bacteria or Pasteurella spp. be seen whereas when chronicity sets in, there may be loss of
or group G beta-hemolytic Streptococci. lashes, telangiectasia and swollen lid margins. Culture of lid
margins is done by scrubbing with moistened (saline or brain
Necrotizing Fascitis heart infusion broth) swab and directly inoculating blood agar
Periorbital necrotizing fascitis is a rare but potentially fatal and other media. Additional swabs may be taken for smear
infection commonly caused by Streptococcus pyogenes and preparations and Gram stain. Isolation of S. aureus indicates
Staphylococcus aureus. 22,23 Other etiological agents like treatment with fusidic acid, erythromycin or tetracycline.
combination of facultative and anaerobic organisms have Isolation of coagulase negative staphylococci is not considered
also been reported.22,23 Unlike neck and scalp, necrotizing significant.
fascitis in periorbital and midfacial tissues may lack obvious
preceding trauma. 24 There is one report of periorbital Canaliculitis
necrotizing fascitis in a healthy young adult caused by Tearing, discharge, red eye and mild tenderness over the nasal
Cryptococcus in which there was a definite history of preceding aspect of the lower or upper lid are the main symptoms. On
trauma with a wooden splinter.25 A series of 18 cases of examination of the eye, erythematous pouting of the punctum
histomorphologic and/or culture proven zygomycotic along with erythema of the skin surrounding the punctum
necrotizing fascitis from India comprised 15 (83%) cases of may be seen. Actinomyces spp. and Arachnia spp., both anaerobic
immunocompetent patients with precedent trauma in 14 bacteria, are the commonest organisms associated with
(77%).26 Interestingly out of eight microbiologically proven canaliculitis. The microaerophilic atmosphere of the
cases, five were Apophysis spp. and two had coexistent canaliculus supports the growth of nonfastidious anaerobic
Aspergillus and Candida spp. This report highlighted the bacteria. Pus, expressed from the canaliculus can be Gram-
importance of fungus as an etiological agent in necrotizing stained and cultured for aerobic and anaerobic bacteria.
fascitis, in a largely immunocompetent subgroup of patients Thioglycollate broth is a good medium to grow actinomycetes
from India. Tropical environment with presence of fungi as which produce "bread crumb" like growth. Irrigating the
saprophytes may be contributory. canaliculus with penicillin, debridement of the canaliculus,
The spreading edge of the necrotizing infection may spread syringing the canaliculus with povidone iodine, etc. are some
very fast. It is a medical emergency requiring large doses of of the treatment modalities.
antibiotics. Surgical debridement may be indicated to prevent
spread. If the infection responds to antibiotics, the necrosis
Dacryocystitis
is confined to the lids leading to typical eschar formation.
The eschar sloughs off eventually and may leave a damaged Distal obstruction of the nasolacrimal duct causes stasis and
lid that requires reconstructive surgery. Ioxoscleromatis of may lead to acute dacryocystitis, most commonly caused by
S. aureus, H. influenzae and S. pneumoniae. The symptoms of Cornea

pain, redness and swelling over the lacrimal sac in the
innermost aspect of the lower eye lid may be recurrent. A Interstitial Keratitis
mucoid or purulent discharge may be expressed from the Nonulcerative stromal keratitis or interstitial keratitis occurs
punctum when pressure is applied. This expressed material when conjunctival and superficial corneal infections extend
can be collected aseptically using two cotton swabs, one for to the stroma, or there is an immune response within the
smear and the other for culture. Chronic dacryocystitis is stroma. Stromal inflammation may also accompany systemic
usually the end-stage of acute or subacute dacryocystitis but diseases such as, syphilis and tuberculosis. There can be many
it may present initially as a subclinical infectious cause of causes of interstitial keratitis (Table 5.3.4). Characteristically,
nasolacrimal duct obstruction. More than 90 percent of the epithelium remains intact while the involved stroma
patients with congenital nasolacrimal duct obstruction undergo becomes edematous. In severe cases, folds develop in
spontaneous resolution by one year of age; therefore, initial Descemet's membrane. Edema and cellular infiltration causing
probing must be postponed until this age. Success rate of a diffuse stromal haze is referred to as "diskiform" keratitis
probings is also very high and a dacryocystorhinostomy is when it occupies the central portion of the cornea. Several
indicated only after failure of repeated probing. conditions can cause "diskiform keratitis", however herpes
simplex keratitis is the most common cause.
INFECTIONS OF THE EYE The byproducts of HSV replication and immune alteration
Conjunctiva of the cornea and iris play an important role in many
destructive corneal conditions. Intact HSV is rarely found in
Apart from noninfectious allergic or toxic inflammations, the cornea, therefore it seems likely that the persistence of
conjunctivitis may be caused by several groups of organisms incomplete viral antigens and the viral immune alteration of
including bacteria, Chlamydia, viruses, fungi, helminths, and cell membranes in the corneal stroma incite inflammatory
protozoa. Acute bacterial conjunctivitis may be acute papillary, reactions that involve programmed host lymphocytes, antiviral
hyperacute purulent or acute membranous conjunctivitis. antibodies, serum complement, polymorphonuclear cells, and
Commonest causes of purulent conjunctivitis are Neisseria macrophages.28,29 Greater amount of glycoproteins have been
(ophthalmia neonatorum) or Staphylococcus infection. These shown in HSV strains that cause stromal disease than those
infections require urgent treatment as Neisseria may penetrate that cause epithelial disease.30 This suggests that stromal
through intact corneal epithelium. Concomitant with urethritis disease is a host immune response to the antigenic
N. gonorrhoeae can cause bilateral purulent conjunctivitis with glycoproteins produced in the ocular tissues by the infecting
or without corneal involvement in adults. Bacterial HSV strain. It may be concluded that both host immune
conjunctivitis may also be caused by S. pneumoniae, H. influenzae factors and viral characteristics play key roles in determining
and Group A Streptococcus. Acute or chronic inflammation of
the conjunctiva may also be caused by viruses, Chlamydia and Table 5.3.4: Causes of nonulcerative stromal
parasites. Isolated fungal infections of the conjunctiva are (interstitial) keratitis
rare. Bacterial infection
Several antigenic types of adenovirus have been shown • Syphilis
to be associated with epidemic keratoconjunctivitis. Recently, • Tuberculosis
• Leprosy
microsporidia was shown to be associated with • Lyme disease
keratoconjunctivitis clinically similar to adenovirus infection.27 • Brucellosis
Some strains of adenoviruses may cause acute hemorrhagic Viral infection
conjunctivitis. Herpetic and molluscum contagiosum associated • Herpes simplex virus
• Varicella zoster virus
viral conjunctivitis are characterized by follicular reaction.
• Epstein-Barr virus
Chlamydia trachomatis is an obligate intracellular parasite that • Mumps
is responsible for several forms of conjunctivitis such as • Rubella
trachoma and inclusion conjunctivitis (adult and neonatal). Parasitic infection
Tests to detect these infections include culture, antigen • Leishmaniasis
• Onchocerciasis
detection by enzyme linked immunosorbent assay (ELISA), • Trypanosomiasis
direct fluorescence antibody (DFA) methods, polymerase chain • Acanthamoeba
reaction (PCR) and DNA probes. • Microsporidiosis
the ultimate expression of clinical disease in ocular herpes. numbers of acid-fast-staining lepra bacilli. As the disease
More details of this condition have been described later in advances, the lesions increase in size, become confluent and
this chapter. there is calcium deposition. Pannus formation ensues in the
Two-thirds of the patients with herpes zoster ophthalmicus superior temporal quadrant, with superficial limbal vessels
have corneal involvement which takes the form of punctate extending between Bowman's membrane and the epithelium.
keratitis (51%), pseudodendrites (51%), anterior stromal Thus, the corneal lesions include opacification of the corneal
infiltrates (41%), sclerokeratitis (1%), keratouveitis - nerves, avascular keratitis, interstitial keratitis, pannus
endothelitis (34%), peripheral ulcerative keratitis (7%), delayed formation and corneal leproma.
mucous plaques (13%), diskifor m keratitis (10%), Among the parasites Onchocerca volvulus causes conjunctival
neurotrophic keratitis (25%), and exposure keratitis (11%).31 and corneal lesions by invasion and subsequent death of the
Corneal sensation may be markedly diminished in even the microfilariae. The live worm usually causes no reaction, but
mildest cases of herpes zoster keratitis. Anesthesia is greater after its death, opacities may develop around the dead
than that seen with simplex keratitis of comparable severity organism. Initially, limbitis develops followed by punctate
and is probably due to the greater severity of ganglionitis in keratitis. The keratitis can occur as either superficial fluffy
zoster. All stromal forms of the disease are clinically stromal opacities or discrete discoid opacities.34
indistinguishable from stromal herpes simplex disease and
may represent the same immune pathogenetic mechanisms. Microbial Keratitis
Syphilis, caused by T. pallidum, is a cause of corneal
Microbial keratitis is a common, potentially sight-threatening
inflammation that is typically nonulcerative and is referred to
ocular infection that may be caused by bacteria, fungi, viruses,
as interstitial keratitis. Most cases involve the deep stroma,
or parasites. Virtually any bacteria can potentially cause keratitis
and neovascularization is a frequent occurrence. Interstitial
(Table 5.3.5). The relative frequency of different bacteria as
keratitis is a common ocular finding of untreated congenital
causative agents in keratitis may vary geographically. There
syphilis and may occur even in acquired syphilis. It may occur
has also been a change in the spectrum of bacteria causing
any time from birth to middle age.32 Lymphocytic infiltration
keratitis with time, especially in the United States. The incidence
most often affects the deep stromal layers in one or more
of pneumococcal keratitis, which is commonly associated
clustered foci. Bilateral nummular infiltrates at various levels
with chronic dacryocystitis,35 has decreased in developed
can be the presenting feature of congenital syphilis. On
countries as a result of modern antibiotics and refinement in
resolution of active inflammation, the sequelae of interstitial
techniques for dacryocystorhinostomy.36 Staphylococcus species
keratitis are stromal scarring, endothelial changes, and corneal
continue to be the predominant cause of bacterial keratitis
ghost vessels. Bilateral involvement is common in most cases
and in several reports Staphylococcus epidermidis or coagulase
of interstitial keratitis caused by congenital syphilis. negative Staphylococci (CONS) are the leading causes.37,38 In
Interstitial corneal inflammation does occur in patients several series from the southern part of the United States,
with tuberculosis, but tubercle bacilli have rarely been Pseudomonas species is reported to be the most commonly
identified or isolated from the corneal tissue. Hypersensitivity isolated organism, especially in association with daily or
to tubercular protein is a postulated cause of the inflammation. extended wear soft contact lenses.39 Being widely distributed
Clinically, the corneal lesions have been called "phlyctenules". in nature, Pseudomonas can easily contaminate ophthalmic
They begin in the deeper layers of the stroma, most often preparations, and cosmetics. Moraxella group of organisms
near the limbus, and may be single or multiple. They are have been reported to cause keratitis in malnourished
characterized by the separation of the corneal lamellae by individuals with diabetes, alcoholism or other conditions,
inflammatory cells in the absence of overlying ulceration.33 however, they have also been reported from keratitis in healthy
In leprosy, the cornea can be affected in either lepromatous individuals.40
or tuberculoid form. The latter rarely affects the eye but can Organisms less frequently reported from bacterial keratitis
cause corneal anesthesia by affecting the trigeminal nerve. include Corynebacterium species, 41 Propionibacterium acnes,42
Lepromatous leprosy produces a nonulcerating, diffuse, Bacillus species,43 Neisseria gonorrhoeae, and members of the
granulomatous stromal inflammation characterized by Enterobacteriaceae family 44 . Corneal involvement with
infiltration with histiocytic (foam) cells and giant cells (globi). Corynebacterium diphtheriae is an event of the past since the
Small collections of lymphocytes and plasma cells are also development of the vaccine, though the organism is known
seen, but they are not a major component of the inflammatory to penetrate intact corneal epithelium.45 While the association
response. The histiocytes and giant cells may contain large of Bacillus species in causing severe post-traumatic
endophthalmitis is well established, corneal ulcers caused by also predispose to bacterial keratitis. Recently popularized
Bacillus species are rare and the largest series (19 eyes of 17 keratorefractive surgery, excimer laser photorefractive
patients) has been described from India.46 Listeria monocytogenes keratectomy (PRK), and excimer laser in situ keratomilieusis
has been infrequently isolated as a cause of corneal (LASIK) have resulted in disastrous bacterial keratitis cases.51
ulceration.47 Nocardia species have been linked with bacterial Patients who have undergone penetrating keratoplasty are
keratitis,48 most cases being caused by Nocardia asteroides. also at increased risk for bacterial keratitis.
However, they remain a rare cause of corneal ulceration. Similar to bacteria, fungi gain access into the corneal
While primary tuberculous keratitis is extremely rare, infections stroma through a defect in the epithelial barrier which may
of the cornea have been reportedly caused by atypical
be due to external trauma, a compromised ocular surface, or
mycobacteria including Mycobacterium fortuitum, 49
previous surgery. Once in the stroma, they multiply and cause
Mycobacterium chelonae, Mycobacterium gordonae, and
tissue necrosis and a host inflammatory reaction. Organisms
Mycobacterium avium-intracellulare. Rare nonsyphilitic
can penetrate deep into the stroma and through an intact
spirochetal infection of the cornea may occur in Lyme disease
caused by Borrelia burgdorferi.50 Descemet's membrane. It is believed that once the organisms
Apart from corneal abrasion, foreign body, or erosion, gain access into the anterior chamber or to the iris and lens,
which may precipitate bacterial keratitis, surgical trauma may eradication of the organism becomes extremely difficult.
Overall, the incidence of fungal keratitis is low in
Table 5.3.5: Bacteria associated with keratitis temperate climates, while higher incidence is reported from
Southern United States and tropical regions of the world
Gram-negative aerobic/facultative anaerobic bacilli
including India.52 A wide variety of species have been reported
• Pseudomonas spp.
• Escherichia spp. from different parts of the world (Table 5.3.6). Prevalent
• Citrobacter spp. species vary from one geographical area to the other.
• Klebsiella spp. Herpes simplex virus (HSV) is the commonest virus
• Serratia spp.
• Proteus spp. associated with keratitis. The spectrum of ocular disease
• Actinobacillus spp. caused by HSV is broad. The clinical sequelae of HSV
• Flavobacterium spp. infection are largely a result of recurrent disease and the
• Haemophilus spp.
immunologic response associated with each episode. Many
Gram-negative anaerobic bacilli
• Bacteroides spp.
factors have been implicated in the activation of recurrent
• Fusobacterium spp. HSV ocular disease. Sunlight, trauma (including surgery), heat,
Gram-negative cocci and coccobacilli (aerobes) abnormal body temperature, menstruation, other infectious
• Neisseria spp. diseases, and emotional stress have all been implicated in the
• Moraxella spp.
• Acinetobacter spp.
activation of HSV infection. Although some type of
Gram-positive aerobic and/or facultative anaerobic cocci
immunoregulation may exist in all of these circumstances, it
• Micrococcus spp. has not been clearly demonstrated. The severity and frequency
• Staphylococcus spp. of disease also depend on the viral genome and its virulence.
• Streptococcus spp.
Recurrent epithelial keratitis is caused by reactivation of
• Pediococcus spp.
• Aerococcus spp. live virus, the most commonly recognized clinical
Gram-positive anaerobic cocci manifestations of which are dendritic and geographic ulcers.
• Peptostreptococcus spp. The features of a dendritic ulcer include a branching, linear
Gram-positive bacilli lesion with terminal bulbs and swollen epithelial borders that
• Bacillus spp. contain live virus (Fig. 5.3.3). This lesion represents a true
• Clostridium spp.
ulcer in that it extends through the basement membrane. An
Actinomycetes and related organisms
• Corynebacterium spp. enlarged dendritic ulcer that is no longer linear is referred to
• Porpionibacterium spp. as a geographic ulcer. The dendritic or geographic ulcer may
• Actinomyces spp. be completely resolved without residual evidence but more
• Arachnia spp.
• Bifidobacterium spp. commonly it leads to the sight-threatening sequel of stromal
• Mycobacterium spp. scarring. Another sequel is stromal disease which may develop
• Nocardia spp. in 25 percent of patients.53 The stromal disease may be either
• Streptomyces spp.
infectious or of immune etiology. Necrotizing keratitis
Table 5.3.6: Types of fungal agents represents true viral infection of the stroma, whereas immune
causing mycotic keratitis stromal keratitis is complement-mediated antibody reactions
1. Hyaline filamentous fungi to viral antigen. Many patients with HSV disease develop
• Aspergillus spp. corneal stromal edema without stromal infiltrate which is
• Acremonium spp. believed to be due to endothelitis.
• Beauveria spp. Common protozoa causing keratitis include Acanthamoeba
• Cylindrocarpon spp.
• Fusarium spp. and microsporidia. The first case of Acanthamoeba keratitis
• Geotrichum candidum in the world was reported in 197354 and a few cases were
• Neurospora spp. recognized between 1973 and 1983. The first case diagnosed
• Penicillum spp.
• Paecilomyces spp.
in India was in 1987. 55 The reported incidence of
• Pseudallescheria boydii Acanthamoeba keratitis all over the world increased dramatically
• Sphaeropsis subglobosa through 1989 and then it reached a plateau, especially in the
• Scopulariopsis
• Ustilago spp.
United States. While the incidence continues to increase in
• Volutella spp. developing countries it is reported to have declined in the
2. Dematiaceous filamentous fungi United Kingdom.56
• Alternaria spp.
Acanthamoeba keratitis occurs in immunocompetent,
• Bipolaris spp.
• Curvularia spp. healthy young individuals. Several important risk factors have
• Cladosporium spp. been identified which are associated with Acanthamoeba
• Drechslera spp. keratitis. In a series of 189 cases of Acanthamoeba keratitis
• Exserohilum spp.
• Exophiala jeanselmei from the United States 85 percent of cases were contact lens
• Lasiodiplodia theobromae related.57 In contrast, the commonly identified risk factor in
• Phialophora spp. patients of Acanthamoeba keratitis seen in developing countries
3. Yeasts and yeast like fungi
• Candida spp. is history of corneal trauma or exposure to contaminated
• Cryptococcus spp. water.58,59 Adhesion of Acanthamoeba trophozoites and cysts
• Rhodotorula spp. to a variety of contact lenses has been shown in vitro.60 Major
• Trichosporon spp.
4. Dimorphic fungi
reviews have dealt with the clinical features and treatment of
• Blastomyces dermatitidis Acanthamoeba keratitis in contact lens related61 as well as
• Paracoccidoides brasiliensis noncontact lens related59 Acanth-amoeba keratitis. The epithelial
• Sporothrix schenkii
5. Others
breakdown and stromal involvement may resemble either
• Mycelia sterilia herpes simplex keratitis or fungal keratitis, however, a
• Rhizopus spp. characteristic form of the stromal disease occurs late as a
• Mucor spp.
typical ring infiltrate (Fig. 5.3.4).
Microsporidial keratoconjunctivitis has been described in
this chapter earlier. The organisms are also associated with
stromal keratitis. 62 Clinically, it is difficult to diagnose
microsporidial stromal keratitis and laboratory diagnosis is
required to make the diagnosis. In the absence of availability
of specific treatment, many of the cases end up with
penetrating keratoplasty.
Sclera
Scleritis is a rare condition. It is usually noninfectious, however,
it may be associated with bacterial (Pseudomonas spp.,
Staphylococcus aureus, Nocardia spp., Atypical mycobacteria)
or fungal (Aspergillus spp.) infection. Infectious scleritis may
be after trauma (accident, surgery), endophthalmitis, or an
Fig. 5.3.3: Slit lamp photograph under diffuse illumination with cobalt
blue filter showing dendritic lesion in the cornea of a patient with
extension of a corneal infection. 63 On rare occasions
herpes simplex virus keratitis (Courtesy: Dr. Sujata Das, LVPEI- tuberculosis may be the cause of scleral nodules.64 Scleritis is
Bhubaneswar). frequently associated with a secondary uveitis (iritis or
the eye and produce endogenous endophthalmitis. Ocular

manifestations of infection by Mycobacterium tuberculosis
include acute or chronic granulomatous iridocyclitis, iris
nodules, multifocal choroiditis, chronic tuberculomas. Acute
tuberculous endophthalmitis is rare. Lepromatous leprosy may
be associated with insidious or acute exudative iridocyclitis.
Lepromas consisting of lymphocytes, fibroblasts, macrophages
along with acid fast bacilli may be seen on iris and ciliary
body. Ocular involvement in tuberculous leprosy is rare.
Among the spirochetes, Treponema pallidum (syphilis) and
Borrelia burgdorferi (Lyme's disease) are known to be associated
with uveitis. In secondary syphilis, iritis may occur with red
spot in the middle third of the iris or yellow to brown papules
at the pupillary margin or ciliary body.65 Ocular findings in
Fig. 5.3.4: Slit lamp photograph in diffuse illumination showing dense
ring infiltrate with hypopyon. Acanthamoeba cysts were seen in corneal
Lyme disease include hemorrhagic conjunctivitis, keratitis,
scrapings and culture grew Acanthamoeba spp. (Courtesy: Dr. Sujata iridocyclitis, pars planitis, retinal vaculitis, optic neuritis, Vogt
Das, LVPEI-Bhubaneswar) Koyanagi Harada (VKH) syndrome, etc.66
Viral Uveitis
choroiditis). The work-up of a patient with active scleritis
includes an evaluation for evidence of vasculitis, connective Herpetic uveitis caused by herpes simplex virus (HSV) or
tissue disease, and infection. Detailed history and appropriate varicella zoster virus is a common complication of herpetic
laboratory tests are important to make an accurate diagnosis. keratitis. It may also occur without keratitis. HSV may cause
The laboratory tests include erythrocyte sedimentation rate, granulomatous inflammation of the iris, iris edema or necrosis
rheumatoid factor, antibody nuclear antibody, fluorescent and unilateral or bilateral acute retinal necrosis. High titer
treponemal antibody absorption (FTA-ABS), etc. antibody to HSV and HSV antigen has been demonstrated in
acute retinal necrosis.67 Like HSV, Epstein-Barr virus (EBV)
Uvea causes conjunctivitis, episcleritis, keratitis, uveitis and optic
neuritis. Acute bilateral severe anterior uveitis and acute
Any inflammation involving the uveal tract is termed uveitis. punctate retinochoroiditis and panuveitis have been described.
It is classified as anterior, intermediate, posterior or panuveitis High EBV antibody titers in the aqueous humor in cases of
based on its location and whether it is either acute or chronic. anterior uveitis have been demonstrated.68 Infection with
Chronic uveitis can be further divided into granulomatous or cytomegalovirus can cause serious disease in utero and in
nongranulomatous. Uveal tract infection may be exogenous immunosuppressed patients. Ocular signs in congenital disease
(corneal ulcer, trauma, surgery) or endogenous from a include chorioretinitis and optic atrophy. Most striking finding
contiguous structure (sinuses, orbital abscess, cellulitis) or in the acquired infection is a necrotizing retinitis characterized
hematogenous. Microorganisms from any of the groups, by multiple, granular, yellow-white areas (cotton wool spots)
bacteria, fungus, virus or parasite, either directly or indirectly associated with extensive retinal hemorrhages and vascular
may cause uveitis. sheathing. The retina is thickened, and its laminar structure is
markedly disrupted. The cells are enlarged and show Cowdry
Bacterial Uveitis type-A intranuclear eosinophilic inclusions with a clear zone
Metastatic bacterial endophthalmitis with associated uveitis resembling owl's eye.69 Nongranulomatous iridocyclitis with
may be anterior, posterior or panophthalmitis. Focal intraocular lymphocytic infiltrate and secondary iris hypoplasia is seen in
inflammation is usually concentrated in one or more discrete congenital rubella syndrome due to direct viral infection.
foci with appearance of whitish nodules or plaques in the
Fungal Uveitis
iris, ciliary, retina or choroid. Anterior diffuse inflammation
is characterized by corneal edema, hypopyon or fibrinous Candida albicans, Histoplasma capsulatum, Cryptococcus
clot in the anterior chamber. Intense inflammatory reaction neoformans and Aspergillus fumigatus are some of the fungi
is seen in the vitreous in posterior diffuse inflammation. associated with choroiditis and chorioretinitis. C. albicans may
During the course of bacteremia any bacteria can lodge in be associated with endogenous endophthalmitis, the risk factors
for which include prior antibiotic therapy, prior surgery, An tibo dy titre in AH /VA An tibo dy titre in ser um
diabetes mellitus, alcoholism, etc. Vitreous culture is usually :
TotalIgG in VA/AH TotalIgG in serum
positive for C. albicans and the organism may be grown from
the blood. C. neoformans has a predilection for the central Local antibody production was considered positive when
nervous system and intraocular involvement may occur as WDC is > 1.74 Detection of ocular antibody production is
either hematogenous spread or direct extension from the most reliable in case of recurrent chorioretinitis, but may be
central nervous system infection. Chorioretinitis consists of negative during the initial stages of reactivation. Titers
multiple, discrete, slightly elevated, amelanotic retinal or determined by the dye test, ELISA, and IFA techniques have
choroidal lesions. Retinal perivascular sheathing, vitritis, and been used to calculate intraocular antibody production. False
anterior uveitis may also occur. This budding yeast is identified positive and false negative results can also be a problem in
by its capsule, inability to form pseudohyphae and urease case of local antibody production. Witmer coefficient,
production. Like Candida it grows well in media like blood Witmer-Goldmann coefficient and Witmer Desmonts'
agar and Sabouraud dextrose agar. Choroiditis and retinitis coefficient are all synonymous names for the same formula.
due to A. fumigatus is generally hematogenous in origin and It is not a reliable technique for congenital disease, or in
occurs mostly in immunocompromised patients. It may also patients who also have recently acquired nonocular disease
cause acute bilateral necrotizing retinitis.70 because of the high level of serum antibodies. PCR
amplification of sequences within B1 and ribosomal genes
Parasitic Uveitis of T. gondii has been assessed in a variety of tissues in both
immunocompetent and immunocompromised individuals.
Toxoplasmosis, toxocariasis and onchocerciasis are some of
Primers directed against B1 and p30 gene were able to detect
the prominent causes of parasitic uveitis. Toxoplasmosis can
50 fg (approx. single tachyzoite) genomic DNA.72 Gene
be congenital, acquired, or reactivation of quiescent tissue
amplification by PCR technique is useful in ophthalmic
cyst, especially in immunocompromised patients or AIDS.
diagnosis, since it enables exceedingly small amounts of nucleic
Ocular toxoplasmosis presents as multifocal or focal
acid to be detected in ocular samples. T. gondii DNA have
necrotizing retinochoroiditis. There is usually necrosis of the
been detected by PCR in ocular tissue section of patients
infected retina with T. gondii found in the inner retina. There
with presumed Toxoplasma retinochoroiditis, even when typical
occurs massive proliferation of the pigment epithelium
tissue cysts are not identified on histopathological examination.
adjacent to the necrotic areas. The underlying choroid is
Exudative posterior chorioretinitis, peripheral
infiltrated by lymphocytes and plasma cells and may itself
retinochoroiditis, optic papillitis, endophthalmitis, motile
undergo necrosis with obliteration of the choriocapillaries.71
chorioretinal nematode, or diffuse unilateral subacute
The diagnosis of T. gondii infection or toxoplasmosis may be
neuroretinitis are some of the manifestations of ocular
established by serologic tests, amplification of specific nucleic
toxocariasis. The disease has a wide range with some infections
acid sequences and histological demonstration of the parasite
producing few clinical signs and others serious ocular
or its antigen and by isolation of the organism. The diagnosis
destruction. The most important differential diagnosis is
of ocular toxoplasmosis is usually based on characteristic
retinoblastoma. A definitive diagnosis depends on the detection
lesions on fundus examination. Currently the clinical diagnosis
of the toxocaral larvae in tissue sections which is usually
of ocular toxoplasmosis is based on the observation of a
very difficult. Serological tests, of which ELISA is most
typical necrotizing lesion on the fundus, response to treatment
promising, may help in diagnosis.
and serological diagnosis.72
Laboratory tests are helpful to support the diagnosis of
toxoplasmosis when the ocular manifestations are atypical. Retina-Vitreous
Witmer Desmonts Coefficient (WDC) is useful to determine
Endophthalmitis
the level of the locally produced specific anti T. gondii antibody
present in the intraocular fluid, in proportion to the antibodies Infection of the vitreous compartment along with retinal and
present in the peripheral blood.73 WDC is calculated by uveal coats of the eye constitutes endophthalmitis. It may be
comparing the concentration of anti-toxoplasma antibodies exogenous, involving intraocular surgery or following
divided by the concentration of the IgG fraction in the penetrating injury to the eye. Organisms causing acute
aqueous humor (AH)/ vitreous aspirate (VA) to that in the endophthalmitis include gram-positive and gram-negative
serum, as shown below: bacteria. Some of the organisms associated with acute
endophthalmitis are Streptococcus pneumoniae, Pseudomonas materials may influence the bacterial adhesion and increase
aeruginosa, Staphylococcus aureus, members of Enterobacte- the risk of infection, silicone IOLs have been shown to carry
riaceae, enterococci, etc. Causes of chronic endophthalmitis a higher risk than heparin surface modified
include coagulase negative staphylococci, Propionibacterium polymethylmethacrylate (PMMA) implants. Prophylactic
acnes, Propionibacterium arachnia, Cor ynebacterium spp., measures in ocular surgery are of paramount importance in
Aspergillus spp., etc. the prevention of postoperative endophthalmitis (Table 5.3.7).
Intraocular infection within six weeks of the causative Evidence in literature suggests that use of antibiotic
event is termed acute endophthalmitis. Postoperative prophylaxis reduces the incidence of postoperative
endophthalmitis can occur after any intraocular surgery, endophthalmitis. However, the antibiotic choice, routes of
though numerically most infections are seen following cataract delivery, timing, and dose regimens are less clear. There is
surgery, for the obvious reason that cataract surgeries lack of comparative data regarding the effectiveness of agents
outnumber other intraocular surgeries. Endophthalmitis is a such as aminoglycosides, neosporin and fluoroquinolones.
rare complication of cataract surgery and the current Despite widespread prophylactic use of topical antibiotics,
worldwide incidence is less than 0.1 percent.75 A large study studies supporting such use have been criticized for
at the Bascom Palmer Eye Institute between 1995 and 2001 methodological flaws.81 There is also the concern among the
found the incidence to be 0.05 percent.76 In recent times a physicians that indiscriminate use of newer agents such as
rise in postoperative endophthalmitis has been reported, fourth generation fluoroquinolones may facilitate emergence
especially associated with clear corneal incision surgery for of bacterial resistance. Nevertheless, preoperative topical
cataract.77 The clinical diagnosis is a constellation of signs
and symptoms which include reduced vision, lid edema, pain Table 5.3.7: Prophylactic measures for
and congested eye. These features may not differentiate an postoperative endophthalmitis
infective from a noninfective endophthalmitis, though lid Preoperative
edema occurs mainly in infective endophthalmitis.78 1. Careful assessment of external ocular surface. Conjunctival
The microbiological diagnosis is based on microscopy and culture recommended if significant external inflammation or
culture of the microorganisms from anterior chamber fluid discharge is present. Routine preoperative culture of conjunctiva
and lids is not recommended.
and/or vitreous (tap or biopsy) fluid. Smears made from 2. Treatment of eyelid infections with lid hygiene, topical antibiotics,
these samples may be examined immediately after staining or systemic antibiotics.
with Gram or Giemsa stain for infecting pathogens. Calcofluor 3. Syringing of lacrimal system if lacrimal duct infection or
obstruction is present.
white may be used when a fungal etiology is suspected.
4. Topical antibiotic therapy up to 24 hours prior to surgery.
Although smear examination is a rapid method, its sensitivity 5. Systemic antibiotic prophylaxis may be considered in high risk
is low.79 Culture on a host of media for bacteria and fungus cases (secondary IOL implantation, vitreoretinal procedures in
is recommended. Inclusion of cassette fluid for culture may diabetic patients, immunocompromised patients).
increase the culture positivity, however it is tedious and time Intraoperative
consuming. Microscopy of the vitreous fluid also demonstrates 1. Sterile draping to exclude eyelids and lashes from the operative
field.
several varieties of cells associated with the infection. 2. 5% povidone iodine use to prepare the ocular surface and eyelid
Presence of six or more polymorphonuclear cells per high margins.
power field has been shown to be indicative of infection 3. 10% povidone iodine solution cleaning of the surrounding skin.
even if microorganisms are not demonstrated in microscopy.79 4. Irrigation of IOLs before insertion.
5. Minimum duration of exposure of IOLs to the operating room
A number of studies have supported the view that the environment before insertion.
most common source of postoperative endophthalmitis is 6. Careful wound closure by any technique.
the extraocular microbial flora of the patient. Ocular 7. Benefit from antibiotic use in infusion fluids is controversial. It
carries risk of wrong dosage and inadvertent infection if the
conditions such as blepharitis and nasolacrimal duct antibiotic is shared between patients.
obstruction with consequent infection increase the risk of 8. Subconjuctival antibiotic injections at the end of surgery are of
postoperative infection. Systemic infections predisposing to unproven benefit and carry the risk of inadvertent injection into
the eye.
endophthalmitis include active infection, especially upper
Postoperative
respiratory tract infection, diabetes and immunocompromised
1. Postoperative instillation of topical 2.5% or 5% povidone iodine
states. Bacterial contamination of the anterior chamber occurs
solution.
in 5 to 43 percent of patients during cataract surgery. 80 2. Antibiotic drops, or antibiotic ointment may be beneficial.
However, the anterior chamber is able to eradicate low level 3. For patients with prolonged surgery, vitreous loss, or severe
of bacterial contamination. Even as intraocular lens (IOL) diabetes, closer postoperative follow-up should be considered.
antibiotics, particularly fluoroquinolones, continue to be widely LABORATORY DIAGNOSIS

used and are believed to reduce the risk of postoperative OF OCULAR INFECTIONS
endophthalmitis. Though not widely accepted, the use of
antibiotics in infusion fluid has also been suggested. A recent Sample Collection
multicenter study has shown significant reduction in the As is true for any infection, the clinical samples for the
incidence of postoperative endophthalmitis by routinely using diagnosis of eye infections must be collected from the site
intracameral cefazolin at the end of cataract surgery.82 of infection. Serum samples are very rarely helpful in the
Bacillus spp. and fungi are most commonly associated diagnosis of eye infections.
with post-traumatic endophthalmitis though other organisms Following are some of the important guidelines:
may be found.83,84 Occasionally Clostridium perfringens may • The samples need to be collected carefully without causing
be associated with soil contamination of a foreign body injury. much pain and discomfort to the patient.
Endogenous metastatic endophthalmitis is less common and • The samples must be collected from the site of lesion
it arises in association with septicemia, subacute infective ensuring minimum loss during collection.
endocarditis, and chronic suppuration with diabetes or • Generally, the sample available is very minute and requires
neoplasms. It can also arise from colonized intravenous lines direct processing without resorting to transport media
or contaminated syringes used by drug addicts. Contaminated (except for virus or Chlamydia isolation).
intravenous infusion have been reported from India to be • Fastidious organisms are commonly associated with eye
associated with Aspergillus endophthalmitis.85 Candida spp. infections therefore; a delay in processing may lead to
is often reported as cause of endogenous endophthalmitis in less than optimum results.
immunocompromised patients with renal transplantation or • Knowledge of expected organisms from eye infections
acquired immunodeficiency syndrome (AIDS). Neisseria helps to determine the significance of the organism
meningitidis can cause unilateral purulent endophthalmitis detected.
following bacteremia. • Prolonged incubation (1–2 weeks) of most media is
Whatever the basis of infection, endophthalmitis is a recommended to allow growth of slow growing/fastidious
potentially blinding disease with irreversible rapid tissue organisms.
damage; therefore, early diagnosis and prompt treatment are Table 5.3.8 describes the type of clinical sample that may
the hallmark of successful management. be collected for the diagnosis of various eye infections. The
Table 5.3.8: Type of sample and recommended procedure for clinical sample collection in various eye infections
Type of Infection Type of sample Recommended device/procedure for sample
collection
Blepharitis Scales/discharge from lid margin Forceps/Cotton swab
Conjunctivitis Fluid/discharge from lower conjunctival sac Calcium alginate/cotton swab
Dacryocystitis Fluid/discharge from lower conjunctival sac Calcium alginate/cotton swab
Keratitis Corneal scraping Kimura spatula, No. 15 surgical blade, bent
needle
Uveitis Anterior chamber fluid Paracentesis (anterior chamber tap) with
tuberculin syringe
Endophthalmitis i. Anterior chamber fluid i. Paracentesis (anterior chamber tap) with
tuberculin syringe
ii. Vitreous aspirate ii. Tuberculin syringe
iii. Vitreous Biopsy iii. Vitrectomy
Panophthalmitis i. Vitreous biopsy i. Vitrectomy
ii. Evisceration contents ii. Evisceration
Deep seated stromal infiltrate Corneal biopsy Lamellar biopsy
in keratitis.
Non-healing keratitis. Corneal buttons Penetrating keratoplasty
requiring keratoplasty.
Contact lens associated Contact lenses, lens cases and lens solution Aseptically removed from the eye. Aseptically
keratitis. collected
Postoperative endophthalmitis Intraocular lens Surgical removal
following intraocular lens
implantation.
Eye injury with iris Iris tissue Surgical removal
prolapse/incarceration.
requirements for the collection of clinical material from the by histopathology and a correlation is sought for appropriate
eye are listed below: reliable diagnosis. Table 5.3.9 provides the direct smear
• Kimura spatula/disposable surgical blade no. 15/sterile examination methods that may be used for detection of
needle. various organisms from ocular samples. Smears are generally
• New, clean, microscopy glass slides, preferably hot air not made from samples such as contact lenses, contact lens
oven sterilized. solutions, intraocular lenses, corneal biopsy/buttons, and iris
• Clean cover slips. tissues. These samples are directly processed for culture of
• Glass marking pencil/pen. bacteria, fungi or parasites in appropriate media.
• Topical anesthetic eye drop. Most samples, except fluids, for polymerase chain reaction
• Media (liquid and solid) as required. (PCR) are placed in sterile phosphate buffered saline pH 7.2
• Sterile cotton/calcium alginate swabs. and submitted to the laboratory where they may be retained
• Coplin jar with 95 percent ethyl alcohol. at –20oC until tested. Aqueous and vitreous fluids can be
• Viral transport medium - Hank's balanced salt solution/ directly used for DNA isolation. They can be stored at
2 sucrose phosphate broth, in quick freeze rack. –20oC until tested. In absence of a –20oC deep freezer, up
• Phosphate buffered saline in microcentrifuge tube. to one week the samples may be retained in the freezer of
ordinary refrigerator, however, storage for longer duration
Sample Processing requires either –20oC or –80oC deep freezer. PCR can identify
Each type of clinical sample requires special handling. As the offending organisms in less than 24 hours. It is considered
mentioned before, no transport medium (except for virus or useful in the diagnosis of bacterial (Propionibacterium acnes) as
Chlamydia culture) is recommended and direct patient-side well as fungal endophthalmitis since the sensitivity of
processing is the rule. In case of nonavailability of the conventional culture methods is low. Prior antibiotic therapy,
microbiology laboratory in the premises of the hospital, the small number of organisms, possible localized infection in
required slides and media may be obtained beforehand and capsular bag and fastidious nature of the organisms are
kept in reserve for use. The slides/media may be transported possible causes of low sensitivity. PCR with primers specific
in secure boxes to the laboratory after collection of the for P. acnes has been successfully used86 on vitreous specimens
samples. Items such as contact lens cases and contact lens negative in smear and culture but positive in PCR by
solutions may be directly submitted to the laboratory for eubacterial primers. DNA sequencing of the universal
processing. The direct smear examination methods and (eubacterial) nested PCR product allows identification of the
common culture media used for isolation of bacteria and causative organism in a number of culture negative cases of
fungi are similar for majority of the samples although the endophthalmitis. PCR has also been found useful in the
method of inoculation may vary. Sample collection for diagnosis of fungal endophthalmitis.
detection of parasites and viruses require special procedures. A rapid diagnosis of viral infection can be established by
Samples such as corneal buttons/biopsies, eviscerated contents observing stained smears of corneal scrapings, conjunctival
or any other tissues need to be simultaneously investigated scrapings/swabs, or centrifuged deposits of aqueous/vitreous
Table 5.3.9: Direct smear examination methods used for the diagnosis of eye infections
Type of sample Type of organism/antigen to be detected Staining methods for smears
Conjunctival swabs/scrapings • Bacteria, fungi, parasites (Microsporidia) • Gram, Giemsa, KOH+Calcofluor white,
Ziehl-Neelsen stain
• Viral antigens • Direct/Indirect immunofluorescence or
immunoperoxidase
Corneal scrapings • Bacteria, fungi, parasite • Gram, Giemsa, KOH+Calcofluor white,
(Acanthamoeba, Microsporidia) Lactophenol cotton blue, Gomori
methanamine silver, Ziehl-Neelsen stain
immunoperoxidase
Aqueous/Vitreous fluids/biopsy • Bacteria, fungi • Gram, Giemsa, Calcofluor white, Gomori
methanamine silver
immunoperoxidase
fluids (cytospin). This may be accomplished by using nonspecific and sensitive when suitable monoclonal or purified
specific staining techniques such as Giemsa, Papanicolaou, polyclonal antibodies are used in the test system. Relatively
and hematoxylin-eosin stain.87 These techniques help visualize higher sensitivity and lower specificity is achieved with purified
multinucleated giant cells, koilocytic changes, and intranuclear/ polyclonal antibody tests while monoclonal antibodies show
intracytoplasmic inclusions, and various inflammatory cells high specificity but lose out on sensitivity. Indirect
which are predominantly lymphocytes. immunoperoxidase (IP) assay has distinct advantages over
Corneal scrapings stained with Gram-stain showing gram indirect immunofluorescence (IF) assay. The former provides
positive cocci (Streptococcus pneumoniae), fungal filaments a permanent preparation for records and utilizes an ordinary
(Aspergillus flavus), Acanthamoeba cysts and microsporidia light microscope while the latter has the inherent problem of
spores are presented in Figures 5.3.5A and B. Figure 5.3.6 quenching (fading) of fluorescence and requires a sophisticated
shows gram-positive bacilli with spores in a vitreous smear and expensive fluorescence microscope. In addition, the IP
stained with Gram stain from a case of post-traumatic technique can be used on paraffin embedded tissue while the
endophthalmitis caused by Clostridium perfringens. IF technique provides better results with frozen tissue sections.
Intranuclear inclusions are more efficiently seen in
Papanicolaou stain than Giemsa stained smears, however, Culture Methods for Bacteria, Fungi
Giemsa stain is good for enumerating cell types. Though these and Parasites (Acanthamoeba)
staining techniques have the advantage of being rapid and Clinically, there can be considerable overlap in the clinical
inexpensive they are often non-specific and offer low sensitivity features of bacterial, fungal and Acanthamoeba keratitis. A
in the diagnosis of viral infection. For example, these stains single protocol is therefore recommended for the culture of
cannot differentiate the intranuclear inclusions of herpes bacteria, fungi, and Acanthamoeba from corneal scrapings.
simplex virus (HSV) from that of varicella zoster virus (VZV). However, in situations where only bacteria and fungi are
Specific cytology techniques used for viral diagnosis are expected (endophthalmitis) the culture for Acanthamoeba is
techniques that indirectly suggest the presence of viral antigen not included. Table 5.3.10 lists the different media that are
in the clinical sample.85,86 Detection of cell associated viral used for culture of common organisms from the ocular
antigen in a corneal scraping or conjunctival scraping is very samples and also the incubation temperature and period
useful in the diagnosis of viral keratitis. Direct and indirect required. Culture of viruses requires cell lines and a separate
immunofluorescence and indirect immunoperoxidase assays protocol is required for collection of the samples as well as
can be used in the diagnosis of HSV, VZV keratitis and processing. The method of inoculation of the samples in
adenoviral keratoconjunctivitis. Both these tests are rapid, culture media is described in Table 5.3.11.
Figs 5.3.5A and B: (A) Double walled, polygonal cysts of Acanthamoeba seen in a corneal scraping smear(OMS/BMP866/LVPEI-B, Gram
stain, ×1000), (B) Brightly fluorescent spores of microsporidia in a corneal scraping smear seen under fluorescence microscope
(OMS/BMP328/LVPEI-Bhubaneswar, calcofluor white stain, ×1000)
The number of media may be reduced as per the

availability of the samples. All media are incubated at 37oC
except Sabouraud dextrose agar, which requires 25 to 27oC
(BOD incubator). Chocolate agar is incubated in three to
five percent CO2 in a candle jar and blood agar for anaerobic
culture requires anaerobic chamber or anaerobic jar with gas
pack. All other media are incubated aerobically.
All media are examined for growth daily and are incubated
for two weeks before discarding. Bacteria such as Nocardia
species, atypical mycobacteria, and Acanthamoeba grow slowly
Fig. 5.3.6: Thick, long and short bacilli with spores are seen among and require prolonged incubation. Although most fungi
polymorphonuclear cells, red blood cells and uveal pigments in a smear associated with eye infections are saprophytes and grow within
of vitreous sample from a patient with post traumatic endophthalmitis a week they may require incubation for two to three weeks
(OMS/BMP546/LVPEI-Bhubaneswar, Giemsa stain, ×1000). The culture
of the sample grew Clostridium perfringens
for proper sporulation and identification.
Table 5.3.10: Media used for culture of bacteria, fungus, Acanthamoeba from ocular samples
Type of sample Culture media Expected organisms
Lid margin scales • Sheep blood agar • Bacteria
• Brain heart infusion broth • Fungi
• *Sabouraud dextrose agar
Conjunctival swab • Sheep blood agar • Bacteria
• Sheep blood chocolate agar • Fungi
• Brain heart infusion broth
Corneal scrapings • Sheep blood agar (aerobic, anaerobic) • Bacteria (aerobic, anaerobic),
• Brain heart infusion broth· • Acanthamoeba
• Thioglycollate broth
• Non-nutrient agar with E.coli
Aqueous/Vitreous • Sheep blood agar (aerobic, anaerobic) • Bacteria (aerobic, anaerobic)
• Brain heart infusion broth • Acanthamoeba
• Thioglycollate broth
Corneal biopsy/buttons • Sheep blood agar (aerobic, anaerobic) • Bacteria (aerobic, anaerobic)
• Brain heart infusion broth· • Acanthamoeba
• Non-nutrient agar with E. coli
Contact lenses • Sheep blood chocolate agar (aerobic, • Bacteria (aerobic, anaerobic)
anaerobic) • Fungi
• *Sabouraud dextrose agar • Acanthamoeba
• Non-nutrient agar with E. coli
Contact lens solutions • Sheep blood chocolate agar • Bacteria
• *Sabouraud dextrose agar • Fungi
• Non-nutrient agar with E. coli • Acanthamoeba
Intraocular lens/iris tissue • Sheep blood agar • Bacteria
• Fungi
* With antibiotics (gentamicin or chloramphenicol) but without cycloheximide. Potato dextrose agar may be used in addition to Sabouraud
dextrose agar for better sporulation. Robertson’s cooked meat medium may be added for the growth of anaerobic bacteria.
Table 5.3.11: Method of inoculation of ocular samples on culture media

Type of sample Media Method of inoculation
Lid margin scales • Solid media plates/slants • Held with forceps, the scales are moved on
the agar surface and placed on it with slight
pressure.
• Liquid media • The scales are dropped/shaken off in the media.
Cotton swabs • Solid media plates/slants· • Held with shaft, the swab is moved on the entire
agar surface. Streaking with loop is not required
unless purulent sample in larger quantity is
available.
• Liquid media • The swab tip is inserted in the medium and gently
squeezed against the wall of the tube 2–3 times.
Corneal scrapings • Solid media plates/slants • “C” shaped several inoculations are made on the
agar plate surface transferring the material
completely.
• Liquid media • The tip of the blade/spatula/needle is inserted in
the liquid medium and the sample is shaken off.
Calcium alginate swabs • Solid media plates/slants • The swab is placed in a measured volume 1%
sodium hexametaphosphate solution, vortexed for
30 seconds to dissolve and the solution is
inoculated in measured quantities on the surface
of agar media (used for quantitation of bacteria/
fungus present in the sample).
Aqueous/Vitreous • Solid media plates/slants • Few drops of the sample received in syringe are
fluids/biopsy directly placed on the surface of the solid media.
Streaking with loop is not done.
• Liquid media • Few drops are placed in the media.
Contact lens • Solid media plates/slants • Aseptically removed contact lens is vortexed in
measured volume of PBS (pH 7.2). Measured
quantity of the solution is inoculated on agar
surface and the lens is cultured by agar
*sandwich technique.
Contact lens cases • Solid media plates/slants • Inside of the case is swabbed with cotton swab
and processed as mentioned before.
Contact lens solutions • Solid media plates/slants • Using sterile pipette measured volume of the fluid
is spread over agar media surface.
• Liquid media • Few drops of the solution is dropped in liquid
media.
Corneal • Solid media plates/slants • The tissue is minced using blade/scissors in a
biopsy/button/iris tissue sterile petri dish and the pieces are moved and
placed over agar surfaces.
• Liquid media • The pieces are dropped in liquid media.
* Contact lens is dropped in 10 mL of molten nutrient agar (45 oC), swirled and poured over a sheep blood chocolate agar plate
(85 mm plate).
Size, color, texture, consistency, and number of colonies may be able to see the characteristic track marks made by
on the inoculation marks are counted and recorded. An the migration of the trophozoites on the E. coli lawn.
arbitrary semiquantitative growth estimation graded in our Acanthamoeba forms no colonies.
laboratory is + ( 10 colonies), ++ (10-50 colonies), and +++ Growth in liquid media appears as turbidity that requires
( 50 colonies). While bacterial and fungal colonies are examined to be subcultured and Gram stained for identification.
with unaided eyes, the observation of Acanthamoeba growth The growth of bacteria or fungus in culture is considered
requires use of microscope. NNA plates (with lid on) are significant if the growth is confluent (more than 10 colonies,
placed under 4 x or 10 x objective lens of the microscope ++) on the site of inoculation on solid media (Fig. 5.3.7), or
and the presence of trophozoites is looked for in the vicinity the organism was seen in the smears, or if the same organism
of the inoculation mark on the surface of the medium. One is grown in more than one medium.
or by IF or IP techniques, which detect viral antigens in the

infected cell lines. Appearance of CPE may take several days
but antigens can be detected even before CPE occurs, thereby
rendering the latter a more rapid method. Viruses may be
cultured in cell lines maintained in tubes (tube culture) or on
cover slips in vials (shell vial). Shell vial technique is a
modification of conventional tissue culture technique wherein
entry of virus into the monolayer of susceptible cells (on a
cover slip in a vial) is facilitated by centrifugation (spin
amplification) of the vial containing cells and the clinical
sample. The virus growth occurs in a shorter period (18-72
hours) by this method and additionally, both IF and IP
techniques can be performed easily on the cover slips
retrieved from the vials for antigen detection. Both these
factors are responsible for increased sensitivity of shell vial
Fig. 5.3.7: Sheep blood agar showing confluent, small, white, glistening, technique in isolation of viruses.
nonhemolytic colonies of Mycobacterium fortuitum after three days
of incubation at 37oC (OMS/BMP378, LVPEI-Bhubaneswar) Molecular Diagnosis of Ocular Infections
By virtue of being extremely sensitive and specific, molecular
techniques, especially polymerase chain reaction (PCR), is
Culture of Ocular Samples for Viruses presently the most sought after test for viral diagnosis and
detection of organisms that are difficult to culture such as
The sample for viral diagnosis always needs to be collected in
Microsporidia, Propionibacterium acnes, Toxoplasma gondii,
an appropriate transport medium (except the smears) and
etc. or that take long time to grow, such as Mycobacterium
sent to the laboratory. Methods of transport would vary
tuberculosis. PCR is also very useful for the detection of
according to the type of sample collected. Hank's balanced
microorganisms that are sparsely present in clinical samples
salt solution or 2 sucrose phosphate broth may be used.86,87
such as aqueous or vitreous fluid. Detailed description of
Samples received in a virolog y laboratory may be
these advanced tools of microbial diagnosis is beyond the
processed using a variety of techniques. The choice of
scope of this chapter.
technique would depend on the type of sample and the
specific virus that is being looked for. Most of the procedures
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multicentre survey in England 1992-6. Br J Ophthalmol 1998; (1995-2001). Ophthalmic Surgery Lasers 2002;33:378-88.
82:1387-92. 77. Taban M, Behrens A, Newcomb RL, et al. Acute endophthalmitis
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Acanthamoeba keratitis in the United States. Am J Ophthalmol Arch Ophthalmol 2005;123:613-20.
1989;107:331-6. 78. Jalali S, Das T, Gupta S. Presumed non-infectious endophthalmitis
58. Davamani F, Gnanaselvam J, Ananda K. Studies on the prevalence following cataract surgery. The clinical profile, management
of Acanthamoeba keratitis in and around Chennai. Indian J Med strategy and treatment outcome. J Cataract Refract Surgery
Microbiol 1998;16:152-3. 1996;22:1492-7.
59. Sharma S, Garg P, Rao GN. Patient characteristics, diagnosis and 79. Sharma S, Jalali S, Adiraju MV, et al. Sensitivity and predictability
treatment of non-contact lens related Acanthamoeba keratitis. of vitreous cytology, biopsy and membrane filter culture in
Br J Ophthalmology 2000;84:1103-8. endophthalmitis. Retina 1996;16;525-9.
60. John T, Desai D, Sam D. Adherence of Acanthamoeba castellanii
80. Ferro JF, De-Pablo M, Logrono MJ, et al. Postoperative
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Infect Dis 1991;13:S419.
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61. Auran JD, Starr MB, Jakobiec FA. Acanthamoeba keratitis. A
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62 Vemuganti GK, Garg P, Sharma S. Is microsporidial keratitis an prophylaxis for cataract surgery: an evidence-based update.
emerging cause of stromal keratitis? -a case series study. BMC Ophthalmology 2002;109:13-26.
Ophthalmology 2005, 5:19, doi 10.1186/1471-2415-5-19. 82. Garat M, Moser CL, Martin-Baranera M, et al. Prophylactic
published 17 August, 2005. intracameral cefazolin after cataract surgery: Endophthalmitis risk
63. Reynolds MG, Alfonso E. Treatment of infectious scleritis and reduction and safety results in a six-year study. J Cataract Refract
keratoscleritis. Am J Ophthalmol 1991;112:543-7. Surg 2009;35:637-42.
64. Nanada M, Pflugfelder SC, Holland S. Mycobacterium tuberculosis 83. Das T, Choudhury K, Sharma S, et al. Clinical profile and outcome
scleritis. Am J Ophthalmol 1989;108:736-7. in Bacillus endophthalmitis. Ophthalmology 2001;108:1819-25.
65. Albert DM, Miller JW, Azar DT, et al. Albert and Jakobiec's Principle 84. Kunimoto DY, Das T, Sharma S, et al. Microbiologic spectrum
and Practice of Ophthalmology, Saunders Elsevier, Philadelphia, and susceptibility of isolates. Part II. Post-traumatic
2008; Vol 2: 3622. endophthalmitis. Am J Ophthalmol 1999;128:242-4.
66. Winterkorn JM. Lyme disease: neurologic and ophthalmic 85. Gupta P, Sachdev N, Kaur J, et al. Endogenous mycotic
manifestations. Surv Ophthalmol 1990;35:191. endophthalmitis in an immunocompetent patient. Int Ophthalmol
67. Lewis ML, Culbertson WW, Post JD, et al. Herpes simplex virus 2008; June 5 (Epub ahead of print).
type 1: a cause of the acute retinal necrosis syndrome. 86. Therese KL, Madhavan HN. Microbiological procedures for
Ophthalmology 1989;96:875. diagnosis of ocular infections. www.ijmm.org/documents/
68. Usui M, Sakai J. Three cases of EB virus-associated uveitis. Int ocular.pdf. Accessed 26.12.2006.
Ophthalmol 1990;14:371. 87. Sharma S, Sreedharan A. Diagnostic Procedures in Infectious
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Chapter 5.4
OCULAR PATHOLOGY
5.4.1 Ophthalmic Pathology for Clinicians

Geeta K Vemuganti
Ophthalmic pathology, like all branches of pathology clinically suspected benign tumors and easily accessible lesions
encompasses the essential nature of disease, especially of are removed in toto as excisional biopsies, e.g. pleomorphic
the structural and functional changes in tissues that cause or adenoma or lacrimal gland, conjunctival cyst, etc. The lesions
are caused by disease. The understanding of any disease which have varied morphology, deep seated, suspected
process includes etiology, pathogenesis, morphology of the malignancies and difficult to access surgically are removed as
lesion, effects of the lesion on course and prognosis, incisional biopsy for diagnostic confirmation, e.g. large
complications, treatment and the dangers of treatment. The infiltrative orbital lesions, fungating conjunctival tumors. The
tissues removed during any surgical procedure are a case is then managed as per the final diagnosis obtained on
storehouse of information. It is therefore important for the histologic examinations. Some of the malignant lesions
ophthalmologist to communicate with the pathologists before, amenable to surgical excision undergo radical surgeries, e.g.
during and after the surgical procedure so that a good exenteration of eye and orbit for invasive squamous cell
clinicopathologic correlation is established and the pathologist carcinoma, while those amenable to chemotherapy or
is able to provide the most accurate interpretation of the radiotherapy are treated accordingly. With the aim of salvaging
the organ and its function and with the advent of more
tissue submitted. In this chapter, the routine and special
effective chemotherapy, the trend towards neoadjuvant
techniques adopted by most of the ophthalmic pathology
chemotherapy is on the rise. Though it is beyond the scope
laboratories is described and practical guidance for handling
of this chapter to describe the individual tissues and the effects
the specimens appropriately and meaningfully interpreting
of treatment, it suffices to inform the readers that it provides
and understanding the report provided by the pathologist is
the pathologist with the tissues that have received various
provided. The tissues routinely submitted to any ophthalmic treatment protocols like laser therapy, cryotherapy, thermo-
pathology lab include tissues removed from the eye and orbit therapy, chemotherapy or plaque brachytherapy. This is not
for diagnostic or therapeutic purposes, e.g. cornea, conjunctiva, only of diagnostic interest but of great academic interest as
lid, orbit, intraocular structures and fluid samples like aqueous it provides the unique opportunity to evaluate the cellular
and vitreous taps and aspiration from cystic lesions. Based effects of the treatment and evaluate its efficacy.
on the nature of the lesion, its location and the presumptive In addition to the basic histologic diagnosis, histochemistry,
clinicoradiologic diagnosis, the specimen from various immunohistochemistry and cytology are used almost routinely
locations is obtained by incision or by excision of the lesion. in ophthalmic pathology as well. Electron microscopy is a
For example, all cystic lesions, well circumscribed lesions, valuable tool for evaluating the ultrastructure of the cells.
However, in view of its elaborate and time consuming the surgical margin involvement can be commented upon
procedure it has paved way for modern molecular techniques on all sections.
like PCR, ELISA, karyotyping, Western blotting, in situ • Grossing an eye: Examination of the eyeball is one of the
hybridization, and multiplex ligand specific probe amplifier. important aspects in ophthalmic pathology. The side of
the eyeball should be identified. A thorough and systemic
HISTOPATHOLOGY examination of the eyeball at various stages is very
important to the pathologist and the clinician.7-9 It involves
Though the technique of tissue processing of ocular tissues
the following steps:
is similar to tissues from rest of the body, a few important
– Fixation of the globe.
issues need to be remembered in ophthalmic pathology
– Review of the clinical features with special instructions
specially related to fixation of tissues and grossing of the
if any.
specimen.
– Appropriate measurement of the eyeball and the optic
Tissue fixation: Fixation is a complex series of chemical events nerve.
that aims at preventing the tissues from autolysis and bacterial – External examination for any abnormality such as tear,
attack, at the same time maintaining them in a state as close rupture, protrusion, scar and pigmentation.
to their living state as possible with no loss of molecules. The – Transillumination to highlight a mass in a normally
most common fixative used in histopathology is ten percent transparent eyeball.
buffered formalin, adequate when the volume used is ten – Before opening, the specimen from the vortex veins
times the volume of the sample.1-4 For electron microscopy, and optic nerve should be collected for suspected
two percent glutaraldehye or a four percent formaldehyde- melanoma and retinoblastoma respectively.
glutaraldehyde mixture is preferred.4 Penetration of fixatives – The eyeball is opened so as to have the pupil-optic
into the tissues is variable and depends on the size of the nerve in one place which is possible through horizontal,
tissue, e.g. small biopsies can be fixed within a few hours, but oblique or vertical axis that goes through the center
the eyeball requires 24 hours fixation before it can be cut of the eyeball (Fig. 5.4.1.1).
open for further fixation. In recent times, microwave energy – A thorough examination of the intraocular structures
is being used to hasten various procedures involved in is made by a dissecting microscope and documented
histopathology, including the process of fixation.5 through specimen photography and appropriate
Grossing: Macroscopic examination of ocular tissue before diagram.
submitting the tissues for processing is very important.6 A – Sections for histologic examination should include the
brief description of the techniques are given below: entire eyeball, abnormal area cross-section of optic
• Corneal button: Gross examination of the corneal button nerve in case of retinoblastoma and sample of at
includes size, thickness, surface and margins for least one of the vortex veins from each of the four
irregularities, translucency, perforation, vascularization, quadrant (Fig. 5.4.1.2).
thinning, ulceration or deposits. Endothelial surface is
examined for the presence of adherent uveal tissue, and
formation of exudates or membranes. After placing the
corneal tissue on a flat surface with the endothelial surface
up, it is bisected into half using a sharp blade. Half is
retained for future studies while half is submitted for
routine processing. In cases of therapeutic keratoplasty,
half of the corneal button is submitted for microbiologic
studies and the rest of the tissue is for processing for
histopathologic studies.
• Lid biopsy: The full thickness lid biopsy is examined for
the lesion. It is preferable to process the surgical margins
and the main lesion in separate blocks after noting down
the details of the specimen. All fresh specimens could be Fig. 5.4.1.1: Section shows the cut section
painted with Indian ink preparation before fixing so that of an eye ball with retinoblastoma
Ocular Pathology 243
Fig. 5.4.1.3: Picture shows the gross photograph of an exenterated

specimen with a collapsed eyeball and a tumor on the ocular surface
Fig. 5.4.1.2: Picture shows the whole mount section of an eyeball extending into orbital tissues
with retinoblastoma. The sections represents the pupil-optic nerve
section with the tumor seen anterior to the optic nerve head and
impinging on the anterior layers of lamina cribrosa
• Exenterated specimen: The specimen should be fixed

overnight. The surgical margins should be taken separately
from the skin, soft tissues, and optic nerve. The specimen
should be measured and cut through the skin, soft tissues
and ocular globle (Fig. 5.4.1.3).
The specimen is examined and described in the following
manner:
• Skin: Shape and length, appearance of lesions present -
with their size, shape, depth of invasion and color, etc.
• Soft tissues for the tumor: Size, shape, contour.
• Ocular globe: Same as done for enucleated eye ball.
Sections for histolog y 10-14 should include tumor,
cutaneous and soft tissue surgical margins, globe with tumor,
orbital soft tissues adjacent to tumor and surgical margin of
optic nerve (Fig. 5.4.1.4). Fig. 5.4.1.4: Picture shows the whole mount section of an exenterated
specimen with a perforated eyeball. Note the presence of a tumor on
Electron microscopy: Transmission electron microscopy (EM) is the surface of the eye, extending into the orbital spaces
used selectively. It has been supplanted by immunohisto-
chemistry that is cheaper, faster and less labor intensive. It is
used as a tool to identify the basic ultrastructural features of
not shown consistent differences between benign, reactive
the cells and tissue and has been well established for ocular
and malignant tumors of the same cell types. In ocular
tissues.15 It is specifically employed to confirm the nature of
pathology, EM is used to characterize the native cells as well
the lesion based on the presence of structures within the cell
confirm the nature of tumors.16
that are identified only by ultrastructure, e.g. the neurosecretory
granules of neuroendocrine tumors and the tennis racket Immunologic and molecular techniques: Diagnosis of lesion is usually
shaped body in Langerhans’ cell histiocytosis. In tumor made on the basis of morphology. However in many
pathology, it is useful in determining the histogenesis (or instances, it has to be aided by immunodiagnosis where in the
differentiation) of various tumors but unfortunately have diagnosis is made based on the property of the given tissue/
cell to express specific antigens. These antigens are detected presence or absence of a segment on the gene using
by using a set of antibodies that bind to specific antigens and appropriate molecular tools and primers. A commonly
are labeled either directly or indirectly with the help of employed technique is the polymerase chain reaction (PCR)
secondary antibodies that are attached to a chromogen or a which amplifies a single strand of nucleic acid thousands of
detecting system.17-19 In addition to academic interest, the times, enabling the pathologic diagnosis.20,21 PCR can now be
common indication for immunohistochemistry (IHC) is in employed on the DNA extracted from formalin-fixed and
diagnosing different types of round cell tumors, e.g. paraffin embedded tissues thus making it more feasible to
differentiating lymphoma from rhabdomyosarcoma, used archived tissues. 22,23 The in situ hybridization
amelanotic melanoma from carcinoma and glioma from other technique24,25 employs nucleic acid probes whose sequences
spindle cell tumors (Figs 5.4.1.5A to D). are complementary to the DNA of the organism or the gene
sought, e.g. detection of human papilloma virus in
Molecular diagnostic tools: Sometimes techniques more specific
conjunctival tumors.26,27 The labeling of probes is usually
than detecting antigens is required to make a diagnosis. With
done by either radioactive substances or biotin and
advancing techniques it is now possible to determine the actual
bromodeoxyuridine. The advantage of in situ hybridization is
Figs 5.4.1.5A to D: (A) The microphotograph shows a round cell tumor with bright pink cytoplasm and necrotic background with many necrotic
cells. The nucleus is hyperchromatic (Hematoxylin and eosin, x 400). (B) The tumor cells show cytoplasmic immunopositivity to Desmin (DAB,
x 400). (C) The microphotograph shows a case of lymphoma with small monomorphic round cells compactly placed (Hematoxylin and eosin,
x 400). Immunohistochemistry reveals the tumor cells to be predominantly labelled with CD20 (B cell marker) (DAB< x 400)
that it allows the visualization of cellular DNA or RNA in TISSUE CULTURE AND KARYOTYPING
the tissue sections, single cells or chromo-some preparation.
Though tissue cultures have been performed in non-ocular
In situ hybridization28 can be with an isotope or non-isotope
tumors,37 a few studies have been done of cultures of
method. In ophthalmic practice, it has been applied to diagnose
retinoblastoma tumors, melanoma and lacrimal gland
various infections from ocular samples, to detect the presence
tumor.38-40 The rationale of tissue culture is to demonstrate
of virus in corneal tissues and in tumors.22,23,26,27 For paraffin
the differentiation of the tumor cells in ex vivo conditions,
sections, the sections are deparaffinized in xylene, tissue will be
undertake karyotyping, immunocytochemistry or ultrastru-
subjected to Proteinase K digestion. DNA is isolated by phenol-
ctural studies. The culture conditions could be modified based
chloroform extraction and ethanol precipitation and amplified
on the objectives of the study. The diagnostic utility of tissue
using primers specific for different DNA sequences of the
cultures is however practically non-existent except that it has
test sample.
contributed extensively as a research tool, including
Another recent development in molecular diagnosis is the
pharmacokinetic studies on drug resistance and may possibly
application of a technique called multiplex ligation-dependent
pave way for development of treatment protocols and
probe amplification (MLPA). This technique can detect copy
vaccines.41,42
number alterations of up to 45 different DNA sequences in
one experiment. The advantage is that it can be done on
PREOPERATIVE AND
fresh as well as formalin-fixed paraffin embedded tissue. When
INTRAOPERATIVE DIAGNOSIS
applied for melanocytic lesions it appears to be a reliable and
efficient method to evaluate DNA copy number changes as Eye and orbital lesions remain an enigma and pose a challenge
86 percent of the loci tested revealed, concordant to the most experienced ophthalmologist with its diverse
comparative genomic hybridization.29-30 etiology. In this section, a simple strategy for the cytologic
and histologic diagnosis of the eye and orbital lesions is
FLOW CYTOMETRY provided. The tissue diagnosis in most instances is the final
diagnosis. After coming to a presumptive clinical diagnosis
Flow cytometry is used for simultaneous measurement of
of orbital lesions based on the clinical and radiologic features,
several parameters while a suspension of cells flows through
a decision needs to be made regarding the procedure to be
a beam of light past stationary detectors.31-33 The instrument
adopted to confirm the nature of the lesion. The methods
allows analysis of 5,000 to 10,000 cells per second for of tissue diagnosis include preoperative fine needle aspiration
information on parameters like cell size, cytoplasmic granules, cytology (FNAC) or biopsy (FNAB) or a routine tissue
cell viability, cell cycle time, DNA content, surface marker diagnosis after a surgical biopsy,43 and has been well established
phenotype and enzyme content. One of the main limitations in ophthalmology for orbital lesions.44-46 A preoperative
is that the cells should be in single cell suspension. This diagnosis is indicated if the suspected tumor can be treated
requirement can be achieved in blood, fluids, fresh tissues, without surgical intervention (e.g. rhabdomyosarcoma,
needle aspirates and now nuclear suspension recovered from sarcoidosis, metastatic tumors, reactive lymphoid hyperplasia,
thick sections of routine formalin-fixed, paraffin-embedded lymphoma, sclerosing orbititis and infections). It is also
tissues. The current clinical uses include: indicated to plan the extent of surgery. The decision for the
• Support a diagnosis when the morphological changes are type of biopsy would depend on the size, site, shape,
equivocal circumscription, encapsulation, consistency, approximation to
• Subclassification of lesions of borderline malignancy the neighboring structures and the accessibility of the lesion
• Prognostic markers, independent of stage and grade from the surgical point of view.
• Monitor response to therapy
• Establish development of tumor relapse. Preoperative Diagnosis
In ocular tissues, it has been used to diagnose
lymphoproliferative lesions of orbit and conjunctiva.34-35 It Fine Needle Aspiration/sampling Technique
has also been used as a research tool specially in characterizing The procedure for fine needle aspiration cytology (FNAC) at
round cell tumor and retinoblastoma. Our group has reported any sites in the body is the same and can be performed either
the presence of putative cancer stem cells in retinoblastoma by the pathologist or a clinician, directly under vision or under
based on the size and presence of certain stem cell markers.36 guidance of CT.46 Usually there is no need of any local
anesthesia injection for this technique except in children where In an incisional biopsy only a portion of the lesion is
general anesthesia may be preferred. The technique of removed to provide a sample for diagnosis. The best place to
obtaining the material could be a "sampling technique" wherein sample the tissue is at the periphery, always including normal
a 23/24 gauge needle is introduced into the lesion and pushed tissue for easier interpretation. The center of the tissue should
in various directions within the lesion and gently not be biopsied especially if there is central ulceration.
withdrawn.47,48 By capillary action, cells are drawn into the
needle. The advantages of this technique are that it is easy, Frozen Sections
simple, less hemorrhagic and causes less apprehension to the
Frozen section is one of the most important procedures that
patient. It could be performed using a syringe attached to the
require experience, knowledge of clinical medicine, pathology,
needle so as to create negative pressure. To obtain greater
good judgment, capacity conservative approach and capacity
possible yield, the needle could be moved back and forth
to make quick decision under pressure. It is generally indicated
within the lesion along the same track with negative pressure
to determine the nature of the lesion, if the resection margins
maintained. Negative pressure should be released when the
are free from tumor or if the surgeon has biopsied
needle is being removed from the lesion. Two different
representative material.54,55 The fresh, unfixed tissue is
methods of fixation and staining are used in FNAC. These
embedded in a freezing media (OCT/water) using a block
are air drying followed by staining with a hematologic stain
holder. The sections are then cut with the help of a cryostat
such as May-Grunwald-Giemsa (MGG), Jenner-Giemsa,
and are stained with a rapid hematoxylin and eosin technique.
Wright's stain, or Diff-Quick; and alcohol fixation and staining
Interpretation can be done within six to ten minutes per block.
with Papanicolaou or hematoxylin and eosin.13,14 Both
The advantages of this technique is that it gives good
techniques are complementary to each other.
architectural details and is extremely useful to comment on
The main advantage of this procedure is obtaining an
the nature of the lesion, surgical margins of malignant lid
early cytological diagnosis of the lesion. It may be done as an
tumors and to differentiate between in situ or invasive lesions.
outpatient procedure with avoidance of anesthesia or
The disadvantages however include the frozen section artifacts
orbitotomy. A few disadvantages include inadequate material,
produced in the sections which most of the pathologists are
hemorrhagic aspirate, bleeding at the site of FNAC.49,50 While,
familiar with. This technique requires a special cryomicrotome,
FNAC can give a diagnostic yield in more than 90 percent of
a technician and a pathologist trained for frozen section
cases, Tijl et al report the diagnostic yield of orbital fine
reporting. It is not very useful for small tissue, fatty tissues or
needle aspiration cytology (FNAC) combined with clinical
bony lesions.
and radiological features as 80 percent.51 Very rare potential
complications include globe penetration, retrobulbar
Squash or Imprint Cytology
hemorrhage, diplopia and ptosis.
The utility of imprint cytology in eye lesions was first described
Intraoperative Diagnosis by Fuchs for uveal melanoma in 1988.56 Imprint cytology
of fresh unfixed tissue specimens and squash cytology of
There is often a need for reliable intraoperative diagnosis,
specifically in situations where a definitive preoperative tissue central nervous system lesions have been extensively used in
the last few decades, but has recently been introduced to
diagnosis is lacking and where the tissue diagnosis is likely to
influence the immediate surgical management.52 It should be ophthalmic pathology practice.57,58 It can be utilized for the
following indications:
remembered that it is not indicated merely to satisfy the
curiosity of the surgeon. The established methods of • Infiltrative lesions, suspected malignant lesions or deeply
located lesions where a preoperative tissue diagnosis was
intraoperative diagnosis include frozen section diagnosis and
intraoperative cytologic diagnosis, each of which has its own not available.
• Discrepancy between a preoperative clinical diagnosis and
merits and demerits. In general, a complete excision of the
mass (excisional biopsy) is indicated for all cystic, well- the intraoperative findings.
• Unusual clinical presentations with diagnostic dilemma.
circumscribed and encapsulated lesions, easily accessible
lesions and all suspected benign lesions.53 For the lesions that Method
are suspected to be malignant, with infiltrative margins, solid Fresh unfixed tissue obtained at the time of diagnostic or
consistency and have a complex surgical approach, an excision biopsy can be used for making squash preparation
incisional biopsy may be indicated. and impressions on glass slides. The procedure for making
squash or imprint smears is usually based on the size, shape, All samples can be subjected to conventional cytologic
consistency and crushable properties of the tissue submitted. procedures, and based on the availability of techniques and
For soft, easy to spread tissues, tiny bit of the fresh tissue is expertise, it could be subjected to immunocytochemistry and
placed between two clean glass slides and gently drawn apart. clonality analysis using polymerase chain reaction. Compared
For large firm specimens, the imprint smears are prepared to the unfixed vitreous specimens, the quality of the
by touching the freshly cut surface of the lesion with clean cytomorphology and immunohistochemistry improved in the
slides and avoiding smearing to retain cell morphology. If HOPE (Herpes-glutamic acid buffer mediated organic solvent
the surface is covered with blood or exudates, more number protection effect) fixed specimens. IgH-PCR and GeneScan
of smears is made, after gently wiping the surface clean. It is analysis demonstrated polyclonal amplification products in
preferable to make a minimum of three slides for each case. the reactive cases, and monoclonal B-cell populations in the
It is advisable to preserve extra unstained smears for further B-cell primary intraocular lymphoma (B-PIOL). 63 The
tests like immunocytochemistry or for any molecular studies specimens can be evaluated for cellularity, cellular appearance,
in the future. cytoplasmic and nuclear features as well as quality of the
These smears are either alcohol fixed for rapid immunostains. Primary intraocular lymphoma (PIOL) is a
hematoxylin and eosin staining, or fixed by air-drying for Diff- rare non-Hodgkin lymphoma, which arises in the retina or
Quick staining. A provisional cytologic diagnosis can be made the vitreous. Though the diagnosis of intraocular lymphoma
by the pathologist based on the cellular and architectural with immunostaining was reported in 80s, there have been
features seen on smears prepared from either or both many advances in terms of obtaining the specimen, diagnosis,
techniques. After reporting on the cytology slides, the classification and use of newer modalities.64,65 It can occur
remaining tissue is fixed in ten percent buffered formalin either together with or independent of primary cerebral
and processed for permanent sections, and stained by nervous system lymphoma (PCNSL). The incidence of the
hematoxylin and eosin, and periodic acid Schiff's stain. Special latter has significantly increased over the past three decades.
and immunohistochemical stains can be done. Though the PIOL remains one of the most difficult diagnoses to establish,
accuracy of combined frozen section and cytology is the particularly due to its ability to mimic other diseases in the
ideal method of intraoperative diagnosis, imprint and squash eye and to the limited material, which is often available for
cytology alone gives 96 percent accuracy.59 examination. The differential diagnosis, includes other
lymphomatous manifestations in the eye, e.g. primary uveal
Fluid (vitreous, aqueous or lymphoma, as well as non-neoplastic uveal diseases.66 B-cell
other fluids) Cytology lymphoma of the retina and CNS is a large B-cell lymphoma
with extensive necrosis. Its incidence is rising because of, and
The most common fluid sample from ophthalmic surgeries
also independent of the rising incidence of AIDS and
is vitreous fluid. The vitreous sample is obtained as a vitreous
transplant recipient. It is seen in elderly persons (5th to 7th
biopsy (undiluted) or from vitrectomy procedures (diluted).
decade) and clinically presents as refractory uveitis and vitritis
The fluid obtained is therefore unfixed and requires urgent
and because of masquerading as orbital inflammation, poses
attention in the laboratory. The samples can be processed in
a diagnostic challenge.67 Early diagnosis is essential because
different ways like celloidin bag techniques, cytocentrifugation,
of its aggressive course. Cyto-diagnostic modalities include
direct smears and by millipore filtration devices.60,61 The most
examination of cerebrospinal fluid, vitreous, anterior chamber
commonly used technique is cytospin, which gives good cellular
aspirate and intraocular fine needle aspiration of retina or
recovery and excellent cytologic details. Here the sample is
uveal lesions. The abnormal lymphoid cells were large (2–4
fed into a plastic tube, and arranged in a holder which contains
times the size of a lymphocyte) and had a high nuclear/
filter paper, a glass slide and the plastic tube. The cytospin is
cytoplasmic ratio, prominent nucleoli, irregular nuclear contours
usually set for ten minutes at 1000 revolutions per minute,
and a fine to coarse chromatin pattern. The cells may be
which concentrates the cells into a focal area on the glass
admixed with degenerating inflammatory cells.
slide. The slides are then fixed either in alcohol or by rapid
air-drying. Depending on the indication of the vitreous biopsy,
Conjunctival Impression Cytology
the sample is then submitted for routine cytology, electron
microscopy, immunocyto-chemistry, special stains and flow Conjunctival impression cytolog y, initially termed as
cytometry. The common indications of vitreous biopsy include conjunctival biopsy was attempted to diagnose squamous
endophthalmitis, lymphoma, and masquerading syndromes.62 metaplasia of the ocular surface, especially for Vitamin A
this speciality. It could be done with the help of a digital

camera or a well equipped photographic system. Ideally, the
photograph of the specimen is taken when it is submerged in
60 percent of ethanol which restores the color of the
specimen even after initial fixation in ten percent
formaldehyde. Use of appropriate lighting, good quality
camera roll, appropriate use of close up and zoom lenses,
clean background free of artifacts, gives good quality pictures.
Similar care should be taken for microphotographs.76,77 The
pictures can be taken with a digital camera or with traditional
films. The pictures should be taken at appropriate
magnification so as to highlight the relevant features of the
case. Even though photoshopping softwares can enhance the
picture, it is ideal to take good pictures in the first instance
which requires minimal modification.
Fig. 5.4.1.6: The impression cytology of a case of squamous cell
carcinoma showing large pleomorphic cells with multinucleated tumor SUMMARY: OPHTHALMOLOGISTS AND
giant cells (Hematoxylin and eosin, × 400) THE PATHOLOGY LABORATORY
To maintain a good relationship between the ophthalmologist
and the pathologist, there should be an effective, timely and
deficiency. It is done using nitrocellulose paper.68,69 This is accurate communication between the two. This is generally
based on the principle that by capillary action the superficial done by the ophthalmologist who fills up the pathology lab
cells of ocular surface are transferred to the filter paper, requisition form, providing information on the age, gender,
which can be stained and interpreted for the type of cells race, laterality, location of the lesion and other clinical details,
lining the ocular surface. The goblet cells and the cellular including the provisional clinical diagnosis. This will allow the
morphology is well identified by PAS, hematoxylin and eosin pathologist to prepare for special fixation as may be indicated
staining. In this technique, a 5 × 5 mm of sterile nitrocellulose by the clinicians provisional diagnosis of the lesion. Care
paper is gently placed in the conjunctival and corneal surface should be taken to fix the tissues in an appropriate manner,
of the diseased eye for five seconds, and then the filter paper in consultation with the pathologist. For all interesting and
is gently peeled off from the surface and dipped in alcohol unusual cases, request for photography should be made at
filled petri dishes. The membrane is stained by modified the time of submitting the sample so that the pathologist can
periodic acid - Schiff stain so as to highlight the epithelial take pictures before grossing the sample. The ophthalmologists
cells as well the goblet cells and the background mucin. are advised to visit the laboratory to look at the slides of all
The presence of large metaplastic squamous cells with the specimens that they had referred to the pathologist. In
absence of goblet cells confirms the diagnosis of squamous case of any discrepancy in clinico-pathological correlation, it
metaplasia (Fig. 5.4.1.6).70,71 The other indications include: is in the interest of the patient and the clinician to discuss the
identification of goblet cells over the corneal region to case in person referring to the complete records of the patient.
confirm conjunctivalization of cornea which is one of the
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5.4.2 Illustrative Ocular Pathology

Seema Kashyap
EYELID LESIONS
Clinical and histopathological views of common eyelid lesions are presented in Figures 5.4.2.1 to 5.4.2.28 comprising a
gamut of viral infections, parasitic infections, cystic lesions and tumors, benign and malignant, of the eyelid.
Fig. 5.4.2.1: Chalazion: Microscopic examination reveals lipogranulo- Fig. 5.4.2.3: Pyogenic granuloma: The mass is composed of
matous inflammation comprising plasma cells, lymphocytes, histiocytes, inflammatory granulation tissue. It comprises of fibroblasts, inflammatory
giant cells and ill defined epithelioid cell granuloma (arrow). Lipid cells and numerous capillaries
dissolved during processing is shown as a large vacuolated area
Fig. 5.4.2.2: Pyogenic granuloma: Low power reveals an oval Fig. 5.4.2.4: Xanthelasma: Low power view reveals clusters of
mass with a narrow pedunculated base and an ulcerated surface lipid laden foam cells in the dermis
Cystic Lesions
Fig. 5.4.2.5: Xanthelasma: Higher magnification reveals

vacuolated cytoplasm of the foam cells Fig. 5.4.2.8: Epidermal inclusion cyst: The cyst is lined by stratified
squamous epithelium with desquamated keratin in its lumen and has a
Viral Infections distinct granular layer
Fig. 5.4.2.6: Molluscum contagiosum: Numerous intracytoplasmic, Fig. 5.4.2.9: Sebaceous cyst: The cyst is lined by stratified squamous
small eosinophilic molluscum bodies are seen in the deeper layers of epithelium without any granular layer. No appendages are identified in
the epidermis. They become larger and basophilic near the surface its wall
after extrusion
Parasitic Infections Benign Surface Epithelial Tumors
Fig. 5.4.2.7: Cysticercosis: Body of a cysticercus larvae with multiple Fig. 5.4.2.10: Squamous papilloma: Histopathology reveals multiple
papillary infoldings. Arrow points to the scolex. The scolex reveals papillary fronds lined by stratified squamous epithelium and the stroma
sucker(s) and hooklets reveals centrally located capillary in the stroma
Malignant Lid Tumors
Fig. 5.4.2.11: Squamous papilloma: Higher magnification reveals Fig. 5.4.2.14: Basal cell carcinoma: Clinical appearance of an
the stratified squamous epithelial lining of the papillary fronds ulcerated mass in the right lower lid with rolled out edges
Pigmented Tumors
Fig. 5.4.2.12: Intradermal nevus: Nests of nevus cells present in the Fig. 5.4.2.15: Basal cell carcinoma: Irregular islands of basophilic
entire dermis except in a narrow tumor free zone between the tumor cells arising from basal layer of the epidermis with characteristic
epidermis and dermis peripheral palisading (arrow) of tumor cells
Fig. 5.4.2.13: Intradermal nevus: Higher magnification reveals Fig. 5.4.2.16: Basal cell carcinoma (Variant): Higher magnification
benign nevus cells with melanin pigment in the superficial cells of a pigmented basal cell carcinoma
Fig. 5.4.2.17: Basal cell carcinoma: Adenoid pattern Fig. 5.4.2.20: Sebaceous cell carcinoma: Comedo pattern
seen in basal cell carcinoma (central necrosis in a tumor island)
Fig. 5.4.2.18: Sebaceous cell carcinoma: Exenteration specimen Fig. 5.4.2.21: Sebaceous cell carcinoma: Moderately differentiated
reveals a large sebaceous cell carcinoma arising from the upper lid sebaceous cell carcinoma showing few cells with vacuolated
cytoplasm and presence of mitotic figures
Fig. 5.4.2.19: Sebaceous cell carcinoma: Well differentiated Fig. 5.4.2.22: Sebaceous cell carcinoma: Higher power view of a
sebaceous cell carcinoma showing sebaceous differentiation (arrow) poorly differentiated tumor showing largely undifferentiated cells with
in the center of a tumor island severe pleomorphism and hyperchromasia
Fig. 5.4.2.23: Sebaceous cell carcinoma: Tumor cells seen Fig. 5.4.2.26: Squamous cell carcinoma: Numerous pearls (arrow)
invading the epithelium known as pagetoid (arrow) spread seen in a well differentiated squamous cell carcinoma
Fig. 5.4.2.24: Sebaceous cell carcinoma: Aspirate from a lid mass Fig. 5.4.2.27: Squamous cell carcinoma: Photograph shows large
reveals intracytoplasmic lipid as orange in color (arrow) which is cells with abundant eosinophilic cytoplasm, hyperchromatic irregular
demonstrated by oil red O stain nuclei with mitosis. Occasional cell shows dyskeratinization (arrow)
in a moderately differentiated squamous cell carcinoma
Fig. 5.4.2.25: Sebaceous cell carcinoma: Tumor cells show Fig. 5.4.2.28: Squamous cell carcinoma: Poorly differentiated
vacuolated cytoplasm and irregular hyperchromatic nuclei on tumor showing no differentiation
impression cytology of an ulcerated lid mass
CONJUNCTIVAL LESIONS Cysts

The histopathology of the normal conjunctiva is presented
in Figure 5.4.2.29. Abnormalities of the conjunctiva, congenital
and acquired comprising degenerations, dysplasia, and tumors
are presented in subsequent slides (Figures 5.4.2.30–5.4.2.45).
Fig. 5.4.2.32: Simple epithelial conjunctival inclusion cyst:

The cyst is lined by conjunctival epithelium
Fig. 5.4.2.29: Normal conjunctiva: Stratified columnar epithelium with
goblet cells (arrow). The stroma is loose with blood vessels and
lymphatics
Developmental Abnormalities
Fig. 5.4.2.33: Simple epithelial inclusion cyst: Higher

magnification reveals numerous goblet cells
Fig. 5.4.2.30: Limbal dermoid: Histologic section of a dermolipoma
reveals stratified squamous epithelium. The stroma is dense containing
hair follicles (h) and fat (f) in the deeper stroma
Fig. 5.4.2.31: Complex choristoma: Dermolipoma containing cartilage Fig. 5.4.2.34: Rhinosporidiosis: Numerous sporangia (arrow) of
(c) and normal lacrimal gland acini (a) within the adipose tissue Rhinosporidium seeberi are seen in the conjunctival stroma
Fig. 5.4.2.35: Rhinosporidiosis: Higher magnification reveals small Fig. 5.4.2.38: Conjunctival amyloidosis: Apple green birefringence
round endospores (arrow) within the sporangia seen under polarized light with Congo red stain
Degenerations Precancerous Lesions
Fig. 5.4.2.36: Pterygium: Histopathology section reveals stratified Fig. 5.4.2.39: Actinic keratosis: Histologic section reveals acanthosis
squamous epithelial lining and subepithelial stroma containing and dysplasia of the surface epithelium. The subepithelial tissue shows
degenerated collagen fibers (arrow) elastotic degeneration (arrow) along with dense chronic inflammatory
infiltrate
Conjunctival Dysplastic Lesions
Fig. 5.4.2.37: Conjunctival amyloidosis: Amorphous hyaline like Fig. 5.4.2.40: Conjunctival dysplasia: Clinical appearance
material is seen in the substantia propria of the conjunctiva of a gelatinous appearing lesion at the limbus
Fig. 5.4.2.44: Squamous cell carcinoma: Right eye exenteration

specimen of another case reveals a large squamous cell carcinoma
Fig. 5.4.2.41: Conjunctival dysplasia: Moderate to severe dysplasia
arising from the limbus
of the squamous epithelial cells on impression cytology
Fig. 5.4.2.45: Squamous cell carcinoma: Well differentiated

squamous cell carcinoma with keratin pearls (arrow) in the stroma
CORNEA
Fig. 5.4.2.42: Conjunctival dysplasia: Histologic section of severe
dysplasia which reveals total loss of cellular architecture involving full
Histopathological section of the normal cornea is illustrated
thickness of the epithelium with dense stromal inflammatory infiltrate in Figure 5.4.2.46. Abnormal conditions of the cornea,
inclusive of inflammatory lesions, degenerations and
dystrophies are demonstrated in Figures 5.4.2.47 to 5.4.2.57.
Conjunctival Malignant Epithelial Tumors
Fig. 5.4.2.46: Normal cornea: Cornea is an avascular structure

consisting of five layers. It is lined by stratified squamous epithelium
(ep) about five cells thick. This is supported by Bowman's membrane
(bm). The bulk of cornea is made of stroma (s) which is made of
Fig. 5.4.2.43: Squamous cell carcinoma: Clinical appearance of a dense collagenous connective tissue. Posteriorly, a thick elastic
large conjunctival mass filling the palpebral aperture and protruding basement membrane called Descement's membrane (dm) lined by a
through the lids layer of flattened endothelial cells is identified
Fig. 5.4.2.47: Stromal vascularization: Numerous Fig. 5.4.2.50: Mycotic keratitis: Histologic section reveals dense
proliferating capillaries are seen in the stroma neutrophilic infiltration, eosinophils and nuclear debris in the stroma
Fig. 5.4.2.48: Bullous keratopathy: Hematoxylin and eosin section Fig. 5.4.2.51: Mycotic keratitis: On silver methanamine stain, fungal
reveals a large subepithelial bulla due to collection of fluid hyphae appear black with septae and acute angle branching
Inflammatory Degenerations
Fig. 5.4.2.49: Tuberculous stromal keratitis: Microphotograph reveals Fig. 5.4.2.52: Spheroidal degeneration: Several hyaline deposits lie
dense stromal inflammatory exudates along with giant cells and within the subepithelial tissues and extend into the stroma
retrocorneal Descemet's membrane
Stromal Dystrophies
Fig. 5.4.2.56: Lattice dystrophy: Apple green birefringence is

demonstrated on Congo red stain in polarized light in the corneal
stroma
Endothelial Dystrophy
Fig. 5.4.2.53: Granular dystrophy: The granules stain deep
eosinophilic on hematoxylin and eosin stain
Fig. 5.4.2.57: Congenital hereditary endothelial dystrophy (CHED):

Histologically marked thickening (arrow) of Descemet's membrane
with paucity of endothelial cells seen
Fig. 5.4.2.54: Granular dystrophy: The granules take up a brilliant ORBITAL LESIONS
red color on Masson's trichrome stain
Clinical, gross and histopathological co-relates of different
types of orbital lesions, cystic, parasitic, inflammatory and
neoplastic, relevant in ophthalmology are presented in Figures
5.4.2.58 to 5.4.2.112.
Cystic Lesions
Fig. 5.4.2.55: Macular dystrophy: Acid mucopolysaccharides are seen Fig. 5.4.2.58: Dermoid cyst: Gross appearance of a cystic mass
in the keratocytes and take up a Prussian blue color by colloidal iron which shows pultaceous material in its lumen. Hairs are also identified
stain within it
Fungal Infections
Fig. 5.4.2.59: Dermoid Cyst: Cyst wall is lined by stratified squamous Fig. 5.4.2.62: Orbital aspergillosis: Gross appearance to show an
epithelium with hair follicle (arrow) and dermal appendages in its wall irregular orbital mass with ill defined borders
Fig. 5.4.2.60: Microphthalmos: Cyst shows a glial fibrous lining on Fig. 5.4.2.63: Orbital aspergillosis: Numerous multinucleate giant cells
the inner wall (arrow) and collagen fibers on the outside seen along with epithelioid cell granulomas (arrow) in an inflammatory
background
Chronic Granulomatous Inflammations
Fig. 5.4.2.61: Tuberculosis of the orbit: Numerous multinucleate giants Fig. 5.4.2.64: Orbital aspergillosis: Aspirate reveals giant cells in
cells along with epithelioid cell granulomas (arrow) are seen in an inflammatory background on Papanicolaou stain
tuberculous infection
Fig. 5.4.2.65: Orbital aspergillosis: Silver methanamine stains the Fig. 5.4.2.68: Orbital mucormycosis: Fungal hyphae appear black in
fungal hyphae black in color. The hyphae have uniform width with color, are aseptate and show irregular width throughout its length
septae and show acute angle branching with right angle branching on silver methanamine stain
Parasitic Infections
Fig. 5.4.2.66: Orbital mucormycosis: Clinical photograph showing a Fig. 5.4.2.69: Hydatid cyst: Gross appearance showing
large ulcerated growth in the periorbital area a pearly white membranous cyst
Fig. 5.4.2.66: Orbital mucormycosis: Hematoxylin and eosin stain Fig. 5.4.2.70: Hydatid cyst: Microscopy reveals a laminated cyst wall
reveals few unstained fungal hyphae in a necrotic background
Fig. 5.4.2.71: Hydatid cyst: Higher magnification to show scolices Fig. 5.4.2.74: Orbital pseudotumor: Higher magnification
(arrow) and hooklets of echinococcus granulosus larvae reveals numerous plasma cells (arrow)
Non-infectious Orbital Inflammation Primary Orbital Tumors
Vascular Lesions
Fig. 5.4.2.72: Orbital pseudotumor: Gross appearance of a well Fig. 5.4.2.75: Capillary hemangioma: Numerous
defined orbital mass proliferating capillaries seen
Fig. 5.4.2.73: Orbital pseudotumor: Focal dense collections of chronic Fig. 5.4.2.76: Capillary hemangioma: Higher magnification
inflammatory cells consisting of lymphocytes and plasma cells along showing prominent endothelial cells (arrow)
with areas of fibrosis (arrow)
Mesenchymal Tumors
Fig. 5.4.2.77: Cavernous hemangioma: Cut surface showing an Fig. 5.4.2.80: Fibrous histiocytoma of the orbit: Cut surface
encapsulated mass with a spongy texture due to collection of large shows an encapsulated tumor mass
sized vascular channels
Fig. 5.4.2.78: Cavernous hemangioma: Large cavernous spaces are Fig. 5.4.2.81: Fibrous histiocytoma: Histology
seen lined by flattened endothelial cells and filled with blood. The shows characteristic storiform pattern
intervening stroma consists of fibrous tissue and smooth muscle cells
Fig. 5.4.2.79: Lymphangioma: Microscopically numerous lymphatic Fig. 5.4.2.82: Fibrous histiocytoma: Higher magnification reveals a
channels of varying sizes lined by flattened endothelial cells (arrow) mixture of fibroblast and histiocyte like plump vesicular nuclei
are seen. Lymphoid aggregrates are seen in the stroma
Neural Tumors
Fig. 5.4.2.83: Embryonal rhabdomyosarcoma: Histologic section

shows a cellular round cell tumor with hyperchromatic nuclei in a
myxoid background. It reveals the primitive nature of rhabdomyoblasts Fig. 5.4.2.86: Schwannoma (Benign nerve sheath tumor): Cut surface
reveals a well encapsulated multilobulated tumor with foci of yellowish
discoloration
Fig. 5.4.2.84: Differentiated rhabdomyosarcoma: The tumor cells

reveal long cytoplasmic processes, some round with eosinophilic
cytoplasm
Fig. 5.4.2.87: Schwannoma: Spindle cell tumor shows cellular Antoni A
areas with verocay bodies and loose myxoid Antoni B areas
Fig. 5.4.2.85: Rhabdomyosarcoma: Desmin stain Fig. 5.4.2.88: Schwannoma: Higher magnification of Antoni A area
is strongly positive in the tumor cells reveals typical verocay bodies showing palisading of nuclei
Fig. 5.4.2.89: Schwannoma: Tumor cells are strongly positive Fig. 5.4.2.92: Non-Hodgkin’s lymphoma: Cut section
for S-100 immunohistochemical stain reveals a fleshy encapsulated mass
Fig. 5.4.2.90: Neurofibroma: Microscopic examination shows Fig. 5.4.2.93: Non-Hodgkin's lymphoma: Diffuse sheets of
numerous proliferating nerve bundles (arrow) in a plexiform monomorphic lymphoid cells with hyperchromatic nuclei on hematoxylin
neurofibroma and eosin stain
Lymphoid Tumors
Fig. 5.4.2.91: Non-Hodgkin's lymphoma of the orbit: Clinical Fig. 5.4.2.94: Non-Hodgkin's lymphoma: Tumor cells are strongly
appearance of a 25-year-old male who presented with a left orbital positive for immunohistochemical stain leucocyte common antigen
mass (LCA)
Fig. 5.4.2.95: Granulocytic sarcoma of the orbit: Clinical Fig. 5.4.2.98: Acute myeloid leukemia: Peripheral smear shows a
appearance of a 5-year-old child with an isolated right orbital mass myeloblast (arrow) with scant cytoplasm and inconspicuous nucleoli.
Sudan black stains the cytoplasmic granules of the myeloblasts black
in color as shown in the inset
Fig. 5.4.2.96: Granulocytic sarcoma: Histopathology shows a Fig. 5.4.2.99: Primitive neuroectodermal tumor (PNET) of the orbit:
malignant round cell tumor in the orbital biopsy Malignant round cell tumor with numerous mitotic figures and vascular
channels transversing the tumor
Fig. 5.4.2.97: Granulocytic sarcoma: The tumor cells are Fig. 5.4.2.100: Primitive neuroectodermal tumor (PNET): Immuno-
positive for myeloperoxidase stain (MPO) histochemical stain MIC2 (CD99) is strongly positive in the tumor cells
Metastatic Orbital Tumors
Fig. 5.4.2.101: Prostatic carcinoma metastatic to orbit: Cytology of Fig. 5.4.2.104: Normal lacrimal gland: Higher magnification reveals
the orbital mass reveals malignant round cells with occasional acini cuboidal epithelium of an acinus around a central lumen. It shows two
(arrow) formation types of cells—secretory cells with strongly stained granular
eosinophilic cytoplasm called serous cells and the other which are
almost unstained are called mucous cells
Fig. 5.4.2.102: Prostatic carcinoma metastatic to orbit: Prostate biopsy Fig. 5.4.2.105: Sjogren’s syndrome: Lacrimal gland acini are replaced
revealed prostate carcinoma in the same patient with orbital mass by sheets of lymphoid cells mimicking a small cell lymphocytic lymphoma
Lacrimal Gland Lesions Tumor of the Lacrimal Glands

(Benign Mixed Tumor)
Fig. 5.4.2.103: Normal lacrimal gland: Lacrimal gland acini are loosely Fig. 5.4.2.106: Pleomorphic adenoma: Cut surface reveals an
present in the fibrous stroma. Arrow points to an intralobular duct encapsulated tumor with yellowish color due to hyalinization
within a lobule of lacrimal parenchyma
Fig. 5.4.2.107: Pleomorphic adenoma: Histology shows a Fig. 5.4.2.110: Adenoid cystic carcinoma: Characteristic swiss cheese
characteristic biphasic pattern consisting of a pale myomatous stroma pattern or cribriform appearance of the tumor on microscopic
and cellular area containing epithelial element examination
Fig. 5.4.2.108: Pleomorphic adenoma: Higher magnification showing Fig. 5.4.2.111: Mucoepidermoid carcinoma: A rare lacrimal gland tumor.
characteristic epithelial ductal structures lined by two layers of It shows both squamous differentiation (s) and mucin secreting (m)
epithelium. The outer myoepithelial layer often undergoes myxoid and cells
even cartilaginous metaplasia whereas the inner layer may secrete
mucus
Malignant Tumors
Fig. 5.4.2.109: Adenoid cystic carcinoma: Gross appearance of an Fig. 5.4.2.112: Mucoepidermoid carcinoma: Higher magnification
adenoid cystic carcinoma showing areas of hemmorhage and necrosis reveals a tumor island displaying both mucous secreting clear cells
and cells with squamous differentiation
UVEA TRACT INCLUDING CHOROID

Normal histopathological sections of the iris, ciliary body
and the choroid are presented in Figures 5.4.2.113 and
5.4.2.114 respectively. Histopathological sections of uveal
pathological lesions are presented in Figures 5.4.2.115 to
5.4.2.126.
Fig. 5.4.2.116: Tuberculous endophthalmitis: Microphotograph shows

intraocular granulomatous inflammation. Epithelioid cell granulomas
are seen as pale areas along with multinucleate giant cells. Area of
necrosis is also seen
Fig. 5.4.2.113: Normal iris and ciliary body: Microphotograph Choroidal Tumors
reveals normal iris (i) tissue and ciliary body (cb)
Fig. 5.4.2.114: Normal choroid: Histologic section reveals Fig. 5.4.2.117: Malignant melanoma: Gross appearance of a
normal sclera and the pigmented choroid pigmented tumor filling the entire cavity of eyeball
Fig. 5.4.2.115: Iris epithelial cyst: They are lined by Fig. 5.4.2.118: Choroidal malignant melanoma (spindle cell type):
non-pigmented columnar/squamous epithelium Histologic section of a spindle cell malignant melanoma
Fig. 5.4.2.119: Malignant melanoma: Higher magnification reveals Fig. 5.4.2.122: Iris and ciliary body medulloepithelioma: Hematoxylin
spindle cells with nuclear grooving (arrow) and moderate amount of and eosin stained section reveals tumor arising from the uveal tract
eosinophilic cytoplasm arranged in solid sheets as well as tubule like structures
Fig. 5.4.2.120: Malignant melanoma (epithelioid cell type): It is made Fig. 5.4.2.123: Iris and ciliary body medulloepithelioma: Higher
of noncohesive cells that contain large nuclei with prominent nucleoli magnification reveals proliferating medullary epithelium forming tubule
(arrow) and abundant eosinophilic cytoplasm with distinct cell borders like structures
Metastatic Tumors
Fig. 5.4.2.121: Iris and ciliary body medulloepithelioma: Gross Fig. 5.4.2.124: Metastatic iris tumor: Clinical picture of a 42-year-old
appearance of a tumor arising from the uveal tract anteriorly and lady showing a creamy white mass covering superior half of iris
perforating through the cornea
Fig. 5.4.2.125: Metastatic adenocarcinoma of the iris: Vitreous aspirate

revealed malignant round cells in clusters as seen on a Papanicolaou
stain Fig. 5.4.2.128: Asteroid hyalosis: Vitreous aspirate reveals
few spherules on Papanicolaou stain
Fig. 5.4.2.126: Metastatic adenocarcinoma of the iris: Hematoxylin

and eosin section from the enucleation specimen revealed a metastatic
adenocarcinoma in the form of glands and irregular tumor islands in
the iris. Patient had a breast carcinoma
Fig. 5.4.2.129: Asteroid hyalosis: Spherules are
VITREOUS birefringent in polarized light
Histopathological views of some common vitreous

abnormalities are presented in Figures 5.4.2.127 to 5.4.2.129. Histopathology of Vitreous Aspirate
Histopathology of vitreous aspirate in retinoblastoma and
malignant melanoma is presented in Figures 5.4.2.130 to
5.4.2.133.
Fig. 5.4.2.127: Persistent primary hyperplastic vitreous (PHPV): Fig. 5.4.2.130: Retinoblastoma: Intraocular aspirate reveals rosette
Histology reveals retrolental mass which is composed of mesenchymal (arrow) with characteristic molding of tumor cells
tissue and adipose tissue (a). Dysplastic retina is also seen
RETINA AND OPTIC NERVE

Histopathological section of retinal dysplasia is presented in
Figure 5.4.2.134. Clinical, gross and histopathological
photographs of retinoblastoma, both intraocular and after
extraocular spread and before and after treatment are
presented in Figures 5.4.2.135 to 5.4.2.147. High and low
power histopathological view of the normal optic nerve is
demonstrated in Figures 5.4.2.148 and 5.4.2.149.
Histopathology of some common optic nerve tumors are
shown in Figures 5.4.2.150 to 5.4.2.152.
Fig. 5.4.2.131: Malignant melanoma: Intraocular aspirate shows a

tumor with nuclear grooving (arrow) and inconspicuous nucleoli on
Papanicolaou stain in a case of spindle cell melanoma
Fig. 5.4.2.134: Retinal dysplasia: Microphotograph

showing numerous rosettes
Fig. 5.4.2.132: Malignant melanoma: Epithelioid malignant melanoma

shows large tumor cells with irregular hyperchromatic nuclei and Retinoblastoma
prominent nucleoli
Fig. 5.4.2.133: Malignant melanoma: Tumor cells show Fig. 5.4.2.135: Retinoblastoma: Clinical photograph of
strong cytoplasmic positivity with HMB 45 a child presenting with leucokoria
Fig. 5.4.2.136: Retinoblastoma: Enucleation specimen showing an Fig. 5.4.2.139: Retinoblastoma: Poorly differentiated
intraocular retinoblastoma with optic nerve infiltration retinoblastoma without any differentiation
Fig. 5.4.2.137: Retinoblastoma: Histologic section from a well Fig. 5.4.2.140: Retinoblastoma: Retinoblastoma cells
differentiated retinoblastoma showing numerous Homer Wright infiltrating into iris and ciliary body
rosettes (arrow). In these rosettes, the pink material in the center
represents tangle of processes of tumor cells
Fig. 5.4.2.138: Retinoblastoma: Section shows Flexner Fig. 5.4.2.141: Retinoblastoma: Entire thickness of the choroid is
wintersteiner rosettes with a central lumen involved by retinoblastoma cells (also called diffuse choroidal
involvement)
Fig. 5.4.2.142: Retinoblastoma: Optic nerve head Fig. 5.4.2.145: Chemoreduced pthisical eyeball: Histologic section
infiltration by tumor cells reveals markedly thickened sclera (s) with all the intraocular contents
present in a disorganized manner. Only few viable tumor cells are
seen
Fig. 5.4.2.143: Retinoblastoma: Areas of calcification identified Fig. 5.4.2.146: Retinoblastoma: Clinical picture of a
child presenting with an extraocular retinoblastoma
Fig. 5.4.2.144: Chemoreduced pthisical eyeball: Gross specimen of Fig. 5.4.2.147: Retinoblastoma: Enucleation specimen
chemotherapy treated pthisical eyeball showing retinoblastoma tumor showing retinoblastoma with an extraocular spread
Optic Nerve
Fig. 5.4.2.148: Normal optic nerve: Cross section reveals Fig. 5.4.2.151: Optic nerve meningioma: Numerous meningothelial
dural sheath (d) and pia-arachnoid whorls (arrow) seen characteristic of meningioma
Secondary Tumors
Fig. 5.4.2.149: Normal optic nerve: Higher magnification reveals nerve

fibers bundles arranged in fascicles (arrow) separated by septae
Tumors
Fig. 5.4.2.152: Metastatic retinoblastoma: Entire optic nerve
including the cut end is infiltrated by the tumor
Fig. 5.4.2.150: Juvenile pilocytic astrocytoma (glioma) of the optic

nerve: Densely cellular areas seen with characteristic Rosenthal fibers
Chapter 5.5
OCULAR AND ADNEXAL RADIOLOGY
5.5.1 Radiological Imaging

in Ophthalmology
Vandana Kohli
Imaging of the eye, orbit and ocular adnexa is a valuable tool where, I = Transmitted intensity
that helps explore their mysteries and the various pathologies I 0 = Intensity of incident X-ray beam
associated with them. CT scanning was developed by Godfrey e = Euler’s constant (2.718)
Hounsfield in the 1970s and clinical MRI scanning technology µ = Linear attenuation coefficient of the object
a developed in the 1970s and 1980s due to the work of x = Thickness of the object.
several scientists including Paul Lauterber, Peter Mansfield, The property of attenuation of X-rays is used both in
Aberdeen and Raymond Damadian. conventional radiography and in CT scanning wherein
X-rays are directed through the human body and the
CT SCANNING
transmitted radiation is captured on a film or on detectors
Physics of CT Scanning and the obtained data is used to create an image of the body.
The differences in conventional radiography and CT scanning
After the discovery of X-rays by Roentgen in 1895, X-ray
lie in the techniques of projection of X-rays, data acquisition,
imaging was soon developed for diagnostic imaging of the
data analysis and data display.
human body. X-rays are a form of electromagnetic radiation
In conventional radiography, X-rays pass through the
that have a wavelength of 10-8 to 10-12 m and a frequency
whole thickness of the body and the transmitted radiation
of 3 × 1016 to 3 × 1020 Hz.1 When they propagate through
space and objects, they are absorbed by the atoms that they obtained at each point of the X-ray film is inversely
come in contact with and the X-ray beam gets attenuated. proportional to the total attenuation of each ray. The total
The attenuation of the beam on passage through physical attenuation of each ray is the net addition of the attenuation
objects depends upon the energy spectrum of the incident caused by all the structures in the path of that ray and further
X-ray beam and the atomic structure and thickness of the subcharacterization of all the structures in this path is not
object. Thus, this attenuation data provides a noninvasive possible. Thus, there is a superimposition of the internal
means of determining the internal structure of the object. structures and the two-dimensional image of the three-
The attenuation of X-rays is expressed by the equation.2 dimensional object obtained is like a shadow of the object
I = I0 e–µx (Fig. 5.5.1.1).
body is that the internal structure of an object can be

reconstructed from multiple projections of an object. In CT
scanning of the human body, an X-ray beam is projected on
one slice of the human body and the attenuation measu-
rements made around the circumference of the slice. The
process is repeated, but now the X-ray projection is done
from a different angle and, hence, a different set of
attenuation data is obtained. This process is repeated several
Fig. 5.5.1.1: Image acquisition in conventional radiography times at different angles. Thus, multiple X-ray projections
are done around the circumference of the slice and a large
amount of data is obtained for one slice. Complex
The procedure of perfor ming CT scan, whereas, mathematical computations are done on this data and
incorporates passing X-rays through a thin slice of the body attenuation value of each voxel of this slice is obtained. The
at a time and measuring X-ray attenuation at different points smallest attenuating volume of tissue that can be measured
around the circumference of the slice. The attenuation data is called a voxel. This attenuation data is then depicted via a
obtained is used to determine the internal structure of the gray scale in the CT films. Thus the steps involved in CT
slice and this is depicted in the CT films that are obtained. scanning can be simplified into:
Thus, a CT image is a display of the anatomy of a thin slice of • Projection of X-rays on the human body
the body and is like a cross-section of the body (Fig. 5.5.1.2). • Detection of the attenuated X-rays
Secondly, in conventional radiography, the transmitted • Analog to digital conversion of the data obtained
radiation is usually directly captured on an X-ray film which • Reconstruction process using complex mathematical
leads to its darkening and a qualitative image is obtained. computations
Subtle differences in the X-ray attenuation are not picked up. • Image display.
In a CT scan, the transmitted radiation is measured by special Methods of X-ray projection, detection and data
detectors that provide quantitative data and even minor computation in CT scanners have undergone several changes
differences in the X-ray attenuation can be picked up. during the years. There has been a doubling of performance
Mathematical computations are done on this quantitative data capabilities approximately every 32 months. In 1972, the
to decipher the attenuation value of each block of tissue in scanning time per slice was 300 seconds. It reduced to 1 second
the slice and these values are then depicted on the CT film in 1990 and to 0.005 second in 2005.3
using a gray scale. The details regarding this procedure are In the first generation scanners, parallel beam geometry was
overviewed in the next section. used for X-ray projection and a translate–rotate principle
used for the tube-detecter combination2,3 (Fig. 5.5.1.3). The
CT Construction of a Cross-section
X-rays were collimated to a beam of approximately 2 × 13
of the Human Body
mm size with the 13 mm being the voxel length and, hence,
The fundamental principle of the mathematical computations the slice thickness. The X-ray beam was passed through the
involved in the CT construction of the cross-section of the human body and the X-rays that had not been absorbed by
Fig. 5.5.1.2: Image acquisition of CT scanning

Ocular and Adnexal Radiology 279
Fig. 5.5.1.3: First generation scannar (1970) - pencil beam and translate-rotate principle
the body were picked up by the detectors. The X-ray tube (Fig. 5.5.1.4).2,3 Multiple detectors were used in a single line,
and the detector system then moved forward linearly and the one adjacent to the other, to pick up the wider beam. The
step was repeated. 160 such steps were carried out in one number of translations and rotations was, thus, decreased
translation. The X-ray tube and the detector system were and the scan time required for one slice decreased to about
then rotated 1° and 160 measurements repeated for this 17 seconds. Gradually, the fan beam width was increased to
rotated position. The translate–rotate process was repeated about 50o to 55o so that the entire width of the human body
180 times around the circumference of the body. Thus, could be covered in one instant.
28,800 (160 × 180) measurements were made for one cross- The third generation machines use wide-angle fan beam
section of the body (one slice). To obtain the CT scanning of and an arc of detectors and the X-ray tube and the detectors
the next slice, the patient’s table moved forward to get the rotate continuously around the patient for 360o. 2,3 (Fig.
next slice in the path of the X-rays and the whole process 5.5.1.5). There is no linear movement of the tube or the
was repeated. The scan time required for one slice was five detectors. There may be 600 to 1000 detectors in one arc.
minutes, which is much more than one breath-hold for most These scanners decrease the scan time further.
humans. Therefore, motion artifacts seriously distorted image Fourth generation machines use wide-angle fan beam and a
quality and it was useful only for relatively immobile parts, rotating X-ray but there is a 360o circle of stationary detectors
such as the head. (Fig. 5.5.1.6).2,3
In the second generation machines, the X-ray beam was Multi-slice CT scanners have cone shaped X-ray beam and
collimated to a fan beam geometry and a linear detector array multiple arcs of detectors. Both the X-ray tube and the
was used, i.e. the X-ray beam was collimated to the shape of detector arcs rotate around the patient. Multi-slice scanners
a fan beam with a diverging angle of 3o to 10o so that a wider cover a thicker section of the body at one instant and, hence,
area of the body could be covered at one instant further decrease the total scan time (Fig. 5.5.1.7).2,3
Fig. 5.5.1.6: Fourth generation scanner (1978)—wide fan beam, a

stationary circle of detectors and continuous rotation of X-ray source
Fig. 5.5.1.4: Second generation scanner (1972)—partial fan beam
and translate-rotate principle
Fig. 5.5.1.5: Third generation scanner (1976)—wide fan beam and Fig. 5.5.1.7: Multi slice scanner—cone shaped X-ray beam, multiple
continuous rotation of both X-ray source and arc of detectors arcs of detectors and continuous rotation of both X-ray source and
arcs of detectors
Axial and Helical Scanning and then the images may be reconstructed in the coronal,
sagittal or parasagittal planes as well
In axial scanning, data is obtained in discrete slices. Each
• It enhances multiplanar or three-dimensional renderings
revolution of the X-ray tube gives the data of one cross-section
• It decreases the total scanning time
of the human body. To get information of the next slice, the
• It decreases motion artifacts, as shorter scan times are
patient table moves a certain amount and the entire process is
required
repeated. The table is motionless during the time that data is
• It decreases patient’s total radiation dose.
being collected. Thus, this is a step and shoot scanning
procedure (Fig. 5.5.1.8). In helical/spiral scanning, whereas,
Attenuation of X-rays by Various Tissues
the patient table moves forwards continuously when the X-ray
tube is rotating around the patient and data is being collected X-ray attenuation is measured in Hounsfield units (HU). A
by the detectors (Fig. 5.5.1.9). This gives several advantages.2,3 2000 HU scale has been formulated with attenuation values
• It increases resolution in the z-axis, as there is a continuous ranging from approximately –1000 to +1000. Air causes the
pool of data least attenuation and is assigned a value of –1000 HU, water
• There is a continuous pool of data; hence, an image can leads to some attenuation and has been assigned a value of
be reconstructed in any plane. For instance, in orbital 0 HU, and dense cortical bone causes the maximum
scanning, spiral scanning may be done in the axial plane attenuation and has a value of +1000 HU.2 Muscle has an
Fig. 5.5.1.8: Axial scanning—step and shoot scanning
Fig. 5.5.1.9: Helical scanning—continuous rotation of both X-ray source and detectors
attenuation value of +50 HU, gray matter has a value of hyperintense. Air allows 100 percent transmission of X-rays
+45 HU and white matter has a value of +35 HU.4,5 The and is therefore hypointense whereas a metal implant allows
approximate attenuation values of different tissues are given only 0.0006 percent transmission of X-rays and is very
in Table 5.5.1.1.2,4,5 These values may vary by 10 to 25 HU hyperintense.3
in different CT scanner machines. Pathologies with high water
content (e.g. edema and necrosis) appear hypointense on CT Display of Attenuation Data
scanning and tissues with high protein content (e.g. lens, clotted The smallest attenuating volume of tissue that can be
blood, tenacious mucus secretions) appear hyperintense.5 measured is called a voxel. The attenuation value of each
Fresh hemorrhage also absorbs X-rays and appears voxel could be displayed in its Hounsfield unit but that would
Table 5.5.1.1: Attenuation values of tissues in the body vessels, lacrimal glands (by 10 HU), extraocular muscles, uvea,
Tissue Attenuation value (HU)
meninges, cavernous sinuses, pituitary stalk, the pineal gland
and any pathology which has a rich vascular supply or has
Air –1000
leaky, fenestrated capillaries or where the blood brain barrier
Fat –30 to –100
Water 0
has been disrupted.5 The normal brain tissue enhances by only
CSF +4 to +10 3 to 5 HU after contrast administration but where the blood
White matter +23 to +35 brain barrier is disrupted, e.g. due to a tumor or an infection,
Gray matter +32 to +45 the brain tissue may enhance by >5 HU. The disadvantage is
Muscle +50 that iodinated contrast agent may cause adverse side effects in
Blood +56 to +76 upto three percent of the patients. Most of the side effects
Calcification +140 to +200 are mild but serious side effects may occur in 1:40,000 patients.
Bone +1000 It has to be given with caution in patients with
• Renal impairment, as it may lead to renal failure.
• Hyperthyroidism, as it may lead to thyrotoxic crisis, a life-
be a non user-friendly way of displaying the data. To make it threatening condition.
user-friendly, a gray scale is chosen to represent the attenuation • Known allergic reaction to iodine.
values, with black representing the least attenuation and white
representing the maximum attenuation. The smallest block PHYSICS OF MRI SCANNING
of gray used for the reconstruction of the image is called a
Magnetic Resonance Imaging (MRI) is an imaging technique
pixel. The number of shades of gray chosen to depict the
based on the magnetic resonance properties of one of the
attenuation is called the window width, e.g. 32 to 64 shades
constituent atoms of an object. MRI of the human body is
of gray may be chosen between black and white to represent
done based on the magnetic resonance properties of the
the different attenuation values. The window level is the
hydrogen atoms in the human body.
Hounsfield unit at which the window is centered and the
window range is the inclusive number of Hounsfield units
Magnetic Resonance
above and below the window level that are to be represented
in the black to white scale. To take a very simplified example, To understand magnetic resonance, we need to recall the
assuming that a soft tissue lesion such as a hemangioma is basic structure of an atom. An atom is constituted by three
being examined, and a window level of +50 HU, a window particles–protons, neutrons and electrons. The protons and
range of 200 HU and a window width of four are chosen. neutrons are present in the core (nucleus) of the atom and
All the structures with attenuation less than –50 HU would the electrons revolve around the nucleus in outer shells
appear black, all those above +150 HU would appear white, (orbitals). One characteristic property of a nucleus is that it
all those between – 50 to +50 HU would appear dark gray spins and this spin is quantified to certain discrete values. A
and all those between +50 to +150 HU would appear light nucleus with an odd number of protons and an odd number
gray. of neutrons has a spin represented by an odd integer such as
For evaluating orbital soft tissue lesions, a window width one, three or five, etc. A nucleus with an odd number of
of 350 to 400 HU and a window level of 80 to 100 HU are protons and an even number of neutrons, or an even number
generally chosen. For evaluating bony changes, bone windows of protons and an odd number of neutrons has a spin
are obtained with a window width of 2500 to 3200 HU and represented by a fraction such as 1/2, 3/2 or 5/2, etc. A
a window level of 600 to 800 HU.5 nucleus with an even number of protons and an even number
of neutrons has a spin of ‘zero’.6 For instance, the nucleus
Contrast Agents of a hydrogen atom, 1H, contains one proton and no neutron;
Iodinated contrast agents are used in certain conditions to hence, its nuclear spin is 1/2. The nucleus of the oxygen
improve the detection of a lesion and to delineate its vascular atom, 16O, has 8 protons and 8 neutrons and, hence, its nuclear
characteristics. The contrast agent is injected intravenously and spin is ‘0’. The nucleus of the carbon atom, 12C, has 6 protons
it distributes into the blood and the interstitial spaces when not and 6 neutrons and, hence, its spin is ‘0’.
stopped by a barrier such as the blood-brain barrier or the The spinning of the nucleus leads to the production of a
blood retinal barrier. Injection of contrast therefore enhances small magnetic field around the nucleus. This magnetic field
is called the magnetic momentum of the nucleus. The Cessation of the short burst of energy leads to the reverting
magnetic momentum depends on the nuclear structure and back of the nucleus to its original state. This return to the
is therefore unique to each element on earth. original state is called ‘relaxation’ and during this process of
Magnetic momentum (also termed magnetic moment) is relaxation, the nucleus emits certain signals. The recordings
comparable to a bar magnet. Just as the magnetic field of a of these signals and their changes on manipulation of the
bar magnet possesses a magnitude and a direction, the external fields provide the basic framework for magnetic
magnetic moment of a nucleus possesses a magnitude and a resonance imaging techniques.
direction (Fig. 5.5.1.10). Its direction is the axis of rotation Magnetic resonance can be done for any element that
of the nucleus and its magnitude is decided by the nuclear possesses magnetic momentum. For MRI of the human body,
structure. It is represented by γ or the gyromagnetic ratio. 1H magnetic resonance properties of the hydrogen atoms in the
has a γ of 42.57 MHz T–1 and 16O and 12C have no magnetic body are used to unravel the internal structure of the body.
field around them as their nuclear spin is ‘0’. The nuclear Hydrogen becomes the element of choice as the human body
spins and gyromagnetic ratios of a few elements found in has a high component of water and fat, both of which contain
nature are given in Table 5.5.1.2.6 hydrogen; the nucleus of hydrogen has a spin of 1/2 and its
The magnetic moment of a nucleus gets altered by response to an applied magnetic field is one of the largest
application of external magnetic fields. When a short burst found in nature. Further, both carbon and oxygen, two other
of energy is applied at the Larmor frequency (to be described elements found in abundance in the human body, do not
later), the nucleus absorbs the energy in quanta and the exhibit magnetic momentum and are, hence, not amenable
direction of its magnetic moment gets altered. This quantized to MRI techniques.
energy absorption is called magnetic resonance absorption.
Magnetic Resonance in the Human Body
Magnetic resonance imaging of the human body can be better
understood by considering the magnetic resonance phenomena
in a block of tissue. A block of tissue contains several
hydrogen nuclei. A hydrogen nucleus consists of one proton
only and therefore, a hydrogen nucleus is often referred to
as a ‘proton’ in clinical MRI techniques. All the hydrogen
nuclei, or protons, have magnetic moments of equal
magnitude but their directions are oriented randomly. Hence,
the net vector sum of the magnetic moments in the block of
tissue is zero, i.e. there will be no net magnetization observed
in the tissue (Fig. 5.5.1.11).
If this tissue is placed in an external magnetic field, B0,
the protons begin to ‘precess’ about this magnetic field, B0,
Fig. 5.5.1.10: Magnetic moment of a nucleus i.e. the axes of rotation of these protons align parallel to B0
Table 5.5.1.2: Spins and magnetic moments of a few elements

Element Nuclear Structure Nuclear Spin Gyromagnetic At 1.5 T (MHz)
Protons Neutrons Ratio γ(MHz T-1 )
1
H, Protium 1 0 1/2 42.6 63.9
2
H,Deutrium 1 1 1 6.5 9.8
3
He 2 1 1/2 32.4 48.6
7
Li 3 4 3/2 16.5 24.8
12
C 6 6 0 0 0
16
O 8 8 0 0 0
19
F 9 10 1/2 40.1 60.1
23
Na 11 12 3/2 11.3 19.9
Fig. 5.5.1.11: Magnetization in a block of tissue
Fig. 5.5.1.13: Effect of an external magnetic

field, B0, on a block of tissue
In clinical imaging, the difference between the numbers

Fig. 5.5.1.12: Effect of an external magnetic field, B0, of protons in parallel versus anti-parallel position is only one
on one magnetic moment to two per million protons, hence, only a small portion of the
total pool of hydrogen nuclei in the body contributes to the
but they tilt slightly away from the axis while rotating just as a MRI signal.7
spinning top whose speed has started decreasing (Fig. 5.5.1.12). This M0 is the basic magnetic signal that is manipulated
The rate or frequency of this precession is called Larmor for MRI activities. The simplest manipulation involves the
frequency or ω0. It is dependent on the strength of the application of a short burst of radiofrequency energy at the
magnetic field and the individual nuclear characteristics. It Larmor frequency. This short burst of radiofrequency energy
can be calculated by the Larmor equation6 is called ‘rf pulse’. When the excitation rf pulse is applied
ω0 = γ B0/2 π perpendicular to B0 (also called a 90° rf pulse and depicted
where ω0 is the Larmor frequency in MHz, by an effective field B1), the protons absorb the energy in
• γ is the gyromagnetic ratio of the nucleus in s-1 T-1 and quanta and start precessing in a direction perpendicular to
• B0 is the magnetic field strength in Tesla units both B0 and B1. Thus, M0 rotates entirely perpendicular to
When placed in the magnetic field B0, most protons align both B0 and B1 and is termed ‘M’ and the longitudinal
parallel to B0 (which is also called the spin up position) but component (z) of M 0 becomes zero (Fig. 5.5.1.14). By
some align opposite to it (which is called the anti-parallel or convention, for the depiction and understanding of MRI
the spin down position). The anti-parallel protons have a higher activities, B0 and M0 are considered to be oriented in the z-
energy state than the protons parallel to B0 and the energy axis of the Cartesian coordinate system, the 90° rf pulse (or
difference between the two (ΔE) is proportional to B0. As B1) is considered to be oriented in the x-axis and M is
more protons are parallel to B0 and lesser are anti-parallel, considered to be oriented in the y-axis. 6
the net magnetization of the tissue, M0 is in the same direction After a few milliseconds, when the transmission of the rf
as B0 and can be calculated by the equation pulse is turned off, the protons begin to lose their absorbed
M0 = χ B0 energy and start returning back to their original position. ‘M’
where χ is the magnetic susceptibility of the substance in the y-axis gradually decreases and M0 in the z-axis starts
(Fig. 5.5.1.13).6 gaining in strength. This process is called ‘relaxation’. During
Fig. 5.5.1.14: Effect of a 90° rf pulse, B1, on M0
Fig. 5.5.1.15: Effect of cessation of rf pulse, B1, on M
this relaxation, the protons emit energy at the frequency ω0. motion is necessary for T1 relaxation to occur. During T1
If a receiver is placed perpendicular to B1 at this time, a relaxation, M in the y-axis gradually decreases and M0 in the
voltage is induced in it and this signal is called free induction z-axis gradually increases. The return of longitudinal relaxation
delay (FID). The FID signal provides the MR signal that is with time, when plotted, yields an exponentially increasing
recorded to obtain MR images (Fig. 5.5.1.15). convex shaped curve.7 The time taken by M0 to return to 63
The B0 conventionally used in modern MRI scanner percent of its original value following the cessation of the rf
machines is 1.5 T, although this may vary from 1 to 8 T pulse is termed T1 relaxation time (Fig. 5.5.1.16).
depending upon the configuration of the MRI scanner. To T 2 or transverse relaxation is the spin-spin relaxation.
have an idea of the scale of things, 1 T is 10,000 Gauss and Immediately following an rf pulse, the individual magnetic
the magnitude of earth’s magnetic field is 0.5 G! The rf moments start precessing in the transverse y-axis and they are
pulse, typically, has a strength of a few microT and lasts a all coherent, i.e. they have the same rotating phase, the same
few milliseconds and the FID signal has a strength of a few direction and the same frequency. On cessation of the rf pulse,
nanoT.7 the excited protons release their energy to return to their original
M0 position. The adjacent protons pick up some of this energy.
T1 and T2 Relaxation This spin-spin energy transfer can occur several times as long
During the process of relaxation, the excited protons release as the spins are in close proximity, have the same precession
their energy and the released energy is absorbed by the frequency and are in the same phase. But gradually, with time,
adjacent protons (spins) and the adjacent surroundings (lattice). due to inter and intra molecular interactions, there is loss of
These two relaxations are termed T2 relaxation and T 1 phase coherence among the protons. They can be compared
relaxation respectively and two relaxation times can be to cars in a race track which start together but gradually spread
measured-T1 and T2 relaxation times. out in the track due to their different speeds.7 The protons are
T1 or longitudinal relaxation is the spin-lattice relaxation. On then unable to transfer their energy to the adjacent protons
cessation of the rf pulse, the excited spins start losing their and there is a gradual loss of M or the transverse magnetization
energy to the surroundings (lattice). Some type of molecular signal. The decay of transverse relaxation with time is an
Fig. 5.5.1.16: T1 relaxation curve—changes in longitudinal magnetization, Mz, with time
Fig. 5.5.1.17: T2 relaxation curve—changes in transverse magnetization, My , with time
exponentially decreasing concave shaped curve and the time Table 5.5.1.3: T1 and T2 relaxation times of some tissues4,7
taken by the transverse component of M to decay to 37 percent Tissue T 1 (milliseconds) T2 (milliseconds)
of its initial value is termed T2 relaxation time (Fig. 5.5.1.17).7
Fat 200 to 250 (180 at 1T) (90 at 1T)
T1 and T 2 values of different tissues vary and these
Muscle (600 at 1T) 30 (40 at 1T)
differences are projected in the MRI images so that they
White matter 740 to 770 64 to 70
may be visually differentiated in the images. In general, protons
Gray matter 980 to 1040 64 to 71
in tissues with more fluid are more mobile and are, hence,
able to transfer their transverse magnetization to the adjacent CSF 2000 to 4000 400 to 1000
protons for a longer time and, therefore, have a long T2. (All the figures are approximate values at 1.5 T unless indicated
otherwise)
They also regain their longitudinal magnetization later and,
hence, have a long T1. Water, vitreous and CSF, therefore,
have a long T2 and a long T1. Tissues those are more viscous
e.g. fat lose their transverse magnetization faster and have a Thus, the basic steps involved in a typical MRI study
short T2. They also regain their longitudinal magnetization are:
fast and, hence, have a short T1. Tissues with a very low 1. A powerful, uniform external magnetic field (B0, usually
proton density (i.e. less number of mobile protons), e.g. air, 1.5 T) is employed to align the magnetic moments of the
bone, teeth enamel and dentine undergo very low protons in the body.
magnetization and hence have a very weak magnetization 2. This alignment (magnetization) is disrupted by the
signal and appear dark on all types of MR sequences. Rapidly introduction of an external rf energy at an appropriate
flowing blood appears hypointense on both T 1 and T2 frequency so as to induce resonance.
sequences. The approximate T1 and T2 values of some tissues 3. Cessation of the rf pulse causes the protons to return
are given in Table 5.5.1.3. back to the position of step 1 via T1 and T2 relaxation.
The signals released in this process are picked by the images are obtained by using sequences with short TRs
external RF detector coils to yield FID signals. (< 700 ms) and short TEs (< 30 ms). With short TEs, repeated
4. Various modifications to the applied magnetic currents 180° signals quickly rephase the dephasing protons and, hence,
are done via pulse sequences and field gradients and the T2 differences of different tissues are not picked up. Short
various FID signals recorded. TRs do not give enough time to tissues with long T1 (e.g.
5. A mathematical process called Fourier transformation is vitreous and CSF) to regain their longitudinal magnetization
used to convert the frequency information in the FID signal and they appear dark, but tissues with short T1 (e.g.
signals to corresponding intensity levels, which are then fat) regain their longitudinal magnetization signal fast before
displayed as shades of gray in a matrix arrangement, e.g. the next 90° pulse and, hence, appear bright. Thus, tissues
a 256×256 pixel matrix. with different T1s are differentiated with these types of
sequences. In orbital MRI, fat appears the brightest in T1 W
MRI Sequences images followed by the muscles, white matter, gray matter,
CSF and vitreous in decreasing order of brightness.
Various sequences are used to highlight the T1 and T 2
T1 W images provide better spatial resolution than T2 W
differences of various tissues. Some of the MRI sequences
images and therefore provide better anatomic details.
useful in orbital and neuro-ophthalmic imaging are:
• T1 Weighted sequences (T1 W)
T2 Weighted Sequences
• T2 Weighted sequences (T2 W)
• Proton Density Weighted sequences (PDW) T2 W sequences use long TRs (>2000 ms) and long TEs (>80
• Short Tau Inversion Recovery sequences (STIR) ms). When long TEs are used, tissues with short T2 (e.g. muscle)
• Fluid Attenuated Inversion Recovery sequences (FLAIR) lose their transverse magnetization signal early and appear dark
• Fat Saturation sequences whereas tissues with long T2 (e.g. vitreous) do not lose their
For all these sequences, a spin echo sequence is a basic transverse magnetization fast and appear bright. Thus, tissues
tool used for obtaining the required data. with different T2 are differentiated with these sequences. Vitreous
and CSF appear the brightest in orbital T2 W images followed
Spin Echo Sequence by fat, gray matter, white matter, and extraocular muscles in
decreasing order of brightness.
TR or the repetition time is the time interval between two
T2 W images provide better contrast resolution than T1
90° rf excitation pulses. For spin echo generation, an 180° rf
W images and therefore provide better pathological details.
pulse is applied after a 90° rf pulse at a time interval of tau
(τ) when T2 relaxation is occurring and the protons are
Proton Density Weighted (PDW) Sequences
gradually becoming incoherent. The 180° pulse reverses their
phases and makes them coherent again. The protons regain Proton density weighted (PDW) sequences use long TRs
their maximum coherence and the FID signal maximally (>2000 ms) and short TEs (<30 ms). Long TRs ensures that
increases in strength at another time interval of tau. This most tissues have enough time to regain their longitudinal
signal of increased magnitude is called a spin echo. The time magnetization and, hence, T1 differences would not be picked
interval between the 90° excitation pulse and the spin echo is up. Short TEs ensure that quick 180° pulses rephase all the
called echo time or ET and is twice the tau.6 Following this protons of most tissues and, hence, T2 differences are not
spin echo, the protons again start dephasing and again, the picked up. The difference in signal intensities is due to the
FID signal strength decreases. Application of a second 180° difference in their proton densities, i.e. the number of mobile
rf pulse reverses the proton phases again and gives another protons in the different tissues, e.g. the proton density of
coherence to the protons, producing another spin echo. Thus, gray matter is 15 percent higher than white matter and appears
the use of multiple 180° rf pulses helps maintain phase brighter than white matter on PDW sequences.
coherence of the protons longer than the use of a single
180° rf pulse. STIR and FLAIR Sequences
STIR and FLAIR are types of inversion recovery sequences
T1 Weighted Sequences
in which an 180° inversion pulse is given prior to the 90°
T1 weighted sequences are sequences that have been designed excitation pulse.6,7 When all the protons are precessing in the
to highlight the T1 differences of the various tissues. T1 W direction of M0 (due to the effect of B0) and an 180° inversion
which are normally bright on STIR sequences, may lose their

bright signal in STIR sequences when contrast is administered.
FLAIR Sequences
Normal CSF has a T1 of 3000 ms at 1.5 T. A TI of 2080 ms
(0.69 of 3000 ms) produces an image with no CSF signal.6
FLAIR sequences are used to suppress the bright signal of
CSF to allow better demarcation of lesions close to the
meninges. This allows easier visualization of gray and white
matter inflammation. However, it decreases the visibility of
cystic lacunae and old ischemic vacuolated foci in the brain.
On routine T2 W sequences, cystic lacunae and old ischemic
vacuolated foci in the brain appear bright due to their high
water content but on FLAIR sequences, they lose their bright
Fig. 5.5.1.18: Effect of 180° inversion pulse appearance and their conspicuity decreases.
on longitudinal magnetization
Fat Saturation Sequences
pulse is given, M0 inverts to –M0 in the opposite direction. On There are two types of sequences that are very useful in
cessation of the inversion pulse, the longitudinal magnetization orbital imaging as they suppress the bright signal of fat and
(Mz) gradually decreases from –M0, becomes zero and then thus permit other tissues to become more visible. The usual
increases to reach the initial M0 due to the influence of B0 MR sequences visualize hydrogen protons from both the
(Fig. 5.5.1.18). On application of a 90° excitation pulse, different water and fat molecules within the tissue. The STIR technique
results are obtained depending on the magnitude and direction is one technique to visualize only the water in the tissues.
of Mz at that point of time. The time difference between the Another method that produces water-only images is the fat
180° inversion pulse and the 90° excitation pulse is called saturation technique. It is based on the difference in the
inversion time (TI). It is a user selectable time. If the TI were resonant frequencies of the protons in fat and water. There
chosen so that at the time of the excitation pulse, a particular is a chemical shift difference of 3.5 ppm (parts per million)
tissue has its M0 as ‘0’, then, on application of the 90° rf pulse, in their resonant frequencies. The resonant frequency of the
M0 would not undergo any flipping to M in the y-axis and, protons in water at 1.5 T is 64 MHz and fat’s resonant
hence, that tissue would not contribute any signal to the final frequency is 220 Hz lower than it. This difference is used to
image. The tissue would thus appear dark on the image. This our advantage in this technique.6 First, one rf pulse centered
time, known as the null time, is determined by the T1 of the at the fat’s resonant frequency is applied to cause the
tissue. It is 0.69 of the T1 of the tissue. The two most common transverse magnetization of the fat protons. This transverse
applications are for fat and CSF suppression in STIR and magnetization of the fat protons is then dephased and
FLAIR sequences respectively. therefore no signal is recorded from the fat protons. A second
rf pulse centered at water’s resonant frequency is now applied.
STIR Sequences This causes transverse magnetization of the water protons.
The FID signals obtained for the MR images are from these
Fat has a T1 of 200 to 250 ms at 1.5 T. Therefore, if a TI of water protons only and the fat protons remain silent. Fat
140 to 160 ms (0.69 of T1 of fat) is selected, an image with suppression technique has two main advantages over STIR
no fat signal is formed.6 Thus, tissues with a bright signal on imaging. One advantage is that it can be incorporated into
T1 images (that are inconspicuous on routine T1 images due any type of imaging sequence. The other advantage is that it
to the bright signal of fat and the consequent lack of contrast can be used with T 1 relaxation contrast agents. Its
between the tissue and fat) become prominent in STIR images disadvantages are that it increases the slice loop time and the
due to the loss of the bright signal of fat. The disadvantage total rf energy deposition and that it is very sensitive to
of STIR is that it cannot be used with T1 relaxation contrast magnetic field inhomogeneity. The resonant frequency of
agents. T1 relaxation contrast agents shorten the T1 of water fat should be individualized to each patient to obtain optimum
to approach that of fat. Hence, tissues with high water content, results.
CT AND MRI PROTOCOLS FOLLOWED thin slices are obtained parallel to a line joining the posterior
IN OPHTHALMOLOGY foramen magnum to the hard palate.5
Most orbital soft tissue structures such as lacrimal glands,
Either CT scanning or MRI scanning may be used in most
extraocular muscles, vessels and uvea show uniform
situations when radiological imaging of the orbit is warranted.
enhancement on contrast administration.5 Contrast administration
Both the modalities have their advantages and disadvantages.
is needed to evaluate the vascular characteristics of a mass, to
CT scanning is the modality of choice when imaging bony
look for any intracranial extension of an orbital mass, e.g. a
lesions, metallic foreign bodies and in detecting calcifications.
meningioma; and in lesions such as sarcomas or metastatic bone
Its disadvantages are that it can cause side effects associated
disease.8 Contrast administration is not necessary in patients with
with ionizing radiation; its soft tissue delineation is not as good
foreign bodies, uncomplicated thyroid ophthalmopathy,
as in MRI scanning and it may not pick up intracanalicular
uncomplicated orbital fractures and osteomas.
optic nerve lesions due to beam hardening artifacts. MRI
scanning is superior when evaluating optic nerve lesions and MRI Scanning Protocols
orbital soft tissues. The contraindication to MRI scanning is
the presence of a ferromagnetic foreign body as it may move A routine MRI scanning protocol may consist of the following
under the influence of the strong magnetic field applied and sequences.
cause serious damage. Its other disadvantages are that it cannot • Sagittal T1W images obtained using short TRs and short
evaluate bony lesions and that it is more time consuming and TEs
expensive as compared to CT scanning. • Axial T2W images obtained using long TRs and long
TEs
CT Scanning Protocols • Additional coronal T1W or T2W images may be obtained.
T1W images are obtained if more anatomical details are
Routine orbital CT scanning consists of axial and coronal
required and T 2 W images are obtained if more
sectioning at intervals of 3 mm. Thinner sections of 1 to 1.5
pathological details are required
mm are required for detecting small foreign bodies, optic
• For optic nerve lesions, parasagittal images in the plane
nerve lesions and for imaging of the eyeball.
of the optic nerve are required
First, a lateral digital scout view (scanogram) is obtained.
• T 1 relaxation contrast agent administration may be
This view shows the levels at which the axial sections have
required. In such a case, T1W axial images are taken
been taken and also shows the slice thickness. The axial sections
before contrast administration and then taken again with
are obtained parallel to the infraorbital meatal line so that the
contrast administration and fat suppression
lens, the optic nerve and the horizontal recti can be seen in
• STIR sequences may also be performed as they suppress
one plane.8 As a routine, the axial sections extend superiorly
the bright signal of orbital fat and increase the conspicuity
from the level of the sella turcica and the frontal sinuses to
of a lesion
the upper part of the maxillary sinuses inferiorly. The extent
• Fat saturation sequences may also be used to subdue the
is increased if required. In patients with orbital tumors,
bright signal of orbital fat to make the soft tissue lesion
additional post-contrast 10 mm imaging of the head is done
more visible.
to look for any intracranial extension of the tumor.
Coronal sections are obtained perpendicular to the REFERENCES
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Ophthalmology. 2nd ed. Missouri: Mosby; 2004;31-6.
more oblique to avoid them (semi coronal views). The sections
2. Miraldi F, Sims MS, Wiesen EJ. Imaging principles in computed
extend from the nasal bones anteriorly to the optic chiasma tomography. In: Haaga JR, Lanzieri CF, Gilkeson RC, editors. CT
posteriorly but may be extended as required. If spiral scanning and MRI imaging of the whole body. 4th ed. Missouri: Mosby;
is available, then direct coronal scanning may be avoided to 2003;2-36.
decrease the radiation dose and computer reformatting may 3. Bae KT, Whiting BR. Basic principles of CT physics and technical
be done to obtain the coronal images. But direct coronal cuts considerations. In: Lee JKT, Sagel SS, Stanley RJ, Heiken JP,
editors. Computed body tomography with MRI correlation. 4th
are advisable for lesions at the 6 and 12 o’clock positions.
ed. Philadelphia: LWW 2006;1-28.
Computer reformatting may also be used to obtain images in 4. Grossman RI, Yousem DM. Techniques in neuroimaging. In:
sagittal, parasagittal or oblique planes.8 Direct sagittal images Grossman RI, Yousem DM, editors. The Requisites -
can also be obtained if required. For imaging the optic canal, Neuroradiology. 2nd ed. Pennsylvania: Mosby 2003;1-35.
5. Müller-Forell WS. Computed tomography. In: Müller-Forell WS, 7. Bellon EM, Diaz PJ, Duerk JL. Magnetic resonance physics: An
editor. Imaging of orbital and visual pathway pathology. introduction. In: Haaga JR, Lanzieri CF, Gilkeson RC, editors. CT
Heidelberg: Springer 2006;15-7. and MRI imaging of the whole body. 4th ed. Vol. 1. Missouri:
6. Brown MA, Semelka RC. Magnetic resonance imaging principles Mosby 2003;37-50.
and applications. In: Lee JKT, Sagel SS, Stanley RJ, Heiken JP, 8. Mafee MF. Orbit: Embryology, anatomy and pathology. In: Som
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ed. Philadelphia: LWW 2006;29-93. Mosby 2003;529-654.
5.5.2 Illustrative Imaging of the Normal Orbit

Vandana Kohli
Abnormalities can be picked up only if the images of the – The frontal lobes of the cerebrum
‘normal’ structures are well understood and to understand – The nasal bones
the images of the ‘normal’ structures: thorough knowledge – The nasal septum constituted by the perpendicular
of the orbital anatomy is a prerequisite. In the following plate of the ethmoid bone superiorly, the septal
illustrations, orbital images have been explained by showing cartilage in between and the vomer inferiorly
the structures usually visible on sequential coronal, axial and – The nasal cavity with the inferior turbinates
sagittal scans of the orbit. – The anterior eyeball wth a cut through the lens
The CT and MR images illustrated below are of different – The trochlea of the superior oblique at the
patients and hence, they do not exactly correspond to each superomedial corner
other. Further, the T1 images have been taken with a slice – The medial canthal tendon
thickness of 3.5 mm whereas the T2 fat suppressed images – The lower eyelid
have been taken with a slice thickness of 3.2 mm, hence, – The malar region
their images do not exactly correspond to each other. – A black void visible below the eyeball corresponds to
However, in the CT scan images, the soft tissue windows and the malar groove between the eyelid and the cheek.
the bone windows depict tissues at the same plane. The The CT scan and MRI scan of the anterior orbit is
description that follows is for the CT images depicted. The illustrated in Figures 5.5.2.1A to F.
MR images have minor variations vis-a-vis the description • Proceeding a little posteriorly (about 5 mm), the floor of
given. the orbit also becomes visible but the lateral wall is still
not visible as it does not extend that anteriorly.
CORONAL VIEWS Approximately half of the eyeball is anterior to the lateral
Coronal views can be understood by identifying the structures wall. Therefore, it can be appreciated that though the
while proceeding sequentially from the anterior sections to lateral wall is the thickest and the strongest orbital wall, it
the posterior sections. provides the least protection to the eyeball. The structures
that can be identified in these sections are illustrated in
Anterior Orbit Figures 5.5.2.2A to F. These include:
– The frontal process and the orbital surface of the
• In the most anterior views, only the roof and the medial maxilla constituting the medial wall and the floor of
wall of the orbit are visible as the floor and the lateral the orbit respectively
wall do not extend that anteriorly. The structures that – The lacrimal fossa with the lacrimal gland and the
may be identified on these sections include: proximal nasolacrimal duct
– The orbital plate of the frontal bone which forms the – The eyeball, the ocular coats and the vitreous body
roof of the orbit – The reflected tendon of the superior oblique
– The frontal sinus – The middle and inferior turbinates.
Figs 5.5.2.1A to F: Coronal views of the anterior orbit at the level of the anterior part of eyeball and trochlea (A) CT - Soft tissue window (B)
CT - Bone window (C) Corresponding diagram of soft tissue window (D) T1W MR image (E) T2W (fat suppressed) MR image (F) Corresponding
diagram of T1W MR image.
EB = eyeball, FB = frontal bone, FL = frontal lobe of cerebrum, FS = frontal sinus, FX = falx cerebri, IO = inferior oblique, IT = inferior turbinate,
L = lens, LE = lower eyelid, MCT = medial canthal tendon, MG = malar groove, ML = malar region, MT = middle turbinate, NB = nasal bone, NC
= nasal cavity, PE = perpendicular plate of ethmoidal bone, SC = septal cartilage, SPO = supraorbital vessels and nerve, T = trochlea, TSO =
tendon of superior oblique, VM = vomer.
On the MRI scans, note the inflammation of the nasal mucosa on the left side.
Figs 5.5.2.2A to F: Coronal views of the anterior orbit at the level of the middle part of the eyeball and the lacrimal sac (A) CT - Soft tissue
window (B) CT - Bone window (C) Corresponding diagram of soft tissue window (D) T1W MR image (E) T2W (fat suppressed) MR image
(F) Corresponding diagram of T1W MR image.
ALV = alveolar ridge, DL = diploe of the frontal bone, EB = eyeball, FB = frontal bone, FC = frontal crest, FL = frontal lobe of cerebrum, FM =
frontal process of maxillary bone, FS = frontal sinus, FX = falx cerebri, IO = inferior oblique muscle, IT = inferior turbinate, L = lens, LS = lacrimal
sac in lacrimal fossa, ML = malar region, MS = maxillary sinus, MT = middle turbinate, NLD = nasolacrimal duct, OM = orbital surface of maxilla,
PE = perpendicular plate of ethmoidal bone, SC = septal cartilage, SPO = supraorbital vessels and nerve, TSO = tendon of superior oblique, VM
= vomer.
Figs 5.5.2.3A to F: Coronal views of the anterior orbit at the level of the middle part of eyeball and the distal nasolacrimal duct (A) CT - Soft
tissue window (B) CT - Bone window (C) Corresponding diagram of soft tissue window (D) T1W MR image (E) T2W (fat suppressed) MR image
(F) Corresponding diagram of T1W MR image.
AEC = anterior ethmoidal cells, ALV = alveolar ridge, CH = chorioretina, DL = diploe of the frontal bone, EB = eyeball, FB = frontal bone, FC =
frontal crest, FL = frontal lobe of cerebrum, FS = frontal sinus, FX = falx cerebri, HP = hard palate, IO = inferior oblique muscle, IR = inferior
rectus, IT = inferior turbinate, M = mucosa covering hard palate, ML = malar region, MR = medial rectus, MS = maxillary sinus, MT = middle
turbinate, OF = orbital fat, OM = orbital surface of maxilla, OPL = opening of nasolacrimal duct into inferior meatus, OR = oral cavity, PE =
perpendicular plate of ethmoidal bone, SCL = sclera, SLC = superior rectus - LPS complex, SO = superior oblique, SPO = supraorbital vessels
and nerve, TG = tongue, TSO = tendon of superior oblique, VT = vitreous.
• Proceeding further posteriorly (about 3.75 mm), the • Proceeding further posteriorly (about 8.75 mm), the
following structures may be identified: structures identifiable remain the same but they come
– The lamina papyracea of the ethmoidal bone closer together. In addition, the diploe of the greater wing
constituting the medial wall of the orbit of the sphenoid, which forms the lateral orbital wall,
– The inferior oblique running from the bone lateral to becomes apparent. This is a very important surgical
the lacrimal fossa towards the eyeball landmark during lateral orbitotomy as it indicates that the
– The reflected tendon of the superior oblique temporal lobe of the cerebrum is close. The anterior end
– The zygomatic process of the frontal bone of the inferior orbital fissure also becomes visible. The
– The anterior ethmoidal air cells structures are identified in Figures 5.5.2.6A to F.
– The distal nasolacrimal duct opening into the inferior
meatus Posterior Orbit
– The anterior maxillary sinus. • Proceeding further posteriorly (about 6.25 mm), the
These structures are identified in Figures 5.5.2.3A to F. following structures are visible at the orbital apex.
• Further posteriorly (about 6.25 mm), the following – The extraocular muscles and the optic nerve bundled
structures become visible: close together and it may not be possible to discern
– The lateral orbital rim constituted by the zygomatic them separately
bone – The inferior orbital fissure opening into the
– The frontozygomatic suture pterygopalatine fossa inferiorly
– All the extraocular muscles and the intermuscular – The posterior ethmoidal air cells
septum – The temporal lobe of the cerebrum laterally
– The lacrimal gland – The temporalis muscle inserting onto the mandible
– The superior ophthalmic vein – The zygomatic arch
– The infraorbital canal – The ramus of the mandible
– The crista galli, the cribriform plate and the olfactory – The masseter muscle.
bulb These structures are identified in Figures 5.5.2.7A to F.
– The maxillary sinus opening into the nasal cavity. • Proceeding further posteriorly (about 5 mm), at the
These structures are identified in Figures 5.5.2.4A to H. superolateral corner of the apex, the superior orbital
fissure can be seen opening into the middle cranial fossa
Mid-orbit and inferiorly the inferior orbital fissure can be seen. The
sphenoid sinus also becomes visible. These structures are
• Proceeding further posteriorly (about 10 mm), the
illustrated in Figures 5.5.2.8A to F.
following structures may be identified:
• Proceeding further posteriorly (about 2.5 mm), the orbital
– All the orbital walls
apex can be seen ending at the optic canal running
– The thick bellies of the recti
superomedially and the superior orbital fissure
– The thin superior oblique at the superomedial corner
superolaterally. The lesser wing of the sphenoid can be
– The superior ophthalmic vein below the LPS-SR
made out and the close proximity of the optic canal to
complex the sphenoid sinus can be appreciated. The transsphenoidal
– The ophthalmic artery near the SO route, thus, provides one route for surgically approaching
– The optic nerve the intracanalicular optic nerve. The temporalis muscle
– The inferior ophthalmic vein below the optic nerve can be seen inserting onto the mandible. These structures
– The infraorbital canal are identified in Figures 5.5.2.9A to F.
– The middle ethmoidal air cells • Proceeding further (about 2.5 mm), the anterior clinoid
– All the turbinates process of the lesser wing of the sphenoid, the posterior
– The zygomatic arch part of the optic canal, the foramen rotundum, the
– The temporalis muscle pterygoid plates and the pterygoid muscles can be
– The masseter muscle originating from the zygomatic arch. appreciated. These structures are identified in Figures
These structures are identified in Figures 5.5.2.5A to F. 5.5.2.10A to G.
• Proceeding further (about 6.25 mm), the anterior clinoid just above the chiasma. These structures are illustrated in
process of the lesser wing of sphenoid, the sphenoid sinus Figures 5.5.2.13A to D.
and the nasopharynx are visible. On serial images, it can be
well appreciated that the optic nerve runs superomedially AXIAL VIEWS
to reach the optic chiasma. These structures are illustrated
Superior Orbit
in Figures 5.5.2.11A to F.
• Proceeding further posteriorly, the optic chiasma, the • When viewing the axial views of CT scans, a view through
pituitary gland situated above the sphenoid sinus in the the most superior part of the orbit would depict the
sella turcica, the internal carotid artery, the cavernous superior orbital rim, the superior parts of the medial and
sinus with the structures in its walls, the middle cerebral lateral orbital walls and a circular shape of the orbital
arteries, the lateral sulcus, insula and the lateral ventricles cavity. The supraorbital vessels may be seen between the
can be identified. These structures are illustrated in Figures roof and the levator palpebrae superioris (LPS). A faint
5.5.2.12A to D. image of the LPS-SR complex is visible. Medial to the
• Proceeding further posteriorly, the optic chiasma may be orbits, the frontal sinuses, the crista galli and the frontal
visible above the pituitary gland and its stalk. The siphon lobes of the cerebrum are visible and lateral to the orbit,
of internal carotid artery and the terminal branches of the temporalis muscle is visible.
the artery—the anterior cerebral artery and the middle In MRI films, the orbital fat, the supraorbital vessels,
cerebral artery are visible. The third ventricle is visible the LPS muscle and the orbital septum can be identified.
Figs 5.5.2.4A to H: Coronal views of the anterior orbit at the level of the posterior part of eyeball (A) CT - Soft tissue window (B) CT - Bone
window (C) Corresponding diagram of soft tissue window (D) Corresponding diagram of bone window (E) T1W MR image (F) T2W (fat
suppressed) MR image (G) T2W (FLAIR) MR image (H) Corresponding diagram of T1W MR image.
AEC = anterior ethmoidal cells, CG = crista galli, CP = cribriform plate, DL = diploe of the frontal bone, FB = frontal bone, FL = frontal lobe of
cerebrum, FZS = frontozygomatic suture, IMS = intermuscular septum, IOC = infraorbital canal, IR = inferior rectus, IT = inferior turbinate, LG
= lacrimal gland, LP = lamina papyracea, LPS = levator palpebrae superioris, LR = lateral rectus, MR= medial rectus, MS = maxillary sinus, MT
= middle turbinate, OF = orbital fat, OPM = opening of maxillary sinus into nasal cavity, SLC = superior rectus - LPS complex, SO = superior
oblique, SOV = superior ophthalmic vein, SR = superior rectus, ZB = zygomatic bone.
The gyrus rectus, optic chiasma, optic tract, infundibulum, artery and posterior cerebral artery may be visible. These
middle cerebral artery, midbrain with its aqueduct and structures are identified in Figures 5.5.2.15A to F.
crus cerebri can be identified. • Proceeding further inferiorly (about 5 mm), the superior
These structures are identified in Figures 5.5.2.14A eyeball becomes visible. The structures that can be
to D. identified include:
• Proceeding inferiorly (about 2.5 mm), the LPS-SR – The superior oblique—its belly, trochlea and the
complex, the trochlea and the reflected tendon of the reflected tendon
superior oblique and the lacrimal gland are depicted very – The lacrimal gland
well on the CT films. On MRI films, the intracranial optic – The superior ophthalmic vein running posterolaterally
nerve, optic chiasma, infundibulum, middle cerebral to reach the lateral part of the SOF
artery, internal carotid artery, posterior communicating – The superior orbital fissure
Figs 5.5.2.5A to F: Coronal views of the mid-orbit (A) CT - Soft tissue window (B) CT - Bone window (C) Corresponding diagram of soft
tissue window (D) T1W MR image (E) T2W (fat suppressed) MR image (F) Corresponding diagram of T1W MR image.
CSF = cerebrospinal fluid, GM = grey matter, IOV = inferior ophthalmic vein, IR = inferior rectus, LP = lamina papyracea, LR = lateral rectus,
MEC = middle ethmoidal air cells, MM = masseter muscle, MR= medial rectus, MS = maxillary sinus, OA = ophthalmic artery, OF = orbital fat,
OM = orbital plate of maxilla, ON = optic nerve, SLC = superior rectus - LPS complex, SO = superior oblique, SOV = superior ophthalmic vein,
ST = superior turbinate, TM = temporalis muscle, WM = white matter, ZA = zygomatic arch, ZB = zygomatic bone.
Figs 5.5.2.6A to F: Coronal views of the mid-orbit at a more posterior level (A) CT - Soft tissue window (B) CT - Bone window (C) Corresponding
diagram of soft tissue window (D) T1W MR image (E) T2W (fat suppressed) MR image (F) Corresponding diagram of T1W MR image.
ES = ethmoidal sinus, GR = gyrus rectus, GW = greater wing of sphenoid, IOF = inferior orbital fissure, IR = inferior rectus, LR = lateral rectus,
MM = masseter muscle, MR= medial rectus, MS = maxillary sinus, OA = ophthalmic artery, ON = optic nerve, SLC = superior rectus - LPS
complex, SO = superior oblique, SOG = superior orbital gyrus, SOV = superior ophthalmic vein, ST = superior turbinate, TM = temporalis
muscle, ZA = zygomatic arch.
Figs 5.5.2.7A to F: Coronal views of the posterior orbit (A) CT - Soft tissue window (B) CT - Bone window (C) Corresponding diagram of
soft tissue window (D) T1W MR image (E) T2W (fat suppressed) MR image (F) Corresponding diagram of T1W MR image.
IOF = inferior orbital fissure, IR = inferior rectus, LR = lateral rectus, MM = masseter muscle, MR= medial rectus, MS = maxillary sinus, ON =
optic nerve, PEA = posterior ethmoidal air cells, PPF = pterygopalatine fossa, RM = ramus of mandible, SLC = superior rectus - LPS complex,
SO = superior oblique, SOV = superior ophthalmic vein, TL = temporal lobe, TM = temporalis muscle, ZA = zygomatic arch.
Figs 5.5.2.8A to F: Coronal views at the orbital apex (A) CT - Soft tissue window (B) CT - Bone window (C) Corresponding diagram of soft
tissue window (D) T1W MR image (E) T2W (fat suppressed) MR image (F) Corresponding diagram of T2W MR image.
CSF = cerebrospinal fluid, CV = cerebral veins, GM = gray matter, IOF = inferior orbital fissure, IT = inferior turbinate, LVT = lateral ventricle,
MM = masseter muscle, MT = middle turbinate, NC = nasal cavity, ON = optic nerve, OX = orbital apex, PPF = pterygopalatine fossa, RM =
ramus of mandible, SOF = superior orbital fissure, SS = sphenoidal sinus, TL = temporal lobe, TM = temporalis muscle, WM = white matter, ZA
= zygomatic arch.
Figs 5.5.2.9A to F: Coronal views at the anterior end of optic canal (A) CT - Soft tissue window (B) CT - Bone window (C) Corresponding
FL = frontal lobe, LPP = lateral pterygoid plate, LVT = lateral ventricle, LW = lesser wing of sphenoid, MPP = medial pterygoid plate, NC = nasal
cavity, OC = optic canal, ON = optic nerve, OX = orbital apex, RM = ramus of mandible, SOF = superior orbital fissure, SS = sphenoidal sinus,
STR = structures passing through superior orbital fissure, TL = temporal lobe, TM = temporalis muscle, ZA = zygomatic arch.
Figs 5.5.2.10A to G: Coronal views at the middle of the optic canal

(A) CT - Soft tissue window (B) CT - Bone window (C) Corresponding
diagram of soft tissue window (D) Corresponding diagram of bone
window (E) T1W MR image (F) T2W (fat suppressed) MR image
(G) Corresponding diagram of T1W MR image.
COR = corpus callosum, FL = frontal lobe, FR = foramen rotundum, LPM
= lateral pterygoid muscle, LPP = lateral pterygoid plate, LVT = lateral
ventricle, LW = lesser wing of sphenoid, MPM = medial pterygoid muscle,
MPP = medial pterygoid plate, NC = nasal cavity, OC = optic canal, ON =
optic nerve, PE = perpendicular plate of ethmoid, RM = ramus of mandible,
SOF = superior orbital fissure, SS = sphenoidal sinus, STR = structures
passing through superior orbital fissure, TL = temporal lobe, TM = temporalis
muscle, VC = vidian canal, ZA = zygomatic arch.
Figs 5.5.2.11A to F: Coronal views at the posterior end of the optic canal (A) CT - Soft tissue window (B) CT - Bone window (C) Corresponding
ACP = anterior clinoid process, COR = corpus callosum, FL = frontal lobe, ICA = internal carotid artery, LPP = lateral pterygoid plate, LVT =
lateral ventricle, NP = nasopharynx, OC = optic canal, ON = optic nerve, SS = sphenoidal sinus, TL = temporal lobe, ZA = zygomatic arch.
Figs 5.5.2.12A to D:Coronal views at the level of the optic chiasma (A) T1W MR image (B) Corresponding diagram of T1W MR image
(C) T2W (fat suppressed) MR image (D) Corresponding diagram of T2W MR image.
COR = corpus callosum, CS = cavernous sinus, HC = head of caudate nucleus, IC = internal capsule, ICA = internal carotid artery, IN = insula,
LN = lentiform nucleus, LSU = lateral sulcus, LVT = lateral ventricle, MCA = middle cerebral artery, OCH = optic chiasma, PG = pituitary gland,
PL = parietal lobe, SS = sphenoidal sinus, TL = temporal lobe.
– The zygomatic bone and the greater wing of the On MRI films, the lacrimal vein joining the
sphenoid forming the lateral orbital wall. Recall that superior ophthalmic vein, intracanalicular optic nerve
the diploe of the greater wing of the sphenoid is an near the sphenoid sinus, internal carotid artery, pons,
important surgical landmark during lateral orbitotomy basilar artery and fourth ventricle may be made out.
as it gives a warning that further posterior nibbling of These structures are illustrated in Figures 5.5.2.16A to G.
the lateral orbital wall cannot be done as the temporal • Proceeding further inferiorly (about 2.5 mm), the visible
cerebral lobe is close structures include:
– The frontal sinuses – The eyeball
– The crista galli and the gyrus rectus of the frontal – The lacrimal gland
lobe – The superior parts of medial and lateral recti
– The anterior clinoid process of the lesser wing of the – The superior part of retrobulbar optic nerve
sphenoid – The ophthalmic artery crossing over anteromedially
– The temporal cerebral lobe, the temporal bone and over the optic nerve
the temporalis muscle. – The anterior ethmoidal vessels
Figs 5.5.2.13A to D: Coronal views at the level of the pituitary stalk (A) T1W MR image (B) Corresponding diagram of T1W MR image
(C) T2W (fat suppressed) MR image (D) Corresponding diagram of T2W MR image.
ACA = anterior cerebral artery, COR = corpus callosum, HC = head of caudate nucleus, IC = internal capsule, ICA = internal carotid artery, IN
= insula, LN = lentiform nucleus, LVT = lateral ventricle, MCA = middle cerebral artery, OCH = optic chiasma, PCP = posterior clinoid process
of the dorsum sella, PG = pituitary gland, PS = pituitary stalk, SS = sphenoidal sinus, TL = temporal lobe.
– Fine orbital vessels – The lacrimal gland

– The optic canal with the optic nerve – The nasal bone, the frontal process of the maxilla,
– The superior orbital fissure the lacrimal bone, the lamina papyracea and the body
– The anterior clinoid process of the sphenoid medially
– The dorsum sella – The ethmoidal and sphenoidal sinuses
– The frontal and ethmoidal sinuses – The nasal cavity and the nasal septum
– The crista galli and the olfactory bulbs. – The superior orbital fissure
These structures are illustrated in Figures 5.5.2.17A to F. – The pituitary gland
– The dorsum sella.
Midorbit These structures are illustrated in Figures 5.5.2.18A to D.
• Proceeding further inferiorly (about 7.5 mm), the
• Proceeding further inferiorly (about 3.75 mm), the structures visible are:
following structures are visible: – The eyeball, often with a cut through the lens if the
– The eyeball and the optic nerve patient is looking inferiorly
– The medial and lateral recti (their muscle bellies and – The medial rectus, lateral rectus and the origin of the
their tendons) inferior rectus
Figs 5.5.2.14A to D: Axial views of the superior orbit at the level of the supraorbital vessels (A) CT - Soft tissue window (B) Corresponding
diagram of soft tissue window (C) T1W MR image (D) Corresponding diagram of T1W MR image.
AQ = cerebral aqueduct, CBL = cerebellum, CC = crus cerebri, FB = frontal bone, FC = frontal crest, FL = frontal lobe of cerebrum, FS = frontal
sinus, GR = gyrus rectus, MB = midbrain, MCA = middle cerebral artery, OCH = optic chiasma, OL = occipital lobe, OT = optic tract, PS =
pituitary stalk, SLC = superior rectus- levator palpebrae superioris complex, SPO = supraorbital vessels and nerve, TM = temporalis muscle,
UN = uncus.
– The ethmoid and sphenoid sinuses – The frontal process of the maxilla, the anterior lacrimal
– The increased mass of temporalis muscle crest, the lacrimal bone and the lamina papyracea
– The nasal cavity and the nasal septum. – The ethmoidal and sphenoidal sinuses
These structures are illustrated in Figures 5.5.2.19A to F. – The nasal cavity and the nasal septum
– The superior and middle turbinates
Inferior Orbit – The inferior orbital fissure
– The pterygopalatine fossa
• Proceeding further inferiorly (about 7.5 mm), the – Foramen rotundum with its maxillary nerve
structures that can be identified are: – The internal carotid artery.
– The inferior eyeball These structures are illustrated in Figures 5.5.2.20A to F.
– The inferior rectus • Proceeding further inferiorly (about 2.5 mm), the
– The insertion of the inferior oblique structures that can be identified are:
– The lacrimal sac in the lacrimal fossa – The inferior eyeball
Figs 5.5.2.15A to F: Axial views of the superior orbit at the level of the superior rectus- levator palpebrae superioris complex (A) CT - Soft
tissue window (B) Corresponding diagram of soft tissue window (C) T1W MR image (D) T2W MR image (E) Corresponding diagram of T1W MR
image (F) Corresponding diagram of T2W MR image.
BA = basilar artery, CBL = cerebellum, FB = frontal bone, FC = frontal crest, FL = frontal lobe of cerebrum, FS = frontal sinus, ICA = internal
carotid artery, LG = lacrimal gland, LPS = levator palpebrae superioris, LV = lacrimal vein, LVT = lateral ventricle, MB = midbrain, MCA = middle
cerebral artery, OCH = optic chiasma, OL = occipital lobe, ON = optic nerve, PCA = posterior cerebral artery, PCM = posterior communicating
artery, PS = pituitary stalk, RN = red nucleus, SLC = superior rectus-levator palpebrae superioris complex, SOV = superior ophthalmic vein,
T = trochlea, TM = temporalis muscle, TSO = tendon of superior oblique.
Figs 5.5.2.16A to G: Axial views of the superior orbit at the level of the
superior oblique (A) CT - Soft tissue window (B) CT - Bone window (C)
Corresponding diagram of soft tissue window (D) Corresponding
diagram of bone window (E) T1W MR image (F) T2W MR image (G)
Corresponding diagram of T1W MR image.
ACP = anterior clinoid process, BA = basilar artery, CBL = cerebellum,
CG = crista galli, DGW = diploe of greater wing of sphenoid, EB =
eyeball, ES = ethmoidal sinus, FL = frontal lobe of cerebrum, FS = frontal
sinus, FV = fourth ventricle, GW = greater wing of sphenoid, ICA =
internal carotid artery, LG = lacrimal gland, LV = lacrimal vein, LVT =
lateral ventricle, OC = optic canal, OL = occipital lobe, OO = orbicularis
oculi, ON = optic nerve, OS = orbital septum, PCA = posterior cerebral
artery, PN = pons, SO = superior oblique, SOF = superior orbital fissure,
SOV = superior ophthalmic vein, SS = sphenoidal sinus, T = trochlea, TL
= temporal lobe, TM = temporalis muscle, TSO = tendon of superior
oblique, ZB = zygomatic bone.
Figs 5.5.2.17A to F: Axial views of the superior orbit at the level of the ophthalmic artery (A) CT - Soft tissue window (B) CT - Bone window
(C) Corresponding diagram of soft tissue window (D) T1W MR image (E) T2W MR image (F) Corresponding diagram of T1W MR image.
ACP = anterior clinoid process, AEV = anterior ethmoidal vessels, BA = basilar artery, CBL = cerebellum, CG = crista galli, DS = dorsum sella,
EB = eyeball, ES = ethmoidal sinus, FOV = fine orbital vessels, FS = frontal sinus, FV = fourth ventricle, GW = greater wing of sphenoid, ICA
= internal carotid artery, LG = lacrimal gland, LR = lateral rectus, LVT = lateral ventricle, MR = medial rectus, NB = nasal bone, OA = ophthalmic
artery, OB = olfactory bulb, OC = optic canal, ON = optic nerve, OS = orbital septum, PG = pituitary gland, PN = pons, SOF = superior orbital
fissure, SS = sphenoidal sinus, STR = structures that pass through superior orbital fissure, TM = temporalis muscle, TSO = tendon of superior
oblique, ZB = zygomatic bone.
Figs 5.5.2.18A to D: Axial views of the mid-orbit (A) CT - Soft tissue window (B) Corresponding diagram of soft tissue window
(C) T1W MR image (D) Corresponding diagram of T1W MR image.
BA = basilar artery, BS = body of sphenoid, CBL = cerebellum, DS = dorsum sella, EB = eyeball, ES = ethmoidal sinus, FM = frontal process of
maxilla, FOV = fine orbital vessels, FV = fourth ventricle, GW = greater wing of sphenoid, ICA = internal carotid artery, LB = lacrimal bone, LG =
lacrimal gland, LP = lamina papyracea, LR = lateral rectus, MR = medial rectus, NB = nasal bone, NC = nasal cavity, NS = nasal septum, OF =
orbital fat, ON = optic nerve, PCP = posterior clinoid process of dorsum sella, PG = pituitary gland, PIN = pinna, PN = pons, SOF = superior orbital
fissure, SS = sphenoidal sinus, STR = structures that pass through superior orbital fissure, TM = temporalis muscle, ZB = zygomatic bone
– The proximal nasolacrimal duct – The inferior oblique originating just inferolateral to
– The beginning of the maxillary sinus the lacrimal fossa and running posterolaterally towards
– The ethmoidal and sphenoidal sinuses the globe
– The nasal cavity, the nasal septum and the middle – The bony nasolacrimal duct
turbinate – The maxillary and the ethmoidal sinuses
– The inferior orbital fissure, the pterygopalatine fossa – The nasal cavity, the nasal septum and the middle
and the infratemporal fossa turbinate
– The zygomatic arch – The inferior orbital fissure, the infratemporal fossa
– These structures are illustrated in Figures 5.5.2.21A – The zygomatic arch
to E. – The temporalis muscle.
• Proceeding further inferiorly (about 3.75 mm), the These structures are illustrated in Figures 5.5.2.22A
structures that can be identified are: to E.
Figs 5.5.2.19A to F: Axial views of the mid-orbit at a lower level (A) CT - Soft tissue window (B) CT - Bone window (C) Corresponding
diagram of soft tissue window (D) T1W MR image (E) T2W MR image (F) Corresponding diagram of T1W MR image.
BA = basilar artery, CBL = cerebellum, ES = ethmoidal sinus, FM = frontal process of maxilla, FOV = fine orbital vessels, FV = fourth ventricle,
GW = greater wing of sphenoid, ICA = internal carotid artery, IR = inferior rectus, L = lens, LB = lacrimal bone, LP = lamina papyracea, LR =
lateral rectus, LS = lacrimal sac, MR = medial rectus, NB = nasal bone, NC = nasal cavity, NS = nasal septum, PIN = pinna, PN = pons, SOF
= superior orbital fissure, SS = sphenoidal sinus, TL = temporal lobe, TM = temporalis muscle, TN = trigeminal nerve.
Figs 5.5.2.20A to F: Axial views of the inferior orbit at the level of the inferior lacrimal sac (A) CT - Soft tissue window (B) CT - Bone window
(C) Corresponding diagram of soft tissue window (D) T1W MR image (E) T2W MR image (F) Corresponding diagram of T1W MR image.
ALC = anterior lacrimal crest, BA = basilar artery, CBL = cerebellum, ES = ethmoidal sinus, FM = frontal process of maxilla, FOV = fine orbital
vessels, FR = foramen rotundum, GW = greater wing of sphenoid, ICA = internal carotid artery, IO = inferior oblique, IOF = inferior orbital fissure,
IR = inferior rectus, LP = lamina papyracea, LS = lacrimal sac, MT = middle turbinate, NS = nasal septum, PN = pons, PPF = pterygopalatine
fossa, SS = sphenoidal sinus, ST = superior turbinate, TL = temporal lobe, TM = temporalis muscle, ZB = zygomatic bone.
Figs 5.5.2.21A to E: Axial views of the inferior orbit at the level of the
proximal nasolacrimal duct (A) CT - Soft tissue window (B) CT - Bone
window (C) Corresponding diagram of soft tissue window (D) T1W
MR image (E) Corresponding diagram of T1W MR image.
BA = basilar artery, CBL = cerebellum, ES = ethmoidal sinus, FM =
frontal process of maxilla, GW = greater wing of sphenoid, ICA =
internal carotid artery, IOF = inferior orbital fissure, IR = inferior rectus,
ITF = infratemporal fossa, MO = medulla oblongata, MS = maxillary
sinus, MT = middle turbinate, NLD = nasolacrimal duct, OV = olive, PB
= petrous bone, PE = perpendicular plate of ethmoid, PPF =
pterygopalatine fossa, PY = pyramid, SC = septal cartilage, SS =
sphenoidal sinus, TM = temporalis muscle, ZA = zygomatic arch, ZB
= zygomatic bone.
• Proceeding further inferiorly (about 5 mm), the structures – Medial to it, the maxillary nerve in the infraorbital canal
that can be identified are: running anteromedially to open into the facial tissues
– The most inferior part of the orbit which is its – The nasolacrimal duct in the lateral wall of the nose
anterolateral corner – The nasal cavity and the nasal septum
Figs 5.5.2.22A to E: Axial views of the inferior orbit at the level of the
inferior oblique (A) CT - Soft tissue window (B) CT - Bone window
(C) Corresponding diagram of soft tissue window (D) T1W MR image
(E) Corresponding diagram of T1W MR image.
CBL = cerebellum, GW = greater wing of sphenoid, IO = inferior oblique,
IOF = inferior orbital fissure, IOV = inferior ophthalmic vein, ITF =
infratemporal fossa, MO = medulla oblongata, MS = maxillary sinus,
MT = middle turbinate, NLD = nasolacrimal duct, PE = perpendicular
plate of ethmoid, SC = septal cartilage, TM = temporalis muscle, VA =
vertebral artery, ZA = zygomatic arch.
SAGITTAL SECTION
On sagittal sections, at the level of the lens, the superior and
inferior recti and the optic nerve can be seen along their length.
– The inferior end of the middle turbinate The sloping of the roof and the floor can be well appreciated
– The inferior turbinate in these views. While repairing an orbital floor fracture, this
– The maxillary sinus factor has to be considered to prevent postoperative
– The zygomatic arch and the temporalis enophthalmos. The pterygomaxillary fissure may be seen behind
– The medial and lateral pterygoid plates and muscles. the maxillary sinus.
These structures are illustrated in Figures 5.5.2.23A to E. These structures are illustrated in Figures 5.5.2.24A to E.
Figs 5.5.2.23A to E: Axial views of the inferior orbit at the most inferior
part of the orbit (A) CT - Soft tissue window (B) CT - Bone window
(C) Corresponding diagram of bone window (D) T1W MR image
(E) Corresponding diagram of T1W MR image.
CBL = cerebellum, EAM = external auditory meatus, ICA = internal
carotid artery, IOC = infraorbital canal, IT = inferior turbinate, LPM =
lateral pterygoid muscle, LPP = lateral pterygoid plate, MO = medulla
oblongata, MPM = medial pterygoid muscle, MPP = medial pterygoid
plate, MS = maxillary sinus, MT = middle turbinate, NLD = nasolacrimal
duct, NS = nasal septum, OF = orbital fat, PIN = pinna, TM = temporalis
muscle, VA = vertebral artery, ZA = zygomatic arch.
Figs 5.5.2.24A to E: Sagittal view of the orbit (A) CT - Soft tissue

window (B) CT - Bone window (C) Corresponding diagram of soft
tissue window (D) T1W MR image (E) Corresponding diagram of T1W
MR image.
ALV = alveolar process of maxilla, CBL = cerebellum, EB = eyeball, FB
= frontal bone, FL = frontal lobe, GM = gray matter, IR = inferior rectus,
LV = lateral ventricle, MS = maxillary sinus, OF = orbital fat, OL =
occipital lobe, OM = orbital surface of maxilla, ON = optic nerve, PMF
= pterygomaxillary fissure, SLC = superior rectus - LPS complex, TL
= temporal lobe, WM = white matter
5.5.3 Diagnostic Ophthalmic Ultrasonography

Karandeep Rishi, Pradeep Venkatesh
Ultrasound is cyclic sound pressure with a frequency greater tumors. Oksala and Lehtinen2 of Finland described clinical
than the upper limit of human hearing. Although this limit examinations with a handheld A-mode transducer. Earlier
varies from person to person, it is approximately 20 kHz transducers had frequency in the range of 4 MHz. Displays
(20,000 Hz) in healthy, young adults and thus, 20 kHz serves were generated on oscilloscopes, and photography was used
as a useful lower limit in describing ultrasound. for recording; biometric results were computed with the use
Medical sonography (ultrasonography) is an ultrasound-based of rulers to measure echo time intervals, producing variable
diagnostic medical imaging technique used to visualize muscles, results. Advances in biometric precision were made by
tendons, and many internal organs, to capture their size, increasing transducer frequencies and using more advanced
structure and any pathological lesions with real time time measurement techniques to replace ruler measurements
tomographic images. of photographed A-mode displays. Initial developments in
The ophthalmic ultrasound requirements differ from other diagnosing ocular diseases emphasized A-mode techniques.
specialities in the need to examine small structures. This Oksala and Lehtinen2,3 studied a broad variety of ocular
requires the use of higher frequencies, which is possible due conditions with a clinical A-mode system. They methodically
to superficial location of eye and water like contents which cataloged echo features for detached retinas, vitreous
absorbs sound waves to a lesser extent. Ophthalmic systems hemorrhages, foreign bodies, and ocular tumors. B-mode
have evolved along two complementary paths: biometry and techniques for ocular examinations were first developed by
diagnosis. A-mode biometric systems were developed to Baum and Greenwood 4 in the late 1950s. Pavlin et al 5
measure the axial length of eye for proper calculation of the introduced a 50 MHz instrument using a polyvinylidene
intraocular lens power. The eventual advent of gray scale difluoride transducer and a sector scanner that provided
systems alleviated much of the need for complementary A- excellent definition of the segments of the anterior segment
mode observations for tissue identification. The first of the eye. They termed this the ultrasonic biomicroscope.
application of diagnostic ultrasound in the eye was reported This permits very high resolution imaging of the entire
by Mundt and Hughes in 1956. 1(Fig. 5.5.3.1) They used anterior segment. The use of computer power to provide
industrial flaw detection equipment for A-mode examination scan storage and reconstruction of serial plane scan data as
of in vitro enucleated eyes and patients with intraocular 3D images, is the new area of development. The first
ophthalmic 3D scans were by Coleman et al6 who showed
the value of measuring volume changes such as in ocular
tumor growth. New techniques like frequency domain
processing help to improve resolution and to characterize
tissue microstructure. Doppler visualization is proving to be
particularly helpful in evaluation of posterior and orbital
tumors. Advanced flow characterization techniques, developed
by Ferrara et al7 and Silverman et al8 have mapped flow
within small vessels of the iris and ciliary body, which may be
helpful in better understanding of diseases like glaucoma.
ULTRASONOGRAPHY
A-Scan
Two primary types of A-scan are used in ophthalmic
Fig. 5.5.3.1: Diagram showing the frequency range of sound ultrasonography; biometric A-scan and standardized diagnostic
waves and the wavelengths used for diagnostic ultrasound A-scan.
Biometric A-scan is optimized for axial eye length ULTRASOUND BIOMICROSCOPY

measurements. It uses a probe with an operating frequency Ultrasound biomicroscopy uses the principle of increasing the
of 10 to 12 MHz and a linear amplification curve. The resolution of the image by increasing the frequency (50 MHz),
primary function of biometric A-scan in ophthalmology is to thus losing depth of penetration (5 mm). The piezoelectric
determine the axial eye lengths for patients undergoing cataract
polymer polyvinylidene difluoride and co-polymer
surgery so that the dioptric power of the intraocular lens to
polyvinylidene difluoride/trifluoroethylene have been used for
be implanted can be determined accurately.
this purpose. A fluid immersion technique is required to prevent
Standardized A-scan is a special diagnostic instrument
contact of the transducer and the eye which may cause
developed by Ossoinig.9,10 It uses a probe with an operating
distortion of the image and corneal abrasion. The structures
frequency of 8 MHz and an S-shaped amplification curve.
Standardized A-scan is designed to display an echo spike for visualized are anterior chamber, cornea with all of its layers,
retina that is 100 percent on the echo intensity scale when AC angle structures, conjunctiva, sclera, muscle insertions, iris,
the sound beam is directed perpendicular to the retina. Highly ciliary body, zonules, lens and ora serrata. It is useful in
dense ocular structures, including choroid and sclera, also glaucoma, corneal and scleral disease, intraocular lens
produce 100 percent echo spikes. All intraocular structures complications, trauma (to look for cyclodialysis clefts, ciliary
that have a density lower than retina, including vitreous body membranes, small foreign bodies), conjunctival and adnexal
opacities and membranes, produce echoes of less than 100 disease, anterior segment tumors, iris tumors, ciliary body
percent intensity. tumors, extrascleral extension of intraocular tumors, corneal
involvement, iridociliary cyst, peripheral choroidal tumors, etc.
B-scan
BIOMETRY
Contact B-scan is a two-dimensional display of echoes using
The measurement of axial eye length is one of the most
horizontal and vertical orientations to show shape, location,
important steps for IOL lens power calculation. An error in
and extension. Dots on the screen represent echoes, and the
axial length measurement of 1 mm can cause an error in
strength of the echo is determined by the brightness of the
IOL power of 2.5D (approximately). A-scan biometry includes
dot. Most ophthalmic ultrasound machines use logarithmic
two main techniques, the contact method and the immersion
or S-shaped amplification and a frequency in the range of 10
technique.
MHz. B-scan evaluation is a dynamic process that requires
specific attention to the mobility of the displayed echoes. Contact Method
Standardized echography, the combined use of contact
Here, the ultrasound probe directly touches the cornea. The
B-scan and standardized A-scan, is often used in clinical
first spike represents the probe tip placed on the cornea,
ophthalmology to evaluate the ocular structures in hazy media.
followed by the anterior lens capsule, posterior lens capsule,
Three basic probe positions used in ophthalmology are:
vitreous cavity, retina, sclera, and orbital tissue echoes. Studies
1. Axial: Probe to face directly over the center of the cornea,
have demonstrated a mean shortening of axial length by 0.1
image passing through the lens, bisecting the optic nerve.
to 0.33 mm using the contact technique compared with
2. Longitudinal: Probe to be placed on the conjunctiva
immersion technique.11,12
overlying the sclera and directed through the vitreous
bypassing the lens along a specific clock hour, displaying
Immersion Technique
the anterior portion of the eye at the top of the screen
and the optic nerve at the bottom. This method eliminates compression of the globe, so it is
3. Transverse: Produce a lateral cross-section of the eye that comparatively more accurate. In the immersion technique, a
results in an image with the superior or nasal aspect scleral shell filled with fluid is placed over the cornea while
displayed at the top of the screen and the inferior or the patient lies supine. The probe is immersed in the fluid
temporal aspect displayed at the bottom of the screen. overlying the cornea. This method is important in eyes with a
Immersion B-scan is valuable in the evaluation of small axial length. In a normal phakic eye, the average
pathology located near the ora serrata (anterior limit of the ultrasound velocity is 1555 m/s. It varies depending on lens
retina), an area that is too anterior to be imaged with contact status and other special conditions. In aphakic eyes, the sound
B-scan and too posterior for ultrasound biomicroscopy. velocity is approx 1532 m/s, in pseudophakia, it is 1556 m/s
in PMMA lens, and 1549 m/s in pseudophakic eyes with

acrylic lens. Silicone oil has a higher refractive index and slower
sound velocity (980 m/s). The patient should be positioned
as upright as possible to keep the silicone oil in contact with
the retina and to avoid it shifting into the anterior chamber.
In eyes with posterior staphyloma, B-scan should be
considered as a complimentary method for biometry. In
pseudophakic eyes, IOL causes multiple echoes within the
vitreous cavity, which may cause difficulty in identifying the
retinal spike.
ULTRASONOGRAPHIC IMAGING OF
THE POSTERIOR SEGMENT
In situations where there is media opacity (e.g. vitreous
hemorrhage, corneal opacity, cataract), echography allows for
Fig. 5.5.3.2: Ultrasonography of the normal eye
evaluation of the vitreous, retina, and choroid that otherwise
would be impossible. Fig. 5.5.3.2 demonstrates the sonogenicity
of the normal eye.
Vitreous Hemorrhage
Most common causes of vitreous hemorrhage (VH) are
posterior vitreous detachment (PVD) with or without retinal
tear and proliferative diabetic retinopathy, followed by ocular
trauma and neovascularization secondary to retinal vein
occlusion.13-16 In a case of fresh vitreous hemorrhage, low
to medium intensity spikes are visible in the vitreous cavity
(Fig. 5.5.3.3). As the hemorrhage becomes older, it becomes
dense, with a more layered structure, with medium amplitude
spikes on A-scan. Sometimes, the inferiorly settled vitreous
hemorrhage can be mistaken for retinal detachment on static
Fig. 5.5.3.3: Dense vitreous hemorrhage
echography (Fig. 5.5.3.4). In a vitrectomized eye, blood can (Courtesy: Dr Sharad Bhomaj)
remain in a liquefied state and high-gain settings are required
to visualize the hemorrhage.
Dynamic ultrasound examination is very important in a
case of vitreous hemorrhage to look for posterior vitreous
detachment (PVD), retinal detachment (RD), tractional
detachment of the macular region, and ruling out any mass
lesion. If a PVD is absent, a retinal tear or rhegmatogenous
RD is unlikely. If PVD is present, retinal detachment should
always be ruled out carefully before ascribing VH to some
other cause.
Posterior Vitreous Detachment

Posterior vitreous detachment (PVD) is a degenerative process
of the vitreous in which the vitreous gel loses its attachment
to the internal limiting membrane. The strongest attachment Fig. 5.5.3.4: Dense suprachoroidal hemorrhage with vitreous
of the vitreous is at the area of vitreous base, so PVD usually hemorrhage (Courtesy: Dr Sharad Bhomaj)
starts at the posterior pole. Ultrasonographically, PVD appears configurations of retinal detachment. It is very important to
as a thin, smooth membrane. It may demonstrate attachment take cuts through the optic nerve as in the case of a retinal
to the retina at sites of retinal tears, areas of detachment, the retina is always attached to the optic disk
neovascularization, the optic disk, or the vitreous base. It has (Fig. 5.5.3.7).
significant movement and after-movement on dynamic B-
scan, except in some cases of trauma and inflammation. PVD
has a low reflectivity and is usually detectable on high gains.
Sometimes, layered blood over its surface may give this
membrane a high reflectivity, which may be differentiated by
decrease in reflectivity as the membrane is traced anteriorly.17
Retinal Detachment
Rhegmatogenous retinal detachment: The etiology of
rhegmatogenous retinal detachment (RD) includes high
myopia, trauma, cataract surgery, ocular infections, lattice
degeneration, etc. In cases of media opacity, rhegmatogenous
RD may be difficult to be differentiated from PVD. Points
mentioned in Table 5.5.3.1 may help differentiation.
Tractional retinal detachment: It is the 2nd most common
Fig. 5.5.3.5: Axial section of an eye with old RD showing fixed
type of RD. Causes include Proliferative diabetic retinopathy retinal folds and retinal cyst
(PDR) penetrating trauma, retinopathy of prematurity, and
proliferative vitreo retinopathy (PVR). In tractional retinal
detachment (TRD), vitreoretinal adhesions cause mechanical
separation of the retina from the underlying RPE causing a
retinal detachment with a tent-like configuration that does
not extend to the ora serrata with reduced mobility.
Exudative retinal detachment: This type of RD has a smooth
surface, with the absence of rugae, the absence of a retinal
tear, and shifting of subretinal fluid with movement to the
most dependant part of the eye. The B-scan also may pick
up choroidal masses or a thickened choroid or sclera.
Total retinal detachment may have an open funnel or
closed funnel configuration. Open funnel RD appears as a
wavy rope-like membrane with mild-to-moderate mobility. A
closed funnel or T-shaped chronic retinal detachment appears
as a thickened, highly reflective membrane with complete Fig. 5.5.3.6: Axial B-scan of an eye with irido-fundal
loss of mobility. Figs 5.5.3.5 and 5.5.3.6 demonstrate different coloboma with RD
Table 5.5.3.1: Ultrasonographic features for differentiating between posterior

vitreous detachment and retinal detachment
Posterior vitreous detachment Retinal detachment
Echogenicity Low-medium High (near 100% spike on A-scan)
Change with gain (dB) Disappears with low gain Visible with low gain
Mobility High Low
Optic disk attachment May be present Always present
Serous CD demonstrates echolucent areas beneath the

choroid, while suprachoroidal hemorrhage shows dense
suprachoroidal opacities on B-scan.
Massive choroidal detachment where the folds of the
choroid touch each other are called “kissing choroidals”. These
are classically seen in severe hypotony (Fig. 5.5.3.8).
Retinal Pigment Epithelium Detachment

A common complication of pigment epithelial detachment
(PED) is retinal pigment epithelium (RPE) tear, which can be
accompanied by bleeding that may extend into the vitreous
cavity causing VH. In cases where VH is obstructing the
view of the posterior segment, B-scan may show a thick,
Fig. 5.5.3.7: Old retinal detachment with subretinal hemorrhage nonmobile, dome-shaped membrane with high reflectivity on
(Courtesy: Dr Sharad Bhomaj) A-scan as a cause of VH.
Retinoschisis
On B-scan, retinoschisis is usually of lower amplitude and
thinner than RD with a focal, smooth, dome and a single
peak on A-scan.18
Postsurgical Changes
Scleral buckle: It produces a convex indentation of the ocular
wall and strong sound attenuation because of the extremely
high reflectivity of the buckling material.
Gas/Air bubbles: Sound penetration does not occur through
the gas/air bubble. B-scan examination may be done with
head-positioning so as to bypass the bubble in case of a small
one. It may not be possible if the whole vitreous cavity is
Fig. 5.5.3.8: Kissing choroidals in a patient with severe hypotony.
Note that the undersurface of the dome shaped elevation is sonoluscent
filled with the bubble.
denoting choroidal detachment in contrast to areas of medium Silicone oil: Silicone oil has a lower sound velocity and decreased
echogenicity seen in Figure 5.5.3.4, denoting suprachoroidal
hemorrhage (Courtesy: Dr Sharad Bhomaj) penetration of sound waves than the vitreous, causing echographic
elongation of the vitreous cavity (Fig. 5.5.3.9) and limiting
observation of the posterior ocular wall. Residual silicone oil
remaining in the eye after it is removed surgically appears as
highly reflective echoes scattered in the vitreous cavity.
Choroidal Detachment
Retained perfluorocarbon liquid: This is visualized as highly
Suprachoroidal hemorrhage has a smooth, thick, convex shape, reflective echoes, which causes shadowing of the orbit.
immobility, with little after-movement on dynamic B-scan
(Fig. 5.5.3.4). INTRAOCULAR TUMORS
Serous choroidal detachment (CD) can be smooth, dome-
Retinoblastoma
shaped or flat on B-scan, with minimal or absent after-
movement and lack of attachment at the optic disk. Echographically, retinoblastoma has an irregular configuration
On diagnostic A-scan, both show a steep, thick, 100 percent with high reflectivity, suggesting the presence of calcium.
double-peaked spike on A-scan and are differentiated from RDs Calcium deposits may present as large, dense areas within the
that show only a single-peaked spike on B-scan. main tumor mass or as collections of small echographic foci.
These calcified areas may produce shadowing of the sclera before treatment, and in posttreatment follow-up examinations
or the orbit. In some cases, this tumor contains little or no (Fig. 5.5.3.11).
calcium. Such noncalcified tumors are frequently diffuse with The tendency for retinoblastoma to extend down the optic
an irregular surface, and pose a particular problem for nerve, toward the brain and orbit, should always be considered.
diagnosis (Fig. 5.5.3.10). The detection of such extension by ultrasonography may be
Retinoblastoma eyes may have longer axial lengths, if
glaucoma from neovascular changes or direct trabecular
meshwork invasion by the tumor has developed. It helps to
differentiate retinoblastoma from other disease states
presenting with leukocoria, such as persistent hyperplastic
primary vitreous, which demonstrates shorter-than-average
axial length (Table 5.5.3.2).
Ultrasound examination is also useful in the long-term
management of retinoblastoma, in measuring tumor size
Fig. 5.5.3.11: Use of calipers to measure the dimensions of a tumor

during B-scan ultrasonography
Table 5.5.3.2: Differential diagnosis of leukocoria

Disease Clinical features Axial B-scan
length characteristics
Retinoblastoma Few months to Normal Intraretinal/
<2 years;possible subretinal
family history, mass with
Fig. 5.5.3.9: Axial scan of a vitrectomized eye filled with silicone oil unilateral/bilateral calcification
showing increased axial length
Retinopathy of Days to few Short RD, Peripheral
prematurity months after birth; retinal loops,
prematurity; oxygen hemorrhages
supplementation, or cholesterol
bilateral debris In the
subretinal
space
PHPV Days to weeks Short Vitreous band
after birth, from lens to
unilateral optic nerve
Toxocariasis Contact with Normal Peripheral
dogs/cats, mass,
unilateral vitreoretinal
band, traction
RD
Medulloepithe- First decade of Normal Ciliary body
lioma life, unilateral mass with cyst
Coats’ disease 4–10 years; Normal Exudative RD,
most commonly subretinal
Fig. 5.5.3.10: Figure shows intraocular mass with calcification in a males, unilateral cholesterol
case of retinoblastoma particles
challenging because of shadowing from the dependent

intraocular calcification. In case such calcification prevents clear
imaging of the optic nerve and orbit, correlation with CT scan
and MR imaging findings should provide better clinical
information.
Uveal Tumors
Benign Uveal Tumors
Choroidal nevus: Moderately elevated, usually not exceeding
3 mm in height. Relatively high reflectivity without internal
vascularity needs close follow-up to look for any growth or
change in internal reflectivity suggestive of malignant
transformation.
Fig. 5.5.3.12: Classical collar-stud or collar-button appearance of an
Uveal melanocytoma: Elevated mildly and dome-shaped, intraocular choroidal melanoma (Courtesy: Dr Sharad Bhomaj)
predominantly involves the optic disk and the surrounding
choroid and retina. Malignant transformation into melanoma • Choroidal excavation on B-scan is frequently seen, but is
is reported in less than two percent of the cases. not pathognomonic for malignant melanoma
• Serous retinal detachment usually extends from the
Choroidal hemangioma
margins of the tumor and may overlay the tumor surface
• Circumscribed choroidal hemangioma: Dome-shaped
(Fig. 5.5.3.13). The tumor also may be accompanied by
configuration and is usually located in the posterior pole,
vitreal, subretinal, or subchoroidal hemorrhage
frequently peripapillary. On A-scan, internal reflectivity is
• Scleritis, usually associated with tumor necrosis, can be
high and regular, with some attenuation and no sign of
demonstrated on B-scan by sclera thickening with dilation
internal vascularity
of Tenon’s space
• Diffuse choroidal hemangioma (Sturge-Weber syndrome):
• Calcification is occasionally observed on the tumor’s
Less elevated, with extension from the posterior pole to
surface.
the periphery. Internal reflectivity is high and regular on
A-scan. Extrascleral extension on B-scan echography is suggested
by the appearance of a small echolucent nodule located just
Malignant Uveal Tumors behind the sclera, adjacent to the tumor’s base.
• Iris and ciliary body melanoma Diffuse melanomas may provide challenges in echographic
• Choroidal melanoma. diagnosis because of following features:
• Minimally elevated
Acoustic criteria for diagnosis of ocular melanoma: 19 Typical • Irregular surfaces
acoustic criteria used for echographic diagnosis of ocular • Indistinct margins
melanoma on B-scan include: • Reflectivity is low to medium and is sometimes irregular
• A collar-button or mushroom shape. The collar-button • Internal vascularity is less well defined
shape suggests a break in Bruch’s membrane through which
Diffuse melanomas have high rates of extrascleral
the tumor invades, and is almost a pathognomonic B-scan
criterion for diagnosis of choroidal melanoma (Fig. 5.5.3.12) extension; particular attention should be devoted to this
• Characteristic A-scan features of choroidal melanoma possibility by the examining ethnographer.
include low to medium internal reflectivity, a regular Differential Diagnosis of Choroidal Melanoma:
pattern of internal reflectivity, and the presence of internal • Circumscribed choroidal hemangioma
vascularity. Large tumors demonstrate sound attenuation • Choroidal metastasis have irregular, lobulated or excavated
in A-scan and acoustic hollowing in B-scan surfaces. Internal reflectivity is usually irregular, medium,
• Tumor vascularity is indicated by spontaneous flickering or high. It grows rapidly over a short time interval
movements of the internal tumor spikes • Leiomyoma
Fig. 5.5.3.13: Choroidal melanoma associated with serous retinal Fig. 5.5.3.14: Axial B-scan through an eye with phthisis bulbi
detachment (Courtesy: Dr Sharad Bhomaj) showing intraocular dystrophic calcification
• Age-related macular and extra-macular degeneration Panuveitis

• Posterior scleritis B-scan ultrasonography of the posterior segment can evaluate
Conditions Associated with and differentiate the pathology associated with panuveitis,
Intraocular Calcification including vitreous membranes, retinal detachments, and
choroidal thickening. Sympathetic ophthalmia and Vogt-
Retinal and RPE Lesions Koyanagi-Harada syndrome exhibit similar echographic
findings which include:
• Retinoblastoma
• Astrocytic hamartoma • Serous retinal detachments
• Chronic retinal detachment • Diffuse choroidal thickening
• RPE metaplasia In the presence of media opacity, ultrasound helps to monitor
• Cysticercosis response to corticosteroid treatment by evaluating the elevation
and extent of retinal detachments and choroidal thickness.
Choroidal Lesions Additionally, UBM may show features such as uveal ciliary body
• Choroidal osteoma changes and thickening, that are not obvious clinically.
• Sclerochoroidal calcification
• Choroidal granuloma Posterior Scleritis
The diagnosis of posterior scleritis is challenging because of
Others its variable clinical presentation, including serous retinal
• Optic nerve head drusen detachment, chorioretinal lesions, retinal pigment epithelial
• Scleral calcification (Cogan’s plaque) changes, choroidal mass lesion or normal fundus. B-scan
• Phthisis bulbi (Fig. 5.5.3.14) ultrasonography is an essential tool for the accurate diagnosis
of posterior scleritis, most frequently revealing the classic T-
OCULAR INFLAMMATORY DISEASES sign, which represents thickened posterior sclera with
underlying fluid collection in the Tenon’s space.
Posterior Uveitis
In cases of severe posterior uveitis, diffuse inflammatory Infectious Endophthalmitis
infiltrates in the vitreous often preclude evaluation of the B-scan ultrasonography has a key role in the evaluation of
posterior segment of the eye. B-scan evaluation reveals patients of endophthalmitis, because the media is hazy due
moderate to dense, diffuse vitreous opacities with moderate to vitreous and corneal opacity which precludes the view of
mobility. It does not differentiate between hemorrhage and the posterior segment. Low to dense intensity spikes are
exudates, which are differentiated based upon clinical features. observed in the vitreous cavity (Fig. 5.5.3.15).
Fig. 5.5.3.15: Dense, medium to low reflectivity echogenic spikes in Fig. 5.5.3.16: B-scan showing orbital tumor with well defined capsule
the vitreous cavity is suggestive of endophthalmitis. Clinical correlation with high internal reflectivity in a case of orbital hemangioma
is required to differentiate vitreous hemorrhage from vitreous exudation
suggestive of endophthalmitis (Courtesy: Dr Sharad Bhomaj)
Normal retrobulbar optic nerves measured at the

arachnoid sheath are 2.2 to 3.3 mm in diameter. A difference
Inflammatory Orbital Diseases of 0.5 mm between eyes frequently indicates an abnormal
thickness in one eye and should raise a suspicion for a retro-
These may be divided into infectious and noninfectious orbital mass lesion.21
conditions.
Papilledema
Infectious Conditions
The diameter of optic nerve sheath correlates directly with
It includes orbital cellulitis. Orbital ultrasound helps in the intracranial pressure. To differentiate between thickening
localizing any pus pockets in the orbit which may need of the parenchyma of optic nerve from that of perineural
drainage surgically. Percutaneous ultrasound-guided sheaths, 30° test22 is done. The patient fixates in the primary
intraorbital wooden foreign body removal has also been gaze (straight ahead position), and the optic nerve perineural
described in literature.20 sheaths are measured anteriorly and posteriorly. The patient’s
gaze is then directed 30° laterally, and the perineural sheaths
Noninfectious Conditions are measured again. The test is based on the presumption that
when the eye is fixated laterally, the optic nerve sheaths are
Orbital pseudotumor may present as myositis (extraocular
stretched and the subarachnoid fluid is spread over a larger
muscle), dacryoadenitis (lacrimal gland), or Tolosa-Hunt
area. A decrease in sheath diameter of greater than 10 percent
syndrome (orbital apex).
in lateral gaze, as compared with primary gaze, is considered a
Graves’ ophthalmopathy may have symptoms similar to
positive test and thus indicative of increased subarachnoid
those of patients who have orbital myositis, but
fluid.
ultrasonography usually reveals enlargement of the extraocular
muscles without involvement of the tendons. Pseudopapilledema: Sometimes eyes with buried optic disk
Figure 5.5.3.16 demonstrates the characteristic appearance drusens especially in the first two decades may simulate
of an orbital hemangioma. Other details regarding orbital papilledema. Ultrasound may help differentiate by showing
ultrasonography is elucidated in the next chapter. calcified buried drusen, normal optic nerve sheath diameter
and a negative 30° test.
OPTIC NERVE DISORDERS
Posterior staphyloma: This can be made out as an excavation in
The optic nerve sheath diameter is measured in two locations: the posterior coat of the eye. The eye is usually myopic and
• 3 mm posterior to the optic nerve head and hence elongated. It may be associated with vitreous
• As close as possible to the orbital apex degenerations (Fig. 5.5.3.17).
Fig. 5.5.3.17: Posterior staphyloma in a high myope associated with Fig. 5.5.3.18: Posteriorly dislocated crystalline
vitreous degeneration (Courtesy: Dr Sharad Bhomaj) lens in a case of blunt trauma
CONGENITAL DISC ANOMALIES Retinal Tear
Optic Disc Coloboma A small, peripheral retinal tear may also be seen as a focal,
highly reflective flap on B-scan. The posterior vitreous is
This presents as a white bowl-shaped excavation that is usually thickened and partially detached but remains adherent
decentered inferiorly in an enlarged optic disc. B-scan clearly to the retina at the location of the tear. When a retinal tear is
delineates the inferior location of these excavations and also diagnosed in the presence of dense vitreous hemorrhage, a
may demonstrate the small diameter of the associated optic vitrectomy is usually required to prevent progression to retinal
nerve. detachment.
Morning Glory Disc Anomaly Hemorrhagic Choroidal Detachment
B-scan is useful to confirm the centralized location of the A rare complication of trauma, choroidal detachment can be
diagnosed and followed up on serial ultrasound examinations.
depression in the morning glory disc as compared with the
The timing of drainage in case of kissing choroidals (Figs
asymmetric inferiorly located depression found in coloboma.
5.5.3.4 and 5.5.3.8) can be determined with the help of USG,
as it helps in visualizing liquefaction of blood dynamic USG
Pseudodoubling of the Optic Disc
which occurs 10 to 12 days after trauma.
In cases of irido-fundal colobomas, there is anastomosis
between the retinal and choroidal circulation which may Lens Dislocation
give the appearance of doubling of the optic nerve. On B-scan, a posteriorly dislocated crystalline lens appears as
Ultrasound may be useful in ruling out any retrobulbar an oval shaped highly reflective mass. A traumatically displaced
optic nerve pathology. intraocular lens appears as a highly reflective linear body with
marked reverberations (Fig. 5.5.3.18).
Avulsion of the Optic Nerve
Intraocular Foreign Body
It appears as a hypolucent area in the region of the optic
nerve head that may be associated with a defect in the Diagnostic ultrasound helps in determining:
posterior sclera. • The precise location, size and orientation of small IOFBs
• Distinguishing between objects composed of different
POSTERIOR SEGMENT TRAUMA materials
– Metallic IOFBs-echo dense at low gain settings and
The following conditions may be diagnosed in cases of media produce shadowing of intraocular structures and the
opacity: orbit (Fig. 5.5.3.19).
– Organic IOFBs produce variable findings on COLOR DOPPLER ULTRASOUND

ultrasound depending on the material. IMAGING
Intraocular air bubble may be confused with a foreign
Christian Andreas Doppler (1803-1853) first described the
body, but may be distinguished by its change in position
principle of using the change in the frequency of waves to
with head positioning and decrease in size over time.
measure the velocity of an object. This principle was applied
to ultrasound in the investigation of human diseases in 1957
COMBINED OCULAR AND ORBITAL
and subsequently became established in routine clinical practice
ULTRA-SONOGRAPHY
for the examination of the larger vessels in the body, such as
In cases of trauma, in congenital anomalies involving both, the the carotid arteries and the heart.23
ocular structures and the surrounding adnexa like, for example, Its uses in ophthalmology are:
microphthalmos associated with congenital cystic eye, and in
patients with phthisis or atrophic bulbi, it may be advisable to Vascular Occlusion
perform both, intraocular and orbital ultrasonography to record
In an examination of patients with recent onset of central
the findings holistically (Figs 5.5.3.20 and 5.5.3.21).
retinal artery occlusion and anterior ischemic optic neuropathy,
absence of flow was found in the central retinal artery and
posterior ciliary vessels.24 Flow returned in these patients
within one week and was normal in patients after three weeks
duration from the onset of the occlusion. Patients with central
retinal vein occlusion have reduced mean peak velocities in
the central retinal vein of the affected eyes as compared to
both their unaffected fellow eyes and controls, despite only
slight changes in the velocities in the central retinal artery.25
Tumors
Intraocular tumors such as choroidal hemangiomas,
metastases, ocular melanoma have a detectable blood supply,
while other lesions which may mimic malignant tumors, such
as age-related macular degeneration, choroidal osteoma and
Fig. 5.5.3.19: Diagram showing retained intraocular choroidal nevi have shown no detectable blood flow.
foreign body with orbital shadowing
Figs 5.5.3.20A and B: Right eye of a patient with cryptophthalmos. The rudimentary cystic eyeball measures 3.21 mm and none of the intra-
ocular structures are well delineated. Left eye of the same patient was microphthalmic with the anteroposterior length of the eyeball being 6.74
mm (Courtesy: Dr Sharad Bhomaj)
changes in small tumors in their earliest stages. 20 MHz

ultrasound offers advantages under circumstances where
opaque media or peripheral location makes OCT impracticable.
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HIGH-RESOLUTION ULTRASONIC Ophthalmol 1980;64(7):469-71.
IMAGING OF THE POSTERIOR SEGMENT 15. Butner RW, McPherson AR. Spontaneous vitreous hemorrhage.
Ann Ophthalmol 1982;14(3):268-70.
Twenty MHz ultrasound can be employed for imaging of 16. Manuchehri K, Kirkby G. Vitreous haemorrhage in elderly patients:
the posterior pole of the eye. It provides a 2-fold improvement management and prevention. Drugs Aging 2003;20(9):655-61.
in resolution relative to the conventional 10 MHz instruments. 17. Freyler H, Egerer I. Echography and histological studies in various
Although not providing the resolution of OCT, ultrasound eye conditions. Arch Ophthalmol 1977;95(8):1387-94.
can be used in the presence of optical opacities and allows 18. Hillman JS, Ridgway AE. Retinoschisis and retinal detachment,
evaluation of deeper tissue structures.32 an ultrasonic comparison. Bibl Ophthalmol 1975;(83):63-7.
19. Barash D, Joan M. Brien O’. The Role Of Ultrasound In The
Ten MHz systems may be advantageous compared with
Management of Ocular Tumors Ophthalmology. Clinics Of North
the 20 MHz systems where deeper penetration is important America. Volume 12 Number 2 * June 1999;205-11.
(orbital pathologies) or very high sensitivity is needed (faint 20. Close JK, Shiels WE 2nd, Foster JA, Powell DA. Percutaneous
vitreous membranes). Twenty MHz ultrasound is the technique ultrasound-guided intraorbital foreign body removal. Ophthal Plast
of choice for diagnosis and monitoring of growth and structural Reconstr Surg 2009;25(4):335-7.
21. Gans MS, Byrne SF, Glaser JS. Standardized A-scan echography dioxide reactivity in orbital vessels (abstract). Invest Ophthalmol
in optic nerve disease. Archives of Ophthalmology 1987;105: Vis Sci (suppl) 1994;35:1254.
1232–6. 27. Regillo CD, Sergott RC, Brown GC. Successful scleral buckling
22. Ossoinig K, Cennamo G, Byrne S. Echographic differential procedures decrease central retinal artery blood flow velocity.
diagnosis of optic nerve lesions. In: Thijssen JM, Verbeek AM, Ophthalmology 1993;100:1044-9.
(Eds). Ultrasonography in ophthalmology. Dordrecht (The 28. Regillo CD, Sergott RC, Ho AC, et al. Hemodynamic alterations
in the acute retinal necrosis syndrome. Ophthalmology
Netherlands): Dr. W Junk 1981;327.
1993;100:1171-6.
23. Satomura S. Ultrasonic Doppler method for the inspection of
29. Tamaki Y, Nagahara M, Yamashita H, Kikuchi M. [Analysis of
cardiac functions. J Acoust Soc America 1957;29:1181-5.
blood flow velocity in the ophthalmic artery by color Doppler
24. Williamson TH, Baxter GM, Dutton GN. Color Doppler imaging. 2. Studies on diabetic eyes]. Nippon Ganka Gakkai Zasshi
velocimetry of the arterial vasculature of the optic nerve head 1993;97:961-6.
and orbit. Eye 1993;7:74-9. 30. Berges O. Color Doppler flow imaging of the orbital veins. Acta
25. Baxter GM, Williamson TH. Color Doppler flow imaging in central Ophthalmol 1992;204:55-8.
retinal vein occlusion: A new diagnostic technique? Radiology 31. Erickson SJ, Hendrix LE, Massaro BM, et al. Color Doppler flow
1993;187:847-50. imaging of the normal and abnormal orbit. Radiology
26. Harris A, Shoemaker JA, Sergott RC, et al. Vasospasm in normal 1989;173:511-6.
tension glaucoma: color Doppler imaging assessment of carbon 32. Coleman DJ, Silverman RH. High-Resolution Ultrasonic Imaging
of the Posterior Segment. Ophthalmology 2004;111:1344–51.
5.5.4 Orbital Ultrasonography

Sumita Sethi, Rachna Meel, Neelam Pushker, Supriyo Ghose
Ultrasonography (USG), first introduced in 1956, has emerged This chapter discusses some general concepts about USG
as a valuable technique for defining soft tissue abnormalities and its uses in the diagnosis and evaluation of some common
of the eye and orbit.1 As high frequency sound waves (5–20 orbital disorders.
MHz) are projected through soft tissues, echoes are produced
at tissue interfaces. These echoes are displayed as either one- PHYSICS OF ULTRASOUND
dimensional amplitude spikes (A-mode ultrasonography), or By definition, ultrasound is an acoustic wave which comprises
as dots integrated into a two-dimensional image representing compressions and rarefactions that propagate within fluid
a thin section through the entire orbit (B-scan and solids. Ultrasonic waves exhibit high frequencies (above
ultrasonography).1 Despite the availability of various other 20 kHz), rendering them inaudible and different from the
imaging modalities, viz. Computed Tomography (CT) and sound waves. The key element in an ultrasonic system is a
Magnetic Resonance Imaging (MRI), USG is a highly useful transducer which generates an ultrasonic wave and in the
diagnostic aid. This can be attributed to its cost effectiveness, time interval between pulses, echoes are received by the same
easy availability, non-invasiveness, and the ease of transducer and recorded.5 The main component in the
repeatability.2 The technique is devoid of ionizing radiation transducer is a piezoelectric material, such as lead zirconate
and has good spatial resolution. If needed, it is possible to titanate, which is responsible for generation and detection of
carry out the examination at the patient’s bedside.3 Possibility ultrasound. During use, a thin layer of coupling gel is used
of dynamic study that can be carried out with eye movements for coating the transformer which is then held in contact
and real time imaging is an added advantage in localization with the globe or lid. The gel provides a path of transmission
of lesions.4 The role of USG in ophthalmic diagnosis may of ultrasonic waves which are otherwise rapidly absorbed in
thus not only be complimentary to other imaging modalities air. This coupling can also be provided by a saline bath in the
but owing to its high sensitivity and resolution may in certain form of fluid in small chamber or surgical drapes.
circumstances often demonstrate those abnormalities which The overall quality of an ultrasonogram is decided on
are otherwise not well seen. the basis of three parameters, sensitivity, resolution and
dynamic range.6 Sensitivity is an indicator of the weakest optic nerve and extraocular muscles have a relatively organized
reflector that can be detected in an ultrasonogram. Resolution tissue structure and thus produce only low amplitude echoes.
is the ability to distinguish two nearby reflectors. Dynamic Thus in a horizontal scan through the optic nerve, the normal
range describes the spread of echo amplitude that can be retrobulbar echo pattern is the W-shaped white area which is
accurately portrayed in an ultrasonogram. acoustically opaque, indented posteriorly by a black notch
(acoustically empty) which widens towards the orbital apex.
ULTRASONOGRAPHY IN
OPHTHALMOLOGY ULTRASONOGRAPHY IN DIAGNOSIS OF
ORBITAL ABNORMALITIES
A-mode and B-mode are the two most commonly used
B-scan ultrasound patterns of various pathologies involving
ultrasonic imaging modalities in ophthalmology, each presenting
the orbit were classified initially by Purnell13 and later described
the relevant information in a distinct display format. The first
in detail by Coleman et al.14-17 who classified the orbital
application of ultrasonic techniques in ophthalmology was
abnormalities into mass lesion, foreign bodies and inflammatory
demonstrated by Mundt and Hughes in 1956 using the A-scan
changes. Common orbital abnormalities as mass lesions,
mode.7 Oksala in 1958 extended its use in ophthalmic diagnosis.8
inflammatory lesions and orbital traumatic lesions are described
During A-scan, the transducer is coupled directly to the eye
in this section.
through the use of methyl cellulose. While the height of the
recorded spike on vertical axis is a measure of the amplitude
Mass Lesions
of the echo, the position of the spike along the horizontal axis
indicates the arrival of the echo at the transducer. The diagnosis Any mass lesion in the orbit produces an abnormal ultrasonic
is based on the basis of amplitude, position, extent, and contour, thus causing a distortion of the retrobulbar fat, optic
movement of abnormal echoes along with the sound attenuating nerve and rectus muscles. DJ Coleman et al have classified
properties of the abnormality.5 In ophthalmology, the A-scan ultrasound B-scan appearances of the orbital abnormalities
mode has a special role in biometry, i.e. axial length, which is into four diagnostic patterns-cystic, solid, angiomatous and
very important for surgical planning. B-scan USG was first infiltrative.2
conceptualized by Baum and Greenwood in 1958.9 It took Cystic Lesions
almost 10 years for the concept to be widely used.10 In B-scan
A fluid filled cystic lesion is characterized ultrasonically by a
technique, the transducer is coupled to the eye by either the gel
well defined regular margin and good transmission of sound
applied to the closed lid or by a saline bath. B-scan refers to a
waves resulting in a clearly seen posterior wall. Since there is
display of two-dimensional cross-sectional images. The echoes
no apparent tissue interface inside the lesion, it is devoid of
in B-scan are displayed as spots and the brightness of echoes
internal echoes.
indicate its amplitude. There are other ultrasonic modalities as
well which are more recently introduced and are clinically less Orbital dermoid cysts (Fig. 5.5.4.1) are examples of
commonly employed including M-scan, swept mode and color choristomas, tumors that originate from aberrant primordial
flow Doppler imaging. tissue and occur usually in children. Ultrasonically they appear
smooth and rounded and are well demarcated from the orbital
ORBITAL ULTRASONOGRAPHY tissues. USG not only assists in diagnosis but also help in
exact localization thus facilitating surgical approach. B-scan
In orbital diagnosis, the topographic outlining capabilities of
is especially useful in cases with no bony changes, the later
B-scan are utilized for the localization and delineation of various
being best assessed with the help of computed tomography.18
abnormalities.2 After an initial localization of the lesion with
B-scan, the combined technique of utilization of both B-scan Mucoceles of the paranasal sinuses may sometimes invade the
and A-scan can be undertaken, the A-scan assisting in tissue orbit resulting in unilateral exophthalmos. On B-scan, the
evaluation and determination of vascular properties of the interior of the lesion looks like a black sonolucent cavity
lesion.2,11,12 In the eye and to a lesser extent on the retro- with rounded margins and A-Scan shows a sonolucent interior
orbital area, the acoustic boundaries correspond to the with few or no internal echoes.19 Since the ultrasonic waves
anatomical boundaries. The retro-orbital fat is a heterogeneous are not absorbed by the cystic structure allowing its easy
tissue comprising many small tissue elements like fat globules, penetration, the posterior extent of the lesion, orbital wall
fibrous septa, multiple vessel and nerves. Thus there are and its apex are clearly seen. The ultrasonic appearance is
multiple tissue interfaces which produce individual echoes. The typical of a cystic lesion and with clearly seen posterior wall.
Fig. 5.5.4.1: Ultrasonography A and B-scan showing an orbital lesion

with high reflectivity suggestive of orbital dermoid. The lesion was
removed surgically and histopathology confirmed the diagnosis
Fig. 5.5.4.2: Ultrasonography A and B-scan showing a cavernous

hemangioma in a 50-year-old male
Cavernous hemangiomas (Fig. 5.5.4.2) are benign, vascular, slow
growing lesions and are the most common intraorbital tumors lesions, they have multiple internal echoes due to poor
in adults.17,20 All cavernous hemangiomas are characterized transmission of ultrasonic waves through them.
by regular rounded outline, a sharply defined anterior acoustic
Optic nerve tumors: B-scan is an important diagnostic aid to
border and good demarcation from surrounding structures
differentiate the optic nerve tumors from various other orbital
(owing to abrupt transition of acoustic velocities between the
tumors. This is important before planning any surgical
fluid filled tumor and the surrounding retrobulbar fat). There
intervention since the optic nerve tumors are best approached
is fair to good transmission of ultrasonic waves through the
by the neurosurgical approach. 2 Ultrasonically, they are
interior of the lesion, good transmission through the blood
characterized by a rounded appearance with a poor outlining
filled vessels and low amplitude echoes from the walls of the
of the orbital wall due to high absorption of the ultrasonic
vessels. With varying frequency of the transducer, there is an
waves. Large blood vessels and collagenous connective tissue
alteration in appearance of the lesion and is best outlined at
in the interior of the lesion leads to acoustic variability leading
10 to 15 MHz.
to low amplitude echoes on A-Scan. There is a characteristic
Besides these orbital tumors having a cystic appearance
enlargement of the optic nerve shadow, converting the normally
on USG, there are certain helminthic infections as well which
acute angled optic nerve shadow to an obtuse angled shadow.
present as orbital cysts including hydatid cysts (Figs 5.5.4.3A
and B) and myocysticercosis (Fig. 5.5.4.4). The appearance is
Angiomatous Tumors
typically that of a cystic lesion with well demarcated margins
and an acoustically empty interior. Betharia et al have described In contrast to the solid and cystic tumors with rounded outline,
the characteristic ‘double-wall’ sign as confirmatory for hydatid angiomatous orbital tumors are characterized by irregular
cyst.21 USG is valuable not only as a diagnostic aid but also outlines.
assists in monitoring of response of the cyst to systemic anti-
Diffuse lymphangioma is a characteristic example of an
helminthic drugs.
angiomatous lesion and demonstrates a moderately well
defined but highly irregular margins, owing to the absence of
Solid Tumors
the capsule and diffuse fingerlike extensions into the
Ultrasonically, the solid tumors are characterized by a rounded retrobulbar fat. The lesion has an acoustically empty interior
outline but unlike the acoustically empty interiors of the cystic and since there is good transmission of ultrasonic waves
Figs 5.5.4.3A and B: Ultrasonography A and B-scan (A) and axial view computed tomographic scan (B) showing a large orbital hydatid cyst
of the posterior extent of the lesion and the orbital walls.16

The margins are irregular, lobulated and are as such
demarcated from the surrounding orbital structures. The
interior of the lesion is solid but homogeneous with no
acoustic discontinuities resulting in absent internal echoes.
Rhabdomyosarcoma is characterized ultrasonically by irregular
outline and solid interiors, similar to other infiltrative tumors.
USG also has a role in demonstrating serial changes in the
tumor and response to management.
Besides these mass lesions, lacrimal gland tumors are
another group where USG forms an important part in the
diagnostic work-up by determining the size, extent and
configuration of the tumors. The most useful part is
differentiating the benign from the malignant tumors by
determining the posterior extent of the tumor and lateral
invasion of the surrounding orbital tissues. However CT and
Fig. 5.5.4.4: Ultrasonography A and B-scan showing a large
MRI remain the best diagnostic modalities for the localization
cysticercus cyst in the medial rectus muscle
of tumors and to look for bone destruction.
through the fluid, the posterior extent of the lesion as well as
Inflammatory Lesions
the orbital wall is well made out.
USG has a role in demonstration of any form of localized
Infiltrative Tumors and diffuse orbital inflammation, including that of the
extraocular muscles, Tenon’s space or the optic nerve.
Ultrasonically this group of tumors is characterized by a highly
In Graves disease, the extraocular muscles become large
irregular outline and a very poor transmission of the ultrasonic
with marked inflammation and interstitial edema. Though
waves through the lesion.
the inferior rectus is the most commonly involved muscle, it
Orbital lymphoma is a characteristic example of an infiltrative is easier to demonstrate changes in the medial and lateral
lesion and is ultrasonically a solid mass with very poor rectus. USG has a role in the demonstration of changes in
penetration of the ultrasonic waves resulting in poor delineation the extraocular muscles as well as in the orbital fat.
Ultrasonically, the normal extraocular muscles appear as foreign body is too small to be picked up by sonography and
hypoechoic black spaces owing to an ordered orientation and if the foreign body is along the posterior sclera or in the
acute angulation of the muscle fibres to the examining beam. retrobulbar fat, the echoes from the body may be lost in the
In Graves disease, the enlargement of the belly is reflected retrobulbar fat echo.2 If the foreign body is surrounded by
by an increase in space between the orbital wall and retrobulbar hemorrhage or oedema or an associated abscess (Figs 5.5.4.5A
fat. The enlarged extraocular muscles may also cause and B), the appearance ultrasonically is that of a cystic area
compression of the retrobulbar fat resulting in indentation within which the echoes from the foreign body can be
of its posterior outline. Though MRI is the documented best appreciated.
way for demonstration of extraocular muscle enlargement,
Orbital hemorrhage (Fig. 5.5.4.6) may present as a more
USG is vital for documentation of changes during the disease
common mass lesion which appears ultrasonically as
course and response to treatment with systemic steroids.
hypoechoic area replacing the orbital fat echoes, well
Dallow in a series of 258 consecutive patients with
demarcated margins and moderate transmission of the
exophthalmos concluded that some patients with Graves
ultrasonic waves through the lesion.2 Another less common
disease may also have an orbital tumor and thus warrant
presentation is as a diffuse infiltrative pattern similar to certain
ultrasonographic and neuroimaging examination during the
cases of orbital cellulitis.2 A very small hemorrhage will show
course of treatment.1
very mild irregularity of the retrobulbar fat echoes.
Inflammation of the optic nerve (optic neuritis) can either occur
Though computed tomography is a universally accepted
as an independent identity or secondary to orbital inflammatory
modality for diagnosis and evaluation of orbital fractures,
diseases. Ultrasonically optic nerve inflammation is seen as
Siegfried Jank et al. in their study have concluded that
doubling of the optic nerve shadow or accentuation of the
ultrasonography with a curved-array transducer is a useful
optic nerve outline. Keeney has described the echolucent “T
alternative method in the investigation of orbital floor fractures.23
sign” as a definite finding in such cases. There is objective
Retro-orbital fat acts as a substantial barrier to the
evidence of fluid within Tenon’s space, communicating into
ultrasonic waves directed at the apex of the orbit and thus
the vaginal spaces beneath the optic nerve sheath appearing as
orbital lesions in this area has to be sufficiently large to be
homogeneous and echolucent areas with concurrent thickening
detected among the retro-orbital fat echoes. USG also has
of the posterior bulbar complex and muscle sheaths evidenced
decreased sensitivity in detection of bony lesions. Ultrasonic
by increased echo density.22
signs of generalized inflammation may be nonspecific in
several disease processes. Despite these limitations, USG of
Orbital Trauma
the eye and orbit has a definite role in the diagnosis of various
USG has a role in detection of orbital foreign bodies, depending orbital lesions and their management decisions. Though CT
on their size, location and orientation. In certain cases the and MRI are more accurate and provide an anatomically
Figs 5.5.4.5A and B: Ultrasonography transocular (A) and paraocular (B) scan of a patient with orbital foreign
body showing an orbital abscess (the foreign body is not demonstrated in the scan)
2nd edition. Philadelphia: Lippincott Williams and Wilkins;

Chapter 2, Ultrasonic systems; 2006;27-44.
7. Mundt GH Jr, Hughes WF Jr. Ultrasonics in ocular diagnosis. Am
J Ophthalmol 1956;41(3):488-98.
8. Oksala A. Observations on choroidal detachment by means of
ultrasound. Acta Ophthalmol (Copenh). 1958;36(4):651-7.
9. Baum G, Greenwood J. The application of ultrasonic locating
techniques to ophthalmology. II. Ultrasonic slit lamp in the
ultrasonic visualization of soft tissues. AMA Arch Ophthalmol
1958;60(2):263-79.
10. Coleman DJ. Reliability of ocular and orbital diagnosis with B-
scan ultrasound. 2. Orbital diagnosis. Am J Ophthalmol
1972;74(4):704-18.
11. Byrne SF, Green RL. Ultrasound of the eye and orbit. 2nd edition.
St.Louis: Mosby; 2002.
12. Dibernardo C, Schachat AP, Fekrat S. Ophthalmic ultrasound: A
diagnostic atlas. 1st ed. New York: Thieme Medical Publishers;
1998;143.
Fig. 5.5.4.6: Ultrasonography A and B-scan of a young male patient 13. Purnell EW. B-mode orbital ultrasonography. Int Ophthalmol
with history of blunt trauma showing the orbital hematoma Clin 1969 Fall;9(3):643-65.
14. Coleman DJ, Jack RL, Franzen LA. B-scan ultrasonography of
orbital mucocoeles. Eye Ear Nose Throat Mon. 1972;51(6):207-
11.
detailed presentation of the orbital lesions, inflammatory 15. Coleman DJ. Reliability of ocular and orbital diagnosis with B-
changes may produce certain morphological tissue changes scan ultrasound. Orbital diagnosis. Am J Ophthalmol
which may be detected earlier with USG.2 The simplicity and 1972;74(4):704-18.
16. Coleman DJ, Jack RL, Franzen LA. High resolution B-scan
innocuous nature of the ultrasonic examination is highly useful
ultrasonography of the orbit. Lymphomas of the orbit. Arch
on those patients where regular follow ups and monitoring Ophthalmol 1972;88(4):375-9.
of the lesion is required.24 Used either alone or in combination 17. Coleman DJ, Jack RL, Franzen LA. High resolution B-scan
with CT and MRI, USG has proven to be an invaluable aid ultrasonography of the orbit. II. Hemangiomas of the orbit. Arch
in orbital diagnosis and surgery. Ophthalmol 1972;88(4):368-74.
18. Chawda SJ, Moseley IF. Computed tomography of orbital
REFERENCES dermoids: a 20-year review. Clin Radiol 1999;54(12):821-5.
19. Motaref B, Lorenz B. Value of 10 MHz ultrasound in diagnosis
1. Dallow RL. Evaluation of unilateral exophthalmos with and follow-up of retrobulbar mucocele. Ultraschall Med
ultrasonography: analysis of 258 consecutive cases. Laryngoscope 2001;22(2):100-3.
1975;85(11 pt 1):1905-19. 20. Yan J, Wu Z. Cavernous hemangioma of the orbit: analysis of 214
2. Coleman DJ, Silverman RH, Lizzi FL, Lyold H, Rondeau MJ, cases. Orbit 2004;23(1):33-40.
Reinstein DZ, Daly SW. Ultrasonography of the eye and orbit. 21. Betharia SM, Sharma V, Pushker N. Ultrasound findings in orbital
2nd edition. Philadelphia: Lippincott Williams and Wilkins; hydatid cysts. Am J Ophthalmol 2003;135(4):568-70.
Chapter 5, Orbital diagnosis; 2006;143-68. 22. Kenney AH, Hafner JN. Ultrasonic evidence of inflammatory
3. McNicholas MM, Brophy DP, Power WJ, Griffin JF. Ocular thickening and fluid collection within the retrobulbar fascia: the
sonography. AJR Am J Roentgenol 1994;163(4):921-6. T sign. Ann Ophthalmol 1977;9(12):1557-63.
4. Munk PL, Vellet AD, Levin M, Lin DT, Collyer RT. Sonography 23. Jank S, Emshoff R, Etzelsdorfe M, Strobl H, Nicasi A, Norer B.
of the eye. AJR Am J Roentgenol 1991;157(5):1079-86. Review. Ultrasound versus computed tomography in the imaging of orbital
5. Ultrasonic investigation (editorial). Br J Ophthalmol floor fractures. Journal of Oral and Maxillofacial Surgery
1979;63(8):531-2. 2004;62:150-4.
6. Coleman DJ, Silverman RH, Lizzi FL, Lyold H, Rondeau MJ, 24. Sutherland GR, Forrester JV. B-scan ultrasonography in
Reinstein DZ, Daly SW. Ultrasonography of the eye and orbit. ophthalmology. Br J Radiol 1974;47(559):383-6.
Chapter 5.6
OCULAR PHARMACOLOGY
J Nirmal, S Senthilkumari, T Velpandian
CONSTRAINTS EXERTED FOR Constraints Exerted by the Cornea

INTRAOCULAR PENETRATION OF DRUGS
The different routes of administration for delivering ocular
Drugs may enter the ocular tissues via anterior or posterior drugs are shown in (Fig. 5.6.2).
route. The entry through anterior route is important for the Even though several routes of drug administration are
treatment of diseases of the anterior segment such as available, topical instillation is very popular in ocular therapy.
inflammation, infections and glaucoma. The delivery of drugs However, the cornea is considered as a major barrier for
drug penetration through the anterior route. The cornea is a
to the posterior segment is often challenged by the presence
typical tissue having relatively lipophilic epithelium of
of blood-retinal barrier (BRB) which restricts the entry of
approximately five to seven cell layers thick, followed by a
drugs from the systemic circulation into the posterior tissues
hydrophilic stromal layer comprising some 85 to 90 percent
such as retina and vitreous.1 Therefore, ocular delivery is
of the corneal thickness and, a single cell layer thick
often challenging because of its anatomical location and
endothelium. The constraints exerted by different layers of
presence of an excellent guarding system2-4 (Fig. 5.6.1). cornea are different (Fig. 5.6.3).
Fig. 5.6.1: Schematic diagram of blood-ocular barriers Fig. 5.6.2: Route of administration for ocular drugs
Fig. 5.6.3: Different layers of cornea
There are two obvious pathways for drugs to move across

Fig. 5.6.4: Permeation across corneal epithelium
the epithelium: Intercellular and transcellular (Fig. 5.6.4).
The intercellular spaces in the basement layers of this
tissue are rather wide due to the columnar nature of the cells Ocular Barriers and Their
so that even a large molecule like horseradish peroxidase Relevance to Therapeutics
(MW 40 kDa), when injected into the anterior chamber,
diffuse into the corneal epithelium.5 However, its movement The blood-ocular barriers (BOB) comprises the blood aqueous
is considerably restrained after reaching the anterior top two barrier and the blood-retinal barrier (BRB).2
The blood aqueous barrier function is enabled by the
to three layers of this tissue, due to narrowing of the
presence of epithelial barrier located in the non-pigmented
intercellular space as the cells undergo transformation from
layer of the ciliary epithelium, posterior iridial epithelium,
a columnar to flattened arrangement. In fact, the total surface and endothelium of the iridial blood vessels. These structures
area of the cornea exposed to the tear that can be attributed are reported to have tight junctions of the “leaky” type. The
to intercellular spaces is rather small. Consequently, unless a permeability of the blood-aqueous barrier shows a significant
drug is extremely water soluble, it would prefer the degree of pressure dependent diffusion associated with
transcellular route on the basis of surface area alone.4 The transport activity, resembling the standing gradient osmotic
endothelium being “leaky” in characteristics is not considered flow model.3
as a significant barrier for most drugs. The optimum partition The BRB is situated between the blood and the retina,
coefficient for corneal drug permeation has been reported thereby, restricts the permeability. This barrier has a well-
to be in the range of 10 to 100. 6-9 Other restrictive defined anatomic structure, particular per meability
mechanisms of the eye include solution drainage and characteristics and appears to play a role of major importance
lacrimation which influences the entry of exogenous in the pathophysiology and therapeutics of retinal diseases.
substances from the internal structures of the eye. Other BRB restricts the movements of substances after systemic
factors which influence corneal permeation of topically and periocular administration to the retina. BRB has been
shown to have similar features with blood-brain barrier (BBB).
instilled drugs are pH, tonicity, viscosity and the presence of
The BRB phenomenon operates fundamentally at two
adjuncts such as chelating agents and preservatives.4 Low
levels, retinal vessels and the chorioepithelial interface, forming
ocular permeability is primarily attributed to the inability of the inner BRB and an outer BRB. The main structures
drug molecules to partition between the lipophilic epithelial involved, for the inner BRB are the endothelial membrane
layer and subsequent hydrophilic layers of cornea.10 Apart of the retinal vessels, and for the outer BRB, the retinal
from physicochemical properties of drugs applied topically, pigment epithelium. Zonulae occludentes are present in these
there could be a physiological protective mechanism membranes forming complete belts around the cells, sealing
responsible for the poor penetration of drugs across the off the spaces between them. Other structures appear to
cornea. play an accessory role.2
Ocular Pharmacology 337
DRUGS USED FOR OCULAR INFECTIONS Dosage and administration: One or two drops (0.3%) for every
four hours and hourly in severe infections.
Antibacterials
Several antibacterials are formulated for topical use in various Quinolones
ocular infections. Topical antimicrobials are classified according Quinolones are synthetic antimicrobials having a quinolone
to their chemical structure.11,12 structure and is primarily active against gram-negative bacteria.
• Aminoglycosides, e.g. gentamycin and tobramycin The newer quinolones are also able to inhibit gram positive
• Fluoroquinolones, e.g. ciprofloxacin, ofloxacin, bacteria.15
levofloxacin, pefloxacin, lomioxifloxacin, moxifloxacin, Fluoroqinolones: Fluoroquinolones are the quinolone
gatifloxacin antimicrobials having one or more fluorine substitutions. The
• Macrolides, e.g. erythromycin fluoroquinolones are potent bactericidal agents against E. coli
• Sulfonamides, e.g. sulfacetamide and various species of Salmonella, Shigella, Enterobacter,
• Others, e.g. chloramphenicol Campylobacter and Neisseria.15
• First generation fluoroquinolones: norfloxacin, ofloxacin,
Aminoglycosides ciprofloxacin, pefloxacin
• Second generation fluoroquinolones: lomefloxacin,
The aminoglycosides consist of two or more amino sugars
sparfloxacin, levofloxacin, gatifloxacin, moxifloxacin
joined in glycosidic linkage to a hexose nucleus called
aminocyclitol. They are bactericidal inhibitors of protein Ciprofloxacin: Ciprofloxacin is a bactericidal antibiotic
synthesis. belonging to the quinolone class fluoroquinolones, which is
active against a broad range of bacteria.
Gentamicin: Gentamicin, a broad-spectrum antibiotic was
Mechanism of action: During transcription or replication, the
derived from species of the actinomycete Micromonospora.
two strands of double-stranded DNA must be separated, a
Mechanism of action: It is a bactericidal antibiotic. It acts by process which results in the excessive positive supercoiling
transporting the aminoglycoside through the bacterial cell wall of the DNA in front of the point of separation of the strands.
and cytoplasmic membrane by binding to ribosomes thereby This positive supercoiling must be corrected by rotation of
inhibiting protein synthesis.13 DNA in the opposite direction in order to allow further
Indications: Gentamicin sulfate sterile ophthalmic solution is transcription or replication to proceed. This function is
indicated in the topical treatment of ocular bacterial infections, performed by the bacterial enzyme DNA gyrase which is a
including conjunctivitis, keratitis, keratoconjunctivitis, corneal type II topoisomerase. Ciprofloxacin inhibits the function of
ulcers, blepharitis, blepharoconjunctivitis, acute meibomianitis, this enzyme. This process of negative supercoiling is of equal
and dacryocystitis caused by susceptible strains of the following importance in mammalian cell. The bacterial selectivity derives
microorganisms: Staphylococcus aureus, Staphylococcus epidermidis, from the fact that the mammalian type II topoisomerase
Streptococcus pyogenes, Streptococcus pneumoniae, Enterobacter aerogenes, enzyme is only inhibited by roughly one thousand fold higher
Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, concentrations of the drug. Ciprofloxacin has in vitro activity
Neisseria gonorrhoeae, Pseudomonas aeruginosa, and Serratia against a wide range of gram-negative and gram-positive
marcescens. organisms. The bactericidal action of ciprofloxacin results
from interference with the enzyme DNA gyrase which is
Dosage and administration: Gentamicin sulfate sterile ophthalmic
needed for the synthesis of bacterial DNA.
solution (0.3) every four hours (once every hour in severe
infections). Indications: Ciprofloxacin eye preparations are used to treat
bacterial infections of the eye such as conjunctivitis. They
Tobramycin: Tobramycin is one of several components of may also be prescribed to treat corneal ulcers.
an aminoglycoside complex (nebramycin) that is produced Ophthalmic solution is indicated for the treatment of
by S. tenebrarius. It is most similar in antimicrobial activity and infections caused by susceptible strains of the designated
toxicity to gentamicin.14 microorganisms in the conditions listed.
Mechanism of action: It acts by interfering with bacteria protein • Corneal Ulcers: Pseudomonas aeruginosa, Serratia marcescens,
synthesis.13 Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus
Indications: Tobramycin ophthalmic solution is a topical pneumoniae, Streptococcus viridans
antibiotic indicated in the treatment of external infections of • Conjunctivitis: Haemophilus influenzae, Staphylococcus aureus,
the eye and its adnexa caused by susceptible bacteria. Staphylococcus epidermidis, Streptococcus pneumoniae
Dosage and administration: Ophthalmic ciprofloxacin is pteridine with aminobenzoic acid through competitive
commercially available as a solution (0.3%) and an ointment inhibition of the enzyme dihydropteroate synthetase. Resistant
for ophthalmic use. strains have altered dihydropteroate synthetase with reduced
Ofloxacin: Ofloxacin is a bactericidal antibiotic of the affinity for sulfonamides or produce increased quantities of
quinolone class. Its pharmacology is similar to ciprofloxacin. aminobenzoic acid.18
It is a fluorinated carboxyquinolone anti-infective for topical Indications and usage: Sulfacetamide sodium (10, 15 and 30%
ophthalmic use. w/v) is indicated for the treatment of conjunctivitis and other
superficial ocular infections due to susceptible microorganisms,
Mechanism of action: Refer to ciprofloxacin.
and as an adjunctive in systemic sulfonamide therapy of
Indications: Ofloxacin ophthalmic solution (0.3%) is indicated trachoma: Escherichia coli, Staphylococcus aureus, Streptococcus
for the treatment of conjunctivitis and corneal ulcers. pneumoniae, Streptococcus (viridans group), Haemophilus influenzae,
Dosage and administration: The recommended dosage regimen Klebsiella species, and Enterobacter species.
for treatment is four times daily for bacterial conjunctivitis Dosage and administration: Two hourly (for trachoma), systemic
and every 30 minutes for bacterial corneal ulcer. administration also recommended.
Moxifloxacin Chloramphenicol: Chloramphenicol is an antibiotic produced
Mechanism of action: Bacterial topoisomerase IV is the major by Streptomyces venezuelae.
target of action. Mechanism of action: Chloramphenicol acts primarily by binding
Indications: Moxifloxacin solution (0.5%) is indicated for the reversibly to the 50S ribosomal subunit (near the binding site
treatment of bacterial conjunctivitis. for the macrolide antibiotics and clindamycin, which
Dosage and administration: One drop (0.5%) is instilled in the chloramphenicol inhibits competitively). Although binding of
affected eye three times a day for seven days. tRNA at the codon recognition site on the 30S ribosomal
subunit is undisturbed, the drug apparently prevents the
Macrolides binding of the amino acid-containing end of the aminoacyl
Macrolide antibiotics contain a many-membered lactone ring tRNA to the acceptor site on the 50S ribosomal subunit. The
(14-membered rings for erythromycin and clarithromycin and interaction between peptidyl transferase and its amino acid
a 15-membered ring for azithromycin) to which are attached substrate cannot occur, and peptide bond formation is
one or more deoxysugars.16,17 inhibited
It is available as an ophthalmic solution of 0.5 percent.
Erythromycin: Erythromycin is the metabolic products of a
Indications: Conjunctivitis and keratitis.
strain of Streptomyces erythreus.
Dosage: One drop four to six times daily.
Mechanism of action: Erythromycin acts by preventing the
bacterial protein synthesis by binding reversibly to the 50S
ribosomal subunit. Thereby, it inhibits the process of Anti-fungal Agents
translocation, whereby a newly synthesized peptide tRNA Fungal infections of the cornea (mycotic or fungal keratitis,
moves from the acceptor to a site on the ribosome to the keratomycosis) are a serious sight threatening condition which
peptidyl or donor (P) site.16,17 warrants prompt diagnosis for effective treatment. The
Indications: For the treatment of superficial ocular infections management of fungal infections poses a great challenge to
involving the conjunctiva and cornea caused by organisms the physician in clinical practice. Ophthalmic indications for
susceptible to erythromycin such as blepharitis and antifungal medications include fungal keratitis, scleritis,
conjunctivitis. endophthalmitis, mucormycosis, and canaliculitis.19-24 They
Dosage and administration: Four to six times daily of 0.5 percent are broadly classified into:
ointment (ocular infections). • Polyene antifungals: Amphotericin, natamycin
• Azole antifungals: Fluconazole, itraconazole, voriconazole
Sulfonamides
Sulfacetamide Polyenes
Mechanism of action: Sulfonamides inhibit bacterial synthesis Natamycin and amphotericin B are the only two drugs in this
of dihydrofolic acid by preventing the condensation of class, approved for the management of fungal mycoses.
Natamycin: Natamycin is a tetraene polyene derived from Histoplasma capsulatum, Sporothrix schenckii, Coccidioides immitis,
Streptomyces natalensis.21 It has been considered the mainstay Paracoccidioides braziliensis, Aspergillus spp., Penicillium marneffei,
of treatment for filamentous fungi. It possesses in vitro activity and the agents of mucormycosis.23
against a variety of yeast and filamentous fungi, including Mechanism of action: Amphotericin B reacts with ergosterol, a
Candida, Aspergillus, Cephalosporium, Fusarium and Penicillium.22 membrane constituent of fungi, forming a pore or a channel
Due to its limited aqueous solubility, it is presented as a five that leads to K+ or small molecule leakage and fungal cell
percent w/v topical suspension. death.
Mechanism of action: Natamycin acts by binding to sterol in Indications: The intravenous administration is the treatment
fungal cell membrane by inhibiting fungal growth or altering of choice for invasive fungal infections but this route may
membrane permeability. Following topical application, cause poor corneal penetration and severe nephrotoxicity.
natamycin is retained in the conjunctival fornices and attains • 0.1 to 0.5 percent (typically 0.15%) topical solution: Yeast
effective concentrations within the corneal stroma. Significant and fungal keratitis and endophthalmitis
drug concentration is usually not attained in the intraocular • 0.8 to 1 mg subconjunctival: Yeast and fungal
fluid and can be achieved only after the removal of corneal endophthalmitis
epithelium. • 5 µg intravitreal injection: Yeast and fungal endophthalmitis
• Intravenous: Yeast and fungal endophthalmitis
Indications: Natamycin ophthalmic suspension five percent is Intracameral injections of amphotericin B may be an
indicated for the treatment of fungal blepharitis, conjunctivitis, effective adjunct treatment of fungal keratitis unresponsive
and keratitis caused by susceptible organisms including to conventional antifungal therapy. Intravitreal amphotericin
Fusarium solani keratitis. is used in fungal endophthalmitis. Topical preparation (0.15%)
As in other forms of suppurative keratitis, initial and is well tolerated.
sustained therapy of fungal keratitis should be determined
by the clinical diagnosis, laboratory diagnosis by smear and Azoles
culture of corneal scrapings and drug response. Whenever
possible, the in vitro activity of natamycin against the responsible The azoles are purely synthetic drugs which was discovered
fungus should be determined. The effectiveness of natamycin in the late 1960s. They are classified as imidazoles or triazoles
as a single agent in fungal endophthalmitis has not been depending upon the presence of two or three nitrogens in
established. the 5-membered azole ring.25 The imidazole antifungals include
clotrimazole, isoconazole, econazole, miconazole and
Dosage and administration: The preferred initial dosage in fungal
ketaconazole. The miconazole and ketaconazole are being
keratitis is one drop of natamycin ophthalmic suspension,
five percent instilled in the conjunctival sac at hourly or two used in the treatment of ocular fungal infections. The triazoles
hourly intervals. The frequency of application can usually be include fluconazole and itraconazole
reduced to one drop six to eight times daily after the first Mechanism of action: Azoles are inhibitors of a cytochrome
three to four days. Therapy should generally be continued P450 fungal enzyme, i.e. 14-alpha sterol demethylase involved
for 14 to 21 days or until there is resolution of active fungal in the conversion of lanosterol to ergosterol which is an
keratitis. In many cases, it may be helpful to reduce the dosage essential sterol in fungal cell membranes. The decrease in
gradually at four to seven day intervals to assure that the ergosterol leads to the accumulation of 14-alpha methyl sterols.
replicating organism has been eliminated. Less frequent initial These methylsterols may disrupt the close packing of acyl
dosage (4–6 daily applications) may be sufficient in fungal chains of phospholipids, impairing the functions of certain
blepharitis and conjunctivitis. membrane-bound enzyme systems such as ATPase and
Amphotericin B: Amphotericin B is a macrolide polyene enzymes of the electron transport system and thus inhibiting
containing seven conjugated double bonds in the trans position growth of the fungi.19
and 3-amino-3, 6-dideoxymannose (mycosamine) connected
to the main ring by a glycosidic bond. The amphoteric Imidazole Antifungals
behavior is due to the presence of a carboxyl group on the Miconazole: Miconazole is usually reserved as a second-line
main ring and a primary amino group on mycosamine which drug in the management of fungal keratitis. It shows broad
confers aqueous solubility at extremes of pH. It is reported spectrum activity against many ocular pathogens including
to be effective against most clinically relevant pathogens like Aspergillus, Candida and Scedosporium. The reported routes of
Candida spp., Cryptococcus neoformans, Blastomyces dermatitides, administration in mycotic keratitis include topical (1%),
subconjunctival (10 mg) and intravenous (600–1200 mg/ tissues. Topical formulation of voriconazole is not available
day). commercially and therefore, it is being extemporaneously
Ketaconazole: Ketaconazole is a synthetic dioxolane prepared from lyophilized IV formulation after reconstituting
imidazole. It is available for oral (200–600 mg/day) and topical with either sterile water for injection or dextrose or saline.28
(1–2%) use. It shows good in vitro activity against Aspergillus
flavus, Candida species, Curvularia species, and some other Antiviral Drugs
ocular fungal pathogens. It is reported to be useful in the Infections of the eye can rapidly damage important functional
treatment of non-severe mycotic keratitis following oral
structures and lead to permanent vision loss or blindness.
administration. The oral preparation is often used
Viruses are obligatory intracellular ‘organisms’ and their
concomitantly with other antifungal agents.
replication is dependent on the host’s metabolism. It has been
difficult to develop treatment that is able to differentiate
Triazole Antifungals
between virus and host cell. However, recognition of viral
Fluconazole: Fluconazole is a bistriazole antifungal agent characteristics, their enzymes and proteins has led to the
with improved physical and pharmacokinetic properties. It development of effective virostatic agents. Viral infections
has good overall activity against Candida species and are a significant cause of ocular morbidity and epidemiological
Cryptococcus neoformans. However, resistance to the drug is studies indicate that they are the most common cause of
encountered in certain non-albicans Candida species such as corneal blindness worldwide. Therefore, there is an obvious
C. krusei and some isolates of C. glabrata.26 It is available as need for efficient prevention and treatment of ocular viral
oral (200 mg), topical (1–2%) and intravenous formulations diseases.
(2 mg/ml). Collectively, the herpes viruses and adenoviruses are the
Itraconazole: Itraconazole is a dioxolane triazole and showed etiologic agents for lesions of viral infections annually.29-32
good in vitro activity against all Aspergillus spp, Candida and Adenoviral infections are some of the most common external
many dematiaceous fungi. However, it showed poor activity eye infections. In children, these are generally accompanied
against Fusarium spp, Lasiodiplodia and zygomycetes.27 It is by mild sore throat and low-grade fever, thus the descriptive
available as an oral capsule (200–400 mg) and as topical name, pharyngoconjunctival fever. These infections present
suspension (1–2%). It is well absorbed orally with 90 percent in adults as hemorrhagic conjunctivitis with an acute, painful
of the drug bound to plasma protein. The major drawback red eye and most notably, an ipsilateral, palpable preauricular
of using itraconazole by the oral route is its poor penetration lymphadenopathy.
into cornea, aqueous humor and vitreous as compared to Herpes zoster occurs as a result of reactivation of latent
fluconazole and ketaconazole. Oral itraconazole was found infection with the varicella-zoster virus. Varicella zoster
to be effective in fungal keratitis caused by Pichia anomala infection or shingles, most commonly affects the first division
and Scedosporium apiospermum when used in combination with of the trigeminal nerve, resulting in the classic presentation
topical amphotericin B and natamycin. Topical itraconazole of herpes zoster ophthalmicus.29 The available antivirals drugs
is showed to be useful for treating infections due to Aspergillus
(Table 5.6.1) are:
or Curvularia species.
Acyclovir: Acyclovir is a guanosine analog that lacks a true
New Azoles sugar moiety and gets monophosphorylated in the cell by the
Voriconazole: Voriconazole is a new triazole anti-fungal agent herpes virus-encoded enzyme, thymidine kinase.
with the broadest spectrum of activity. This is a synthetic Monophosphate analog gets converted to di- and triphosphate
derivative of fluconazole approved by the FDA for the forms by the host cells. Acyclovir triphosphate competes with
treatment of invasive aspergillosis, esophageal candidiasis and deoxyguanosine triphosphate as a substrate for the viral DNA
other systemic indications. It demonstrated a broad spectrum polymerase and gets itself incorporated into the viral DNA
of activity against Aspergillus species, Blastomyces dermatitidis, causing premature DNA chain termination and inactivation
Candida species, Paecilomyces lilacinus, Coccidioides immitis, of the enzyme. The drug is effective against herpes simplex
virus-1 (HSV-1), herpes simplex virus-2 (HSV-2), varicella-
Cryptococcus neoformans, Histoplasma capsulatum, Penicillium
zoster virus (VZV) and is resistant to cytomegalovirus (CMV).
species, Scedosporium species, Curvularia species and others
in vitro. It has 96 percent oral bio-availability and reaches Valacyclovir: Valacyclovir is a pro-drug of acyclovir. Because
peak plasma concentrations two to three hours following oral it is a pro-drug, it has enhanced bioavailability and a longer
administration with good distribution into the body fluids and half-life than the parent compound, acyclovir. Due to the
Table 5.6.1: Antiviral agents for ophthalmic use

Generic name Route of administration Indication for use
Trifluridine Topical (1% solution) Herpes simplex keratitis
Herpes simplex conjunctivitis
Vidarabine Topical (3% ointment) Herpes simplex keratitis
Herpes simplex conjunctivitis
Acyclovir Oral, intravenous Herpes zoster ophthalmicus
(200 mg capsules, 400 mg and 800 mg tablets) Herpes simplex iridocyclitis
Valacyclovir Oral (500 mg, 1000 mg tablets) Herpes simplex keratitis
Herpes zoster ophthalmicus
Famciclovir Oral (125 mg, 250 mg, 500 mg tablets) Herpes simplex keratitis
Herpes zoster ophthalmicus
Foscarnet Intravenous Cytomegalovirus retinitis
Intravitreal
Ganciclovir Intravenous, oral Cytomegalovirus retinitis
Intravitreal implant
Formivirsen Intravitreal injection Cytomegalovirus retinitis
Cidofovir Intravenous Cytomegalovirus retinitis
enhanced pharmacodynamics, valacyclovir is used three times retinitis leads to visual problems and blindness. This
a day rather than the five times a day for acyclovir. complication usually occurs with advanced immunosuppression
Famciclovir: Famciclovir, an oral prodrug of penciclovir, is and usually patients with CMV retinitis have CD4+
well absorbed orally. Penciclovir is active against HSV-1, HSV-2 lymphocyte counts of less than 100 cells/mm3. The diagnosis
and VZV with potency and spectrum of activity similar to of CMV retinitis is usually made clinically on the finding of
acyclovir. Penciclovir selectively affects viral DNA synthesis yellowish white areas of retinal necrosis and edema that follow
and inhibits replication. a vascular distribution. There may be hemorrhagic areas in
Trifluridine: Trifluridine is a fluorinated pyrimidine nucleo- the retina (salad cream and tomato sauce appearance), severe
side that inhibits HSV type 1 and 2. It inhibits viral DNA posterior chorioretinitis and mild anterior uveitis.33
synthesis. Trifluridine-monophosphate irreversibly inhibits
thymidylate synthase and is a competitive inhibitor of DNA Ganciclovir and valganciclovir: Ganciclovir and
polymerase that incorporates thymidine triphosphate into the valganciclovir are acyclic guanine nucleoside analogs.
DNA. The adverse reactions include hypersensitivity, irritation, Valganciclovir is a prodrug effective against CMV. The
etc. It is the current drug of choice for topical treatment of mechanism of action is similar to acyclovir as it inhibits viral
primary and recurrent HSV keratitis types 1 and 2. DNA synthesis. These provide ten times more intracellular
Idoxuridine: Idoxuridine is an iodinated thymidine analog concentration than acyclovir and can be given topically, IV
that inhibits replication of DNA virus. The drug is effective or intravitreally. The adverse reactions include headache,
against HSV and Poxvirus. The phosphorylated derivative behavioral changes, convulsions and coma. Ganciclovir has
inhibits viral DNA but the exact mechanism is still unknown. also been shown to be active against HSV keratitis.
Adverse reactions include pain, inflammation and
hypersensitivity edema of the eyelid. Cidofovir: Cidofovir is a cytidine nucleotide analog that
inhibits herpes, papilloma, polyoma and adenovirus. It acts
Vidarabine: This drug was initially designed to treat herpes by inhibiting viral DNA synthesis (mechanism similar to
zoster (varicella zoster virus). Therefore the standard, usual acyclovir). It has low oral bioavailability, and is therefore given
dosage recommendations are for zoster disease. It is highly intravitreally. A number of clinical studies have already shown
effective against herpes simplex disease for corneal epithelial the efficacy of cidofovir to the treatment of acute adenoviral
keratitis. keratoconjunctivitis.30 The side effects include nephrotoxicity
in addition to the intravitreal side effects viz. vitritis, hypotony
Drugs for Cytomegalovirus Retinitis and visual loss.
Cytomegalovirus (CMV) infection occurs commonly in the Foscarnet: Foscarnet is an inorganic pyrophosphate analog.
general population. The virus is a herpes virus that can remain It inhibits herpes and human immunodeficiency virus (HIV)
latent in the body for many years after initial infection. CMV by inhibiting herpes virus DNA polymerase, reversibly
blocking the pyrophosphate binding site of viral polymerase Hydrogen peroxide disinfection is the oldest chemical care
and inhibiting its cleavage from deoxynucleotide. It can be system for soft contact lenses. This care system was introduced
given by intravenous and intravitreal routes. The adverse in Canada in 1969. Hydrogen peroxide is used for contact
reactions comprise nephrotoxicity, symptomatic hypocalcemia lens disinfection due to its broad antimicrobial activity.
and CNS adverse reactions including headache, tremors, Hydrogen peroxide is an effective microbial disinfectant,
irritability, seizures and hallucinations. destroying pathogens by oxidation. It is active against the
Fomiversen: Fomiversen is an antisense oligonucleotide that resistant cyst for m of Acanthamoeba when used at a
is complementary to the mRNA, for the major early concentration of three percent with an exposure time of at
transcriptional region of CMV and inhibits CMV replication. least four to six hours. However, hydrogen peroxide is toxic
It is active against CMV strains resistant to ganciclovir and to the cornea and must be neutralized before lens wear to
foscarnet. Ocular side effects include iritis, vitritis, cataracts, avoid pronounced stinging, lacrimation, hyperemia, and
and increased IOP. possible corneal damage.35
Benzalkonium chloride (BKC): Transoak (0.01%
Anti-Acanthamoeba Formulation benzalkonium chloride (BAK) and 0.2% disodium edetate).
BKC has the greatest biocidal activity. It is associated
Acanthamoeba represent microorganisms which occur
with the C12-C14 alkyl derivatives. The mechanism of
ubiquitously worldwide. Acanthamoeba is a genus of amoebae,
bactericidal/microbicidal action is thought to be due to
one of the most common protozoa in soil, and is also
disruption of intermolecular interactions. BKC can cause
frequently found in fresh water and other habitats. The cells
dissociation of cellular membrane lipid bilayers, which
are small, usually 15 to 35 µm in length and oval to triangular
compromises cellular permeability controls and induces
in shape when moving. Their double-walled cysts are extremely
leakage of cellular contents. They are active against bacteria
resistant against desiccation and spread through the air easily, and some viruses, fungi, and protozoa. Bacterial spores are
making frequent contact with this micro-organism almost considered to be resistant. Gram-positive bacteria are generally
inevitable.34 more susceptible than gram-negative bacteria. Activity
Acanthamoebae can cause infections of several organs, increases substantially at higher temperatures and prolonged
including eye, skin, lung and brain. Except for Acanthamoeba exposure times
keratitis, these infections are linked to immunodeficiency.35
They provoke the so called Acanthamoeba keratitis, which is a DRUGS USED FOR OCULAR
chronic and very often seriously progressive disease occurring INFLAMMATION
predominantly in contact lens wears. They are also responsible Inflammation is a characteristic response of the mammalian
for chronic granulomatous amoebic encephalitis (GAE) and tissue to injury. Injury to the tissue may be inflicted by physical
several disseminating infections in the immunocompromised or chemical agents, invasion of pathogens, ischemia, and
host, including dermatitis and pneumonitis.34 Acanthamoeba is a excessive hypersensitivity or inappropriate (autoimmune)
free-living amoeba causing a potentially blinding infection of operation of immune mechanisms. Signs and symptoms of
the cornea. Contact lens wearers are most at risk from ocular inflammation include pain, photophobia, redness,
infection, accounting for approximately 95 percent of itching, heat and swelling. In ocular tissues, arachidonic acid
reported cases. Infection results from contamination of lens is metabolized by cyclooxygenase to prostaglandins which are
care products, notably the lens storage case, from which the the most important lipid derived mediators of inflammation.
organism adheres to the contact lens and is inoculated onto Ocular inflammation, if left untreated, may lead to temporary
the cornea.35 or permanent vision loss.36 Commonly, inflammation in the
The two most common methods of contact lens eye results due to uveitis, allergic conjunctivitis and
disinfection are the multipurpose solutions in which a single postoperative ocular inflammation after cataract surgery.
solution is used for disinfecting, cleaning, and storing lenses Uveitis affects 0.2 percent of individuals in the developed
and hydrogen peroxide-based systems. Table 5.6.2 provides world and one to two percent in developing countries, although
details of some of the commercially available anti- results from a recent study suggest that the incidence may be
acanthamoebic formulas for contact lens care. three times that of previous estimates.36 Ocular allergy may
affect 15 to 20 percent of individuals in the world and 25
Hydrogen peroxide: AOSept (3% hydrogen peroxide with percent of patients seen by ophthalmologists complain of
0.85% sodium chloride), Oxysept (3% hydrogen peroxide). symptoms of dry eye.37
Table 5.6.2: List of commercially available antiacanthamoebic formulations for contact lens care
Solution trade name Manufacturer Active ingredients (mg/ml) Preservatives Types of
contact lens
Bausch & Lomb Multi Bausch & Lomb Polyaminopropyl biguanide (Dymed) 0.11% (wt/vol) Soft
purpose Solution (0.0005); sodium borate (1.20); Disodium edentate
sodium chloride (4.9);
poloxamine 1107 (10.00);
boric acid (6.40)
Complete Allergan Polyhexamethylene biguanide (0.001) Soft
Duracare Allergan 0.004% Polyvinyl alcohol 0.004% Benzalkonium Gas
chloride;0.004% Permeable
Sodium edetate
Hydrocare Cleaning/ Allergan Alkyl triethanol ammonium 0.002% Thiomersal Soft
Soaking Solution chloride (0.3)
Optifree Alcon 0.001% m/v Polyquad Soft
(polyquaternium-1);
0.05% (wt/vol)
sodium edentate
Optisoak Alcon 0.75 g polyvinyl alcohol; Polyquad, ie (polyquaternium-1) Gas
0.005 g polysorbate 80;0.65g 0.005% (wt/vol)edetate permeable
hydroxyethyl cellulose sodium 0.1% (wt/vol) and hard
(all per 100 ml) +
sodium chloride +
sodium phosphates
Oxysept 1 Allergan Hydrogen peroxide (31.0) Soft
Oxysept 1 Step Allergan 3% Hydrogen peroxide Soft
Total Allergan Polyvinyl alcohol (25.0) 0.004% benzalkonium chloride Gas perme-
able and
hard
Transoak Chauvin 0.01% (wt/vol) benzalkonium chloride 0.2% (wt/vol) disodium edetate Gas
Pharmaceuticals permeable
Ltd and hard
Transol Wetting Chauvin 1 g polyvinyl alcohol/50 ml 0.004% benzalkonium chloride; Gas
Solution Pharmaceuticals 0.02% (wt/vol)disodium edetate permeable
Ltd and hard
The pharmacological approach for the management of pseudotumor and optic neuritis may require the need for
ocular inflammation involves administration of anti- oral corticosteroids. However, topical steroids are available
inflammatory agents. After the recognition of anti- for the management of some ocular inflammatory conditions
inflammatory activity of adrenocortical extracts in the early like uveitis and chalazion. Topical corticosteroids include
1940s, use of various systemic and topical corticosteroids hydrocortisone, cortisone, prednisolone, prednisone,
started followed by the advent of nonsteroidal anti- dexamethasone, betamethasone, triamcinolone, paramethasone,
inflammatory drugs (NSAIDs), for controlling various fludrocortisone, medrysone, fluorometholone, loteprednol and
inflammatory conditions of eye. Both these classes of anti- rimexolone. The currently available ophthalmic corticosteroids
inflammatory agents affect the arachidonic acid cascade, are given in Table 5.6.3.
thereby preventing the formation of prostaglandins (PGs)
Mechanism of action: Corticosteroids act by blocking the enzyme
and their intermediary by-products which is the main factor
phospholipase A2 to inhibit the production of arachidonic
behind ocular inflammation.
acid, thereby preventing the synthesis of all the PGs,
Steroidal Anti-Inflammatory Drugs thromboxanes and eicosanoids.
Several ocular inflammatory conditions including uveitis, Therapeutic uses: Corticosteroids are used as the mainstay in
scleritis, arteric anterior ischemic optic neuropathy, orbital the treatment of ocular inflammation. However, their use is
Table 5.6.3: Ophthalmic corticosteroid formulations

Corticosteroid base Derivative Formulation Strength (%) Indications Dosage
Prednisolone Acetate Suspension 0.125 and 1.0 Steroid responsive inflammatory Four times daily
Prednisolone Sodium Solution 0.125 and 1.0 conditions of the palpebral and
phosphate bulbar conjunctiva, cornea, and
anterior segment of the globe,
such as allergic conjunctivitis,
acne rosacea, superficial punctate
keratitis, herpes zoster keratitis,
iritis, cyclitis, Corneal injury from
chemical, radiation, or thermal burns,
or penetration of foreign bodies
Dexamethasone Alcohol Suspension 0.1 Acne rosacea keratitis, allergic Four times daily
Dexamethasone Sodium Solution 0.1 conjunctivitis, corneal abrasion,
phosphate corneal ulcer, cyclitis, herpes zoster
keratitis, iridocyclitis, iritis, ocular
inflammation, postoperative ocular
inflammation, punctate epithelial
keratopathy, uveitis
Fluorometholone Alcohol Suspension 0.1 Steroid responsive inflammatory Four times daily
Fluorometholone Acetate Suspension 0.1 conditions of the palpebral and
bulbar conjunctiva, cornea, and
anterior segment of the eye
Medrysone Alcohol Suspension 1.0 Allergic conjunctivitis, vernal Four times daily
conjunctivitis, episcleritis, and
epinephrine sensitivity
Loteprednol Etabonate Suspension 0.5 and 0.2 Steroid responsive inflammatory Four times daily
conditions of the palpebral and
bulbar conjunctiva, cornea and
anterior segment of the globe such
as allergic conjunctivitis, acne
rosacea, superficial punctate
keratitis, herpes zoster keratitis,
iritis, cyclitis, selected infective
conjunctivitides, when the inherent
hazard of steroid use is accepted
to obtain an advisable diminution in
edema and inflammation
Post-operative inflammation
following ocular surgery
Rimexolone Suspension 1.0 Treatment of postoperative Four times daily
inflammation following ocular
surgery, for the treatment of
anterior uveitis, and for the
treatment of corticosteroid
responsive inflammation of
the palpebral and bulbar
conjunctiva, cornea, and anterior
segment of the globe
limited due to serious side effects. Topical corticosteroids are delay the wound-healing process by decreasing fibroblast
used in managing significant ocular allergy, anterior uveitis, infiltration, thereby reducing potential scarring of the surgical
external eye inflammatory diseases associated with some site.
infections and ocular cicatricial pemphigoid, and postoperative Mode of administration: Steroids are commonly given
inflammation following refractive, corneal, and intraocular systemically and by sub-Tenon’s capsule injection to manage
surgery. After glaucoma filtering surgery, topical steroids can posterior uveitis. Intravitreal injection of steroids now is being
used to treat a variety of retinal conditions including age- Bendazac: Bendazac is structurally related to indomethacin.
related macular degeneration, diabetic retinopathy, and cystoid Its lysine salt (0.5% w/v) is used for delaying the progression
macular edema. Parenteral steroids followed by tapering oral of cataract has been reported to be absorbed better than the
doses are the preferred treatment for optic neuritis. parent compound.41
Toxicity of corticosteroids: Side effects include increased Diclofenac: For ophthalmic use, diclofenac is commercially
intraocular pressure (glaucoma), risk of cataract formation available as 0.1 percent aqueous solution of its sodium salt.
after long term use, worsening of viral infection, decreased
Ketorolac: Ketorolac ophthalmic solution is a racemic mixture
resistance to infection and corneal wound healing. Many cases
of R–(+) and S–(–) ketorolac tromethamine. It is marketed
of uveitis, mydriasis and ptosis due to their usage have also
as 0.4 percent solution. Ketorolac tromethamine ophthalmic
been reported.
solution has been safely administered in conjunction with
Non-Steroidal Anti-Inflammatory other ophthalmic medications such as antibiotics, beta blockers,
Drugs (NSAIDs) carbonic anhydrase inhibitors, cycloplegics, and mydriatics.
Nepafenac: It is a prodrug which showed six times faster
Various side effects of corticosteroids brought NSAIDs into
permeation than that of diclofenac and after penetration, it
the field of interest. NSAIDs have been proven to be safe
is deaminated by intraocular hydrolases to amfenac, a potent
and effective alternatives to corticosteroids in the management
inhibitor of COX1 and COX2.
of ocular inflammation.
Bromfenac: It is structurally similar to amfenac with the
Mechanism of action: NSAIDs exert their anti-inflammatory
action by inhibiting the enzymes cyclooxygenase (COX1 and exception of bromine atom at C4 position which makes it
COX2). more lipophilic, facilitates corneal penetration, increased
duration of action and enhanced COX-2 inhibitory activity.42
Classification of Ocular NSAIDs Aqueous drops containing equivalent of 0.09 percent w/v
bromfenac have been used in the management of
Salicylates: Aspirin. postoperative ocular inflammation and pain in patients who
Indole acetic acid derivatives: Indomethacin, bendazac. have undergone cataract extraction.
Aryl acetic acid derivatives: Diclofenac, ketorolac, nepafenac, Tolmetin: Ocular anti-inflammatory activity of aqueous
bromfenac and tolmetin. tolmetin (0.5%) ophthalmic solution was found to significantly
Aryl propionoc acid derivatives: Ibuprofen, flurbiprofen, reduce the signs and symptoms of ocular inflammation in
ketoprofen, naproxen, oxaprozin, pranoprofen and suprofen. sodium arachidonate-induced ocular inflammation in rabbits.43
Enolic acid derivatives: Piroxicam. Flurbiprofen: Aqueous solutions of flurbiprofen sodium
(0.03%) are used to inhibit intra-operative miosis during
Therapeutic Uses of NSAIDs cataract surgery and to control postoperative inflammation
Topical NSAIDs are widely used in the inhibition of intra- of the anterior segment of the eye.40 It has also been used in
operative miosis, management of post-operative the topical treatment of cystoid macular edema. The S–(+)
inflammation, treatment of seasonal allergic conjunctivitis, isomer of flurbiprofen has been found to be 100 times more
prevention and treatment of cystoids macular edema and in potent inhibitor of prostaglandin synthesis than the
the control of pain after photorefractive keratectomy.38 R–(–) isomer.44
Aspirin: Topically administered aspirin was found to Naproxen: Topical administration of aqueous naproxen
significantly block arachidonic acid induced lid closure and sodium eye drop (0.1% and 0.2%) was reported to control
chemosis in rabbits. It was found to be clinically efficacious the ocular inflammation in patients having phacoemulsification
and safe in the treatment of pollen induced allergic and intraocular lens implantation.
conjunctivitis.39 Pranoprofen: Topical aqueous solution (0.1%) is used in the
Indomethacin: Topical indomethacin (0.5% or 1% w/v) is management of ocular inflammation and it has been
used to prevent miosis during cataract surgery and to prevent demonstrated to possess analgesic and ocular anti-
cystoids macular edema.40 inflammatory activity comparable to flurbiprofen in
endotoxin–induced uveitis model. It has also been found to DRUGS USED FOR ALLERGIC
be as effective as diclofenac sodium (0.1% w/v) in reducing CONDITIONS
pain and inflammation after strabismus surgery.45 Ocular allergy refers to a variety of hypersensitive disorders
Suprofen: Suprofen one percent eye drops are applied that affect the lid, conjunctiva and/or cornea. They are
topically to inhibit intraoperative miosis during ocular surgery. commonly associated with immune–mediated inflammatory
Suprofen eye drops have been found to be useful in the reactions.49 Various clinical forms include seasonal allergic
treatment of contact lens associated giant papillary conjunctivitis (SAC), perennial allergic conjunctivitis (PAC),
conjunctivitis. Suprofen does not interfere with stromal wound vernal keratoconjunctivitis (VKC), atopic keratoconjunctivitis
healing. Suprofen eye drops may cause local reactions including (AKC), giant papillary conjunctivitis (GPC) and contact or
discomfort, itching, pain and photophobia. drug-induced dermoconjunctivitis. Their clinical features are
Piroxicam: Pre-treatment with topical piroxicam (0.5%) in presented in Table 5.6.4. SAC and PAC are the most common
glaucoma patients undergoing argon trabeculoplasty effectively allergic conditions accounting for almost 90 percent of ocular.
inhibited ocular PGE2 synthesis. Topical piroxicam (0.5%) Conditions confined to lid and conjunctiva (e.g. SAC) have
was also found to possess ocular anti-inflammatory activity allergic disease good prognosis but those involving the cornea
comparable to diclofenac sodium (0.1% w/v) and may result in visual impairment (e.g. AKC).
indomethacin (0.1%) and ocular tolerance better than
diclofenac sodium (0.1%).46 Pathophysiology of Ocular Allergy
NSAIDs also have local irritant effects like transient The pathophysiology of ocular allergy primarily involves a
burning, stinging, conjunctival hyperemia and corneal type-I hypersensitive mechanism associated with preferential
anesthesia. In conditions resistant to the actions of steroids production of IgE in response to certain antigens (allergens).
and NSAIDs, immunosuppressants have proven useful. They IgE has very high affinity for its receptor on mast cells and
act as cytotoxic agents (cyclophosphamide, chlorambucil, basophils. A subsequent exposure to the same allergen cross
methotrexate, azathioprine, colchicines) to block lymphocyte links the cell-bound IgE and triggers the release of various
proliferation or immunomodulators (cyclosporine A, dapsone pharmacologically active substances. Cross-linking of IgE Fc-
and tacrolimus) to block the synthesis of lymphokines.37 receptor is important in mast cell triggering. Mast cell
Although a number of immunosuppressants are used for the degranulation is preceded by increased Ca++ influx. This
treatment of intraocular inflammation, their usefulness is cascade is associated with the release of inflammatory
reduced by their iatrogenicity and by an efficacy limited to mediators such as histamine, tryptase, prostaglandins and
around 50 percent of the cases.47 Consequently, need for an leukotrienes. These trigger the clinical manifestations of the
alternative therapy was felt. Some newer generation drugs acute phase of the disease (early phase). Mast cell degranula-
like rimexolone, fluorometholone, loteprednol etabonate (LE), tion also induces activation of vascular endothelial cells and
are powerful topical corticosteroids with lower risk of IOP thus the expression of chemokines and adhesion molecules.
spike. LE is an ester corticosteroid with high anti-inflammatory These factors initiate the recruitment phase of inflammatory
efficacy and improved safety compared with other cells in the conjunctival mucosa, leading to late–phase reac-
corticosteroids.36 Clinical trials suggest NSAIDs as an effective tion50 which corresponds to the persistent clinical inflammation
alternative to steroid therapy.48 Clinical trial for Nepanefac that characterizes perennial and chronic allergic diseases.
ophthalmic suspension (0.1%) had found it to be safe and Ocular allergic reaction is sometimes also mediated by
type-IV hypersensitivity with the participation of secondary
effective for preventing and treating ocular inflammation and
inflammatory cells such as T-helper (Th) cells, eosinophils
pain after cataract surgery.48 Clinical trial for bromfenac
and their chemical mediators. T-helper lymphocytes (CD4+)
ophthalmic solution 0.09 percent (Xibrom) also found no
are the predominant T-cell population in conjunctival tissues.
serious ocular adverse events and it rapidly cleared ocular An altered balance between Th1 and Th2 types of cytokines
inflammation and reduced ocular pain after cataract is thought to be responsible for the development of allergic
extraction. Intravenous immunoglobulins (IVIGs) are found disorders.51,52 In addition to typical Th2-derived cytokines,
to be efficient with sustained improvement of visual function increase of TNF-α has also been documented in both VKC
and rare severe side effects for the treatment of chronic and AKC suggesting the involvement of cell mediated
ocular inflammation.47 hypersensitivity.53
Table 5.6.4: Types of various ocular allergic conditions

Type Symptoms Cause Immunopathogenesis
Seasonal allergic Itching, redness and puffy eyes Seasonal allergic rhinitis Type-I hypersensitivity – Ig E mediated
conjunctivitis (SAC) reactions to environmental airborne allergens
such as grass and tree pollens, mites, mold
and animal dander
Perennial allergic Itching, redness and puffy eyes Permanent contact Type-I hypersensitivity – Ig E mediated
conjunctivitis (PAC) with environmental allergen reactions to environmental airborne allergens
such as mites, mold and animal dander
Vernal Severe inflammation, foreign Occurs in children Type-IV hypersensitivity
keratoconjuctivitis body sensation, photophobia (11–13 yrs) with a history Th2 lymphocyte-mediated
(VKC) and occasionally blurring of atopy
of vision
Atopic Intense itching, abundant Atopic dermatitis Type-IV hypersensitivity
keratoconjunctivitis mucus discharge, Th2 lymphocyte-mediated
(AKC) photophobia, blurring
of vision
Giant papillary Giant papillae, foreign body Any type of contact lenses, Type-IV hypersensitivity
conjunctivitis (GPC) sensation, blurring of vision, exposed sutures, ocular Th2 lymphocyte-mediated
mucus discharge, prosthesis or ocular surface
conjunctival hyperemia, irregularities.
limbal infilterates and
lens deposits
Classification of Ocular Antihistamines

Anti-allergic Drugs
Topical antihistamines are the first line drugs in the treatment
Currently available topical drugs for allergic conjunctivitis of ocular allergy. Antihistamines act by reversibly blocking
are classified as follows: the histamine receptors in the eyelids and conjunctiva, thus
preventing their stimulation.
Classification Drugs
I. Vasoconstrictors Naphazoline First Generation Topical Antihistamines
II. Antihistamines Pheniramine, antazoline, Pheniramine and antazoline: The first generation topical
levocabastine and emedastine
antihistamines are available as pheniramine maleate (0.3%)
III. Mast cell stabilizers Cromplyn sodium, nedocromil,
lodoxamide NAAGA and pemirolast
in association with vasoconstrictor naphazoline (as naphazoline
IV. Dual-action Olopatidine, ketotifen, HCl 0.025%) and antazoline (phosphate–0.5%) plus
anti-allergic drugs azelatine and epinastine naphazoline HCl (0.05%). It showed rapid onset of action
V. NSAIDs Ketorolac following topical instillation.
VI. Corticosteroids Loteprednol, fluormethalone,
desonide, rimexolon, Dosage: One drop four times daily.
dexamethasone, prednisolone
Adverse reactions: Mydriasis, increase IOP, burning sensation,
Vasoconstrictors hyperglycemia, cardiac irregularities, hypertension and
drowsiness.
The alpha-adrenergic agonists are commonly used topically
for the relief of conjunctival redness.54 However, topical Second Generation Topical Antihistamines
vasoconstrictors are not usually recommended in allergic Levocabastine: This is the first H1-receptor antagonist
conditions because they are non-specific and not developed for topical ophthalmic application as single agent
pharmacologically active in the cascade of events that leads therapy. It is structurally unrelated to any other antihistamines
to the allergic reactions. These agents are usually coupled in current use. It is 15,000 times more potent than
with topical antihistamines. chlorpheniramine. Levocabastine HCl ophthalmic preparation
is available as 0.05 percent w/v suspension. It has a fast Nedocromil: Nedocromil is more potent than cromolyn
onset of action and significantly reduces the classic symptoms sodium and is approved for twice daily dosing. It appears to
and signs of ocular allergy in both adults and children. inhibit mast cells, eosinophils, epithelial cells and sensory
Dosage: One drop four times daily. nerves by a common pathway.
Adverse reactions: Mild stinging sensation. Adverse reactions: Unpleasant taste.
Emedastine: Emedastine is a potent, selective, and topically Lodoxamide: Lodoxamide (0.1%) ophthalmic preparation
effective histamine H1 antagonist with a rapid onset of action. contains lodoxamide tromethamine equivalent to lodoxamide
In vitro and in vivo examinations of emedastine’s affinity for 1 mg/ml. It is for mulated to treat seasonal allergic
histamine receptors (H1, H2 and H3) demonstrate 10,000 conjunctivitis. It is 2500 times more potent than sodium
fold selectivity for the H1 histamine receptor and concentration- cromolyn. Lodoxamide is shown to be superior to cromolyn
dependent inhibition of histamine-stimulated vascular and N-acetylaspartylglutamate (NAAGA) for the treatment
permeability in the conjunctiva following topical ocular of VKC and equal or superior to cromolyn for the treatment
administration. Emedastine is devoid of effects on adrenergic, of allergic conjunctivitis.
dopaminergic and serotonin receptors. It is much more potent Mechanism of action: Its mechanism of action is similar to
than other antihistamine eye drops, levocabastine and antazoline. cromolyn sodium. It acts by inhibiting eosinophil activation
The drug is used as 0.05 percent solution for allergic and degranulation. This is the proposed mechanism for its
conjunctivitis in patient’s older than three years of age. efficacy against corneal signs such as keratitis and shield ulcers
Dosage: One drop four times daily. in severe allergic disease.
Adverse reactions: Ocular adverse effects include hyperemia, Dosage: Four times daily.
dry eye, corneal staining, eye fatigue, foreign body sensation, Side effects: Not significant.
blurred vision, tearing, infiltrate, irritation. Other side effects
Pemirolast: Pemirolast ophthalmic solution (0.1%) is used
include headache, asthenia, abnormal dreams, dermatitis, taste
for allergic conjunctivitis.
perversion.
Mechanism of action: Pemirolast inhibits antigen-induced release
Systemic antihistamines can be used for the treatment of ocular
of inflammatory mediators (e.g. histamine, LTC4, -D4 and –
allergy especially in allergic rhinoconjunctivitis. First-generation
E4) from human mast cells and subsequently prevent the
H1-receptor antagonists may provide some relief of ocular
signs and symptoms associated with allergic conjunctivitis.
itching, but are sedating and have anticholinergic effects such
as dry mouth, dry eye, blurred vision and urinary retention. Dosage: Four times daily.
The second-generation antihistamines offer the same efficacy Side effects: Side effects of pemirolast are mild. Headache,
as their predecessors, but with a low sedating profile and lack cold or flu-like symptoms, rhinitis and burning are associated
of anticholinergic activity. These drugs attenuate the early with its usage.
phase and some of the features of the late-phase ocular NAAGA: It is dipeptide N-acetyl-aspartyl glutamic acid
response, including swelling and redness. available as 1 percent solution for the treatment of allergic
conjunctivitis, VKC and GPC.
Mast Cell Stabilizers Mechanism of action: NAAGA is known to inhibit leukotriene
synthesis, histamine release by mast cells and complement
Mast cell stabilizers inhibit degranulation by interrupting the
derived anaphylatoxin production. It is also known to directly
normal chain of intracellular signals resulting from the
inhibit leucocyte adhesion to endothelial cells induced by pro-
crosslinking and activation of high affinity receptor for Ig E
inflammatory stimuli, and abrogates TNF-alpha induced
(FceRI) by allergen. Several mast cell stabilizers are available expression of adhesion molecules on granulocytes and
for use in the eye. endothelial cells. These pharmacological properties confer a
Cromolyn sodium: Cromolyn sodium acts by inhibiting the potential anti-inflammatory activity to NAAGA.
mast cell degranulation, the release of histamine and other Dosage: Four times daily.
preformed mediators and arachidonic acid cascade. It is
available as cromolyn sodium 4 percent solution. Dual-Action Anti-Allergic Drugs
Dosage: One drop four times daily. This is a new class of molecules which have dual mechanisms
Side effects: Mild stinging sensation. that inhibit histamine release from mast cells and competitively
inhibits histamine binding to H1-receptors. Moreover, these Dosage: Twice daily.

drugs offer an advantage of rapidity in the symptomatic relief Side effects: Unpleasant taste.
given by immediate histamine receptor antagonism. This in
Epinastine: Epinastine is a new–generation H1-receptor
turn alleviates itching and redness, coupled with long-term antagonist with mast cell stabilizing activity and no effect on
disease modifying benefit of mast cell stabilization. This class muscarinic receptors. The ophthalmic formulation is available
of drugs includes olopatidine, ketotifen, azelastine and as 0.05 percent solution.
epinastine.
Mechanism of action: It acts by suppressing the allergic
Olopatidine: Olopatidine is a tricyclic compound showing inflammation not only through its strong anti-histamine and
H1-receptor antagonist and mast cell stabilization.55 The antimediator effects but also by inhibiting eosinophilic
ophthalmic solution (0.1%) is widely approved and marketed chemotaxis and the expression of adhesion molecules involved
for the treatment of ocular signs and symptoms of seasonal in chemotaxis.
allergic conjunctivitis. Olopatidine 0.2 percent w/v solution
Dosage: Twice daily.
is approved by the FDA for the treatment of ocular itching
associated with allergic conjunctivitis. Both formulations are Side effects: Burning sensation in the eye, folliculosis, hyperemia,
preserved with 0.01 percent benzalkonium chloride. and pruritis
Mechanism of action: Olopatadine is an inhibitor of the release NSAIDs
of histamine from the mast cell and a relatively selective
histamine H1-antagonist that inhibits the in vivo and in vitro Ketorolac (0.5%) is the only ophthalmic NSAID currently
type-1 immediate hypersensitivity reaction including inhibition approved by FDA for use in acute seasonal allergic
of histamine induced effects on human conjunctival epithelial conjunctivitis for the relief of ocular itching.
cells. Olopatadine is devoid of effects on alpha-adrenergic, Mechanism of action: NSAIDs act by inhibiting the enzyme
dopamine and muscarinic type-1 and 2 receptors. COX, thereby blocking the synthesis of prostaglandins
Dosage: One drop twice daily. particularly PGD2, which is known to incite significant and
immediate allergic symptomatology.
Side effects: Side effects reported by a minority of patients are:
headache, blurred vision, burning or stinging, dry eye, foreign Dosage: Four times daily.
body sensation, hyperemia, hypersensitivity, keratitis, lid Side effects: Burning sensation, superficial keratitis.
edema, nausea, pharyngitis, pruritis, rhinitis, sinusitis, and taste
perversion. Corticosteroids
Ketotifen: Ketotifen is used as 0.025 percent solution. Corticosteroids are powerful anti-inflammatory drugs and
Mechanism of action: Ketotifen acts by inhibiting the release of should be the last choice in treating allergic disease. They
inflammatory mediators from mast cells, basophils and should be avoided in SAC and PAC.
neutrophils to inhibit the production and release of Mechanism of action: Corticosteroids inhibit phospholipase A2,
leukotriene C4 (LTC4), leukotriene B4 (LTB4). PAF production thereby reducing the production of arachidonic acid from
by normal human neutrophils and eosinophils and eosinophil membrane phospholipids. They also inhibit the release of
chemotaxis. cytokines and activation of various immune effector cells.
Dosage: Twice daily. Side effects: The use of corticosteroids is restricted to severe
Side effects: Burning/stinging/irritation of the eye, headache, allergic conditions because of their well-known side-effects
stuffy/running nose, unpleasant taste and increased sensitivity such as cataract, glaucoma, superinfection and corneal
to light may occur. melting.
Azelastine: Azelastine was approved in the past for rhinitis The list of corticosteroids available for allergic conditions
and later it has been approved for the treatment of ocular is given in Table 5.6.5.
itching associated with allergic conjunctivitis. The ophthalmic
preparation is marketed as 0.05 percent. ANTI-CATARACT DRUGS
Mechanism of action: It reduces inter-cellular-adhesion molecule Numerous studies of lens proteins indicate that post-
(ICAM-1) expression on conjunctival epithelium and translational modifications occur in lens proteins during
inflammatory cell infiltration during both early and late phase cataract formation and are the result of chemical actions
allergic reactions. that include oxidation, glycation, Schiff base formation,
Table 5.6.5: List of topical corticosteroids for allergic conditions

Corticosteroid base Salt Formulation Strength (%) Indications Dosage
Prednisolone Acetate Suspension 0.125 and 1.0 AKC, VKC Four times daily
Prednisolone Sodium phosphate Solution 0.125 and 1.0
Dexamethasone Alcohol Suspension 0.1 AKC, VKC
sodium phosphate Solution 0.1
Ointment 0.5
Fluormetholone Alcohol Ointment 0.1 AKC, VKC
Suspension 0.1
Acetate Suspension 0.1
Loteprednol Etobonate Suspension 0.5 and 0.2 GPC, SAC
Rimexolone Suspension 1.0 Not been approved for
allergic conjunctivitis
Desonide – – 0.25 SAC
proteolysis, transamidation, carbamylation, phosphorylation the typical age-related baseline loss. It is the second leading
and elevated calcium levels.56,57 Various pharmacological cause of blindness in the world.60 Prevalence models estimate
agents which are capable of altering the above events had that 8.4 million individuals suffer from glaucoma-induced
been tested for anti-cataract potential to prevent or to delay bilateral blindness in 2010, rising to 11.1 million in 2020.60
the progression of cataract. The anti-cataract agents claimed Current therapy for the chronic treatment of glaucoma
to be effective in vitro, in vivo and in epidemiological studies includes beta blockers, prostaglandin analogues, adrenergic
may be broadly classified in the following categories; aldose receptor agonists, carbonic anhydrase inhibitors, cholinergic
reductase inhibitors (ARIS), non-steroidal anti-inflammatory or miotic agents and hyperosmotics. But still, the search for a
drugs, vitamins, minerals and antioxidants, agents acting on good anti-glaucoma drug without the side effects of current
glutathione and miscellaneous agents.58 There are number therapies is going on.
of AR inhibitors known to possess anticataract potential and
delaying the galactose induced cataract in different animal Cholinergics
models. Some of these include alrestatin, sorbinil, sulindac, Mechanism of action: These drugs mimic the actions of
naproxen, aspirin, tolrestat, statil and bioflavonoids. Among acetylcholine. Pilocarpine directly stimulates the muscarinic
the ARls only sorbinil reached the advanced clinical trial stages receptors producing increased aqueous outflow.
in cataract prevention programme. However, it was not Echothiophate iodide enhances action of acetylcholine by
successful. The NSAIDs extensively studied are aspirin, inhibiting cholinesterases.
paracetamol, ibuprofen, naproxen, sulindac and bendazac. Indications: Pupillary block glaucoma.
The agents which acted on glutathione to prevent cataract in
Dosage: Pilocarpine eye drop (0.25%, 0.5%) one drop two to
the experimental animal models are amino acids glutathione
three times a day.
plus arginine, inositol, pyridoxine and ascorbic acid. The
vitamins, minerals and anti-oxidants which proved to be Anticholinergics
effective in experimental animal models are vitamin C, E,
Mechanism of action: Drugs that block the response of
riboflavin, betacarotene, ascorbate and pyruvate. The
acetylcholine at the receptor are called parasympatholytics or
various other agents are calcium dobesilate, Itone, lipoic
cholinergic antagonists. Examples of this class of compounds
acid, patathine, glutathione isopropyl ester, DL-
are atropine, cyclopentolate and tropicamide which are not
penicillamine, catalin, cineraria, benzyl alcohol and various
routinely used for the glaucoma treatment. However, they
herbal drugs.58,59
have a role in the management of inflammatory and malignant
ANTI-GLAUCOMA DRUGS glaucomas.
IOP Lowering Drugs Adrenergics

Glaucoma is a multifactorial, progressive optic neuropathy Alpha adrenergic agonists: These drugs act by stimulating
with characteristic loss of retinal ganglion cells (RGCs) beyond alpha receptors (α2) in the ciliary epithelium and thereby
decrease the rate of aqueous production and IOP. Two types Dosage: Latanoprost (0.005%, one drop at bed time),
of alpha adrenergic receptors are identified in human Brimoprost (0.03%, one drop at bed time).
nonpigmented ciliary epithelium and ciliary muscle. 61
Activation of alpha adrenergic receptors reduces IOP by Antioxidants
decreasing the rate of aqueous production at the ciliary Oxidative stress plays an important role in the pathogenesis
epithelium level62,63 and potentially by enhancing uveoscleral of glaucoma. Glaucomatous trabecular meshwork cells highly
outflow.64 Brimonidine is an important component of topical express peroxiredoxin 2 when compared with normal
glaucoma treatment that is most limited by local ocular trabecular meshwork cells. Nipradilol and timolol but not
intolerance.65 Clonidine is believed to exert its IOP reduction latanoprost induce the expression of peroxiredoxin–2 through
effect by constriction of afferent vessels in the ciliary the activation of the FOXO3a transcription factor. TM cells
processes. showed reduced sensitivity to H2O2 when cells were treated
with either nipradilol or timolol but not with latanoprost. In
Indication: Open angle glaucoma. addition, both FOXO3a and PRDX2 expression was
Dosage: Dipivefrin eye drops (0.1%, one drop, two to three enhanced by drug induced signal transduction through its
times a day), Brimonidine eye drops (0.15% one drop, two to receptor. These results indicate that both nipradilol and timolol
three times a day). possess a novel mechanism of action and function as potent
protective agents against oxidative stress.67
Beta Adrenergic Antagonists
Mechanism of action: Beta blockers bind to beta adrenergic Neuroprotectants
receptors and block sympathetic transmission and lowers IOP
Loss of vision in primary open-angle glaucoma (glaucoma) is
by reducing aqueous production.
caused by retinal ganglion cells dying at a seemingly steady
Indication: Open angle glaucoma. and variable rate in different patients. Therapies directed at
Dosage: Timolol (0.25%, 0.5% eye drops) one drop one to neuronal loss, either prophylactically or after the insult has
two times a day, Betaxolol (0.5%) one drop twice a day. occurred, are currently being investigated.68 The target is retinal
ganglion cell (RGC) loss, not the elevated IOP that indirectly
Carbonic Anhydrase Inhibitors (CAI) causes the death of the RGC.69 Ganglion cells are induced
Mechanism of action: Inhibits carbonic anhydride II (CA-II) to die by different triggers in glaucoma, suggesting that
isoenzyme thereby reducing the production of aqueous neuroprotectants with multiple modes of actions are likely to
humor. Dorzolamide and brinzolamide are two topical CA reveal clearer results. Therefore, the idea of neuroprotection
inhibitors which are currently available to treat ocular in glaucoma must not be abandoned.70
hypertension and/or glaucoma. Dorzolamide is a very potent There are many treatment strategies being evaluated. One
inhibitor of CA-II and its site of action is local, within the includes a neuroprotectant only, whereas a complete therapy
eye. management approach includes a neuroprotective agent
Indication: Open and closed angle glaucoma. supplemented by an IOP-lowering therapy. This dually
targeted therapy would provide several potential benefits,
Dosage: Acetazolamide tablets (125 mg, 250 mg) 125-250 mg
including direct preservation of the optic nerve, decreasing
two to four times a day.
one of the most important factors that cause glaucoma
damage, and potentially reducing the significant economic71,72
Prostaglandin Analogues
and quality-of-life73,74 consequences associated with disease
Mechanism of action: Prostaglandin receptors and their associated progression.
mRNAs have been located in the trabecular meshwork, ciliary Although the drugs, such as memantine, calpain, erythro-
muscle, and sclera, providing evidence that endogenous poietin, have demonstrated exciting results for neuroprotection
prostaglandins have a functional role in aqueous humor in laboratories, the phase III clinical trial of memantine failed
drainage. Prostaglandin analogues act through (PG F2 alpha) to prove such activity. So far, none of neuroprotection drugs
and thus enhancement of aqueous outflow. Examples are has been approved by the FDA for clinical use with the failure
latanoprost, brimoprost and tafluprost. The reduction in IOP of memantine clinical trials indicating that the gap between
achieved by preservative-free tafluprost is equivalent to that basic science research and clinical application in glaucomatous
obtained with the preserved formulation. The preservative- optic neuroprotection remains to be filled. To convert the
free formulation is generally well tolerated.66 dream of optic neuroprotection into reality, implementation
Indication: Open angle glaucoma. new perspective strategies of integrating technologies and
findings from the researches of human genomics, proteomics, • Anti-inflammatory agents: Topical corticosteroid, topical
stem cells, and gene-transferred animal models is required.75 cyclosporin, oral tetracyclines and topical NSAIDs
• Secretogogues: Cholinergic agents and mucin inducers
Cannabinoids • Nutritional supplements: Essential fatty acids-omega-3-fatty
The discovery of ocular cannabinoid receptors implied an acids, omega-6-fatty acids, topical retinol
explanation for the induction of hypotension by topical • Hormonal therapy: Topical estrogen and androgen
cannabinoid applications, and has stimulated a new phase of
Tear Substitutes
ophthalmic cannabinoid research. Featured within these
investigations is the possibility that at least some cannabinoids Artificial tear substitutes: The mainstay of treatment for dry
may ameliorate optic neuronal damage through suppression eye disease is artificial tear substitutes which have been
of N-methyl-D-aspartate receptor hyperexcitability, successfully used as lubricants to relieve the symptoms for
stimulation of neural microcirculation, and the suppression decades. The other actions may include replacement of
of both apoptosis and damaging free radical reactions, deficient tear constituents, dilution of proinflammatory
among other mechanisms. Separation of therapeutic actions substances, reduction of tear osmolarity, and protection against
from side-effects now seems possible through a diverse array osmotic stress. The artificial tear substitutes have a complex
composition including not only mucins, water, and lipids, but
of novel chemical, pharmacological, and formulation
also electrolytes, proteins, growth factors, vitamins, amino
strategies.76
acids, and glucose.79-81 A wide variety of artificial tear products
Over a period of several decades numerous scientific
are available commercially, which differ with respect to a
researches has proven that regardless of the route of
number of variables that include:82
administration, cannabinoids are able to decrease intraocular
• Electrolyte composition: Potassium and bicarbonate mimic
pressure. What is more, these compounds are characterized the composition of natural tears
by neuroprotection and vasodilatation properties, that • Osmolarity/osmolality: Artificial tears with hypoosmolarity
additionally substantiate it’s therapeutic utility in conservative is preferable to one with normal osmolarity
treatment of glaucoma. So far, the mechanism lowering • Viscosity: Higher viscosity increases tear retention time
intraocular pressure by cannabinoids has not been described. and may help protect the ocular surface, but is more
Nevertheless, the presence of endocannabinoid receptors in likely to cause visual blurring. Viscosity agents used in
structures of the eye responsible for formation and outflow artificial tears include carboxymethyl cellulose (CMC), HP-
of aqueous humor is an explanation for the effectiveness of guar, and lipids such as those that make up castor oil or
these compounds, when administered in topical form.77 mineral oil. Lipid-containing products are intended to
decrease tear evaporation by restoring the lipid layer of
DRY EYE MEDICATIONS the tear film. HP-guar is believed to form a bioadhesive
Dry eye syndrome refers to a spectrum of ocular surface gel, mimicking the mucous layer of the tear film
disorders. It is a multifactorial disease of tears and ocular • Preservatives: There are two main types of preservatives,
surface that results in symptoms of discomfort, visual detergent (e.g. benzalkonium chloride) and oxidative
disturbance and tear film instability. The complex tear film is (e.g. stabilized oxychloro complex). Detergents can irritate
made up of layers of oil, aqueous and mucin, which are or damage the ocular surface with frequent use; oxidative
produced by the meibomian glands, main and accessory preservatives are less likely to do so. Preserved tears are
lacrimal glands, and by the goblet cells, respectively.78 usually well tolerated in mild dry eye condition when used
no more than four to six times daily. If more frequent
Treatment for Dry Eye application is required, unpreserved tears should be used.
The preservatives like stabilized oxy-chlorocomplex is
The goals of dry eye treatment are to improve symptoms, recently been used in formulations
improve tear film quantity and stability, and reverse ocular • Compatible solutes: These are small nonionic molecules
surface damage. The agents which are available for the (e.g. glycerin) that are taken up by ocular surface epithelial
treatment of dry eye are classified as: cells. Because they increase intracellular osmolarity without
• Tear substitutes: Artificial tear substitutes and autologous disrupting cellular metabolism, they may protect against
serum osmotic stress.
Commercially Available Artificial Tear Substitutes Topical corticosteroids: Methylprednisolone and loteprednol
1. Carboxymethylcellulose artificial tears (CMC) decrease the inflammation and improve the integrity of the
• Optive: 0.5 percent CMC, purite preserved. It protects ocular surface by transcription of specific mRNA and
against cell damage by osmoprotection synthesis of protein. Although effective, these agents are
• Refresh Tears: 0.5 percent CMC generally recommended only for short-term use because
• Refresh plus Tears: 0.5 percent CMC but not preserved prolonged use may result in adverse effects including ocular
• Refresh liquigel: 1 percent CMC, purite as preservative infection, glaucoma, and cataracts.
• Thera Tears: 0.25 percent CMC, Preservative free. Oral tetracyclines: Based on limited evidence, oral tetracyclines
2. Polyethylene glycol artificial tears (PEG) have been used off-label to treat dry eye, primarily dry eye
• Systane: PEG 4000.4 percent, PG 0.3 percent, associated with ocular rosacea.
Hydroxypropyl Guar (Gel forming matrix), Topical cyclosporine: Topical cyclosporine is currently the only
Polyquaternium as preservative pharmacologic treatment that is FDA approved specifically
• Systane Ultra: PEG 4000.4 percent, PG 0.3 percent, for dry eye. Cyclosporine reduces conjunctival IL-6 levels,
Borate, Hydroxypropyl Guar (Gel forming matrix), decreases activates lymphocytes in the conjunctiva, reduces
Polyquaternium as preservative conjunctival inflammatory and apoptotic markers and
• Blink Tears: PEG 4000.4 percent, Sodium Chlorite has increases conjunctival goblet cell numbers in patients with
Hyaluronic acid as preservative which promotes dry eye disease. Although its onset of action is relatively slow,
healing of corneal epithelium. it is safe for long-term use and appears to be disease-modifying
3. Hydroxytoropyl methyl cellulose (HPMC) artificial tears rather than merely palliative. The most common adverse
• Bion Tears: 0.3 percent HPMC, 0.1 percent Dextran effects are transient burning or stinging. Because blood levels
70, Preservative free are negligible even after long-term use, the risk of systemic
• Tears Naturale Forte: 0.3 percent HPMC, 0.1 percent toxicity is minimal.
Dextran 70, 0.2 percent Glycerine, Polyquad 0.001 Topical NSAIDs: Topical NSAIDs have been used off-label
percent as preservative in dry eye condition; however, their use is controversial
• Tears Natural-II: 0.3 percent HPMC, 0.1 percent because they can promote corneal melting in patients with a
Dextran 70, Polyquad 0.001 percent as preservative compromised ocular surface.
• Tears Natural Free: 0.3 percent HPMC, 0.1 percent
Dextran 70, preservative free Secretagogues
• Geneteal: 0.3 percent HPMC, Genaqua as preservative Cholinergic agents: (i.e. muscarinic acetylcholine receptor
• Genteal Mild: 0.2 percent HPMC, Genaqua as agonists) are sometimes given orally to treat aqueous-deficient
preservative dry eye condition. Two agents, pilocarpine and cevimeline,
• Visine Tears: 0.2 percent HPMC, 0.2 percent Glycerine, have FDA-approved indications for treatment of dry mouth
0.1 percent polyethylene glycol 400, Benzalkonium associated with Sjögren syndrome; however, these are off-
chloride 0.01 percent as preservative. label usage for treatment of dry eye.
Autologous Serum Drugs under clinical trials: Diquafosol is an eye drop that
stimulates the release of natural tear components targeting
Autologous serum tears are produced from the patient’s
all three mechanisms of action involved in tear secretion—
serum. The topical application of autologous serum suppresses
mucin, lipids and fluid. Diquafosol works in an independent
inflammation as it contains proteins, peptides, nutrients and
mechanism via P2Y2 receptors to stimulate fluid secretion
growth factors that protect and heal the ocular surface.83
from non-lacrimal gland tissue.
These tears are used in patients with severe dry eye syndrome.
Pimecrolimus, a secretagogue that selectively inhibits
Autologous serum tears have biochemical and mechanical
inflammatory cytokine synthesis, is in Phase II clinical trials.
properties that are similar, but not identical, to those of normal
It belongs to the same family as cyclosporine, and it is a
aqueous tears. They are usually unpreserved, but can be stored
molecule that inhibits T-cell activation.
frozen, for three to six months so that blood donation is
required two to four times a year. Mucin inducers: Rebamipide, an amino acid analog of
quinolinone increases tear aqueous, film volume and
Anti-inflammatory Agents stimulates mucin secretion. Rebamipide ophthalmic suspension
This class of drugs includes topical corticosteroids, oral is a medication that causes mucus secretion and is currently
tetracycline, topical cyclosporine and topical NSAIDs used orally in Japan as ulcer therapy to stimulate mucus
production by the lining of the stomach. The topical ANTI-ANGIOGENIC DRUGS

preparation is being investigated for dry eye is in Phase III The formation of new blood vessels out of pre-existing
clinical trials in the United States. capillaries or angiogenesis is a sequence of events that is of
Nutritional Supplements key importance in a broad array of physiologic and pathologic
processes.85 Abnormal angiogenesis is frequently the final
Essential fatty acids (EFAs): These may, theoretically, benefit
pathway leading to the vast majority of diseases that result in
dry eye condition in two ways, by reducing inflammation and
catastrophic loss of vision, e.g. proliferative diabetic
by altering the composition of meibomian lipids. There are
retinopathy, wet age related macular degeneration, retinopathy
at least two essential fatty acid nutritional supplements
of prematurity, etc. These diseases may benefit from the
marketed specifically for dry eye condition, one containing
therapeutic inhibition of angiogenesis. Several compounds
omega-3 fatty acids from flaxseed and fish oil and another
(both of natural as well as synthetic origin) are under clinical
containing a blend of omega-3 and omega-6 fatty acids
trials that have been shown to have potent angiostatic effects
(docosahexaenoic acid/eicosapentaenoic acid [DHA/EPA]
in the pre-clinical phases. The switch to the angiogenic
from cod liver oil and gamma-linolenic acid [GLA] from phenotype involves a local equilibrium between the positive
black currant seed oil, respectively. However, evidence for and negative regulators of angiogenesis and these regulators
EFA efficacy is limited and conflicting. as well as the various steps involved in angiogenesis offer
Topical vitamin A (retinol): Vitamin A deficiency is a known numerous potential targets for therapeutic intervention. Tie
cause of xerophthalmia; however, most dry eye patients are 1 and Tie 2 receptors are selectively expressed on vascular
not vitamin A–deficient. Because retinol is present in tears, it endothelial cells and are required for vascular development
has been hypothesized that in a dry eye condition, they may in conjunction with their respective ligands, angiopoietins. An
be associated with local retinol deficiency at the ocular surface. ideal anti-angiogenic agent is one with robust angiostatic effect
Based on this hypothesis, topical retinol has been used to that inhibits neovascularization regardless of the inciting cause
treat various forms of dry eye conditions with variable and possesses good ocular bioavailability along with robust
results.84 ocular and systemic safety profiles.
Hormone Replacement Therapy AGE RELATED MACULAR
Epidemiological and laboratory evidence suggests that DEGENERATION
androgen and estrogen supplementation is a possible
Age related macular degeneration is a chronic, progressive
therapeutic option for dry eye disease. Topical estrogen and
eye disorder that cause visual loss in patients over 60 years
the combination of estrogen and androgen drug as a systemic
therapy has been associated with improvement of symptoms of age.86 It is the leading cause of blindness in the western
of dry eye. Topical testosterone is under Phase II trial and world and the third most common cause globally after cataract
has shown improvement in dry eye symptoms without any and glaucoma, causing 8.7 percent of all legal blindness across
complications. the world.87 Wet or neovascular ARMD is associated with
rapidly deteriorating vision and severe visual impairment and
Recent Developments accounts for 90 percent of cases of severe visual impairment
The mechanism, exploration and advancement in the due to ARMD.
understanding of disease pathology have led to a variety of There are various classes of ocular angiostatic agents
novel strategies. Out of more than 20 products that have based upon the mechanism of action, that are under clinical
undergone clinical testing in United States, only one drug trials for the treatment of neovascular age related macular
formulation has received FDA approval as therapeutic drug degeneration include angiostatic steroids (glucocorticoids,
for dry eye disease. It has been difficult for sponsors to cortisones, squalamine); VEGF inhibitors (pegatanib sodium,
generate data to fulfil the FDA’s criteria of primary efficacy ranibizumab, VEGF trap, siRNA-027); Protein Kinase C
endpoints of at least one sign and one symptom that should (PKC) inhibitors (Ruboxistaurin); Receptors Tyrosine kinase
be statistically significant. The main problem in clinical trials (RTK) inhibitors; Integrin antagonists; Extracellular proteinase
is the placebo effect. This implies that a patient receiving (MMP and uPA) inhibitors; NSAIDs (Nepafenac, Celebrex);
placebo or drops with no active ingredients shows notable proteins/peptides pigment epithelium derived factor (PEDF)
improvements. angiostatin, endostatin); Immunomodulatory agents
(Infliximab, Rapamycin and Daclizumab) and agents that (siRNA) exerts its antiangiogenic action by down regulating
suppress VEC proliferation (Thalidomide, 2-medroxyestradiol, VEGFR-1 expression.
Canbutastatin). Clinical indication: Under clinical trial for the treatment of wet
AMD.
VEGF Inhibitors
Bevacizumab VEGF Trap
Mechanism of action: Bevacizumab is a recombinant, VEGF Trap is a high-affinity antagonist of VEGF consisting
humanized, anti-VEGF antibody that binds all VEGF isoforms of the immunoglobulin domain 2 of human VEGFR1 and
and inhibits the VEGF-receptor interaction and thereby blocks domain 3 of human VEGFR2 fused to an Fc-fragment of
both increased vascular permeability and angiogenesis. human IgG. It is designed to bind and neutralize VEGF both
Clinical indication: It is indicated for metastatic colorectal cancer in the circulation and within tissues. VEGF Trap binds all
(FDA approved) and wet ARMD. isoforms of VEGF with high affinity as well as the related
Route of administration: Intravitreal injection (1.25 mg/0.05 angiogenic factor, placental growth factor (PIGF). Nguyen
ml) on a fixed schedule of once every four weeks for one et al, 2006 reported the efficacy of VEFG Trap in AMD
year. whereby they showed that the drug inhibited the growth of
new blood vessels when given intravenously as well as when
Ranibizumab administered directly into the eye.
Ranibizumab is recombinant humanized Fab fragment of Clinical indication: Clinical trials with intravitreal VEGF trap
anti-VEGF antibody that binds all VEGF isoforms with high are currently underway in wet AMD.
affinity and assures better penetration through the retina than
obtained with a larger full sized antibody after an intravitreal Angiostatic Steroids
injection. Anecortave Acetate
Clinical indication: It has been approved by FDA in 2006 for
The angiostatic activity of a novel cortisone derivative,
the treatment of choroidal neovascularization (CNV) due to
anecortave acetate is independent of the inciting cause of
ARMD.
neovascularization and the clinical studies in ARMD utilize a
Route of administration: Intravitreal injection every four weeks. unique posterior juxtascleral depot delivery method, requiring
administration every six months. The advantage offered by
Pegatanib this unique angiostatic agent is that its activity is not dependent
Pegatanib is an RNA aptamer directed against the VEGF- on inhibition of a specific angiogenic agent and is devoid of
165 isoform and is used for the treatment of AMD. It is conventional glucocorticoid activity. It inhibits angiogenic
first aptamer (an oligonucleotide ligand that binds to its proteolytic cascade and inhibits vascular endothelial cell
molecular target with high affinity) approved for therapeutic proliferation and differentiation and inhibits elaboration of
use in humans. angiogenesis growth factors and their receptors.
Clinical indications: It was FDA approved for treatment of wet Route of administration: Clinical studies in wet AMD patients
AMD in 2004 and is also indicated for diabetic macular edema. are currently underway using posterior juxtascleral depot (PJD)
delivery method and the drug administered every six months.
Route of administration: Intravitreal injection once every six
weeks Squalamine
siRNA-027 A novel steroid spermidine conjugate, squalamine isolated

from the dogfish shark Squalus acanthias possess antiangiogenic
RNA interference (RNAi) is a new method to inhibit the effects by inhibiting Na-H exchanger (isoform NHE3)
production of VEGF by the post transcriptional silencing of resulting in inhibition of H-ion efflux from endothelial cells
gene expression and it has been shown that siRNA against with subsequent reduction of cellular proliferation and is
VEGF is a potent strategy for inhibiting growth and leakage currently under Phase II clinical trials for the treatment of
of CNV in neovascular AMD.88 The short interfering RNA age related macular degeneration.
Clinical indication: Currently, systemically administered Ongoing studies are trying to identify the pharmacological
squalamine under investigation in Phase II trials for CNV receptor responsible for the angiostatic activity of various
AMD. antiangiogenic agents including proteomic and genomic studies
In addition to the pivotal role played by angiogenesis in order to identify the proteins and genes in vascular
regulators in AMD, recent information supports that the endothelial cells and the retina that are specifically regulated
decline of the ocular down regulatory immune environment by the individual compounds in order to obtain better
plays an important role in AMD and it has been suggested understanding of the mechanism of action of each.
that immunotherapy could positively alter the course of
the disease.89 OTHER DRUGS AND AGENTS USED IN
DIAGNOSTIC PRACTICE
DIABETIC RETINOPATHY
Ophthalmic Dyes
Diabetic retinopathy (DR) is an inevitable consequence of
The dyes fluorescein, rose bengal, and lissamine green are used in
diabetes leading to vision loss. It is estimated that diabetes
evaluating these problems.
mellitus affects four percent of the world’s population, almost
half of whom have some degree of diabetic retinopathy at Fluorescein sodium: Available both as a two percent alkaline
any given time. DR can be classified into two clinically distinct solution and as an impregnated paper strip, fluorescein reveals
stages, non-proliferative and proliferative. In the posterior epithelial defects of the cornea and conjunctiva and aqueous
segment of the eye, uncontrolled retinal vascular proliferation, humor leakage that may occur after trauma or ocular surgery.
as a result of diabetes-associated retinal hypoxia, can lead to Therapeutic uses: In the setting of epiphora, fluorescein is used
fibrosis and traction retinal detachment, a dreaded to help determine the patency of the nasolacrimal system. In
complication of advanced diabetic retinopathy.90 addition, this dye is used as part of the procedure of
Various classes of angiostatic drugs are under clinical applanation tonometry (intraocular pressure measurement) and
trials for the treatment of proliferative DR including to assist in determining the proper fit of rigid and semirigid
VEGF antagonists (pegatanib, ranibizumab, VEGF-Trap); contact lenses. Fluorescein in combination with proparacaine
protein kinase C (PKC) inhibitors (PKC412; Ruboxistaurin or benoxinate is available for procedures in which a disclosing
mesylate), etc. agent is needed in conjunction with a topical anesthetic.
Fluorexon (FLUORESOFT), a high-molecular-weight
Protein Kinase C (PKC) Inhibitors
fluorescent solution, is used when fluorescein is contrain-
PKC412: PKC412 is an orally administered small molecular dicated (as when soft contact lenses are in place).
weight tyrosine kinase inhibitor which binds intracellular,
For posterior segment diagnosis: The integrity of the blood-retinal
enzymatically active domain of VEGF receptor and inhibits and retinal pigment epithelial barriers may be examined directly
tyrosine kinase activity by preventing receptor phosphorylation by retinal angiography using intravenous administration of
and hence activation of a series of cytoplasmic signaling either fluorescein sodium or indocyanine green. These agents
proteins (VEGF signaling cascade). It not only inhibits commonly cause nausea and may precipitate serious allergic
VEGFR2 but also inhibits several other tyrosine kinases such reactions in susceptible individuals.
as (KIT) PDGF and protein kinase C (PKC). The compound
Rose bengal and lissamine green: Rose Bengal and lissamine
has shown significant results in 141 patients with diabetic
green, which also are available as a one percent solution and
macular edema but the associated systemic side effects may
as saturated paper strips, stain devitalized tissue on the cornea
further limit its use (Campochiaro, 2004). Ruboxistaurin
and conjunctiva.
mesylate is an orally administered selective inhibitor of PKC-β,
which is activated during vasculature in hyperglycemia and
Ocular Anesthetics
enhances the process of neovascularization. The drug was
well tolerated and ameliorated diabetes-induced abnormalities Anesthetic Agents
in retinal circulation time in a clinical trial consisting of 29 Anesthetic agents produces surface anesthesia when applied
diabetic patients with no or very mild diabetic retinopathy in drop form to the eye or anesthetize a regional area when
(Aiello et al, 2006). administered by injection. 91 These drugs block nerve
Ruboxistaurin: Ruboxistaurin is a orally administered selective conduction when applied locally to any type of nerve fiber in
inhibitor of PKC-β that gets activated in vasculature during appropriate concentrations.
hyperglycemia. Mechanism of action: Their main site of action is cell membrane,
Clinical indication: Under clinical trials for diabetic retinopathy. where they block the increase in membrane permeability to
sodium ions that normally occurs with depolarization of the Indications: It does not cause vasoconstriction or hyperemia,
membrane. Blockade of sodium transport is due to binding therefore it is well suited for diagnostic procedures. It is
of the local anesthetic to a specific binding site located within chemically and bacteriologically stable.
a voltage-gated sodium channel present in the cell membrane. Dosage and administration: Although it is used in the form of
Proparacaine: Proparacaine hydrochloride 0.5 percent is a 0.2 percent solution but clinically 0.4 percent solution acts
topical anesthetic prepared as a sterile aqueous ophthalmic more rapidly and is well tolerated by the tissues.
solution. Lignocaine: A two percent solution is effective at cornea
Indications: It is used in procedures, e.g. suture removal from giving it more rapid, intense, extensive and prolonged effect.
the cornea, tonometry, gonioscopy, removal of foreign bodies, It occurs as odorless crystals, freely soluble as HCl salt in
conjunctival scraping for diagnostic purposes and other short water and is extremely stable.
corneal and conjunctival procedures.
Indications: It is used in tonometry, gonioscopy, fundus and
Dosage and administration: For tonometry and other procedures contact lens examination, anterior segment examination and
of short duration, one or two drops instilled just prior to diagnostic refraction.
evaluation. For prolonged anesthesia, one or two drops in the Dosage and Administration: For tonometry one to two drops in
eye every five to ten minutes for three to five doses are each eye before operating it.
instilled.
Cocaine: It is unique among local anesthetics because it
Tetracaine: It is an ester of para-aminobenzoic acid, has exhibits both anesthetic and adrenergic agonist activity. It is
been widely used for topical anesthesia of the eye. It is not commercially available in an ophthalmic solution.
available in a 0.5 percent solution, with or without a
preservative. Indications: It may be used to deepithelialize the cornea for
glaucoma procedures or for lamellar corneal grafts.
Indications: It is used in various surgical procedures. Tetracaine
one percent solution has been used to provide anesthesia Dosage and administration: The usual concentration for topical
during phacoemulsification cataract surgery and intraocular ocular use is one to four percent. One drop of two percent
solution produces excellent corneal anesthesia within five to
lens implantation. But it is less desirable than proparacaine,
as it is more irritating and causes pain on instillation. ten minutes. Complete anesthesia lasts approx 20 min, with
incomplete surface anesthesia lasting for approximately one
Dosage and administration: Onset of anesthesia required for to two hours.
tonometry or other minor procedures involving the superficial
cornea and conjunctiva is 10 to 20 seconds, and duration of EDTA
anesthesia is 10 to 20 minutes.
EDTA is a divalent cation chelating agent with high affinity
Lidocaine: It is one of the popular anesthetic agents, for many metals. Sodium EDTA is effective in prevention
administered by injection during various surgical procedures. of biofilm formation of Staphylococcus aureus.92 It is especially
Indications: It is effective for 40 to 60 minutes but can be used in the treatment of band keratopathy to remove visual
extended by adding epinephrine to the solution, usually in a axis opacities and/or stabilize the ocular surface and lime
dilution of 1:200,000. injury (those who work related to painting).93 The 0.3 percent
Dosage and administration: The maximum dose of lidocaine in disodium salt of EDTA is used for removing calcium ions
children is 4.5 mg/kg as 0.25 percent to 0.5 percent solution. from Bowman’s membrane. When topical EDTA is used for
treating calcific band keratopathy alone, it produces spotty
Bupivacaine: It is a long-acting injectable anesthetic and is
cleaning of the corneal opacities, giving a Swiss-cheese-like
not commercially available as a topical ocular anesthetic.
appearance. By itself, EDTA does not have a highly toxic
Indications: Its onset of action and duration of anesthetic effect on cells. It is also used for irrigation of the epithelium-
activity is similar to that of proparacaine. denuded cornea for emergency treatment of alkali burns.
Dosage and administration: Three drops of 0.5 percent
bupivacaine is effective in blocking the corneal reflex, initiated EXTEMPORANEOUSLY PREPARED
by a cotton wisp, for 24 minutes. OCULAR DRUGS
Oxybuprocaine: It is a synthetic derivative from the p- Certain topical antibiotics are not commercially available or
aminobenzoic acid series with surface anesthetic action. not available in the higher concentration needed for various
ocular complications. Most of the topical antibiotic glaucoma filtering, pterygium and strabismus surgery. It also
formulations are prepared extemporaneously. used in the postoperative healing process after excimer laser
Amphotericin B (0.05%): Amphotericin B is obtained from keratomileusis.101
Streptomyces nodosus. It is polyene type of antifungal effective Polymycin: Polymycin are extracted from products of growth
against yeast and fungi such as Candida albicans, Histoplasma of the B. polymyxa and is effective against Gram-negative
capsulatum, Cryptococcus neoformans, Blastomyces dermatitides, bacilli including the Ps. pyocyaneus. It is effective against corneal
Coccidioides immitis, Torulopsis, Rhodotorula, Aspergillus and infection and is less toxic, non-irritant when applied to the
Sporothrix. It is mainly used in the treatment of fungal eyelids and conjunctival sac and no allergic reaction. It is
endophthalmitis by intravitreal injection and it does not penetrate mainly used in the treatment of blepharitis and corneal
the vitreous cavity by other modes of administration.94 ulceration and is useful as a prophylactic agent against
ocular wound infection.102
Acetyl cysteine (10%): N-Acetylcysteine was first used as a
mucolytic agent for the liquefaction of tenacious bronchial Tobramycin (1.3%): Tobramycin is an aminoglycoside antibiotics
secretions. It produces least irritation and is most stable among and it is obtained from S. tenebrarius and is effective against
several sulfhydryl agents. It is mainly used in keratoconjun- Pseudomonas and Proteus. It is mainly used for treatment
ctivitis sicca, filamentous keratitis, corneal catarrh and alkali- of pseudomonal corneal ulcers.103
burned corneas.95 Vancomycin (5%): Vancomycin is a glycopeptide, bactericidal
antibiotic that inhibits bacterial cell wall synthesis and is
Benzyl penicillin (25,000 IU): Benzyl penicillin (Penicillin-G) is
effective against Gram-positive organism such as Strep. viridans,
a narrow spectrum antibiotic, active against gram positive Enterococcus and Cl. difficile. It is usually added to the
bacteria such as Streptococcus aureus, Neisseria gonorrhoeae, and irrigation solution during cataract surgery to prevent
Neisseria meningitides. Penicillin provides effective treatment endophthalmitis.104
of conjunctivitis and keratitis caused by nontypeable strain
Voriconazole (1%): Voriconazole, a second generation of
of S. pneumoniae.96 triazole, it is mainly effective against fungal endophthalmitis
Cefazolin (5%): Cefazolin is a first generation cephalosporine. It caused by Candida, Aspergillus and Fusarium species.105
is effective against endophthalmitis caused after cataract
The authors/editors do not any financial interest in any product procedure
surgery.97 mentioned in this chapter.
Ceftazidime (5%): Ceftazidime is a third generation of
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Chapter 6.1
CORNEA: APPLIED ANATOMY

AND FUNCTIONS
Rajesh Ramanjulu, Rakhi Kusumesh, M Vanathi
CORNEA ANATOMY AND FUNCTIONS cuboidal cells. In week eight, these cells produce a basement
membrane, Descemet’s membrane.6,7
[Medieval Latin: corneus-horny, from corn ū-horn] Basal lamina is the first component of the epithelial
Cornea is a transparent avascular tissue at the anterior part adhesion complex to appear at eight to nine weeks. At 13
of the eye, that is highly specialized to refract and transmit weeks, the hemidesmosomes, anchoring fibrils and type VII
light and is essential for ideal visual function.1 It has a smooth, collagen have been noted.
convex surface and concave inner surface which resembles a At 13 weeks in addition to anchoring fibrils and
watch glass. The important functions which it subserves hemidesmosomes, a palisade of fine filaments is observed
include: extending perpendicular to the newly formed basal lamina.
• Refraction of light This has been postulated as the precursor of Bowman’s
• Contain the intraocular pressure membrane. Further development results in enlargement of
• Provide a protective interface with the environment. the cornea and dehydration of its stroma to form a transparent
Cornea forms the principal refractive surface, accounting structure.
for about 70 percent (40 to 44 diopters) of the total refractive The corneal diameter enlarges from 4.2 mm at 16 weeks
power. to 10 mm at birth. This five fold increase in area and 2.3-
fold increase in the corneal diameter is accompanied by 2.3
EMBRYOLOGY times decrease in the endothelial cell density. At birth the
central endothelial cell density is around 5000 cells/mm2. As
At five to six weeks of gestation the surface ectoderm the endothelium has a very limited regenerative capacity and
separates from the lens vesicle to form the epithelium which because aging results in progressive cellular senescence,
is one to two cell layers thick. There is a loose acellular layer particularly in the central regions, there is a well-documented
destined to become the stroma. By the end of week six, decline in the central cell density. This decrease occurs in two
junctional complexes appear between cells. In week seven, phases. The rapid phase occurs in infancy due to the growth
mesenchymal cells derived from the neural crest migrate of the cornea as mentioned above which causes an exponential
forward from around the lens vesicle in three waves: decrease of cells to 3500 cells/mm2 by 5 years of age.
a. The first wave of cells migrates between the surface Thereafter, it decreases at a linear rate of 0.3 to 0.6 percent
ectoderm and lens to form the corneal and trabecular per year.8
endothelium.2-4
b. The second wave migrates between the corneal epithelium MACROSCOPIC FEATURES
and endothelium to form the corneal stroma.5
Optical Properties
c. The third wave migrates between the corneal endothelium
and lens to form the iris stroma. In front the cornea appears elliptical, being 11.7 mm wide in
Epithelium: The final adult epithelium is attained by 37 the horizontal meridian and 10.6 mm in the vertical. The
weeks. The corneal endothelium forms as a two-cell layer of posterior surface appears more spherical and measures about
366 Cornea and External Eye Diseases
11.7 mm in diameter. This difference is due to greater overlap epithelial surface, which is an important pre-requisite for good
of conjunctiva and sclera above and below than laterally. functional visual acuity.10,11
The axial thickness of cornea is 0.52 mm with the peripheral Corneal transparency is derived from three factors:12,13
thickness being 0.67 mm.9 At birth the cornea is slightly thicker • Collagen fibrils are very ineffective scatterers of light
than that in children, perhaps reflecting the onset of • Despite this, the waves scattered by different fibrils
endothelial function close to birth. The surface area is 1.3 destructively interfere with one another.
cm2, one-sixth the surface area of the globe. • Scattering is directly proportional to the thickness, and
The cornea forms part of what is almost a sphere, but is the cornea is thin.
more curved in vertical axis when compared to the horizontal. In 1957, Maurice proposed the lattice theory explaining
This results in “with the rule astigmatism”. The normal cornea that the, cornea is transparent because. (Fig. 6.1.1):14
is a prolate shaped that flattens peripherally especially in the • The uniform fibrils are arranged in a regular lattice so
nasal region. The center optical zone has a radius of curvature that the scattered light is destroyed by mutual interference.
measuring about 7.5 mm, which equates to an average central • Fibrils are regularly arranged in lattice, separated by less
power of 43.5 D. However, the range of central power in than a wavelength of light (4000-7000 Å).
normal humans is 39 to 48D. The posterior surface has There is evidence that refractive elements whose
smaller radii of curvature, the average being 6.5 mm, giving dimensions are small (<2000Å) compared with wavelength
it a refractive power of 40-44 D. of light (<5000Å) should not scatter much light.15 Only one
Though on casual look, the cornea seems circular, in fact percent light is scattered in the cornea, because the diameter
it is not so. Corneal diameter is not equal in horizontal and of its collagen fibrils are uniformly small (300 Å) and
vertical meridian. This difference makes the cornea uniformly spaced (550 Å apart).
horizontally oval and the cause of this difference is due to Direct summation of fields published, in 1986, by Freund
constant pressure of the lid over the cornea making the cornea et al16 elaborated a method to compute light scattering from
more curved vertically resulting in a more myopic vertical the cornea. This method can be used to demonstrate that
axis. In the newborn, the cornea is flatter than in adult and its light scattering in the cornea will increase if:
curvature is more in the periphery. The mean corneal • Order in the spatial arrangement of the fibrils is destroyed;
diameter of 10 mm, at birth it increases rapidly to reach • Fibril diameters increase;
adult size by the end of the first year. Corneal diameter more • Fibril density increases; there is an increased refractive
than 12.7 mm is called megalocornea while diameter smaller index imbalance between the hydrated fibrils and the
than 10 mm in adults and less than 9 mm in newborns, is extrafibrillar matrix;
called microcornea. • Corneal thickness increases.
Cornea is highly ordered and complex in arrangement. Factors responsible for maintenance of corneal
Its transparency mainly depends on the special anatomical transparency include the following:
arrangement of collagen fibers in the stroma. The corneal • The corneal stroma naturally imbibes water because of
epithelium and tear film helps in maintaining a smooth two forces:
– The glucosaminoglycans exert an osmotic pressure
(swelling pressure: SP) of approximately 60 mm Hg
that pulls water into the stroma
– The IOP forces aqueous humor into the stroma.
• The endothelium counteracts this hydrophilic tendency
and maintains corneal transparency in two ways:
– Its barrier function decreases the flow of water into
the stroma
– Its metabolic pump transport ions from the stroma
to aqueous humor and water follows by diffusion.
The endothelium has both an active pump and passive
fluid barrier function.2 The endothelial pump consist of
enzymes, dependent on ATP, catalyzes the movement of
Fig. 6.1.1: Crosssectional view depicting regular ions from the stroma to the aqueous humor, creating an
arrangement of fibrils in the cornea osmotic gradient that draws water from the stroma.
Cornea: Applied Anatomy and Functions 367
Innervation of the Cornea facilitate cell mitogenesis and migration, DNA synthesis,
neurite extension and survival, keratocyte proliferation, and
Postmortem studies reveal that nerve fiber bundles in the
sub-basal plexus of the human cornea form a regular dense regulation of epithelial stem cells. Within 12 to 24 hour of
meshwork with equal density over a large central and central- corneal nerve impairment or loss, the epithelial cells swell
peripheral area.17 The thin sensory nerves, derived from the and lose their micro-villi, and begin to slough at an accelerated
first and to a small extent, from the second division of the rate. Denervation of the cornea clearly impairs the ability of
trigeminal nerve run parallel to the Bowman’s layer in the the epithelium to heal after injury and newly healed tissue is
subepithelial plexus.18 A-delta-fibers run straight and parallel at the high-risk of spontaneous breakdown.
to the Bowman’s layer beneath the basal epithelial plexus while A further complication of denervation is dry eye. In
the C-fibers, after a short run, parallel to the Bowman’s layer, studies, on unilateral dysfunction of the first division of the
send multiple branches penetrating epithelial cell layers, ending trigeminal nerve, reduced aqueous tear production was noted.
blindly in the superficial cells. Studies by Muller et al19 reveal Schirmer test values were also significantly reduced.20,21
that there are about 6000 nerve bundles in the human
sub-basal plexus each of which gives upto seven axons Vascular Supply of the Limbus
resulting in about 19000 to 44000 axons. These in turn give
off 10 to 20 nerve terminals which may be extrapolated to The anterior ciliary artery, branch of the ophthalmic artery
result in roughly 7000 nociceptors/mm2 making the cornea anastomoses with vessels derived from the facial branch of
the most highly innervated structure in the body (Fig. 6.1.2). the external carotid to form a vascular arcade.
The sub-basal nerve plexus comprises of unmyelinated sub-
basal nerve fiber bundles which are straight and beaded fibers, MICROSCOPIC FEATURES
that course in the basal aspect of the basal epithelial cell layer
and are easily seen in confocal microscopy imaging. Individual Epithelium
beaded fibers branch from the sub-basal bundles and
The human corneal epithelium is stratified squamous and
terminate in the more superficial epithelium as free nerve
endings which are not visible with tandem scanning confocal non-keratinized and measures about 50 to 90 μm in thickness.
microscope.19 It is continuous with the conjunctival epithelium at the limbus
The existence and function of these nerves, along with a but is different in not possessing goblet cells. It consists of
few sympathetic nerves which also supply the cornea is critical five to seven layers of nucleated cells, which includes:
to the health of various corneal tissue. They along with the • Two to three layers of terminally differentiated cells with
stromal keratocytes secrete a number of neuropeptides, which the largest surface area as compared to others and
Fig. 6.1.2: Sub-basal nerve plexus

increasingly flattened towards the surface called the epithelium. The aqueous humor is the most important source
superficial cells; of glucose for the corneal epithelium, though it may also be
• Two to three layers of polyhedral cells which cap the derived from glucose stores within the cells.
basal cells and are called the wing cells; and
• A single layer of columnar basal cells which perfectly aligns Bowman’s Layer
on a basal lamina and forms the germinative layer of the The Bowman’s layer is now considered as an acellular modified
epithelium. Basal cells of the corneal epithelium adhere to region of the anterior stroma. It is a narrow acellular
the basement membrane via the hemidesmosome that are homogeneous zone, 8 to 14 μm thick, immediately subjacent
linked to anchoring fibrils of type VII collagen. The basal to the basal lamina of the corneal epithelium. It is anteriorly
cells secrete type VII collagen, the long fibrils of which infiltrated by the lamina densa while posteriorly it merges
aggregate side-by-side to form a strap-like structure. The with the stroma. The fibrils of the Bowman’s layer are half
anchoring fibrils penetrate the basement membrane and to two-thirds as thick as that of the stroma. Ultrastructurally
course into the stroma, where they form an anchoring it is a meshwork of fine collagen fibrils of types I, III, V, and
plaque. VI as shown by immunoelectron microscopy and
immunofluorescence microscopy with type I constituting the
Basal Lamina: Basal lamina, a delicate membrane 40 to 60 nm
bulk of collagen present. Type IV and VII collagens are
thick, is secreted by the basal cells, which also synthesize the
present in association with the anchoring complexes of
hemidesmosomal structures concerned in the attachment of
uniform size. It is relatively resistant to trauma, both
the epithelium to the lamina. This is divided into deep
mechanical and infective. Once destroyed it cannot regenerate
osmophilic lamina densa and a superficial lamina lucida. It is but is replaced by scar tissue. Prolonged hypotony and
normally thicker in the periphery as compared to the center degenerative changes cause ridges which contribute to
but is abnormally thickened in diabetics and certain disorders. secondary anterior crocodile shagreen on the Bowman’s layer.
Fine anchoring filaments travel in the lamina lucida to mesh
into the larger anchoring fibrils of the lamina densa. These Stroma
thicker fibrils unite to form narrow bundles and insert into
the subjacent stroma terminating in anchoring plaques which The stroma constitutes 90 percent of the corneal structure
are composed of type VII collagen. The lamina lucida contains and consists of regularly arranged lamellae of collagen bundles,
and measures to a thickness of 500 μm. In the proteoglycan
the glycoprotein laminin, and the bullous pemphigoid antigen,
ground substance, relatively small populations of cells called
while the lamina densa contains type IV collagen.
keratocytes are distributed (keratocytes are responsible for
The corneal epithelium is maintained by the equilibrium
the production of stromal collagen, proteoglycan and
between cell loss by shedding of the surface epithelium and
structural glycoproteins). Proteoglycans constitute most of
cell replacement by proliferation of basal epithelial cells and
the ground substance of the stroma that includes keratan
the centripetal movement of peripheral cells. The mitotic
sulphate, chondroitin sulphate and dermatan sulphate. It has
rate of basal epithelial cells is about 10 to 15 percent per day been postulated that the proteoglycans are responsible for
and these cells migrate at a velocity of approximately 123 maintaining the relative positions of the collagen fibrils and
μm per week. Therefore basal epithelial cells are said to migrate restricting fibril growth. The lamellae are arranged in layers
from the limbus to the central cornea over a period of parallel with each other and with the corneal surface. In the
approximately a year. The corneal epithelium turns over superficial layer, angled less than 90°, they run from limbus
approximately every 7 to 14 days by division of basal epithelial to limbus, while that of the deeper layers run orthogonally
cells and sloughing of the surface epithelial cells into the tear and form strap-like ribbons which run approximately at right
film. The corneal epithelium consumes oxygen at a rate that angles to those in the consecutive layers. Each lamella
is 10 times more than the corneal stroma. Oxygen is comprises connective tissue collagen which show typical 64-
predominantly obtained from the atmosphere and inhibition nm periodicity. On transmission electron microscopy, corneal
of oxygen uptake leads to mild swelling of the corneal collagen fibrils are regular in diameter at all corneal locations
epithelium. Cornea obtains its energy requirements through and depths and are not significantly altered with aging. The
glucose metabolism (by glycolysis, tricarboxylic acid cycle and density of the fibrils is 1.12 times greater in the posterior
hexose monophosphate shunt under both hypoxic and stroma compared to that of the anterior stroma, in the central
normoxic conditions), of which 90 percent occurs in the cornea. Though the layers are arranged together, they can be
easily separated. This forms the basis of lamellar corneal membranes are in contact with the Descemet’s membrane,
grafting. Additional cells may also be seen occasionally, which being attached to it by modified desmosomes. Complex
include lymphocytes, macrophages and polymorphonuclear interdigitations exist between adjacent cells and they are bound
cells. Corneal fibrils are mainly composed of type I collagen, together by cell junctions and junctional complexes. The
and collagen types of III, V, VI, XII and XIV have also been posterior cell membranes exhibit multiple microvilli whose
detected in the stroma. functions are unclear.
The human cornea contains about 2 to 3.5 million Endothelial cells have the second highest aerobic metabolic
keratocytes, which comprise about 9 to 17 percent of the total rate in the eye only next to the photoreceptors.22-24 As the
stromal volume. Each keratocyte is flat (about 1 μm thick) endothelium has a very limited in vivo regenerative capacity
with numerous cell processes of up to 50 μm long that extend and because aging results in progressive cellular senescence,
multidirectionally, parallel to the corneal surface. These stellate particularly in the central cornea there is a well documented
processes are in contact with those of the other keratocytes in decline in the cell density. During adulthood endothelial cell
the same horizontal plane, while anteroposterior connections density decreases at a rate of approximately 0.6 percent per
between adjacent planes have not been found to occur. year, the causes of which are not clear but perhaps apoptosis
and/or necrosis due to light induced oxidative damage could
Descemet’s Membrane be responsible. The decrease in the density of cells can be
divided into:
Descemet’s membrane is the basal lamina of the endothelium. • Rapid phase: The cells decrease exponentially to 3500 cells/
Its synthesis continues throughout adult life, increasing in mm2 by the age of five years and to 3000 cells/mm2 by
thickness from 3 to 4 μm at childhood to 10 to 12 μm at 14 to 20 years.25-27
adult life. It is a relatively strong and resistant sheet and sharply • Slow phase: The central cell density decreases at a steady
defined from the overlying stroma. The major constituent state of 0.3 percent to 0.6 percent per year, resulting in
includes type IV and VII collagen. Despite the absence of 2500 cells/mm2 by adulthood.24,26,28
elastic tissue, the Descemet’s membrane coils inwards towards As the corneal endothelium maintains its contiguity by
the stroma upon mechanical injury (while a similar basal migration and expansion of surviving cells, it is not surprising
membrane, the anterior capsule coils outwards when exposed that the percentage of hexagonal cells decreases and the
to trauma). Long spacing collagen that results as an aging coefficient of cell size variation increases with age.25
process gets deposited in this layer as excrescence. Though The lateral borders of the cells are markedly convoluted
they resemble guttae, they are not associated with any clinical to produce a complex interdigitation with the neighboring cells,
abnormality in the corneal function. while the posterior surface has 20 to 30 microvilli per cell.
Electron microscopy of the Descemet’s membrane shows
that this is laminated consisting of 2 distinct layers. The Function: Endothelium acts as a barrier and prevents the bulk
anterior banded layer comprises of one-third of the flow of aqueous into the corneal stroma, but at the same
Descemet’s membrane and corresponds to that part produced time allows the moderate flow of nutrients, water and other
during the fetal life. It has fibrils that are arranged in a metabolites to cross over. The cornea is thought to maintain
vertically banded pattern (with 100 to 110 nm spacing). The its deturgescence by a pump-leak mechanism, as hypothesized
by David Maurice,29 in which the endothelial cells maintain
posterior non-banded layer comprises the remaining two-thirds
both a barrier to solute and fluid movement into the stroma
of the Descemet’s membrane and corresponds to the part
from the aqueous humor and an active pump of solute out
produced after birth, consisting of fibrogranular homogeneous
of the stroma into the aqueous humor. Water accompanies
material that thickens with age.
the solute movement passively, responding to local osmotic
gradients.
Endothelium
Clinically, the barrier function can be assessed by:
In the infant cornea, the endothelium is composed of a single • Direct fluorescein photometry by assessing the
layer of approximately 5,00,000 neural crest derived cells permeability. The basis for the use of this measurement is
with an average cell density of 5000 cells/mm2.22-24 They the assumption that the permeability of the endothelial
are uniform in size and are hexagonal in shape, and in cross- monolayer to the small molecule, fluorescein, is proportional
section are approximately 4 to 6 μm thick and 20 μm in to its permeability to other solutes. An increase in the
diameter. Each cell has a centrally located oval shaped nucleus endothelial permeability to fluorescein represents a
of approximately 7 μm in diameter. The anterior cell decrease in the endothelial barrier function.30-32
• Indirect specular and confocal microscopy, by assessing • Termination of the wound healing process: Cell numbers begin
the endothelial cell density and morphology. to decline and return to normal within 3 to 6 days postinjury.
REGENERATION/HEALING Endothelium: As mentioned previously, corneal endothelial

wound healing occurs predominantly by cell migration and
Epithelium: Epithelium renews itself within approximately five enlargement rather than proliferation. Thus injury results in
to seven days with the superficial cells being constantly shed increase in cells with abnormal shape (pleomorphism—
into the tear pool. Terminal differentiation of cells, coupled normally being <50%) and size (polymegathism—normally
with cell death by apoptosis, prompts the cell loss by <45%).37,38
desquamation, which is aided by blinking. The maintenance
of the corneal epithelium is thought to be achieved by the
unipotent stem cells located in the basal epithelium of the LIMBAL STEM CELLS
corneoscleral limbus. Studies of induced exfoliation of a The corneal limbus is a highly vascularized, innervated and
monolayer of epithelial cells with a biologic detergent indicate pigmented zone between the cornea, conjunctiva and the
recovery of the paracellular barriers and transepithelial electric sclera. It consists of pigmented spikes called the palisades of
resistance in approximately one hour. 33 The epithelium
Vogt which are proposed to bear the limbal stem cells. 39 It is
completely turns over in approximately seven days.34 Once
here that the location the limbal epithelial crypt has recently
injured, a high degree of motility ensures coverage of a
been identified, with an estimated six such structures per human
denuded area by adjacent basal cells, followed by replacement
of the normal complement of cell layers. Using limbus.
immunohistochemical staining for antibodies to keratins, Wiley Adult stem cells are defined by a number of key features
and associates found regional heterogeneity indicating that including:
the superior corneal periphery and limbus have the greatest • Slow/long cycling time during homeostasis in vivo;
numbers of stem cells producing replacement epithelial cells.35 • Poorly differentiated with primitive cytoplasm;
Limbal stem cell deficiency may result in conjunctival • High capacity to maintain a normal and stable genome
epithelium invasion of the cornea, leading to vascularization, during replication;
the appearance of goblet cells, and an irregular or unstable • Proliferation without maturation; and
epithelium that reduces visual acuity and may produce pain • Generate a large number of functional differentiated
or discomfort.36 The delicate balance of self renewal explained progeny via transient amplifying cells (TACs). It is
above can be easily understood by the X-Y-Z hypothesis.37 hypothesized that the limbal stem cells, give rise to transient
Stromal: The response to any injury, which includes corneal amplifying cells (TACs), which migrate centripetally
surgery involves: towards the center of the cornea. As these TACs migrate
• Removal of damaged tissue: Primary response being spreading away from the limbus and upward from the basal layer
death of keratocytes immediately adjacent to the wound they become terminally differentiated. The exact cues
site, which peaks by four hours and lasts for as long as that trigger the differentiation process have not yet been
one week. This is followed by appearance of inflammatory identified, and are likely to involve a subtle combination
response varying from 3.5 to 12 hours and begins to of changes in basement membrane, soluble factors and
resolve by 48 hours. cell to cell connections.
• Proliferative and migratory phase: Subtle changes appear in The current evidence of the limbal location of stem cells
the keratocytes within 6 hours of the injury. They appear
can be summarized as:
enlarged with increase in size and number of nucleoli.
• Limbal basal epithelium lacks the corneal epithelial
The cytoskeleton is also remodeled as the keratocytes get
transformed into fibroblasts. differentiation associated keratin pair, keratin 3 and keratin
• Phase of repair and replacement: Repair cells migrate into the 12.40-42
acellular zone within 24 hour of the injury and 72 hours • Limbal basal epithelium cells have higher proliferative
after the injury, fibroblasts proliferate. Myofibroblasts also potential in culture.43-45
appear, first under the epithelium and then engulf the • Abnormal corneal wound healing with conjunctivilization
entire region. The appearance of myofibroblasts and its is noted in partial/complete removal of the limbal
contraction are associated with scar formation. epithelium.45-48
Identification Markers 7. Wulle KG. Electron microscopy of the fetal development of the
human corneal endothelium and Descemet’s membrane of the
The various identification markers49 include: human eye. Invest Ophthalmol 1972;11:897-904.
• Cytokeratin: Absence of expression of the cytoskeletal 8. Edelhauser HF. Castrovejo lecture : the resiliency of the corneal
proteins, cytokeratins 3 and 12 (terminal markers of endothelium to the refractive and intraocular surgery. Cornea
2000;19:263-73.
corneal epithelial differentiation) by the limbal basal
9. Minisha S. Corneal thickness. Surv Ophthalmol 1968;133:57-96.
epithelial cells,50,51 and expression for cytokeratin 19 of 10. Ishida R, Kojima T, Dogru M, et al. The application of new
limbal basal cells is considered possible stem cell or TAC continuous visual acuity measurement system in dry eye syndromes.
phenotype.51 Am J Ophthalmol 2005;139:253-8.
• Cytosolic proteins: α-enolase and PKC-gamma have been 11. Kojima T, Ishida R. Dogru M, et al. A new non-invasive tear
identified as specific to limbus. stability analysis system for assessment of dry eyes. Invest
• Nuclear protein: P63.
12. Meek KM, Leonard DW. Transparency, swelling and scarring in
• Cell surface proteins: Cx43, E-cadherin, Beta-cadherin, the corneal stroma. Eye 2003;17:927-36.
integrins. 13. Farrell RA, McCally RL. Corneal transparency. In: Albert DM,
Jakobiec FA (Eds). Principles and practice of ophthalmology WB
EMERGING AND FUTURE Saunders: Philadelphia, PA, 2000;629-43.
14. Maurice DM. The structure and transparency of the cornea.
TECHNOLOGIES J Physiol 1957;I36:263-86.
• Stem cells for stromal repair : Autologous stem cell 15. Benedek GB. Theory of transparency of the eye. Appl optics
1971;10:459.
transplantation has been proven effective for restoration
16. Freund DE, McCally RL, Farrell RA. Direct summation of fields
of badly damaged ocular surfaces. Harvesting sufficient for light scattering by fibrils with applications to normal corneas.
numbers and its in vitro expansion has provided adequate Appl Opt 1986;25: 2739-46.
pluripotent cells for transplantation. Though the success 17. Muller MJ, Vrensen GF, Pels L, et al. Architecture of human
for allogenic transplantation remains low, it provides corneal nerves. Invest Ophthalmol Vis Sci 1997;38:985-94.
promise for the future. 18. Guthoff RF, Wienss CF, Hahnel G, et al. Epithelial innervation
• Gene therapy: It has the potential to reverse myofibroblast of human cornea: A three dimensional study using confocal laser
scanning fluorescence microscopy. Cornea 2005;24:608-13.
differentiation or inhibit the expression of transforming 19. Muller LJ, Marfurt CF, Kruse F, Tervo TM. Cornea nerves:
growth factor-β (TGF-beta) to reduce postoperative structure, content and functions. Exp Eye research 2003;76:521-
scarring and photorefractive keratectomy (PRK) induced 42.
stromal haze. A plasmid vector-encoding tissue 20. Heigle TJ, Pflugfelder SC. Aqueous tear production in patients
plasminogen activator has shown promise in reducing with neurotrophic keratitis. Cornea 1996;15:135-8
fibrin formation. 21. Gipson IK, Joyce NC, Zieske JD. The anatomy and cell biology of
human cornea, conjunctiva, and adnexa. In: Foster CS, Azar DT,
Dohlman CH (Eds). The cornea: scientific foundation and clinical
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3. Fitch JM, Linsenmayer TF. Monoclonal antibody analysis of ocular
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24. Dawson DG, Edelhauser HF, Grossniklaus HE. Long-term
4. Hayashi K, Sueishi K, Tanaka K, Inomata H. Immunohistochemical
evidence of the origin of human corneal endothelial cells and histopathology findings in human corneal wounds after refractive
keratocytes. Graefes Arch Clin Exp Ophthalmol 1986;224:452-6. surgical procedure. Am J Ophthalmol 2005;139:168-78.
5. Ozanics V, Rayborn M, Sagun D. Observations on the morphology 25. Hogan MJ, Alavarado JA, Weddell E. Cornea; The limbus. In:
of the developing primate cornea. Epithelium: Its innervation Histology of the human eye. An Atlas and textbook. Philadelphia
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6. Murphy C, Alvarado J, Juster R. Prenatal and postnatal growth of 26. Edelhauser HF, Castroviejo Lecture: The resiliency of corneal
the human Descemet’s membrane. Invest Ophthalmol Vis Sci endothelium to refractive and intraocular surgery. Cornea 2000;
1984;25:1402-15. 19: 263-73.
27. Yee RH, Matsuda M, Shultz RO, et al. Changes in the normal 40. Schermer A, Galvin S, Sun TT. Differentiation related expression
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Eye Res 1985; 4: 671-8. 1986;103:49-62.
28. Armitage WJ, Dick AD, Bourne WM. Predicting endothelial cell 41. Chen Z, de Paira CS, Luo L, et al. Characterization of putative
loss and long-term corneal graft survival. Invest Ophthalmol Vis Stem cells phenotype in human limbal epithelia. Stem cells 204;
Sci 2003;44(3):326-31. 22:355-66.
29. Maurice DM. The cornea and sclera. In: Davson H (Ed). The Eye. 42. Kurpakas MA, Maniaci MT, Esco M. Expression of Keratins
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30. Jones RF, Maurice DM. New methods of measuring the rate of Curr Eye Res 1994;113: 85-4.
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Techniques in Ophthalmology. Springer-Verlag, New York 45. Chen JJ, Tseng SC. Abnormal corneal epithelial wound healing in
1990;248-80. partial limbal deficiency. Inves Ophthalmol Vis Sci 1990; 31:
33. Wolosin JM. Regeneration of resistance and ion transport in rabbit 1301-14.
corneal epithelium after induced surface cell exfoliation. J Membr 46. Chen JJ, Tseng SC. Abnormal corneal epithelial wound healing in
Biol 1988;104:45. partial thickness removal of limbal epithelium. Inves Ophthalmol
34. Hanna C, Bicknell DS, O’Brien JE. Cell turnover in the adult Vis Sci 1991;32:2219-33.
human eye. Arch Ophthalmol 1961;65:695. 47. Huang AJ, Tseng SC. Corneal wound healing in the absence of
35. Wiley L, SunderRaj N, Sun TT, et al. Regional heterogeneity in
Limbal epithelium. Inves Ophthalmol Vis Sci 1991; 32: 96-105.
human corneal and limbal epithelia: An immunohistochemical
48. Kruse FE, Chen JJ, Tsai R, et al. Conjunctival trans differentiation
evaluation. Invest Ophthalmol Vis Sci 1991;32:594.
is due to incomplete removal of limbal basal epithelium. Inves
36. Dua HS, Azuara-Blanco A: Limbal stem cells of the corneal
epithelium. Surv Ophthalmol 2000;44:415.
49. Schrehardt US, Kruse FE. Identification and characterization of
37. Honda H, Higushi OS, Kani K, et al. Cell movements in a living
limbal stem cells. Exp Eye Res 2005; 81:247-64.
mammalian tissue: long-term observation of individual cells in
50. Schermer A, Galvin S, Sun TT. Differentiation-related expression
wounded endothelia of cats. J morphol 1982;174: 25-39.
of a major 64K corneal keratin in vivo and in culture suggests
38. Matsuda M, Sawa M, Edelhauser HF, et al. Cellular migration and
limbal location of corneal epithelial stem cells. J Cell Biol
morphology in corneal endothelial wound repair. Invest
1986;103(1):49-62.
39. Torczynski E. Sclera. In: Jackobiec FA, (Ed). Ocular Anatomy, 51. Kasper M, Moll R, Stosiek P, Karsten U. Patterns of cytokeratin
Embryology and Teratology. Philadelphia. Harper and Row; and vimentin expression in the human eye. Histochemistry.
1982;587-9. 1988;89(4):369-77.
Chapter 6.2
EVALUATION OF THE CORNEA
6.2.1 Specular Microscopy of the Cornea

M Vanathi, Rajesh Ramanjulu
HISTORY optical interface between endothelium and aqueous humor.4

A slit beam of light is projected onto the cornea, such that
Light striking a surface can be reflected, transmitted, or
the angle of the incident light and the corresponding angle of
absorbed. Generally, some combination of these three effects
reflected light to the reflecting surface are equal. Due to this
occurs, the relative proportion of which depends upon factors
design, non-specular light rays are not observed. A projected
such as:
slit light is focused on the posterior endothelial surface by an
• Wavelength of light
objective lens. The light that is reflected from this surface is
• Relative transparency of the medium
collected by the same objective lens and is focused onto a
• Relative refractive indices on each side of the surfaces.
focus plane, generally either a film plane or sensor of a video
The importance of reflected light in studying the
morphology of cornea was first demonstrated by Maurice in camera.
1968.1 He used an epi-illuminated microscope that focused a Figure 6.2.1.1 shows a narrow slit of light from a specular
slit of light onto the posterior corneal surface of an enucleated microscope that is focused onto the posterior corneal surface.4
rabbit eye to capture specular images (image from a smooth
surface) of the corneal endothelium, and hence suggested the
name “specular microscope” for this instrument. The
usefulness of this instrument in clinical ophthalmology was
discovered by Hoefle and co-workers,2 who utilized it in
evaluating the endothelial morphology of the donated human
cornea before keratoplasty. Laing and colleagues modified
Maurice’s instrument, producing photomicrographs of
sufficient resolution to demonstrate individual cell boundaries
and to differentiate numerous intracellular structures. Thus,
the technique of clinical specular microscopy as it is known
today, was launched.3
Principle
Specular microscope is a reflected-light microscope. It projects Fig. 6.2.1.1: Diagrammatic representation of principle of
light onto the cornea and captures the light reflected from the specular microscope
The incident light illuminates the precorneal tear film or Specular microscopic evaluation of the corneal
coupling fluid, the epithelium, Bowman’s layer, the stroma, endothelium enables to obtain a non-invasive morphological
Descemet’s membrane, the endothelium and the aqueous objective analysis of the imaged endothelial cell layer. The
humor. The amount of light reflected from each of these specular image analysis provides a measure of the endothelial
interfaces has been calculated as:8 cell physiologic reserve from aging, ocular surgical procedures,
• Objective lens-saline interface = 0.36 percent (refractive pharmaceutical exposure, and general health of the corneal
index of lens =1.517) endothelium. Pachymetry, fluorophotometry, and volume
• Saline-corneal epithelial interface = 0.25 percent (refractive stress index include other methods of assessment for the
index of saline =1.333) corneal endothelium. Analysis of the endothelial cell
• Corneal endothelium-aqueous interface = 0.22 percent physiologic reserve is essential to study endothelial changes
(refractive index of cornea = 1.376 and of aqueous = 1.33). due to aging, its response to ocular surgical procedures and
(Intra-corneal interfaces such as between epithelium and pharmaceutical exposure and to assess the general health of
Bowman’s membrane or stroma and Descemet’s membrane the endothelium. Specular microscopy is superior to slit lamp
also reflect light, but the fraction of light reflected cannot be specular examination as it provides higher magnification and
calculated). greater accuracy of estimation besides giving a permanent
If a sufficiently narrow slit of incident light is used one printed record and a comparative computer-assisted analysis.
can appreciate four zones, which include: Uses of the specular microscopy include:
• Lens-coupling fluid interface/Bright zone/Zone 1. • Assessment of eye bank donor (EB) corneal endothelium
• Stromal region/Zone 2. • Monitoring different modes of anterior segment surgery
• Endothelial region/Zone 3. • Assessment of surgical techniques
• Aqueous region/Zone 4. • To study the action of agents in clinical use
(It has to be noted that the interface between Zone 3 and • To study the effects of naturally occurring diseases.
Zone 4 is called as the ‘dark boundary’, while that between Zone Study of human endothelial morphologic changes,
2 and Zone 3 is called as the ‘bright boundary’. quantitated by specular microscopy and computer-assisted
At the film plane of the specular microscope, light from morphometry have established normal baselines of various
various corneal regions and interfaces overlap. Depending on morphologic parameters. 5-8 Cellular polymegathism and
the slit width of the illumination source, a typical endothelial cellular pleomorphism has been reported to increase with age.8
photomicrograph contains three or four distinct zones.4 The Corneal endothelial cell counts range to about 350,000 cells/
appearance of the boundary between the endothelial cell cornea.8 The estimated human endothelial cell count variation
pattern and the adjacent dark zone, called the dark boundary, with age is as follows:
reflects the configuration of the endothelial cell-aqueous • At birth: 3000 to 4000 cell/mm2
humor interface and provides important information about • At middle age: 2500 cell/mm2
the posterior corneal surface. • At old age: 2000 cells/mm2.
The size of each cell and the number of cells captured in The minimal acceptable endothelial cell count is considered
a single frame depends on the width of the slit projected. If to be 1500 cells/mm2 while a critical cell count, described as
the angle of the incident light is increased, a wider slit can be the critical limit for endothelial decompensation is said to be
used and a larger field of endothelial cells can be captured. 700 cells/mm2.
This wider slit also causes increased back-scattering of light Types of specular microscopes are:
from the anterior stroma. The net result is a decrease in the a. Contact specular microscopes have higher magnification
contrast of the endothelial image and a loss of cellular and resolution. It functions using contact objective lenses
definition. that touch the cornea and inhibit eye movement.
b. Non-contact specular microscopes have lower
Narrow slit Wide slit magnification and resolution. It functions using non-
1. Less field captured 1. More field captured
contact objective lenses that do not touch the cornea.
2. Good contrast 2. Poor contrast Advantages of non-contact specular microscopes are that
3. Good image of the endothelium 3. Poor image of the they are operator independent and non-invasive. Disadvantages
4. Only 3 zones, Zone 2 disappears endothelium
while Zone 3 is enlarged
of non-contact specular microscope are that the exact point
of imaging is not known accurately and hence is less
Evaluation of the Cornea 375
reproducible and it is time consuming. Clinical use is limited 6.2.1.2). The side lengths are equal and the angle of
to corneas free of edema, scarring, deposits or opacities that intersection is approximately 120o. Cell size, as well as
may distort light transmission. Contact method has its own changes in the shape (Figs 6.2.1.3A and B) can occur as a
disadvantages of risk of infection and epithelial damage and result of number of corneal disorders, e.g. keratoconus,
also requires a skilled operator. where the cells appear to be aligned in the same direction
McCarey et al’s review of corneal endothelial specular and follow lines of stress. Contact lens wear can cause
microscopy for FDA clinical trials of refractive procedures, transient (bleb) morphology changes while chronic
surgical devices, and new intraocular drugs and solutions morpholog y changes such as pleomorphism and
elaborated the normal and stressed endothelial cell polymegathism may be discernible.10
morphology, the techniques for determining the morphology • Cell boundaries: Cell boundaries often appear as dark,
parameters, and clinical trial applications.9 It describes the straight, narrow lines with three angles of intersection of
image quality obtained on specular microscopes as good, fair, 120o. Additional types of cell boundaries collectively
poor and impossible quality depending on the endothelial cell referred to as doubled boundaries have been observed.
image quality, viewable field of contiguous cells, and number Cell boundaries intersection can also vary considerably
of cells counted per field.9 from 120°.
The normal endothelial cell: The specular image of a normal
endothelial cell appears as a white body with dark borders.
The cell borders always appear black, as the incident ray on
the cell boundary is irregularly reflected and thus prevents its
collection by the viewing optics.
The degree of irregularity or roughness of the posterior
corneal surface can also be determined by evaluation of the
dark boundary in the micro-photographs. Four types of
posterior corneal surfaces recognized include:
Type Features
Smooth All incident rays are directed back to the
collection optics
Rough Dark boundary with linear irregularities
Wavy
Surface with Sides of excrescence appear dark while the
excrescence apex reflects light and appears bright
Fig. 6.2.1.2: Regular hexagonal pattern of endothelial cells
ANALYTIC MEASUREMENTS
Analytical measurements of the specular image can be
qualitative and quantitative. Qualitative examination involves
analysis of cell configuration, cell boundaries and their
intersections, configuration of the dark boundary and presence
of acellular structures such as guttate, intracellular bodies, base
of an endothelial cilia, and intracellular vacuole or bleb.
Intercellular dark structures represent invading inflammatory
cells. Quantitative analysis includes calculation of cell area
(µm2), cell density (cells/mm2), polymegathism (coefficient
of variation) and pleomorphism (percentage of hexagonal
cells).
Qualitative Analysis
• Cell conformation: Normal endothelial cells as seen in the Figs 6.2.1.3A and B: Endothelium showing
young are quasi-regular or quasi-hexagonal in shape (Fig. polymegathism and pleomorphism
• Posterior corneal surface: Based upon the appearance of the Quantitative Endothelial Cell Morphology
dark boundary, which is the interface between the • Variation of individual cell area—polymegathism
endothelial cell and the adjacent dark zone produced by (coefficient of variation of cell size).
the aqueous humor, the endothelial surface can be divided • Variation of individual cell shape—pleomorphism
into 4 types as previously mentioned: (% of hexagonal cells).
• Endothelial cell density (number of endothelial cells/mm2).
Surface Dark boundary
Standard Deviation (SD) of cell area
Smooth Straight and regular Coefficient of variation (CV) = _____________________________________________
Rough Irregular Mean cell area µm2
Wavy Smooth and uneven
Excrescence Localized irregularity (CV values of normal young adult—0.27 to 0.28, expressed as
27–28).
• Miscellaneous structures: Various inter and intra-endothelial The effect of number of cells per image to the
cell structures noted include: coefficient of variation is as follows:
– Dark structure with dark sides and a central bright spot • SD increases with increasing CV
which disrupts the normal endothelial cell pattern • SD decreases with increasing number of cells counted
represent guttae. • SD stabilizes with >100 cells counted.
– Intracellular bright structure usually represent the nucleus.
– Two more dark structures: One supposed to represent the Corneal Endothelial Cell Density
cilia of the cell while the other which is much larger Determination Methods
represents the vacuole or bleb.
• Comparison Method: Comparison is made to a known
“honeycomb” pattern.
Qualitative Analysis
• Frame Method: The number of cells within a frame (variable
or fixed frame) is counted.
Two different methods can be utilized to measure the cell
• Corner Method: Cell area is determined from a polygon
density:
digitization by locating cell border intersections.
a. Fixed-frame analysis: In this method, the number of cells
• Center Method: Cell area is determined from adjacent
within a frame or window of constant area is counted. All polygon centers, “center to center”.
cells lying completely within the frame are counted as whole
cells. Each cell that is only partially within the frame is In comparison method, the endothelial cell count is obtained by
counted, regardless of the fractional area of the cell located comparing the cells imaged to standard set hexagonal cell size
within the frame. A symmetry principle is commonly used design with endothelial count conforming to that cell size.
to speed up the process. Cells on two boundaries are Frame method: In the frame method, all cells within a frame are
counted and those on the other two boundaries are not counted. The observer has to adjust for cells extending outside
considered. The size is ultimately derived by dividing the of frame, counting partial cells as full cells on two adjacent
cell count by the area of the frame. The area of the frame frame sides. The cells counted are expressed as cells/mm2.
must be calibrated to the endothelium. The size of the frame determines the number of cells to
b. Variable-frame analysis: In this method, the variable area be counted. The decision on partial cells and cell borders is
occupied by an integral number of the cells is measured. also to be considered.
The cell density is then calculated by dividing the number Cell count = No. of cells counted in frame × R
of cells that have been traced by the area of the frame. 1
• Individual cell analysis: In fixed frame analysis, only average Where R (multiplier factor) = _______________
cell size can be determined. The same holds true for Frame area
variable frame analysis if only a group of cells is For example, if frame area = 0.036 mm2 and number of
circumscribed. However, in variable frame technique single cells counted in frame = n, then,
cells can be traced and individual cell analysis can be done. Cell count = n × 27.8
If frame area is 0.018 mm 2 , number of cells • Corneal guttae: A common condition, the incidence of which
= n, then Cell Count = n × 55.6 increases with age.6 Corneal guttae are focal accumulations
of collagen on the posterior surface of the Descemet’s
Variable frame analysis: Certain computer based analysis system
membrane. There are five types of guttae:
eliminate the problem of counting fractional cells along the
a. Primary central corneal guttae: commonly associated with
boundary, thereby enabling an accurate determination of mean
aging.
cell size than fixed frame analysis. The observer first measures
b. Hassal Henle excrescences: located in the peripheral cornea,
the variable area occupied by an integral number of cells by
increases with age but are not pathological.
tracing around a contiguous group of cells and then marks c. Primary corneal guttae as a part of Fuch’s endothelial dystrophy.
each cell by clicking on it. The computer then calculates the d. Secondary corneal guttae: occurs secondary to toxic/
cell density by dividing the number of marked cells by the inflammatory insult to the endothelium.
area of the frame. Mean cell area, can also be obtained by e. Pseudo-guttata.
dividing the frame area by the number of cells.
Changes with cataract extraction varies from no detectable cell
Center method: In this method, the center of contiguous cells is loss (as in phacoemulsification with IOL implantation) to 40
marked by a dot to facilitate counting. It is ideal to count in a percent (ICCE).
circle.
In the corner method, the cell border corners are taken Evaluation Criteria of Donor Cornea
into account for counting. The presence of abnormal endothelial cells most likely
Individual Cell Analysis may be performed by tracing single indicates that the cornea is functionally deficient and
cells with the stylus of planimeter or digitizer. This provides compromised. Features on specular microscopy suggesting
much more information about endothelial cell pattern. that the cells are abnormal include:
• Can be done manually, semi-automatically, or fully • Cell density less than 1500 cells/mm2
automatically. The cell density or mean cell area can be • Severe polymegathism or pleomorphism
obtained by averaging the data on a group of cells. In • Presence of corneal guttata
addition, a frequency distribution (or histogram) of cell • Presences of several abnormal shaped cells
size can be obtained. • Abnormal single cell deficit
In two corneas with same cell density, the one with low • Extensive areas of severe edema
CV and higher percentage of hexagonality will be the more • Presence of ghost vessels in the stroma.
stable cornea to withstand the trauma of the surgical procedure. Specular microscopy may be used for corneal thickness
measurement by determining the difference in the focal planes
IN VIVO FINDINGS OF between the corneal epithelium and endothelium. Though the
SPECULAR MICROSCOPY reproducibility is good with non-contact specular microscopy,
• Aging: In most individuals the endothelial cell density values obtained with non-contact specular microscopy have
decreases (or mean cell area increases) throughout lifes.4 not been found to be consistent with that of ultrasound
Cell loss is most rapid from birth to the first few years of pachymetry.14,15 Contact and noncontact specular microscopes
life, partly due to the enlarging globe. It stabilizes from are not comparable in measuring corneal thickness due to the
the age of 20 through 50 years.5 After the age of 60 years, differences in the imaging techniques, possibly due to the
on an average the endothelial cell loss is approximately 0.5 corneal compression during contact specular microscopy, and
percent per year. 5 Specular microscopy of successful the effects of anterior corneal refractive power and variations
corneal transplant has revealed substantial but variable in air-corneal refractive indices in non-contact specular
endothelial cell loss well above that found in normal microscopy.
eyes.11,12 Ing et al have demonstrated that 5 to 10 years The limitations with specular microscopy lie with the fact
after successful penetrating keratoplasty, endothelial cell that as its optical system requires perpendicularity and
loss progresses at a rate seven times faster than normal.13 reflections from both the epithelial and endothelial surfaces
Endothelial cell loss is most rapid during the operative cause interruptions resulting from these reflections giving rise
procedure and early post-operative period but gradually to poor readings, thereby excluding its use in corneal edema,
slows down.13 scarring and opacities.13
REFERENCES 8. Yee RW, Matsuda M, Schultz RO, Edelhauser HF. Changes in the
normal corneal endothelial cellular pattern as a function of age.
1. Maurice DM. Cellular membrane activity in the corneal Curr Eye Res 1985;4(6):671-8.
endothelium of the intact eye. Experimentia 1968;24:1024. 9. McCarey BE, Edelhauser HF, Lynn MJ. Review of corneal
2. Hoefle FB, Maurice DM, Sibley R. Human corneal donor material: endothelial specular microscopy for FDA clinical trials of refractive
a method for examination before keratoplasty. Arch Opthalmol procedures, surgical devices, and new intraocular drugs and
1970;84(6):741-4. solutions. Cornea 2008;27(1):1-16.
3. Leibowitz HM, Laing RA, Sandstorm MM. Corneal endothelium. 10. Schoessler. Schoessler JP. Contact lens wear and the corneal
The effect of air in the anterior chamber. Arch Ophthalmol endothelium. J Am Opto Assoc 1987;58(10):804-10.
11. Obata H, et al. Corneal endothelial changes in penetrating
1974;92:227.
keratoplasty. Jpn J ophthalmol 1991;35:411-6.
4. Laing RA, Sandstrom MM, Leibowitz HM. Clinical specular
12. Bourne WM. Cellular changes in transplanted human corneas.
microscopy. I. Optical principles. Arch Ophthalmol 1979;97(9):1714- Cornea 2001;20:560-69.
9. 13. Ing JJ, et al. Ten years postoperative results of penetrating
5. Sherrad ES, Navokovic P, Speedwell L. Age-related changes of keratoplasty. Ophthalmology 1998;105:1855-65.
the corneal endothelium and stroma as seen in vivo by specular 14. Bovelle R, Kaufman SC, Thompson HW, Hamano H. Corneal
microscopy. Eye 1987;1:197-203. thickness measurements with Topcon SP 2000P specular microscope
6. Bourne WM, Hodge DO, Nelson LR. Corneal endothelium five and an ultrasound pachymeter. Arch Ophthalmol 1999;117:868-70.
years after transplantation. Am J Ophthalmol 1994;118:185-96. 15. Suzuki S, Oshika T, Oki K, et al. Corneal thickness measurements:
7. Lorenzetti DW, et al. Central corneal guttae. Incidence in the general scanning slit corneal topography and noncontact microscopy versus
population. Am J Ophthalmol 1967;64:1155-8. ultrasonic pachymetry. J Cataract and Refrac Surg 2003;29:1313-8.
6.2.2 Corneal Topography

Corneal topography by way of which measurements of the video image of the reflected keratoscopic rings from the
corneal shape are recorded may be done by several ways.1 corneal surface. A graphic depiction of this information is
These include the conventional reflection based topography systems presented as color coded corneal topographic maps.
(keratometry, photokeratoscopy, videokeratoscopy) and the Radius of curvature of the cornea can be calculated either
recent, projection based systems (rasterstereography, laser globally (axial radii of curvature) or locally (tangential radii of
interferometry, moiré interference etc).2 Data measurement curvature), and then converted to dioptric power using the
and presentation by various corneal topography systems standard keratometric index. Global (axial/sagittal) radius of
depend on the proper image acquisition. Projection-based curvature measures the distance of points from the optical
systems measure the true shape of the cornea in terms of the axis, and therefore has a spherical bias. Local (instantaneous/
height, or elevation, above a reference plane. This data is used tangential) radius of curvature calculates the curvature at each
to calculate surface slope, curvature and power. Reflection- point with respect to its neighboring points, and is therefore
based systems measure the slope of the corneal surface from more accurate for local irregularities and in the peripheral
which the curvature and power is derived with additional cornea.3 Axial curvature (sagittal curvature) measures the
measurements and certain assumptions made. Computer curvature at a certain point on the corneal surface in axial
assisted videokeratography, the most commonly used, direction relative to the center. Meridional curvature (tangential/
combines concentric ring keratoscopy with analysis by instantaneous curvature) measures the curvature at a certain
computer programs to produce a high resolution imaging of point on the corneal surface in meridional direction relative
the corneal topography. The computer calculates the dioptric to the other points on the particular ring. Meridional curvature
power and the radius of the curvature at hundreds of points maps are more sensitive measures of local curvature change.
on the anterior corneal surface on the basis of the captured Axial curvature maps can be derived from meridional maps.
Axial value at a certain point equals the average meridional Selecting the appropriate display format remains the key
curvature along the radius from the map center to the point in maximizing the information obtained from a topography
of interest, thereby approximating the average refractive power. examination.4 The raw image of the reflected placido rings
Axial and meridional maps should theoretically be displayed depict the corneal pathology or tear film abnormalities.
in the units of radii of curvature (i.e. mm) at each corneal Videokeratoscopy mires appear closer together in steep areas
surface point. When the display curvature is in units of and are further apart in flat areas. Every topographic map has
keratometric dioptres they are called axial or meridional power a color scale assigning a particular color to a certain
maps. The power of the cornea (in diopters) is a measure of keratometric dioptric range. Interpretation is not to be based
the anterior corneal refractive effect. Radius of curvature is on color alone, but also on the keratometric value. The
converted to power using the standard keratometric index (SKI most common display presentation format of topography in
= 1.3375). This is an approximate figure derived from the color-coded scale is representation of the steep areas by
assumptions about the thickness and refractive index of the the warm colors (red and orange) and the flat areas by the
cornea, and the shape of its posterior surface. cool colors (green and blue). When using the absolute
Height or elevation maps define the distance of each of point (standardized) scale, the same colors represent the same power
on the surface from a flat reference plane, which is used to on every map.4 The normalized (relative) scale, the step interval
interpret the overall shape of the cornea.3 Elevation is not fills the range of each map. In systems permitting an adjustable
measured directly by Placido-based topographers, but certain scale, the step interval can be selected by the operator.5 As
assumptions allow the construction of elevation maps. absolute maps have a preset color scale with the same dioptric
Elevation of a point on the corneal surface displays the height steps, dioptric minimum and maximum assigned to the same
of the point on the corneal surface relative to a spherical colors for a particular instrument, they allow direct comparison
of two different maps. However, because the steps are in large
reference surface (with the reference surface chosen in most
increments (generally 0.5 D), their disadvantage is that they
instruments being a sphere). Best mathematical approximation
do not show subtle changes of curvature and can miss subtle
of the actual corneal surface called best-fit sphere is calculated
local changes (e.g. early keratoconus). Normalized maps have
by the instrument software for every elevation map separately.
different color scales assigned to each map based on the
More recent developments in terms of wave-front analysis
instrument software that identifies the actual minimal and
provide information about the refractive power of the eye as
maximal keratometric dioptric value of a particular cornea.
a whole, rather than just the effect of the anterior corneal
Hence the dioptric range assigned to each color generally is
surface. smaller compared to the absolute map depicting more detailed
Most videokeratoscopes use similar mechanisms but vary description of the corneal surface. Two different maps can
in some of their features, such as the size of the cone of then be compared based on the interpretation of the
placido rings, and whether focusing is manual or automated. keratometric values of their different color scales.
Alignment and focusing of the reflected placido rings should Statistical indices depict a particular feature of the cornea,
be optimized while using videokeratoscopes in order to obtain such as its symmetry, regularity or asphericity. Interpretation
good measurement data. Accurate alignment, centration and of maps involves a systematic approach to study the
focusing is important to avoid the introduction of artifactual topographic pattern. This includes the following:
abnormalities. Tear film irregularities also contribute to • Patient details, laterality of eye, date of examination
artifacts. The reflected image of the placido rings is captured • Scale
on video camera and digitized. The computer analyzes the • Type of measurement (e.g. elevation, curvature, power)
position of each of the 15 to 38 circular mires along 256 to 360 • Step interval
semi-meridians, theoretically providing about 6,000 to 11,000 • Map
data points1. Algorithms then compute the curvature at each • Statistical information (indices)
point. The accuracy of measurements is about 0.15D in the • Comparison with prior maps of the same eye (it is
central zone of a normal cornea, but is commonly less in other important to ensure that the scale is the same)
situations due to the assumptions and approximations made • Comparison with the topography of the fellow eye (it is
by the algorithms. important to ensure that the scale is the same).
Astigmatic corneas show bowtie appearances with the red

bows lying along the steep meridian. In oblate corneas (as
those undergone flattening by surgery), the bows are blue and
lie along the flat meridian. Based on the various pattern
descriptions,8 combination patterns of regular astigmatism
such as prolate symmetric bowtie, prolate asymmetric bowtie,
oblate symmetric bowtie, oblate asymmetric bowtie and
irregular astigmatism such as prolate irregular, oblate irregular,
mixed patterns and others such as steep/flat pattern, localized
steepness pattern, triple pattern, horseshoe pattern have also
been elaborated.
Common indications for corneal topography in practice:
• Refractive surgery patients
– Preoperative assessment
Fig. 6.2.2.1: Normal corneal topography patterns based on – Postoperative follow-up
computer assisted videokeratography – For augmentation procedures.
• Diagnostic
– Screening for ocular disease
Corneal profile on topography might be categorized into
– Corneal ectasia
three profiles, viz prolate, oblate or mixed. The normal cornea
– Contact lens-induced corneal warpage.
is prolate, with the center being the steepest and gradually
• Planning surgical incision (cataract, astigmatic keratotomy)
flattening towards the periphery.
– Incision location, length, depth
Topographic patterns of the normal corneas can be described
• Contact lens fitting in irregular corneas
astigmatic patterns of the cornea in accordance to its pattern
• Intraocular lens power calculation in special situations
characteristics as follows (Fig. 6.2.2.1):6-8
• Management of astigmatism
• Round pattern: The ratio of the shortest to the longest
– Adjustment of incisions or sutures.
diameter at the color zone is 2/3 or more.
• Keratoplasty follow-up
• Oval pattern: The ratio of the shortest to the longest
• Others:
diameter at the color zone is less than 2/3.
– Suture manipulation/removal
• Regular astigmatism pattern:7 This is seen when the two
– Patient education
principal meridians are oriented at approximately right
– Communication with colleagues
angles to each other. The angle between the axis of the
– Documentation for medicolegal purposes.
two halves of the bowtie of less than 20o is defined as
regular astigmatism.
Corneal Topography in Common Clinical
– Symmetrical bowtie
Situations in Cornea Practice
i. A central constriction is identified in the color zone
ii. The ratio a0 / a1 or a0 / a 2 is 1/3 or less Contact lens (CL)-induced corneal warpage: Corneal topographic
iii. The ratio of a1 / a2 or b1 / b 2 is 2/3 or more. changes following contact lens wear are thought to occur
– Asymmetrical bowtie directly as a result of the mechanical pressure exerted by the
i. A central constriction is identified in the color zone lens. Patients with corneal warpage may be asymptomatic, have
ii. The ratio a0 / a1 or a0 / a 2 is 1/3 or less reduced spectacle corrected acuity or contact lens intolerance.
iii. The ratio of a1 / a2 or b1 / b 2 is less than 2/3. The changes are most severe and persistent in wearers of rigid
• Irregular astigmatic pattern: This pattern is defined when the gas permeable (RGP) lenses. Many topographic patterns can
angle between the two steepest semimeridia is greater than be induced, but they tend to comprise flattening in the areas
20o and would represent a bi-oblique bowtie pattern or of lens bearing, with possible adjacent steepening. The
when no pattern is discernible. topographic changes produced by CL induced warpage are
highly variable with the most common one being a presentation Myopic treatment zone is delineated by a central flattened
similar to early keratoconus. Others include central irregular zone while hyperopic correction shows central steepening
astigmatism, changed axis of astigmatism, loss of normal surrounded by a ring of relative flattening at the edge of the
progressive flattening from the center to the periphery and a treatment zone, where corneal tissue has been removed. In
correlation between the resting position of the CL and astigmatic treatments, the treatment zone is oval. Decentration
topographic pattern.9 Contact lens wear should cease six weeks is identified by comparing the first week post-operative map
prior to pre-operative assessment for hard or rigid lenses, and with a pre-operative map. Similar post-operative appearance
two weeks prior to soft contact lens fitting. Surgery is not may also be seen in pre-existing asymmetric astigmatism, or
advisable till stabilization of topography pattern. an asymmetrical healing response. Decentrations of large
diameter (6 mm) optical zones tend to be clinically significant
Post-keratoplasty: In such highly irregular corneas, topography
if greater than 1 mm, or in patients with relatively large pupils.
assessment using computer assisted videokeratography is more
Eight topographic patterns after PRK have been identified.
accurate than refraction or keratometry for determining axis
Patients with a homogeneous pattern have least astigmatism.
of greatest astigmatism, and the axis of tight sutures. Prolate
Those with regular patterns (homogeneous or toric) have a
patterns of topography are commonly seen after single
better refractive predictability, visual acuity and level of
continuous suturing. Suture adjustments are effective in bowtie
satisfaction than those with irregular patterns. The irregular
patterns. Suture removals may affect decrease in astigmatism
patterns include semi-circular, keyhole, central islands, focal
in bowtie patterns and not in oval/steep flat patterns.
irregularities and irregularly irregular. A central island is present
Corneal ectasias: Keratoconus and pellucid marginal degeneration when any part of the treatment zone is surrounded by areas
(PMD) is characterized by presence of irregular astigmatism of lesser curvature on more than half of its circumference.
and inferior (commonly) corneal steepening on topography. They are classified according to the power and diameter of
Corneal topography serves as one of the most sensitive the central steep area. The refractive and topographic changes
methods for detection of early keratoconus, as it may provide after LASIK are similar to PRK, but the over-correction is
the clinician with characteristic clues before clinical signs not as large, and usually early stability is achieved. Decentration
become evident. It is also imperative to be able to differentiate is more common and tends to be more significant. Epithelial
true early keratoconus from other similar conditions such as a in-growth at the periphery of the flap-stromal interface is
normal cornea with asymmetric bowtie or contact lens-induced characterized on topography by an area of steepening at the
warpage. Corneal topography of mild inferior steepening with edge of the treatment zone, which can progress centrally.
normal corneal thickness and no evident clinical signs of
keratoconus is termed “keratoconus suspect” and needs apt Quantitative Descriptors of
attention of the clinician in decision making to proceed with Corneal Topography
refractive surgery.
Quantitative descriptors of corneal topography provide useful
Terrien’s marginal degeneration of the cornea is
topographic information that enhance the utility of these
characterized on topography by noticeable flattening of the
machines in clinical practice and research. Simulated
cornea with high against the rule astigmatism.
keratometry provides an estimate of measurement that can
Refractive surgery: Refractive corneal procedures alter the central be obtained with a keratometer. Simulated keratometry
corneal curvature and hence the asphericity of the cornea. measurements characterize corneal curvatures in the central
Myopic refractive ablation treatments flatten the central optical 3-mm area. The steep simulated K-reading is the steepest
zone resulting in a cornea that is less prolate, or even oblate, meridian of the cornea, using only the points along the central
while hyperopic treatment steepens the optical zone, causing pupil area with 3-mm diameter. The flat simulated K-reading
the cornea to become increasingly prolate. Changes in corneal is the flattest meridian of the cornea and is, by definition, 90°
topography can be depicted in difference or subtraction maps apart. These readings give an idea about the central corneal
in which a later map is subtracted from an earlier one. When curvature that is frequently visually most significant. The 3-
topography is used to guide ablation, height maps are used so mm diameter is chosen primarily from historical reasons for
that the treatment can be applied to the peaks, rather than the the purpose of comparison with standard keratometry that is
steep sides, of any elevation. used for analysis of 4 central points, 3.2 mm apart.
Central corneal regularity correlates BCVA in normal eyes, analysis. In this method, the anterior corneal surface is imaged
such as the SRI (surface irregularity index) on the Tomey using the analysis of reflected images of multiple concentric
topography, the CIM (corneal irregularity measurement) on rings projected on the cornea. The basics of the most common
the Humphrey topography and the diagnostic summary on clinical method of Placido-based corneal topography has been
the Eyesys topography. Keratoconus detection programs are briefly reviewed. Limitations of corneal topography include
automated algorithms and those such as the Klyce/Maeda errors of corneal topography under optimal conditions of
and the Rabinowitz algorithms are available on the Tomey the range of ±0.25 D or 2 to 3 µm, and could be higher in
autotopographer.10,11 abnormal corneas. Corneal topography imaging based on the
A few orbscan maps of common clinical conditions have placido based systems requires an intact epithelial surface and
been included (Figs 6.2.2.2 to 6.2.2.6). tear film. Different technologies use different measurement
methods and algorithms; thus, the output data are not directly
SUMMARY comparable. As technologies undergo advancements,
interpretation of the results of studies comparing the
Corneal imaging techniques are rapidly evolving into higher
instruments, become rapidly redundant and difficult for
standards and understanding their significance is imperative
practical clinical purposes.
in management of common corneal refractive clinical
situations. Corneal topography instruments used in clinical The author/editors have no financial interest in any product/procedure mentioned
practice most often are based on Placido reflective image in this chapter.
Fig. 6.2.2.2: Orbscan quad map — OD post LASIK

Fig. 6.2.2.3: Orbscan quad map—OS post LASIK ectasia
Fig. 6.2.2.4: Orbscan quad map of keratoconus suspect

Fig. 6.2.2.5: Orbscan quad map of keratoconus suspect
Fig. 6.2.2.6: Orbscan quad map of patient who underwent triple procedure, 11 months postop with sutures off
REFERENCES 7. Bogan SJ, Waring GO, Ibrahim O, Drews C, Curtis L. Classification

of normal corneal topography based on computer-assisted
1. Corbett MC, Rosen ES, O’Brart DPS. ‘Corneal Topography: videokeratography. Arch Ophthalmol 1990;108:945-49.
Principles and Applications’. BMJ Publishing Group, London 1999. 8. Kharbatsas Ch, Cook SD, Sparrow JM. Proposed classification
2. Roberts C. Corneal topography: A review of terms and concepts. for topographic patterns seen after penetrating keratoplasty. Br J
J Cat Refract Surg 1996;22:624-9. Ophthalmol 1999;83:403–9.
3. Corbett MC, O’Brart DPS, Stultiens BA Th, Jongsma FHM, 9. Wilson SE, Lin DTC, Klyce SD, et al. Contact lens induced change
Marshall J. Corneal topography using a new moiré image-based in corneal topography. Ophthalmology 1990;97:734–44.
system. Eur. J Implant Ref Surg 1995;7:353-70. 10. Smolek MK, Klyce SD. Current keratoconus detection methods
4. Wilson SE, Klyce SD, Husseini ZM. Standardized color-coded compared with a neural network approach. Invest Ophthalmol
maps for corneal topography. Ophthalmology 1993;100:1723-7. Vis Sci 1997;38:2290-9.
5. Wilson SE, Klyce SD. Quantitative descriptors of corneal 11. Rabinowitz YS, Rasheed K. KISA% index: A quantitative
topography. A clinical study. Arch Ophthalmol 1991;109:349-53. videokeratography algorithm embodying minimal topographic
6. Dingledein SA, Klyce SD. The topography of normal cornea. Arch criteria for diagnosing keratoconus. J Cataract Refrac Surg
Ophthalmol 1989;107:512–8. 1999;25:1327–35.
6.2.3 Keratometry
Shalini Mohan, Rajesh Ramanjulu, M Vanathi
Cornea is one of the major refracting elements that contribute refraction through two rotating glass plates, which are then
to two-thirds of the vergence power of the eye. This adjusted so that the lower edge of one image coincides with
converging power is attributed to the radii of curvature as the other; if the eye moves during the process, both images
well as to its refractive index. It follows that the curvature of move together, and therefore difficulties in adjustment are
the posterior surface of cornea is a little greater than that of avoided. This was later modified by Javal and Schiotz (1881).4,5
the anterior and may therefore be considered as a weak concave The next improvisation came in the 1980s with the
lens. In isolation it would in fact have a slight diverging power, development of auto-keratometer. In recent times
but in the eye it acts in a converging fashion because, the keratometers are merged with auto-refractors for convenience
aqueous has a refractive index differing only slightly from that and there are several such commercially available automated
of the corneal substance. instruments.
‘Kerato’ means cornea, and ‘metry’ means measurement.
Keratometric measurements are useful in determining the Clinical Applications
corneal contribution to overall refractive state of eye and for
detection of distortions of cornea which might be important • Objective method for determining curvature of the cornea,
in the diagnosis of various corneal conditions. The first attempt amount and direction of corneal astigmatism, quality and
to measure the curvature of the anterior surface was made by stability of the corneal refracting surface
Cristopher Scheiner (1619) who compared the corneal reflex • Pre-surgical workup for cataract surgery (helps determine
with the image of the cross-bars on a series of graduated power of IOL)
marbles. 1 The accurate measurement of such an image, • Establishes baseline data
however raises a problem, since it is impossible to immobilize • Should be performed on all new patients
the living eye completely while the image is under observation. • In cases of hazy media due to corneal pathologies where
This has been overcome by the use of a device, the principle it is difficult to perform refraction, keratometry is a valuable
of visible doubling, which was originally introduced by tool
Servington Savery (1753) in the heliometers, and was adopted • Invaluable in contact lens (CL) fitting and follow-up
in the ophthalmometer devised by Jesse Ramsden (1796),2 and • Base curve selection in rigid gas permeable (RGP) contact
perfected by von Helmholtz (1856).3 The image is doubled by lens and hydrogel lens fitting
• “Over keratometry” can help detect CL surface irregula- there was a problem in measuring the image since the eye has
rities or poor wetting qualities an involuntary movement. To overcome this problem, a prism
• Monitoring corneal changes produced by wear was incorporated in the optical system of keratometer. This
• Monitoring the changes in the curvature in corneal ectatic biprism makes two images of an object (image doubling) and
disorders and detection of irregular astigmatism both of these images move equally as the eye moves. However
• Detection of keratoconus with resultant in steep curves, the amount of doubling is dependent upon the position of
high astigmatism, and distorted mires the prism with respect to the objective lens. If this distance is
• Pterygium reduced then the extent of doubling increases and if it is
• Corneal scarring however, unfortunately if the curvature increased, the extent of doubling decreases. At a particular
changes are significant as in advance stages, keratometer point the prismatic displacement is equal to the size of the
is of limited usags. image. By recording the position of the prism, the exact size
• Determining the nature of ametropia. of the image can be calculated. The critical element
determining the accuracy of the measurement is sharp
Principle and Theory
focussing on the reflecting image and precise determination
The working principle is based on the reflective properties of of its size when viewed through a kerato-meter with various
the cornea, which acts as a convex mirror. Corneal curvature amount of doubling. Alignment can also be obtained by
is obtained by measuring the size of an image formed by the altering the size of the mires, where amount of doubling is
reflection of the cornea (First Purkinje Samson image), of an kept constant. Therefore in different instruments, different
object of known size and position. The device then converts ways are used such as either of variable doubling with fixed
the image size into the corneal radius using vergence mires (e.g. Bausch and Lomb Keratometer) or variable mires
relationship of convex mirrors. with fixed doubling (e.g. Javal Schiotz Keratometers).
The radius of curvature, r, of a spherical mirror is The instrument is calibrated using spherocylinders and
proportional to the ratio of image to object size:3 hence irregular aspheric cornea may result in significant error.
r = 2 × h′/h
As shown in Figure 6.2.3.1 that image h′ is formed behind Types of Keratometer
the mirror as a virtual, erect and minified image of the object
h. Then dioptric power can be calculated by following formula:6 a. One position instrument
D = (n′ - n)/r b. Two position instrument.
where n′ is the index of refraction of the medium into Because the axis of a toric surface are always at 90 degrees
which light passes and n is the index of refraction from which to each other most of the instrument manufacturers have
the light originates. designed keratometers that incorporates two separate doubling
Theoretically, the size of image mire can be easily measured systems which operate in mutually perpendicular meridians.
by keeping the graticule with in the microscope. But practically Although these instruments still have to be rotated about their
anterior and posterior axis in order to find one of the principle
meridians of a toric cornea, once this position has been found,
no further rotation of the instrument is necessary to obtain a
radius measurement along the second principle meridian. This
type of keratometer is known as one position instrument (e.g.
Bausch and Lomb Keratometer). Keratometers that require
rotation through 90 degrees in order to measure the second
principle meridian are known as two position instruments (e.g.
Javal Schiotz Keratometer).
While the principle meridian of a toric lens is always at 90
degrees to each other, that of the cornea need not be so. This
is because the corneal surface closely approximates a toric
ellipse than a toric surface and when an off axis measurement
Fig. 6.2.3.1: Ray diagram of a image as seen of a toric ellipse is taken the principle meridian need not
after reflection from a convex mirror necessarily be at right angles to each other.
Area of Cornea Measured • The patient is to seated comfortably with the chin firmly
in the chin rest and forehead positioned against the band.
The portion of the image mire used in keratometers is not
This is very important when performing keratometry
reflected through the exact center of the cornea but from two
because even small movements of the head can lead to
small areas on either side of the instrument axis. The size of
difficulty in trying to maintain focus.
these areas is dependent upon the effective aperture of the
• The patient is instructed to look into the center of the
keratometers objective. These areas are separated by 3 mm,
instrument and the other eye is occluded.
varying with the design of the instrument and the radius of
• The keratometer is aligned with the optical axis of the eye
curvature of the cornea and the principle upon which the
by sighting along the silver pin on the side of the
keratometer is based, assuming that the cornea is spherical
keratometer and adjusted until the light falls on the portion
between these two areas where the measurement is taken. It is
of the eyelid that covers the cornea.
a well known fact that cornea is aspheric and flattens towards
• The mires are seen looking into the eyepiece and adjusted
its periphery. Because of this and because different
with the focusing knob.
keratometers reflect their mires from different regions of the
• The double circle is focused into a single clear circle with
cornea, two readings of the same cornea with two different
the cross in the center (Fig. 6.2.3.2A).
keratometers is not exactly the same. One of the other
• Location of the axis is done by turning the “horizontal”
problems of keratometry is that the radius of curvature of
drum, until the tips of the plus signs are almost touching
the cornea is determined from a small corneal area and only
(Fig. 6.2.3.2B), and aligned perfectly. The horizontal axis
central corneal measurements can be taken.
is to be read from the horizontal mark, and the vertical
axis, from the mark on top of the keratometer.
Sources of Errors
• After the axis is aligned, the horizontal reading is noted,
• Improper calibration of the instrument by turning the horizontal measuring drum until the plus
• Faulty positioning of the patient signs overlap.
• Lack of proper fixation by the patient • The vertical reading is obtained by turning the vertical drum
• Reduced visual acuity or uncorrected refractive error of until the minus signs are superimposed (Fig. 6.2.3.2C).
the examiner • The focus has to be constantly adjusted during the
• Accommodative fluctuation of the examiner measurement process as there are micro movements of
• Localized corneal distortions or opacities, poor tear the head and the eye.
exchange, abnormal lid position
• Improper eye piece focusing
• Misalignment of mires.
Limitations
• Area measured is a 0.1 mm annular ring with a 3.0 mm
diameter
• One position keratometers assume that meridians of least
and most cylinder are orthogonal (perpendicular)
• Assumed corneal index may cause problems when
comparing keratometry values from different instruments
• Autokeratometers do not evaluate the quality of the cornea.
Keratometry: Procedure
• The eyepiece is adjusted. This adjustment is a must in order
to increase the accuracy of measurement. The eyepiece is
turned anticlockwise, and then turned clockwise slowly,
until the reticule just comes into focus. This is the correct
position for commencement of measurement.
• Room lights may be dimmed. Fig. 6.2.3.2A: Mires of Bausch and Lomb keratometer
Fig. 6.2.3.2B: Horizontal alignment of mires Fig. 6.2.3.2C: Vertical alignment of Mires
• Readings are recorded with the horizontal power with its REFERENCES
corresponding axis, and the vertical power with its axis 1. Duke Elder. System of Ophthalmology: Ophthalmic optics and
(e.g. to 42.25 @ 180/43.75 @ 90). refraction. Mos by, St louis, 1970;5:98
• Range of the keratometer is 36.00 to 52.00. To increase 2. Mandell R. Jesse: Inventor of the ophthalmometer. Am J Optom
the range: Arch Am Acad Optom 1960;37:633-8.
– A +1.25D lens is placed in front of the aperture to 3. Helmontz H von. Handbook per physiologicshen optik: Hamburg,
Germany, Leopold Voss, 1909.
extend range to 61D (Additional of 9D)
4. Javal L, Schiötz H. Un opthalmomètre pratique. Annales
– A –1.00D lens is placed in front of the aperture to d’oculistique, Paris 1881;86:5-21.
extend range to 30D (Subtraction of 6D) 5. Maeda N, Klyce SD, Smolek MK, et al. Disparity of keratometry
readings and corneal power within the pupil after refractive surgery
The ranges conform to the values set by the commercially available Bausch &
for myopia. Cornea 1997;16:517-24.
Lomb Keratometer, Inc, Rochester, NY, USA.
6. Gullstarnd A. The cornea. In: South Hall J, ed. Helmontz’s treatise
The authors/editors have no financial interest in any product/procedure mentioned on physiological optics. New York: Optical Society of America,
in this chapter. 1924.
6.2.4 Pachymetry
Shalini Mohan
Pachymetry (Greek words: Pachos = thick + metry = to measure) The peripheral corneal thickness/central corneal thickness
is term used for the measurement of corneal thickness. It is ratio indicates ocular maturity (the greater the ratio, the greater
an important indicator of corneal health status especially with the development of the eye).7 This ratio can be used to assess
regard to corneal endothelial pump function.1 It also measures the maturity of the cornea at a given age.
corneal rigidity and consequently has an impact on the accuracy
of intraocular pressure (IOP) measurement by applanation FACTORS AFFECTING CENTRAL
tonometry.2 Recent emergence of refractive surgeries has CORNEAL THICKNESS
increased its value as a clinical variable. The central corneal thickness (CCT) has been found to be
higher in younger patients, male patients and diabetic patients.8
CORNEAL THICKNESS IN NORMAL EYES
Central corneal thickness does not correlate with refraction
The normal corneal thickness varies from central to peripheral or systemic hypertension. Several investigators have recently
limbus. It ranges from 0.7 to 0.9 mm at the limbus and varies provided further evidence that African-American patients tend
between 0.49 mm and 0.56 mm at the center. The central to have thinner corneas than their white counterparts.9
corneal thickness (CCT) reading of 0.7 mm or more is A significant although small variation is seen in corneal
indicative of endothelial decompensation.3 The mean CCT thickness. It has been found to increase in morning.10 The
as shown by various studies is 0.51 to 0.52 mm (standard PITX2 mutation seen in Axenfeld-Rieger malformations
deviation 0.02–0.04 mm).1 It has been found that cornea is results in reduced corneal thickness.11
significantly thicker in the age group of 40 to 80 years than in
the individuals below 40 years as it seems to undergo age- ROLE IN CLINICAL PRACTICE
related anatomic changes. Peripheral corneal thickness is Pachymetry has a role in the following clinical situations:
asymmetric with the temporal cornea being the thinnest • Glaucoma: For applying correction factor in actual
followed by the inferior cornea. intraocular pressure (IOP) determination.
• Congenital glaucoma: To assess the amount of corneal edema.
CORNEA IN NEWBORN AND INFANTS • Refractive surgeries:
The importance of corneal thickness in the newborn arises in – Screening of patients for refractive surgery
cases such as buphthalmos as pachymetric readings are – Surgical planning of keratorefractive procedures like
important to adjust intraocular pressure readings in all type radial keratotomy and astigmatic keratotomy.
of glaucomas. It has been found that, the cornea on day one • Corneal endothelial function evaluation in keratoplasty eyes:
of life is significantly thicker and decreases in thickness as the Following up patients with keratoplasty to determine the
child grows older. It is said that, it may result from the fact endothelial cell function and its recovery and to detect
that the eyes in utero have remain closed for a long time. The early graft decompensation.
decreasing thickness after the first day suggests that a hydration • Contact lens: To assess corneal edema and in orthokerato-
control becomes operative.4 This does not occur in the case logy.
of buphthalmos. The corneal edema persists until the IOP is • Corneal ectasia: Assessing the thinness of the cornea in
controlled. It is therefore important to know about corneal corneal disorders like Terrien’s and Pellucid marginal
thickness in newborns and infants. Corneal configuration in degenerations, keratoconus, keratoglobus, and post LASIK
newborns is similar to that of the adult cornea.4 The corneal ectasia.
thickness of the child reaches that of the adult by the age of • Corneal decompensation: For monitoring and evaluating
three years. The average corneal thickness in infants is 585 ± corneal edema and endothelial function in corneal disease
52 microns5 which is lesser in blacks than white children.6 function as in herpetic endothelitis.
Role in Glaucoma Conversely, the true IOP in low tension glaucoma may
not be as low as previously assumed, whereas the true
Goldmann tonometry is the gold standard in glaucoma
IOP in ocular hypertension may be within the normal
measurement. The main advantage of Goldmann tonometer
range, after taking central corneal thickness into account.
over its predecessors is that it is capable of adjusting IOP
– Similarly, CCT was found to be lower in patients with
measurements for scleral rigidity. The impact of central corneal
pseudoexfoliation syndrome (PXS) and in primary
thickness (CCT) on applanation tonometry was first discussed open angle glaucoma (POAG). In a study done by
by Goldmann.2,12 He assumed that the resistance of the cornea Brandt JD et al in 2004 on PXS, corneas were found
to indentation was compensated by the surface tension of the to be thinner regardless of presence of glaucoma.18,19
tear film. This assumption was only true for a central corneal – There is no difference in corneal thickness in
thickness of 520 μm, when otherwise; the accuracy of individuals with pigmentary glaucoma and primary
applanation tonometry can be considerably impaired. angle closure glaucoma (PACG).17,20
Applanation tonometry is based on Imbert Fick’s law,2 which
assumes that the cornea is a perfect flexible, dry, sphere which Effect of CCT on Tonometers
is infinitely thin. Therefore, increase in the tissue in a thicker
Owing to the variable corneal thickness, Goldmann appla-
cornea makes it less compliant, leading to overestimation of
nation tonometry has been found to be of lower reliability
IOP. Conversely thinner cornea leads to underestimation of
and has led to innovations in alternate methods for IOP
IOP.
assessment which are either independent of this variable or
Ocular Hypertension Treatment Study (OHTS) group
incorporate corneal thickness before displaying the IOP values.
published a landmark report in 2002 that central corneal
thickness (CCT) was an important independent risk factor for Dynamic contour tonometry is a newer promising modality, affected
progression from ocular hypertension to early glaucoma.13,14 to a lesser degree by CCT.21 Therefore, it is wise to measure
IOP by this instrument in individuals in whom corneal
Correction factor: In order to get a correct IOP reading, various thickness is deviating from the normal value. It has an
correction factors have been reported by various researchers. electronic strain gauge embedded in a contoured plastic tip
It is recommended that in chronic eye diseases like glaucoma and which creates a tight-fitting shell on the corneal surface without
glaucoma suspects for every 50 µm increase, the correction applanation of the corneal tissue when the tip comes in contact
done is 2.5 mm Hg.15 For acute onset diseases it was recommended with the cornea. It is assumed that the tonometer compensates
to correct by 10 mm Hg for every 50 microns.16 for all forces exerted on the cornea, allowing the strain gauge
A general recommendation supported by the data so far is to measure IOP largely independent of corneal biomechanical
that one can ensure better care of patients simply by properties.
categorizing corneas as thin, average, or thick, just as it is
important to recognize that optic discs as small, medium, and Clinical Implications in Glaucoma
large, thereby allowing the clinician to interpret disk
• Increased corneal thickness can produce falsely high IOP
configurations accordingly.
readings, and decreased corneal thickness can produce
Facts about CCT in Glaucoma falsely low IOP readings even on goldmann applanation
tonometry (GAT).
• It has been confirmed that CCT bears an inverse relation • Corneal pachymetry appears to be an essential tool in
with the risk of developing glaucomatous damage.12 predicting the progression from ocular hypertension to
• CCT may vary systematically in different forms of POAG. Lower CCT is considered as a risk factor for the
glaucoma. Bechmann in 2000 found the following development of glaucomatous damage in OHT
associations of CCT with different forms of glaucoma.17 patients.13,14
– Increased CCT measurements are found in patients • It has been reported that refractive surgical procedures
with ocular hypertension, which can lead to falsely such as excimer photorefractive keratectomy (PRK) and
elevated IOP readings. laser in situ keratomileusis (LASIK) tend to lower IOP
– Decreased CCT is found in patients with low tension readings due to laser induced reduced corneal thickness.
glaucoma, resulting in falsely reduced IOP measure- There is a decrease in 1 mm Hg IOP for every 37.8 microns
ments. reduction in central corneal thickness.22
Evidence Based Guideline for Corneal – Optical low coherence interferometry

Pachymetry in Glaucoma – Confocal microscopy
– Laser Doppler interferometry.
Corneal pachymetry may be appropriate for patients who have
• Newer Techniques:
risk factors for developing primary open angle Glaucoma.
– Pentacam
Patients who have one or more of the following characteristics
– Pachycam
would be considered at risk for developing glaucoma and
– Ocular response analyzer (ORA).
therefore corneal pachymetry is recommended:
• Elevated intraocular pressure repeatedly measured > 24
Ultrasonic Pachymetry
mm Hg
• African descent This is the most commonly used method and is regarded as
• Advancing age (>65 years old) the gold standard.
• Family history of glaucoma
Principle: The ultrasonic pachymetry measurements depend on
• Diabetes mellitus (controversial).
the reflection of ultrasonic waves from the anterior and
posterior corneal surfaces. It is the measurement of the time
TECHNIQUES OF PACHYMETRIC
difference (transit time) between echoes of ultrasonic signal
MEASUREMENTS
pulses from the transducer of the probe and the reflected
There are two types of pachymetric techniques: signal from the front and back surface of the cornea to the
a. Spot measurements: These technologies include traditional transducer.
optical pachymetry, specular and confocal microscopy, Corneal thickness is calculated by following simple
ultrasound pachymetry, and optical low-coherence formula:23
reflectometry. (Transit time × Propagation velocity)
b. Wide area mapping: These provide the capability to map a Corneal thickness = _________________________________________
wide area of the cornea. Pachymetric mapping technologies 2
include slit scanning optical pachymetry and very high– The sound velocity through normal cornea is taken as 1640
frequency ultrasound imaging. m/sec. Kremer et al selected this sound velocity because this
gave the average reading of 0.512 ± 0.035 mm which was
Pachymetric mapping provides several advantages over
same as given by optical pachymetry.23
spot measurements:
There are three major components of ultrasonic
• Mapping can reveal abnormal patterns such as keratoconus
pachymeter:
and pellucid marginal degeneration.
a. Probe handle: This consists of a piezoelectric crystal which
• It also allows preoperative planning for surgeries that
vibrates at a frequency of 10 to 20 MHz. This is a hand
primarily do not concern just the center of the cornea,
held probe which is very small, light and easier to use
such as astigmatic keratotomy, intracorneal ring segment
clinically. Some probes also have digital read outs where
(ICRS) implantation, phototherapeutic keratectomy, and
the readings can be read directly.
deep anterior lamellar keratoplasty (DALK).
b. Transducer: It sends ultrasound rays through the probe to
Despite these advantages, conventional ultrasound spot
the cornea and receives echoes from the cornea.
pachymetry is still the standard because of its reliability,
c. Probe tip: The diameter of the tip should not be more than
ease of use, and relative low cost.
2 mm, so that the ultrasound beam spreads over a lesser
area and the place where the tip of the probe is kept can
Methods of Measurements
be seen. A wide probe tip and a wide transducer beam
• Ultrasonic Techniques reduce the accuracy of the corneal thickness reading. The
– Conventional ultrasonic pachymetry probe tip should be smooth enough to avoid damage to
– Ultrasound biomicroscopy (UBM). the corneal epithelium.
• Optical Techniques: When performing the measurement, the probe tip has to
– Manual optical pachymetry be placed perpendicular to the center of cornea. As corneal
– Specular microscopy thickness increases peripherally, lateral displacement of the
– Scanning slit technology probe may cause elevated readings as well as shift of the probe
– Optical coherence tomography (OCT) out of the correct perpendicular position.
Advantages
• Fast
• Simpler and therefore easier for paramedical staff to use
• Requires minimal observer judgment and is therefore
consistent and repeatable between observers thereby
eliminating interobserver variation24
• Portable
• Dry (no coupling medium required)
• Can be used intraoperatively.
Disadvantages
• Contact method.
• Accuracy is dependent on the perpendicularity of the
probe’s application to the cornea.
• Reproducibility relies on the precise probe placement on
the center of the cornea.
Fig. 6.2.4.1: Ultrasound Biomicroscopy
• Difficult to control the patient’s gaze during repeated
measurements, so that the placement of the probe is
difficult to reproduce. Disadvantages
• There is variable sound speed in wet and dry tissues. • The main drawback is the inconvenient requirement of
• Furthermore, the exact points of sound reflection in immersing the eye in a coupling fluid.
ultrasonic pachymetry are ill defined and the applanation • The patient has to lie supine during the examination and
force may disturb the anterior reflecting surface by pushing hence the device cannot be used in all situations.
away the precorneal tear film and by thinning of the • The device cannot be used intraoperatively.
epithelium. • It is difficult to standardize.
• Low resolution.
• Not accurate in edematous corneas/extremely thin corneas Manual Optical Pachymetry
Thus, the examiner’s experience can influence the reliability
of measurements. The central corneal thickness can be measured with the Haag-
Streit slit lamp using the pachymeter attachment (Haag-Streit
Ultrasound Biomicroscopy AG, Koeniz, Switzerland).28 This is the prototype of optical
pachymeter. A slit beam is projected perpendicularly to the
Ultrasound biomicroscopy (UBM) (Paradigm Med Ind, Inc. cornea through the narrow diaphragm of the instrument. To
Salt Lake City, UT) is a high resolution ultrasound machine ensure the perpendicularity of the incident beam on the corneal
which images anterior segment of eye.25,26 It has a 12.5 to 50 surface, it comes with or without a Mishima-Hedbys fixation
MHz probe so that the depth of penetration is lesser (4 mm) attachment. The instrument contains two plano glass plates
than conventional ultrasound. It gives real-time images of that splits the image of the corneal parallelepiped. A uniocular
anterior segment. Corneal thickness can be measured by the right-sided split-image eyepiece replaces the regular eyepiece
caliper incorporated in the machine or through the UBM of the slit-lamp.
software after acquisition of images (Fig. 6.2.4.1).27 There are two methods to measure corneal thickness:28
a. “Just touch” method: The observer moves the scale of the
Advantages
instrument until the focused upper half of the corneal
• Anterior segment examination (high resolution) can be image is positioned so that its posterior surface (endothelial
carried out along with measurement of corneal thickness. border) just touches the anterior surface (epithelial border)
• Especially useful in cases where the cornea is opaque. of the lower image. This method is easier and more
• Various layers of the cornea can be identified. practical.
b. “Overlap method”: The bright line of endothelial border

overlaps with the bright line of epithelial border.
The corneal thickness is then directly read from the scale
on the instrument. The range of measurement is from 0 to
1.2 mm, with a least gradation of 0.02 mm.
Disadvantages
• Lack of accuracy in measurements; with the usual range
of error with an optical pachymeter being ± 2 percent is a
major disadvantage.29 It has been suggested that the
accuracy of the optical pachymeter readings using the
Haag-Streit attachment can be increased by correcting for
the corneal curvature.
• Lack of repeatability is because of following factors:
– Fixed position of the fixation target Fig. 6.2.4.2: Orbscan pachymetric map
– Slit-beam does not intersect cornea at the same angle
on repeat measurements
– End point is not consistent and is subjected to
observers bias
• Requires slit lamp and therefore has poor portability and
cannot be used in operating room.
Specular Pachymetry
Specular microscope is primarily used for counting the corneal
endothelial cells. The principle is that it measures the thickness
of cornea which depends on the reflection of light rays from
the back of cornea unlike sound waves in ultrasound
pachymeter which measures reflected rays both from anterior
and posterior surface of the cornea.30
Slit-scanning Pachymetry Fig. 6.2.4.3A: Anterior segment OCT maps of corneal thickness
The Orbscan II (Bausch & Lomb, Rochester, NY, USA) is an

elevation based system which uses scanning slit technology.30 Optical Low Coherence Reflectometry
It is capable of assessment of multiple functions in the cornea, (The Haag-Streit OLCR)
including thickness profile, anterior and posterior topography,
elevation, and anterior chamber depth. It gives a pictorial The instrument is attached to a slit lamp and is a single mode
representation of corneal topography in the form of quad fiber-optic based Michelson’s interferometer with a high
map (Fig. 6.2.4.2).31 repetition rate.33 This system can measure corneal thickness
This has been elucidated in a previous chapter. to a precision of one micron.34
Anterior Segment Optical Confocal Microscopy

Coherence Tomography This imaging modality in vivo provides important insights into
Anterior segment optical coherence tomography (ASOCT) the structure and function of the cornea. Confocal microscopy
(Visante-Carl Zeiss Meditec AG, Jena, Germany) is a high- finds useful application in the observation of the anatomy of
resolution, non-contact optical coherence tomography the anterior parts of the eye, the investigations of these
customized for the anterior segment.32 It provides high- structures after local administration of drugs and in the
resolution corneal images. It gives color coded map of the diagnosis of ocular diseases. 35 The amount of light
corneal thickness (Figs 6.2.4.3A and B) backscattered by the central section of each image is also
Fig. 6.2.4.3B: Anterior segment OCT maps of corneal thickness
The center of the cornea is measured very precisely

because of this rotational imaging process. The corneal
thickness is displayed as a color image, showing the entire
area from limbus to limbus.
Pachycam
The Oculus Pachycam is compact and portable non-contact
pachymeter with built-in keratometer. It automatically corrects
the IOP in accordance with various correction tables to obtain
the “real” IOP. It is also based on the Scheimpflug principle
of the horizontal 4 mm cut image which is evaluated and
represented. It also gives central keratometry values as well as
the local keratometry readings on the 4 mm cut.
Fig. 6.2.4.4: Confocal microscopy intensity profile curve

Ocular Response Analyzer
recorded, allowing the generation of an intensity profile curve Ocular response analyzer (Reichert Ophthalmic Inc. NY) is a
(Fig. 6.2.4.4).15 newer modality for measuring biomechanical properties of
cornea. It measures corneal hysteresis (CH) that is a result of
Pentacam viscous damping in the corneal tissue.36 It utilizes a rapid air
impulse, and measures delays in the inward and outward
Pentacam (Oculus Inc., Germany) analyses the complete
applanation events of cornea, resulting in two different
anterior segment, corneal topography, quantification of lens
pressure values. The difference between these two pressure
density, anterior chamber, angle measurements, and utility to
monitor new therapeutic modalities like collagen crosslinking values is a measure of corneal hysteresis. Central corneal
treatment for keratoconus. It is based on the principle of true thickness is measured by built-in 20 MHz ultrasound
elevation measurement and images the anterior segment pachymeter.
(cornea and lens) of the eye by a rotating Scheimpflug camera The authors/editors have no financial interest in any procedure/product
measurement which supplies pictures in three dimensions.10,34 mentioned in this chapter.
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2008;54:227-33. 23. Kremer FB, Walton P, Gensheimer G. Determination of corneal
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6.2.5 Corneal Esthesiometry

M Vanathi
Von Frey1 first performed corneal sensitivity measurements The bending of the thread under its own weight, particularly
in 1894 using various lengths of horse hair to mechanically when the thread is long makes it difficult to make an accurate
stimulate the cornea. Among various esthesiometer that have observation of the end-point. Subject apprehension also
been developed subsequently, three techniques are currently compromises the testing.
used to determine corneal sensitivity in clinical and research
Non-contact corneal esthesiometr y (NCCE): This was
practices.1-4
developed in 1996 by Murphy et al3 and uses controlled pulses
Qualitative measurement: Gross assessment of corneal sensation of air to stimulate the cornea. It measures the corneal nerve
is usually performed in the clinical setting by using a cotton threshold by using a composite stimulus consisting of air
wisp with cotton teased out to make a fine end. The subject is pressure, tear evaporation and disruption. In the NCCE, an
instructed to view a distance object and then approaching from adjustable valve couples with a pressure sensor to control the
the side, the central cornea is touched gently with the tip of output from a compressed air reservoir to within 0.01 mbar.
the cotton wisp. The presence of the blink reflex is observed The stimulus is applied to the eye through a stimulus jet
and any subjective differences in the sensations between the comprising a brass tube of length 35 mm and diameter of 6
two eyes are asked for. This test does not provide any mm with a central 0.5 mm diameter longitudinal bore. The
quantitative assessment of the corneal sensitivity. settings for stimulus duration that are available include 0.5, 0.9
and 1.5 seconds. A stimulus threshold of 0.9 mm has been
Contact esthesiometry with the Cochet-Bonnet esthesiometer: This was recommended as standard setting presuming that a longer
developed in 1960 and is currently the most widely used duration might result in corneal drying and shorter duration
technique. This instrument consists of a fine nylon thread of might be too quick for the subject’s response. A slit lamp
adjustable length that is used to measure the corneal sensitivity. attachment enables positioning the stimulus jet close to the
A conversion table is provided. The instrument may be eye examined. A clear plastic centimeter ruler attached to the
mounted on the slit lamp using a modified Bleshoy applicator mount enables setting the testing distance at 1 cm. The stimulus
that permits manipulation in X, Y, Z axis. A nylon thread 60 jet is aligned to the center of the cornea. Testing is started
mm in length, 0.12 mm in diameter is moved with application of suprathreshold stimulus and the patient
in a perpendicular direction towards the cornea in a smooth usually responds describing it at a cold sensation or pressure
controlled manner. The application of the stimulus to the type of sensation. On approaching the threshold, the stimuli
cornea is indicated by slight visible bending of the thread. may be difficult to describe.
Stimuli is presented 4 to 8 times and the patient is requested Forced choice double-staircase technique is used to
to respond when it can be appreciated. When a negative response determine the corneal sensitivity. Starting with suprathreshold
is elicited for a given length of the nylon thread, the thread is stimulus, it is gradually decreased until the subject is no longer
shortened in length in steps of 5 mm until the stimulus able to detect it. This cross-over point is recorded and a sub-
presented becomes appreciable. The corneal touch threshold threshold is presented and increased in intensity until a positive
is defined as the length of nylon thread at which the subject response is obtained. The mean of these cross-over point is
responds to 50 percent of the number of stimulations. Corneal the corneal sensitivity expressed as air pressure in millibars
sensation is expressed as thread length (mm/cm) or the (mbar). Advantages of the NCCE include the possibility of
manufacturers conversion table may be used to convert the use of continuous range of stimulus intensity and also ruling
length into pressure (g/mm2). out of the apprehension factor of the patient. There is also
The limitations with this technique are that it is invasive, no danger of damage to the corneal epithelium.
and can cause epithelial damage thereby producing an increased
sensitivity due to the presence of free nerve endings within REFERENCES
the corneal epithelium. Thus the minimum stimulus is also 1. Millodot M. A review of research on sensitivity of the cornea.
suprathreshold and the range of stimulus intensities is limited. Ophthalmic and physiological optics 1984;4:305–18.
2. Murphy PJ, Lawrenson JG, Patel S, Marshall J. Reliablity of non- 3. Murphy PJ, Patel S, Marshall J. A new non-contact corneal
contact corneal aesthesiometer and its comparison with the Cochet- aesthesiometer (NCCA). Ophthalmic and Physiologic Optics
Bonnet aesthesiometer. Ophthalmic and Physiological Optics 1996;16:101-7.
1998;18:532-9. 4. Lawrenson JG. Corneal sensitivity in health and disease.
Ophthalmic and Physiological Optics 1997;17(suppl):S17-22.
6.2.6 Confocal Microscopy of the Cornea

M Vanathi, Sankaranarayana P Mahesh
Clinical techniques have evolved over the years to enable the confocal microscope were subsequently produced
examination of the living human cornea at macroscopic and commercially.
cellular level resulting in the development of specular Svishchev produced the scanning two sided mirror
microscopy, computerized corneal topography, high frequency confocal microscope in 1969 to observe the living neural
ultrasound and in vivo confocal microscopy. Light microscopy tissue.1-3 This design was modified by Thaer to enable real
and electron microscopy are invasive methods, limited by the time scanning.1-3
effects of tissue degeneration and processing artifacts and the
availability of suitable corneal tissue. In vivo confocal CONFOCAL MICROSCOPY
microscopy is an non-invasive method of corneal evaluation IN OPHTHALMOLOGY
beyond slit lamp biomicroscopy that enables study of the living Non-invasive imaging of the cornea has been popular in
human cornea at the cellular or microstructural level. The ophthalmology for the last two decades, even though it has
challenge of imaging thin optical sections of transparent not gained widespread use in clinical practice. It offers the
cornea that can reflect one percent of the incident light has advantages of evaluating the various changes in the ocular
been made possible with the development of the in vivo surface in vivo at higher magnification thus helping in the
confocal microscopy, which has made it an useful tool in clinical diagnosis of various corneal pathologies.2,4,5 Compared to the
and research settings to study healthy and pathological states conventional slit lamp examination, it offers several unique
of the human cornea. advantages:5
This chapter deals with the principles of confocal • Quantitative analysis at the microscopic level of the various
microscopy and the descriptions of confocal microscopic layers of the corneal surface
appearances of the normal human cornea and in a few • An ex vivo examination of the ocular surface in its
pathological conditions. physiological state. In addition, it offers longitudinal
examination of the same cornea over time as well as
HISTORY detailed information on the different layers including
nerves, and cells in the different layers.
Minsky invented the confocal microscope in 1955 and the
original prototype was called the “double focusing stage
Confocal Microscope: Principle
scanning microscope”, that allowed examination of tissue
specimens mounted onto a stage consisting of an electrically All confocal microscopes use the same principle of enabling
driven tuning fork.1 The first tandem scanning microscope optical sections of a (relatively) thick light scattering object
was developed by Petran et al in 1968, in which simultaneous such as the cornea. In brief, light is passed through an aperture
scanning of multiple points of a stationary specimen was done and focused by an objective lens onto a small area of the
using a Nipkow disk, and was used to study unstained brain specimen of interest. The reflected light from the specimen
and ganglion cells of salamanders and frogs.1-3 Only 20 years passes through a second objective lens. This light is focused
later, Lemp et al first used the tandem scanning microscope onto a second aperture which is arranged such that the ‘out
to examine full thickness cornea, both human cornea ex vivo of focus’ light is eliminated. As the illumination and detection
and of rabbit cornea tissue in situ.3 The clinical versions of paths share the same focal plane the term “confocal” is used.
Light reflection and scattering from structures adjacent to systems use a pair of slit apertures, which scan across the
the focal plane results in poorer image resolution thereby field for imaging different areas of the cornea.
limiting usefulness in conventional microscopy. In confocal The speed at which a single image of the field is acquired
microscopy, as described by Goldmann and later by Minsky,1 determines the temporal resolution of the microscope. Poor
light scattering from ‘out of plane’ structures is overcome by temporal resolution is associated with increased motion
having both the illumination (condenser) and observation artifacts when examining living human subjects, where
(objective) systems to be focused on a single point (have involuntary movements due to pulse, respiration and eye
common focal points). Utilizing the confocal principle and movements are invariably unavoidable. Signals produced by
eliminating ‘out of focus’ information, results in higher the reflected light of the in vivo confocal microscopes are
resolutions (lateral resolution: 1 to 2 µm, axial resolution: typically detected by electronic detectors such as cameras based
10 to 20 µm) and higher magnification of up to 600X.6 on charged-coupled device (CCD camera). Video and digital
In practice, this is achieved in a confocal microscope by a image capture systems along with softwares provide image
pinhole aperture. The instrumentation consists of a high acquisition and enable analysis.
numeric-aperture objective lens, which focuses light from a The quality of an image depends on two main factors –
point source of light through a pinhole aperture onto the contrast and resolution. The resolution depends on the
imaging plane. The reflecting light is collected by a detector numerical aperture of the objective lens, illumination levels,
system through a separate aperture to cut off the out of focus reflectivity of the specimen studied and the wavelength of
rays (Fig. 6.2.6.1). The illuminating point source and observa- the illuminating light. The axial resolution depends on the slit
tion aperture are conjugate with the same point of the tissue width in slit scanning confocal microscope (SSCM) and the
and are confocal.7 pinhole diameter in tandem scanning confocal microscope
The confocal system offers two advantages: (i) Illumination (TSCM).
is brightest at the focal point and tapers off at planes above
and below. (ii) Minimal amount of light reflected from planes Confocal Microscopes: Prototypes
above and below is imaged by the detector. Hence a higher
There are three different types that are used clinically in
resolution can be achieved compared to a conventional
ophthalmology:8
microscope. Since the area of imaging is limited, it is necessary
a. Tandem scanning confocal microscope: Tandem Scanning (TSCM,
to rapidly scan the focal point across the sample and
USA)
reconstruct the image. In clinical confocal microscopes,
b. Slit scanning confocal microscope: ConfoScan four slit-scanning
however, multiple small apertures are used to examine at the
confocal microscope (SSCM, Nidek Technologies, USA)
same time and reconstruct the image.6,7 Alternatively, some
c. Confocal laser scanning microscope: Heidelberg retina
Tomograph Rostock Corneal Module (HRT3, Heidelberg
Engineering, Germany)
Tandem Scanning Confocal

Microscope (TSCM)
Confocal microscopy through focusing (CMTF) using tandem
scanning in vivo confocal microscope (TSCM) is an objective
method for measuring corneal sub-layer thickness and provides
three-dimensional reconstruction from a stack of two-
dimensional images. In the tandem scanning confocal
microscope (Fig. 6.2.6.2), multiple apertures (Nipkow wheel)
spaced apart is used to scan thousands of light beams over
Fig. 6.2.6.1: Diagrammatic representation of the optical the fixed object, generating a high scan rate.3 TSCM consists
principle of the confocal microscope: White light that passes of 2 sets of conjugate apertures arranged in tandem, i.e. as
through the first pinhole is focused on the focal plane in the cornea diametrically opposed pairs. Illuminating light passes through
by the condensing lens. Returning light is diverted through the one pinhole and is then reflected back through the
objective lens and a conjugate exit pinhole and reaches the observer
camera. Scattered out of focus light from below or above the focal
corresponding pinhole situated in the opposite pair. The high
plane (interrupted lines) is limited by the pinholes and does not speed rotation of the disk enables the light beam to scan the
reach the observer full field of view several times in a second, thus producing a
Fig. 6.2.6.2: The TSCM4 contains a rotating Nipkow disk that has 64000 pinholes arranged in Archimedian spirals. The pinholes are 20
to 60 µm in diameter depending on the model of the microscope and each pinhole has an equivalent conjugate pinhole diametrically
opposite it on the disk. The disk rotated at 900 revolutions per minute with the illuminating light passing through approximately 100 holes
at a given time. Reflected light passes through the conjugate pinholes on diametrically opposite side of the disk. The rapid disk rotation
allows scanning of the whole specimen. The ratio of disk area to holes determines the light transmission which ranges from 0.5 to 1
percent (0.5% for 20 µm pinholes). The relatively poor light transmission of confocal microscopy is compensated in TSCM by use of a
very bright illuminating light source as Xenon or Mercury arc lamp
real time image. Excellent lateral resolution and thin optical Improved brightness and contrast along with resolution is
sections are achieved with scanning of full thickness of the achieved with the use of wider slit aperture instead of small
cornea in 7 to 10 seconds. However, the smaller apertures pinhole aperture in TSCM.9 In addition, this also helps in use
result in insufficient illumination causing patient discomfort of less illumination resulting in less discomfort. However,
(due to need of a stronger illuminating source), less brightness, SSCM images have poor axial resolution.
poor contrast and visualizing smaller structures.
Confocal Laser Scanning Microscope
Slit Scanning Confocal Microscope (SSCM)
This system uses a combination of the Heidelberg retina
The scanning slit confocal microscope (Fig. 6.2.6.3) uses a tomography (HRT II) and the newly developed Rostock cornea
light source with one-dimensional slit apertures instead of two- module, which is available as add-on feature. The HRT
dimensional spot scanning. The use of slit illumination has confocal laser scanning microscope uses computer controlled
two advantages. hydraulic linear scanning device and a water contact objective
a. Light output is significantly higher than TSCM. Hence, and a diode laser beam of 670 nm wavelength, as the light
a weaker illumination source such as 12 V halogen lamp source.10 The Rostock scanning laser confocal microscope
can be used and longer periods of up to 30 minutes of provides reproducible images of high resolution (lateral 1-
continuous examination is possible without inducing microns, axial 4-microns as reported by manufacturer) with
after image. uniform illumination. Optical sections can do scanning of the
b. Several points are scanned in parallel and hence scanning different layers both manually and by automated control. With
time is shorter. (The use of the slit means that this the current models only 80 microns depth is possible through
microscope is only tr uly confocal in the axis automated control. The HRT II cornea module also enables
perpendicular to the slit height.) imaging of the conjunctiva and limbus.
Fig. 6.2.6.3: The SSCM uses two optically conjugate slits for illumination and detection of reflected light. A rapidly oscillating two sided
mirror scans the image onto the microscope objective and descans the reflected light from the object
Confocal Microscopy of
the Normal Human Cornea
Understanding and recognizing the normal appearance of the
corneal layers on confocal images, is necessary for
differentiating different pathologies. Most anatomical layers
and cell types may be viewed easily including epithelial cells
(superficial, intermediate and basal), nerve plexi, stromal layers
with keratocytes, Descemet’s membrane, endothelial cells, and
immune response cells. Cross-sectional views may also be seen
in oblique scans.
Epithelium
Corneal epithelium consists of 5 to 6 layers of nucleated cells
that are subdivided functionally and morphologically into three
zones: superficial, intermediate and basal.11
Superficial cells (Fig. 6.2.6.4A) are round with clear visible
cell borders, bright cytoplasm and hyper-reflective nuclei.
These cells are characteristically polygonal in shape, of various
size and reflectivity. Cells undergoing desquamation have
brightly reflective cytoplasm with brightly appearing pyknotic
cell nucleus with its dark perinuclear space, with nearly 1/7th
desquamating every 24 hours. Superficial cells are 20 to 30
µm in length and approximately 5 µm in thickness.
The intermediate layer of wing cells comprises of cells
smaller than the superficial cells, with bright cell borders and
dark cytoplasm. These cells are fairly uniform in size and shape.
The basal epithelial cells (Fig. 6.2.6.4B) are located just
above the Bowman’s membrane and are seen as a distinct
mosaic, with light cell boundaries. The basal epithelial cells
are the smallest cells in the epithelium. These brightly bordered Figs 6.2.6.4A and B: Confocal microscopic image of superficial
cells with cell nucleus not visible show minimal variation in (A) and basal epithelial cells(B)
cell size and shape, with homogeneous reflectivity of cytoplasm. of cellular structures. The cell bodies, keratocytes processes
The basal epithelial cells are seen as a distinct mosaic, which and stromal collagen are not usually visible in the normal
have light cell boundaries. Limbal stem cells in the periphery cornea with SSCM and TSCM.
appear smaller and round. The center cell density ratio of The irregular shaped nuclei of the keratocytes scattered
superficial/, wing/, and basal cells of the epithelium are by light in the corneal stroma can be detected on confocal
1:5:10.12-14 The mean cell density and mean cell area of microscopy.15 Counting of keratocyte nuclei from stromal
superficial cells do not appear to change with age. Basal cells images adjacent to the Bowman’s layer and endothelium
are 10 to 15 µm in diameter. represent the anterior (Fig. 6.2.6.6A) and posterior stromal
(Fig. 6.2.6.6B) keratocytes respectively.16 The anterior stromal
Sub-basal corneal nerves: They are located between the basal
keratocytes are more abundant and oval in shape as compared
epithelium and the Bowman’s layer (Fig. 6.2.6.5). They consist
to the posterior stromal keratocyte nuclei that are less abundant
of straight and beaded nerve fibers with beaded fibers located
and oblong in shape. The keratocyte density seems to decrease
in the periphery of the bundle. The beads have been identified
with aging by 0.45 percent per year.17,18
as axonal efferent sensory terminals and consist of
accumulations of mitochondria and glycogen. In in vivo
confocal microscopy (CM) sub-basal nerves appear as beaded
well-defined linear structures with homogeneous reflectivity.
Dichotomous (Y shaped) and thinner interconnecting nerve
fibers (H shaped) are seen. Studies have elaborated nerve
density (µm/mm2), nerve diameter, and beading frequency.
Bowman’s Layer
In the normal cornea, the Bowman’s layer appears as a
homogeneous acellular layer. Bowman’s membrane can be seen
distinct from the epithelial basement membrane.
Stroma
The stroma constitutes 90 percent of total corneal volume
and all the structures including keratocytes and nerves can be Fig. 6.2.6.6A: Anterior stromal keratocytes
appreciated on confocal images. Only five percent is composed nuclei imaged on SSCM
Fig. 6.2.6.5: Confocal microscopic image of Fig. 6.2.6.6B: Posterior stromal keratocytes
sub-basal nerve fiber layer nuclei imaged on SSCM
Langerhan’s cells are seen as bright corpuscular particles

with dendritic cell morphology and diameter up to 15 µm.
Depending on the stage of maturation they can be identified
as mature larger cells with dendrites in the periphery that form
a network or smaller cells lacking dendrites more central in
location. They are less abundant in the center and more in the
periphery. Immature cells capture antigen, while mature ones
sensitize T cells through the major histocompatibility complex
(MHC) molecules and secretion of cytokines and
costimulatory molecules.
Corneal nerve fibers are nonmyelinated and are about 0.2
to 10 µm thick. In the limbal region they are seen as whitish
structures and their branching pattern is also evident as thick
stretched highly reflective structures by confocal imaging.19
Stromal nerve fibers appear as thick reflective linear structures
Fig. 6.2.6.7: Confocal microscopic image of endothelium
of various orientations which branch in a dichotomous pattern
and no internal detail of stromal nerves is seen.
Studies by Muller et al20 reveal that there are about 6000 Descemet’s Membrane and Endothelium
nerve bundles in the human sub-basal plexus, each of which Like the basement membrane, the Descemet’s membrane is
gives upto seven axons resulting in 19000-44000 axons. These, amorphous and about 6 to 10 µm thick. The normal
in turn, give rise to about 10 to 20 nerve terminals. The sub- Descemet’s membrane is not visible in young subjects and is
basal nerve plexus comprises unmyelinated sub-basal nerve more discernible with age. It is seen as an amorphous layer
fiber bundles which are straight and beaded fibers, that course between the posterior stroma and endothelium.
in the basal aspect of the basal epithelial cell layer and are Endothelial cells are seen as a bright array of hexagonal
easily seen on confocal microscopy imaging. Individual beaded shaped structures, with bright cell bodies and dark cell borders,
fibers branch from the sub-basal bundles and terminate in the without any nuclear reflection and are of fairly uniform size.
more superficial epithelium as free nerve endings which are Endothelial cell counts are comparable to those obtained by
not visible with tandem scanning confocal microscope.20 specular microscopy (Fig. 6.2.6.7).22 Endothelial cell density
Nerve fiber bundles enter anterior and central stroma in is found to decrease with age at a rate of 0.33 percent per
the periphery in a radial pattern while the deeper stroma is year. Increasing cell polymegathism has also been noted.
devoid of nerves.
Corneal thickness measurements with confocal microscopy: In confocal
In the anterior stroma, nerve fiber bundles show three
microscopy, image intensity measurements are relative as
patterns. These are:21
camera sensitivities and light output from the microscope’s
a. Subepithelial plexus penetrating Bowman’s membrane.
bulb varies with age and voltage. Strong peaks are observed at
b. Nerve penetrating Bowman’s membrane at right angles
the superficial epithelium and the endothelium, and smaller
between basal cell layers of epithelium towards center
peaks are seen at the level of the sub-basal nerve plexus and
forming basal epithelial plexus.
the anterior stroma. The distance between these peaks are
c. As free endings in the center of the basal epithelial
used to measure the corneal thickness. Corneal thickness
plexus, which ends as Y or T, shaped branches giving a
measurements with CMTF show good repeatability. There has
predominant ‘string of pearl’ appearance.
been a difference of 1.67 percent in corneal thickness measured
The subepithelial nerve plexus lies at the interface between with CMTF and ultrasound pachymetry, while a difference of
the Bowman’s layer and the anterior stroma. This plexus is 39 µm (7%) and 24 µm (4.4%) has been found between CMTF
sparse and patchy in distribution, and the network seems to with ultrasound pachymetry and Orbscan II pachymetry
be limited to the mid-peripheral cornea and is probably absent respectively. Errors in estimation arise due to the involuntary
in the central cornea. These nerves are of low contrast with antero-posterior movement of the subject. The slit scanning
granular texture and irregular edges and show varicosities and confocal microscopy has poor repeatability for corneal
beading. thickness measurements, due to the long working distance of
the microscope. The recently developed ‘z-ring encoder’ Confocal Microscopy in

(which can be mounted on the objective lens and rests on the Pathological Conditions
cornea by a light spring, and senses the distance between the
cornea and the objective lens) has been said to improve the Infectious Keratitis
accuracy of the corneal thickness measurements. The plane • Acanthamoeba keratitis: Acanthamoeba cysts appear as
of measurement in the Heidelburg Retina Tomograph II circular hyper-reflective structures of approximate 26 µm
Rostock Corneal Module (Heidelburg Engineering, GmBH, with indentations. Dormant cystic forms are seen as round
Germany) (RCM) laser scanning in vivo confocal microscope or ovoid hyper-reflective structures ranging between 10
is altered by the movement of the objective lens relative to to 26 µm in diameter. A double walled structure of cysts
the applanating cap. The focal plane position is automatically with a visible endocyst and surrounding ectocyst may also
displayed on the monitor screen and recorded for each image be seen.
that is saved. Corneal thickness measurements using RCM have The active trophozoite form is irregular in shape
to be studied further, with an expected accuracy in ranging from 11 to 25 µm in diameter. It may be difficult
measurement to be similar to that with central mountain to differentiate between acanthamoeba cysts and
training foundation (CMTF). keratocytes nuclei and inflammatory cells. Irregularly
thickened hyper-reflective stromal nerves can also be
Applications visualized.
There are numerous clinical situations where corneal • Bacterial keratitis: Bacteria are smaller than acanthamoeba
microscopy may be useful.8 Some of the common clinical or fungi and are observed as multiple small hyper-reflective
scenarios where confocal microscopy may be useful include: structures of 2 µm in diameter. In infectious crystalline
• Detection and management of infectious keratitis: Viral, bacterial, keratopathy, needle like opacities and amorphous
parasitic (acanthamoeba), and fungal intrastromal deposits may be seen at varying levels in the
• Detection and management of corneal dystrophies: Fuchs stroma.
• Fungal keratitis: Multiple interlocking white lines of
endothelial dystrophy, lattice dystrophy, epithelial basement
approximate width of 6 µm and length 200 to 400 µm are
membrane dystrophy, granular dystrophy, and corneal stem
seen in the stroma which represent the fungal hyphae.
cell deficiency
• Monitoring contact lens induced corneal changes
• Pre-and post-refractive surgery assessments: LASIK and LASEK Laser Refractive Surgery
flap evaluations and radial keratotomy • Photorefractive keratectomy (PRK): Corneal epithelium regains
• Monitoring corneal grafts, with the capability to distinguish normal morphology in about a month’s time following
between corneal edema due to corneal graft rejection PRK. Epithelial thickness remains significantly thinner than
(caused by presence of inflammatory cells) and endothelial pre-operative values and matches preoperative levels by 3
decomposition (caused by low endothelial cell counts months. Stromal nerves appear sharply cut following PRK
without presence of inflammatory cells). and in 1 to 2 months, sprouting nerve fibers are seen in
• Conjunctival and limbal structures may be monitored for the anterior stroma at the wound margin. At 3 months
cysts, inflammation and proliferation of cells. Edges of single non-branched sub-basal nerve fibers are seen and
healing blebs may also be monitored. (Conjunctiva, at 5 to 8 months they are fully regenerated, though it may
peripheral cornea and limbus are better examined at the take up to a year to attain normal morphology. Corneal
surface and at medium depth with the HRT II- RCM than haze following PRK may be seen as increased subepithelial
with the standard confocal microscopy. reflectivity, which peaks by 3 months and thereafter
• Endothelial cell counting capabilities. With for a semi- decreases but does not return to normal even after a year.
automated cell count of any layer in the cornea. Monitoring Anterior keratocyte activation with bright keratocytes nuclei
of cell densities anywhere from epithelium to endothelium and visible cell process are seen postoperatively which
may be done. return to preoperative appearance by 6 to 12 months.
• Corneal thickness/flap thickness measurement. Anterior keratocytes density also increases postoperatively
and returns to normal by 6 to 12 months. Preoperative 6. Niederer RL, McGhee CN. Clinical in vivo confocal microscopy
finding of highly reflective microdot structures in the of the human cornea in health and disease. Prog Retin Eye Res.
corneal stroma in contact lens wearers remain unchanged 2010 Jan;29(1):30-58.
7. Erie JC, McLaren JW, Patel SV. Confocal microscopy in
postoperatively in PRK patients. Highly reflective rod and
ophthalmology. Am J Ophthalmol. 2009 Nov;148(5):639-46.
needle shaped deposits occur in all stromal layers in the 8. Chiou AG, Kaufman SC, Kaufman HE, Beuerman RW. Clinical
PRK ablation zone, ranging from 1 to 50 µm in size and corneal confocal microscopy. Surv Ophthalmol 2006;51(5):482-
are considered to represent keratocytes that have 500. Review.
undergone cystic change during wound healing. 9. Hollingsworth J, Prez-Gomez I, Mutalib HA, et al. A population
• Laser in situ keratomileusis (LASIK): Decreased epithelial study of normal cornea using an in vivo slit scanning confocal
thickness is observed in post-LASIK patients. Microfolds microscope. Optom Vis Sci 2001;78:706-11.
10. Eckard A, Steve J, Guthoff RF. In vivo investigations of the corneal
at the level of Bowman’s layer is seen and may decrease
epithelium with the confocal rostock laser scanning microscope
with time. These appear as dark lines with varying thickness (RLSM). Cornea 2006; 25: 127-31.
and length and are observed to be vertical in orientation. 11. Mustonen RK, McDonald MB, Srivannaboon S, et al. Normal
Interface particles (thought to represent cellular and human corneal cell population evaluated by in vivo scanning slit
inorganic debris) are seen postoperatively in maximal confocal microscopy. Cornea 1998;17:485-92.
density during the initial few days and decrease with time. 12. Tomii S, Nishida K, Yokoi, Kinoshita S, Nakauchi M. Evaluation
Anterior keratocytes density remains at preoperative levels of human corneal epithelial basal cells by tandem scanning confocal
till three months after LASIK and thereafter a decrease is microscope. Invest Ophthalmol Vis Sci 1994; 35(ARVO suppl.):
4.
noted at six months and one year postoperatively.
13. Guthoff RF, Baydown C, Steve J. In: Atlas of confocal laser
Keratocytes adjacent to the lamellar cut disappear on both microscopy: In vivo microscopy in opthalmology, Spinger, New
sides of the cut as early as three to eight days after the York, 2006.
procedure. Keratocytes behind the interface are activated 14. Romano AC, Espana EM, Yoo EM, et al. Different cell sizes in
appearing larger than normal with oval hyper-reflective the human limbal and central corneal epithelia measured by
nuclei and identifiable processes. confocal microscopy and flow cytometry. Invest Ophthalmol Vis
• Keratoconus: Superficial epithelial cells appear to be elongated Sci 2003;44(12):5125-9.
15. Patels, McLare J, Hodge D, et al. Normal human keratocyte density
and arranged in whorl like pattern in the region of the
and corneal thickness measurement by using confocal microscopy
cone. Mean total keratocytes density is lesser than normal in vivo. Invest Ophthalmol Vis Sci 2001;42:333-9.
by about 19 percent. Corneal stromal thinning with abrupt 16. Prydal JI, Franc F, Dilly PN, Kerr Muir MG, Corbett MC, Marshall
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seen. analysis of confocal images. Eye 1998;12 (Pt 3a):337-42.
• Corneal dystrophies: Confocal microscopic changes are 17. Berlau J, Becker HM, Stave J, Oriwol C, Githoff RF. Depth and
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4. Cavanagh HD, Jester JV, Essepian J, Shields W, Lemp MaA. confocal microscopy. Clin Exp Ophthalmol 2002; 30:187-90.
Confocal microscopy of the living eye. CLAO J 1990;16:65-73. 22. Imre L, Nagymihaly A. Reliability and reproducibility of corneal
5. Bohnke M, Masters BR. Confocal microscopy of the cornea. Prog endothelial image analysis by in vivo confocal microscopy. Graefes
Retinal Res 1999;18:553-628. Arch Clin Exp Ophthalmol 2001;239:356-60.
6.2.7 Corneal Hysteresis: Relevance

in Current Clinical Practice
Shibal Bhartiya
Biomechanics is the study of the equilibrium and deformation independent pressure values are thus derived from the inward
of tissues submitted to any force. Corneal biomechanics is and outward applanation events.
determined by the following extrinsic factors, intraocular The information obtained from the applanating event can
pressure, ciliary muscles, extraocular muscles, atmospheric be represented in graphic form where two well-defined peaks
pressure and eyelids. Its intrinsic determinants include the correspond to the inward and outward applanation events (Fig.
central pachymetry, viscosity, elasticity, hydration of the cornea 6.2.7.1). This is representative of the force required to flatten
and regional pachymetry. The biomechanical properties of the the cornea, as the air pressure rises (P1) and the force at which
cornea are thought to be indicative of that of the globe, and the cornea flattens as the pressure falls (P2). The difference
are hence of increasing relevance to the clinician.1 between these two pressures is corneal hysteresis.3
Due to its viscoelastic characteristics, the cornea resists
CORNEAL HYSTERESIS the dynamic force of the air pulse, causing a delay in the inward
and outward applanation events, resulting in two different
Corneal hysteresis is a recently characterized viscoelastic pressure values. The ORA, therefore, also measures two
property of the cornea which is a measure of its stiffness or different pressure values, the Goldmann-correlated IOP
rigidity. Corneal hysteresis (CH) is an indication of viscous (IOPg) and the corneal-compensated IOP (IOPcc). The IOPg
damping in the cornea, reflecting the capacity of the tissue to is the average of the P1 and P2 applanation pressures and the
absorb and dissipate energy. It may also be described as the IOPcc is a value that compensates for the corneal
capacity of tissue to recover its original shape after external biomechanical properties.
force is applied.1-3 The time required for the cornea to initially applanate is
An analogous example would be that of the memory foam recorded as the ‘time in’ and the time needed for outward
material used to make pillows. Applying pressure deforms the applanation is referred to as the ‘time out’.
material, but upon releasing the pressure, the material returns ORA provides an additional reading of the corneal
to its original shape slowly (a viscoelastic response) rather than resistance factor (CRF). It is derived from the formula (P1 – k
instantly like a stretched rubber band upon release (which is a P2), where k is an empirically determined constant, so that
purely elastic response).1 the CRF is more strongly associated with the central corneal
thickness (CCT) than the corneal hysteresis.1-4
Measurement of Corneal Hysteresis:
Normal Corneal Hysteresis
Ocular Response Analyzer
The corneal hysteresis and the corneal resistance factor of
The Ocular Response Analyzer (Reichert Ophthalmic the normal eyes range from 8 to 16 millimeters (mm), and 7
Instruments, Buffalo, NY) noninvasively measures corneal to 15 mm respectively. 2,5-8 In addition, no linear correlation
hysteresis. It uses a rapid air impulse to apply force to the has been observed between age and corneal hysteresis or
cornea, and the deformation is monitored by an advanced corneal resistance factor. 6-8,9 In contrast, Moreno-Montañes
infrared electro-optical system. In one measurement, the and colleagues reported that both corneal hysteresis and the
instrument records two applanation events. The precisely corneal resistance factor correlated with age but the correlation
metered collimated-air-pulse causes the cornea to move was unlikely to be clinically relevant. All parameters measured
inwards, past applanation and into a slight concavity. by the ORA had a positive correlation with central corneal
Milliseconds after applanation, the air pump shuts off and thickness, except for IOPcc. The corneal resistance factor had
the pressure declines in a smooth fashion. As the pressure a stronger correlation with the central corneal thickness than
decreases the cornea begins to return to its normal configu- the corneal hysteresis, which may indicate that the CCT plays
ration, again passing through an applanated state. Two a more important role in the corneal elastic properties.8
Fig. 6.2.7.1: Graphic representation of the applanating events as recorded by the ORA (The Reichert Ocular Response Analyzer graph
measures the pressure values at applanation, when the cornea is moving in and moving out. Corneal hysteresis is the difference in
values, which is a measure of viscoelastic damping)
Corneal Hysteresis and Glaucoma detachment, rigidification of the cornea, and retinal
microvascular alterations.13 It has also been reported that
Since, the cornea and the optic nerve are contiguous structures,
glucose can act as a collagen cross-linking agent with the help
corneal hysteresis could represent a biomechanical property
of AGEs.13,14 Advanced Maillard products accumulate in
that may be associated with the ability of the optic nerve to
collagen proteins, result in the formation of covalent cross-
tolerate intraocular pressure. The relationship between
linking bonds, and may lead to increased corneal thickening
glaucoma, IOP, and ocular structures may not be confined to
and biomechanical changes14,15 resulting in an overestimation
the consideration of CCT. A low CH value could be
of the “true” IOP. Goldich et al reported that diabetes resulted
responsible for underestimation of IOP. CH could also be a
in an increased CH, CRF, and CCT.16 Sahin et al however were
risk factor for glaucoma, independent of IOP.
of the view that diabetes results in lower CH values than those
Congdon and coworkers measured CH in a cohort of
in healthy control subjects, which may cause clinically relevant
glaucoma patients and found that low CH was predictive of
high IOP measurements independent of CCT.17 Castro et al
visual field progression.10 Abitbol et al also reported that CH
found that primary open-angle glaucoma patients with diabetes
was lower in glaucomatous than in normal eyes.11 Iordanidou
have significantly higher CH values than those without diabetes,
evaluated the modifications in corneal biomechanics and
with correlation between CH and CCT.18 Hager et al concluded
intraocular pressure after deep sclerectomy and reported that
that even though CH is assumed to be an indicator for acquired
CH statistically increased between preoperative and
changes due to diabetes, CCT is a more characteristic parameter
postoperative day one, and the change remained statistically for the individual patient.19 Regardless, CH may provide more
significant after 8 and 30 days.12 information about changes of the extracellular matrix in
diabetes, and therefore offer a new monitoring parameter.
Hysteresis and Diabetes
Nonenzymatic glycosylation of proteins (the Maillard reaction) Hysteresis and IOP Measurement
results in the formation of advanced glycosylation end There are inconsistencies regarding the relationship between
products (AGEs), and this results in liquefaction of the CH and IOP. CH has been reported to be IOP dependent
vitreous body leading to diabetic retinopathy and retinal and known to decrease in a given eye when IOP is elevated.20
On the contrary, in a study by Luce,3 CH was found to be both keratorefractive surgical procedures, PRK and LASIK,
IOP independent. Oncel et al found that IOP readings detected reduced CH and CRF depending on the amount of myopic
by dynamic contour tonometry (DCT) and IOP-ORAcc were correction, indicating that both can affect the biomechanical
not found to be clinically interchangeable with GAT and NCT parameters of the cornea, especially when a large amount of
readings. IOP-ORAcc and DCT readings however may be laser ablation is required in highly myopic eyes. They also
regarded as comparable and independent of CCT, in the range demonstrated that LASIK significantly decreased CH and CRF
of the normal IOP. 21 Diurnal variation of corneal more than PRK. This may be due to the fact that LASIK
biomechanics and intraocular pressure in normal subjects was requires both surgical tissue removal and flap creation, whereas
assessed by Oncel et al who found that CRF and CH were PRK requires tissue removal only. In addition, LASIK ablates
both found to be positively correlated to CCT and constant more of the deeper layers of the corneal stroma than PRK.20
throughout the day in healthy eyes.22 Kotecha et al however Seiler et al reported that the residual corneal bed thickness
were of the view that measured IOP and corneal characteristics was critical for determining the mechanical strength of the
vary during office hours, and a small proportion of the change cornea after LASIK.27 These findings are also confirmed by
in IOP measurements made with the GAT during office hours the fact that as many as 26 percent of patients developed
could be attributed to change in CH.23 Bagga et al reported iatrogenic keratoconus after hyperopic automated lamellar
that though both IOP and central corneal thickness display a keratoplasty, which intentionally attempts deeper tissue
24-hour rhythm with peaks during the nocturnal period, there dissection.28 Kirwan et al recently reported that the decrease
is no correlation between central corneal thickness and 24- in CH was not statistically different after LASIK and laser-
hour IOP variation in normal and glaucoma patients. Corneal assisted subepithelial keratectomy (LASEK), indicating that
biomechanical properties (corneal hysteresis and corneal LASIK involving a thin 120-mm flap did not induce additional
resistance factor) remain relatively stable during the 24-hour biomechanical change.29
period and are not associated with 24-hour IOP fluctuation.24 Investigators have found that the biomechanical measures
Shen et al reported that diurnal variation of CH was not of CH and CRF decreased similarly after PRK and LASIK
detectable in healthy Asian eyes. However, CRF was increased using laser or mechanical flap creation. However, LASIK using
a few minutes after sleeping, a change that was correlated to femtosecond laser flap creation caused a significantly more
the changes of IOPg.25 predictable change in corneal biomechanics, which correlated
Avitesov reported that elevated intraocular pressure was strongly with ablation depth (AD). CH and CRF has been
associated by a lower corneal hysteresis-corneal resistance found to be significantly lower after refractive surgery in all
factor ratio.26 groups has been found.3,30,31 With planned AD controlled via
inclusion criteria, there was no significant difference in the
Hysteresis and Refractive Surgery mean change in CH or CRF between the three groups. These
findings are similar to those of Kirwan and Durrie et al in
Patients with thinner corneas are considered to be at higher
their prospective contralateral eye study of PRK versus thin-
risk for developing post-LASIK corneal ectasia, and corneal
flap LASIK.29,32,33
hysteresis is believed to provide a more complete
characterization of the biomechanical state of the cornea than
Hysteresis and Keratoconus
the measure of CCT alone. Corneal hysteresis measurement
can thus be a useful tool for eliminating LASIK candidates Keratoconus is a progressive ectasia of the cornea resulting
who are at risk of developing post-LASIK ectasia. It also has from non-inflammatory thinning of the corneal stroma.
potential uses in post-LASIK follow-up. Studies have shown Ortiz et al reported that the corneal hysteresis and corneal
that the anterior portion of the stroma contributes more to resistance factor values were significantly lower in keratoconic
the strength of the cornea than the posterior stroma. It has eyes, with the decrease in CH and CRF corresponding to the
been demonstrated that the LASIK flap does not contribute keratoconus grade.34 Liu et al also concurred that the CH and
to the biomechanical stability of the cornea, even after its CRF were significantly lower in keratoconic eyes than in normal
repositioning in the stromal bed.27 There is growing evidence eyes.35 Corneal biomechanical properties, characterized by
that there are differences in the wound-healing response and corneal hysteresis and the corneal resistance factor, thus
biomechanical effects on the cornea depending on whether a provide new indicators for the diagnosis and evaluation of
flap is created by a microkeratome or femtosecond laser or progression of keratoconus.35 Saad et al were of the opinion
no flap is created (i.e. PRK). Kamiya et al demonstrated that that CH and CRF alone cannot be used to identify keratoconus
suspect corneas.36 Analyzing signal curves obtained with the REFERENCES

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6.2.8 Slit Lamp Biomicroscopy Evaluation

and Diagrammatic Representation
Swapnali Sabhapandit Sharma, Shraddha Shrikant Puranik, M Vanathi
A slit lamp is a high powered binocular compound microscope DESIGN PRINCIPLE

with a slit shaped illumination source that enables a detailed
The basic design of the slit lamp comprises of the following
examination of the anterior segment of the eye. This
parts:
instrument can be regarded today as an ophthalmologist’s best
• Astronomical telescope
friend as it can provide not only information on the anterior
• Galilean telescope with telecentric optical path
ocular structures, but also be used to aid in various other
• Porro Abbe inverting prism
functions like measurement of intraocular pressure, posterior
• Objective lens
pole evaluation, gonioscopy, specular microscopy, and corneal
• Illumination system
pachymetry, with the help of added optical attachments. This
• Binocular viewing system.
instrument gives the benefit of binocular vision and Electrical supply needed includes a low-voltage supply
stereoscopic examination. (mains power pack), halogen lamp and a rheostat which varies
the lamp voltage.
HISTORY
Slit lamp biomicroscopy is an important method of clinical
The history of slit-lamp biomicroscopy can be summarized as: 1 evaluation that enables high magnification stereoscopic
1806 Himley used a convex lens for observation.
examination of the ocular tissues. The slit lamp comprises of a
1823 Purkinje used magnifying lens for better observation. microscope and illumination system. The illumination column
1854 Liebreich invented monocular (and later binocular) is mounted so that it rotates about the same axis as the
microscope.
microscope. The slit is thus parfocal with the microscope. The
1897 Czapski combined a diffuse illuminating light bulb mounted illuminating system consists of a halogen lamp along with a
on a movable track to improve the variety of angles of
illumination with a binocular stereoscopic microscope. system of condensing lenses and an adjustable diaphragm which
1908 Gullstrand designed the first slit lamp with the facility of focal
allows variations in the slit beam width and height. The main
illumination using a slit aperture. components of the microscope system are convergent binocular
1916 Koeppe and Henker combined the Gullstrand slit lamp with tubes and a Galilean telescope. A Galilean telescope consists
stereoscopic microscope both mounted on the same stand. of a convex objective lens and a concave eye-piece lens separated
1920 Vogt altered the optics so that the filament of the bulb was by the difference in their focal lengths. The image produced is
focused on the condensing lens. virtual, magnified and upright.
1926 Comberg designed a vertical illumination system to make the Power of the eye piece lens (Diopters)
instrument compact, and Koeppe placed the slit lamp and the Magnification =
microscope on a common vertical axis for co-axial rotation. Power of the objective lens (Diopters)
Multiple steps in magnification are available ranging from
INTERACTIONS THAT OCCUR WHEN 6× to 40× which may be selected using a rotating Galilean
THE LIGHT STRIKES THE CORNEA lens barrel.
• Transmission and refraction: If a substance transmits all the SLIT LAMP EXAMINATION TECHNIQUES
light incident upon it, it appears transparent. Majority of There are various methods for using the slit lamp for
the refraction occurs at the tear-air interphase.2,3 biomicroscopic examination:
• Reflection: Cornea reflects and scatters light. The reflection • Direct illumination
is in a specular manner to create a catoptric image. The – Direct diffuse
phenomenon of scattering occurs in presence of corneal – Direct focal
edema or opacity.2,3 i. Optical section
• Absorption: Light can be absorbed partially or completely by ii. Conical beam
the presence of an opacity or blood vessel in the cornea.2,3 iii. Parallelepiped.
• Indirect illumination • To examine epithelial surface pathologies like intraepithelial

– Indirect focal cysts and bullae
– Retroillumination • To assess depths of foreign bodies, scars and opacities
– Sclerotic scatter • To estimate the anterior chamber depth
– Specular microscopy. • To identify the anatomical location of lens opacities.
DIRECT ILLUMINATION Recommended settings:

Illumination:
Direct Diffuse Illumination • Biomicroscope directly in front of the patient’s eye
The main purpose is to illuminate as much of the eye and its • Illumination angle at about 45 degrees
adnexa like eyelids, lid margin, lacrimal puncta at once. Diffuse • Illumination mirror in “click” position
illumination enables detection of gross abnormalities but is • Slit width 0.25 mm wide and 7 to 9 mm high
insufficient for defining details or determining the depth of the • To mention use of filters as well to increase patient comfort.
corneal lesions. A wide, unnarrowed, beam of light is directed
Magnification:
at the cornea. The microscope is positioned directly in front of
• M = low to medium (7X to 10X)
the patient’s eye and focus is on the anterior of the cornea.
• A point of fixation such as the fixation light.
Applications Once the cornea is in sharp focus, the entire cornea is
scanned from the temporal limbus to the nasal limbus. To
• Examination of sclera maintain a clear, distortion-free view, the illumination source
• Assessment of the tear film (qualitative and quantitative) is always moved to the opposite side when crossing the mid-
• General observation of the surfaces of cornea and lens line of the cornea at the center of the pupil. With a clearly
• General survey of anterior segment focused optic section slightly temporal to the center of the
• Staining pattern of the ocular surface cornea, the magnification can be increased to 16X and above.
• Assessment of contact lenses fitting. The following structures are seen:
Recommended settings • Front surface bright zone is the tear film
Illumination • The next darker gray line is the epithelium
• Slit fully opened (annular diaphragm) • The next brighter thin line is Bowman’s Membrane
• Diffuser inserted • The gray wider granular area is stroma
• Microscope positioned at 0° • The last bright inner zone is the endothelium.
• Angle of slit illumination system approx. 30° to 50°. To attain an optic section of the crystalline lens, the angular
separation of the illumination source is reduced until the light
Magnification beam just touches the edge of the pupil and the vertical height
M = 5X to 12X (for overall view) can be reduced to approximate the pupil size. When the beam
M = > 30X (assessment of lacrimal film) cuts just across the edge of the pupil, the crystalline lens will
appear sectioned and the degree of nuclear opalescence and
Direct Focal Illumination
color can be evaluated and graded. Different magnifications
Direct focal illumination is done by using a narrow vertical may be used, but medium and high give the best detail.
slit beam angled to one side with respect to the microscope. van Herick’s technique for grading the anterior chamber
This technique reveals thickness of transparent or translucent angles uses an optic section placed near the limbus with the
structures, indicates depth of the features observed and light source always at 60 degrees.
demonstrates their contours.
Conical Beam
Optical Section
Examination of the anterior chamber for cells or flare must
Applications: be performed before either dilation or applanation tonometry.
• To determine the depth or elevation of a defect of the Dilation often results in an increase in the number of cells
cornea, conjunctiva and fluorescein used in applanation tonometry causes an
• To detect changes in corneal and conjunctival thicknesses increase in flare.
Recommended settings: a clear undistorted view must be maintained by positioning

the light source to the opposite side when crossing the mid-
Magnification:
line of the cornea. Tear film status, corneal nerves (white
M = 16 to 20X
thread-like structures that bifurcate and trifurcate and are
Illumination: located anywhere within the cornea), new blood vessels
• High or the level the patient will tolerate (diagnostic of chronic or acute insult or inflammation), ghost
• To reduce the beam to a small circular beam of 1 mm. vessels (diagnostic of past corneal inflammation), corneal scars
• Light source at 45 to 60 degrees temporally and directed (white in color), corneal striae (white, vertical thread-like
into the pupil. twisting lines found in the Descemet’s membrane and posterior
This method is used to detect floating aqueous cells and stroma), and endothelial pigmentation, are some of the
flare by the Tyndall effect, much like seeing dust floating in common pathological findings in the cornea.
the air of a sun filled window. The biomicroscope is positioned
directly in front of the patient’s eye with as bright an INDIRECT ILLUMINATION
illumination as the patient tolerates and high magnification.
The examiner must allow himself a period of time for dark Indirect Focal Illumination
adaptation. The conical beam is focused between the cornea With this method, light enters the eye through a narrow to
and the anterior lens surface and observation is concentrated medium slit to one side of the area to be examined. The axes
on the dark zone between the out of focus cornea and lens. of illuminating and viewing path do not intersect at the point
This zone is normally optically empty and appears totally black. of image focus which is done by decentering the illuminating
Flare (protein escaping from dilated vessels) makes the prism by rotating it about its vertical axis off the normal
normally optic empty zone appear gray or milky when compared position. In this way, reflected, indirect light illuminates the
to the uninvolved eye. Cells (white blood cells escaping from area of the anterior chamber or cornea to be examined. The
dilated vessels) will reflect the light and be seen as white dots observed corneal area then lies between the incident light
(which can be counted on high magnification after making a section through the cornea and the illuminated area of the
parallelepiped). There are different gradings described for flare iris. Observation is thus against a comparatively dark
and cells. background.
Parallelepiped Applications: Examination of objects in the direct vicinity
A parallelepiped is essentially an optic section, except the slit of corneal areas of reduced transparency (e.g. infiltrates,
width is greater and the height may vary, providing a more corneal scars, deposits, epithelial or stromal defects).
three dimensional view of the cornea or crystalline lens. The Recommended Settings:
three-dimensional view permits observation of distinguishable
Illumination:
details within the cornea and the crystalline lenses known as
• 2 to 4 mm
“zones of discontinuity”.
• Decentered slit.
Recommended settings:
Magnification:
Illumination: Approx. M = 12X (depending on object size)
• Biomicroscope is placed directly in front of the patient’s
eye Retroillumination
• Illumination source is placed at about 45 degrees
• Slit width is 2.0 to 4.0 mm In certain cases, illumination by optical section does not yield
• Illumination mirror is in the “click” position. sufficient information, for example, when extensive zones or
spaces of the ocular media are opaque. Then the scattered
Magnification: light that is not very bright normally is absorbed. A similar
M = 10X to 16X situation arises when areas behind the crystalline lens are to
The angle between the illumination source and the be observed. In this case the observation beam must pass
biomicroscope may be varied to expose more corneal through a number of interfaces that may reflect and attenuate
epithelium, stroma and endothelium. The whole cornea should the light. These situations are overcome by using
be scanned using a parallelepiped. When scanning the cornea, retroillumination. This observation uses transmitted light
where the object structures are recognized by differences in opacities, and foreign bodies, light scatter occurs allowing any
absorption. Transmitted light requires a light source on the disturbances, including mild edema, small scars and very fine
other side of the object. With retroillumination, the light is opacities to be seen as shadowing on faint illumination.
produced secondarily by irradiation.
Magnification:
There are two types of retroillumination:
• Medium.
a. Direct retroillumination caused by direct reflection at surfaces
such as the iris, crystalline lens or the fundus.
Specular Microscopy
b. Indirect retroillumination caused by diffuse reflection in the
medium, i.e. at all scattering media and surfaces in the This method of examining the endothelial cells of the cornea
anterior and posterior segments. requires higher magnification (minimum 25X) settings
Recommended Settings: Recommended Settings:
Illumination: Illumination:
• Slit width: 1 to 2 mm Maximum power in accordance to the patient’s tolerance.
• Slit height: 4 to 5 mm. Light beam source is positioned to one side at about 45
Magnification degrees and the observing microscope to the opposite
direction at 45 degrees. The light beam is superimposed on
M = medium the bright light reflex coming from the instrument’s lamp, in
The biomicroscope and the light source are placed in direct the posterior stroma. The endothelial area just adjacent to this
alignment with each other. They are both positioned directly has a dim reflex, which on further focusing, shows the
in front of the eye to be examined. hexagonal cell mosaic.
The common findings include: Magnification
Cornea: Vascularizations, micro cysts, vacuoles, edema, • M = 25X to 40X.
deposits like amyloid, particles in tear film, defect or folds in
Applications:
the Descemet’s membranes, keratic precipitates.
• To evaluate the endothelial cells for size and shape.
Iris: Transillumination defects like iris atrophy, cysts, holes, • To identify the irregularities in the Descemet’s membrane,
growth, iridoschisis, etc. e.g. guttata in early diagnosis of Fuchs’ endothelial dystrophy.
• Pigment deposits and keratic precipitates on the
Lens: Opacities, coloboma, foreign body, etc.
endothelium.
Sclerotic Scatter
DIAGRAMMATIC REPRESENTATION
In this method of indirect examination of the cornea, light OF CORNEAL PATHOLOGY
beam is transmitted through the corneal parenchymal layers IN CLINICAL PRACTICE
according to the principle of total internal reflection of light.
In its normal physiological state, the cornea is fully transparent Color coding for cornea
and appears completely clear. Color used Corneal pathology depicted
Recommended settings: Black Limbus, scars, degenerations, foreign bodies,

suture, contact lens
Illumination: Blue Edema, small circles for epithelial edema or
Slit width: >0.5 mm stroma, wavy lines for Descemet’s folds
• Maximum illumination. Brown Melanin, iron pigmentation, pupil, iris
With this type of illumination, a wide light beam is directed Red Blood vessels and Rose Bengal staining, wavy
onto the limbal region of the cornea at an extremely low angle lines for subepithelial vessels and straight lines
for stromal vessels
of incidence and with a laterally decentered illuminating prism.
Orange Leukocytes, hypopyon, keratic precipitates (KPs)
The slit is directed to the scleral region directly adjacent to the
Green Fluorescein staining of epithelial defects,
limbus. If the eccentricity of the light is properly adjusted a lens and vitreous
bright shining ring is visible around the entire limbus. With Yellow Stromal infiltrates
irregularities in the structure caused by inclusions, scars,
Diagrammatic representation of the cornea and its various

pathologies is essential to every ophthalmologist. Such
diagrams help in proper documentation, follow-up and
archiving of data. Although, with the advent of modern
methods of slit lamp photography, schematic diagrams are
less done in clinics, yet they are needed for the day-to-day
monitoring of cases as photography involves cost and storage
space. Attempts have been made in previous years to formulate
guidelines for schematic representation of the cornea. Here,
some of the common methods for diagrammatic represen-
tation of the cornea will be discussed.
The earliest attempt in systematic documentation of Fig. 6.2.8.1A: Plan view of cornea
corneal findings was done by AJ Bron in 1973.4 Cornea is
depicted in the plane view by a circle, with the pupil shown in
dashed lines (Fig. 6.2.8.1A).4
Different abbreviated words were used to depict different
findings (such as Ep. = Epithelium, Str. = Stroma, Des. =
Descemet’s membrane, End. = Endothelium, the location of
any pathology in the stroma was denoted in slit view as a =
anterior; m = middle; p = posterior). Bron used a grading
system to document the degree of change of any pathology
in the cornea 4 (1 – minimal change, 2 – mild change,
3 – moderate change, 4 – severe change). Corneal scar or
opacity was depicted as vertical hatching and denoted by ‘S’
(Fig. 6.2.8.1B), corneal edema was depicted in pencil shading Fig. 6.2.8.1B: Stromal corneal scars of differing density located at
and denoted by the letter ‘O’ corneal infiltrate was denoted by different stromal levels
oblique single hatching with letter ‘I’ corneal abscess was drawn (Figures 6.2.8.1A and B reproduced from “A simple Scheme for
with oblique double hatching and denoted by ‘A’, corneal documenting corneal disease,” AJ Bron, British journal of
opthalmology 1973, Volume 57, page 629-634, copyright notice
thickness was denoted by ‘T’ and then graded as 1, 2, 3, 4. February 2011 with permission from BMJ publishing Group Ltd)
Color coding was introduced for various clinical findings.4
Corneal vessels were depicted using a color code; red for deep
vessels and blue for superficial vessels. The superficial vessels
were drawn starting outside the limbal line while the deep
vessels were at the limbal line. Staining reactions indicated
with a color code, using green for fluorescein staining and red
for staining with Rose Bengal stain. An ulcer was shown by a
ring of appropriate shape in red or green. Keratic precipitates
were indicated as small round circles annotated with the letters
‘K.P.’ Anterior synechiae were indicated as crosses and
annotated by writing in full. Hypopyon was indicated in yellow
(Fig. 6.2.8.2). Certain pathological findings were difficult to
depict schematically, e.g. transition from “severe infiltrate” to
“abscess”. 4 Another shortcoming in this method of Fig. 6.2.8.2: Corneal graft with corneal edema related to the site of
documentation was the inability to distinguish between scar anterior synechiae at the graft/host junction. The pupil is deformed
and edema, which was rectified in later diagram schemes. and elongated, there are keratic precipitates over the lower portion
of the graft, and a hypopyon is present (Reproduced from “A simple
Another attempt on establishing a standard practice of
Scheme for documenting corneal disease,” AJ Bron, British journal
corneal diagram was by George O Waring III in 19775 in which, of opthalmology 1973, Volume 57, page 629-634, copyright notice
a black circle approximately 35 mm in diameter was drawn to June 2011 with permission from BMJ publishing Group Ltd)
represent the corneal margin of the limbus in frontal view shading as given by Bron4 was simplified in this scheme.
(Table 6.2.8.1). The brown pupil served as a landmark for the Waring’s method of diagrammatic representation was
accurate placement of corneal pathologic abnormalities. In modified by Rao and Aquavella in 1986. 6 A composite
this scheme, the density of shading was proportionate to the profile of the condition of eyelids, precorneal tear film,
severity of the lesion, although one might indicate the severity and changes in the anterior segment of the eye was given
by 1 + to 4 + labels. More complex problems could be drawn i n t h e i r work . Eyelid outlines with the relative
quadrant by quadrant. Anterior chamber findings (e.g. hyphema position of the lids were added to the slit view diagram. The
– red), iris pathologic abnormality (e.g. iridodialysis – brown), normal tear meniscus was drawn in the slit view diagram by a
and lens changes (green) were added to the frontal sketch, or straight line joining the base of the eyelash on the lower lid to
if it was too complex, to a separate sketch. Slit view was drawn the corneal epithelial surface. In the frontal view, the cornea
to denote the depth of the pathologies (Fig. 6.2.8.3). Color was divided into four quadrants by two continuous lines
coding for the anatomical and pathological findings have been connecting 12 and 6 o’clock and 9 and 3 o’clock positions
elaborated (Fig. 6.2.8.4). The cross hatching and complex (Fig. 6.2.8.5). Additional dotted lines were drawn to connect
Table 6.2.8.1: Corneal drawing
Frontal View Epithelium indicated as two lines with defects, edema, and
A circle (about 35 mm in diameter) to represent corneal microcysts
limbus is drown Stromal opacities and vessels to be drawn at accurate
Pupil is added level
All lesions scar, degeneration, infiltrate, and edema Posterior findings such as Descemet’s folds, cornea
are outlined guttata, pigment, and keratic precipitates to be included
Vessels, pigment, posterior deposits, or folds are depicted Anterior chamber, iris, lens, and anterior vitreous pathology
Iris, lens, and anterior vitreous pathology (on separate to be included.
diagram if needed) to be depicted Vital Staining
Slit View Staining to be documented by diagrams/photographs
Location of slit section to be indicated by line Measurements
Freehand outline to show variations in corneal thickness Measure lesions with continuously variable slit or
reticle
Fig. 6.2.8.3: Frontal and slit view of a corneal pathology diagram

KP = Keratic precipitates; HSV = Herpes simplex virus
Fig. 6.2.8.4: Color code used in corneal drawing
In present times, commonly used method for diagrammatic

representation of the anterior segment is as designed by Rao
and Aquavella.6 This system is found to be extremely useful
in clinical practice for recording the clinical features of corneal
alterations, external diseases, contact lens problems, and other
anterior segment lesions. Refractive surgery, uveitis, intraocular
lens findings, lens capsulotomy and cataractous lens findings
are depicted in the drawings.
Figs 6.2.8.5: Cornea is divided into four quadrants connecting 12 REFERENCES

and 6, and 9 and 3 o’clock position. Each quadrant is further
subdivided by discontinuous lines connecting the remaining clock 1. Corneal disorders, clinical diagnosis and management. 2nd edn.
hours. Pupil is drawn in the center HM Leibowtiz. George O Waring. page no. 56.
2. Berliner ML. Development of biomicroscopy. In: Berliner ML
(Ed): Biomicroscopy of the eye: Slit Lamp biomicroscopy of living
eye New York, Paul B Holber 1943.
the remaining clock hours, helping in a more precise portrayal 3. Duke Elder S, Abrams D. opthalmic optics and refraction Vol V.
of corneal lesions, minimizing the need for measuring the In: Duke Elder (Ed): System of ophthalmology: St Louis, CV
lesions. The maximum diameter of an ulcer was marked with Mosby 1970,30.
arrows. The anterior chamber depth was shown in slit view 4. AJ Bron. A simple scheme for documenting corneal disease. Brit.
J. Ophthal 1973;57:629.
diagram. Iris and lenticular opacities were drawn in yellow
5. George O. Waring III. A Systematic Method of Drawing Corneal
within the outline of the crystalline lens. Vitreous was drawn Pathologic Conditions. Arch Ophthalmol 1977;95:1540-42.
in green. This diag rammatic method gave a more 6. James V Aquavella, et al. Schematic Documentation of Cornea
comprehensive representation of the anterior segment of the and Anterior Segment Problems in Clinical Practice. Cornea 1985/
eye. 1986;4:220-24.
Chapter 6.3
DISORDERS OF THE PEDIATRIC CORNEA
M Vanathi, Shalini Mohan, Rakhi Kusumesh
Congenital corneal disorders are important causes of

childhood blindness which can occur in isolation or in
combination, or as part of a syndrome. Visual deprivation in
the early months of life due to corneal opacification can lead
to long-term changes in the central nervous system.1
Pediatric corneal opacifications may be classified as follows:1
• Congenital opacities-Congenital hereditary endothelial
dystrophy (CHED)
• Congenital opacities-Non-CHED
– Frequently associated with glaucoma
i. Congenital glaucoma
ii. Peter’s anomaly
iii. Other anterior segment dysgenesis
– Infrequently associated with glaucoma
i. Sclerocornea
ii. Dermoid
iii. Metabolic causes
iv. Birth Trauma
v. Corneal keloid
vi Aniridia
vii. Posterior polymorphous dystrophy
viii.Keratoconus
• Acquired traumatic corneal opacification
• Acquired nontraumatic
– Infectious keratitis
– Keratomalacia
• Allergic disorders
CONGENITAL OPACITIES
Congenital hereditary endothelial dystrophy (CHED) presents
as bilaterally symmetrical diffuse corneal opacification and
edema of varying degree (Figs 6.3.1 and 6.3.2).2-4 The stromal Figs 6.3.1A and B: Congenital hereditary endothelial dystrophy
opacity is supposed to result from terminal misdifferentiation (CHED) showing varying degrees of corneal haze at presentation
of the endothelial cells. Corneal clouding in the autosomal neural crest cell migration resulting in congenital glaucoma
recessive type of congenital hereditary endothelial dystrophy and neural crest cell differentiation resulting in CHED.10
is present at birth or within the neonatal period, with nystagmus Abnormalities of crest cell migration, proliferation and
often present. Patients with autosomal dominant type of differentiation contribute to disorders of the corneal stroma,
CHED usually have clear corneas early in life with corneal endothelium, trabecular meshwork and iris. Concurrent
opacification being slowly progressive. CHED may also occur management of glaucoma and corneal opacification is
in concurrence with congenital glaucoma. The autosomal sometimes required in infants with severe congenital glaucoma
dominant type may have associated deafness. The AD form if timely visual rehabilitation is to be achieved.
of CHED has been mapped to the pericentromeric region Peter’s anomaly: Peter’s anomaly is one of the most
of chromosome 20.5 Mutations in the SLC4A11 gene cause common congenital corneal opacification other than CHED.
autosomal recessive CHED. 6,7 The dystrophy might be It is bilateral in approximately 80 percent of the cases. This
commonly misdiagnosed as congenital glaucoma. CHED can rare congenital malformation of the anterior segment of the
lead to amblyopia in children. Penetrating keratoplasty eye is characterized by a central corneal opacity with
(Fig. 6.3.2) in congenital hereditary endothelial dystrophy is corresponding defects in the posterior stroma, Descemet’s
moderately successful, and graft survival and visual outcome membrane and endothelium. Iris strands typically arise from
is better in cases of delayed onset. Early surgical intervention the collarette and extend to the periphery of the corneal
is helpful to prevent development or progression of amblyopia. leukoma. The peripheral cornea is usually relatively clear;
varying degrees of haziness may accompany the central
Congenital Opacities-Non-CHED opacification. Peter’s anomaly is not a homogenous corneal
disease. It is associated with a wide range of congenital ocular
The non-CHED congenital corneal opacities can be subdivided and systemic abnormalities and commonly occurs as a
into (1) those that are frequently associated with glaucoma, sporadic disorder. A few inheritance patterns have been noticed
and (2) those that are infrequently associated with glaucoma. (autosomal recessive and autosomal dominant).11,12 The co-
existing glaucoma can complicate the graft and visual prognosis
Frequently Associated with Glaucoma in the management of these cases.
The extent of ocular involvement varies from mild to
Congenital glaucoma: The causes of congenital corneal severe. Mild disease is defined by the presence of normal
opacification associated with glaucoma include congenital iris and lens (Fig. 6.3.3). Moderate disease is defined by the
glaucoma, Peter’s anomaly with glaucoma, and CHED with presence of central iridocorneal adhesions (anterior synechia),
glaucoma. The combination of CHED with congenital or other iris defects such as atrophy, abnormal vasculature
glaucoma occurs infrequently.8,9 The combination of CHED or coloboma. Severe disease is defined by the presence of
or Peter’s anomaly with congenital glaucoma9 originates from corneo-lenticular adhesion, or by the presence of corneal
defects in the neural crest cell contribution, with abnormal staphyloma with or without corneal adhesions.13
Fig. 6.3.2: Penetrating keratoplasty in a CHED Fig. 6.3.3: Peter’s anomaly — mild
Disorders of the Pediatric Cornea 419
Peter’s anomaly has been associated with congenital and a high incidence of associated glaucoma. The age at
anterior and posterior segment anomalies as well as congenital which A-R syndrome is diagnosed usually varies from birth
systemic abnormalities.14 Glaucoma is the most common of to childhood, most commonly being diagnosed during early
the ocular anomalies observed in 30 to 70 percent of eyes infancy or childhood. Clinical features include peripheral
and is diagnosed shortly after birth. Peter’s anomaly patients anterior segment anomalies, iridocorneal abnormalities with
are at risk for developing glaucoma if they present without or without other associated ocular and systemic anomalies.
glaucoma at the outset. Microphthalmia occurs in 25 to 50
percent of the eyes. Iris abnormalities, chorioretinal coloboma, Infrequently Associated with Glaucoma
staphyloma, retinal dysplasia, cataract, ptosis, persistent
Dermoid: Dermoids are classified as choristoma and the
hyperplasic primary vitreous, optic nerve hypoplasia, foveal
opacification is usually peripheral rarely extending to the center
hypoplasia, macular pigment epitheliopathy and colobomas
(Fig. 6.3.5A). They present as round or oval, whitish or
have also been found to be associated. Systemic anomalies
seen in 60 percent of the patients include developmental yellowish mass protruding on the anterior surface of the
delay, central ner vous system defects, craniofacial eyeball. They consist of ectodermal (keratinized epithelium,
abnormalities, microcephaly, seizure disorder, fetal alcohol hairs, sebaceous and sudoriferous glands, nerves, smooth
syndrome and autism. Other defects such as congenital cardiac muscles and, less frequently, teeth) and mesodermal elements
malformations, skeletal deformities, genitourinary (fibrous tissue, fat, blood vessels and cartilage) combined in
malformations, ear defects as well as cleft lip and palate may different proportion.16 Most cases may require simple excision
also be present. with or without amniotic membrane or only lamellar
keratoplasty in form of patch grafts (Figs 6.3.5B and C).
Other mesenchymal dysgenesis: The terms mesenchymal
dysgenesis (Fig. 6.3.4) and anterior chamber cleavage Metabolic causes: Metabolic diseases are usually associated
syndrome refer to a spectrum of congenital ocular disorders with clear corneas at birth followed by progressive
ranging from posterior embryotoxon in its simplest form to opacification. Corneal clouding may be a part of many
Peters anomaly at its most complex. Other conditions that metabolic disorders including those involving aminoacids,
are included in this spectrum of congenital ocular disorders lipids, carbohydrates, purines, etc. Systemic mucopolysacc-
are Axenfeld anomaly, Reiger anomaly and syndrome and haridosis (MPS) are lysosomal storage disorders that affect
posterior keratoconus.15 All patients with the Axenfeld-Reiger the glycosaminoglycan metabolism. Seven types of MPS have
(A-R) syndrome, irrespective of their ocular manifestations, been described depending on the range of enzymes affected.
share the same general features including a bilateral Since cornea contains glycosaminoglycans, corneal clouding is
developmental disorder of the eyes, a frequent family history, a part of many of these MPS syndromes. MPS I-H (Hurler’s),
no sex predilection, frequent systemic developmental defects, MPS I-S (Scheie), MPS- IV (Morquio), MPS VI (Maroteaux-
lamy) and MPS VIII (Sly’s) are associated with variable
amounts of corneal clouding. Hurler’s syndrome and Scheie’s
syndrome share the deficiency of the same enzyme (alpha–
iduronidase). The corneal clouding in the former is more
diffuse and central whereas the latter has peripheral clouding
progressing centrally with age.17 Open angle glaucoma may
be associated with both.18, 19 Intelligence, stature and lifespan
is better in Scheie’s syndrome compared to Hurler’s syndrome.
Pigmentary retinopathy and optic atrophy are usually seen
complicating the visual prognosis in these syndromes.20
Morquio syndrome and Maroteaux-lamy syndrome
present with marked dwarfism, chest wall deformities,
cardiovascular abnormalities and corneal clouding. The
corneal involvement shows diffuse ground glass stromal
opacification in Morquio syndrome 21 and is of varying
severity in Maroteaux-lamy syndrome. The more recently
Fig. 6.3.4: Anterior segment mesodermal dysgenesis described MPS VIII (Sly’s syndrome) also have ocular
abnormality in terms of corneal clouding (mild to severe),

papilloedema and retinal pigmentary degeneration. 20
Sclerocornea: Sclerocornea is a primary, nonprogressive
anomaly in which scleralization of a peripheral part of the
cornea, or the entire corneal tissue, occurs. In the peripheral
type of sclerocornea, the affected area is vascularized with
peripheral arcades of superficial scleral vessels. In total
sclerocornea, the entire cornea is opaque and vascularized.
The corneas in sclerocornea may be smaller in diameter with
diffuse anterior stromal opacification and may be associated
with focal nebular densities and extensive superficial
vascularization.
Sclerocornea can present either as a primary anomaly or
in association with cornea plana22-24 and has been reported to
occur in isolation or with associated ocular and systemic
anomalies.24-29 Histopathologically, vascularized collagenous
tissue occupies the anterior one fourth of the corneal stroma
and with bundles of collagen fibrils 75 to 90 nm in diameter.
Descemet’s membrane shows abnormal anterior lamination.30
Birth trauma: Birth trauma caused by forceps blade placement
across the orbit and globe during delivery can result in a
blunt trauma and rupture of Descemet’s membrane. The
Descemet’s tears in birth trauma are usually central, unilateral
and in a vertical or oblique pattern. Diffuse stromal and
epithelial edema in the immediate postpartum period due to
birth trauma usually clears within weeks or months. The
residual high astigmatism necessitates penetrating keratoplasty
when contact lens wear is not possible.
Corneal keloid: Congenital corneal keloids are a rare entity.
Corneal keloids present as white glistening benign protuberant
masses, appearing as single, solitary nodules or involving the
entire corneal stroma (Fig. 6.3.6). Keloids occur more
frequently in males than females. Corneal keloids are
uncommon lesions that can occur at any age, from a congenital
form to those occurring in late adulthood and may be unilateral
or bilateral. Congenital keloids usually occur in the presence
of other ocular anomalies.31 Reported, associated ocular
anomalies include peripheral iridocorneal adhesions, anterior
segment mesenchymal dysgenesis, aniridia and cataract with
anophthalmia and subluxated lenses. Corneal keloids also have
been described in children with Lowe’s syndrome, Rubinstein
Taybi syndrome and progressive fibrodysplasia ossificans.
Corneal keloid can also mimic a limbal dermoid in presentation.
It has been postulated that the failure of normal differentiation
of the corneal tissue during embryogenesis results in the
Figs 6.3.5A to C: (A) Epibulbar dermoid, (B) Simple shave excision
for limbal dermoid, (C) Dermoid excision with peripheral lamellar occurrence of keloids of the cornea. Corneal keloid in Lowe’s
patchgraft with human fibrin glue syndrome is a major cause of visual disability in patients with
Lowe’s syndrome past the age of six or seven years, in whom keratopathy, hydroxyapatite deposition in the corneal stroma,
glaucoma and cataract have been treated surgically. In cases posterior keratoconus have also been reported in PPMD.
of Lowe’s syndrome, it has been suggested that aminoacids Keratoconus: Keratoconus is a noninflammatory ectatic
can filter into the cornea from abnormal vessels or that,
disorder of cornea where cornea becomes cone shaped due
substances from within the anterior chamber can get through
to stromal thinning. Commonly seen as an isolated anomaly,
a defective endothelium. Histopathologically, keloids are
it usually starts at puberty and progresses until 3rd to 4th
characterized by a haphazard arrangement of fibroblasts,
collagen bundles, and blood vessels. decade. In the initial stage, patients may not have any
symptoms or may have mild refractive error. Later in the
Aniridia: In aniridia, the most apparent clinical finding in course, patients may have increased visual distortion and visual
aniridia is the absence of iris tissue but additional ocular loss due to irregular astigmatism. Various clinical signs
structures are often affected and mutations of the Pax 6 include:33
gene have been identified in families with members affected • Stromal thinning with protusion of cornea in the inferior
by aniridia (Fig. 6.3.7). Corneal lesions in aniridia include
or inferotemporal region.
peripheral pannus and epithelial abnormalities that may
• Munson’s sign: Protusion of the lower eyelid while looking
advance centrally, resulting in the need for penetrating
keratoplasty. Aniridic keratopathy remains a significant cause down
for visual loss. Poor vision in aniridic eyes may be the result • Rizutti’s phenomenon: Sharply focussed beam of light at the
of macular hypoplasia, nystagmus, amblyopia, cataract, nasal limbus produced by lateral illumination of the cornea
glaucoma, and corneal disease, termed aniridic keratopathy. • Vogt’s stria: Are the vertical lines parallel to the vertical
axis of the cone and disappear on pressure.
Posterior polymorphous dystrophy (PPMD): PPMD32 is • Fleischer’s line: A line of iron deposition seen at the base of
autosomal dominant in inheritance with good penetrance. It the cone
is a bilateral disease, may be asymmetrical, usually
• Prominent corneal nerves
asymptomatic and typically occurs in the second or third
• Stromal scarring
decade of life. It may also be congenital or develop early in
life. It may be seen in Alport’s syndrome. The corneal lesions Sudden visual loss may be seen in these patients due to
in PPMD seen at the level of the Descemet’s membrane and formation of ‘hydrops’ because of break in Descemet’s
endothelium may be vesicle like lesions, band lesions or diffuse membrane and seeping of aqueous into the corneal stroma.
opacities. Endothelial guttae can also be seen in PPMD. In The management options include both conservative and
severe cases, corneal edema ranging from severe stromal surgical modalities. Medical therapy includes topical steroids,
edema to bullous keratopathy may be seen. Peripheral anterior cycloplegics, hyperosmotic agents along with systemic
synechia, raised intraocular pressure, corectopia, calcific band analgesics. Surgical options include intracameral injection of
Fig. 6.3.6: Congenital corneal keloid Fig. 6.3.7: Aniridia

sulfur hexafluoride (SF6)34 or perfluoropropane (C3F8), which in young children resulting from vitamin A deficiency is
is associated with early resolution of hydrops. predisposed by multiple factors like malnutrition, systemic
Retroillumination techniques, scissoring of retinoscopic diseases and lack of immunization. Acute corneal melting
reflex and “Charleux” oil droplet can be used as an adjuvant results from the ocular pathological changes in severe vitamin
for diagnosis. Videokeratography, keratometry, and pachymetry A deficiency and is invariably accompanied by malnutrition
should be done in such cases. and systemic disease. Illiteracy, lack of health education, poor
Treatment options available in early cases are refractive access to primary health care facilities, delay in diagnosis and
error correction. Best possible correction is obtained with treatment, compound the ocular morbidity due to infectious
contact lens. Recently corneal collagen cross linking with keratitis and keratomalacia in the developing nations.
riboflavin has been used to reduce the defect by acting at a Keratomalacia in children is hastened by protein-caloric
biochemical level. Intrastromal corneal ring segments have malnutrition precipitated by childhood communicable diseases
been used with limited success in early cases. Late cases may such as measles.35
be treated with deep anterior lamellar keratoplasty, penetrating
keratoplasty or epikeratoplasty. Excimer laser photothera- Vitamin A Deficiency Disorders
peutic keratectomy can be tried in patients with superficial The major cause of blindness in children worldwide is
corneal opacities or irregular corneal surface. xerophthalmia caused by vitamin A deficiency.38 Vitamin A
deficiency is the single most frequent cause of blindness
Managements of Congenital among preschool children in developing countries.37 The term
Corneal Opacities vitamin A deficiency disorders (VADD) has been introduced
to cover the whole clinical spectrum of disease.38
Penetrating keratoplasty is required for providing a clear visual
axis and to prevent onset of dense amblyopia.35-37 Vitamin A deficiency affects growth, the differentiation
(Refer to section on pediatric keratoplasty) of epithelial tissues, and immune competence. The younger
the child, the more severe is the disease and the higher the
ACQUIRED TRAUMATIC risk that corneal destruction will be followed by death.38
CORNEAL OPACIFICATION Vitamin A deficiency affects growth, the differentiation of
epithelial tissues, and immune competence. Vitamin A
Penetrating injuries remain an important cause of acquired deficiency occurs when body stores are exhausted and supply
corneal scarring in the pediatric age group. Penetrating corneal fails to meet the body’s requirements, either because there is
trauma leads to tissue loss, severe anterior segment distortion a dietary insufficiency, increased requirements or poor
and corneal decompensation, with the resultant corneo-iridic intestinal absorption, transport and impaired metabolism as a
scars required to be managed by keratoplasty.1 The most result of conditions such as diarrhea.
important issue to be considered in keratoplasty in children for
penetrating trauma is the threat of amblyopia. Hence, the timing Clinical Features:
of surgery in cases corneal trauma should he at the earliest in • Night blindness.
order to avoid visual deprivation and amblyopia. • Bitot’s spot—Triangular keratotic, foamy areas in the
interpalpebral bulbar conjunctiva.
ACQUIRED NONTRAUMATIC • Xerosis of the conjunctiva and cornea: Xerophthalmia
CORNEAL OPACIFICATION — dry lusterless poorly wettable ocular surface.38
• Corneal ulceration and necrosis of the cornea.
One of the most common causes of acquired corneal scarring
in the western nations before six years of age is herpes simplex Prevention:
keratitis. However, in developing nations, infectious keratitis, • Short-term measures: Administration to vulnerable groups
corneal ulceration with perforation and post-infectious keratitis of single, large doses of vitamin A on a periodic basis
corneoiridic scars remain the main etiological indications for (200,000 IU every 3 to 6 months).38
pediatric corneal morbidity. Penetrating keratoplasty for post • Medium-term measures: Fortification of a dietary vehicle
keratomalacia corneal melts are also more common. (e.g., sugar, monosodium glutamate, butter) with vitamin
Keratomalacia due to vitamin A deficiency is an important A can be initiated.38
cause of preventable corneal opacification.38 Ocular surface • Long-term measures: Increased dietary intake of vitamin
changes include xerosis, keratinized plaques, stromal punched A through home gardening and nutrition education
out ulcers and focal or diffuse stromal melting. Keratomalacia programs.38
Treatment: Oral administration of 200,000 IU vitamin A on abnormalities, blepharitis, neurotrophic keratitis and exposure
two successive days and third dose to be given on keratitis play a minor role in children.42
15th day. Cellular mechanisms: Specific inflammatory responses that occur
during pediatric microbial keratitis are not known in detail,
Pediatric Keratitis but it is likely that cytokines and polymorphonuclear leukocytes
Corneal blindness presents an enormous problem to both are major factors, as they are in adult microbial keratitis.
developing and developed countries in terms of human Cellular mechanisms causing corneal ulceration include
morbidity, economic loss and social burden. World Health following:49
Organization (WHO) has reported that of the 1.5 million • Epithelial cell loss – Trauma, chemical injury.
blind children worldwide, 70,000 have active corneal • Impaired epithelial adherence – Dystrophies, recurrent
involvement.39 Ocular trauma and corneal ulceration are corneal erosion syndrome.
significant causes of corneal blindness that are often under • Impaired epithelial cell replacement – Limbal stem cell
reported and may be responsible for 1.5 to 2.0 million new insufficiency.
cases of monocular blindness every year.40 Infectious keratitis • Direct cytopathic effect – HSV, bacteria, fungi, protozoa.
is one of the leading cause of preventable and treatable • Denervation – Trigeminal ganglion lesion, HZO.
monocular blindness in the developing world. Causes of • Disturbed epithelial cell nutrition – Tear film dysfunction,
childhood blindness (about 1.5 million worldwide with 5 million corneal exposure.
visually disabled) include xerophthalmia (350,000 cases • Disrupted stromal support – Stromal inflammation.
annually), ophthalmia neonatorum, measles, 41 and less
Bacterial keratitis: The most common cause of keratitis is
frequently seen ocular diseases such as herpes simplex virus
bacterial (Figs 6.3.8A and B) followed by mixed bacterial and
infections and vernal keratoconjunctivitis.40
fungal infections.43
Infectious Keratitis Microbiology: The microbiology of childhood keratitis does
Childhood keratitis, though less common than that in adults,42 not differ markedly from keratitis in adults. The most
is more challenging to diagnose and treat, as children are commonly associated pathogens are found to be gram positive
often unwilling and sometimes unable to cooperate during cocci. 43-47 Staphylococcus epidermidis is most commonly
active management. Besides this, the history available is often reported.43 Gram-positive bacilli also account for substantial
incomplete, unreliable and misleading. A delay in management proportion of cases.43,44 Other researchers have reported
may lead not only to blindness but also to amblyopia, especially S. aureus as the commonest gram-positive cocci isolated,
when severe unilateral corneal infection occurs in the early followed by S. pneumoniae and S. epidermidis.41,45 The most
years of life. Microbial keratitis in children is different from commonly isolated gram-negative organism is Pseudomonas
adult keratitis because of severe inflammatory response. The aeruginosa. 39,41-47 It is found that Pseudomonas and fungal
predisposing factors, poor compliance during examination infections are commonly seen at southern latitudes where as
and complications with adverse impact on vision collectively Staphylococus and Streptococcus infections are commonly seen
make it different from adult keratitis. in cooler climates. Keratitis caused by enteric bacilli is rare in
patients younger than 20 years of age.42 Shigella keratitis is
Predisposing factors: Trauma is the most common predisposing
also seen in patient less than 2 years of age. It is reported to
factor.39,42-48 The other important predisposing factors are
directly penetrate the cornea and result in hypopyon
associated systemic illness, previous ocular surgery (e.g.
formation.42
congenital glaucoma surgery), malnutrition and others. Besides
this increased colonization during birth is another important Gram-positive cocci—Staphylococcus epidermidis, Streptococcus
factor. Recently contact lens wear has been found to be most pneumoniae, S. aureus, S. viridans, Corynebacterium species,
common factor in adolescent age group.43 It may be a minor Bacillus species.
trauma, such as a minute abrasion from a small foreign body,
Gram-negative bacilli—Pseudomonas aeruginosa, Klebsiella
or due to causes as tear insufficiency, malnutrition, or contact
species, Moraxella species, Enterobacter species, Serratia species,
lens use. Corneal injury contaminated with vegetable matter
Proteus species.
is responsible for maximum of traumatic cases.39 Vitamin A
deficiency is associated with a breach in epithelium and Clinical features:
therefore, an increase in the incidence of bacterial keratitis.42,43 The Clinical Features are:
Many of the age related risk factors in adults including Symptoms: The patient usually is an irritable child having severe
tear film dysfunction, acquired external ocular disease, lid ocular pain with redness, photophobia, lacrimation, inability
to open eyes and decrease of vision. Purulent or mucopur-

ulent discharge may be present.
Signs: The signs can be graded according to Jones criterion.50
Severity grade of microbial keratitis
Severity grade
Feature Nonsevere Severe
Rate of progression Slow, moderate Rapid
Suppuration: Area <6 mm diameter > 6 mm diameter
Depth Superficial 2/3 Inner 1/3
Depth of ulceration Superficial 1/3 Inner 1/3
Perforation Unlikely to occur Present, imminent
Scleral suppuration Absent Present
(This table was published in Ophthalmology 1981, Vol 88(8), Jones DB.
Decision making in the management of microbial keratitis, p 814-820, copyright
Elsevier, copyright permission March 2011.)
Depending upon the severity, the ulcers may be mild, moderate

or severe in nature.
Grading of severity of keratitis
Factor Grade I Grade II Grade III
Location Nonaxial Central or Central or
peripheral peripheral
Area 2 mm 2-6 mm >6 mm
Depth Superficial Superficial Extending to
1/3rd 1/3rd-2/3rd inner 1/3rd
Anterior None/mild Moderate to Hypopyon
segment severe fibrinous
inflammation infiltrates
Bacterial corneal ulcers are nonspecific as to the etiology

in children; with only 30 percent cases having hypopyon at Fig. 6.3.8A and B: Bacterial keratitis in pediatric patients
presentation.42 A round or oval ulcer may be situated centrally
or peripherally. It’s sides and floor are gray and ragged in cotton swabs and a blood agar plate. Following instillation of
appearance with stromal infiltration and edema. There is proparacaine, ulcer debris is removed using the blade, and
associated conjunctival and circumciliary congestion. Normal the sides and base of the ulcer scraped and smear is prepared.
iris pattern is lost because of iris edema and increase in the Acridine orange is a sensitive stain for staining bacteria, which
permeability of iris vasculature that leads to anterior chamber requires fluorescent microscope. Special stains like Ziehl-
cells, flare, fibrinous exudates and hypopyon. If infection is Neelsen stains are used for Mycobacteria, Nocardia and
not controlled by appropriate treatment then it spreads both Actinomyces. Fluorescent Gram’s stain is also available which
peripherally and into the deeper layers of the cornea. This stains gram positive bacteria as reddish orange and gram
can result in destruction of the stroma as seen in adults, leading negative bacteria as bright green. Children with Shigella
to formation of descemetocele. Subsequent leukocytic infections must have cultures for their stool done, as it is
enzymatic degradation, trauma or raised IOP can result in a commonly seen due to fecal contamination.42
spontaneous perforation.48 With appropriate therapy, the ulcer Scraping should be immediately inoculated in blood agar,
resolves by cicatrization. chocolate agar, nonnutrient agar with E coli, Sabouraud’s
Investigations and Laboratory Diagnosis—General Guidelines: dextrose agar, potato dextrose agar, thioglycollate broth and
Scraping should be done with Kimura spatula or No. 15. BP brain heart infusion for culture and sensitivity.51 Blood agar
knife. Minimum requirements for a scraping kit are 3 slides, is the standard medium for aerobic bacteria and ‘C’ streaks
one each for Grams, Giemsa staining and KOH mount, sterile should be directly made on the culture plate. Saprophytic
fungi can also grow on this agar. Chocolate agar and percent. Treatment with topical fluoroquinolone plus
thioglyacolate broth allow growth of anaerobic bacterium cephalosporin, particularly in areas where streptococci and
along with aerobic. Sabouraud’s dextrose agar and brain heart resistant staphylococci are common, offers a good alternative.
infusion are used for fungal growth. Thayer Martin media is Newer fluoroquinolones such as gatifloxacin and moxifloxacin
specific for N. gonorrhoeae whereas Lowenstein - Jensen’s media offer some theoretical advantages but recent studies have
is used for growth of Mycobacterium. found no significant difference in the rate of healing, cure
Growth of an organism is considered significant when it rate and complications when fortified cephazolin and
is grown on two or more media, grown heavily on solid media tobramycin, was compared with ofloxacin, or moxifloxacin.52
‘C’ streaks, or when growth on one medium is consistent Antibiotic therapy should be changed only if the pathogen is
with smear result. Routine microscopy of smears is helpful reported to be resistant to initial therapy and if the corneal
to screen out fungal infections, arrive at a presumptive ulcer continues to worsen.
etiological diagnosis while culture results are awaited and to The side-effects of these medications must be taken in
corroborate with culture results. to account as these ulcers may require prolong therapy.
Aminoglycosides produce well recognized epithelial toxicity.
Management: The protocol is usually the same as in adults
Prolonged intensive treatment leads to marked epithelial
except that it is difficult due to children’s inability to cooperate,
toxicity with pain, redness, punctate staining, and eventual
both for examination and therapy. They often require
retardation of epithelial healing. Nonhealing epithelial defects
hospitalization to ensure proper examination and treatment.
are far more common in aminoglycoside treated keratitis.53
Prevention: Decreasing incidence of malnutrition in children Ciprofloxacin, ofloxacin and sparfloxacin produces white
and ensuring proper and timely immunization are the keystones epithelial deposition, which can mask the underlying signs
of prevention. and will retard epithelial healing until the drug deposits wash
Early diagnosis: This is the key to proper treatment and early out.53,54
visual rehabilitation of the child. Antibiotic therapy should include systemic administration
following perforation.
Treatment: The objective of therapy is to: Specially care is to be taken to increase compliance in
• To rapidly eliminate the infective organism cases of children. Cycloplegics must be given. Atropine one
• Reduce the inflammatory response percent eye ointment is preferable because of strong ciliary
• Prevent structural damage to the cornea and promote muscle tone in children and infants.
epithelial healing.
• Provide symptomatic relief to the patient Surgical: Small perforations may be managed with fibrin glue/
cyanoacrylate glue.
Medical: Extra care must be taken to ensure nontoxicity due Corneal patch graft may be required for perforations not
to blood adsorption of antibiotics. New microbial keratitis manageable with glue application.
treatments are being developed and these mainly focus on
new antimicrobials, antivirulence agents (such as vaccination Therapeutic Penetrating Keratoplasty is required for larger
against microbial toxins) or specific anti-inflammatory agents. perforations.
Treatment can be started empirically with antibacterials even Fungal Corneal Ulcer:
before the culture sensitivity report is available. The treatment Microbiology: These are responsible for lesser number of
can thereafter be modified as per culture sensitivity reports. cases than bacteria. Filamentous fungi are more commonly
Small peripheral lesions, if not vision threatening, can be isolated.42-44 Aspergillus flavus, A. fumigatus, Fusarium species,
treated with fluoroquinolones alone. Bipolaris species, Alternaria species, Curvularia species,
For a large central sight threatening keratitis, corneal scrape Penicillium species are found to be associated. Vegetable
is mandatory to both isolate resistant organisms as soon as matter is most common cause for fungal corneal ulcer. Corneal
possible and also to identify organisms that may respond injury contaminated with vegetable matter is responsible for
poorly to initial therapy. maximum number of cases.45
The preferred drugs are broad spectrum antibiotics that
cover both gram-positive and gram-negative organisms. Initially Signs and symptoms: Clinical signs and symptoms do not differ
the treatment consists of a combination of fortified from adults, with symptoms not corroborating with the clinical
antibiotics. Cefazolin five percent and Tobramycin 1.3 signs. Ulcer is dry looking with satellite lesions. Hypopyon
may be associated. Feathery hyphate margins of the infiltrate allows widespread ulceration. Recurrent infection if present
can be seen within the stroma. In some cases Wessley immune is typical as in adults.
ring can be seen indicating antigen antibody reaction. Brown • Active infectious epithelial keratitis
or black discoloration of ulcer can be seen in cases of – Punctate keratitis (corneal vesicles)
dermataceous fungi. Untreated ulcers may lead to stromal – Dendritic ulcer
necrosis, desmetocele formation and perforations. – Geographic ulcer (Amoeboid)
– Dendrogeographical
Investigations: Corneal scraping followed by KOH mount and – Marginal keratitis (Limbal ulcer)
lactophenol cotton blue for visualization of fungal hyphae in • Neurotrophic keratopathy (Metaherpetic)
culture should be done. Other stains available for identification • Stromal Keratitis
of fungal elements include Gomori methenamine silver, PAS, – Disciform keratitis
acridine orange and calcoflour white. Gomori methnamine – Diffuse necrotizing stromal keratitis
silver is the best stain for fungal hyphae but the longer time – Immune stromal keratitis (interstitial keratitis)
required. – Limbal vasculitis
Sabouraud’s dextrose Agar and brain heart infusion are • Endothelitis
the culture media used for growth of fungi. Fungi can be – Diffuse
identified in three days time. But media should be observed – Linear
at least for two weeks before declaring it to be negative. – Disciform
Antifungals: Among antifungals, polyenes are the mainstay of Investigations: The diagnosis primarily is clinical. Smears with
the treatment. These include amphotericin B, nystatin and Giemsa stain show ballooning degeneration and a monocyte
natamycin. The polyenes are first line drugs for filamentous white cell infiltrate. Papanicoalau stain and immuno-
fungi, and azoles for yeasts. fluorescence show intranuclear antibodies (Lipshutz bodies)
In addition to topical polyenes, topical imidazoles like in Herpes Simplex and Varicella Zoster virus.
fluconazole or itraconazole may be added. Intracameral use Virus isolation is considered a standard procedure for
of Amphotericin B is helpful in cases of deep kertomycosis.55 diagnosis of viral infections; but it is a relatively time
Severe fungal ulcers require systemic oral or intravenous consuming procedure and depends on viable infectious
fluconazole56 or the newer agent Voriconazole.57 material that usually needs to be transferred to a special virology
laboratory for processing. Rapid diagnostic tests, either enzyme
Viral Keratitis: or fluorescence based immunological detection of HSV-1
Risk Factors: Risk factors for recurrent herpetic infections antigen or polymerase chain reaction (PCR) based detection
include infections, local trauma, sunlight, heat, surgery, of viral DNA may be used.
emotional stress. Treatment: Topical antiviral eye ointment acyclovir 3 percent
is to be given five times daily for 14 to 21 days. It is the least
Microbiology: Commonly, Herpes simplex (HSV), Herpes Zoster
toxic and most potent antiviral available. Gentle debridement
(HZV).
is recommended before application of topical drugs. Other
Clinical Features: Signs and Symptoms: HSV infections are usually antivirals which can be used are trifluorothymidine 1 percent
primary infections, which are mostly seen from 6 months to drops, adenine arabinoside 3 percent ointment and 0.1 percent
5 years of age. Neonates are protected upto 6 months of drops, idoxouridine 0.5 percent ointment and 0.1 percent
age because of maternal antibodies. Clinically disease is drops. Topical steroids are not recommended. Long-term
confined to the epithelium. It is self-limiting but establishes a suppressive oral acyclovir therapy reduces the rate of
latent infection in the trigeminal ganglion. Recurrent infection recurrent HSV epithelial keratitis and stromal keratitis.
is rare in children. Acyclovir is beneficial for patients who have experienced prior
Clinical infection presents as diffuse branching epithelial HSV stromal keratitis.59
keratitis or coarse punctate keratitis.58 This evolves into With frequent application, of a acyclovir eye ointment
multiple scattered microdendritic figures. There may be blurred vision, and foreign body sensation occur and cause
wandering linear serpiginous ulcers across the entire corneal difficulty for patients to follow treatment. Oral acyclovir and
surface. The diffuse nature of this primary epithelial valacyclovir is an effective and safe option for patients with
involvement is due to the host’s nonimmune state, which herpetic keratitis60 in indicated cases.
Parasitic Keratitis: limbus and phlycten. Superficial pannus is associated and

Protozoa: The most common associated organism is ulcer may perforate. Peripheral part heals but central ulcer
Acanthamoeba.61 Other organisms are Entamoeba, Micros- spreads.65,66
poridia, Trypanosoma, Leishmania, Toxoplasma and Giardia. Treatment: Phlycten can be treated with topical corticosteroids.
Long-term topical cyclosporin 2 percent therapy is a safe
Nematodes: Wucheraria bancrofti, Brugia malayi, Onchocercus, Loa
and effective alternative in children with phlyctenular
loa, Dirofilaria.
keratoconjunctivitis associated with severe steroid-dependent
Cestodes: Cysticercosis. corneal inflammation.64
Trematodes: Schistosomiasis. Blepharokeratitis/Blepharokeratoconjunctivitis: This is a
Only Acanthamoeba keratitis is discussed here as other types chronic external ocular and adnexal inflammatory condition
are rarely seen. marked by erythematous and edematous lid margins, crusting
Acanthamoeba keratitis: Acanthamoeba keratitis is rare and scaling of lid margins, meibomian gland inflammation
among children. These are commonly found in fresh water and inspissation of gland secretions, and conjunctival
sources, including, swimming pools, hot tubs, and tap water. hyperemia.
Contact lens solutions are also a source of these organisms. The keratitis involves the inferior cornea (Fig. 6.3.9). The
It can be seen in children using aphakic contact lens. But characteristic features include punctate epithelial keratopathy,
non-contact lens related keratitis is also seen.36 Keratitis occurs marginal stromal infiltrates, phlyctenules, marginal keratitis67,68
in patients with minor corneal trauma and the majority of ulceration, corneal thinning, scarring, and vascularization.
reported cases have been soft contact lens wearers. Suspicion
is the key to diagnose this condition. Treatment:
• Lid hygiene: Removing debris and crusts along the lid
Signs and Symptoms: Patients often present with pain, margin, using cotton wool tipped swab sticks with diluted
photophobia, and irritation. Patients are acutely symptomatic, bicarbonate solution, diluted baby shampoo, and warm
with pain being out of proportion to the corneal signs. Clinical water
characteristics63 include pseudodendrites, stromal ring infiltrate, • Topical corticosteroids
epithelial haze, endothelial infiltrates and radial keratoneuritis. • Topical antibiotics
Later on multifocal stromal infiltrates may lead to disciform
• Oral erythromycin (30-40 mg/kg body weight) is used in
keratitis. A ring infiltrate has been described as pathognomonic
children instead of oral tetracycline and its analogs which
for Acanthamoeba keratitis.60
are used in adults.
Investigations: Slides may be stained with methenamine silver,
Periodic Acid Schiff, Mason trichrome and iron hematoxylin Rosacea keratitis: Sterile corneal ulcers are reported to be
and eosin stains, calcoflour white stain, immunoperoxide stains associated with Acne rosacea.69 Other manifestations include
for Acanthamoeba, fluorescein conjugated lectin (concavalin
A).62 Samples should be inoculated into the center of a plate
of nonnutrient agar with E. coli overlay.
Treatment: The drugs available for treatment include:
• Polyhexamethylene biguanide (PHMB)
• Propamidine isothionate 0.1 percent
• Dibromopropamidine isotheonate 0.15 percent
• Miconazole one percent
• Chlorhexidine
• Neosporin
• Systemic ketoconazole
Other Pediatric Corneal Diseases

Fascicular keratitis: This is associated with phlyctenular
conjunctivitis.64 Corneal phlyctenules usually develop near
limbus and spread centrally. There is no clear zone between Fig. 6.3.9: Healed blepharokeratitis in a child
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inspissations and lid margin telangiectasis, in conjunction with dermoid: a clinicopathologic correlation and review of the
conjunctival injection or episcleritis literature. Can J Ophthalmol 1986;21:23-6.
17. Scheie H, Hambrick G, Barness L. A newly recognised forme
Treatment: Includes management of the meibomian gland fruste of Hurler’s disease (gargoylism). Am J Ophthalmol
1962;53:753.
dysfunction, systemic doxycycline and topical corticosteroids.
18. Quigley HA, Maumenee AE, Stark WJ. Acute glaucoma in systemic
(Allergic diseases are discussed in the section on conjunctival mucopolysaccharidosis I-S. Am J Ophthalmol 1975;80:70.
diseases). 19. Spellacy E, Bankes KJL, Crow J, et al. Glaucoma in a case of
Hurler disease. Br. J Ophthalmol 1980;64:773.
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44. Kunimoto DY, Sharma S, Reddy MK, Gopinathan U, Jyothi J, evaluation of carbocyclic oxetanocin G eyedrops in the treatment
Miller D, et al. Microbial keratitis in children. Ophthalmology of herpes simplex corneal ulcers. Br J Ophthalmol 1996;80(5):
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45. Ormerod LD, Murphree AL, Gomez DS, Schanzlin DJ, Smith 61. Daniell M. Overview: Initial antimicrobial therapy for microbial
RE. Microbial keratitis in children. Ophthalmology 1986;93:449- keratitis. Br J Ophthalmol 2003; 87:1172-4.
55. 62. Sharma S, Garg P, Rao GN. Patient characteristics, diagnosis, and
46. Vajpayee RB, Ray M, Panda A, Sharma N, Taylor HR, Murthy GV, treatment of non-contact lens related Acanthamoeba keratitis Br
Satpathy G, Pandey RM. Risk factors for pediatric presumed J Ophthalmol 2000;84:1103-8.
microbial keratitis: a case-control study. Cornea 1999;18:565-9. 63. Hassanlou M, Bhargava A, Hodge WG. Bilateral acanthamoeba
47. Bharathi MJ, Ramakrishnan R, Meenakshi R, Padmavathy S, keratitis and treatment strategy based on lesion depth. Can J
Shivakumar C, Srinivasan M. Microbial keratitis in South India: Ophthalmol 2006:41;71-3.
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Ophthalmic Epidemiol 2007;14(2):61-9. Xuan T. Topical cyclosporine A in severe steroid-dependent
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clinical diagnosis and management II Ed WB Saunders 2006;141:62-6.
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Chapter 6.4
CORNEAL DYSTROPHIES
Jaya Gupta, Radhika Tandon
Corneal dystrophies are a heterogeneous group of inherited • Lisch epithelial corneal dystrophy (LECD) C2
corneal diseases that are typically bilateral, symmetric, slowly • Gelatinous drop-like corneal dystrophy (GDLD) C1
progressive and without relationship to environmental or systemic
factors. They have been typically classified by level of the cornea Bowman Layer Dystrophies
that is involved which separates these entities into: • Reis-Bücklers corneal dystrophy (RBCD)—Granular
• Epithelial corneal dystrophy type 3 C1
• Subepithelial • Thiel-Behnke corneal dystrophy (TBCD) C1, potential
• Bowman layer variant C2
• Stromal • Grayson-Wilbrandt corneal dystrophy (GWCD) C4
• Descemet’s membrane
• Endothelial. Stromal Dystrophies
Advances in molecular genetics over the past years have • TGFBI corneal dystrophies
provided an insight into the defects leading to various corneal – Lattice corneal dystrophy:
dystrophies, such that there is a shift towards integration of i. Lattice corneal dystrophy, TGFBI type (LCD):
the genetic information into the existing method of Classic lattice corneal dystrophy (LCD1) C1,
classification.1-4 In the recently proposed IC3D classification1 variants (III, IIIA, I/IIIA, and IV) are C1
of corneal dystrophies (www.corneasociety.org/ic3d) there are ii. Lattice corneal dystrophy, gelsolin type (LCD2)
4 categories of which the most defined dystrophies belong to C1 (This is not a true corneal dystrophy but is
category 1 (a well-defined corneal dystrophy in which a gene included here for ease of differential diagnosis).
has been mapped and identified and specific mutations are – Granular corneal dystrophy C1:
known) and the least defined belong to category 4 (a suspected i. Granular corneal dystrophy, type 1 (classic)
dystrophy where the clinical and genetic evidence is not yet (GCD1) C1
convincing). ii. Granular corneal dystrophy, type 2 (granular-
lattice) (GCD2) C1
THE IC3D CLASSIFICATION iii. Granular corneal dystrophy, type 3 (RBCD)—
Epithelial and Subepithelial Dystrophies Reis-Bücklers C1.
• Epithelial basement membrane dystrophy (EBMD) — • Macular corneal dystrophy (MCD) C1
majority degenerative, some C1 • Schnyder corneal dystrophy (SCD) C1
• Epithelial recurrent erosion dystrophy (ERED) C4, • Congenital stromal corneal dystrophy (CSCD) C1
(Smolandiensis variant) C3 • Fleck corneal dystrophy (FCD) C1
• Subepithelial mucinous corneal dystrophy (SMCD) C4 • Posterior amorphous corneal dystrophy (PACD) C3
• Mutation in keratin genes—Meesmann corneal dystrophy • Central cloudy dystrophy of Francxois (CCDF) C4
(MECD) C1 • Pre-Descemet’s corneal dystrophy (PDCD) C4
Corneal Dystrophies 431
Descemet’s Membrane and so called maps, i.e. geographic lesions consisting of irregular
Endothelial Dystrophies islands of thickened hazy epithelium delimited by scalloped
borders associated or not with dots, fingerprints and blebs.
• Fuchs endothelial corneal dystrophy (FECD) C1, C2, or C3 Cogan’s dots are round, oval (50–500 microns in diameters)
• Posterior polymorphous corneal dystrophy (PPCD) C1 or comma-shaped grayish opacities clustered in an archipelago-
or C2 like manner in the central cornea. Fingerprint lines correspond
• Congenital hereditary endothelial dystrophy 1 (CHED1) C2 to parallel, curvilinear lines best seen in retro-illumination.
• Congenital hereditary endothelial dystrophy 2 (CHED2) C1 Bron’s blebs are clumped subepithelial transparent cysts (15–
• X-linked endothelial corneal dystrophy (XECD) C2 100 microns in diameter) best seen on retro-illumination.
[C = CATEGORY, (C1) Category 1: A well-defined corneal The location and degree of dots, maps or fingerprint
dystrophy in which the gene has been mapped and identified opacities can fluctuate with time.
and specific mutations are known. (C2) Category 2: A well-
defined corneal dystrophy that has been mapped to one or Histopathology
more specific chromosomal loci, but the gene(s) remains to
be identified. (C3) Category 3: A well-defined corneal EBMD occurs due to synthesis of abnormal multilaminar
dystrophy in which the disorder has not yet been mapped to basement membrane both in normal location and
a chromosomal locus. (C4) Category 4: This category is intraepithelially. As the intraepithelial basement membrane
reserved for a suspected new, or previously documented, thickens, it blocks normal migration of epithelial cells towards
corneal dystrophy, although the evidence for it, being a distinct the surface. Trapped epithelial cells degenerate to form
entity, is not yet convincing.] intraepithelial microcysts that slowly migrate to the surface.
Abnormal basement membrane produces map and fingerprint
(Republished from Cornea, The IC3D classification of the corneal dystrophies, changes and microcysts produce the dot pattern seen clinically.
Weiss JS, et al, 2008, Vol 27, Suppl 2: S1-83, with permission from Lippincott
Williams and Wilkins, Wolters Kluver Health, copyright notice March 2011)
Treatment
EPITHELIAL AND SUBEPITHELIAL Treatment in EBMD is directed towards improving blurred
DYSTROPHIES vision or managing recurrent corneal erosion. It consists of
lubricants, hypertonic saline drops, patching or bandage
Epithelial Basement Membrane Dystrophy contact lenses. Mechanical debridement of the loosened
(Map-dot-fingerprint dystrophy, Cogan’s epithelium with or without diamond burr polishing can be
microcystic epithelial dystrophy, anterior attempted. With more recalcitrant recurrent corneal erosions
basement membrane dystrophy) anterior stromal reinforcement or puncture with a bent 24 or
25 gauge needle or else if the recurrent erosion is in the visual
Epithelial basement membrane dystrophy (EBMD) is the most
axis, excimer laser phototherapeutic keratectomy (PTK) can
common of the anterior corneal dystrophies with no definite
be undertaken.
hereditary pattern but at times may be inherited as an
autosomal dominant trait. The genomic localization is
Meesmann’s Juvenile
unknown; however two distinct TGFB1 mutations have
Epithelial Dystrophy
recently been reported.
(Juvenile hereditary epithelial dystrophy,
The first description of this slowly progressive early adult
Stocker-Holt variant)
onset corneal dystrophy was given by Vogt in 1930 and was
further characterized by Cogan (dots=microcysts), Guerry This rare, bilaterally symmetric, hereditary epithelial dystrophy
(maps) and Bron (blebs). is inherited in an autosomal dominant pattern with the two
genetic loci been identified on chromosome 12q13 and 17q12
Clinical Features corresponding to the genes coding for two constitutive
intermediate filaments of the cornea, keratin 3 (KRT3) and
The condition is either asymptomatic or may cause recurrent 12 (KRT12). These proteins are coexpressed in the anterior
erosions with pain on waking in the morning, photophobia corneal epithelium to form heterodimers for intermediate
and reduced visual acuity with the lesions presenting in one filament assembly required for the structural integrity of the
particular area of cornea. Slit lamp examination reveals the cell. The mutant protein has a dominant negative effect with
aberrant assembly of intermediate filaments, causing occur. Direct illumination shows localized gray opacities in
disruption of keratinocyte filament architecture and cell lysis different patterns: whorl-like, radial, band shaped flame/
when subject to mild trauma. feathery shaped and club shaped. Indirect illumination
demonstrates multiple, densely crowded clear cysts. The
Clinical Features surrounding epithelium is clear. There is no difference
Onset is typically in early childhood with the appearance of observed between males and females.
multiple intraepithelial vesicles/ microcysts, which increase in
Histopathology
number through life. The epithelial microcysts are present
primarily in the visual axis and in the midperiphery best seen Light microscopy demonstrates diffuse cytoplasmic
on retroillumination. Grey serpiginous lines and subepithelial vacuolization of the affected epithelium across its whole
opacities may also be seen in advanced cases. Vision is usually thickness, containing osmophilic, partly homogeneous and
good in the first few years of life and diminishes gradually if partly lamellar material upon electron microscopy.
the cysts increase in number and cause irregularity of the
surface. Symptoms are usually mild or nonexistent, may Treatment
manifest with photophobia, recurrent punctiform epithelial
Usually treated with refraction and lubricating eye drops.
erosions and lacrimation.
Phototherapeutic keratectomy (PTK) can be done if and when
Histopathology clinically indicated, provided corneal thickness is adequate.
The epithelium always demonstrates intraepithelial cysts. Cysts Gelatinous Drop-like Corneal Dystrophy
are filled with periodic acid Schiff-positive ‘peculiar substance’ (Subepithelial amyloidosis, primary familial
shown to be keratin aggregates under electron microscopy. amyloidosis)
There is slight acanthosis and thickening of epithelium
and basal membrane. Gelatinous drop-like corneal dystrophy (GDLD) (Figs 6.4.1A
When imaged by in vivo confocal microscopy, these to I) is a rare autosomal recessive disorder known to be caused
intraepithelial cysts appear as hyporeflective areas in the basal from mutations in the tumor-associated calcium signal
epithelium ranging from 40 to 150 µm in diameter with transducer 2 (TACSTD2) gene located on the short arm of
potential reflective spots inside. This may represent the chromosome 1 (1p32).5,6 The abnormalities in this gene
‘peculiar substance’ and tonofilament bundles observed in affects epithelial cell junctions resulting in increased epithelial
electron microscopy studies. permeability and thus subepithelial amyloid deposition caused
by the penetration of tear components and serum factors
Treatment into the subepithelium.7,8
As symptoms are minimal and visual loss is rare, patients Clinical Features
usually do not require much treatment. Lubricants for minute
erosions may be required. First described by Nakaizumi in 1914 in a Japanese patient,
GDLD is characterized by the deposition of amyloid material
Lisch Corneal Dystrophy in the subepithelial space of the cornea. GDLD corneas
(Band shaped and whorled microcystic demonstrate various clinical phenotypes:9 band keratopathy
dystrophy of the corneal epithelium) type, stromal opacity type, kumquat like type and typical
mulberry type which may depend on secondary factors such
This slowly progressive bilateral epithelial disorder, first as tears, micro scars of the epithelium, eyelid, glands, systemic
described in 1992, has been reported to have X-linked disease and trichiasis apart from other modulating factors at
dominant inheritance with the genetic locus being mapped the genetic level. Initially, the subepithelial lesions may appear
on the short arm of chromosome X (Xp22.3). similar to band-shaped keratopathy or there may be groups
of small multiple nodules, that is, mulberry configuration.
Clinical Features These lesions demonstrate late staining with fluorescein,
The patients remain asymptomatic as long as the visual axis indicating extremely hyperpermeable corneal epithelium.
is uninvolved, which may last until the third decade of life Corneal neovascularization also accompanies advanced
when slight photophobia and ultimately blurred vision can cases. 10 In later life, patients may also develop stromal
Figs 6.4.1A to I: Gelatinous drop–like corneal dystrophy (A) Kumquat–like type (B) Mulberry type (C) Band keratopathy type (D) Hematoxylin
and eosin staining—amyloid deposition (arrow); (E to G) in vivo confocal microscopy showing bright reflective material at basal epithelium; (H
and I) Drop-like globular structures in confocal microscopy
opacification or develop larger nodular lesions, that is, Treatment

kumquat-like lesions Corneal transplantation is a major therapeutic option besides
Clinical symptoms of photophobia, tearing and ocular lamellar keratoplasty, photoablation, keratectomy and limbal
foreign body sensation often manifest within the first decade stem cell transplantation. 12 However, the recurrence rate is
of life. The deposits typically enlarge with increasing age; their significant.
accumulation within and beneath the corneal epithelium or
within the anterior stroma eventually leads to severe bilateral BOWMAN LAYER DYSTROPHIES
vision loss by the third decade of life.
Reis–Bücklers Corneal Dystrophy
Histopathology (Corneal dystrophy of Bowman layer, type I
(CDB I), Superficial granular corneal
Histopathology demonstrates amyloid in the subepithelium and
dystrophy, Granular corneal dystrophy, type 3)
anterior stroma and Bowman’s membrane is usually absent.11
In vivo confocal microscopy has shown accumulations of Although first described by Reis in 1917 and later delineated
brightly reflective amyloid material within or beneath the by Bucklers in 1949, this clinical entity (Figs 6.4.2A to F) was
epithelium and within the anterior stroma. In addition drop- frequently confused with Thiel-Behnke corneal dystrophy until
like globular structures at basal epithelium are seen in the band the molecular basis of these closely related conditions was
keratopathy.6 unambiguously identified by Okada in 1998.
Figs 6.4.2A to F: Reis-Bücklers corneal dystrophy (A and B) Diffuse, illumination, (C) Slit beam demonstrating reticular superficial opacity; (D)
Recurrence in grafted eye; (E and F) in vivo confocal microscopy showing homogeneous reflective material in the basal epithelium
Reis-Bückler’s corneal dystrophy (RBCD) has an auto- opacities with peripheral cornea typically uninvolved. Opacities
somal dominant pattern with a mutation of Arg124Leu can progress to deep stromal layers and corneal periphery.
(R124L) at 5q31 gene locus.13,14 Recurrent corneal erosions cause ocular discomfort and pain
in the first and second decade. Gradual visual impairment
Clinical Features develops later. Erosions are less frequent and the onset of
Onset is during the first decade with recurrent corneal erosions visual impairment is later than in RBCD.
leading to early marked visual impairment. Clinically, confluent
Histopathology
irregular and coarse geographic-like opacities with varying
densities develop at the level of Bowman layer and superficial Light microscopy demonstrates a destructed Bowman’s layer
stroma, initially separated from one another. Opacities may replaced by a fibrocellular layer between epithelium and stroma
extend to the limbus and deeper stroma with time. with a pathognomonic wavy saw-toothed pattern. CDB II
stains only equivocally to Masson’s stain. Presence of
Histopathology keratoepithelin stain positive ‘curly’ collagen fibers seen by
transmission electron microscopy is pathognomonic and
Light microscopy typically displays a sheet like connective
tissue layer, replacing the Bowman’s layer with granular Masson distinguishes this dystrophy from RBCD.
trichrome-red deposits which in advanced cases can extend to In vivo confocal microscopy demonstrates focal deposits
the subepithelial stroma. Electron microscopy allows the of reflective material almost exclusively in Bowman’s layer.15,16
identification of electron-dense rod-shaped bodies
Treatment
staining positively for keratoepithelin, the product of TGFB1
(BIGH3). Initially treatable with refraction and lubricating eye drops,
In vivo confocal microscopy shows focal deposition of a more severe opacification warrants therapy with photo-
homogeneous reflective material in the basal epithelial cell therapeutic keratectomy (PTK) or lamellar keratoplasty (LK).
layer.15,16 The Bowman layer is replaced by highly reflective As patients with a tendency to keloid formation or excessive
irregular material. scarring can sometimes have exuberant fibrosis and excessive
corneal opacification after PTK, careful history and case
Treatment selection is important.
Early in the course of the disease when only recurrent corneal
erosions occur, they can be managed similar to the therapy STROMAL DYSTROPHIES
of recurrent erosion due to EBMD. For later presentations TGFB1 Dystrophies
with superficial corneal scarring excimer laser phototherapeutic
Lattice Corneal Dystrophy, TGFB1 Type
keratectomy is now the treatment of choice. Lamellar and
penetrating keratoplasty is performed in advanced cases with (Classic Lattice Corneal Dystrophy (LCD1)
deep scarring and opacities. Recurrence of the dystrophy in and Variants, Biber-Haab-Dimmer)
the graft is frequent.
Biber reported the first description of lattice corneal dystrophy
Thiel-Behnke Corneal Dystrophy (LCD) (Figs 6.4.3A to I) in his medical thesis in Zurich.
(Corneal dystrophy of Bowman layer, Numerous variants of TGFB1 related lattice dystrophy have
type II (CDB II), Honeycomb-shaped been reported (types IIIA, intermediate I/IIIA and IV).
corneal dystrophy) It has an autosomal dominant mode of inheritance and is
The initial report of this slowly progressive autosomal characterized by amyloid deposition within the stroma in a linear
dominant disorder was published in 1967 by Thiel and pattern. The disease results from mutations at 5q31 gene locus
Behnke. A TGFB1 mutation of Arg555Glu (R555Q) is the (Arg124Cys; Ala 546Asp; Pro551Gln and Leu518Pro).13,14
predominant causative mechanism. Further genetic
Clinical Features
heterogeneity is implied by the identification of a locus on
chromosome 10q24.13,14 The dystrophy manifests in the first or second decade with
the appearance of thin branching refractile lines and/or
Clinical Features subepithelial, whitish, ovoid dots. The lines start centrally and
In Thiel-Behnke corneal dystrophy (TBCD) from an early more superficially, spreading centrifugally and deeply but
age, there are symmetrical subepithelial reticular (honeycomb) leaving the peripheral 1 mm and Descemet’s membrane and
endothelium clear. A diffuse stromal, ground-glass haze usually intensely with Congo red, and shows birefringence and
develops later, accompanied by recurrent erosions. The dichroism. Electron microscopy shows fine filaments of 8 to
number of lattice lines may differ between the two eyes 10 nm intermingled with collagenous fibers.
(unilateral cases have also been described). In vivo confocal microscopy shows linear and branching
Ocular discomfort, pain, visual impairment starts early as structures in the stroma with changing reflectivity and poorly
in the first decade of life, with recurrent erosions being frequent. demarcated margins.16,17
Histopathology Treatment
Histological analysis shows amorphous deposits (amyloid) in Recurrent erosions are treated with routine patching,
anterior stromal layers extending posteriorly which stain hypertonic agents, artificial tears or a therapeutic contact lens.
Figs 6.4.3A to D: Lattice corneal dystrophy TGFB1 type (classic lattice): (A and B) Thin branching lattice
lines and dots in retroillumination; (C and D) Magnified view of slit beam
Figs 6.4.3E to I: (E) Magnified view of slit beam. (F) Opacification in more advanced disease. (G and H) At the levels of superficial and
middle stroma highly reflective branching filaments are observed in in vivo confocal microscopy; (I) Normal endothelium
Excimer laser PTK has also been described as an optional LCD Variants
treatment. If visual acuity is impaired, lamellar or penetrating LCD variants (type IIIA, I/IIIA, IV and polymorphic
keratoplasty can be performed. amyloidosis) have a delayed onset compared with classic LCD
Recurrence can appear in the graft as early as three years (LCD, type I). The lattice lines may be larger, with a limbus
after keratoplasty; however recurrence of lattice lines is to limbus ropy appearance (type IIIA), thinner (type I/IIIA)
unusual. More commonly diffuse dot like or filamentous or even absent (polymorphic amyloidosis), although one has
subepithelial opacities or diffuse anterior stromal haze is seen. to remember that the lattice pattern is very much age-
dependent. Corneal erosions are a typically presenting sign Granular Corneal Dystrophy, Type 1
of LCD type IIIA and I/IIIA but are virtually absent in (Classic)
LCD type IV and polymorphic corneal amyloidosis which (Groenouw Type I corneal dystrophy)
probably reflects the anterior to posterior (type IIIA and I/
First described in 1890 by Groenouw, granular corneal
IIIA) or posterior to anterior (type IV) progression of the
dystrophy. dystrophy (GCDI) (Figs 6.4.4A to H) is transmitted as an
autosomal dominant trait with 100 percent penetrance and
Lattice Corneal Dystrophy, Gelsolin Type variable expressivity. In the vast majority of cases, the disease
causing mutation is a substitution of arginine in position 555
(LCD2)
by a tryptophane (R555W) in the TGFB1 (BIGH3) gene on
(Finnish type, Familial amyloidosis, Meretoja
chromosome 5q31. Discrete mutants such as R124S (arginine
syndrome)
replaced by serine) also causes this subtype.
This form of autosomal dominant lattice corneal dystrophy
is distinct from lattice I, III and IIIa and is characterized by Clinical Features
multisystem manifestations due to systemic amyloidosis. It
Onset is in the first decade of life becoming obvious at puberty.
occurs due to mutation of gelsolin gene (Asp187Asn and
Clinically small, discrete, sharply demarcated, grayish-white
Asn187Tyr) that is located on chromosome 9q34. Gelsolin is
opacities in the anterior central stroma are seen. The opacities
an actin filament modulating protein with an actin-regulating
are usually grouped into three basic morphologic types: drop
domain found in leucocytes, platelets and other cells. The
amyloid protein in the Finnish type of hereditary amyloidosis shaped, bread crumb shaped and ring shaped (clear center).
is a fragment of the actin-filament binding region of a variant The overall pattern of deposition is ray or disk-shaped.
gelsolin molecule. The mutant protein is abnormally processed Progression results in an increase in the number, density, size
resulting in aberrant secretion of an amyloidogenic fragment. and depth of opacities; however the intervening stroma and
peripheral cornea remain characteristically clear (unlike macular
Clinical Features corneal dystrophy). Homozygotes have more severe
manifestations. Symptoms include pain from recurrent
Clinical corneal changes are seen in 3rd to 4th decade with
epithelial erosions and decreased vision due to subepithelial
recurrent epithelial erosions and visual loss not as frequent
scarring or dense stromal deposits.
or severe as in other LCD. Slit examination reveals fewer,
more peripheral lattice lines in the corneal stroma, spreading
Histopathology
centripetally from the limbus. The central cornea is relatively
spared. Pronounced dermatochalasis is typical and Multiple stromal deposits may extend from deep epithelium
lagophthalmos common later in life. Glaucoma may also be to Descemet’s membrane. The hyaline opacities stain with
present and this is thought to be secondary to amyloid Masson trichrome. On electron microscopy, dense rod-like
deposition in the trabecular meshwork. deposits are seen within and near keratocytes. These abnormal
Systemic features are due to cranial and peripheral deposits react with antibodies to transforming growth factor
neuropathies—facial paresis, bulbar palsy, lagophthalmos and beta-induced protein (keratoepithelin).
autonomic nervous dysfunction. Lax skin, nephrotic syndrome, When imaged by in vivo confocal microscopy, hyper-
renal failure and cardiomyopathy have also been described. reflective opacities located between basal and intermediate cell
Histopathology layer obscuring other microstructural details are seen.16,17 In
milder cases, well defined reflective deposits with a variety of
Amyloid is deposited in cornea in lattice lines as a morphological forms may be observed in the anterior and
discontinuous band under Bowman layer and within the sclera. intermediate stroma.
Deposition of mutated gelsolin is detected in conjunctiva,
sclera, stroma of ciliary body, along choriocapillaris, in Treatment
perineurium of ciliary nerves, in walls of ciliary vessels and
in optic nerve. Most patients with granular dystrophy do not require
Thick anterior and midstromal filaments located between treatment. Recurrent epithelial erosions are managed routinely
collagen lamellae are observed in in vivo confocal microscopy. with therapeutic contact lenses and artificial tears. With
Prominent deposits, presumably amyloid, are seen contiguous progression of the lesions, epithelial scraping, superficial
to basal epithelial cells and stromal nerves. keratectomy or lamellar keratoplasty can be performed. The
Figs 6.4.4A to F: Granular corneal dystrophy Type 1 (A and B) Discrete stromal opacities (note variation in shape of opacities) axially
distributed with clear intervening stroma (C) Slit beam view; (D) Bread crumb like deposits; (E) Verticillate opacity; (F) In retroillumination;
Figs 6.4.4G and H: In vivo confocal microscopy; showing large hyper-reflective opacities
phototherapeutic keratectomy (PTK) with argon fluoride Initial slit lamp signs are subtle superficial stromal tiny
excimer laser can be used to treat superficial granular whitish dots. In the next stage, rings or stellate-shaped
dystrophy. A penetrating or deep anterior lamellar keratoplasty snowflake opacities appear between the superficial stroma
would be needed for more advanced cases. and the midstroma. The lattice lines seen in some patients
Recurrences of the disease in the graft can be seen as a are typically located deeper than the snowflake stromal
diffuse haze in the periphery or granular lesions in the stroma. opacity. In the final stage, there is more superficial,
translucent flattened breadcrumb opacity which may
Granular Corneal Dystrophy, Type 2 coalesce in the anterior stroma. The stromal haze seen in
(Granular-Lattice) patients with advanced granular and lattice opacities become
(Combined granular-lattice corneal more prominent with age.
dystrophy, Avellino corneal dystrophy) Vision decreases with age only if the central visual axis is
The initial description of this entity, granular corneal dystrophy affected. Pain may accompany recurrent erosions which are
type 2 (GCD2) was independently recognized by Weidle and however rare.
Foldberg. The condition (Figs 6.4.5A to D) has been named
Histopathology
Avellino after the Italian province near Naples where the
first affected families originated. Inheritance is autosomal The opacities, upon light microscopy, extend from basal
dominant with near complete penetrance and incomplete epithelium to deep stroma, and stain either with Masson
dominance. The disease causing mutation is a heterozygote Trichrome or with Congo red, indicating deposition of both
substitution of arginine to histidine at residue 124 in the hyaline and amyloid keratoepithelin-positive material. Rod-
TGFB1 (BIGH3) gene on chromosome 5q31.13,14,18 shaped bodies and fibrils are the corresponding EM findings.
Clinical Features When imaged by in vivo confocal microscopy, highly
reflective granular materials with irregular edges are observed
Disease onset is in the second decade and the cornea in superficial stroma. Linear branching deposits suggestive of
demonstrates both granular and lattice-like, branching deposits lattice lesions may or may not be seen.17,18
within the stroma. The granular opacities located in the
subepithelial and anterior stromal corneal layers are fewer Treatment
than in GCDI and have an earlier onset than the lattice-like
deposits. The lattice lines develop in the second and third decade Treatment is conservative and includes hypertonic saline and
or even later and differ from the ones present in typical lattice bandage contact lenses for recurrent erosions. PTK has been
corneal dystrophy in being larger, denser, whiter, and more used to treat corneal erosions and to clear the central cornea
spiculated.19,20 of granular and lattice deposits. Penetrating/deep anterior
Figs 6.4.5A to D: Avellino corneal dystrophy, (A) Ribbon like and disk shaped opacities in a genetically confirmed R124H mutation; (B) Same
family probands daughter had crumb like opacities with few ray like linear deposits in superficial stroma; (C) Highly reflective granular material
seen in the basal epithelial layer in in vivo confocal microscopy; (D) Surrounding stromal keratocyte nuclei appeared normal
lamellar keratoplasty is required in late in the course of disease. N-acetylglucosamine-6-sulfotransferase (carbohydrate

Recurrences do occur and the granular lesions seem to appear sulfotransferase 6) gene (CHST6) on chromosome 16q21.21-23
first. CHST6 encodes the enzyme, corneal N-acetylglucosamine-
Injury to the central cornea results in exacerbation of the 6-sulfotransferase which initiates sulphation of keratan
corneal dystrophy with increased opacification. LASIK is sulphate (KCS) in the cornea. The pathogenesis of macular
contraindicated in this dystrophy. dystrophy is thought to result from incomplete
glycosaminoglycan sulfation.
Macular Corneal Dystrophy
(Groenouw corneal dystrophy type II, Clinical Features
Fehr spotted dystrophy)
Clinically the disease is recognizable between the 1st and 3rd
Macular corneal dystrophy (MCD) is a slowly progressive decade by a diffuse stromal haze initially affecting the central
condition (Figs 6.4.6A to H) first reported in 1890 by cornea, then extending to the limbus. Later superficial central
Groenouw and is transmitted as an autosomal recessive trait. elevated irregular whitish opacities (macules) develop. Unlike
The disease is linked to the transmission of mutations in the granular dystrophy, there are no clear areas between corneal
opacities. There are also more posterior peripheral white affected as the host keratocytes invade its superficial and
lesions. The cornea is thinner than normal in early disease deeper layers.
and is probably due to close-packing of collagen fibrils.24 In
the advanced stage the corneal endothelium is affected and Schnyder Corneal Dystrophy
Descemet’s membrane develops guttate excrescenses. In (Schnyder Crystalline Corneal Dystrophy)
addition the stroma thickens from the imbibition of water Schnyder corneal dystrophy (SCD) is a rare stromal dystrophy
from endothelial decompensation.
with an autosomal dominant inheritance. It was first described
Vision is significantly reduced between the 3rd and 4th by Van Went and Wibaut and the characteristics were further
decade. Painful attacks and photophobia occur due to recurrent described by Schnyder. The responsible gene has been mapped
erosions. to chromosome 1p36 and is due to mutations in the UBIADI
gene.
Histopathology
Glycosaminoglycans (GAGs) staining with Alcian blue and Clinical Features
colloidal iron, accumulate intracellularly and extracellularly in
Onset is early in life, primarily presenting with a central discoid
the corneal stroma as well as in the Descemet’s membrane
opacity just posterior to Bowman’s membrane, in the anterior
and endothelium. The extracellular matrix observed in electron
stroma. The opacity consists of small, needle-shaped refractile
microscopy contains clumps of fibrillogranular material
crystals that are either white or polychromatic and have the
staining positively for glycosaminoglycans while keratocytes
appearance of ‘glass wool’. These deposits may extend
also stain positive for GAGs.
irregularly into deeper layers causing the entire cornea to
In systemic mucopolysaccharidoses, the abnormal material
appear hazy. Only 50 percent of patients demonstrate the
accumulates in lysosomal vacuoles and there is a generalized
corneal crystals.
abnormality in the breakdown of mucopolysaccharides.
Both affected and unaffected members of the pedigrees
MCD when imaged by in vivo confocal microscopy, highly
may have hyperlipoproteinemia.
reflective deposits without distinct borders are observed in
Vision decreases with age as does the corneal sensation.
basal epithelial layer and superficial stroma. Also homogeneous
reflective material with dark striae like images is seen in Histopathology
superficial and middle stroma.17
Histologically abnormal deposition of intra-and-extracellular
Additional Findings esterified and unesterified phospholipids and cholesterol is
seen in basal epithelial cells, Bowman’s layer and stroma.
Macular corneal dystrophy is divided into three subgroups
Imaging in vivo confocal microscopy reveals multiple
on the basis of immunohistochemical studies and serum
deposits of brightly reflective crystalline material, most
analysis of antigenic keratan sulfate (AgKS).
abundant in the stroma.
Macular corneal dystrophy type I: No AgKS reactivity in
the cornea or in the serum. Treatment
Macular corneal dystrophy type IA: Keratocytes manifest
AgKS reactivity but the extracellular material does not. Serum Penetrating keratoplasty is required as the visual acuity
lacks AgKS. deteriorates. Recurrence of cholesterol crystals may occur in
Macular corneal dystrophy type II: All the abnormal either lamellar or penetrating grafts.
accumulations react positively with AgKS and the serum has
normal or lower levels of AgKS. Congenital Hereditary Stromal Dystrophy
Described by Turpin in 1939, this rare nonprogressive,
Treatment
bilateral, congenital, inherited opacification of the cornea is
Penetrating keratoplasty is the surgical modality of choice not related to abnormal endothelial cell function. It is probably
since there is an involvement of almost all layers of the related to disordered stromal fibrogenesis. The heredity is
cornea. However, recurrences are seen in both lamellar and autosomal dominant and is determined by mutations in the
penetrating grafts. The periphery of the graft is the most decorin gene (DCN) on chromosome 12q22.
Figs 6.4.6A to F: Macular corneal dystrophy: (A and B) Early disease with few gray white round deposits separated by hazy intervening
stroma; (C and D) More advanced disease with stromal opacities at multiple levels and diffuse stromal haze; (E) Slit beam view; (F) Highly
reflective deposits seen in the superficial stroma, in confocal microscopy
Figs 6.4.6G and H: (G and H) Dark striae like images seen in superical to mid stroma in in vivo confocal microscopy
Clinical Features nonprogressive endothelial dystrophy which was first

described by Koeppe in 1916. It usually demonstrates
The diagnosis is done at birth in the presence of diffuse
autosomal dominant inheritance and mutations in VSX1
bilateral corneal clouding with flake-like, whitish opacities, both
homeobox (on chromosome 20q11) and COL8A2 (on
equally distributed throughout the stroma. Epithelium and
chromosome 1p) gene has been identified.25-28
endothelium are normal. The stromal thickness is not
increased. There are no signs of vascularization or staining
Clinical Features
with fluorescein.
Moderate to severe visual loss, dense amblyopia and Onset is highly variable and often seen in adulthood, but may
searching nystagmus may develop. be present at birth. Clinically PPCD is characterized by the
presence of endothelial lesions which have been classified into
Histopathology three main forms: vesicular, band and diffuse. Vesicles appear
There is fibrillar dissociation of corneal lamellae which upon as endothelial blisters or blebs on slit lamp examination and
electron microscopy corresponds to abnormal layers of thin these may be isolated or form clusters or curvilinear patterns.
filaments randomly arranged in an electron lucent ground Band lesions are characterized by strips of guttate-like
substance, which separate lamellae of normal appearance. The irregularities of Descemet’s membrane and diffuse PPCD is
collagen fibril diameter in all lamellae is roughly half that of seen as diffuse irregularities in Descemet’s membrane often
normal collagen fibrils. associated with corneal edema. Peripheral iridocorneal
adhesions and rarely secondary subepithelial band keratopathy
Treatment may be seen. Glaucoma and keratoconus are other associations
described with PPCD.
Penetrating keratoplasty at an early age to prevent dense Endothelial alterations are often asymptomatic, rarely
amblyopia is often indicated. Recurrence in the corneal graft extensive and progressive visual impairment due to stromal
is rare. clouding may be seen.
PPCD and iridocorneal endothelial (ICE) syndrome share
DESCEMET’S MEMBRANE AND
many clinical features, however the sporadic nature and
ENDOTHELIAL DYSTROPHIES
unilateral involvement of ICE may at times help distinguish
Posterior Polymorphous Corneal the latter.
Dystrophy
(Schlichting dystrophy) Histopathology
Posterior polymorphous corneal dystrophy (PPCD) (Figs The Descemet’s membrane consists of an abnormal anterior
6.4.7A to K) is an uncommon bilateral hereditary, typically band and an abnormal posterior collagenous layer manifesting
Figs 6.4.7A to E: (A to D) Slit-lamp biomicroscopic photographs of

PPMD. (E) Specular microscopy in PPMD
Figs 6.4.7F to K: Confocal microscopy images in PPCD

focal fusiform or nodular excrescences. In the periphery the disease include presence of iridocorneal adhesions and
endothelial cells show metaplasia and epithelialization with increased intraocular pressure. PPCD can recur after
desmosomal attachments, microvilli and intermediate filaments transplantation.
and are multilayered.
The focal presence of two to three or even four to five Congenital Hereditary
layers of epithelial-like endothelium is highly unusual and a Endothelial Dystrophy
described pathologic change. It however does not represent a Congenital hereditary endothelial dystrophy (CHED) (Figs
simple change from endothelium to normal surface epithelium. 6.4.8 A to C ) a rare cause of congenital corneal edema,
In vivo confocal microscopy has revealed a variety of associated with both autosomal dominant (CHED 1) and
endothelial morphologies in PPCD including focal endothelial recessive (CHED 2) modes of inheritance. It was first clinically
vesicular lesions, curvilinear hyper-reflective bands and lesions and histologically characterized by Maumenee in 1960.
with scalloped edges consisting of dark and bright bodies.29 Although both CHED 1 and CHED 2 have been linked to
chromosome 20, they have been linked to distinct loci, with
Treatment CHED 1 having been mapped to the originally described
Surgical intervention is usually not required unless the disease PPCD locus. Recently, mutations in NaBC1 encoded by the
is very extensive and progressive. Risk factors for severe SLC4A11 gene has been identified in individuals affected
Figs 6.4.8A to C: Congenital hereditary endothelial dystrophy CHED 2; (A) Diffuse illumination showing ground glass opacification; (B) Slit
beam demonstrating diffuse stromal thickening; (C) Secondary spheroidal degeneration
with CHED 2.30 CHED results from a primary dysfunction endothelium. This condition, also named, familial corneal guttae,
of the endothelial cells. exists in a classic late-onset form (4th decade and later) and an
early onset variant (first decade). Heredity is autosomal
Clinical Features dominant with genetic heterogeneity. The classic FECD has
already 3 loci, namely FECD1 on chromosome 13pTel-
Recessive CHED is more common with diffuse corneal
13q12.13, FECD2 on 15q and FECD3 on chromosome
clouding being present at birth or in the first few days of life.
18q21.2-q21.32.31,32 The early onset variant is linked to
These children often present with nystagmus. CHED 1 is less
mutations in the Col8A2 gene on chromosome 1p34.4-p32.
severe and although it may be present at birth is likely to
manifest in early childhood. CHED presents as a bilaterally
Clinical Features
symmetrical, gray blue, ground glass haziness of the corneal
stroma extending to the limbus with no intervening clear zones. Disease onset usually occurs over the age of 40 in predisposed
There is associated marked corneal thickening often two to females with wart-like excrescences (guttata) visible in the
three times normal. Stromal dots and flakes of greater central cornea. Corneal guttae in adult onset Fuchs endothelial
opacification in the deeper cornea are also seen. No other corneal dystrophy are larger than those seen in early onset
anterior or posterior segment abnormalities are associated. FECD. Pigment dusting is often present on the endothelium.
Rarely congenital glaucoma may coexist. With time the guttatae spread to a larger area and coalesce to
Visual acuity may be affected to varying degrees leading produce a beaten metal appearance. Endothelial
to amblyopia in children. There may be associated photophobia decompensation causes stromal edema with increased
and tearing. Sensorineural hearing loss beginning in the second pachymetric values evolving towards a bullous keratopathy with
to third decades of life has been reported in association with subepithelial fibrous scarring and peripheral superficial
CHED 2. vascularization in case of chronicity.
CHED is however a diagnosis of exclusion, and other Impaired vision in the morning, spontaneously improving
causes to be ruled out includes congenital glaucoma, forceps during the day, with or without erosions due to rupture of
injury, congenital infections, congenital hereditary stromal epithelial bullae is typical of the symptomatology.
dystrophy, early onset PPCD and metabolic diseases. FECD has been associated with open angle glaucoma and
recently familial keratoconus has also been reported.
Histopathology
Diffuse thickening and lamination of Descemet’s membrane Histopathology
is seen on light microscopy. The endothelial cells are sparse Light microscopy reveals a diffuse laminar thickening of the
and atrophic. Presence of degenerative changes in stroma and Descemet’s membrane associated with hyaline excrescences
Bowman layer in the form of secondary amyloid deposits, and atrophic enlarged endothelial cells. Electron microscopy
band shaped keratopathy and elastotic degeneration demonstrates newly produced layer of abnormal basement
(spheroidal deposits) is seen. On electron microscopy, multiple membrane material containing neocollagen consisting of fibrils
layers of basement membrane-like material can be seen within of various diameter (collagen VIII).
the posterior collagenous layer of Descemet’s membrane, When imaged by in vivo confocal microscopy, the
which contains collagen types I, III, V and laminin, supporting endothelium may resemble the surface of a strawberry,
a fibroblast-like change of the endothelium. consisting of hyporeflective round areas separated by hyper-
reflective regions. The endothelial cell density is decreased and
Treatment the cells show varying amounts of polymegathism and
Penetrating keratoplasty in CHED is moderately successful pleomorphism.
and graft survival and visual outcomes are better in cases
with delayed onset. Treatment
The medical management of patients with visually significant
Fuch’s Endothelial Corneal Dystrophy
edema includes topical hypertonic saline solutions, dehydration
Fuch’s gave the first clinical description in 1910 of Fuch’s of the cornea by a blow dryer and reduction of IOP. Bandage
endothelial corneal dystrophy (FECD) (Figs 6.4.9A to E), contact lenses are used for the treatment of recurrent erosion
the most common primary disorder of the corneal caused by epithelial bullae.
Figs 6.4.9A to E: Fuchs endothelial corneal dystrophy; (A) Slit beam

photographs showing corneal guttae; (B) Advanced disease with
endothelial decompensation with epithelial microcystic and bullous
edema;(C) Specular microscopy pictures showing corneal guttae; (D
and E) Pleomorphism and polymegathism of endothelial cells noted in
in vivo confocal microscopy
Penetrating/endothelial (DLEK/DSEK/DSAEK/ 14. Munier FL, Korvatska E, et al. Kerato-epithelin mutations in four
DMEK) keratoplasty is the treatment of choice for patients 5q31-linked corneal dystrophies. Nat Genet 1997;15:247-51.
15. Kobayashi A, Sugiyama K. In vivo laser confocal microscopy findings
with significant reduction in vision. With coexistent cataract,
for Bowman’s layer dystrophies (Thiel-Behnke and Reis-Bücklers
assessment for vision loss due to the cataract versus FECD, is corneal dystrophies). Ophthalmology 2007;114(1):69-75.
to be done, before determining the best surgical course. 16. Werner LP, Werner L, Dighiero P, et al. Confocal microscopy in
Anticipating the correct intraocular lens power for a patient Bowman and stromal corneal dystrophies. Ophthalmology
undergoing cataract surgery alone followed by Descemet 1999;106:1697-1704.
stripping endothelial keratoplasty (DSEK) or combined 17. Kobayashi A, Fujiki K, Fujimaki T. In vivo laser confocal
microscopic findings of corneal stromal dystrophies. Arch
cataract surgery with DSEK/DSAEK requires understanding
Ophthalmol 2007;125:1168-73.
of the hyperopic shift that can occur with DSEK/DSAEK 18. Paliwal P, Gupta J, Tandon R, et al. Clinical and Genetic profile of
and incorporating this correction preoperatively in the Avellino corneal dystrophy in 2 families from North India. Arch
intraocular lens power selection. Ophthalmol 2009;127:1373-76.
19. Holland EJ, Daya SM, Stone EM, et al. Avellino corneal dystrophy:
clinical manifestations and natural history. Ophthalmology
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21. Sultana A, MS Sridhar, et al. Novel mutations of the carbohydrate
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the evolving molecular, genetic and imaging revolution. Clin
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22. Akama TO, K Nishida, et al. “Macular corneal dystrophy type I
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4. Aldave AJ, Sonmez B Elucidating the molecular genetic basis of
23. Iida-Hasegawa, NA Furuhata, et al. “Mutations in the CHST6 gene
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2007;125:177-86.
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5. Alavi A, Elahi E, Tehrani MH, et al. Four mutations (three novel,
2003;44(8):3272-7.
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Ophthalmol Vis Sci 2007;48(10):4490-7. dystrophy: reduction in both corneal thickness and collagen
6. Paliwal P, Gupta J, Tandon R, et al. Identification and interfibrillar spacing. Curr Eye Res 1990;9:393-8.
characterization of a novel TACSTD2 mutation in gelatinous drop- 25. Aldave AJ, Yellore VS, Principe AH, et al. Candidate gene screening
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7. Takaoka M, Nakamura T, Ban Y, et al. Phenotypic investigation of 26. Heon E, Mathers WD, Alward WL, et al. Linkage of posterior
cell junction-related proteins in gelatinous drop-like corneal polymorphous corneal dystrophy to 20q11. Hum Mol Genet
dystrophy. Invest Ophthalmol Vis Sci 2007;48(3):1095-10. 1995;4:485–8.
8. Nishida K, Quantock AJ, Dota A, et al. Apolipoproteins J and E 27. Shimizu S, Krafchak C, Fuse N, et al. A locus for posterior
co-localize with amyloid in gelatinous drop-like and lattice type I polymorphous corneal dystrophy (PPCD3) maps to chromosome
corneal dystrophies. Br J Ophthalmol 1999;83(10):1178-82. 10. Am J Med Genet 2004;130:372–7.
9. Ide T, Nishida K, Maeda N, et al. A spectrum of clinical 28. Yellore VS, Rayner SA, Emmert-Buck L, et al. No pathogenic
manifestations of gelatinous drop-like corneal dystrophy in Japan. mutations identified in the COL8A2 gene or four positional
Am J Ophthalmol 2004;137(6):1081-4. candidate genes in patients with posterior polymorphous corneal
10. Yoshida S, Yoshida A, Ishibashi T, et al. Presence of vitronectin in dystrophy. Invest Ophthalmol Vis Sci 2005;46:1599-1603.
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Clinicohistopathologic finding of gelatinous droplike corneal borate cotransporter SLC4A11 cause recessive congenital hereditary
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Chapter 6.5
CORNEAL ECTASIAS
Reena Sharma, M Vanathi
KERATOCONUS Theories:
The corneal ectatic conditions discussed in this chapter include – Isolated sporadic
keratoconus, pellucid marginal corneal degeneration and – Heredity
Terrien’s marginal degeneration. – Association with systemic conditions
In 1748, the German oculist Burchard Mauchart – Eye rubbing
provided an early description of a case of keratoconus, which – Hormonal changes: There is no direct evidence of a
he called staphyloma diaphanum.1 However, it was not until cause-and-effect relationship, but the condition often
1854 that British physician John Nottingham clearly described first develops at the time of puberty and occasionally
keratoconus and distinguished it from other ectasias of the during pregnancy or advances during pregnancy.
cornea.1 – Rigid contact lens wear.
Keratoconus, a non-inflammatory corneal ectasia, is It is commonly an isolated ocular condition but sometimes
characterized by progressive corneal thinning and apical coexists with other ocular and systemic diseases.5
protrusion.2 The word has its origin from Greek terminology: • Systemic disorders:
kerato-horn, cornea; and konos cone. Typically, the patients – Down syndrome, Turner syndrome
present in early adulthood and visual symptoms result from – Ehlers-Danlos and Marfan syndromes, osteogenesis
irregular astigmatism and increasing myopia. Many early imperfecta, mitral valve prolapse
studies of keratoconus reported that the prevalence of – Atopic dermatitis
keratoconus was much higher in women than in men. – Bardet-Biedl syndrome, Crouzon’s syndrome,
However, more recent studies have found that the prevalence Laurence-Moon-Biedl syndrome, Goltz-Gorlin
is higher in men or that there is no significant difference.3 It syndrome, Nail-patella syndrome.
is reported to have bilateral involvement in over 90 percent • Ocular disorders:
of patients, with asymmetric presentation. Data on incidence – Vernal keratoconjunctivitis
of keratoconus vary greatly in different studies. Best estimates – Leber’s congenital amaurosis
range from 50-230/100,000. 2-5 The prevalence of – Retinitis pigmentosa
keratoconus is 54.5 per 1 lakh population.5 Asians have a – Blue sclera, aniridia, ectopia lentis.
fourfold higher incidence, are younger at presentation and Particularly significant risk factors include history of atopy,
require corneal grafting at an earlier age compared with white contact lens wear, and constant eye rubbing.
patients.6 Life expectancy of keratoconus patients has not
been found to be any different from general population.7 Pathophysiology
Etiology: The proposed etiology of keratoconus involves Many of the clinical features of keratoconus can be explained
biochemical and physical corneal tissue changes, but no one by a biomechanical hypothesis, which proposes that corneal
theory fully explains the clinical findings and associated ocular thinning and ectasia is the result of an interlamellar and an
and non-ocular disorders. interfibrillar slippage of collagen within the stroma, due to a
loss of cohesion between collagen fibrils and the Signs

noncollagenous matrix.8,9 In addition to these biomechanical
events, there is an extensive body of literature supporting External Signs
the occurrence of biochemical changes within keratoconus • Munson’s sign: This is the indentation of lower lid caused
corneas. The concept of tissue degradation is based on the by the protruding apex of the keratoconus. It is seen in
demonstration of collagen loss and proteoglycan changes in advanced cases of keratoconus (Fig. 6.5.1A).
affected corneas and on the upregulation of degradative
• Rizutti’s sign: A light reflex projected from the temporal
enzymes like cathepsins, gelatinases, etc.10
side will be displaced beyond the nasal limbal sulcus when
Genetics of Keratoconus high astigmatism and steep curvatures are present.
Although not a pathognomonic sign, it may aid in a
Most keratoconus cases appear spontaneously, although diagnosis especially when a biomicroscope or other tools
approximately 6 to 14 percent of them present with evidence to aid in diagnosis are not available (Fig. 6.5.1B).
of genetic transmission.3,5 Majority of the cases have an
autosomal dominant transmission with incomplete penetrance,
though autosomal recessive and X-linked transmissions have
also been documented. Defects on chromosomes 21, 17,
and 13 have been detected in cases of keratoconus though
exact defects are not known.11
Histologic Findings
All layers of the cornea are affected by keratoconus.5 It is
characterized by severe corneal stromal thinning and focal
deficits in epithelium and Bowman’s layer, the latter being
the earliest of the abnormalities. Superficial epithelial cells
located at the apex of cone are elongated and arranged in a
whorl-like fashion. There is a decrease in the number of
stromal collagen lamellae and also a loss of the fibular
arrangement within the lamellae. Iron deposition in the basal
corneal epithelial cells forms the characteristic Fleischer ring. Fig. 6.5.1A: A patient with advanced keratoconus showing
conical protrusion of lower lid by cornea (Munson’s sign)
Ruptures in Descemet’s membrane are associated with influx
of fluid into corneal stroma in acute hydrops. The endothelium
is usually normal.
Clinical Features
The clinical course of keratoconus is highly specific. Although
keratoconus can present in any age group, it most commonly
affects patients in their late teens or early twenties. The
condition is almost always progressive but the rate of
progression and ultimate severity are quite variable. It tends
to progress more rapidly in young patients. About 10 to 20
percent of patients will eventually need a corneal transplant.5
Symptoms
• Deteriorating visual acuity, distortions, glare
• Frequent changes in refraction
• Visual acuity not refractable to 6/6 Fig. 6.5.1B: A patient with advanced keratoconus
• Monocular polyopia or ghosting showing Rizutti sign
Corneal Ectasias 453
Slit Lamp Signs • Corneal apical scarring: Approximately 20 percent of eyes

with moderate keratoconus develop corneal scarring. It
• Vogt’s striae: Approximately 40 percent of eyes with
occurs as a part of natural progression of the disease but
moderate keratoconus develop Vogt striae (fine stress lines)
is worsened by the wearing of rigid contact lenses. It usually
in the deep stroma (Fig. 6.5.1C). It is often the earliest slit
appears at the apex of the cone, and may start as fine
lamp finding noted in keratoconus.
lines and then develop into nebular scarring which can
• Fleischer ring: Approximately 50 percent of eyes with
progress (Fig. 6.5.1E).
moderate keratoconus develop the deposition of iron in
• Hydrops: An acute rupture in Descemet’s membrane
the basal epithelial cells in a (often partial) ring shape at
causes development of sudden onset redness and pain
the base of the conical protrusion called the Fleischer’s
due to imbibition of aqueous into corneal stroma causing
ring (Fig. 6.5.1D). This ring is faint and broad in early
it to swell (Figs 6.5.2A and B).
keratoconus and becomes thinner and more discrete as
the condition advances.
Retroillumination Signs
• Prominent corneal nerves: It is not likely that the nerve
fibers are more numerous in keratoconic patients, but • Scissoring reflex on retinoscopy: The reflex appears to spin
only that they are more easily seen due to changes in or swirl around a point corresponding to the apex of the
density. cone.
• Oil droplet sign (“Charleaux” sign): This sign is noticed on
distant direct ophthalmoscopy.
Photokeratoscopic Signs
• Compression of mires inferotemporally or centrally
• “Egg shaped mires”
Videokeratography Signs
• Localized increase of surface power which is usually
present in the inferior or inferotemporal cornea
(approximately 80% of cases) (Fig. 6.5.3).
• Inferior superior diopteric asymmetry.
• Relative skewing of steepest radial axes above and below
the horizontal meridian (SRAX pattern).
Fig. 6.5.1C: Vogt’s Striae in a patient of keratoconus
Fig. 6.5.1D: Fleischer’s ring at the base of keratoconus Fig. 6.5.1E: Keratoconus with scarring at the apex of an oval cone
Figs 6.5.2A and B: (A) Keratoconus with acute hydrops demonstrating increased corneal thickness and diffuse corneal edema at
presentation; (B) At three months later with healed hydrops with stromal scarring and break in the Descemet’s membrane
Fig. 6.5.3: Videokeratography of a keratoconus showing localized increase of corneal power, inferosuperior diopteric power asymmetry
and relative skewing of the steepest radial axes above and below the horizontal meridian
Figs 6.5.4A to C: A diagrammatic representation of the three types of keratoconus cones—nipple, oval and globus cones
Classification of Keratoconus Differential Diagnosis

• Cone type and position (Figs 6.5.4 A to C) Pellucid marginal degeneration: This is often considered a variant
– Nipple cone is a small, near central cone, less than of keratoconus, in which corneal thinning occurs about a
5.0 mm in diameter. millimeter above the inferior limbus. It is differentiated
– Oval cone is the most common type of cone found, from keratoconus using videokeratography which shows
especially in advanced keratoconus. Apex of cone is against-the-rule corneal astigmatism (inferior lobster claw–
displaced well below the midline resulting in varying like map).
degrees of inferior mid-peripheral steepening.
Terrien marginal corneal degeneration: This is an inflammatory
– Globus cone is a large cone often affecting nearly disease that affects the superior limbus, and induces irregular
three quarters of the corneal surface, more than 6.0 against-the-rule astigmatism and corneal thinning (often with
mm in diameter. vascularization and lipid deposits).
• Corneal curvature (keratometry) 12
The classification of keratoconus based on keratometry Keratoglobus: This is a rare condition that causes corneal
values12 is follows: thinning primarily at the margins, resulting in a spherical, slightly
– Mild <48D enlarged eye.
– Moderate 48 to 54 D Posterior keratoconus is another extremely rare disease in which
– Severe >54D the posterior corneal surface suffers a loss of substance.
• Slit lamp findings, retinoscopy and corneal topography
Rabinowitz13 described this classification, based on the Diagnosis
obser vation of the topographic progression of
keratoconus-suspect and early keratoconus to clinically Careful refraction, slit lamp biomicroscopy, keratometry and
significant keratoconus. corneal topography aid the clinician in the diagnose of
• Keratoconus: Stromal corneal thinning by slit lamp keratoconus.
examination accompanied by one or more of the following • Keratometry: The keratometry mires commonly are steep,
clinical signs—Vogt’s striae, Fleischer’s ring, Munson sign, highly astigmatic, irregular, and often appear egg-shaped
scissoring of the retinoscopic reflex an asymmetric bow rather than circular or oval, in keratoconus patients. It
tie with skewed radial axes videokeratography pattern (AB/ also shows increased keratometry values typically between
SRAX). 45 to 52D or more, which are also used to grade the
severity of keratoconus.
• Early keratoconus: No slit-lamp findings but scissoring of
• Videokeratography: It commonly shows inferior corneal
the retinoscopic reflex with a fully dilated pupil examination
steepening in keratoconus, although a small percentage
with an AB/SRAX videokeratography pattern.
of patients show central astigmatic changes. An even
• Keratoconus-suspect: No clinical signs of keratoconus, no
smaller number of patients may show superior steepening.
scissoring on retinoscopy but an AB/SRAX videokerato-
graphy pattern. The Rabinowitz diagnostic criteria consist of three corneal
• Normal: No clinical signs of keratoconus, no scissoring topography derived indices, which, when abnormal, should
on retinoscopy, no AB/SRAX pattern on videokerato- alert the clinician to consider a diagnosis of keratoconus.
graphy. These indices are as follows:
• Keratometry value quantifies the central steepening of Contact Lenses

the cornea that occurs in keratoconus. A value of 47.20
Spectacles may fail to provide the patient with a satisfactory
D or greater is suggestive of keratoconus.
degree of visual acuity as the condition progresses, and most
• I-S value quantifies the inferior versus superior corneal
clinical practitioners will then use contact lenses to manage
dioptric asymmetry that occurs in keratoconus. A value
the condition. Contact lenses improve vision by means of
of 1.4 D or greater is suggestive of keratoconus.
tear fluid filling the gap between the irregular corneal surface
• KISA percent incorporates the K and I-S values with a
measure, quantifying the regular and irregular astigmatism and the smooth regular inner surface of the lens, thereby
into one index. creating the effect of a smoother cornea. In 1888, a French
KISA percent = K × I-S asymmetry × AST (degree of ophthalmologist, Eugene Kalt, began work on a crude glass
regular corneal astigmatism) × SRAX × 100 shell designed to “compress the steep conical apex thereby
This index is highly sensitive and specific in correcting the condition.” This was the first known use of a
defferentiating the normal from keratoconic corneas. A contact lens for keratoconus patients.17
value of greater than 100 percent is highly suggestive of Traditionally, lenses for keratoconus have been the “hard”
frank keratoconus, and the range from 60 to 100 percent or rigid gas-permeable contact lens variety. For rigid gas
represents keratoconus suspects.14 permeable (RGP) lens fitting, most contact lens fitting
On the other hand, Maeda and Klyce have also methods use keratometry values in combination with the
described a software program, based on the linear fluorescein pattern for selection of the back optic zone radius.
discriminant analysis of eight indices drawn from the For most patients with keratoconus, a three point touch contact
corneal map and a binary decision tree.15 This program lenses design is ideal, and is preferred over apical clearance
assigns the topographical map a quantitative percentage and apical touch designs. The base curve should be steep
score of the severity of keratoconus called the KPI percent enough to provide a slight central touch, shown by thinning
(keratoconus prediction index). A value of greater than of fluorescein, at the corneal apex and slight touch mid-
zero is believed to be suggestive of keratoconus. peripherally at 3 and 9 o’clock along the horizontal meridian.
• The Orbscan corneal topography II system uses the This creates three point lens touch along the horizontal
combination of a placido and scanning optical slit design.16 meridian. The most accurate way to fit keratoconic patients
The high-resolution video camera captures 40 slit images is to place a diagnostic lens on the eye, check the fit, and then
at the 45 degree angle projected through the cornea similar modify the fit. Since each individual cone is different, it is a
to that seen during slit lamp examination. The instrument’s trial and error process, and may require trying on several
software then analyzes 240 data points per slit and different lenses.
calculates the corneal thickness and posterior surface of In mild to moderate keratoconus, the lens diameter
the entire cornea. It provides an anterior elevation map selected is usually 7.5 to 8.5 mm. A small size facilitates tear
(based on a best fit sphere), a posterior map (derived exchange and allows a steeper fit to accommodate the cone.
mathematically), a corneal map and a pachymetry map Central nipple cones do best with small diameter lenses. When
(Figs 6.5.5A and B). The most important parameters on the cone is displaced peripherally, as with oval and globus
orbscan used to assess keratoconus are anterior corneal cones, fitting a larger, flatter lens may be required.
elevation and posterior corneal elevation.16 Several especially designed contact lenses have been
developed to facilitate fitting in advanced, difficult to fit
Treatment Modalities keratoconus cases. Soper lenses are one of the best known lenses.
This is a bicurve design with a steep central curve to
Spectacle Correction
accommodate the cone and a flatter peripheral curve to align
The patient’s refractive error can often be successfully managed with the peripheral cornea. They are fitted by varying the sagittal
with spectacle lenses in the early stages of keratoconus. It is depth of lenses. Hybrid lenses have been developed which are
important to inform the patient that there is no evidence to lenses with rigid gas permeable optic zone surrounded by a soft
support the theory that early contact lens use is of benefit in skirt to ensure a comfortable fit. Soft or hybrid lenses do not
preventing or decreasing the progression of the disease. however prove effective for every patient. Some patients also
However, contact lenses provide better visual acuity, than that find good vision correction and comfort with a “piggyback” lens
can be obtained with glasses by neutralizing the regular and combination, in which gas permeable rigid lenses are worn over
irregular refractive errors induced by the condition. soft lenses, both providing a degree of vision correction.
Figs 6.5.5A and B: Orbscan of a keratoconus patient showing increased anterior and
posterior corneal power and localized corneal thinning
The Rose K lenses are a unique keratoconus lens design

with nor complex computer-generated peripheral curves based
on precollected data. The system (26 lens set) incorporates a
triple peripheral curve system—standard, flat, steep—in order
to achieve the ideal edge lift of 0.8 mm.
There are various other specific contact lens systems for
keratoconus that are commercially available.
Scleral lenses are sometimes prescribed for cases of advanced
or very irregular keratoconus; these lenses cover a greater
proportion of the surface of the eye and hence can offer Fig. 6.5.6: Intracorneal ring segments inserted in the midperipheral
corneal stroma act by shortening the corneal arc length and hence
improved stability and comfort.18 They have been worn with flattening the central cornea
all day wearing comfort in many rigid lens intolerant patients.
The larger size of the lenses may make them unappealing or
uncomfortable to some, however their easier handling can
find favor with patients with reduced dexterity, such as the
elderly. High cost prohibits the widespread usage of these
lenses.
(Refer to the section on contact lenses also)
Refractive Surgery
Laser in situ keratomileusis (LASIK) or photorefractive
keratectomy (PRK) is contraindicated in these patients because
of a greater risk for scarring and excessive thinning leading
to possible post-LASIK corneal ectasia. Thorough topographic
evaluation should be done to rule out forme fruste
keratoconus or suspect before considering these refractive
procedures. Phototherapeutic keratectomy (PTK) has been Fig. 6.5.7: Placement of INTACS rings in the corneal stroma using a
described to be helpful for some selected keratoconus patients temporal clear corneal incision. They are placed circumferentially into
the tunnels created in superior and inferior cornea
to reduce steepness of the cone in patients who have become
contact lens intolerant.19 The resultant flattening of the cone
makes contact lens fitting easier. INTACS are flatter and less centrally placed than the Ferrara
rings.
Intrastromal Corneal Ring Segments Clinical studies on the efficacy of intrastromal rings on
keratoconus are encouraging, though they have yet to enter
A recent surgical alternative to corneal transplant is the
into wide acceptance with all refractive surgeons.21-23 Potential
insertion of intrastromal corneal ring segments (ICRS) (Fig.
complications of intrastromal rings include accidental
6.5.6).20 These inserts are designed to be placed at a depth
penetration through to the anterior chamber when forming
of approximately two-thirds the corneal thickness and are
the channel, post-operative infection of the cornea, and
surgically inserted through a small radial incision into a track
migration or extrusion of the segments. The rings offer a
created within the corneal stroma (Fig. 6.5.7). They act by
good chance of vision improvement even in otherwise hard
shortening the corneal arc length and have a net effect of
to manage eyes and can always be a good reversible option
flattening the central cornea. The amount of flattening is
before taking up the patient for surgery.
determined by the insert’s thickness. Rings are available in
thicknesses varying from 0.25 mm to 0.45 mm. ICRS are
Corneal Collagen Cross-linking with Riboflavin
indicated for contact lens intolerant patients with early
(C3R)
keratoconus who have minimal central stromal scarring.
The two principal types of intrastromal rings available Corneal stroma soaked in riboflavin 0.1 percent eyedrops in
are known by the trade names of INTACS and Ferrara rings. 20 percent dextran and activated by approximately 30 minutes
illumination with UV-A (370 nm) light, results in collagen 8.5 mm are used. Generally, the second eye is not grafted
cross-linking within the corneal stroma and so recovers some until the first eye is successfully rehabilitated usually keeping
of its mechanical strength (Fig. 6.5.8).24 The treatment has an interval of twelve months. Contact lenses are often
been shown to slow down or arrest the progression of required after this procedure for best visual rehabilitation.
keratoconus, and in some cases even reverse it, particularly An alternative is lamellar keratoplasty, a partial thickness
when applied in combination with intracorneal ring segments. corneal transplant. The host cornea is removed upto the depth
The need for keratoplasty thus might be significantly reduced of posterior stroma, and the lamellar donor corneal button is
in these patients. Clinical trials are continuing, and the technique sutured in place. This technique requires less recovery time,
is definitely showing promise in treating early cases of the and poses less chance for corneal graft rejection or failure.
disease.25-27 However it is technically difficult and visual acuity is inferior
to that obtained after penetrating keratoplasty. As a result,
Management of Acute Hydrops use of lamellar keratoplasty and epikeratoplasty is largely
confined to the treatment of large cones or keratoglobus
Acute corneal hydrops in keratoconus can be managed
when tectonic support is needed.
medically with hyperosmotics, oral and topical acetazolamide
and antiglaucoma medications. Intracameral air injection is a
safe and useful therapy to shorten the period of corneal
edema in acute hydrops secondary to keratoconus. The use
of intracameral air, iso-expansile fluoropropane or sulfur
hexafluoride injections in management of acute hydrops in
keratoconus had been described.28-30.
Corneal Transplant
Approximately 10 percent of keratoconus cases will progress
to a point where vision correction is not possible, thinning of
the cornea becomes excessive, or scarring as a result of contact
lens wear causes problems and a corneal transplantation
becomes required.1,2
Penetrating keratoplasty has been the gold standard surgery
for keratoconus patients with success rates of more than 90
percent. 31 In this procedure, the keratoconic cornea is
prepared by removing the central area of the cornea, and a
full-thickness donor corneal button is sutured in its place
(Figs 6.5.9A and B). Usually corneal trephines between 8.0 to
Fig. 6.5.8: C3R causes increased collagen cross-linking within the Figs 6.5.9A and B: (A) Clinical photograph of a keratoconus patient
corneal stroma to enhance its mechanical strength (decreased amount with central cone with stromal scarring; penetrating keratoplasty was
of cross-links between collagen fibrils is believed to be the done in this patient, (B) Shows the first postoperative day clinical
pathogenesis for the ectasia in keratoconus) picture (Courtesy: Prof J S Titiyal)
Lamellar keratoplasty has recently been almost replaced Pellucid Marginal Corneal
by an alternative highly rewarding procedure of deep anterior Degeneration
lamellar keratoplasty (DALK).32 In DALK (Figs 6.5.10A and
Pellucid marginal degeneration was coined in 1957 by
B), the patient’s corneal endothelium is retained, giving
Schlaeppi. Pellucid marginal corneal degeneration (PMCD)
additional structural integrity to the post-graft cornea. As a
is an ectatic corneal disorder characterized by a non-
graft rejection usually begins in the endothelium, the chance
inflammatory peripheral band of thinning of the inferior
of a rejection episode is greatly reduced. This technique also
cornea35-37 and is characterized by thinning of the inferior
requires less recovery time. It is however a technically
peripheral cornea concentric to the limbus between 4 to 8
demanding procedure.
o’clock positions (Figs 6.5.11 and 6.5.12A and B). Usual onset
Phakic intraocular lens implantation has been recently
is between 20 to 40 years. The zone of thinning is generally 1
considered for keratoconus patients. Anterior chamber phakic
to 2 mm wide and separated by 1 to 2 mm from the limbus
intraocular lens have been combined with INTACS with good
by an area of normal cornea. Against the rule astigmatism is
results.33,34 Phakic lens corrects the major part of refractive
seen in these cases. There is no associated vascularization or
error especially, high myopia, and INTACS is used to correct
scarring. PMCD and keratoconus can coexist in the same
the residual error.
eye. Some believe PMCD to be a variant of keratoconus.
The major differentiating features being absence of
Fleischer’s ring or conical protrusion, area of ectasia is
cylindrical and not conical. No scarring is seen at the level
of Bowman’s membrane and an area of inferior corneal
steepening along with against the rule astigmatism with a lobster
claw pattern seen on topography.37
During the clinical course of pellucid marginal corneal
degeneration, acute hydrops with corneal edema in the lower
half might develop.38 Cases of keratoconus and pellucid
marginal corneal degeneration, complicated by acute corneal
hydrops (Fig. 6.5.13) and perforation are infrequently
encountered in clinical practice. Acute hydrops occurs when
Descemet’s membrane and the endothelium of the ectatic
cornea separates allowing aqueous humor to enter the stroma.
Allergy and eye-rubbing have been reported to be important
risk factors in the development of hydrops.35,36
Figs 6.5.10A and B: (A) Clinical photograph of a keratoconus patient

with apical scarring and (B) deep anterior lamellar keratoplasty
performed (Courtesy: Prof J S Titiyal) Fig. 6.5.11: Pellucid marginal degeneration
Figs 6.5.12A and B: Pellucid marginal degeneration showing inferior ectasias (note the eye is pseudophakic)
follow-up (8 years or more) are common causes that are

significantly associated with surgery.36 C-shaped lamellar
keratoplasty using multiple trephines of different sizes, with
deliberate undersizing of the donor graft for a controlled
compressive effect has been described for severe corneal
astigmatism in PMCD.46
TERRIEN’S MARGINAL DEGENERATION
Terrien’s Marginal Degeneration (TMD) consists of slowly

progressive thinning of the peripheral cornea (Fig. 6.5.15). It
commonly occurs in men. It can occur at all ages and is
commonly bilateral. It starts with deposition of refractile
yellowish-white dots in the peripheral anterior stroma followed
by the appearance of a narrow gutter parallel to the limbus
Fig. 6.5.13: Acute hydrops in PMCD with progressive thinning (Figs 6.5.16A and B). The thinning
commonly starts in the superior region and may extend 360
The treatment in PMCD consists of optical correction degrees. The epithelium is intact and in advanced cases,
with contact lenses in initial phases.35,39,40 With progress to superficial vascularization in a radial fashion (Fig. 6.5.17) is
advanced stages, surgical procedures are necessary such as seen with characteristic lipid deposition. Management includes
wedge resection, lamellar crescentic resection, penetrating optical correction with glasses or contact lenses in the early
keratoplasty, lamellar keratoplasty, epikeratoplasty and, recently, phases. Tectonic peripheral lamellar crescentic grafts (Fig.
intracorneal ring segments.35,36,41-45 Surgical management 6.5.18) and keratoplasty may also be required.
modalities commonly performed include lamellar crescentic
lamellar keratoplasty (Figs 6.5.14A and B) and penetrating KERATOGLOBUS
keratoplasty (Fig. 6.5.14C). The effectiveness of tectonic
crescentic lamellar graft in improving astigmatism in pellucid It is a very rare condition that causes corneal thinning prima-
marginal degeneration has been reported. While nonsurgical rily at the margins, resulting in a spherical, slightly enlarged
modalities remains the mainstay in the management of PMCD, eye (Fig. 6.5.19). This can occur in association with systemic
poor best-corrected visual acuity at presentation and long conditions such as Ehlers-Danlos syndrome.
Fig. 6.5.15: Terrien’s marginal degeneration
Figs 6.5.14A to C: Pellucid marginal degeneration with healed hydrops:

(A) Preoperative; (B) Post peripheral tectonic crescentic lamellar graft Figs 6.5.16A and B: Terrien’s marginal degeneration (in varying
followed by (C) Penetrating keratoplasty one year later in the same eye magnifications) showing significant superior ectasia of the right eye
Fig. 6.5.20: Anterior segment OCT showing a posterior keratoconus
Fig. 6.5.17: Advanced Terrien’s marginal degeneration

Posterior Keratoconus
It is another extremely rare condition in which the posterior
corneal surface suffers loss of substance (Fig. 6.5.20).
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Chapter 6.6
LIMBUS ABNORMALITIES
6.6.1 Diseases of the Corneal Limbus

R Revathi, Sathyarekha
ANATOMY Limbal stem cells: The stem cells have long lifespan with an
unlimited capacity of self-renewal. They reside adjacent to
Anatomically the limbus refers to the circumcorneal
tissues that undergo constant and rapid turnover. All stem
transitional zone of the conjunctivocorneal and corneoscleral
cells need a special microenvironment called niche. The limbal
junction.
stem cells are pluripotential since on stimulation they give rise
Conjunctivocor neal junction: The columnar bulbar to a specific cell line, corneal phenotype. Logically, limbus is
conjunctiva stops and continues as stratified squamous an ideal place for the corneal stem cells to reside. Its rich
epithelium on cornea. vascular stroma provides the niche. These cells are thought to
Sclerocorneal junction: The transparent corneal lamellae be protected in the deepest layer of the limbal basal cells. The
become oblique, circular and opaque fibers of the sclera. indirect evidences of their presence in limbus are:
Limbus is seen as a rim of tissue that forms an ellipse • Trauma to the limbus as in ocular burns results in corneal
around the clear cornea, denoted by pigmentation. It contains surface being covered by conjunctival type of epithelium
multiple horizontal ridges called ‘palisades of Vogt’ (refer to with goblets cells and blood vessels.
Fig. 6.6.1.1). The epithelium of limbus is made up of 8 to 10 • Transplantation of limbal tissue helps in establishing
layers stratified squamous cells. The basal layer undulates into corneal type of avascular stratified squamous epithelium
the underlying stroma. The epithelium also has melanocytes devoid of goblet cells.
and Langerhans’ cells. The stroma has a rich supply of cells • The limbal basal cells do not express keratin 3, a marker
from immune system like macrophages, mast cells, lymphocytes characteristic of corneal epithelial cells.
and plasma cells. The conjunctival and episcleral vessels from Developing specific markers to clinch the presence of
anterior ciliary vessels end in a rich vascular plexus at limbus limbal stem cells is an active area of extensive research. Since
and leave the cornea avascular. The peripheral corneal these structures are interrelated anatomically and functionally,
nourishment is thought to be derived from the limbus. The disorders of limbus includes diseases of:
limbal stroma also holds lymphatics and unmyelinated nerve • Perilimbal conjunctiva
fibers. These characteristics render the limbal stroma a rich • Episclera
source of infective, immune and degenerative lesions involving • Peripheral cornea
peripheral cornea. • Limbal stem cells.
Pathological Classification Infections

of Limbal Disorders – Bacterial
– Fungal
• Neoplastic – Viral
• Metabolic disorders – Chlamydial.
• Depositions
• Degenerations NEOPLASTIC DISEASES
• Immune/Inflammatory/Hypersensitivity disorders
• Infections. Limbus as a transitional zone with high mitotic activities is
the ideal location for neoplastic lesions.
Classification of Peripheral Limbal dermoid: This benign congenital lesion grows
Corneal Disease minimally with the growth of the eye and does not undergo
• Neoplastic malignant transformation (Fig. 6.6.1.1). Treatment is done for
– Limbal dermoid cosmetic purpose or sometimes as they cause astigmatism or
– Conjunctival intraepithelial neoplasia (CIN) refractive amblyopia. Treatment includes excision and
– Invasive squamous carcinoma sometimes a lamellar patch graft becomes necessary.
– Melanoma
Squamous neoplasia: (Refer to section on ocular oncology also)
• Degenerative diseases
Malignant lesions arise in conjunctiva or limbal stem cells.
Peripheral corneal deposits
These lesions range from mild dysplasia, non-invasive
– Vogts limbal girdle
– Arcus senilis carcinoma in situ to invasive squamous cell carcinoma.
– Band keratopathy Dysplasia is characterized by hypercellularity, atypia of the
– Spheroidal degeneration basal epithelium. Dysplasia involving the entire thickness of
– Kayser-Fleischer ring. the epithelium with intact basement membrane is carcinoma
Thinning disorders in situ. 1,2
– Terriens marginal degeneration Human papilloma virus infection and exposure to
– Furrow degeneration ultraviolet radiation are proposed as possible predisposing
– Pellucid marginal degeneration. conditions.
• Diseases associated with contiguous structures
Conjunctival diseases
– Dellen
– Pterygium
– Superior limbic conjunctivitis
– Limbal vernal keratoconjunctivitis
Sclerokeratitis
• Inflammatory/Ulcerative disease
Microulcerative
– Marginal punctate keratitis
i. Drug toxicity
ii. Associated with bacterial conjunctivitis
– Associated with blepharitis
i. Catarrhal ulcer
ii. Phlyctenulosis
iii. Rosaceae keratitis
Macroulcerative
– Secondary to systemic vasculitis
i. Rheumatoid arthritis, Wegener’s granulomatosis,
Polyarteritis nodosa
ii. Rheumatoid marginal furrow
iii. Moorens ulcer Fig. 6.6.1.1: Dermoid at limbus
Limbus Abnormalities 467
The tumors are asymptomatic and discovered on routine

ophthalmic examination. Clinically the lesion presents as a
sessile papilloma or a gelatinous mass or an elevated keratinized
plaque (Figs 6.6.1.2A and B).
In most cases the appearance of the lesion is characteristic
enough for a definitive diagnosis and management. Impression
cytology needs experienced pathologists to interpret. An
excision biopsy is both diagnostic and curative.
Management—Complete surgical excision with a wide 2-
4 mm conjunctival margin and a double circle application of
partial freeze thaw cryotherapy of the conjunctival margin is
recommended to eradicate the tumor. The resulting raw area
can be covered with amniotic membrane to facilitate normal
healing. The tissue specimen is sent for histopathological
examination with proper orientation of the margins marked.
Fig. 6.6.1.2A: Squamous neoplasia (keratinized plaque)
If the margins show involvement, an additional topical
chemotherapy with 0.04 percent mitomycin C (MMC) four
times a day in weekly cycles with intermittent recovery time is
recommended. Two to four cycles can be considered according
to the size of the lesion. Topical MMC can cause significant
irritation. Punctal occlusion with finger while applying MMC
is advised. Topical chemotherapy can also be done by applying
one percent 5-fluorouracil four times a day for about four
weeks. Topical chemoreduction can also be considered in very
large tumors before surgical excision. Topical chemotherapy
is the treatment of choice for recurrences to minimize extensive
ocular scarring and limbal stem cell deficiency associated with
repeated extensive surgical interventions. Sub-conjunctival and
topical interferon as chemotherapy is also found to be
effective.3-6
Pigmented tumors: Pigmented lesions range from benign
nevus to malignant melanomas (Figs 6.6.1.3A and B). Primary
acquired melanosis can affect the perilimbal conjunctiva also
(Fig. 6.6.1.4). The melanocytic tumors as in parts, can spread
through lymphatic channels. Rarely, a tumor from underlying
ciliary body can break through anteriorly.
Neoplastic lesions of lymphocytes may be a part of mucosa
associated lymphatic tumors (MALT). Clinically they appear
as pinkish soft elevated subepithelial nodules (Fig. 6.6.1.5).
Histopathologically they range from reactive lymphoid
hyperplasia, monoclonal B cell neoplasia, Hodgkins lymphoma,
T-cell lymphomas to plasmocytoma.
Conjunctival inclusion epithelial cysts: Inclusion cysts arise
from implanted epithelial cells in the substantia propria by
trauma, surgery and inflammation. They are more common
Fig. 6.6.1.2B: OSSN (Papillomatous growth) near fornices. They appear as clear, translucent lesions. A cystic
lesion at the pterygium head usually is a degenerative change,

but rarely it can be a malignant lesion of the overlying
epithelium (Fig. 6.6.1.6). It is important to send the excised
tissue for histopathological examination.
METABOLIC DISEASES
Many systemic metabolic disorders can affect limbus and
peripheral cornea. The lesions are caused by abnormal
metabolic products that diffuse from limbal vasculature. They
are progressive and associated with systemic manifestations
of the disease.
Fig. 6.6.1.5: Mucosa associated lymphatic tumours (MALT)
Figs. 6.6.1.3A and B: (A) Conjunctival nevus

(B) Conjunctival melanoma
Fig. 6.6.1.4: Primary acquired melanosis Fig. 6.6.1.6: Cystic degeneration of a pterygium
Extraocular involvements like liver dysfunction, neurological

involvement and renal dysfunction are of serious nature.
Treatment with D-pencillamine causes the ring to disappear
in the reverse order of formation.
Arcus Juvenalis
Pathology: Plasma lipoproteins exude from limbal vessels and
get deposited as cholesterol esters, phospholipids and
triglycerides in the peripheral corneal stroma.
Ocular: It presents as white or yellowish, partial or complete
ring at corneal periphery, separated from the limbus by a clear
zone.
Arcus juvenalis occur congenitally in Lecithin-cholesterol acyl
transferase (LCAT) deficiency and in young people with type
2, 3 and 4 hyperlipidemia.
Fig. 6.6.1.7A: KF ring in Wilson’s disease
Systemic: When present in patients younger than 50 years this
is an important indicator of familial hypercholesterolemia and
coronary arterial diseases. Presence of this lesion calls for
serum lipid analysis and further management.
Arcus senilis is age related change in elderly people and not
significant clinically.
Gout
Pathology: This is a disorder of purine and pyrimidine
metabolism. The ocular and systemic manifestations are due
to deposition of urate crystals.
Ocular: The crystal deposition is seen at the limbus as mass
like lesions around episcleral vessels causing episcleritis and
scleritis.
Systemic: Acute painful arthritis usually involving metatarsal
joints, most commonly the big toe.
Fig. 6.6.1.7B: Early appearance of KF ring Treatment: Non-steroidal or steroidal anti-inflammatory drugs
(Courtesy: Dr M Vanathi)
and colchicine.
Wilson’s Disease Cystinosis

Pathology: Autosomal recessive disease of copper metabolism This autosomal recessive metabolic disorder is characterized
caused by reduced ceruloplasmin results in copper deposition by conjunctival and peripheral corneal deposition of needle
in tissues. like refractile cystine crystals due to defective transport across
lysosomal membrane.
Ocular Features
Systemic: Nephropathy which could be fatal in infants and
Kayser-Fleischer Ring: This is an important diagnostic finding in youngsters below 30 years of age.
Wilson’s disease. A ring like deposition of copper at Descemet’s Ocular: Polychromatic crystals deposited more densely in
level, in peripheral cornea. Biomicroscopically the ring appears peripheral cornea, causing recurrent epithelial erosions.
as a golden brown to green deposit (Figs 6.6.1.7A and B). It is Treatment: Topical cysteamine 0.1 percent in normal saline
best seen in gonioscopy. applied every hour as eye drops can reverse the crystal
A sunflower cataract can also be associated. deposition.7
Alkaptonuria While lattice corneal dystrophy is a form of local

amyloidosis affecting stroma, gelatinous drop like familial
Pathology: Homogentisic acid oxidase deficiency leading to
amyloidosis affects the corneal epithelium and limbus mainly
homogentisic acid accumulation in connective tissue. This
(Fig. 6.6.1.8). Both dystrophies may be characterized by
autosomal recessive disease is characterized by dark
vascularization which is uncommon in other corneal
pigmentation of skin, cartilage.
dystrophies.
Ocular manifestations include scleral pigmentation near
horizontal recti muscles insertion, pigmented pinguecula, Vitamin A deficiency: Seen in malnourished children and in
brown oil-droplet like deposits at limbus and corneal periphery, adults with malabsorption syndrome.
at the level of Bowman’s membrane or epithelium. Bitot’s spot is the characteristic lesion in the bulbar
conjunctiva adjacent to limbus. They are gray, white, foamy
Amyloidosis dry lesions.
(Refer to the section on diseases of the conjunctiva also)
Pathology: Amyloid is an abnormal protein deposited in
various tissues as primary or secondary metabolic disorder. Other metabolic disorders causing limbal deposits include:
Ocular: In primary systemic amyloidosis, fleshy nodular lesions • Gaucher’s disease—cerebroside lipidosis
are seen in the conjunctiva near limbus. • Porphyria
• Cryoglobulinemia—in multiple myeloma.
LIMBAL, CONJUNCTIVAL AND

CORNEAL DEPOSITIONS
Many systemic drugs can get deposited in the cornea from
the limbal vessels.
Cornea verticillata: A whorl like epithelial deposition caused
by amiodarone (Fig. 6.6.1.9), chloroquine, chlorpromazine and
indomethacin. Usually withdrawing the drug will reverse the
deposition.
Topical Drug Depositions

Ciprofloxacin deposits: Topical ciprofloxacin deposits can
result in chalky white precipitate within an epithelial defect. A
Fig. 6.6.1.8: Primary amyloidosis—Gelatinous drop like lesions crystalline pattern may be observed in other fluoroquinolones
involving corneal epithelium and stroma up to limbus also.
Fig. 6.6.1.9: Amiodarone deposits in whorl pattern

Argyriasis: Silver compounds were commonly used in the pre- periphery (Fig. 6.6.1.11). They become pathognomonic if
antibiotic era in treatment of infections. It consists of a slate present in the center as guttata.
grey or silver discoloration of the bulbar and palpebral
Band keratopathy (Fig. 6.6.1.12) is calcium hydroxyl apatite
conjunctiva. The condition is permanent.
deposition at the level of Bowman’s membrane, epithelial
Adrenochrome: Long standing administration of epinephrine basement membrane and stroma, from limbal vessels.
compounds may lead to dark brown or black deposits in It is associated with diseases of calcium and phosphorous
conjunctiva and cornea. The deposits are harmless but metabolism like hyperparathyroidism, systemic diseases like
sometimes mistaken for conjunctival melanosis. sarcoidosis which causes hypercalcemia. It is also seen in eyes
with chronic inflammatory diseases and in eyes that have
Chrysiasis: Gold deposits seen in patients treated with gold
suffered trauma.
salts for arthritis.
Clinical presentation: It starts in corneal periphery in horizontal
Chalcosis: Copper deposits are seen in Wilson’s disease and
meridian as white powdery deposits, later coalesce to form
retained intraocular copper foreign bodies.
Iron deposits: Most iron lines are at areas of tear pooling related
to surface irregularities. At the limbus, they are seen at the
advancing edge of the pterygium (Stocker’s line) and at the base
of filtering bleb (Ferry’s line). The Hudston Stahli line is located
at the junction of the upper two thirds and lower one-third of
the cornea. Siderosis is a diffuse iron deposition due to retained
metallic foreign bodies (Fig. 6.6.1.10).
DEGENERATIVE DISORDERS
White limbal girdle of Vogt is an extremely common condition
that increases in frequency with age. It is a thin white line
immediately adjacent to and parallel to the limbus just beneath
the epithelium. The limbal girdle is of no clinical significance
and requires no treatment.
Hassal-Henle bodies are age related wart like excrescence of
Descemet’s membrane seen as white nodules at the corneal Fig. 6.6.1.11: Hassal-Henle bodies
Fig. 6.6.1.10: Siderosis Fig. 6.6.1.12: Band shaped keratopathy

elevated plaques with well demarcated round clear areas, 1). In grade 2, this extends to the central cornea compromising
involving the exposed interpalpebral area (Fig. 6.6.1.12). the visual acuity. In grade 3, fine nodules coalesce to form
Treatment includes chelation with EDTA 150 mg/ml. This elevated excrescences, when epithelial erosions and secondary
solution is applied after removing the epithelium and left in infections can complicate the disease. Secondary CDK occurs
place for about 5 minutes. The softened material is then scraped over corneal scars (Fig. 6.6.1.13).
off. A bandage contact lens or an amniotic membrane graft
will facilitate epithelial healing. Phototherapeutic keratectomy Superior Limbic Keratoconjunctivitis
helps to obtain a smoother surface. Recurrence is common This is inflammatory condition which presents as a bilateral
after treatment. localized superior conjunctival inflammation with adjacent
limbal and corneal degenerative changes. This is a highly
Spheroidal Degeneration symptomatic condition which can be associated with thyroid
This is corneal degenerative lesion and is also known as climatic dysfunction. Clinically this is seen as prominent superior bulbar
droplet keratopathy (CDK). The primary type is associated conjunctival vessels with localized boggy loose conjunctiva,
with exposure to ultra-violet rays either direct or reflected from superior limbal thickening and peripheral corneal epithelial
flat snow covered surfaces and sea. Prevalence is more in stippling, and filaments (Figs 6.6.1.14A and B). Of late this is
middle-aged men who are more exposed to sunlight due to considered as a localized form of conjunctivochalasis, where
their occupation. Usually starts as small (10-30 microns) golden Tenon’s support is lost and the loose conjunctiva is inflamed
yellow translucent nodules at Bowman’s layer in corneal due to mechanical friction caused by lid movements. Topical
periphery at the interpalpebral area (3 and 9 o’clock—grade steroidal therapy is of dubious value. Mechanical tightening
Fig. 6.6.1.13: Spheroidal degeneration
Fig. 6.6.1.14A: Superior limbic keratoconjunctivitis Fig. 6.6.1.14B: Superior conjunctivochalasis in SLK
of the loose conjunctiva with localized cauterization or

supporting it with amniotic membrane is found to be effective
in giving symptomatic relief.
Pterygium
This well known clinical entity still remains an enigma in
understanding its etiology and management.
Clinically it appears as a wing of vascular conjunctival tissue
growing over the corneal periphery across the interpalpebral
limbus.
Histopathology of the pterygium tissue shows both
degenerative and proliferative changes. In addition to elastotic
degenerative changes in collagen, epithelial hyperplasia, newly
for med blood vessels and fibrous connective tissue Fig. 6.6.1.15A: Pterygium
components are also demonstrated.
Pathogenesis
Degenerative changes are caused by chronic exposure to UV
radiation.
Proliferative changes caused by UV radiation are also
proposed, as in squamous neoplasia. Overexpression of p53
oncogene is also demonstrated. The fibroblasts in the
pterygium tissue also showed abnormal proliferative capacity.
The high propensity for recurrence shown by both primary
and secondary pterygia also indicates a proliferative
component. Limbal stem cell failure is another proposed
pathology. A localized form of interpalpebral limbal stem cell
failure due to chronic exposure to UV rays focused at the
nasal and temporal inter-palpebral limbus is proposed as a
triggering factor for this disorder.8-10 Fig. 6.6.1.15B: Post conjunctival autograft
Treatment options include excision of the pterygium with
intraoperative application of mitomycin C, 0.02 percent, for 2 fine yellowish white lipid infiltrations at the sharp vertical inner
minutes, with conjunctival auto graft/conjunctival limbal edge of the gutter (Fig. 6.6.1.16). Histopathologically this is
autograft to cover the excised area (Figs 6.6.1.15A and B). proved to be a degenerative disorder affecting basal epithelial
Amniotic membrane grafting may also be done to cover the layer, basement membrane and anterior stromal complex. The
bare area. β irradiation to prevent recurrence is not widely peripheral ectasia causes central corneal flattening and against
practiced due to high incidence of complications like scleral the rule astigmatism. In severe cases irregular astigmatism can
melts. be managed with scleral contact lenses.
(Refer to the section on diseases of the conjunctiva also) (Refer to the section on Corneal Ectasias also)
Terrien’s Marginal Ectatic Degeneration Pellucid Marginal Degeneration

This is non-inflammatory, progressive, bilateral ectatic corneal Though previously considered as a degenerative disorder, this
thinning disorder. Commonly seen in young men between is now considered as a variant stage of ectatic corneal trio of
20 to 30 years, starts in superior corneal periphery as a white keratoconus, pellucid and keratoglobus. Like Terrien’s, this
opacity like arcus. The clear cornea in between this opacity condition affects young individuals. Both sexes can be affected.
and limbus gradually thins out with fine parallel vessels running Usually inferior corneal periphery is affected. A thin band of
on the floor of the gutter. The epithelium remains intact with corneal thinning of 1 to 2 mm width starts from the 4 to 7
Fig. 6.6.1.16: Terrien’s marginal degeneration Fig. 6.6.1.17: Vernal keratoconjunctivitis–Tranta’s spots
o’clock position, about 1 to 2 mm above the limbus (Fig.

6.6.1.18A). The cornea just above the thin band protrudes out.
Rarely a similar picture is described in superior periphery also.
The central cornea will appear elongated with marked flattening.
These changes will result in significant against the rule
astigmatism both clinically and topographically (lobster claw
pattern). Spontaneous Descemet’s tear and acute corneal hydrops
also are possible. This condition is difficult to manage. A large
diameter custom made scleral contact lens like Boston lenses
can be of help. Peripheral crescent shaped customized lamellar
keratoplasty can give tectonic support as well as visual
improvement, but technically challenging.1
(Refer to section on Corneal Ectasias also)
Fig. 6.6.1.18: Perilimbal pigmentation in VKC
HYPERSENSITIVITY DISORDERS
OF LIMBUS
Clinically two forms are seen—limbal and palpebral. The
Vernal Keratoconjunctivitis (VKC) and palpebral variety is characterized by diffuse papillary
Atopic Keratoconjunctivitis hypertrophy of upper tarsal conjunctiva. Limbal VKC has a
thickened gelatinous appearance (Fig. 6.6.1.17). Horner
Pathogenesis: Seasonal recurring, bilateral inflammation Tranta’s spots are whitish dots that represent macro aggregates
predominantly occurs in male children who frequently have a of degenerated eosinophils and epithelial cells. Perilimbal
family history of atopy. The immunopathogenesis is pigmentation of the bulbar conjunctiva is an important feature
multifactorial and involves Type 1 and Type 4 hypersensitivity
seen in dark skin people15 (Fig. 6.6.1.18). Chronic limbal
reactions, enhanced activities of various growth factors
inflammation can cause stress on stem cells and manifest as
resulting in conjunctival fibroblastic stimulation, increased pannus and chronic epitheliopathy. Non-infectious epithelial
substance P and increased estrogen and progestogen receptors
ulcers, oval or shield shaped (shield ulcers), may develop in
in the conjunctiva.11-13 A genetic component cannot be ruled
the superior or central cornea. These ulcers are thought to be
out since this disease was reported to be transmitted through caused by mechanical rubbing by tarsal conjunctival papillae
bone marrow transplantation.14
or from eosinophilic degranulation. VKC is considered as an
Symptoms: Itching, blepharospasm, photophobia, blurred important association with keratoconus which can be better
vision and copious mucoid discharge. appreciated by video keratography.16-18
Management: Symptomatic relief in less severe cases is

achieved by mast cell stabilizers. Severe limbal changes need
immunotherapy with steroids, cyclosporine or tacrolimus to
prevent per manent stem cell damage and epithelial
keratopathy. 19-21 Surgical intervention like superficial
keratectomy and amniotic membrane grafting are needed for
recalcitrant shield ulcers.22
IMMUNE MEDIATED PERIPHERAL

CORNEAL DISORDERS
(Refer to section on Immunological diseases of the cornea also)
The vascular limbus and the adjacent peripheral cornea form
an ideal location for immune mediated diseases. The antigen
presenting Langerhans’ cells are present in corneal periphery Fig. 6.6.1.19: Catarrhal ulcers
and the limbal epithelium. The limbal vasculature brings
antibodies, immune and inflammatory cells to the avascular
cornea.
Classification
Microulcerative: Lesions are single or multiple, less than two
clock hours with fewer tendencies to ulcerate and generally
do not progress centrally.
Macroulcerative: Lesions are more than two clock hours have
a tendency to ulcerate and progress centrally.
Microulcerative Peripheral Keratitis

Catarrhal Ulceration: They are seen in association with Fig. 6.6.1.20: Phlycten
blepharitis as gray white anterior stromal infiltrates parallel to
the limbus and separated by clear zone of 1 mm wide (Fig. with oral doxycycline. In endemic areas, tuberculin testing and
6.6.1.19). Each lesion is less than one clock hour in size and chest X-ray is mandatory.
have a predilection for 2, 4, 8 and 10 clock hour positions.
Sometimes they coalesce to form a large ring infiltrate. Initially Rosacea Keratitis
the epithelium is intact but later epithelial defect may develop.
This disease primarily affects facial skin over malar areas, chin
A toxic or Type 3 immune response to bacterial exotoxins
and forehead. Vascular engorgement and sebaceous gland
and antigen is proposed as pathogenesis.23 Topical antibiotic
pustules are the classical features. Long standing disease can
and steroid application give good response.
cause connective tissue hypertrophy. The exact etiology is not
Phlyctenulosis: They are abscess like elevated lesions with known. Demodex folliculorum is implicated in etiology.
ulceration of the surface (Fig. 6.6.1.20). Commonly occur at Ocular lesions include meibomian dysfunction with
the limbus but can occur in the bulbar conjunctiva also. They erythema of lid margins. Conjunctival congestion is more
are seen in children and young adults. Sometimes a migrating pronounced inferiorly. The corneal lesions are also seen in
lesion at the apex of a leash of vessels called fascicular ulcer inferior quadrants as punctate epithelial erosions and superficial
is seen. It is a Type 4 inflammatory response in which there is vascularization. Recurrent episodes lead on to deeper stromal
infiltration of lymphocytes, macrophages plasma cells and involvement resulting in scarring and thinning. Treatment
PMN cells. This condition is thought to be associated with includes topical steroids and oral doxycycline 100 mg twice
tuberculosis or staphylococcal blepharitis.23 This lesion daily and is slowly tapered and maintained for a long period
responds well to topical steroids. Blepharitis needs to be treated of time. Comanagement with a dermatologist will be needed.
Fig. 6.6.1.21: Peripheral corneal melt in rheumatoid arthritis Fig. 6.6.1.22: Peripheral ulcerative keratitis
Macroulcerative Peripheral Keratitis • Diffusion of immune complexes, components of

complement system into the peripheral cornea, activation
Marginal furrow of rheumatoid: Corneal melt associated
of classical complement pathway, release of cytokines
with rheumatoid arthritis. The most frequent site appears to
be inferior cornea (Fig. 6.6.1.21). The mildest form includes attracting inflammatory cells into perilimbal conjunctiva,
non-progressive areas of localized epithelial thinning with producing collagenase lead to corneal stromal destruction.
intact overlying epithelium. In advanced cases, lesions are Proinflammatory cytokines like IL-1 stimulate MMP
elliptical and develop epithelial defect rapidly, that melt and activation.
perforate. They differ from vasculitic PUK, in that they are • Cell mediated cytotoxicity is also suspected in ANCA
cured by improving the ocular surface wetting. Corticosteroids positive vasculitides.
hasten melt and must be used with caution. • The mechanism in PUK following trauma and surgery
appears to be an aberrant immune response to altered tissue
Peripheral Ulcerative Keratitis (PUK): Peripheral ulcerative antigens.
keratitis is a destructive ulceration of the peripheral cornea About 50 percent of the non-infectious PUK are
with a typical overhanging progressive edge and limbitis (Fig. associated with collagen vascular diseases. Often this is
6.6.1.22). This is an autoimmune disease either directed to the associated with adjacent scleritis. Rheumatoid arthritis (RA)
corneal antigens as in Mooren’s ulcer or a manifestation of a is the most commonly associated vasculitis. In RA, the disease
systemic immune vasculitides like rheumatoid arthritis (RA), manifests long time (mean 19.5 years) after the onset of
Wegeners granulomatosis (WG), polyarteritis nodosa, systemic systemic disease but much earlier in Wegener’s granulomatosis.
lupus erythematosus (SLE), relapsing polychondritis, Sjogrens Bilateral disease is seen in 40 percent of cases. Since PUK can
disease, Behcets, progressive systemic sclerosis and be the first manifestation of a systemic vasculitic disease, timely
inflammatory bowel disease.24 recognition and management with proper immuno-suppressive
Systemic infections like hepatitis C, Salmonella gastro- therapy is mandatory to reduce mortality.24,29,30
enteritis and ocular infections like herpes simplex, varicella-
zoster, Acanthamoeba and fungi are also found to be Mooren’s Ulcer: Though first described in 1849 by Bowman,
associated with PUK.25-28 it is identified with Mooren, a later observer. This painful
ulceration of the peripheral cornea which in severe cases can
Pathophysiology:
destroy the whole cornea but sparing the sclera is mostly a
• Ischemic necrosis: The circulating antigen-antibody
clinical diagnosis (Fig. 6.6.1.23).
complexes deposited in the limbal vessels causing occlusive
vasculitis and resulting ischemia incites inflammatory Epidemiology and pathogenesis: It is presumed to be an autoimmune
ulceration. disease. Gottsch et al demonstrated antibodies to a cornea
• Non-inflammatory degenerative thinning—Terrien’s

marginal degeneration, Pellucid marginal corneal
degeneration.
• Inflammatory disorders—staphylococcal marginal keratitis.
• Peripheral corneal ulcers due to mechanical causes—poor
contact lens fitting, exposure keratitis.
Investigations: Mooren’s ulcer is a diagnosis of exclusion of other
systemic diseases associated with secondary PUK. One study
showed that in 90 percent cases, patients with the clinical
diagnosis of Mooren’s ulcer failed to show any evidence of
systemic involvement either by clinical or serological work-
up.35
Vasculitic PUK can be associated with immune scleritis.
In one retrospective study, 25 of 47 patients with PUK were
found to have associated systemic disease and in 25 percent
Fig. 6.6.1.23: Mooren’s ulcer
of them it remained undiagnosed previously.36 A retrospective
study of 172 scleritis patients showed 14 percent were
specific antigen calgranulin C (COAg), present in corneal
associated with PUK.37 Hence, it is important to do a detailed
epithelium of patients with Mooren’s ulcer.31 This disease is
systemic examination in all cases of PUK.
more common in west, central and South African states and
southern India. It is not only common in certain racial groups, History: For early morning stiffness, severe respiratory
but also found more in next generation migrants to other parts disorders, dermatological disorders, recurrent painful swelling
of the world. This fact suggests a genetic predisposition which of cartilaginous structures likes ear lobe, abdominal pain is to
is supported by observations that showed a correlation be elicited.
between HLA-DR 17(3) and DQ2 and Mooren’s ulcer patients,
Systemic Examination includes examination for rheumatoid
when compared to ethnically matched controls.32 A study in
arthritis with characteristic deformities of patients hands and
south Indian population also confirmed HLA DR17
skin lesions in SLE/acne rosaceae.
correlation.33 Epidemiological studies showed other triggering
factors like trauma, previous cataract surgery, helminth Laboratory Investigations
infections and viral (hepatitis C) infections.34 Chest X-ray: To look for large cavities-(Wegener’s
granuolomatosis), hilar shadows-(sarcoidosis) and cavities-
Watson’s Criteria:
(tuberculosis).
• The presence of a painful crescent shaped peripheral
corneal ulcer Serological: Investigations include complete blood count–
• The presence of extensive undermining of the central edge elevated ESR, rheumatoid factor, anti-nuclear antibodies
of the ulcer (ANA)–in SLE
• Dense corneal infiltrates along the leading edge • Anti-neutrophil cytoplasmic antibodies located in
• Absence of scleritis cytoplasm (c-ANCA) in WG, Syphilis, Hepatitis C.
• Absence of systemic disease. Corneal scraping and culture from the lesion is to be done
Clinically the benign type presents as a slowly progressing to rule out infectious cause.
unilocular lesion in elderly people and responding to treatment. Treatment
In aggressive malignant form which affects usually younger Medical treatment: Topical corticosteroids are given if
adults bilaterally, this disease can be devastatingly destructive. inflammation is present but to be avoided in cases of significant
Often this type can be recalcitrant to therapy and needs corneal thinning and in presence of infection. Topical
maximum systemic immuno-suppression. lubrication with systemic anticollagenases like doxycycline 100
Differential Diagnosis for PUK: mg twice a day is recommended in such cases.
• Infectious peripheral corneal ulcerations should be kept Systemic immunosuppression is needed in severe cases.
in mind and a routine microbiological work-up is • Usually this is started with oral prednisolone 1 mg/kg up
mandatory in these cases. to 60 mg/day, given until remission and tapered in steps
of 10 mg per week up to 40 mg/day, 5mg per week up to clinical picture from that which occur in central cornea. They
20 mg/day and 2.5 mg per week thereafter. can spread to adjacent limbus and sclera earlier than in a central
• A pulse therapy of IV methylprednisolone 1 mg/kg for keratitis. On the other hand, a scleral infection can spread on
three days can be given in very severe cases. to the corneal periphery. Peripheral corneal ulcers acquire an
Blood glucose, lipids, electrolytes, bone density and blood epithelial defect and seen commonly at the area of peripheral
pressure are to be monitored periodically. corneal degenerations like climatic droplet degeneration and
Calcium with vitamin D supplements is needed. exposure following poor eyelid closure. Deeper infections can
Non-steroidal immunosuppression is indicated in cases be seen in association with surgical wounds (Fig. 6.6.1.26).
where steroids show inadequate response or where there is These infections can be of bacterial, fungal, chlamydial
steroid intolerance. and protozoal etiology.
• Methotrexate up to 25 mg per week is the most commonly The common bacterial infections are staphylococcal,
used drug. It is advisable to start these drugs with initial Streptococcus pneumoniae, Pseudomonas and Moraxella.
course of glucocorticoids and taper the latter faster. Moraxella infection usually develops in peripheral cornea in
• Cyclophosphamide (upto 2 mg/kg/day), azathioprine up
to 200 mg daily, mycophenolate mofetil 1 gram twice daily
are the other agents tried.
• Biological agents like infliximab and rituximab are also
tried as second line drugs.
• Sub-conjunctival recombinant human interleukin one
receptor antagonists, antibodies to α-TNF and anti-CD4
monoclonal antibodies have shown short term therapeutic
success.
Patient should be closely monitored for bone marrow
suppression, hepatic or renal toxicity and potential
infections.38-40
Surgical treatment: Necrotic microangiopathy is the common
pathological change shown in 89 percent of the conjunctival
biopsies from PUK patients, proving that the conjunctiva is
the main reservoir for collagenase producing inflammatory
cells.31 A surgical approach of conjunctival resection one clock Fig. 6.6.1.24: Healed PUK after conjunctival resection
hour on either side of ulceration and 4 mm posterior to the
limbus is thought to remove these immune and inflammatory
components temporarily to promote healing (Fig. 6.6.1.24).
However this procedure will not alter the basic course of the
disease. Tissue glue will serve as a block for the immune
mediators from limbus and also help in sealing
microperforations.
Tectonic peripheral corneal grafting (Fig. 6.6.1.25) in severe
cases can break the disease process for sometime by
introducing newer antigens, but may need systemic
immunosuppressive agents to prevent recurrence. In very
severe cases with contact lens cornea, lamellectomy to remove
the remaining antigens will arrest the disease. PKP for visual
rehabilitation is done in long standing, quiescent disease.41,42
INFECTIOUS DISEASES
Peripheral cornea is less susceptible to infectious agents than
central cornea. Peripheral corneal infections present a different Fig. 6.6.1.25: Peripheral patch graft for PUK
Fig. 6.6.1.26: Deep peripheral corneal infection Fig. 6.6.1.27: Peripheral dendrites
from a surgical wound
alcoholics as shallow gray white ulcers. Pneumococcal

infections are common in degenerated corneas and spread
towards center as serpiginous ulcer. Pseudomonas infections
at the periphery can be very severe as ring abscess with poor
prognosis.
Post-operative corneal or corneoscleral wound infections
are commonly caused by, non-tuberculous mycobacteriae or
Nocardia. Peripheral corneal ulcers can occur following
hyperacute conjunctivitis (Neisseria gonorrhoeae), fungal
keratitis, Acanthamoeba and herpes simplex keratitis.
Fungal keratitis at the corneal periphery can have a better
prognosis than a central ulcer, due to the proximity of limbal
vasculature.
A herpetic dendrite at the periphery can give a different
picture. Usually it will be accompanied by significant stromal
cellular infiltration. This picture could be confused with Fig. 6.6.28: Limbal stem cell failure—corneal surface covered
catarrhal ulcers and get treated with corticosteroids which with vascularized epithelium
would worsen the condition. Peripheral viral keratitis runs a
prolonged refractory course when compared to central
infection (Fig. 6.6.1.27).
Non-infectious peripheral corneal ulcers can result from The clinical characteristics of limbal stem cell failure are
systemic infections like bacillary dysentery, brucellosis, mumps, conjunctival ingrowth of the corneal surface across the limbus,
infectious mononucleosis and dengue fever. vascularization, chronic inflammation, and fibrous ingrowth.
Limbal stem cell disorders can be classified as:
LIMBAL STEM CELL DISORDERS • Primary deficiency/Secondary deficiency
Or
Whenever the limbal stem cell barrier is affected, epithelial • Partial stem cell deficiency/Total stem cell deficiency.
cells from the adjacent conjunctiva will invade across the limbus
to cover the denuded corneal surface (Fig. 6.6.1.28). Since, Primary limbal stem cell deficiency includes:
these cells are phenotypically different from corneal epithelium, • Aniridia
abnormalities like recurrent erosions, vascular invasion of the • Multiple endocrine deficiency
corneal surface, and presence of goblet cells are common. • Erythrokeratodermia.
Secondary stem cell disorders includes: 4. Wilson MW, Hungerford JL, et al. Topical mitomycin C for the
• Burns of the ocular surface (chemical and thermal) treatment of conjunctival and corneal epithelial dysplasia and
neoplasia. Am J Ophthalmol 1997;124:303-11.
• Irradiation
5. Vann RR, Karp CL. Perilesional and topical interpheron alfa-2b
• Multiple surgeries for conjunctival and corneal neoplasia. Ophthalmology 1999;
• Contact lens induced 106:91-97.
• Chronic inflammatory and immune disorders 6. Midena E, Angeli CD, Valenti M, et al. Treatment of conjunctival
– Stevens-Johnson syndrome squamous cell carcinoma with topical 5-fluorouracil. Br J
– Ocular cicatricial pemphigoid Ophthalmol 2000;84:268-72.
7. Kaiser-Kupfer MI, Gazzo MA, Datiles MB, et al. A randomized
– Infective keratitis
placebo-controlled trial of cysteamine eye drops in nephropathic
– Vernal keratoconjunctivitis cystinosis. Arch Ophthalmol 1990;108:689-93.
• Neoplastic lesions. 8. Austin P, Jacobiec FA, Iwamoto T. Elastodysplasia and
elastodystrophy as the pathologic bases of ocular pterygia and
Treatment: Usually this requires surgical management in pinguecula. Ophthalmology 1983;90:96-109.
addition to controlling inflammation and restoring lubrication. 9. Dushku N, Reid TW. p53 expression in altered limbal basal cells
Pre-operative planning and preparation is based on the of pingueculae, pterygia and limbal tumors. Current Eye Research
extent of the stem cell loss, laterality and associated ocular 1997;1179-92.
surface conditions like inflammation and structural 10. Kwok LS, Coroneo MT. A model for pterygium formation. Cornea
1994;13:219-24.
abnormalities like symblepharon.
11. Bonini S, Coassin M, Aronni S, Lambiase A. Vernal
Generally, stem cell replacement surgeries are not preferred keratoconjunctivitis. Eye 2004;18:345-51.
in the presence of inflammation, avascularity and exposure. 12. Abu El-Asrar AM, Al-Mansouri S, Tabbara KF, Missotten L,
The surgical plan will be: Geboes K. Immunopathogenesis of conjunctival remodelling in
Unilateral/bilateral, partial limbal stem cell deficiency vernal keratoconjunctivitis. Eye 2006;20:71-9.
(LSCD): 13. Kato N, Fukagawa K, Dogru M, Fujishima H, Tsubota K.
Mechanisms of giant papillar y formation in vernal
• Sequential sectoral conjunctival epitheliectomy
keratoconjunctivitis. Cornea 2006;25:S47-52.
• Amniotic membrane transplantation 14. Tabbara KF, Nassar A, Ahmed SO, Al Mohareb F, Aljurf M.
• Conjunctivo-limbal autograft Acquisition of vernal and atopic keratoconjunctivitis after bone
Unilateral/bilateral total LSCD: marrow transplantation. Am J Ophthalmol 2008;146:462-5.
• Live-related conjunctivo-limbal allograft 15. Luk FO, Wong VW, Rao SK, Lam DS. Perilimbal conjunctival
• Cadaveric conjunctivo-limbal allograft pigmentation in Chinese patients with vernal keratoconjunctivitis.
Eye 2008;22:1011-4.
• Exvivo expanded limbal autograft
16. Tabbara KF. Ocular complications of vernal keratoconjunctivitis.
(Refer to the following section on Limbal Stem Cell Deficiency for further Can J Ophthalmol 1999;34:88-92.
details). 17. Lapid-Gortzak R, Rosen S, Weitzman S, Lifshitz T. Videokerato-
graphy findings in children with vernal keratoconjunctivitis versus
SUMMARY those of healthy children. Ophthalmology 2002;109:2018-23.
18. Dada T, Konkal V, Tandon R, Singh R, Sihota R. Corneal
The corneal limbus and peripheral cornea are affected by a topographic response to intraocular pressure reduction in patients
variety of disorders because of their unique anatomical with vernal keratoconjunctivitis and steroid-induced glaucoma. Eye
characteristics and exposure to immune system components. 2007;21:158-63.
19. Mantelli F, Santos MS, Petitti T, Sgrulletta R, et al. Systematic review
It is important to understand the underlying pathology and and meta-analysis of randomized clinical trials on topical treatments
their systemic associations in these disorders in order to for vernal keratoconjunctivitis. Br J Ophthalmol 2007;91:1656-61.
manage them effectively. 20. Lambiase A, Bonini S, Rasi G, Coassin M, Bruscolini A, Bonini S.
Montelukast, a leukotriene receptor antagonist, in vernal
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3. Shields JA, Shields CL, et al. Surgical management of conjunctival amniotic membrane patch in the treatment of corneal plaque of
tumors. Arch Ophthalmol 1997;115:808-15. vernal keratoconjunctivitis. Eur J Ophthalmol 2008;18:131-3.
23. Mondino BJ, Kowalski R, Ratajczak HV, et al. Rabbit model of 33. Zelefsky JR, Taylor CJ, Srinivasan M, et al. HLA-DR17 and
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1981;99:891-5. 34. Srinivasan M, Zegans ME, Zelefsky JR, et al. Clinical characteristics
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Ulcerative Keratitis. Surv Ophthalmol 1999;43:379-96. 35. Michael E Zegans, M Srinivasan, Thomas McHugh, et al. Mooren
25. Kedhar SR, Belair ML, Jun AS, Sulkowski M, Thorne JE. Scleritis ulcer in South India: serology and clinical risk factors. Am J
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26. Yang J, Baltatzis S, Foster CS. Peripheral ulcerative keratitis after Rheum Dis Clin North Am 2007;33: 835–54.
Salmonella gastroenteritis. Cornea 1998;17:672-4. 37. Tauber J, Sainz de la Maza M, Hoang-Xuan T, Foster CS. An analysis
27. Moreira AT, Prajna NV. Acanthamoeba as a cause of peripheral of therapeutic decision making regarding immunosuppressive
ulcerative keratitis. Cornea 2003;22:576-7.
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29. M Reza Dana, Ying Qian, Pedram Hamrah. Twenty-five year
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ulcerative keratitis and corneal transplant rejection. Cornea 39. Odorcic S, Keystone EC, Ma JJ. Infliximab for the treatment of
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6.6.2 Limbal Stem Cell Deficiency

Kunjal Sejpal, Soundarya Lakshmi Madhira, Geeta K Vemuganti, Virender Sangwan
Stem cells are defined as undifferentiated (primitive) cells that loss of proliferative capacity of the corneal epithelium. Stem
are capable of self-renewal (dividing) and differentiation cells are also located in the conjunctiva, but the corneal and
(changing into cells which have different structural conjunctival epithelia are phenotypically different. However,
characteristics and function). Stem cells have a high recently it has been shown in animal models that the entire
proliferative potential and a long cell cycle. They can undergo ocular surface contains oligopotent stem cells with the capacity
error free proliferation. Schofield, in 1983 proposed the ‘niche to generate individual colonies of corneal and conjunctival
hypothesis’.1 It was proposed that the stem cells exist in an cells and that these oligopotent stem cells have the capacity to
optimal niche that promotes their maintenance in an generate goblet cells if provided with a conjunctival
undifferentiated condition. Following stem cell division, only environment.3,4
one of the daughter cells can re-enter the niche, while the Figure 6.6.2.1 explains the steps in the multiplication of
other daughter cell enters the pathway of terminal limbal stem cells and their differentiation:
differentiation. • The stem cells divide asymmetrically to form daughter cells.
The corneal stem cell niche lies at the limbus, in the • The daughter cell becomes the transient amplifying cell
palisades of Vogt.2 Loss of limbal cells is characterized by the (TAC) which has limited proliferative capacity, high
Fig. 6.6.2.1: Schematic diagram showing different stages of differentiation of stem cells. M1, M2 and M3 represent mitotic cycles
mitotic activity and is poorly differentiated. It is located

at the basal layer of the corneal and limbal epithelium.
The other daughter cell goes back to the stem cell
compartment.
• The TAC forms the post mitotic cell (PMC) which has no
proliferative capacity and is moderately differentiated. It
is located in the superficial layers of the epithelium.
• PMC then forms the terminally differentiated cell (TDC)
which is well differentiated and located in the superficial
layers of the epithelium.
THE XYZ HYPOTHESIS Fig. 6.6.2.2: X, Y, Z hypothesis of Thoft and Friend
The XYZ hypothesis proposed by Thoft and Friend5 explains

the maintenance of the corneal epithelium. X represents the
proliferation of the basal epithelial cells, Y represents the integrity, maintain its clarity. The conjunctival epithelium lies
proliferation and centripetal migration of the limbal cells and on a vascularized stroma and contains mucin-secreting goblet
Z is the epithelial cell loss from the surface (Fig. 6.6.2.2). cells. The limbus acts as a barrier preventing the growth of
Corneal epithelial maintenance can thus be defined by the the conjunctiva onto the cornea. In the absence of a healthy
equation: X+Y = Z. The equation states that if the corneal limbus, the conjunctival epithelial cells tend to migrate in and
epithelium is to be maintained, cell loss must be balanced by envelop the corneal surface. This is called conjunctivalization.
cell replacement.
Classification of Limbal Stem Cell Deficiency
LIMBAL STEM CELL DEFICIENCY
• Etiological classification
The corneal epithelium is smooth, non-keratinized and devoid – Primary
of goblet cells. The stromal avascularity and the epithelial – Secondary
• According to the extent of damage

– Partial: Only a part of the limbus is damaged
– Total: 360° of the limbus is damaged.
Limbal stem cell deficiency (LSCD) classification is elaborated
as denoted in Table 6.6.2.1.
Clinical Features of LSCD

Presenting symptoms: This includes foreign body sensation,
dryness, pain, tearing, photophobia, decreased vision and
blepharospasm.
Signs: Conjunctivalization of the cornea is noted. The palisades
of Vogt are not visible. There is an increase in the permeability Fig. 6.6.2.3: Conjunctival stippling seen after fluorescein staining
of fluorescein and the conjunctivalized cornea has a stippled in limbal stem cell deficiency
appearance when stained with fluorescein (Fig. 6.6.2.3).
Extensive vascularization, repeated epithelial breakdown,
persistent epithelial defects and stromal scarring are the other
findings. The condition may ultimately progress to corneal
melting and perforation. Thus, conjunctivalization,
vascularisation and chronic inflammation are the hallmarks
of LSCD.6 Figures 6.6.2.4 and 6.6.2.5 show partial and total
LSCD, respectively secondary to chemical injury.
Table 6.6.2.1: Classification of LSCD

Primary LSCD Secondary LSCD
• Aniridia Trauma
• Multiple endocrine deficiency • Chemical: acid, alkali, others
• Sclerocornea • Thermal
• Erythrokeratoderma • Radiation
Iatrogenic Fig. 6.6.2.4: Slit-lamp photograph showing partial limbal stem
• Multiple ocular surgeries cell deficiency with conjunctivalization
• Excision of pterygia, limbal
neoplasms
• Cyclocryotherapy
• Antimetabolites–topical
mitomycin-C
• Systemic chemotherapy
Systemic conditions
• Mucous membrane
pemphigoid
• Stevens-Johnson syndrome
• Multiple endocrine disorders
• Vitamin A deficiency
Ocular Diseases
• Post infectious keratitis
• Neurotrophic keratitis
• Keratoconjunctivitis sicca
• Severe vernal
keratoconjunctivitis
• Tumors
• Pterygium
• Contact lens use
Idiopathic Fig. 6.6.2.5: Slit-lamp photograph showing total limbal stem cell
deficiency and conjunctivalization in a patient with chemical injury
Evaluation of a Patient with LSCD periodic acid-Schiff stains identify glycosaminoglycans

within the goblet cells of tissue specimens. However,
• Best corrected visual acuity: Visual acuity may be good if
goblet cells may not be detected in the presence of
scarring does not involve the visual axis. In severe cases,
inflammation or in cases that have severe squamous
especially secondary to chemical injury, scarring is
metaplasia with loss of goblet cells on conjunctival
extensive.
surface as well.
• Lid examination: Trichiasis, distichiasis, meibomitis,
Cytokeratins are a group of proteins that form inter-
lagophthalmos, entropion, ectropion, ptosis may be seen
mediate filaments in epithelial cells and are expressed in
as sequelae of the primary injury. The extent of
distinct patterns during epithelial development and
symblepharon if any and forniceal shortening must be
differentiation. Cytokeratin 3 (CK3) and cytokeratin 12
noted. These must be corrected before attempting any
(CK12) are characteristic of suprabasal corneal cell layers,
surgical intervention for the limbal deficiency.
and are regarded as markers of corneal epithelial
• Tear film examination: Mucin and aqueous tear
differentiation. Cytokeratin 19 (CK19) is a conjunctiva
deficiency results due to goblet and accessory lacrimal
specific cytokeratin. 7 Immunocytochemistry for
gland damage. Detailed dry eye work-up should be done.
cytokeratin markers can distinguish the source of
• Slit-lamp examination: Any hyperemia and keratinization
epithelial cells on corneal surface whether they are of
of the conjunctiva must be noted. Surgical intervention
corneal or conjunctival lineage.
is not advisable in an inflamed eye and treatment with
• Fluorophotometry: quantifies the corneal barrier
topical steroids is recommended.
dysfunction at the subclinical level and confirms the
Corneal findings are as stated above. The extent of
diagnosis of LSCD.
the limbal damage must be noted to plan the treatment.
• Pachymetry: Assessment of the corneal thickness by
Areas of thinning must be looked for. This may be
ultrasound pachymetry, anterior segment OCT or
relevant during surgical removal of the pannus and may
pentacam can be performed when indicated.
necessitate additional lamellar or penetrating
Ocular surface failure may be of two types depending
keratoplasty. Both the eyes must be carefully examined
on the epithelial phenotype as identified by impression
and areas of healthy limbus must be marked, to decide
cytology. Type 1 failure is characterized by squamous
the site for donor limbal tissue in case of cultivated limbal
metaplasia where the non-keratinized corneal epithelium
epithelial transplantation. Details of anterior chamber
is converted to a keratinized epithelium. Type 2 failure
and cataract if any must be noted.
is characterized by LSCD where the normal corneal
• The intraocular pressure must be measured and
epithelium is replaced by conjunctival epithelium.
controlled if high.
• Posterior segment: Evaluation by indirect ophthal-
Management
moscopy is performed if possible. Ultrasound B-scan
must be done with special note of the optic disc status The goal of treatment (Table 6.6.2.2) in these patients is:
in case the fundus is not visualized. • To first restore the ocular surface and
• General examination: Systemic examination to look for • Then perform surgery for visual rehabilitation if
lesions in the mouth, throat, vagina, urethra, anus and required.
the skin must be performed as in cases of Stevens- Unilateral partial LSCD may only require observation8 if
Johnson syndrome the patient is asymptomatic. Repeated mechanical debridement
• Electrophysiological tests: ERG/VEP: These are known as sequential sector conjunctival epitheliectomy,8 amniotic
important in extensively damaged eyes and in children membrane transplantation9 and ipsilateral limbal translocation10
for prognosis and surgical intervention. to an area of LSCD are therapeutic options available.
• Conjunctival impression cytology (CIC): Impression Amniotic membrane promotes epithelialization and
cytology is a clinical test that allows for collection of reduces angiogenesis and inflammation. It preserves and
the most superficial layers of the ocular surface by maintains the epithelial progenitor cells and thus can be used
applying a nitrocellulose filter paper so that cells adherent instead of limbal transplantation, in the management of partial
to that surface are subsequently removed from the tissue. limbal stem cell deficiency ranging from 40-330°.9,11,12 Total
The presence of goblet cells on the cornea helps to unilateral LSCD requires an autograft which may be harvested
diagnose LSCD in suspicious cases. Alcian blue and from the healthy fellow eye, and either transplanted directly
Table 6.6.2.2: Management of limbal stem cell deficiency
Unilateral LSCD Partial Observe Mechanical debridement Amniotic membrane grafting, ipsilateral
limbal translocation
Total CLAU Cu-LAU Lr-CLAL (one-eyed)
Bilateral LSCD Partial KLAL Lr-CLAL Cu-LAU
Total KLAL Lr-CLAL Cu-LrLAL
CLAU: conjunctival limbal autograft, KLAL: keratolimbal allograft, Lr-CLAL: living related conjunctival
allograft, Cu-LAU: cultured limbal autograft, Cu-LrLAL: cultured, living related limbal allograft
or following cultivation of stem cells ex vivo. Large limbal from the corneo-scleral rims obtained from discarded or post-
autografts from the normal eye may induce iatrogenic limbal penetrating keratoplasty, or limbal biopsies from fellow eyes
deficiency in that eye. Successful transplantation of 8 clock of patients with LSCD are now being used for cell culture.18,19
hours of conjunctival limbal autograft from the healthy fellow Fresh tissues have been shown to have a higher potential for
eye for a large series of cases with unilateral LSCD was first growth over cadaveric ones owing to concerns of donor age,
reported by Kenyon and Tseng in 1989.13 An allograft may death to enucleation time and duration of storage in the eye
have to be used in one-eyed patients. In patients with a bank.20 Limbal tissues stored at room temperature, in
phthisical eye, the intact limbus can be used to culture the refrigerators21 or in liquid nitrogen22-24 are as good as fresh
limbal stem cells. biopsies, but the possibilities of initial delay in growth initiation
In total bilateral LSCD, the allograft tissue may be from explants in stored biopsies cannot be ruled out.
obtained either from a cadaveric donor or a living related donor
and either transplanted directly or after culturing the stem cells.
Media
It is essential to monitor the donor after surgery, as there may
be stem cell attrition due to inflammation and sub-clinical Culture media is essentially a combination of growth factors
donor disease.14,15 Living related allograft transplantation has and cytokines, salts, amino acids, electrolytes, hormones, or
the advantage of providing fresh tissue with more viable stem peptide growth factors25 and carbohydrates maintained at a
cells and is technically easier. Cadaveric limbal allo- specific pH, used with or without a serum supplement and
transplantation should be performed from a donor generally is shown to play an integral role in the type and quality of
under 50 years of age. The transplantation should be cultured cells.
performed within 72 hours, else viability of stem cells is The media used for limbal cultures is similar to that
doubtful.16 It has the advantage of 360° limbal coverage, but formulated for epidermal keratinocytes. Human corneal
the chances of rejection are more than living related allo- epithelial medium (HCEM)20,26 or Dulbecco’s minimal
transplantation.17 essential medium (DMEM)27 supplemented with 10 percent
However, allografts require prolonged immuno- serum of fetal bovine or autologous origins have been widely
suppression. Due to the problems associated with prolonged used. Other media such as CnT20 from Millipore, TMEM28
immunosuppression, cultivated oral mucosal transplantation and VitroGroTM complex,29 are also being experimented for
is now being tried and is described later. cultivation of limbal epithelial cells (LECs).
In partial bilateral LSCD, healthy limbal tissue from an
unaffected site may be cultured and transplanted.
Choice of Substrate
Culture Technique A substrate to be used for cultivation of LECs should satisfy
The establishment of limbal tissue as a source of stem cells the criteria of high optical clarity, appropriate refractive index,
for corneal regeneration5 has opened avenues for new dimensions as that of cornea, be adequately robust for
treatment modalities of ocular surface reconstruction by implantation, nontoxic, non-immunogenic, non-inflammatory,
transplanting limbal stem cells as direct tissue termed as limbal and most importantly promote regeneration of corneal cells
transplantation or as cultivated cells termed as cultivated and nerves. Several such substrates of biological or biosynthetic
limbal stem cell transplantation. Limbal stem cells harvested origin have been applied for ocular surface reconstruction.
Biological substrates: Human amniotic membrane (HAM) which sources being explored as feeder layers include human adult
is the innermost layer of placenta, satisfying most of the above uterine endometrial cells, human adult breast parenchymal cells
said criteria is the most common biological substrate used for and embryonic fibroblasts55 and human amniotic epithelial
in vitro cultivation and transfer of limbal,30 conjunctival31 and cells.56
oral mucosal32 cells for ocular surface reconstruction. Its role
in maintaining the stemness of stem cells33 and providing niche Explant Culture Technique
for limbal stem cell proliferation34 has also been studied. Both Bits of limbal tissues (explants) from limbal biopsies are
fresh and preserved HAM have been found to function equally inoculated onto intact or denuded HAM17 or 35 mm plastic
well on transplantation to ocular surface, but subject to the culture plates,57 allowed to adhere and cultivated to obtain
concerns of serological testing of donor and placenta to limbal epithelial cultures.
eliminate risk of disease transmission. Standard protocol by Though HAM can be used with or without its native
Kim et al35 for the preparation of HAM from placenta is epithelium, Schwab et al,58 and our group prefer to use the
followed by various laboratories where placenta from cesarian de-epithelialized membrane as it facilitates good visibility of
deliveries is washed with Ringer solution containing antibiotics, cultured cells and confluent growth of cells. However
amnion (separated from chorion) is spread on a nitrocellulose argument in favor of intact amniotic membrane epithelium52
paper with epithelial side up, cut into required dimensions is that it retains stem cell characteristics, promotes growth
and stored in DMEM Glycerol at 70oC. HAM is thawed at rate with better stratification.59 After explanting the fragmented
37oC before use. limbal tissues on the membrane, the cells are fed with 3-4 ml
Apart from major reports on the use of HAM, isolated of medium, incubated at 37oC, 5 percent CO2 and monitored
reports of substrates such as fibrin36-38 human anterior lens for growth on alternate days. The culture is terminated when
capsule,39 corneal or limbal stroma,40 therapeutic contact lens a monolayer of the cells growing from the explants becomes
using Lotrafilcon A41 are also available in literature. confluent, in 10 to 14 days. The monolayer proliferates in
vivo to produce stratified epithelium after transplantation.
Tissue Engineered Substrates: Increased risk of disease
transmission, allograft rejection and handling difficulties
Suspension Culture Technique
opened doors for biosynthetic materials custom fabricated as
stromal substitutes, using principles of tissue engineering as Single cell suspensions of LECs from dispase II digested limbal
substrates for cultivation and transplantation of limbal tissues are seeded onto HAM60 or plastic tissue culture dishes,18
epithelial cells. Collagen scaffolds,42 temperature responsive allowed to adhere and cultured to obtain a monolayer of cells.
gels43 using thermoregulatory polymers such as Mebiol,44 Conflicting reports61 state that suspension culture technique
myogels,45 chitin, etc.46 are a few such scaffolds, which rely on yields superior quality of cells to explant cultures.
the extracellular matrix components as the major constituents
of the substrate. In addition, coated surfaces with basement Organ Culture Technique
membrane proteins (laminin, fibronectin and collagen-IV),47,48 Corneal organ culture technique which uses entire
matrix derived from HAM49 have been extensively used as corneoscleral rim with approximately 4 mm of limbal
substrates. conjunctiva and endothelial concavity filled with gel containing
minimal essential medium, agarose and rat tail tendon collagen,
Techniques of Cultivation cultured as a whole unit was established as an in vitro model
to study corneal wound healing.62
Since the first demonstration by Sun et al,50 many groups have
explored various principles of tissue culture with respect to
Airlift Technique
matrix, medium submerged or air-lift technique and use of
feeder cells. Most of the adult stem cell cultures have Air-liquid interface system or “Airlift” technique is known to
necessitated the use of mitotically inactive and metabolically simulate stratification in many epithelial cell systems including
active feeder cells such as 3T3 cells from mouse embryonic LECs 63 by unknown mechanisms. In this technique,
fibroblasts.51,43,52 MRC-5, a human embryonic fibroblast cell stratification of cultured monolayer of cells is believed to be
line, and J2 3T3 mouse fibroblasts53 have been used for the stimulated by lowering the level of medium64,17,65 or using
cultivation of limbal, conjunctival and oral mucosal cells. culture inserts40 and further cultured for two to three weeks
Alternatively the stromal cells emerging from delayed explant thus making a minimum culture duration of 30 days. 60
cultures could also confer similar effects.54 Alternative human Necessity of an airlift technique for culture of limbal epithelial
cells is also a matter of debate, as some groups believe in in edge of the explants, while the paraffin sections of late cultures
vivo stratification and airlifting may reduce the proliferative show stratification with two to four layers of cuboidal epithelial
potential.66 cells (Fig. 6.6.2.6D). Ultrastructural studies reveal cuboidal cells
arranged as layers with distinct intercellular desmosomes and
Characterization hemidesmosomes on the underlying substrate and numerous
Characterization of the cultivated LECs is aimed to answer microvilli on the apical cells.
the extent of morphological, molecular and immuno-
phenotypic similarity of cultivated cells to native corneal Label Retaining Cell Studies
epithelium.
Slow cycling nature of the cultured cells is established by
Morphology calculating the labeling index using DNA labels (Tritiated
Cultured explants initially show clusters of round cells at the thymidine [3H1] or bromo-, chloro- or iodouridine26,67 that
edge of the explant, which adhere and expand on the are incorporated during the synthetic phase of cell division.
membrane as cuboidal cells with pushy margins. In 10 to 14 Labeled cells are quantified using immunohistochemistry,
days, they form a uniform monolayer of closely packed immunofluorescence or confocal microscopy (for both in vitro
cuboidal cells covering the entire membrane (Figs 6.6.2.6A to and in vivo assays). Non-radioactive nature of Bromodeoxy-
C). Examination of the cells at this stage show a monolayer uridine (BrdU) has made it the most widely accepted label for
of polygonal cells with vesicular nuclei originating from the these studies.
Figs 6.6.2.6A to E: Morphology, histology and cytokeratin profile of cultivated limbal epithelium on Human Amniotic Membrane. Figures
A to C represent the morphology of cultivated cells as seen under the phase contrast microscope (all at a magnification of 100×). The
figures show limbal explant (yellow arrow), cells originating from the explants (white arrow) and denuded amniotic membrane (blue
arrow) (A); Growing edge of the epithelial monolayer (green arrow) (B); and a confluent monolayer of cuboidal limbal epithelial cells
covering the amniotic membrane; (C); Figures also show multilayered (2-4 layers) epithelium of cultured limbal cells (D); and expression
of cytokeratin 3 (E); A corneal differentiation specific marker as seen by immunohistochemistry using anti-human CK3 (chemicon)
Gene Expression Profiles from holoclone to meroclone to paraclone.82 Similar clonal

patterns have also been shown in the limbal stem cells.83-85
Gene expression profiles of native and cultured limbal
The turnover of these clonal transitions is supposed to take a
epithelial cells evaluated by various groups68,69 have revealed
duration of 3 weeks in uninjured corneal epithelium86 inferring
a set of 100 genes differentially expressed in limbal versus
an alternative source of residual dividing cells.
corneal epithelial basal cells, up-regulation of genes for
epiregulin, basic keratin complex 2, FGFr1 and Dab2 in the
Side Population Studies
limbus and three genes in cornea suggesting a signature set of
genes similar to that in neural, hematopoietic and embryonic Side population cells which are immature cells, growth arrested,
stem cells. smaller in size, expressing ABCG2, Bmi-1, increased nestin
expression, low expression of Integrins a6 and b1, constituting
Proteomics to about 0.73 +/- 0.14 percent of the epithelium have been
shown in many tissues including limbus.87
Proteomic analysis by different groups showed an enhanced
secretion of anti-angiogenic factors – endostatin and restin, Alternative Sources for LECs
stratifin,70 proteins such as SPARC, vimentin, serine protease,
collagen alpha 2 precursor, tissue inhibitor of metallo- Graft rejection and prolonged immunosuppression, the most
proteinase 2 and 5,10-methylenetetrahydrofolate reductase important considerations of allografts lead the search for
(FADH2) selectively expressed by limbal fibroblasts.71 autologous sources of cells for limbal epithelial transplantation.
An alternative tissue source for limbal epithelial cells should
Immunophenotyping satisfy the features of a non-keratinized squamous epithelium,
non-vasculogenic nature and function as limbal epithelial cells
The proliferative pool of epidermis is comprised of stem cells post transplantation. Oral mucosal epithelial cells, 32,88
and transient amplifying cells which have a poorly distinct epidermal adult stem cells derived from ear skin,89 conjunctival
immunophenotype.72 Studies by various groups72,73 have epithelial cells90,91 and embryonic stem cells92 are some of such
shown this pool to possess a large nucleus to cytoplasm ratio, sources evaluated for ocular surface reconstruction in animal
small and relatively undifferentiated cells, both biochemically models and humans.
and ultrastructurally. Since definitive phenotype of the cultured
limbal epithelial cells is not yet known, a combinatorial Oral Mucosal Epithelium
immuno-profile of markers such as cornea specific cytokeratin
Oral mucosal epithelium is a non-ocular, non-keratinized
pair K3/12 (Fig. 6.6.2.6E), CK19, integrin b1, DNp63
(keratinized at regions) epithelium. The cultivated oral epithelial
isoforms (more specifically DNp63a),74 connexin 43, EGFR,
cells closely resemble corneal epithelial cells with tight cell
Ki-67,57 a low granularity and high N/C ratio75 with recent
junctions and numerous microvilli on the apical side. They
inclusions of low affinity nerve growth factor receptor 75
also express keratin-3, a reliable marker for corneal
(p75),76-78 pan-cytokeratin and vimentin, ABCG2, gap junction
differentiation. The vascularity of oral mucosa is a major
intercellular communication (GJIC), 79 c-kit 74 aldose
concern as vascularization of the cornea post transplantation
dehydrogenase 1 (ALDH1) and RHAMM/HMMR expression,
would merely make it a cosmetic surgery with no improvement
etc.80 supported by results from side population studies, BrdU
in the visual acuity.
incorporation studies (LRCs) or colony forming unit (CFU)
Cultivation of oral mucosal cells for ocular surface
assays are being widely used.
reconstruction32, 93,94 have used both a feeder free95 or a feeder
cell43,96 technique on substrates such as HAM32 or temperature
Clonal Assays/Colony Forming Assays
responsive gels95 similar to limbal epithelial cell cultivation as
Three clonal types of multiplying epidermal keratinocytes have described above. In the longest study reported so far, cultured
been described based on the difference (decreasing abilities) oral mucosal epithelial cells were transplanted in patients with
in the frequency with which they give rise to terminal progeny LSCD and followed for up to 34 months.97 The results from
as holoclones,81 paraclones and meroclones with unidirectional this study are promising, showing formation of a stable ocular
transition (due to progressively restricted growth potential) surface in patients and improvement in visual acuity.
SURGICAL TECHNIQUE FOR LIMBAL patient), with a conjunctival spring scissors, a conjunctival
TRANSPLANTATION peritomy is made 2-3 mm from the limbus and dissection of
the conjunctiva is carried forwards to 1 mm beyond the limbal
Limbal stem cell transplantation is a good surgical option for
arcade. The harvested tissue should exclude the Tenon’s capsule
LSCD secondary to chemical injury, but may not be so effective
and should include the palisades of Vogt. A 1 × 2 mm2 piece
in cases of Stevens-Johnson syndrome (SJS) or ocular cicatricial
of tissue is excised and placed in Human Corneal Epithelial
pemphigoid (OCP). In primary LSCD, the stromal
Medium (HCEM). The tissue is sent to the stem cell laboratory
microenvironment is unable to support stem cells. Hence
immediately and processed.
limbal transplantation may not be useful.
Limbal transplantation: This is performed approximately 14
Conjunctival Limbal Autograft days after the limbal biopsy. The fibrovascular pannus covering
the ocular surface is excised from the cornea. Dissection of
This technique can be used for patients with partial or complete the fibrovascular pannus is started 3-4 mm beyond the limbus
limbal stem cell deficiency, usually secondary to chemical using a conjunctival spring scissors until the limbus and
injuries. In this technique, a peritomy is made in the healthy beyond. Hemostasis can be achieved by using dilute adrenaline
fellow eye, parallel and 3 to 4 mm away from the limbus, under (1:10,000). Deeper dissection of the cornea is avoided by using
local or general anesthesia. The conjunctival flap without the a bevel-up Beaver blade. Symblepharon is released if present.
underlying Tenon’s is reflected onto the cornea and Fornix reconstruction is also done where needed. The amniotic
undermined upto the limbus and minimally into the corneal membrane with the monolayer of cultivated limbal epithelial
stroma. This donor tissue is sutured on the recipient eye, with cells with the epithelial side up is spread over the defect. Fibrin
10-0 nylon sutures, or secured with fibrin glue. A similar glue or sutures (10/0 nylon on corneal side and 8/0 vicryl on
procedure is followed for a live related conjunctival-limbal the scleral side) can be used to secure the amniotic membrane
allograft, in one-eyed patients or in patients with bilateral to the surface. Figures 6.6.2.7A to C are preoperative and
LSCD. The donor is preferably HLA matched. The preparation postoperative photographs of a patient with limbal stem cell
of the recipient eye has been described along with the deficiency after chemical injury, treated with cultivated limbal
technique for cultivated limbal epithelial transplantation. stem cell transplantation.
In cases with severe corneal thinning, a lamellar or
Keratolimbal Allograft penetrating keratoplasty may have to be performed
In cases where the donor tissue is obtained from a cadaver simultaneously.98 Similarly, a keratoplasty may be essential to
eye, a corneoscleral button or whole globe can be used. In restore vision in cases with significant residual corneal scarring
cases of a corneo-scleral button, the scleral rim should be and is performed at a later stage.30 Simultaneous penetrating
atleast 4 to 5 mm wide and a conjunctival rim of 3 to 4 mm keratoplasty and limbal transplantation can also be performed.
width is generally preserved. The central cornea is trephined However, a greater risk of rejection of corneal grafts exists
and the corneo-scleral rim is used for lamellar dissection which with an inflamed and vascularized recipient corneal stroma.99
is upto 1/3 to 1/2 depth of the sclera. This lenticule is sutured It is recommended to wait for atleast three months following
over the recipient limbus, covering 360° of the recipient limbus. limbal transplantation.16 Some recommend waiting for a year
and performing a deep lamellar keratoplasty if the endothelium
Cultivated Autologous Limbal is healthy.100
Epithelial Transplantation In patients with extensive ocular surface damage with
symblepharon and LSCD, transplantation of cultured limbal
Limbal stem cell harvest: A limbal biopsy is taken from the
and conjunctival epithelium may be beneficial.101
contralateral eye in unilateral cases. In bilateral cases with
asymmetric involvement and partial LSCD in one eye, the
Postoperative Management
biopsy may be taken from the eye with less severe damage. In
bilateral cases with total LSCD, the only option is an allograft Postoperatively, the patient is treated with topical antibiotics
harvested from a live-related donor or a cadaver. Informed for approximately two weeks and topical steroids, preferably,
consent is taken from the patient or the guardian. Under strict preservative-free. Indefinite immunosuppression is needed
aseptic precautions with topical, peribulbar or general after allograft transplantation. The most commonly used
anesthesia (depending on the age and compliance of the immunosuppressives are cyclosporine A (3 to 12 mg/kg) along
with systemic steroids (oral prednisolone 1 mg/kg,

dexamethasone 8 mg/day, or intravenous methylprednisolone
2 mg/kg). Others include azathioprine and mycophenolate
mofetil (2 g/day), tacrolimus (FK506) (0.1-0.2 mg/kg per day).
A combination regimen consisting of systemic FK506 in the
dose of 0.5 mg/kg/day, starting one week before the surgery,
along with 2 g/day of mycophenolate mofetil, 0.5mg/kg/day
prednisolone and acyclovir 200 mg 5 times a day starting 3
days before surgery has been found to be more effective than
cyclosporine alone.102
Complications
• Intraoperative complications include bleeding during
Fig. 6.6.2.7A: Photograph showing total LSCD with persistent pannus dissection, injury to recti during extensive
epithelial defect in a patient with chemical injury symblepharon release and deeper corneal dissection leading
to perforation.
• Postoperative complications include epithelial breakdown,
persistent epithelial defect, thinning, perforation, limbal
allograft rejection, graft rejection and failure, infective
keratitis and secondary glaucoma.
Outcome
Rao et al103 performed CLAU in 16 eyes with chemical injury
and reported an improvement in BCVA of more than two
Snellen lines in 13 (81.3%) of 16 patients. Kwitko et al104
performed living related conjunctival allograft
transplantation in 12 eyes. 11/12 eyes had successful transplant
with improvement in vision in 5/11 eyes. Wylegala et al105
Fig. 6.6.2.7B: Seven weeks post cultivated autologous limbal stem performed living-related conjunctival limbal autograft (lr-
cell transplantation, the ocular surface is stable with residual scarring CLAL) in 26 eyes and keratolimbal allograft (KLAL)
in the same patient
transplantation in 43 eyes and the three and five years graft
survival rates were 76.1 percent and 61.9 percent, respectively.
For keratolimbal allograft alone, the survival of the
allograft was noted to decrease from 54.4 percent at 1 year,
33.3 percent at 2 years, and 27.3 percent at 3 years in a series
by Ilari and Daya.100
Use of ex vivo cultured autologous limbal stem cells has
been reported by Rama et al in 18 eyes with an improvement
of BCVA of two Snellen lines in seven (38.9%) of 18 eyes. In
another series by Sangwan et al,106 ocular surface stability was
achieved in 73.1 percent of 88 eyes. Shimazki et al107 used
cultivated allolimbal epithelium in 13 cases and reported ocular
surface stability in 46.2 percent cases.
SUMMARY
Fig. 6.6.2.7C: Ten months postoperatively, there is a reduction in
the density of scar and surface is stable with Snellen visual acuity The primary objective of surgical intervention in limbal stem
of 6/7.5 with contact lenses cell deficiency is ocular surface stability and symptomatic relief.
Visual recovery is a secondary goal. Visual rehabilitation may preparation by eye banks, and standard surgical technique. Cornea
require use of contact lenses or additional surgical 1999;18:52-8.
17. Tsai RJF, Li LM, Chen JK. Reconstruction of damaged corneas
interventions like lamellar and penetrating keratoplasty.
by transplantation of autologous limbal epithelial cells. N Engl J
However, careful selection of cases is warranted. Patients with Med 2000;343:86-93.
reduced tear function may have a poor outcome. Some patients 18. Lindberg K, Brown ME, Chaves HV, Kenyon KR, Rheinwald JG.
may need a repeat transplantation. The prognosis, side effects In vitro propagation of human ocular surface epithelial cells for
of prolonged immunosuppression and need for multiple transplantation. Invest Ophthalmol Vis Sci. 1993;34:2672-9.
surgeries and frequent follow-ups must be discussed with the 19. Fatima A, Iftekhar G, Sangwan VS, Vemuganti GK. Ocular surface
changes in limbal stem cell deficiency caused by chemical injury: a
patient. Pediatric patients need timely intervention for visual
histologic study of excised pannus from recipients of cultured
rehabilitation and amblyopia therapy. Short and intermediate corneal epithelium. Eye 2008;22:1161-7.
term results are promising, but long term survival of limbal 20. Vemuganti GK, Kashyap S, Sangwan VS, Singh S. Ex-vivo potential
transplantation needs evaluation. of cadaveric and fresh limbal tissues to regenerate cultured
epithelium. Indian J Ophthalmol 2004;52:113-20.
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composed of autologous oral mucosal epithelium. N Engl J Med 104. Kwitko S, Marinho D, Barcaro S, Bocaccio F, Rymer S, Fernandes
2004;351:1187-96. S, Neumann J. Allograft conjunctival transplantation for bilateral
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allograft transplant for severe corneal burns. Ophthalmol Surg
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99. Gottsch JD, Jakobs FM, Stark WJ. Regrafting In : Brightbill FS, 106. Sangwan VS, Matalia HP, Vemuganti GK, Fatima A, Ifthekar G,
editor. Corneal surgery : Theory, Technique and Tissue. 3rd ed. St. Singh S, Nutheti R, Rao GN. Clinical outcome of autologous
Louis : Mosby, Inc 1999;508. cultivated limbal epithelium transplantation. Indian J Ophthalmol
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Chapter 6.7
INFECTIONS OF THE CORNEA

AND EXTERNAL EYE
6.7.1 Bacterial Conjunctivitis and Keratitis

R Revathi, Parameshwar Bhat, Abhishek Saraf
Bacterial infections of the external eye may be broadly Clinical Manifestation of blepharitis: Symptoms include burning
considered under the following subheadings: sensation, foreign body sensation, itching and crusting of the
Lid lid margins typically in the early morning. Signs include lid
• Blepharitis margin erythema, matting of the lashes, hard crusts overlying
• Hordeolum small ulcers at the base of the lashes (Fig. 6.7.1.1). On healing
• Blepharoconjunctivitis the ulcers cause small scars leading onto irregularity of the lid
margin with trichiasis, madarosis and poliosis. Bulbar
Conjunctiva conjunctival congestion and tear film instability are associated
• Acute conjunctivitis features.
• Chronic conjunctivitis
• Neonatal conjunctivitis
Cornea
• Keratitis
BLEPHARITIS/
BLEPHAROCONJUNCTIVITIS
This is characterized by infection and inflammation of the
eyelid margin. It may be of the squamous or the ulcerative
type.
Pathogenesis
Infectious — Staphylococcus aureus, Moraxella lacunata
Inflammatory — Seborrhea:
• Meibomian gland dysfunction
Usually both etiologies overlap and are with associated
with conjunctival and corneal changes that manifest as either
blepharoconjunctivitis or blepharokeratoconjunctivitis. Fig. 6.7.1.1: Ulcerative blepharitis
Blepharoconjunctivitis is characterized by chronic INFECTIONS OF THE SEBACEOUS

conjunctivitis due to inflammation resulting from toxins of GLANDS OF THE EYE LIDS
bacteria affecting the lidmargins and the meibomian gland
Hordeolum externum: This is caused by an infection of Zeiss or
secretions.
Moll glands (modified sweat glands) and present just anterior
Signs include bulbar conjunctival congestion, papillary
to the lash line.
reaction of the inferior tarsal conjunctiva. Corneal inferior
epithelial stippling, marginal ulcers and phlyctenular lesions, Hordeolum internum: Meibomian gland infection in the posterior
are also associated with chronic Staphylococcal lid margin or pus point on the tarsal conjunctival side. Hordeola
blepharokeratoconjunctivitis (Fig. 6.7.1.2). are painful conditions with marked lid edema which can mask
the localized infection. Careful palpation will identify tender,
Angular blepharoconjunctivitis: Excoriation of the mucocutaneous
indurated abscess base.
junction at lateral canthus, frothy secretions covering superficial
Evacuation of the pus can be done with epilation of the
ulcerations with adjacent conjunctival congestion are the
infected eye lash in hordeolum externum. Since hordeolum
characteristic features of Moraxella lacunata infection.
internum is on the tarsal conjunctival side, surgical intervention
Management: In acute blepharitis or blepharoconjunctivitis a is avoided. Warm compress and lid massage can be attempted.
broad spectrum antibacterial therapy is started with lid hygiene. Systemic antibiotic therapy is recommended.
When the response is not satisfactory microbiological work
up is recommended to identify the organism and sensitivity. BACTERIAL CONJUNCTIVITIS
IN ADULTS
Lid hygiene: The crusts should be removed with warm
compresses and mild scrubs like diluted baby shampoo. An Acute bacterial conjunctivitis - Acute Catarrhal Conjunctivitis
antibiotic ointment with least toxicity and efficacy mainly caused by bacteria is usually self-limiting. Infection spreads
against staphylococcal species is preferable to avoid resistance. from distant source by hand, aerolized contact or from adjacent
Macrolide antibiotics like erythromycin or azithromycin are structures like lacrimal sac and upper respiratory tract. Bilateral
preferred. The inflammatory component is addressed with involvement occurs in up to 80 percent cases thus bilateral
mild steroids and oral doxycyclin. Tear film instability is treatment can be started even when presenting unilaterally.1
managed with non-preserved lubricants. The treatment should Acute conjunctivitis is defined by onset within three weeks
be continued for several weeks to months. of presentation. Hyperpurulent conjunctivitis manifests with
profuse purulence, lid edema, chemosis, and subconjunctival
hemorrhages.1 Chronic conjunctivitis defined by persistence
for at least three weeks is mostly caused by Staphylococcus aureus
or Moraxella lacunata.1
Pathogenic Micro-organisms
Childhood conjunctivitis: Hemophilus influenzae comprise 58 percent
of bacterial cases. Streptococcus pneumoniae, Staphylococcus aureus and
Moraxella catarrhalis are other causative organisms.1
Acute catarrhal conjunctivitis: Staphylococcus aureus is the
most frequent cause followed by Streptococcus pneumoniae,
Hemophilus influenzae, and Moraxella species.1
Hyperpurulent conjunctivitis: Classically caused by Neisseria
gonorrheae and Neisseria meningitidis, though Streptococcus and
Staphylococcus species may be causative.1
Acute membranous conjunctivitis: Streptococcus pyogenes and
Corynebacterium diphtheriae.1
Symptoms include acute swelling of eyelids, crusting and
Fig. 6.7.1.2: Marginal ulcers with blepharitis matting of lashes more in early morning and mucopurulent
Infections of the Cornea and External Eye 497
discharge. Signs include marked lid edema, matted lashes, marked lid swelling with cellulites, massive chemosis obscures
purulent discharge and conjunctival chemosis. Petechial the cornea. The cornea is seen at the bottom of a well caused
hemorrhages are rare, pseudomembrane can occur. by the chemosed conjunctiva and shows diffuse epithelial haze.
Management: Treatment is usually initiated before receiving Pooling of frank purulent discharge at limbus will lead onto
marginal corneal infiltrations and melt.
culture results, or in some cases, culture may not be done.2
The infection is usually self-limiting, but current consensus Treatment: Systemic antibiotics constitute mainstay therapy.
supports the use of topical antibiotics3-6 as they: Since penicillin resistance strains are emerging, IV Ceftrioxone
• provide symptomatic relief 1 gm twice a day for three days or Ciprofloxacin 500 mg bid
• hasten microbial remission for five days is recommended. Topical antibiotic ointment will
• shorten disease duration reduce matting of lids. Conjunctival secretions containing toxic
• reduce risk of developing sight-threatening complications byproducts of inflammation have to be washed out repeatedly.
• reduce rate of re-infection
• prevent infection spread BACTERIAL CONJUNCTIVITIS
Hyperpurulent conjunctivitis, membranous conjunctivitis IN NEONATES
when not attributed to adenovirus and chronic follicular Neonatal conjunctivitis is defined as an external ocular infec-
conjunctivitis should be cultured.1 Staphylococcus epidermidis, tion occurring during the first month of life.7 It represents a
Streptococcus viridans, and diphtheroids usually are not believed public health problem in developing countries as it can cause
to be pathogenic, may also cause infection.1 Empirical, broad irreversible blindness.7 About 2 to 12 percent of newborns
spectrum antibiotic therapy is usually started immediately. develop conjunctivitis in their first 28 days of life.
Fluoroquinolone eye drops are long acting, with a good Conjunctivitis develops in neonates because of their immature
antibacterial spectrum and relatively well-tolerated. The lacrimal duct systems, immature immune systems, absence of
recommended dosing is eight times daily for the first two days, lymphoid tissue in the conjunctiva, absence of tears at birth
then four times daily thereafter for one week.4 Recommended and because colonization of the conjunctiva can occur during
dosing schedule for moxifloxacin ophthalmic solution is thrice neonatal care.8
daily for seven days.4 First-generation aminoglycosides, such
as gentamicin and tobramycin, are widely prescribed as first- Predisposing Factors
line therapy for the treatment of external ocular infections.5
However, approximately 20 to 30 percent of isolates usually • Organisms in birth canal
• Premature rupture of membranes
are resistant to these compounds.5 Recent aminoglycoside
• Prolonged labor
netilmicin shows excellent activity against the most common
• Low levels of immunoglobulins
microorganism involved in ocular infections.5 Azithromycin
• Trauma to epithelial barrier
1.5 percent twice daily for the first two days and once daily for
• Indiscriminate prophylactic use of broad spectrum
subsequent treatment days is also an effective option. 6
antibiotics and antiseptics can change the normal
Associated respiratory infections or otitits media are treated
conjunctival flora making neonates liable to chlamydial
with systemic antibiotics. Repeated conjunctival irrigation with
conjunctivitis7
topical lubricants in mild cases and by actual irrigation in severe
• Prematurity: Conjunctivitis may develop more frequently
cases will wash out infective and inflammatory products.
in premature infants
Treatment failure may occur because of viral infection, other
• Infants in the neonatal intensive care unit (NICU) -
nonbacterial infections, resistant bacteria, a noninfectious
Hospital acquired (nosocomial) conjunctivitis is defined
cause, or noncompliance.1
as occurring 48 hours or more after hospitalization and is
caused by bacterial or viral pathogens unrelated to maternal
HYPERACUTE CONJUNCTIVITIS
infection.8 Neonates in NICU are at particularly high risk
Neisseria gonorrheae and Neisseria meningitidis can cause hyperacute for such infections because of the severity of their illness
infections with ocular morbidity. N. meningitidis conjunctivitis and their exposure to invasive mechanical devices and
may be followed by fatal meningitis. In adults the gonococcal resistant microorganisms.9 Other risk factors that have
infections occur through hand contamination and in neonates been identified include direct conjunctival trauma
by contamination occur during vaginal delivery. Signs include associated with routine care, exposure to nasolacrimal
secretions via mechanical ventilation, and oxygen delivery corneal opacification may be present. (Refer to chapter on
by nasal cannula.9 Chlaneydial infections also).
Gonococcal conjunctivitis is the most serious, usually
Causative Organisms occurring 24 to 48 hours following birth. Typically, patients
develop hyperacute conjunctivitis, associated with marked lid
Chlamydia trachomatis: This obligate intracellular parasite has
edema, chemosis, and purulent discharge. A conjunctival
been identified as the most common infectious cause of
membrane may be present. Corneal ulcer may occur and rapidly
neonatal conjunctivitis.10 The reservoir of the organism is the
progress to perforation, if treatment is delayed.
maternal cervix or urethra. Infants who are born to infected
mothers are at high risk for developing an infection. Other bacterial conjunctivitis: Pseudomonas can rarely cause neonatal
conjunctivitis, resulting in devastating consequences, such as
Neisseria gonorrheae: This gram-negative diplococcus is
rapid progression to corneal ulceration and perforation; if left
potentially the most dangerous and virulent infectious cause
untreated, it even can lead to endophthalmitis and subsequent
of neonatal conjunctivitis. Gonococci have the ability to
death.
penetrate intact epithelial cells and to divide rapidly inside the
epithelial cells. Gonorrheal conjunctivitis must be absolutely Neonatal conjunctivitis is to be differentiated from
excluded in every case of neonatal conjunctivitis to avoid chemical conjunctivitis and herpetic conjunctivitis. Chemical
serious consequences. conjunctivitis is aseptic neonatal conjunctivitis most often
caused due to silver nitrate solution, that is instilled for
Other bacteria: The most commonly identified gram-positive prophylaxis of infectious conjunctivitis. Chemical conjuncti-
organisms include Staphylococcus aureus, Streptococcus pneumoniae, vitis is not as common anymore because of the use of
Streptococcus viridans, and Staphylococcus epidermidis. Gram-negative erythromycin ointment instead of silver nitrate solution for
organisms, such as Escherichia coli, Klebsiella pneumoniae, Serratia the prophylaxis of infectious conjunctivitis. Silver nitrate, which
marcescens, and Proteus, Enterobacter, and Pseudomonas species, also is a surface-active chemical, facilitates agglutination and
have been implicated. There has been one case report of inactivation of gonococci, is toxic to the conjunctiva. Chemical
neonatal conjunctivitis being caused by Eikenella corrodens.11 conjunctivitis secondary to silver nitrate solution application
Low birth weight and low gestational age among infants in usually occurs in the first day of life and resolves by two to
the neonatal intensive care unit (NICU) who have clinical signs four days. The clinical picture of chemical conjunctivitis is
of conjunctivitis should raise the suspicion for a gram-negative
mild, transient tearing and conjunctival injection. If one percent
cause.12
silver nitrate used for neonatal conjunctivitis is provided in a
large bottle, the solution can evaporate and become
Incubation Period
concentrated over time. Concentrated silver nitrate solution
• Gonococcal conjunctivitis tends to occur three to five days may result in more severe responses (e.g. lid edema, chemosis,
after birth but can present later exudate, membranes or pseudomembranes, permanent damage
• Chlamydial conjunctivitis usually has a later onset than to the conjunctiva or the cornea).
gonococcal conjunctivitis; the incubation period is Herpetic conjunctivitis in neonates typically occurs within
5 to 14 days the first two weeks after birth. Ocular involvement may follow
• The incubation period for other nongonococcal, non- systemic herpes infection or vesicular lesions on the skin or
chlamydial conjunctivitis is two to five days as for lid margins. Patients may present with nonspecific lid edema,
Staphylococcus aureus, two days for Streptococcus pneumoniae, moderate conjunctival injection, and nonpurulent and often
Hemophilus spp, Enterococci and 5 to 18 days for Pseudomonas serosanguineous discharge, which may be unilateral or bilateral.
aeruginosa. Microdendrites or geographic ulcers, rather than typical
dendrites as seen in adults, are the most typical signs of herpetic
Signs and Symptoms keratitis in newborns. Conjunctival membrane may be present.
Chlamydial conjunctivitis: Patients typically present with unilateral Serious systemic complications, such as encephalitis, may occur
or bilateral watery discharge, which may become more copious in these neonates due to their poor immunologic response.
and purulent later. Most cases may be mild and self-limited, Culture for HSV is indicated if a corneal epithelial defect is
but might be severe occasionally. Pseudomembranes, thickened present or if vesicles present on the eyelids or other parts of
palpebral conjunctiva, significant peripheral pannus, and/or the body, and if the diagnosis is not clear. Treatment comprises
of systemic acyclovir to reduce the chance of a systemic • Prophylaxis- Ointment tetracycline or erythromycin within
infection. one hour after birth.
Laboratory studies include conjunctival swab for Gram
stain, culture on chocolate agar and/or Thayer-Martin for BACTERIAL KERATITIS
N gonorrhoeae, culture on blood agar for other bacteria. For
• Predisposing factors
suspected chlamydial infection, conjunctival scraping stained
• Principal causes [bacteriology]
with Giemsa stain for intracytoplasmic inclusion bodies or,
• Pathogenesis
preferably, a direct immunofluorescent antibody assay is
• Clinical features
recommended. Polymerase chain reaction (PCR) might have
• Histopathology
a higher sensitivity and similar specificity in diagnosing
• Laboratory diagnosis
neonatal chlamydial conjunctivitis compared to conventional
• Treatment
methods.13
Predisposing Factors
Treatment
Normal Host Defence
Bacterial Conjunctivitis
• Eyelids and adnexa provide a physical barrier
• Erythromycin or bacitracin ointment for gram-positive
• Blinking process washes away any organisms which have
organisms
entered
• Gentamicin or tobramycin drops for gram-negative
• Many proteins in the tear film, such as secretory
organisms
immunoglobulins, complement components, and various
• Fortified topical antibiotics for Pseudomonas
enzymes including lysozyme, lactoferrin, betalysin,
• Neosporin or soframycin eye drops also cover most
ceruloplasmin have antibacterial effects
bacteriae
• An intact corneal epithelium prevents invasion of most
• 0.5 percent moxifloxacin ophthalmic solution dosed three
bacteriae except for Corynebacterium, Diphtheriae, Haemophilus
times daily has found to be faster and more effective than
aegyptius and Listeria monocytogenes
polymyxin/trimethoprim dosed four times daily for the
• Normal conjunctival flora prevents overgrowth of
treatment of bacterial conjunctivitis in children at 48
exogenous bacteria
hours14
• Conjunctiva Associated Lymphoid Tissue -This specialized
• 50,000 u/kg IV penicillin G in 2 divided doses for 7 days
lymphoid tissue of conjunctiva is composed of immune-
for N. gonorrhoeae
inflammatory cells such as Langerhans’ cells, macrophages,
• Because of the prevalence of penicillin-resistant
lymphocytes, neutrophils, plasma cells and mast cells which
N. gonorrhoeae, the treatment of choice for this organism
provide both afferent and efferent immunological pathway
is topical erythromycin or bacitracin ointment and systemic,
for acquired defenses against antigenic stimuli.
third-generation cephalosporin (ceftriaxone 30 to 50 mg/
kg/d in divided doses IV or IM, not to exceed 125 mg)
Bacteriology
• Infants with gonococcal ophthalmia15 should have their
eyes irrigated with saline frequently until the discharge is The common bacteria/causing bacterial keratitis include:
eliminated. A single dose of cefotaxime (100 mg/kg IV or • Gram-positive cocci
IM) is an alternative treatment. – Staphylococcus aureus
– Staphylococcus epidermidis
Chlamydial Conjunctivitis – Streptococcus pneumoniae
• This infection is treated with oral er ythromycin • Gram-positive bacilli
(50 mg/kg/d divided qid) for 14 days – Corynebacterium diphtherioids
• Topical treatment alone is ineffective. Topical erythromycin – C. xerosis
or tetracycline one percent ointment may be beneficial as • Gram-negative bacilli
an adjunctive therapy – Pseudomonas aeruginosa
• Since the efficacy of systemic erythromycin therapy is – Acinetobacter species
approximately 80 percent, a second course sometimes is – Enterobacteriaceae—Klebsiella, Serratia, Proteus,
required Escherichia coli
• Gram-negative diplobacillus—Neisseria gonorrhoeae, Neisseria

meningitidis
• Gram-negative diplobacillus—Moraxella lacunata
• Gram-negative coccobacillus—Hemophilus influenza,
Hemophilus aegyptius
• Gram-positive filaments—Nocardia asteroides, Nocardia
brasiliensis
• Non-tuberculous mycobacterium—Mycobacterium fortuitum,
Mycobacterium chelonae.
Bacteria isolated vary among different geographic
locations. Staphylococcus, Streptococcus and Pseudomonas are the
commonly isolated pathogens from keratitis. Coagulase
negative Staphylococcus is identified more often recently.16
Etiopathogenesis Fig. 6.7.1.3: Contact lens induced Pseudomonas keratitis
Risk Factors
Break in the barrier function: Bacterial keratitis occurs when micro-
organisms overcome host defences. An intact corneal precautions is an important source for devastating bacterial
epithelium is an important defence factor. Only few bacteria infections like Pseudomonas keratitis.16
like Neisseria gonorrhoeae, Corynebacterium diphtheriae, Hemophilus
aegyptius and Listeria monocytogenes can penetrate an intact corneal Pathogenesis
epithelium.20 The pathophysiology of infective keratitis is determined by:
External risk factors: An epithelial defect following a trauma is • Microbial factors
a major risk factor for infection. Corneal abrasion, foreign • Host factors
body or erosion may precipitate development of bacterial • Therapy effects
keratitis. In India, common traumatic agents are soil, sand, Microbial factors, in turn, consist of virulence, bacterial
stone and vegetative matter.16 load and sensitivity to commonly used antimicrobial agents.
Ocular surface pathologies: Chronic inflammatory ocular surface Factors Determining Bacterial Virulence
diseases cause tear film instability and structural changes
Bacterial adherence: Bacteria adhere to the wounded corneal
of the epithelium which will invite infections. 16,17 Lacrimal
surface and avoid clearance by tear film. This is aided by
passage obstruction is another important source of bacterial
adhesins, a protein moiety which attaches to protein or
infection.
carbohydrate specific host cell components. The glycocalyx, a
Iatrogenic: Contaminated eye drops preparations, preservative biological slime produced by bacteria not only helps in
free formulations which are used for long term like artificial adhesion to host cell but also helps them to resist
tear substitutes and anti glaucoma agents are important source phagocytosis.20
of Pseudomonas keratitis.
Bacterial invasion: Bacterial capsule and other surface
Contact lens use: In developed countries, this is the most common components are important in bacterial invasion.
risk factor for bacterial keratitis. Microorganisms can get Lipopolysaccharides, the subcapsular constituents of bacteria
attached to the contact lenses. Mechanical abrasions render are major mediators of corneal inflammation. Bacteria also
the hypoxic cornea susceptible to infections. Infections are release many proteases, which damage basement membrane
more common with soft and extended wear lenses.18,19 and facilitate invasion.20 After inoculation, bacteria infiltrate
• Pseudomonas is the most common isolate of bacterial the surrounding epithelium and into deeper stroma. Viable
keratitis associated with contact lens use. (Fig. 6.7.1.3). bacteria tend to be found at peripheral margins and deep within
Corneal foreign body removal without strict sterility the ulcer crater.
Pseudomonas aeruginosa is a good example to show the Detailed slit lamp biomicroscopy examination is of para-
pathogenic effects of various bacterial extracellular products. mount important (Tables 6.7.1.1 and 6.7.1.2). The hallmark
It can produce enzymes like alkaline protease, elastase which clinical signs that are distinctive for infectious keratitis include,
degrade basement membrane and extracellular matrix and ulceration of the epithelium with suppurative stromal
exotoxins like hemolysin and exotoxin A and phospholipidase infiltration. Presence of diffuse cellular infiltration in the
C causing stromal necrosis. adjacent stroma and anterior chamber reaction is highly
Gram-positive bacteria also secrete distinct toxins. suggestive of infectious keratitis. Anterior chamber reaction
Coagulase positive Staphylococci elaborate staphylokinase, may vary from mild flare and cells to hypopyon formation.
lipase, hyaluronidase, coagulase and lysozyme and Staphylococcus Hypopyon in bacterial keratitis is usually sterile unless the
epidermidis also produce distinct toxins. Streptococcal enzymes Descemet’s membrane is not intact.
are streptokinases, streptolysin O and S and streptodornase. Certain characteristic clinical features may be suggestive
Streptococcus pneumoniae produce collagenase for invasion.20 of specific corneal pathogens, although clinical observation
Corneal inflammatory response: Recruitment of acute inflammatory alone should not replace laboratory investigation.
cells occurs within a few hours of bacterial inoculation. Gram-positive cocci typically cause localized round or oval
Vascular dilatation and limbal vessels are associated with ulcerations with greyish white stromal infiltrate with distinct
increased permeability, resulting in an inflammatory exudation borders with minimal surrounding edema. Gram-negative
into tear film and peripheral cornea. Polymorphonuclear corneal infections usually follows rapid paced inflammatory
neutrophils can enter injured cornea anteriorly via tear film, destructive course.
but most migrate from the limbus.
This influx of neutrophils is directed by bacterial proteins INFECTIOUS CRYSTALLINE
via chemotaxis toward the area of infection. As neutrophils KERATOPATHY
accumulate at the site, more cytokines and complement Infections crystalline keratopathy (ICK) was first reported in
components are released to attract additional leukocytes. 1983, characterized by white crystalline conglomerate of
Collagenase released from PMNs, matrix metallo proteases bacterial colony within the corneal stroma with branching linear
by host tissues, proteases produced by the pathogen lead to extensions with almost absent host inflammatory reaction.21,22
rapid tissue lysis. Macrophages subsequently begin to migrate A low virulent or nutritionally different micro-organism gains
to cornea to ingest invading bacteria. entry through a suture track or other injury and starts
Once the infection is controlled with treatment, the healing proliferating along the stromal lamellae but fails to incite
process leads to scaring.
Uncontrolled infective and inflammatory reactions may
lead to corneal perforation.
Table 6.7.1.1: Evaluation of ocular surface
and adnexa in keratitis
Clinical Features
Eyelid margins Meibomian gland dysfunction, margin
Presentation: Clinical signs and symptoms depend on many ulceration, eyelash abnormalities, punctal
factors like virulence of organisms, duration of infection, pre- abnormalities
existing corneal conditions, immune status of the host, and Tear film Dry eye, debris
previous use of antibiotics or corticosteroids. Bacterial keratitis Conjunctiva Discharge, inflammation, structural
usually has a history of rapid onset of pain, photophobia, alterations like follicles, papillae,
cicatrization, keratinization, membrane,
decreased vision, conjunctival injection, anterior chamber foreign bodies, limbal health, filtering blebs
reaction and/or hypopyon. But some bacteria like atypical Sclera Inflammation, ulceration, scarring, thinning
mycobacterial infections present with an insidious onset and and nodules
indolent course. Cornea - epithelial Location, density, size, shape, satellite
defects, stromal lesions, character of infiltrate margin,
Clinical examination: A detailed history is important and should infiltrate, thinning/ color of infiltrate, status of endothelium
include ocular symptoms, review of previous ocular history, perforation, punctate
and also a review of medical problems. Most common epitheliopathy
symptom is pain and accompanied by variable degree of Lacrimal apparatus Regurgitation of purulent material on
pressure on lacrimal sac area
diminished vision, watering, photophobia, blepharospasm.
Table 6.7.1.2: Clinical features of bacterial keratitis
Gram-positive Cocci
Staphylococcus Frequently encountered in compromised
aureus corneas such as bullous keratopathy,
chronic herpetic keratitis, dry eyes, ocular
rosacea. May present with marked
suppuration, deep stromal abscess.
Staphylococcus Indolent course, may also lead onto
epidermidis stromal abscess.
Streptococcus Presents with a deep, oval, central stromal

pneumoniae ulceration having a progressive edge
(Fig. 6.7.1.4) while the other edge is healing. Posterior
corneal abscess and hypopyon are usually
due to reactions to the exotoxins released
by the pathogen.
Gram-negative bacilli
Pseudomonas Severe inflammatory signs with greenish Fig. 6.7.1.4: Streptococcus pneumoniae ulcer — one
aeruginosa yellow discharge. Rapid progression, edge (active and leading) with hypopyon
(Fig. 6.7.1.5) marked stromal melt, ring infiltrate, and
later descemetocele formation or
perforation. Surrounding stroma shows
ground glass appearance, diffuse greying
of epithelium. Mucopurulent discharge
Proteus Similar to pseudomonas
Klebsiella More often associated chronic epithelial
disease
Moraxella Produces keratitis after trauma in
debilitated, alcoholic, malnourished or
diabetic patients. An indolent ulceration
with mild to moderate anterior chamber
reaction
Neisseria gonorrhea Rapidly progressive, hyperpurulent
conjunctivitis, with marked chemosis with
stromal infiltration Fig. 6.7.1.5: Pseudomonas keratitis with greenish pus
and melting corneal ulceration
Nocardia (Fig. 6.7.1.6) Indolent ulcerations after minor trauma
particularly exposure to contaminated soil.
Characteristically, raised, superficial, pin-
head like infiltrates in a wreath like
configuration, brush fire like border with
multifocal lesions.
Non-tuberculous Causes a slowly progressive keratitis,
mycobacteria usually by contaminated sharp instruments
(atypical like knife, blade and sutures. Occurs after
mycobacteria) corneal trauma or corneal surgery,
(Figs 6.7.1.7A and B) particularly after LASIK. Lesions can be
M.fortuim, solitary or multifocal infiltrates with spoke
M.chelonae like margins. They tend to heal very slowly.
Bacillus cereus Gram positive bacillus, keratitis usually
follows trauma or wound contamination.
Keratitis cahracterized by a distinctive
stromal ring infiltrate remote from the site
of injury, with rapid progression to stromal
abscess. Fig. 6.7.1.6: Nocardia keratitis showing wreath
like arrangement of dot like infiltrates
needle. Polymerized chain reaction and DNA typing is a

recently added advanced tool to diagnose the infective
etiology.36
HISTOPATHOLOGY OF
MICROBIAL KERATITIS
Histopathological analysis shows distinct stages.
Stage 1: Stage of progressive infiltration: Includes adherence and
entry of the organism, diffusion of toxins and enzymes, and
resultant tissue destruction. Shortly after the bacterial
adherence, polymorphonuclear leukocytes arrive at the site.
Stromal damage caused by bacterial and neutrophil enzymes
facilitates progressive bacterial invasion.
Fig. 6.7.1.7A: Early mycobacterial infiltration
Stage 2: Stage of active ulceration: There is progressive tissue
necrosis with subsequent sloughing of the epithelium and
stroma, resulting in a sharply demarcated ulcer with
surrounding neutrophilic infiltration. If organisms penetrate
deeper into the stroma with progressive tissue necrosis, it may
result in descemetocele formation or perforation.
Stage 3: Regressive stage: Characterized by improvement in clinical
signs and symptoms. Natural host defence mechanisms
predominate and humoral and cellular immune defence
mechanisms together with antibacterial therapy try to retard
bacterial replication, promote phagocytosis of the organism
and cellular debris. Vascularization may start if the ulceration
is of long duration.
Stage 4: Healing stage: Characterized by epithelialization of
Fig. 6.7.1.7B: Mycobacterial stromal infiltration
ulcerated area, replacement of necrotic stroma with scar tissue,
with spoke like extensions which is produced by fibroblasts.
LABORATORY DIAGNOSIS
inflammatory response.23,24 Most commonly reported in Laboratory investigations of microbial keratitis include corneal
corneal grafts adjacent to sutures, local or systemic scraping to obtain specimens for microbiological staining and
immunocompromised conditions and even after post LASIK cultures.
procedure.21-28 Most common organism causing this condition Although majority of bacterial keratitis resolve with
is alpha-hemolytic Streptococci. Others organisms include empirical antibacterial therapy alone, cultures are indicated in
Streptococcus pneumoniae, Staphylococcus epidermidis, Peptostreptococcus, cases with large corneal infiltrates, infiltrates that extend into
Hemophilus aphrophilus, enterococci, Pseudomonas, Mycobacterium and deeper stroma, that is chronic in nature or is unresponsive to
fungi like Candida and Alternaria.23-33 The biofilm glycocalyx empirical therapy or that has clinical features of fungal,
produced by these organisms is thought to be the reason for amoebic or mycobacterial keratitis.
failure of host reaction as well as ineffectiveness of topical Corneal specimen is usually obtained by heat sterilized
therapy to eradicate the infection.34,35 platinum [Kimura] spatula or 15 number blade. In cases with
Definitive diagnosis requires isolation of the causative primary involvement of deep stroma, a small trephine may be
organisms, either with use of corneal biopsy or 25 gauge used to obtain a corneal biopsy.
Stains
The material for smear is applied on a clean glass slide to
make a thin, even film.
Gram's stain: This method has sensitivity of 55 to 79 percent.
It can also identify fungal filaments and amoebic cysts. Gram-
positive bacteria appear bluish-purple whereas Gram-negative
bacteria appear pink. In addition, it can also identify filamentary
bacteria like Nocardia (Figs 6.7.1.8A to C).
Giemsa stain: It is primarily used to distinguish the types of
inflammatory cells and intracytoplasmic inclusions. It can
distinguish bacteria from fungi. Chlamydia inclusion bodies
may be identified with Giemsa stain.
Fig. 6.7.1.8A: Gram-positive diplococci
Ziehl-Neelsen acid fast staining: This is done for identification of
suspected mycobacterium, Actinomyces or Nocardia.
Mycobacterium is acid fast, Nocardia variably stained while
Actinomyces is not acid fast.
Acridine orange and calcofluor white stains are fluoro-
chromatic dyes which stain micro-organisms and fluoresce.
Culture
As corneal scraping specimens are usually very small in quantity,
they should be inoculated directly onto the culture plates
directly. The commonly used culture media are shown in Table
6.7.1.3.
While plating the culture media, specimen should be
inoculated in C streaks to distinguish valid bacterial growth
from plating contamination.
Fig. 6.7.1.8B: Gram-negative bacteria Standard disc diffusion or microdilution techniques are
used to determine the antimicrobial susceptibility.
Table 6.7.1.3: Culture media

Routine culture media Purpose
Blood agar Aerobic and Facultative, Anaerobic
Bacteria, Including P.aeruginosa,
S.aureus, S.pneumoniae.
Chocolate agar Aerobic and facultative, anaerobic
bacteria, including H.influenzae,
N.gonorrheae, and Bartonella
species.
Thioglycollate broth Aerobic and facultative, anaerobic
bacteria
Supplemental media
Lowenstein-Jensen media Mycobacteria, Nocardia
Thayer-Martin agar Pathogenic Neisseria species
Fig. 6.7.1.8C: Gram-positive fine filaments of nocardia Anaerobic blood agar P.acnes, Peptostreptococcus
Table 6.7.1.4: Antibacterial agents and preparations Sensitivity pattern is of paramount importance in chronic
Organism Antibiotic Preparation
cases, multidrug resistant bacterial infections in order to tailor
the effective management.
Gram positive Cefazolin 5% 500 mg IV preparation
Cefuroxime 5% mixed in 10 ml of If the causative pathogen is not isolated and the keratitis
artificial tears (AT) is not responding satisfactorily, all antibiotics are stopped
Multidrug resistant Vancomycin 2–5% IV vancomycin in AT for a wash out period of 48 hours and the culture is repeated.
Gram positive 2–5% Amikacin or NaCl Non responding keratitis or progress to perforation will require
Gram negative Tobramycin 14 mg/ml Diluted in AT therapeutic keratoplasty.
multidrug resistant Cefotoxime 5%
Gram negative Ceftazidime 5% 500 mg in 10 ml AT REFERENCES
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6.7.2 Viral Conjunctivitis and Keratitis

VIRAL CONJUNCTIVITIS weeks. Viral conjunctivitis commonly occurs as epidemics in

families, offices, etc. and transmission occurs through contact
Viral conjunctivitis can occur at all ages, and is characterized with infected upper respiratory droplets, fomites, and
by acute follicular conjunctivitis associated with preauricular contaminated swimming pools.
lymphadenopathy, frequent corneal involvement and systemic Of the various viruses causing conjunctivitis, the common
signs of viral infection.1-6 Viral conjunctivitis, is usually benign ones include:
and self-limiting, but may have a longer course than acute • Adenovirus
bacterial conjunctivitis, lasting for approximately two to four • Herpes simplex virus (HSV)
• Varicella-zoster virus (VZV) Conjunctival chemosis, hemorrhages, lid edema and papillary
• Picornavirus (enterovirus 70, Coxsackie A24) hypertrophy may also be seen. In severe cases, inflammatory
• Poxvirus (molluscum contagiosum, vaccinia) membranes and pseudomembranes lining the tarsal and
• Human immunodeficiency virus (HIV) palpebral conjunctiva may be observed. In the acute phase,
Conjunctivitis may also occur during systemic infection three to four days following acute follicular conjunctivitis,
with influenza virus, Epstein-Barr virus, paramyxovirus corneal lesions in form of superficial punctuate keratitis occur.
(measles, mumps, Newcastle), and rubella. Viral conjunctivitis Conjunctival inflammation subsides in two weeks with corneal
can affect all age groups. Adenovirus commonly affects involvement lasting much longer. Nummular subepithelial
patients aged 20 to 40 years, while HSV and primary VZV infiltrates, 1 to 2 mm in diameter develop around the second
infection usually affect young children and infants. Herpes to third week of infection, involving the entire corneal extent
zoster ophthalmicus results from reactivation of latent VZV or limited to the center. They disappear gradually over several
infection and may present in any age group. Picornaviruses years and may result in photophobia, glare and decreased visual
typically affects children and young adults in the lower acuity secondary to irregular astigmatism or visual axis
socioeconomic classes. involvement.
Acute anterior uveitis, disciform keratitis, dendritic keratitis
Adenoviral Conjunctivitis are rare in adenoviral keratoconjunctivitis. A chronic rare form
of adenoviral keratoconjunctivitis in form of papillary
Adenoviral conjunctivitis is the most common cause of viral
conjunctivitis and recurrent keratitis has been reported in
conjunctivitis. Adenoviruses are non-enveloped double
association with serotypes 2, 3, 4, 5 and 19.
stranded DNA viruses. The virus replicates within the nucleus
Pharyneal conjunctival fever commonly occurs in children
of the host cell. The general reservoir for adenovirus is only
and consists of pharyngitis, acute follicular conjunctivitis and
humans. Clinical features occur as a result of viral infection
fever with tender regional lymphadenopathy. It is associated
and immune response with cellular infiltration comprising of
with serotypes 3, 4, and 7 with the ocular symptoms and signs
lymphocytes, histiocytes and fibroblasts, of the Bowman's layer being similar to EKC. The secretions are usually serous with
and underlying stroma.
corneal involvement being more mild and restricted to
There are 47 adenovirus serotypes (six subgroups A to F) superficial punctate keratopathy and subepithelial involvement
described based on genomic descriptions. Clinical
being less common.
presentations depend on the various causative serotypes and
include:1 Treatment: Antiviral therapy is not beneficial in adenoviral
• Epidemic keratoconjunctivitis (EKC) keratoconjunctivitis. Treatment is mainly symptomatic such
• Pharyngeal conjunctival fever as cold compresses and sunglasses to decrease glare. Topical
• Nonspecific follicular conjunctivitis antibiotics help to prevent superinfection. Topical steroids are
• Chronic papillary conjunctivitis to be used with extreme caution and are beneficial in decreasing
Epidemic keratoconjunctivitis is commonly associated with the severity of the immune subepithelial infiltrates and in cases
serotypes 8, 19, 37 and 5. Patients present with complaints of of uveitis and membrane formation. Appropriate preventive
ocular itching, foreign body sensation, tearing, redness, and measures, counseling regarding proper hygiene and care to
photophobia (in cases with corneal involvement as in epidemic reduce transmission, exemption from school, work, etc. are
keratoconjunctivitis). All adenoviral infections occur as a result also helpful.
of close contact as in schools, homes, workplace setting or
camps. Seasonal epidemics are associated with swimming Herpetic Conjunctivitis
pools. Iatrogenic sources of infection also result from The most significant ocular viral infections are due to the family
ophthalmic setup resulting from contact with infected surfaces of herpes viruses (HSV - 1, HSV - 2, varicella-zoster virus
such as unwashed hands, contaminated diagnostic instruments cytomegalovirus and Epstein-Barr virus).
and ophthalmic solutions. The incubation period is about seven Herpes is a double stranded DNA virus. Transmission is
to nine days and the virus replication may last on the ocular through contact with infected secretions, fomites or
surface for up to two weeks following onset of infection. equipments. Humans are the only natural reservoir of HSV.
Adenoviral keratoconjunctivitis is commonly bilateral with one Primary ocular herpes simplex infection is common in children
eye involvement being more severe than the other. and usually is associated with a follicular conjunctivitis.
Acute follicular conjunctivitis associated with preauricular Infection usually is caused by HSV type I, although HSV type
lymphadenopathy is seen. No systemic signs are present. II may be a cause, especially in neonates. Recurrent infection,
typically seen in adults, usually is associated with corneal Varicella Conjunctivitis

involvement. Primary infection occurs during childhood usually
Varicella zoster virus (VZV) can affect the conjunctiva during
in age group of 1 to 5 years, followed by latency in the neuronal
primary infection (chickenpox) or secondary infection (zoster).
bodies of the ganglia. Primary infection is manifested in only
1 to 6 percent of cases. Herpetic conjunctivitis occurs during Infection can be caused by direct contact with VZV or zoster
the primary infection while corneal lesions may occur in the skin lesions or by inhalation of infectious respiratory secretions.
recurrences. Primary ocular HSV infection predominantly The incubation period is 12 to 17 days after contact, with the
affects young children and infants, but it may occur in patients being contagious from two days before rash until the
individuals of all ages. Patients usually present with a red, time the rashes have crusted. Transmission is by contact with
irritated, watery eye. Often, concomitant eyelid skin infected lesions or infected secretions. VZV is characterized
involvement with multiple vesicular lesions is present. by a generalized vesicular eruption, fever, and constitutional
Reactivation of infection is said to be precipitated due to symptoms. Ocular infection usually is unilateral and presents
stress, trauma, surgery, menstruation or UV radiation as small papular lesions that erupt along the lid margin or at
exposure1. The risk of recurrence of primary infections is the limbus and may be accompanied by a mild follicular
supposed to be high in the event of occurrence of corneal conjunctivitis. Small papular lesions that erupt along the lid
infection along with palpebroconjunctival lesions during the margin or at the limbus are present with varicella conjunctivitis.
primary infections.1 These lesions heal without sequelae, or they may become
Ocular herpes has been classified into three groups: pustular and form painful reactive conjunctival ulcers.
congenital/neonatal, primary and recurrent.2 Herpes zoster ophthalmicus is the reactivation of latent
Congenital and neonatal is rare. It is caused by HSV-2, as VZV infection of the trigeminal ganglion. It presents with a
the infection is acquired during the late prenatal period or prodrome of fever, malaise, nausea, vomiting, and severe pain
during passage through the infected birth canal. Presentation and skin lesions along the ophthalmic division of the trigeminal
of ocular herpes in the newborn includes conjunctivitis, nerve. Skin involvement presents as vesicles, which may
epithelial keratitis, stromal immune reaction, cataract and become necrotic, resulting in pitted scarring of the skin.
necrotizing chorioretinitis. An associated vesicular eruption
Conjunctival involvement includes hyperemia, follicular or
in the skin might be seen. Treatment includes intravenous
papillary conjunctivitis, and a serous or mucopurulent
acyclovir to be started immediately in order to alleviate systemic
discharge. Preauricular adenopathy is common. In the initial
complications. An effective dose is 30 mg/kg/day IV divided
phases, multiple fine dendritic corneal lesions may be present,
tid, but most experts recommend higher doses (45–60 mg/
kg/d). The recommended minimal duration is 14 days, but a which disappear over a few days without treatment.
course as long as 21 days may be required. Infants with neonatal Treatment of VZV eye disease includes oral acyclovir, 800
HSV keratitis should receive a topical antiviral therapy. mg, 5 times daily for 7 to 10 days, to terminate viral replication.
Primary herpetic ocular involvement presents as acute Recurrent episodes are treated with oral 400 to 800 mg bid
follicular conjunctivitis or keratoconjunctivitis with for 7 to 10 days. Treatment is to be initiated immediately upon
nonsuppurative preauricular adenopathy with vesicular lesions onset of symptoms of recurrent episodes.
of periocular skin. Pseudomembranes may be seen in the
fornices. Herpetic blisters may be located along the lid margins. Acute Hemorrhagic Conjunctivitis
Primary HSV keratitis is atypical, presenting as superficial Picornaviruses are viruses with single stranded RNA genome
punctate keratitis evolving into a scattered microdendritic that cause an acute hemorrhagic conjunctivitis that is clinically
pattern, or serpiginous ulcer. Primary disease always is restricted similar to adenoviral conjunctivitis but is more severe and
to epithelial involvement. With HSV infection, vesicles may
hemorrhagic. Infection is highly contagious and occurs in
be present on the eyelid or face, the eyelids may be swollen,
epidemics. Two major picornaviruses (enterovirus 70 and
and an ulcerative blepharitis may be present.
coxsackie virus A2) have been isolated as etiologic agents.
Treatment: Patients with conjunctivitis caused by HSV are Crowded living conditions, low socioeconomic status, poor
treated with topical antiviral agents. Adjunctive therapy hygiene are significant risk factors for acute hemorrhagic
including topical antibiotics, artificial tears is helpful. Oral conjunctivitis. Children and young adults are commonly
acyclovir 400 mg bid, can be used to prevent recurrent herpes affected with females being more affected than males.2
simplex infections and inflammations. Transmission occurs through infected hands and soiled linen
and mean incubation period is about 24 hours.1 Patients usually lesion is treated. The central core of the lesion is to be removed
complain of a rapid onset of watery discharge, foreign body or inducing bleeding within the lesion is also helpful to resolve
sensation, burning, and photophobia within 24 hours of the infection. Surgical excision may be required. Treatment
exposure. consists of excision and curettage of the lid lesions which is
Clinical presentation includes acute follicular conjunctivitis usually preferred over cryotherapy.
with subconjunctival hemorrhage (with predilection for Vaccinia virus has become a rare cause of conjunctivitis
supertemporal region or can be diffuse). Chemosis, lid edema, because with the elimination of smallpox.
ecchymoses, papillary hypertrophy and preauricular
lymphadenopathy may all be present. Corneal involvement Papillomavirus Conjunctivitis
occurs as superficial punctuate keratopathy. Membrane
Papilloma virus conjunctivitis is caused by a double stranded
formation is rare. Resolution is seen in about 5 days. Systemic
DNA papilloma virus of the papova family. Infection is
associations of fever, myalgia, fatigue, headache, and cough
common in children and spreads by contact. Hypervascularized
may also be observed. Neurological involvement (peripheral
pedunculated lesions of the bulbar, tarsal or caruncle
or cranial nerve (mainly facial nerve) palsy preceded by radicular
conjunctiva or sessile lesions of the limbus may occur
pain) due to motor neuronal injury of the anterior horn of
associated with papillary conjunctivitis. Treatment involves
the spinal cord has also been reported.1
surgical resection with cryotherapy or cautery.
Treatment of acute hemorrhagic conjunctivitis is
supportive as in adenoviral infection, with bed rest, cold
Other Forms of Viral Conjunctivitis
compresses, and analgesics. Antibiotics have no useful role
unless bacterial superinfection is present. Measles is associated with acute conjunctivitis without
superficial epithelial keratitis. Corneal scarring can also occur.
Molluscum Contagiosum Conjunctivitis An acute follicular conjunctivitis with superficial epithelial
Molluscum contagiosum is a pox virus infection (double keratitis is seen to occur in rubella infection which is usually
self-limiting in immunocompetent patients. Bacterial
stranded DNA virus), occurring due to viral replication in the
epidermis, inducing hypertrophy and hyperplasia of the superinfection and scarring might occur in the
immunocompromised patients. Acute follicular conjunctivitis can
epithelial cells. Humans are the exclusive hosts for this pox
virus infection. Children are commonly affected and occur due cytomegalovirus infection in immunocompromised
patients.
transmission is by direct contact or through swimming in
infected pools. Incubation period varies from one to three Human immunodeficiency virus (HIV) is the etiologic
agent of acquired immunodeficiency syndrome (AIDS). Ocular
weeks. Molluscum contagiosum can produce a chronic
follicular conjunctivitis in association with an irritative eyelid abnormalities in patients with AIDS primarily affect the
posterior segment, but anterior segment involvement also
lesion. Multiple lesions may be present, especially in patients
who are HIV positive. occurs. When conjunctivitis occurs in a patient with AIDS, it
tends to follow a more severe and prolonged course than in
Clinical presentation involves appearance of translucent
painless cutaneous nodules with umbilicated centers and patients without AIDS. In general, patients with AIDS may
develop a transient nonspecific conjunctivitis, characterized
erythematous base, commonly occurring on the face, abdomen
or genitalia, 2 to 4 mm in size or larger. Ocular involvement is by irritation, hyperemia, and tearing, that requires no specific
treatment. Microsporidia has been isolated from the cornea
seen in cases with palpebral lesions, in form of chronic
follicular conjunctivitis. Molluscum contagiosum may produce and conjunctiva of several patients with AIDS and
keratoconjunctivitis. In such patients, symptoms include
a chronic follicular conjunctivitis that occurs secondary to
shedding of viral particles into the conjunctival sac from an foreign body sensation, blurred vision, and photophobia.
irritative eyelid lesion. Corneal lesions may be seen as superficial
INVESTIGATIONS
epithelial keratitis, pseudodendrites or pannus. Diagnosis is
based on clinical finding and histopathological examination Diagnosis of viral conjunctivitis is mainly by clinical features
reveals characteristic intracytoplasmic eosinophilic inclusions alone. Conventional laboratory identification is expensive and
(molluscum bodies). For conjunctivitis associated with time-consuming. Conjunctival scraping specimens may be
molluscum contagiosum, the disease will persist until the skin taken for culture and smear in cases with severe inflammation,
in chronic or recurrent infections, with atypical conjunctival to HSV due to primary infection they acquired in earlier age.
reactions, and those that fail to respond to treatment. Giemsa Recent surveys showed a changing trend of more HSV1
staining of conjunctival scrapings will reveal an inflammatory primary infections that occur commonly in adolescent years
response of mononuclear cells and lymphocytes. Viral isolation rather than in childhood. This trend is considered to be reason
methods may be helpful in the diagnosis of acute follicular for the rise in pubertal HSV2 infections in developed countries,
conjunctivitis, but they are not indicated in chronic due to absence of partial immunity to HSV2 acquired after an
conjunctivitis. Direct immunofluorescence monoclonal early HSV1 infection.7 Primary infection spreads by direct
antibody staining and enzyme-linked immunosorbent assay contact to secretions from the infected lesion. Neonatal
(ELISA) are rapid detection techniques. Other alternative infections occur during passage through the birth canal.
methods include immunoperoxidase, electron microscopy, and Asymptomatic viral shedding is the major cause for
polymerase chain reaction (PCR) and serology tests. transmission and it occurs in primary, latent and recurrent
infective stages.7 Majority of primary infections are sub-clinical
VIRAL KERATITIS and may pass for a respiratory infection.
The virus remains dormant in the trigeminal ganglion.
Viral keratitis can be caused by:
Molecular biological studies showed virus in 100 percent of
• Herpetic group of viruses
the cadaver specimens of more than 60 years of age.7–9 After
– Herpes Simplex 1 and 2 (HSV1, HSV2)
the primary infection, recurrence rate is approximately 25
– Varicella-zoster (HZV)
percent in 2 years and 63 percent in 20 years.7 A cohort clinical
– Cytomegalovirus (CMV)
study in 108 patients for 15 years showed recurrence in 32
– Epstein-Barr virus (EBV)
percent of which single episodes were seen in 49 percent, 2 to
• Non-Herpetic viruses
5 episodes in 40 and 11 percent had 6 to 15 recurrences.7
– Adenoviruses
Primary herpetic keratitis doubles the chances for a recurrent
– Pox viruses
keratitis. Leisegang suggested an older age of onset of primary
– New-castle virus
infection and more severe manifestation of ocular disease.7
– Rubella
While the prevalence of bilateral disease is 12 percent, in atopic
– Rubeola
individuals the risk is up to 25 to 40 percent.7 35 percent
Herpes group of viruses are the most common cause of
bilaterality has been reported in an Indian study.10
keratitis.
Herpetic viral keratitis: There are 8 herpes viruses recognized Clinical Disease
and five of them are known to have ocular manifestations. Herpetic diseases are characterized by
While herpes simplex 1 and 2, HZV, EBV and CMV cause • Primary infection of the end organ
keratitis, Human Herpes virus 8 causes Kaposi Sarcoma.7 • Latency of the virus
• Reactivation at intervals manifesting as recurrent disease
Herpes Simplex Viral Keratitis
Pathology
These are neurotrophic viridae and antigenically and
biologically are differentiated as HSV1 and HSV2.8 Generally Primary infection: Herpes virus has a DNA core within a
nucleocapsid which, in turn, is covered by an envelope. Primary
HSV 1, thought to reside in cervical ganglia causes orofacial
infection occurs along mucocutaneous distribution of the
lesions and HSV 2 in sacral ganglia, causes genital herpes.
trigeminal nerve. After primary infection, the virus spreads
Recent analysis by polymerized chain reaction and in situ
from the infected epithelial cells to nearby sensory nerve
hybridization showed both types exists equally in any spinal
endings and the unenveloped non-infectious form is
ganglia suggesting host factors to determine the site of
transported along the nerve axon to the cell body located in
reactivation.7
the trigeminal ganglion. Evidence suggests that same strain
of virus cause5 both primary and recurrent infections.7,11
Epidemiology
After primary infection, the surface antigens of the affected
Herpetic viral keratitis is a major public health problem world- cells are altered. Circulating antibodies to these antigens appear
wide. This is the most common cause of uniocular corneal and remain life-long. These antibodies are of significance in
blindness. Almost up to 80 percent of adults have antibodies diagnosing primary disease but have no value in recurrent disease.
Latency and reactivation: The virus genome enters the • Late ophthalmic sequelae to local and disseminated
nucleus of a neuron, where it persists indefinitely in a latent systemic diseases are:
state. HSV recurrent ocular disease can also result from a – Ocular motility disorders
primary infection along maxillary or mandibular division of – Chorioretinal scars
the trigeminal nerve, through interneuronal spread within the – Optic atrophy
ganglion. – Cortical blindness
The reactivated virus in enveloped infectious form spreads
centrifugally down the sensory nerve to cause recurrent disease Differential Diagnosis of Viral Keratitis
in the ocular tissue. Viral particles were demonstrated in the • Bacterial, chlamydial conjunctivitis
corneal stromal scars by electronmicroscopy, immuno- • Viral dendritic keratitis: Acanthamoeba keratitis may also
histochemistry and by polymerase chain reaction studies but show a dendritic presentation.
rarely isolated by culture. However, a corneal latency is not • Stromal lesion: Peter's anomaly, CHED, sclerocornea and
clearly established. This finding also explains herpetic keratitis birth injuries.
in transplanted donor corneas.12-15
Severity and recurrence: It is not clear whether the severity CLASSIFICATION OF HERPETIC
and the site of recurrence are determined by the host immune CORNEAL DISEASE
system or viral antigens.16 Host immunodeficiency can worsen Herpetic ocular disease can be a primary ocular infection or
the herpetic infection. It was believed that recurrences are can occur as recurrent eye disease (Flow chart 6.7.2.1).
triggered by physical injuries to ocular or skin tissues, systemic
immunosuppression, psychological stress and hyperthermia. Primary Ocular Infection
Animal studies showed that UV-B is optimal for reactivation
and the activation was seen within two days in the trigeminal Primary infection usually occurs in children and young adults.
ganglion and subsequently in the cornea.17 Malarial fever has It manifests as:
been reported as an important triggering factor.10 However • Blepharoconjunctivitis: Follicular conjunctivitis with vesicles
the Herpetic Eye Diseases Study did not confirm the in periocular skin and lid margins (Fig. 6.7.2.1). Epithelial
significance of any extraneous triggers.18 microdendrites (Fig. 6.7.2.2) and pre-auricular
The severity and the site of recurrence may be determined lymphadenopathy can be present. Cutaneous vesicles
by viral factors. The strains which produce large amounts of usually heal without scaring 5 to 10 days. About 21 percent
antigenic glycoproteins cause more stromal disease.10 The of the acute conjunctivitis may be caused by Herpes
strains that prefer cooler temperature cause corneal infections Simplex virus7
whereas those that grow better in warmer temperature cause • Diffuse vesicle eruption of oral mucosa can occur
mucocutaneous infections. • Cutaneous primary herpes infection occurs due to direct
Seasonal variations in the incidence of recurrence are also inoculation.
reported. While winter and autumn were associated more with
recurrences in western countries, summer episodes were found
to be common in tropical countires, such as India.10 Flow chart 6.7.2.1: Classification of viral keratitis
Clinical Manifestations
Neonatal infections occur in utero or intrapartum. HSV 2 is
thought to be the common cause but type 1 also causes
neonatal herpes. The disease is manifested in three types:
a. Skin, mouth and eye alone
b. CNS with/without the above lesions
c. Disseminated to multiple viscera
Ocular infections manifest as:
• Keratitis—Superficial punctate keratitis, macrodendrites
and reversible edema
Fig. 6.7.2.1: Vesicular blepharoconjunctivitis with corneal lesion in Fig. 6.7.2.3A: Dendritic ulcer in recurrent
primary Herpes Simplex showing vesicles with erythematous base herpes simplex keratitis
Fig. 6.7.2.2: Microdendrites in primary Herpes Simplex keratitis Fig. 6.7.2.3B: Fluorescein staining of the
same lesion shows terminal bulbs
In immunocompromised and atopic individuals, cutaneous Blepharoconjunctivitis

infection can spread rapidly over body surface causing a fatal
Recurrent disease is similar to primary in manifestation and is
hemorrhagic disease called Eczema herpeticum.
to be managed similarly.
Management: Primary herpes infection is a self-limiting
condition. Topical antiviral therapy with Acyclovir three Epithelial Keratitis
percent eye ointment is sufficient for blepharoconjunctivitis.
Oral therapy may hasten the resolution but periodic Symptoms of Epithelial keratitis presents with irritation,
asymptomatic viral shedding through tear film will not be photophobia and blurred vision.
prevented.
Signs include mild conjunctival congestion with ciliary flush.
Recurrent Disease With recurrent disease corneal sensation will be reduced.
The recurrent ocular herpetic disease manifests as: Biomicroscopically infective corneal lesions present as:
• Blepharoconjunctivitis • Superficial punctate keratitis which coalesce to form
• Epithelial keratitis dendritic ulcers
• Stromal keratitis • Dendritic ulcers—branching linear lesions with terminal
• Iridocyclitis bulbs (Figs 6.7.2.3A and B). The dendrites are better
appreciated with double staining technique where the

infected cells at the margin stain with Rose Bengal and the
ulcer bed stain with fluorescein (Fig. 6.7.2.4). Even after
healing a ghost of the dendrite can be seen as sub-epithelial
scarring.
Marginal dendrite—uncommon epithelial lesion occurs at
corneal periphery. The ulcer bed will be soon infiltrated with
WBCs, making the recognition of the overlying dendrite
difficult.
If left untreated the dendrites coalesce to form large
geographic ulcer (Figs 6.7.2.5A to C).
Differential Diagnosis
• Varicella Zoster keratitis
• Epithelial fusion line caused by regenerating epithelium Fig. 6.7.2.4: Double staining
• Early fungal keratitis with hyphate edges
• Staphylococcal marginal keratitis - marginal dendritic ulcer
• Post-traumatic/contact lens induced epithelial keratitis
• Acanthamoeba keratitis
Management
Therapy shortens the course but does not prevent recurrent
disease. Treatment includes topical antiviral agents, antibiotics
to prevent secondary infection along with lubricants. Epithelial
debridement may be done gently with a cotton swab. Vigorous
rubbing can cause spread of the virus into the stroma. Topical
antiviral application has to be discontinued after 14 days to
avoid ocular surface toxicity. Antiviral therapy will not affect
stromal involvement or further recurrence.
Corticosteroids are contraindicated in active infective
epithelial keratitis. In immunocompromised patients oral Fig. 6.7.2.5A: Dendrogeographic ulcer - coalition of the dendritic
antiviral agents also may be needed. lines mimic geographic map contour
• Non-preserved topical lubricants help in healing
• Cycloplegic agents reduce ciliary spasm and light sensitivity.
Stromal Keratitis
The roles of infective and immune reactions in recurrent
stromal keratitis are interesting and have been extensively
studied.13
Recurrent stromal keratitis is predominantly an immuno-
pathological lesion. Various animal studies suggest that the
herpetic stromal disease is an immune reaction to either
nonreplicating viral components or altered corneal antigens.13
Stromal keratitis is also found to be less common in patients
with acquired immunodeficiency.
A variety of immune reactions have been proposed in its
pathogenesis. Cytology of the involved stroma demonstrates
T cells, macrophages and PMN cells suggesting cell mediated Fig. 6.7.2.5B: Rose Bengal staining of dendrogeographic ulcer
Fig. 6.7.2.5C: Dendrogeographic ulcer
immune reactions like delayed hypersensitivity involving T

helper cells, cell death mediated by cytotoxic T cells. Antibody
dependent cell-mediated cytotoxicity (ADCC), a cytotoxic
reaction against infected cells coated with antibodies to viral
antigens is also proposed. Stromal release of soluble viral
glycoproteins can activate antigen-antibody complex mediated
complement pathway with cellular chemotaxis. A T cell
mediated reaction involving both CD4 and CD8 through a
bystander mechanism has also been proposed.13,19,20
Recurrent stromal keratitis clinically manifests in three
forms:
a. Stromal interstitial keratitis
b. Stromal necrotic keratitis
c. Endotheliitis
Fig. 6.7.2.6A: Disciform stromal keratitis
Stromal Interstitial Keratitis
This immune stromal keratitis presents as single (Fig. 6.7.2.6A)
or multiple areas of stromal cloudiness resulting from cellular
infiltration, which obscures endothelial details. An antibody-
complement cascade to retained viral antigen within the stroma
is believed to be the underlying mechanism. These deposits
may manifest as a granular grayish ring called Wessley immune
ring. Recurrent episodes result in scaring and vascularization
with significant visual loss.
Infectious Stromal Keratitis

Stromal necrotic keratitis: This rare form presents as a necrotic
stromal lesion with epithelial ulceration and deep
vascularization (Fig. 6.7.2.6B). This intrastromal destructive
lesion is believed to result from viral replication in stromal
keratocytes and severe host inflammatory response. Fig. 6.7.2.6B: Stromal interstitial keratitis - dense stromal
descemetocele formation might also be seen (Fig. 6.7.2.6C). opacification with active vascularization
Corneal perforation can result within a short period of time infiltrate or neovascularization (Figs 6.7.2.7A and B). A mild-
in necrotizing keratitis (Fig. 6.7.2.6D). The lesion may be to-moderate iritis is frequently seen. Immunologic reaction to
indistinguishable from suppurative lesions caused by fungal viral antigens within corneal endothelial cells has been
or bacterial infections. Diagnosis is usually by exclusion of proposed as the underlying pathogenesis. However, active viral
other causes. replication may also play a role.13 The inflammation directed
at the endothelium may cause endothelial decompensation and
Differential diagnosis: overlying stromal and epithelial edema.
• Fungal keratitis HSV endotheliitis can manifest as:
• Bacterial keratitis • Disciform
• Acanthamoeba keratitis • Diffuse
• Retained foreign bodies with necrosis • Linear
• Topical anesthetic agent abuse Disciform Endotheliitis presents as localized, demarcated,
central or para-central stromal edema through which keratic
Endotheliitis
precipitates on the underlying endothelium can be appreciated.
Clinical signs of endotheliitis include keratic precipitates (KPs),
Diffuse endotheliitis shows scattered KP and diffuse
overlying stromal and epithelial edema and absence of stroma
corneal edema. In severe form can be associated with
secondary glaucoma due to trabeculitis.
Fig. 6.7.2.6C: Stromal thinning and descemetocele

formation in a necrotizing viral keratitis
Figs 6.7.2.7A and B: Disciform endotheliitis - localized stromal

Fig. 6.7.2.6D: Rapid progression to perforation edema overlying an inflamed area of endothelium. Localized keratic
in necrotizing viral keratitis precipitates can be appreciated through the edematous cornea
Linear endotheliitis appear as linear arrangement of keratic scaring and neovascularization, relieve pain and to restore
precipitates, progressing centrally from the limbus, with vision.
peripheral corneal edema trailing the migrating line of KPs.
Regimen: Topical dexamethasone one percent five times a day
This line of KPs can be sectoral or circumferential.
with antiviral therapy in equal frequency.
This dosage is maintained till the stromal haze starts
LABORATORY INVESTIGATIONS
clearing. The tapering is done in 50 percent frequency steps
Diagnosis of viral keratitis is mainly clinical. Laboratory with doubling duration. In disciform endotheliitis topical
investigations21,22 are not done frequently in routine clinical steroids can be stopped after a short course once the lesion
practice. clears. Since, the stromal lesion is only a localized edema,
Giemsa stain - shows multinucleated giant cells. permanent scaring is rare in this condition. In stromal inters-
Papanicolaou stain - shows intranuclear eosinophilic titial keratitis, steroids have to be continued for a long time to
inclusion bodies. prevent significant scaring. However, complications secondary
Viral culture - Vesicles, dendritic or geographical ulcers to prolonged steroid therapy should be kept in mind and the
specimens are taken and cultured on cell cultures. Specific cell dosage has to be titrated optimally with close monitoring of
lines are needed for different viruses. intraocular pressure. A diluted corticosteroid may be continued
Immunohistochemistry for viral antigens is not done in maintenance dose of once a day or for several months.
routinely since sophisticated laboratory facilities are needed.21 Often, chronic inflammation as a result of inadequate steroid
Impression cytology using a glass slide was described as use will be mistaken for frequent recurrences.
an alternative, inexpensive method.22
Polymerase chain reaction (PCR) is a sensitive test gaining Systemic Corticosteroids
popularity recently. When the clinical picture is inconclusive
of viral etiology, this investigation can be tried. Presence of It is logical to consider systemic steroids than topical in
HSV DNA can be demonstrated from corneal tissue and endotheliitis, in order to achieve a good concentration in the
aqueous humor. aqueous humor. The duration should be short to avoid steroid
related systemic side effects.
MANAGEMENT
Herpetic Iritis
Treatment recommendations of the Herpetic Eye Disease Herpetic iritis is characterized by ischemic necrosis of iris,
Study (HEDS)23-26 a multicenter, prospective clinical trial are: usually segmental and may extend onto ciliary body. This results
• Topical corticosteroids with antiviral agents reduce in iris atrophic patches after resolution. Invariably the iritis is
progression of stromal keratitis and shorten the duration. associated with secondary glaucoma due to associated
• Long-term oral acyclovir in suppressive dose of 400 mg/ trabeculitis. Polymerase chain reaction (PCR) of the aqueous
twice daily reduces recurrences and it is recommended in demonstrates viral particles.
patients with frequent recurrences.
• Oral acyclovir with corticosteroids in active stromal Differential diagnosis: Chronic anterior uveitis due to other
interstitial disease is not necessary. etiologies including retained intraocular toxic foreign bodies
Since, penetration of topical antiviral agents is very poor, should be ruled out.27
in endotheliitis and stromal necrotic keratitis, oral antiviral
Management: Oral antiviral therapy with systemic corti-
therapy is recommended along with topical steroids.
costeroids, topical cycloplegics and anti-glaucoma therapy.
Oral antiviral therapy is also recommended in patients
Limbal vasculitis is a rare manifestation. This is an Arthus
undergoing keratoplasty for herpetic scar.
reaction, resulting in peripheral ulcerative keratitis or anterior
segment necrosis.
Corticosteroid Therapy in
Herpetic Stromal Keratitis Meta-Herpetic Disease
In herpetic stromal lesions which are immune mediated, A non-infective epithelial disease associated with herpetic
corticosteroids are the choice in management. Topical therapy keratitis, manifests as epithelial erosions or persistent epithelial
in tapering regimen is recommended. The purpose is to reduce defects as a result of:
• Damaged basement membrane

• Anti-viral toxicity
• Neurotrophic component
Differential diagnosis: Geographic ulcer which consists of
irregular map like edges in contrast to regular heaped up
margins with a smooth ovoid contour of neurotrophic ulcer
(Fig. 6.7.2.8A).
Medical management comprises withdrawal of all toxic
drugs, topical preservative free lubricants, bandage contact lens.
Oral doxycycline 100 mg once daily serves to act as an anti-
collagenase by chelating action. Cases not responding to
medical therapy may need tarsorrhaphy. Non-healing
neurotrophic herpetic disease also responds to multilayered
amniotic membrane grafting- onlay/ inlay with onlay amniotic
grafting (Figs 6.7.2.8B and C). Fig. 6.7.2.8A: Metaherpetic non-healing horizontally oval
ulceration with heaped up epithelial margin
Surgical Treatment
Penetrating keratoplasty for corneal scars can be considered
after quiescence of one to two years. Recurrence of HSV is
the main cause for graft failure. Oral antiviral agents (Table
6.7.2.1) are to be given in therapeutic dosage in the
perioperative period and then to be maintained in suppressive
dose for life-long. Oral antiviral therapy along with
corticosteroids improves the graft survival up to 70 percent.28
Recurrent inflammation, vascularization and glaucoma can also
lead on to graft failure.
HERPETIC EYE DISEASE STUDY (HEDS)
Background
Fig. 6.7.2.8B: Multilayered amniotic membrane inlay with onlay
This is a multicenter, prospective study conducted in USA on grafting in a case of neurotrophic ulcer with secondary infection
herpetic eye disease. Recurrent herpetic disease is a major cause
for corneal blindness. The therapy of this chronic blinding
disease was largely emphiric. The role of corticosteroids and
oral antiviral drugs were uncertain. Experimental animal studies
were also inconclusive.
Purpose
• To evaluate the efficacy of topical corticosteroids in treating
herpes simplex stromal keratitis in conjunction with topical
trifluridine.
• To evaluate the efficacy of oral acyclovir in treating herpes
simplex stromal keratitis in patients receiving concomitant
topical corticosteroids and trifluridine.
• To evaluate the efficacy of oral acyclovir in treating herpes
simplex iridocyclitis in conjunction with treatment with Fig. 6.7.2.8C: Healed neurotrophic ulceration after amniotic
topical corticosteroids and trifluridine. membrane grafting
Table 6.7.2.1: Antiviral agents

Agent Mode of action Dosage Indication Comments
Trifluridine Phosphorylated by both Topical 1 percent solution HSV keratitis Toxic to both
cellular and viral thymidine 2 hourly infected
kinase - Competitive inhibition and uninfected
of viral DNA polymerase host cells
Iodoxy-uridine Phosphorylated by both 0.1 percent drops hourly/ HSV keratitis Toxic to both infected
IDU cellular and viral thymidine 0.5 percent ointment at and uninfected
kinase - Competitive inhibition of bed time host cells
viral DNA polymerase
Acyclovir (ACV) Phosphorylated selectively by Topical - 3 percent ointment Therapeutic selectively affects
viral Thymidine 5 times a day - active recurrent infected cells
kinase - Competitive inhibition of Oral - therapeutic 800 mg x epithelial HSV - less toxic topically.
viral DNA polymerase 5 times a day - Stromal keratitis Systemic - gastro-
Prophylatic - 400 mg - endothelial keratitis intestinal distress,
twice daily - HZO acute phase renal toxicity
Valacyclovir Prodrug to ACV Oral 1 gm three times Prophylactic Dosage convenience
HSV - recurrent Systemic toxicity -
stromal keratitis Thrombotic purpura
Famcyclovir Prodrug to pencyclovir Oral 500 mg three times Dosage convenience
Description either to oral treatment with acyclovir capsules (400 mg five

times daily) for 10 weeks or to the identical dose of placebo
HEDS-I consisted of three randomized, placebo-controlled
capsules. Patients also received topical prednisolone phosphate
trials. All patients received the topical antiviral trifluridine as
in the dosage schedule described above for the SKN trial.
prophylaxis against recurrences of HSV epithelial ulceration.
Patients were evaluated weekly for 10 weeks, alternate weeks till
16 weeks, and again at 6 months. The primary outcome was Herpes Simplex Virus Iridocyclitis, Receiving
time taken for the development of preset criteria for treatment Topical Steroids (HEDS-IRT)
failure during the 16 weeks period of examination.
Patients with active HSV iridocyclitis were randomized either
to oral treatment with 200 mg acyclovir capsules (400 mg five
Herpes Stromal Keratitis, Not on
times daily) for 10 weeks or to the identical dose of placebo
Steroid Trial (HEDS-SKN)
capsules. Patients also received topical prednisolone phosphate
Patients with active HSV stromal keratitis who had not used a in the dosage schedule described above for the SKN trial.
topical corticosteroid in the preceding 10 days were
randomized to treatment with topical prednisolone phosphate Patient Eligibility: Eligibility criteria common to the three
drops or topical placebo drops. protocols included: Age 12 years or older, no active HSV
A treatment schedule, starting with eight drops a day of epithelial keratitis, no prior keratoplasty of the involved eye,
one percent prednisolone phosphate for seven days, was and pregnancy ruled out.
progressively decreased over 10 weeks in such a way that
patients received one drop per day of 1/8 percent prednisolone Results
for the last three weeks of treatment. Placebo drops were given
by the same schedule. HEDS-SKN: In this trial, 106 patients were enrolled.
Compared with the patients in the placebo group, the patients
who received prednisolone phosphate drops had faster
Herpes Stromal Keratitis, on
resolution of the stromal keratitis and fewer treatment failures.
Steroid Treatment (HEDS-SKS)
However, delaying the initiation of corticosteroid treatment
Patients with active HSV stromal keratitis who already were did not affect the eventual outcome of the disease, in that
being treated with a topical corticosteroid were randomized visual acuity was similar in the two groups at 26 weeks.
HEDS-SKS: In this trial, 104 patients were enrolled. Over the Clinical Features—Systemic
16 weeks follow-up period, there was no difference in the rate
Prodromal stage comprises malaise and fever. Sometimes
of treatment failure between the two groups.
intense neuralgia is observed along the ophthalmic division
Thus, there was no apparent benefit in the addition of
of the trigeminal nerve and the patient presents with
oral acyclovir to the treatment regimen of a topical
unexplained severe eye pain.
corticosteroid and a topical antiviral.
HEDS-IRT: Only 50 of the originally planned 104 patients Exanthema
were enrolled during a 4-year recruitment period. Treatment
Erythema, maculopapular lesions occur. Vesicles along the
failures occurred at a higher rate in the placebo group than in
the acyclovir group. nerve course, strictly following laterality. Secondary bacterial
infection can lead onto pustules and scabs. Hemorrhagic skin
Although the number of patients enrolled in this trial was
too small to achieve statistically conclusive results, the trend ulcerations can occur due to occlusive ischemic vasculitis (Fig.
6.7.2.9). Deep pitting scars with pigmentation may result.
in the results suggests a benefit in adding oral acyclovir to the
treatment of HSV iridocyclitis in patients receiving topical Eyelid scaring may lead onto trichiasis, madarosis, ectropion
or entropion. In immunocompromised patients more than
corticosteroids and trifluridine prophylaxis.
one division of trigeminal nerve can be involved.
VARICELLA-ZOSTER DISEASE
Ophthalmic Manifestations
This virus of the herpes group causes chicken pox as primary
infection. Latent infection can present as recurrent disease - Keratitis
Zoster (Shingles).
Infective lesions are corneal punctate epithelial keratitis,
Primar y infection occurs usually in children as
microdendrites. Dendrites are different from those of HSV.
exanthematous fever. Ophthalmic involvement presents as
eyelid vesicles and follicular conjunctivitis. Phlyctenulosis, SPK They are short, without central ulceration and terminal bulbs.
and short microdendrites are uncommon manifestations.29 There can be wiped off - painted on, appearance.
Congenital lesions can present as cutaneous scars, CNS and Dendrite form mucous plaques - appear in 13 percent after
ocular abnormalities.30 8 to 12 weeks. They are elevated grayish plaques/
pseudodendrites (Fig. 6.7.2.10). Migratory, transitory and self-
Management
• Oral Acyclovir 800 mg 3 to 5 times for 5 days— reduces
severity of signs and symptoms and viral shedding. Topical
Acyclovir 5 times a day.
HERPES-ZOSTER OPHTHALMICUS
Reactivation of the virus occurs in 20 percent of the chicken
pox affected individuals. Ophthalmic zoster is seen in seven
percent.29
Risk Factors
• Age: commonly between 60 to 90 years
• Immune compromised individuals: HIV infected, diabetes
mellitus, immunosuppressive therapy, malignancy
• Physical trauma like surgery or radiation.
Defective cell mediated immunity is the major risk factor.
Herpes Zoster Ophthalmics (HZO) is 15 times more common
in HIV infected individuals, warranting a search for this disease
in HZO patients.31 Fig. 6.7.2.9: Varicella-Zoster cutaneous hemorrhagic lesions
Therapy
Acute Exanthematous Stage

Topical antivirals are of limited use.
Oral antiviral therapy with acyclovir 800 mg/5 times a day
or Famciclovir 500 mg two - three times per day or Valacyclovir
1 gm three times per day. When started with 72 hours after
the onset of skin lesions, will reduce viral shedding, severity
of the disease, systemic dissemination but has no effect on post
herpetic neuralgia (PHN). Since the viral shedding was
demonstrated for a long time, prolonged therapy with oral anti-
viral may be needed.31
Systemic corticosteroids should be given with antiviral
coverage. This will reduce severity of the acute signs and
Fig. 6.7.2.10: Mucus plaques on a corneal graft post HZO
symptoms but not the incidence or severity of PHN.
Post-herpetic Neuralgia
limiting lesions they are thought to be healing epitheliopathy
and no specific therapy is needed.32 Liesegang quotes several Neuralgic pain persists for more than a month beyond healing
and lasts for more than six months. Some patients complain
reports which showed viral particles by PCR in these lesions
of insect crawling or burning sensation in trigeminal
and a positive response to antiviral therapy.31
dermatome. The pain can be severe enough to result in sleep
Stromal—involvement in form of nummular lesions -
disturbance, anorexia and depression. Elderly individuals,
multiple discrete grayish haze at different depth of the stroma,
immuno-compromised and those with initial severe rash and
can occur.
pain are more likely to be affected.
Interstitial, disciform keratitis with anterior uveitis and
Pathology involves ischemic vasculitis of the nerves
glaucoma are rare and indistinguishable from HSV lesions. resulting in fibrotic scar involving large fibers.
Corneal anesthesia is profound and often leads onto Treatment of PHN comprises of Tricyclic antidepressants.
recalcitrant neurotrophic ulceration. They alter transport and activity of inflammatory substances
like serotonin, prostaglandin.
Zoster Uveitis Amitriptyline, Imipramine and Doxepin have anticho-
linergic, cardiac and CNS side effects.
Uveitis was reported in 43 percent of HZO patients. Usually,
Nortriptyline is non-sedative and preferred in cardiac
it is a short-lived single episode resolving within 2 months in
patients.
68 percent of affected individuals. However, a chronic disease
Amitriptyline is prescribed for anxious patients in a dose
cannot be ruled out. High incidence of secondary glaucoma,
of 25 to 50 mg, increased up to 75 to 100 mg.
with 15 percent requiring surgical intervention was also
Capsaicin 0.025 percent skin cream depletes substance
reported.33
P - a tachykinin that transmits pain impulse and prevents re-
Other ocular lesions include episcleritis, scleritis and limbal
accumulation.
vasculitis. Occlusive vasculitis can affect orbital soft tissue and
central nervous system. Manifestations include ptosis, oculo-
ADENOVIRAL KERATITIS
motor palsies, papillitis, retrobulbar neuritis, optic neuritis and
proptosis. Acute retinal necrosis - progressive acute retinal Adenoviruses are DNA viruses without an external lipid
necrosis can occur in HIV patients. envelope. There are 49 serotypes, divided into 6 sub-groups
Zoster sine herpete comprises of typical neuralgia and (A-F). Each sub-group attaches to specific tissues causing
ocular lesions without skin lesions. distinct clinical disease.
Clinical presentation includes: Follicular conjunctivitis,

pharyngoconjunctival fever—caused by serotypes 3, 7 and
epidemic keratoconjunctivitis—sub-group 6 / Serotypes 8, 19,
37.
Transmission: Generally viral envelope is easily damaged by
environmental assaults such as UV light, antiseptics, alcohol
and detergents. Being a non-enveloped virus, adenovirus can
resist such insults and survive for weeks in the environment
causing epidemics. They can be transmitted through infected
secretions. Transmission in hospital environment through
contaminated investigational instruments and eye drops are
an important source of out-breaks.
Pathophysiology: In the infective stage, viral replication in
conjunctival and corneal epithelial cells is seen with
inflammatory reaction.
In this immune stage, the viral antigen is filtered down to
the Bowman layer and causes immune reaction.
Continual genetic change and immune evasion prevents
permanent immunity.
Clinical features: Prodromal stage is associated with upper
respiratory infection.
First week is conjunctival stage manifests as acute follicular
conjunctivitis characterized by marked inflammatory reactions
like lid edema, bulbar conjunctival chemosis, tarsal conjunctival
pseudomembrane and sub-conjunctival hemorrhages. Pre-
auricular lymphadenopathy is an important associated feature
Figs 6.7.2.11A and B: Post-adenoviral sub-epithelial keratopathy
helps in the clinical diagnosis. Initial tearing progresses to dry - multiple coin like grayish opacities in sub-epithelial plane
eyes in the later stages due to lacrimal gland inflammation.
Conjunctival membrane can result in localized symblepharon.
The first affected eye has a more severe presentation. Treatment in acute stage is mainly supportive therapy for
Second week is the corneal stage presents as punctate the inflammatory changes. Topical preservative free
epithelial erosions initially and discrete fine punctate keratitis lubricants improves patient's comfort. Prophylactic
later. In severe cases a large epithelial defect lasts for several antibiotics also help. Antiviral therapy will reduce viral
days to heal. antigen load and the subsequent immune disease.
Third week—the infectious and inflammatory signs Unfortunately, none of the available antiviral agents is
subside and immune reaction takes over. Clinically subepithelial effective against adenovirus. Treatment for SEK haze
keratopathy (SEK) presents as multiple discoid lesions causing includes steroids to suppress the reaction. Systemic NSAID
considerable morbidity in visual acuity if present in the visual in the acute stage helps to reduce the inflammatory changes.
axis (Figs 6.7.2.11A and B). The glare makes night driving
hazardous. Fortunately, this highly symptomatic condition is REFERENCES
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Baudouin, C Creuzot-Garcher. New York: Georg Thieme Verlag
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• SPK: keratitis medicamentosum 2. Viral keratitis and conjunctivitis. In Smolin G, Thoft R. The Cornea
• Thygeson's SPK: recurrent, coarse lesions appear in crops Scientific foundations and clinical practice. Third Edition. Little
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Regional hospital prevalence of viral keratitis 1984;32(4):205-8. controlled trial of topical corticosteroids for herpes simplex stromal
11. Asbell P, et al. Analysis of viral DNA in isolates from patients keratitis. Ophthalmology 1994;101:1883-95.
from recurrent herpetic keratitis. Invest Ophthalmol Vis Sci 25. Herpetic Eye Disease Study Group. Acyclovir for the prevention
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12. Asbell PA, Centifanto-Fitzgerald YM, Chandler JW, Kaufman HE. epithelial keratitis. The Epithelial Keratitis Trial. Arch Ophthalmol
Analysis of viral DNA in isolates from patients with recurrent 1997;115:703-12.
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6.7.3 Fungal Keratitis

Sujith Vengayil, M Vanathi
The fungal infections of cornea are unique in many ways. The of tissue seldom produce pathological lesions. Saprophytic
etiology, presentation, diagnostic tests and their pick up rate, fungi grow on dead tissue and are seldom pathogenic.
response to treatment and the sequelae all differ from other However, under condition of impaired immune defense these
common bacterial infections. The fungal infections vary in can become pathogenic.
incidence also depending upon the geographic location and The majority of the pathogenic species are classified within
the climatic variation. The tropical climes and the temperate the Phyla Zygomycetes, Basidiomycetes, Ascomycetes, or the
climes show varying predilection to different fungal species. group Fungi Imperfecti. Classically, there are two broad groups
In this chapter we will be considering the etiopathogenesis, of fungi: yeasts and moulds. While not mutually exclusive,
clinical presentations and the treatment modalities to various mould spores germinate to produce the branching filaments
fungal infection of cornea. known as hyphae. Yeasts, on the other hand, are solitary
rounded forms that reproduce by making more rounded forms
FUNGAL CORNEAL ULCERS through the mechanisms as budding or fission. In a growing
colony of filamentous fungus, the mycelium can be divided
Microbial infection is the most important cause of corneal
into vegetative mycelium which grows into the medium and
ulceration. It is important because of its sight threatening
aerial mycelium, which projects from the surface. All molds
nature.1-14 Whenever there is corneal ulceration and stromal
of medical importance in corneal disease form septate hyphae.
inflammation, infection should be assumed until proved
otherwise. Various causative organisms responsible are bacteria,
BROAD GROUPS OF FUNGI
fungi, viruses and parasites. In this chapter we will concentrate
PATHOGENIC TO EYE
only on fungal causative agents.
Keratitis is the most frequent presentation of fungal The fungi pathogenic to the eye include:16,17
infection of eye. Fungi are opportunistic in the eye, since they • Filamentous fungi
rarely infect healthy, intact ocular tissues unlike certain virulent – Aspergillus
bacterial species. Ocular fungal infections or ophthalmic – Fusarium
mycoses are being increasingly recognized as an important – Curvularia
cause of morbidity and blindness more so in tropical countries – Paecilomyces
and developing nations. This is mainly attributed to the fact – Phialophora
that the main working population in such countries is involved • Other emerging fungi
in the agricultural sector where they are exposed to vegetable – Aureobasidium
matter and other organic contaminants. The varied types of – Rhodotorula
presentation, indolent and chronic nature of the ulcer along – Fonanscea
with the difficulty in isolating the organism from the specimen – Penicillium sp
have complicated the matter. Injudicious usage of antibiotic/ • Yeast
steroid drops, alarmingly increasing trend of self medication – Candida
and the usage of traditional home made contaminated
medication have led to the increasing frequency of the fungal PATHOGENESIS
corneal ulcers.15
Fungi are eukaryotic plant-like micro organisms and are Ocular infections usually occur as a result of a breach in the
one among the five kingdoms of life. There are over 100,000 healthy interaction between the three important deciding
species of fungi. Since fungi do not have chlorophyll, they factors, viz. host factor, pathogen and the environment.
absorb food from others. As they don't use light to make food, While the normal eye has its own defense mechanisms,
they can live in damp and dark places. Opportunistic fungi are the eyes with compromised cornea or ocular surface provide
harmless commensals which under normal living conditions the ideal stage for the invasion by the pathogenic organisms.
The most common predisposing factors are trauma, foreign HYPOPYON ULCER
body, bullous keratopathy, existing corneal ulceration, herpetic
In presence of very virulent organisms, the toxin which is
eye disease, severe tear film deficiency and contact lens wear.
secreted by them diffuses in the deeper corneal tissue and
The infection can be either exogenous or endogenous. The into the anterior chamber which ultimately leads to excessive
most common route is external via ocular surface epithelium. exudation from the limbal as well as iris and ciliary body vessels.
One or more components of the flora may take advantage of These sort of virulent ulcers also have deep and thicker
a situation to penetrate the cornea (an endogenous source of infiltrate. The exudation in the anterior chamber is not sterile
infection). Alternately, organisms may be inoculated from the as in most cases of bacterial infection. In cases of fungal
external environment at the time of injury (an exogenous infection the anterior chamber exudation also may contain
source of infection). The virulence of the pathogen, the size the hyphal elements due to the penetration of the stroma by
of the inoculums and the competence and nature of host the invasive hyphae. This is more common than in bacterial
defense mechanisms decide the severity of subsequent ulcers due to this invasive nature of most filamentous fungal
infection. hyphae.
The pathogenic mechanisms of fungi include direct
physical damage caused by invasion and growth of fungal SPECIFIC FUNGAL PATHOGENS
elements, damage from infiltrating leukocytes and damage The specific ocular pathogenic fungi16,17 include the following:
produced by fungal toxins and enzymes. The invasion of • Aspergillus: Aspergillus18-23 is a filamentous and ubiquitous
mycelia usually occurs parallel to collagen lamellae or may be fungus commonly isolated from soil, plant debris, and
perpendicular with more virulent organisms. This leads to indoor air environment. Among these, Aspergillus fumigatus
disruption of normal collagen fiber arrangement. The surface is the most commonly isolated species, followed by
mannoprotein adhesions of hyphae or pseudohyphae also Aspergillus flavus and Aspergillus niger. Aspergillus spp. are well-
inhibit the attachment of neutrophil thus escaping known to play a role in three different clinical settings in
phagocytosis. man: (i) opportunistic infections; (ii) allergic states; and
Fungal hyphae are large enough to preclude ingestion by (iii) toxicoses. Immunosuppression is the major factor
neutrophils. However, attempts at phagocytosis results in extra predisposing to development of opportunistic infections.
cellular release of lysosomal enzymes and oxygen metabolites. Since Aspergillus spp. are found in nature, they are also
This sets in motion the inflammatory cascade involving common laboratory contaminants.
plasmin and corneal matrix-derived metalloproteinase with • Fusarium: Fusarium24-26 is a filamentous fungus widely
activation of collagenase, proteinase, etc. which digest the distributed on plants, in soil and found in normal mycoflora
stromal collagen perpetuating the corneal damage. of commodities, such as rice, bean, soyabean, and other
The fungal cultures of A. flavus and F. solani contain serine crops. While most species are more common at tropical
proteinase and metalloproteinase activity while Candida albicans and subtropical areas, some inhabit the soil in cold climates.
strains produce gliotoxin - like metabolite. This can act on a Fusarium is one of the emerging causes of opportunistic
wide-variety of tissue proteins and is thought to contribute to mycoses. The most virulent Fusarium spp. is Fusarium solani.
invasiveness of the organism. The status of the host defense Fusarium spp. produces mycotoxins.
mechanisms further, determines the threshold of inoculum • Dematiacious Fungi: These saprophytic fungi 27-29 are
at which infection occurs. distinguished by the brown pigmentations of their colonies.
In some cases of mycotic keratitis which are responding A number of their members including Curvularia, Alternaria,
well to antifungal therapy, a sudden deterioration accompanied and Cladosporium have been reported as opportunistic
by renewed tissue destruction (in the absence of a demonstrable pathogens.
microbial cause) has been noted. This phenomenon is thought – Curvularia30,31 is a dematiaceous filamentous fungus.
to occur because dying fungal hyphae may elicit a type of Most species of Curvularia are facultative pathogens
hypersensitivity reaction. of soil, plants, and cereals in tropical or subtropical
Administration of corticosteroids can predispose to fungal areas, while the remaining few are found in temperate
keratitis by inhibiting chemotaxis thus suppressing ocular zones. Curvularia lunata is the most commonly
immune mechanisms and ingestion by phagocytes. They also encountered species. Importantly, the infections may
block degranulation, and reduce the production of phagocytes. develop in patients with intact immune system.
However, similar to several other fungal genera,

Curvularia has also recently emerged as an opportunistic
pathogen that infects immunocompromised
individuals.
– Alternaria is the most common fungus of this group
and is isolated from human infections.32-34 The species
have emerged as opportunistic pathogens particularly
in patients with immunosuppression, such as the bone
marrow transplant patients.
– Aureobasidium pullulans-an emerging pathogen,35-37
which comes under Phaeohyphomycoses, is a
dematiaceous fungus. It is found as a saprophyte in
waste water, soil, rock, plants and even air. Though
the pathogenicity of phaeohyphomycosis was
questioned towards corneal disease, the reports are
Fig. 6.7.3.1: Superficial mycotic keratitis with ulceration
increasing. One needs to be careful in both clinical and
microbiological evaluation for this organism as it has
certain clinical characteristics and require specific
microbiological evaluation. The ulcers are usually
central in location with multiple round ball like
infiltrates around the ulcer with extension to periphery.
• Yeasts: The majority of yeast infections38 are due to various
Candida species predominately C. albicans. The Candida
keratitis is more frequently encountered in temperate
climates while it is a rare entity in tropical climate.
• Unusual fungal pathogens: Case reports are available in
literature about keratitis involving unusual fungal
pathogens like Scedosporium, Phialophora, Metarrhizium
Anisopliae, etc.39-42
CLINICAL FEATURES
OF FUNGAL ULCERS
Fig. 6.7.3.2: Fusarium keratitis
The clinical features of fungal keratitis are non-specific and
may be confused with indolent ulcer of viral and bacterial
origin. Varying presentations of superficial mycotic keratitis
(Figs 6.7.3.1 to 6.7.3.3) and deep mycotic keratitis (Fig. 6.7.3.4)
can be seen vividly in these clinical pictures.
The distinctive features of the fungal ulcer are as follows:
• Hyphate ulcer: Fungal ulcer has a dry appearing epithelial
surface with a rough texture and dirty gray-white color
(Fig. 6.7.3.5). The epithelium may be elevated and intact
or occasionally it may ulcerate. It has delicate feathery
branching hyphae with surrounding stromal infiltrate. The
extension of the hyphate margins beyond the ulcer edge
present a distinctive feature and is a useful diagnostic
finding.
• Severe ocular reaction: The typical fungal keratitis produces
violent ocular reaction. There is appreciable ciliary flush
and flare in anterior chamber (Fig. 6.7.3.6). Fig. 6.7.3.3: Superficial mycotic keratitis
• Hypopyon: Hypopyon is invariably present in fungal keratitis

and usually result from sterile reaction to fungus and its
toxins. However, fungi may invade the anterior chamber
through intact Descemet's membrane and result in a fixed
hypopyon (Fig. 6.7.3.7).
• Satellite lesions: Satellite lesions are discrete stromal infiltrates
that surround the ulcer and are separated by clear cornea
(Fig. 6.7.3.7).
• Pigmented Ulcers: The ulcer infiltration can be pigmented29
(e.g. brown) in infection due to dematiaceous fungi (Figs
6.7.3.8 and 6.7.3.9).
• Endothelial plaque: An endothelial plaque is composed of
fibrin and leukocytes. It is located under the stromal lesion
and may be present in the absence of hypopyon. Micro
abscesses, satellite lesion and ring infiltrates are non-specific
Fig. 6.7.3.4: Deep mycotic keratitis with
chronic smouldering infection and represent an immune response.
Fig. 6.7.3.5: Deep mycotic ulcer with Fig. 6.7.3.7: Fixed hypopyon in an eye with fungal corneal ulcer
peripheral hyphate extensions
Fig. 6.7.3.6: Fungal corneal ulcer with hypopyon Fig. 6.7.3.8: Mycotic ulcer due to dematiaceous fungi
The commonly used techniques for identification of

etiological agents:
• Direct microscopic examination
• Culture
Method of Sample Collection
Corneal Scraping
After obtaining consent from the patients and proper
explanation of the procedure, the affected eye should be
anesthetized with 0.5 percent proparacaine eye drops for
corneal scraping.47,48 All sterile surgical precautions should be
taken to avoid contamination while sample is collected. After
application of a Barraquer wire speculum, the superficial debris
and mucus strands are to be cleaned and the ulcer should be
Fig. 6.7.3.9: Deep mycotic ulcer due to dematiaceous fungi scraped from the base and the leading edge with blunt tipped
iris repositor. Care should be taken not to perforate by avoiding
thinned necrotic areas and the direction should be always
towards one side rather than making to and fro movements.
In advanced cases, the entire cornea becomes homo-
Also cases with intact epithelium and deep abscess with
geneously yellowish-white and can resemble any microbial
comparatively less infiltrate superficially should be scraped in
keratitis. Stromal ulceration and necrosis may lead to perfo-
depth with due care to prevent perforation.
ration and endophthalmitis. This is especially a threat with
Fusarium solani keratitis in association with inappropriate use Anterior Chamber (AC) Paracentesis
of topical corticosteroids.
Yeast keratitis causes a small oval ulceration with an In very rare circumstances like suspected fungal infection with
expanding, discrete, sharply demarcated, dense, yellowish-white repeated negative culture reports but progressive infection,
stromal suppuration lacking delicate features of filamentous AC paracentesis is indicated.49 It is also called for, when there
organisms. is scanty material available from scraping and there is thick
Many patients receive some sort of treatment before hypopyon. Sharp 22/20 gauge needle is inserted into the
presenting to the corneal physician for expert opinion which anterior chamber between 6 o'clock and 7 o'clock area directly
may alter the morphology of the ulcer causing more confusion into the hypopyon and the material is aspirated. The procedure
to the etiological diagnosis. Thorough examination of lid must be carried out under aseptic precautions like routine
margin and both bulbar and palpebral conjunctiva of the intraocular surgery.
ipsilateral eye is essential to rule out any offending object.
Initial measurement of size of epithelial defect along with Corneal Biopsy
infiltration should be carried out and documented with proper It is indicated in cases with deep stromal abscess or in case
color coding. This will guide the clinicians for monitoring the where repeated culture shows negative reports but there is
lesion. Limbal/scleral extension should be found out to modify strong suspicion of infection. The cornea is anesthetized and
the standard therapy. Posterior segment evaluation is indicated 0.2 to 0.3 mm trephine is used to outline the area to be biopsied.
if there is suspicion of endophthalmitis. Usually a depth of about 0.1 to 0.2 mm is dissected out. The
tissue is then sent for histopathological as well microbiological
MICROBIOLOGICAL EVALUATION
analysis.
A microbiological work up of a suspected infectious ulcer Post LASIK cases: Fungal infection after LASIK though
must be done before the start of antibiotic treatment.43-46 rare are reported in literature.50-53 Sample collection from
Corneal scraping provides material for microbiological corneal infection after LASIK surgery requires special
diagnosis, debrides necrotic tissues and enhances antibiotic precaution. Scraping of the surface is not indicated in these
penetration. eyes due to fear of button holing of the flap. It can be
performed by lifting of the flap, as following infection the Acridine orange stain has also been found useful to detect
flap becomes edematous and thus provide little resistance. fungal hyphae in corneal scrapes.58 A fluorescence microscope
Therefore, careful handling of the flap is mandatory. The fitted with appropriate filters is needed for this technique.
specimen collection should be done both from the bed and Fluorescein-conjugated concanavalin A was found to provide
undersurface of the flap. If there is necrosis of the flap, either consistently bright staining of the fungal structures in corneal
excision or amputation of the flap should be done to reduce scrapes and is thought to be a promising first-line
the load of infection. fluorochromatic stain to visualize fungi in ocular samples.59
Direct immunofluorescence of fungi have been studied but not
Transportation and Processing used routinely due to demanding technical requirements that
of Collected Material are difficult to achieve in all cases. They can be employed in
situation where some atypical forms of organisms are
The collected sample should then be transferred to cotton
encountered or when infectious elements are sparse.
tipped applicator from the tip of repositor and dipped into
the bacterial culture tube and the Sabouraud's dextrose agar, Culture Technique
(the fungal culture media).
Culture is the 'gold standard' technique of investigation in
The final part of the sample collected should be used for
microbial keratitis. The specimen collected from the corneal
preparing slides for the KOH wet mount and Gram's staining.
scraping should be cultured for bacteria and fungi regularly.
The commonly used staining techniques employed are:
This should be done routinely in case of repeat cultures where
• Gram's staining
the clinical course is progressive in spite of logical treatment.
• Wet potassium hydroxide (KOH) (10%) mount
The specimen for the culture and sensitivity should be ideally
Other staining techniques used in detecting fungus include: taken before any antibacterial/anti fungal medication is started,
• Geimsa staining as this may affect the culture growth. If the patient is already
• Gomori Methenamine Silver (GMS) on medication, it is recommended to stop the treatment for
• Periodic acid-Schiff (PAS) 24 to 48 hour under strict supervision of the clinician before
• Calcofluor white culturing to enhance the chance of positive growth. Though
• Acridine orange liquid medium is highly sensitive for demonstration of
• Acid Fast Bacilli Staining pathogen, they are less specific than solid media because
Identification of the fungal genus by direct examination quantification is lacking in the former.
is generally not considered possible. Studies have suggested The commonly used culture media:
that calcium alginate swabs yield significantly greater growth • Sabouraud's dextrose agar incubated at 25°C,
than blade in mycotic ulcers though not significant for bacteria • Brain heart infusion broth incubated at 25°C,
and mixed ulcers.54 • Thioglycolate broth
The KOH wet mount and its modifications like Ink KOH Composition of Sabouraud's media commonly consists
are widely used for the rapid detection of fungal hyphae.55 of glucose 20 g, peptone 10 g, agar 15 g, water 1L which is
The ink in the ink KOH technique gives a good contrast which steamed to dissolve and pH adjusted to 5.4. It is then
helps the examiner in detecting the hyphae from otherwise autoclaved at 115oC for 15 minutes with added gentamicin
colorless background. and chloramphenicol. Antibacterial antibiotics, such as
The Giemsa stain, Gomori methanamine silver (GMS)56 and chloramphenicol or a penicillin-streptomycin combination, are
the periodic acid-Schiff (PAS) stains are special stains for detection usually incorporated in fungal culture media to suppress
of fungi in tissue. Various studies have reported varying bacterial growth and permit the isolation of fungi alone. But
sensitivities for these stains. chemicals like cycloheximide suppress the growth of fungus.
The fungal culture tubes are stored at 25oC in biological oxygen
In recent years, nonspecific fluorochromatic stains like
demand (BOD) incubator and taken out every third day for
Calcofluor white have become popular for the detection of fungi
observing growth. If any growth is noted, the Lacto Phenol
in ocular samples.57 Calcofluor white is more sensitive than
Cotton Blue (LPCB) staining is done to study the detailed
KOH wet mounts in detecting the common ocular fungi such
morphology of the species.
as F. solani and A. fumigatus in corneal scrapes. A fluorescence
microscope fitted with appropriate filters is required in this Jones criteria for diagnosis from culture: It comprises of clinical signs
technique. of infection plus isolation of bacteria (10 or more colonies)
on one solid medium and one additional medium or isolation show the efficacy of confocal microscopy in detecting
of fungi (any detectable growth) on any two media or one organisms. It provides epithelial, stromal, endothelial details
medium in the presence of a positive smear. In the presence and makes it possible to observe microorganisms in vivo
of incomplete criteria, the process may be judged as suspicious without use of dyes, stains or tissue fixation. In cases of
for infection and then the clinical judgment becomes the fungal keratitis with deep seated infiltrates and delayed
deciding factor in therapy. The results of corneal cultures must growth in culture, confocal microscopy can detect fungal
be considered in view of the clinical situation, adequacy of filaments accurately and thus preclude the need for more
sampling and likelihood of contamination. invasive procedures like corneal biopsy.
Growth of Organisms in Culture Medium MEDICAL TREATMENT
Almost all majority of fungi (filamentous) can grow within The general guidelines of treatment for fungal keratitis are
three days, but it is not unusual for them to take five to seven same as those for most of the other infective keratitis, but the
days to grow and upto one-fourth may take upto 14 days. duration is usually much longer.70,71
Therefore, culture plates should be kept for three weeks time Antifungal treatment is usually not started as an empirical
for ocular fungi isolation. therapy unless very strongly suggested by the clinical
More recently 'E test' is considered as an efficient means appearance of the ulcer or mode of injury.
of selecting optimal pharmacotherapy for fungal keratitis. Antifungal should be instituted at the earliest following
the availability of the smear report. The culture report, as
mentioned previously takes time to give conclusive evidence.
Alternative Emerging Investigations
Therefore, presence of hyphae in wet KOH mount or Gram's
• Molecular techniques: Polymerase chain reaction (PCR) is smear is enough evidence to start antifungal medication. The
being more commonly used in diagnosing microbial newly introduced faster molecular techniques using PCR may
keratitis because of its rapid results and ability to pick up also prove to be beneficial in this respect.
cases in even partially treated cases.60-65 The common class of agents used as antifungals (Table
• Clinical aids like confocal microscopy is also being used 6.7.3.1) include;
for identifying fungal keratitis whereby actual fungal • Polyene antibiotics
elements can be visualized in vivo.66-69 Various studies out • Imidazoles
Table 6.7.3.1: Antifungal agents

Antifungal group Mechanism of action Agents Concentration (topical) Main Sensitivity
Polyene 72,73 Interact with cell membrane Amphotericin B 0.15%-0.3% For yeast and resistant
antibiotics sterols primarily ergosterol. filamentous fungi esp
Cause increased permeability Natamycin 5% Aspergillus.sp
of cell membrane Filamentous fungi
(fusarium>asperg.)
Imidazoles Anti -mycotic activity Clotrimazole, 1% Broad spectrum
Miconazole 1% drops
2% ointment
Ketoconazole 1%
Triazoles Fluconazole 74,83,84 0.3% Broad spectrum
Itraconazole75,84 1%
Voriconazole85-95
Pyrimidines Antimetabolites Flucytosine 1% Candida, cryptococcus,
aspergillus, penicillium
Nystatin Binds to ergosterol, it forms 100.000 IU eye Molds and yeast
pores in the membrane that ointment
lead to K+ leakage and death
of the fungus.
Echinocandins Glucan synthesis inhibitors Caspofungin, Candida and
Micafungin Aspergillus sp
Anidulafungin
• Triazoles Oral antifungal agents may be used in fulminant and

• Pyrimidines progressive cases as adjunctive to topical medication. It is also
• Nystatin recommended in deep keratitis, associated scleritis and
• Echinocandins endophthalmitis. It is also part of treatment following
Polyene antibiotics interact with cell membrane sterols penetrating keratoplasty for therapeutic purpose in a case of
primarily ergosterol, which causes increased permeability and deep fungal keratitis. The usually used agents are ketoconazole
leads to cell lysis. The two main agents in this group are (200-600 mg/day) for filamentous fungal keratitis and
Amphotericin B and Natamycin. The imidazoles show a fluconazole (200-400 mg/day) and itraconazole (200 mg/day)
combination of mechanisms by which they affect antimycotic for severe yeast keratitis. Itraconazole also shows activity
activity. Clotrimazole, miconazole, ketoconazole belong to this against Aspergillus but lesser towards Fusarium species.
group. Fluconazole and itraconazole are the main agents in Newer antifungals with different mechanisms of actions have
the triazole group. They have broader spectrum of activity been introduced recently. The glucan synthesis inhibitors are
than the imidazole group with lesser side effects. Pyrimidines agents which are presumed to block fungal cell wall synthesis
are group of antimetabolites with known antifungal activity. (rather than cell membrane) by inhibiting the enzyme 1, 3-β
Flucytosine (FC) is a fluorinated pyrimidine and is the main glucan synthase. There are three such agents at present with
agent in this group. all three belonging to the chemical family also known as the
Natamycin (5%) is the first line of defense against the Echinocandins. The agents are Capsofungin, Micafungin and
filamentous fungi. Fusarium sp. is more susceptible to Anidulafungin. Their spectrum of activity is mainly against
Natamycin than Aspergillus sp. Topical Amphotericin B (0.15%- Candida and Aspergillus sp. with limited activity against
0.2%) is the most efficacious agent for yeast infections. Fusarium sp.
Amphotericin B is also recommended for the resistant Voriconazole is a newer triazole, which is structurally
filamentous fungal infections especially that caused by related to fluconazole which acts by inhibiting cytochrome
Aspergillus sp. 5-FC is often added to Amphotericin B to give P450 14 α demethylase. This is fungistatic to Candida but
additive effects. fungicidal to Aspergillus. It also has broad spectrum of activity
Miconazole one percent has a broad spectrum of activity that includes Fusarium sp. It is being tried intracorneal in many
against Aspergillus, Candida, Curvularia, Paecilomyces, Microsporum,
difficult cases with encouraging results as reported in
etc. Fluconazole also has a wide spectrum of activity against
literature.85-95
many pathogens. Topical solution is available as one percent
Posaconazole96-100 is also a new triazole antifungal agent,
concentration in sterile water.
with few available reports in literature showing utility in difficult
If the initial natamycin therapy is found to be less effective
cases of fungal keratitis.
in controlling the infection amphotericin or azole group may
be added. Resistance to antifungals is rarely seen except for
flucytosine for which it has been reported.76,77 Topical Surgical Treatment
antifungals may have to be used for prolonged duration. At
Surgical treatment should be resorted to if the ulcer is not
least six weeks to three months of treatment may be needed
responding to medical therapy. Penetrating keratoplasty is the
depending upon the extent of involvement. The frequency
most often done procedure for cases of worsening fungal
of medication can be decreased by 10 days to 2 weeks if clinical
keratitis.101,102 The procedure is same as for other indications.
improvement is noticed.
The penetration is poor for topical antifungals. Deposits The trephination should be done in such a way that at least 1
caused by the medications prevent proper assessment of mm of clear zone is achieved without clinical infiltration. The
progression or regression. The penetration can be aided by anterior segment should be cleaned of all suspected fungal
repeated scraping off of the epithelium. Subconjunctival hyphal elements. Intracameral and intravitreal antifungal, esp.
administration is not usually preferred due to toxic effects of amphotericin, can be an adjunctive depending upon the severity
the drugs. Miconazole is one agent that is least toxic and better of the case. During suturing cheese-wiring is often encountered
tolerated for this purpose. due to unhealthy peripheral tissue. Longer bites should be
Intracameral and intracorneal/Intrastromal administration may taken to avoid this. Post operatively systemic antifungal can
be considered in some cases with intraocular extension or be added to the treatment. Use of topical steroids is
anterior chamber involvement. (Amphotericin B 5-10 µgm/ controversial in any stage though it can be helpful if all signs
0.1 ml).78-82 of infections have subsided in the postoperative course.
CONCLUSION C, Kredics L. Mycotic keratitis due to Aspergillus nomius. J Clin

Microbiol 2009;47(10):3382-5.
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6.7.4 Acanthamoeba Keratitis

R Revathi, Hemal J Kansagra
Acanthamoeba keratitis (AK) is a painful, sight-threatening, These are rare and usually associated with disseminated
and difficult-to-treat corneal infection caused by pathogenic disease in an immunocompromised host.
protozoa Acanthamoeba. Although, Acanthamoebae have been found to penetrate
Descemet's membrane and feed on iris cells, it is uncommon
MICROBIOLOGY for keratitis to progress to posterior segment involvement,
Acanthamoeba are free living, parasitic protozoa. unlike other forms of microbial or fungal keratitis, where this
can rarely occur.
Habitat: Acanthamoeba are ubiquitous in nature. As these free
living protozoa feed on other bacteria, fungi and other
Acanthamoeba Keratitis
protozoa, they are found in sources where these
microorganisms are available. They can survive various adverse Incidence and epidemiology: The first definitive case of AK was
conditions like heat, desiccation and chemicals like chlorine. diagnosed in 1973 by Dan Jones in an American farmer with
The common water sources as sea, lakes, hot baths, swimming ocular trauma and exposure to contaminated water. 3 An
pool and domestic water as well as soil and dust. epidemic increase in the incidence of AK in the late 1980s in
Acanthamoebae can also be isolated from nasopharyngeal the United States has been attributed to the increase in soft
swabs in asymptomatic individuals. contact lens wearers, particularly those who used home-made
saline for disinfection. Overall, contact lens wear accounts for
Life cycle: Acanthamoeba exist either as active trophozoites
measuring 25 to 40 µm in length or as dormant cysts, 15 to 28 85 to 90 percent of cases of AK, majority being in soft lens
µm in length. The trophozoite has spoke like acanthopodia wearers.1,4 Acanthamoeba keratitis can still occur in noncontact
and pseudopodia which bind to and engulf epithelial cells. lens wearers and are associated with trauma and contamination
When subject to lack of food source or other unfavorable with water or soil especially in the developing countries.5,6
environment, they encyst. Cysts are known to survive even up The incidence of this protozoal keratitis seems to be
to 24 years at 410o C. The mechanism by which encystation increasing. Various reasons have been put forward, this
and excystation occurs is not known. The cysts have double including increase in awareness, better facilities for diagnosis
walls, which merge at some places and gives a hexagonal and alterations in water quality and water treatment
appearance. procedures.7-9
Classification: At least 8 pathogenic Acanthamoeba subspecies Risk Factors

cause keratitis.
The major subspecies causing keratitis in humans are: Contact Lens: The most common risk factor for developing
• Acanthamoeba castellani acanthamoeba keratitis is contact lens wear. The incidence is
• Acanthamoeba polyphaga reported as 1 in 30,000 contact lens wearers.2 Soft hydrogel
• Acanthamoeba culbertsoni lenses accounts for 88 and 12 percent is due to rigid gas
Most pathogenic Acanthamoeba strains which cause keratitis permeable lenses.2 Acanthamoebae readily colonize contact lens
in humans belong to genotype T4, while others belong to cases and adhere to contact lenses, particularly if biofilm is
genotypes T11 and T3.1,2 present. The biofilm of bacteria acts as a food source for
Acanthamoebae.10 Rigid-gas-permeable orthokeratology users
ACANTHAMOEBA OCULAR INFECTIONS also have a high predilection for AK, accounting for 40 percent
Noncorneal of keratitis associated with orthokeratology in 1 series.10
• Uveitis Poor Personal Hygiene: Lack of meticulous attention to contact

• Iris granulomas lens hygiene such as using tap water to rinse lenses, home-
• Choroidal infiltrates made saline, biofilm buildup on contact lenses and sleeping in
• Endophthalmitis contact lenses, increase the risk of AK.
Antecedent Trauma: Corneal injury, with exposure to

contaminated water and vegetative materials, is another major
factor in establishing infection.
Clinical Features
The clinical presentation of Acanthamoeba keratitis is
remarkably varied and non-specific. A high level of suspicion
is paramount to recognize this condition, even in noncontact
lens wearers. Pain out of proportion to corneal findings is
typical and must be differentiated from drug-seeking behavior.
No therapeutic response to variety of antimicrobial agents is
common. The course may wax and wane, and is often initially
misdiagnosed as herpes simplex virus keratitis, fungal infection,
or topical anesthetic abuse.
Early epithelial signs include:
• Epithelial roughening and irregularities mistaken for
punctate epitheliopathy Fig. 6.7.4.1: Perineuritis
• Elevated epithelial lines — dendritiform, grayish white,
plaque like with adjacent epithelial ulceration
• Fine epithelial and subepithelial curvilinear opacities
• Microcystic edema
Limbitis can also appear in the early stage of the infection.
Early stromal signs include radial perineuritis. This is an early
sign in the superficial stroma (Fig. 6.7.4.1). This granular
infiltration along the corneal nerves is thought to be the reason
for the severe pain associated with the infection from early
stage. Some corneas showed reduced sensation.
Late stromal signs include a white or grayish infiltration in the
anterior stroma, in a ring form. This is seen from 4 days to 21
months after the onset of symptoms (Fig. 6.7.4.2). It was
reported, that in about 83 percent of cases, it presented after
2 months thus making it characteristic of late stage of the
infection.1 The central cornea within the ring will show marked
Fig. 6.7.4.2: Stromal grayish ring infiltrate
edema with anterior uveitis. Hypopyon helps to differentiate
the immune ring associated with viral keratitis. Later frank
stromal necrosis can mimic any other suppurative keratitis (Fig.
6.7.4.3).
Scleritis, usually diffuse and anterior, can be contiguous
with the keratitis. Rarely posterior scleritis with optic neuritis
was also reported.1,11 On resolution scleral ectasia can occur.
Though it is considered to be an immune phenomenon,
acanthamoeba has been demonstrated in sclera histologically.12
Acanthamoeba corneal infections can also present as a plaque
or peripheral ulcerative keratitis.13,14
Diagnosis
The chances for isolating the organism are good if the
microbiological investigations are done in the early epithelial Fig. 6.7.4.3: Late phase necrotic lesion
and dissolution of the corneal stromal matrix. A

granulomatous type of tissue reaction with typical giant cells
and macrophages was also reported in corneal stroma with
scleral involvement. A cell mediated immune response is
implicated in these cases. Targeting these pathological steps
for effective therapy has been widely studied.17-20
Management
Anti-amoebic agents include biguanides, diamidines,
aminoglycosides, and azole antifungal agents like, clotrimazole,
itraconazole, miconazole and ketoconazole.
Diamidines: Propamidine (0.15%) or Hexamidine (0.1%): These are
Fig. 6.7.4.4: Double walled cyst in 10 percent KOH wet mount aromatic diamidine compounds that kill trophozoites and cysts,
although they are 2 to 4 times more effective against
trophozoites than cysts. Toxicity to these agents is reported.
phase of the infection. Deep scraping is necessary to obtain
They can be combined with neomycin or azoles for topical
specimen for microbiological evaluation. Culturing is done on
treatment.
non-nutrient agar plates with E. coli overlay. The amoebae use
the bacteria as food and wavy travel lines can be seen on the Polyhexamethylene biguanide (PHMB) and Chlorhexidine: These are
surface. cationic surfactant with detergent like properties which cause
Hexagonal, double walled cysts can be seen in 10 percent structural membrane and intracellular damage to the
KOH wet mount, Grams, Giemsa and Calcoflour white stain trophozoites and cysts. PHMB induces the cell membrane to
preparations (Fig. 6.7.4.4).15,16 shrink from the cyst wall, whereas chlorhexidine produces
Confocal microscopy is useful in demonstrating the swelling of the cyst. Concentrations of 0.02 percent (200 µg/
presence of this organism in the corneal tissue in clinical set- mL) PHMB and 0.02 percent chlorhexidine are typically used.
up. The amoeba is seen as ovoid refractile bodies.1,9 Biguanide resistance of cysts is postulated to be due to reduced
Polymerase chain reaction is also reported to be a useful uptake by the cysts. Biguanides can be combined with
tool in diagnosing this infection.1,2 propamidines.
Indirect fluorescent antibody or iimmunoperoxidase
Neomycin can be used with propamidine. However, its efficacy
technique can be used to demonstrate Acanthamoeba in either
is suboptimal as cysts are usually resistant to it. Seal
epithelial samples or in corneal tissue removed at the time of
recommends against using this agent over concerns of
penetrating keratoplasty.
promoting resistant mutants and the risk of hypersensitivity,
Impression cytology is also demonstrated to be effective
which is common with neomycin.20
in diagnosing Acanthamoeba keratitis.
Antifungal agents: Azoles are used as topical agents along with
Differential Diagnosis biguanides or diamidines. Oral therapy with itraconazole or
ketoconazole also can be tried in deep infections.
Viral keratitis is the most common misdiagnosis in AK. Both
epithelial and stromal stages are mistaken for HSV keratitis. Alkylphosphocholines: These are phosphocholines esterified to
Fungal keratitis can also be suspected in perineuritis stage and aliphatic alcohols. They exhibit in vitro and in vivo antineoplastic
stromal ring stage. activity and have been shown to be cytotoxic against Leishmania
donovani, Trypanosoma cruzi, and Entamoeba histolytica. A recent
Pathogenesis study has demonstrated that particularly hexadecylphospho-
choline is highly effective against various strains of
The pathogenesis of Acanthamoeba keratitis involves parasite
Acanthamoeba.20
mediated cytolysis and phagocytosis of corneal epithelial cells
and induction of programmed cell death. Acanthamoeba Choice and combinations of the therapeutic agents: Both
elaborate a variety of proteases which may facilitate cytolysis cationic antiseptics (PHMB and chlorhexidine) show good
of the corneal epithelium, invasion of the extracellular matrix, and uniform in vitro amoebicidal activity.20,21 Diamidines in
vitro sensitivity patterns were reported variably from good to Understanding pathogenesis of this protozoal infection
relative insensitivity to cysts. Medical therapy seems to have is also an area of interest. The two important steps in the
better results in early stages of the infection. Monotherapy of pathogenesis are:
either one of the amoebicidal agents can be tried at this a. Mechanism of Acanthamoeba adherence to corneal
stage.22,23 epithelial cells and
Combination regimens were also found to be effective in b. The invasion in to the stroma.
deeper infections. The combinations include diamidines with The host reactions are also studied with great interest. It
biguanides or either one of them with azoles or neomycin. was found that immunization via mucosal surfaces induces
Chlorhexidine have an additive effect with propamidine anti-acanthamoeba IgA antibodies in the tears and provides
in vitro and in vivo.24,25 solid protection against the development of Acanthamoeba
Therapy with higher concentration of the drug is also keratitis. The adaptive immune apparatus prevents
recommended in deeper infections since persistent and Acanthamoeba infections of the cornea by simply preventing
recurrent infections may be due to failure of the drug to reach the attachment of the parasite to the epithelial surface.1,18,19
cysticidal concentration in deeper tissues. The problem of
toxicity should be kept in mind. Apparently, much higher CONCLUSION
concentrations of chlorhexidine is needed to affect the
Acanthamoeba keratitis shows an increasing trend in the last
mammalian cells than the minimum cysticidal concentration.26
2 decades. Early recognition and treatment is very important
Resistance to the amoebicidal agents is reported but very
for the success of medical therapy. Better diagnostic procedures
difficult to prove by in vitro sensitivity, since the resistant
like, PCR and confocal microscopy are a step towards this
mutants are highly temperature sensitive and may not be
early recognition. Further research in improving contact lens
isolated in room temperature.27
care, identifying better therapeutic agents and manipulating
Several reports also reiterated the lack of correlation
the pathological events to treat this infection are necessary.
between in vitro sensitivity pattern and in vivo response, which
may be affected by host responses also.28 REFERENCES
Duration of treatment: Topical applications are started as 1. Illingworth CD, Cook SD. Acanthamoeba keratitis. Surv
hourly application and maintained till there is a clear clinical Ophthalmol 1998;42:493-508.
response. Then after gradual tapering, twice day maintenance 2. Seal DV. Acanthamoeba keratitis update-incidence, molecular
of PHMB can be continued for 6 to 12 months. epidemiology and new drugs for treatment. Eye 2003;17:893-905.
Epithelial disease responds to 3 to 4 months of therapy, 3. Jones DB, Visvesvara GS, Robinson NM. Acanthamoeba Polyphaga
Keratitis and Acanthamoeba uveitis associated with fatal
where as stromal disease requires 6 to 12 months treatment.
meningoencephalitis. Trans Ophthalmol Soc UK 1975;95:221.
Corticosteroids: Corticosteroid use in AK is controversial. 4. Moore MB, et al. Acanthamoeba keratitis associated with soft
Since they can suppress host immune system, they should be contact lenses. Am J Ophthalmol 1985;100:396.
5. Sharma S, Srinivasan M, George C. Acanthamoeba keratitis in non-
used with utmost caution only in uveitis, scleritis and post
contact lens wearers. Arch Ophthalmol 1990;108:676-8.
keratoplasty cases. 6. Chang PCT, Soong HK. Acanthamoeba keratitis in noncontact
Penetrating keratoplasty: Penetrating keratoplasty is reserved lens wearers. Arch Ophthalmol 1991;109:463-4.
7. Ibrahim YW, Boase DL, Cree IA. Ibrahim YW, Boase DL, Cree
for impending or actual perforations in acute stage of the
IA. Factors affecting the epidemiology of Acanthamoeba keratitis.
infection. This is mainly done to preserve globe integrity since Ophthalmic Epidemiol 2007;14(2):53-60.
reinfection and failure of the graft are very common. 8. Foulks GN. Acanthamoeba keratitis and contact lens wear: Static
As a late rehabilitative procedure, this is done after six or increasing problem? Eye Contact Lens 2007;33(6 Pt 2):412-4.
months of quiescence. 9. Awwad ST, Petroll WM, McCulley JP, Cavanagh HD. Updates in
Acanthamoeba keratitis. Eye Contact Lens 2007; 33(1):1-8.
Current Research 10. Hammersmith KM. Diagnosis and management of Acanthamoeba
keratitis. Curr Opin Ophthalmol 2006;17(4):327-31.
Since most of the infections are still associated with contact 11. Mannis MJ, Tamar u R, Roth AM, et al. Acanthamoeba
lens wear, improvements in contact lens maintenance are one sclerokeratitis: determining diagnostic criteria. Arch Ophthalmol
of the current areas of research interest. 1986;104:1313-7.
12. Dougherty PJ, Binder PS, Mondino BJ, Glasgow BJ. Acanthamoeba 21. Kosrirukvongs P, Wanachiwanawin D, Visvesvara GS. Treatment
sclerokeratitis. Am J Ophthalmol 1994; 117:475-9. of acanthamoeba keratitis with chlorhexidine. Ophthalmology
13. Sahu SK, Das S, Sharma S, Vemuganti GK. Acanthamoeba keratitis 1999;106(4):798-802.
presenting as a plaque. Cornea 2008;27(9):1066-7. 22. Wysenbeek YS, Blank-Porat D, Harizman N, Wygnanski-Jaffe T,
14. Moreira AT, Prajna NV. Acanthamoeba as a cause of peripheral Keller N, Avni I. The reculture technique: individualizing the
ulcerative keratitis. Cornea 2003;22(6):576-7. treatment of Acanthamoeba keratitis. Cornea 2000;19(4):464-7.
15. Sharma S, Srinivasan M, George C. Diagnosis of acanthamoeba 23. Hay J, Kirkness CM, Seal DV, Wright P. Drug resistance and
keratitis-a report of four cases and review of literature. Indian J Acanthamoeba keratitis: the quest for alternative antiprotozoal
Ophthalmol 1990;38(2):50-6 chemotherapy. Eye 1994;8(Pt 5):555-63.
24. Berger ST, Mondina BJ, Hoft RH, et al. Successful medical
16. Sawada Y, Yuan C, Huang AJ. Impression cytology in the diagnosis
management of Acanthamoeba Keratitis. Am J Ophthalomol.
of acanthamoeba keratitis with surface involvement. Am J
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Ophthalmol 2004;137(2):323-8.
25. Cassella JP, Hay J, Seal DV. Rational dr ug targeting in
17. Vemuganti GK, Pasricha G, Sharma S, Garg P. Granulomatous
Acanthamoeba keratitis: implications of host cell-protozoan
inflammation in Acanthamoeba keratitis: an immunohistochemical interaction. Eye 1997;11(Pt 5):751-4.
study of five cases and review of literature. Indian J Med Microbiol 26. Ficker L, Seal D, Warhurst D, Wright P. Acanthamoeba Keratitis -
2005;23(4):231-8. Resistance to medical therapy. Eye 1990;4:835-8.
18. Clarke DW, Niederkorn JY. The pathophysiology of Acanthamoeba 27. Perez-Santonja JJ, Kilvington S, Hughes R, Tufail A, Matheson M,
keratitis. Trends Parasitol 2006; 22(4):175-80. Epub 2006 Feb 24. Dart JK. Persistently culture positive acanthamoeba keratitis: in
19. Niederkorn JY. The role of the innate and adaptive immune vivo resistance and in vitro sensitivity. Ophthalmology
responses in Acanthamoeba keratitis. Arch Immunol Ther Exp 2003;110(8):1593-600.
(Warsz). 2002;50(1):53-9. 28. Seal D, Hay J, Kirkness C, et al. Successful medical therapy of
20. Seal D. Treatment of Acanthamoeba keratitis. Expert Rev Anti Acanthamoeba keratitis with topical chlorhexidine and
Infect Ther. 2003;1(2):205-8. Review. propamidine. Eye 1996;10(Pt 4):413-21.
6.7.5 Microsporidial Keratitis

Manotosh Ray
Microsporidia are obligate intracellular, spore-forming, frequency.4-6 The recent outbreak of microsporidial keratitis
eukaryotic protozoal parasites with two distinct developmental in different parts of the world could be related to increased
phases — shizogenic and sporogenic. They are ubiquitous in awareness, high level of suspicion, precise knowledge of the
nature and capable of infection in wide range of vertebrates disease and better diagnostic methods.
and invertebrates. Six genera with at least 12 different species
of microsporidia are known to cause human infection. MICROSPORIDIA: CLASSIFICATION
Generally these are opportunistic pathogens. Microsporidia AND TAXONOMY
affect many human system including gastrointestinal, The scientific classification of microsporidia is still evolving.
pulmonary, ocular, kidney and sinus, especially in those who The current classification is being fiercely debated. Initially
are immunocompromised. With increased prevalence of microsporidia was thought to be a protozoan. However, recent
human immunodeficiency virus (HIV) infection, more and studies using DNA technology indicate that microsporidia
more cases of microsporidiosis are being reported. belongs to fungi kingdom or at least to the sister kingdom of
Ashton and Wirasinha reported the first human case of fungi. Traditional species identification method includes
microsporidial keratitis in 1973.1 They isolated microsporidia physical characteristics of the spores, life cycle and its
from a vascularized corneal scar, unsuspected of infectious relationship to the host. Recent scientific studies suggest that
etiology. Sporadic cases of microsporidial keratoconjunctivitis genetic tools using the markers are more accurate method of
have been reported in immunocompromised individuals since species identification. Thus the origin and that of fungal nature
1991.2,3 More recently, the disease is being diagnosed even in of microsporidia are now being challenged with newer
non-immunocompromised individuals with increased technology. Despite all these, more than 1200 species with
Fig. 6.7.5.1: Microsporidia Life Cycle
143 genera have been identified. However, more studies are Table 6.7.5.1: Microsporidia classification
required to better understand the origin of microsporidia. Family Genera Species
Table 6.7.5.1 depicts the current classification of micro-
Nosematidea Brachlola B algerae,
sporidia. Among these, genus enchalitozoon, microsporidium B vescularum
and nosema are known to cause ophthalmic infection. *Microsporidia Microsporidium M Ceylonensis,
M africanum
Life Cycle: Microsporidia spores are quite resistant to Enterocytozoonidea Enterocytozoon E bleneusi
environmental changes. Once ingested or otherwise contracted, *Encephalitozoonidea Encephalitozoon E cuniculi,
E intestinalis
the spores germinate and release polar tubules. The common *Nosematidea Nosema N ocularum, N connori
mode of transmission is ingestion or inhalation. The Pleistophoridea Trachipleistophora T hominis,
germinated spores get attached to the host cells through the T anthopophthera
polar tubule. Sporoplasms are injected into the host cell *Known to cause ocular infection
through polar filaments. The sporoplasms undergo merogony
to produce sporoblasts inside the host cell. Sporoblasts caused by the genus encephalitozoon. Deep stromal keratitis,
undergo further merogony and maturation to form spores. on the other hand, is commonly encountered in immuno-
The new spores grow to fill up the host cells, which eventually competent individuals. The genus responsible for stromal
burst and release the spores (Fig. 6.7.5.1). The newly released keratitis is nosema and microsporidium (Table 6.7.5.1).
spores go on to infect more host cells or can be passed to new However, most of the recent reports suggest that superficial
hosts through feces or urine. punctate keratoconjunctivitis may involve even the
immunocompetent subjects.4-6
CLINICAL TYPES
PREDISPOSING FACTORS
Two distinct clinical types of microsporidial keratitis have been
described. The mode of ocular microsporidial infection is yet to be
a. Diffuse superficial punctate keratoconjunctivitis ascertained. Ocular trauma, use of topical steroid and exposure
b. Deep corneal stromal keratitis to contaminated water are thought to be the major
Superficial punctate keratoconjunctivitis is known to occur predisposing factors. However, most of the authors could not
more commonly in immunocompromised subjects. This is identify any risk factor in significant number of cases in their
published case series. The possible predisposing factors are

enumerated below.
• Ocular trauma
• Contaminated water
• Topical steroid
• Contact lens
• Immunosuppression
• Pets
• Travel history
• Soil exposure
In a retrospective non-comparative case series, Joseph J
et al described ocular trauma as major predisposing factor
that accounted 42 percent of the total cases.4 Other factors
identified were contaminated water and long-term use of Fig. 6.7.5.2: Epithelial lesions in microsporidial
keratoconjunctivitis
topical steroid. In another retrospective case series, Chan et al5
described contact lens and ocular trauma as possible risk
factors. The authors were unable to identify any risk factor in
four out of six cases in their series. The largest series of
microsporidial keratitis till date is reported from Singapore.
Loh et al7 reported 134 cases of microsporidial keratitis in
124 eyes. In this large retrospective non-comparative case series
the authors identified soil exposure as major risk factor
accounting for 50 percent of total cases followed by contact
lens wear (21.1%) and topical steroid treatment (17.1%).7
CLINICAL FEATURES
Superficial Punctate Keratoconjunctivitis

Microsporidial keratoconjunctivitis presents like any other red
Fig. 6.7.5.3: Subepithelial form of microsporidial
eye syndrome. The usual symptoms include pain, redness, keratoconjunctivitis
tearing, photophobia and mild to moderate blurring of vision.
Most of the patients are referred to ophthalmologist when
symptoms do not subside after reasonable period.
Microsporidial superficial punctate keratoconjunctivitis
(SPK) is characterized by diffuse, multifocal, coarse, punctate,
raised, round or oval epithelial lesions (Fig. 6.7.5.2). These
lesions are distributed all over the cornea depending on the
severity of the disease. Focal epithelial lesions are generally
less that a millimeter in size. These lesions are stained with
fluorescein (Fig. 6.7.5.2). Over the next few days to weeks
subepithelial (Fig. 6.7.5.3) and anterior stromal infiltrations
(Fig. 6.7.5.4) are noted. By this time most of the epithelial
lesions are resolved. Occasionally fine keratic precipitates (Fig.
6.7.5.5) with mild anterior chamber inflammation are seen if
there is extensive stromal involvement. Mild to moderate non- Fig. 6.7.5.4: Stromal infiltration of Microsporidial
purulent conjunctivitis is a universal feature. keratoconjunctivitis
No definitive predisposing factor has been identified. Since

the routine microbiological investigations are negative, many
ophthalmologists tend to treat deep stromal keratitis with
simultaneous multiple therapy. This leads the considerable delay
in actual diagnosis. Difficulty in isolation of microsporidia
further complicates the matter and makes the establishment
of diagnosis extremely difficult.
Usual history is non-resolution of signs and symptoms
with conventional anti-microbial treatment. Occasionally
keratitis may improve with temporary resolution of signs and
symptoms only to recur again in few weeks time. Slit lamp
biomicroscopy reveals a central mid to deep stromal infiltrate
with surrounding edema. Overlying epithelium is generally
Fig. 6.7.5.5: Keratic precipitates intact with some epithelial edema. Endothelial exudates are
not uncommon. Anterior chamber inflammation varies from
none to gross hypopyon depending on the stage and severity
of the disease. Severe conjunctival injection and lid edema
indicate the chronicity of the disease. Some corneas may
perforate even before the diagnosis is established necessitating
tectonic corneal graft.
DIAGNOSIS
The microbiological diagnosis is established essentially by
isolating the microsporidial spores from the affected eye. The
diagnosis is often difficult due to inadequate samples obtained
from corneal scrapings. Samples can ideally be taken from
cornea, although occasionally conjunctival scrapings may also
isolate the organisms. One can use no. 15 blade with Bard-
Fig. 6.7.5.6: Microsporidial stromal keratitis Parker handle or a large gauze needle to scrape the cornea.
Conjunctival scrapes are taken from the lower fornix.
Staining Methods: Wide variety of stains can be used to identify
Deep Stromal Keratitis
the microsporidial spores. Previous studies have successfully
Microsporidial deep stromal keratitis is a chronic refractory used calcofluor white, Gram's stain, Giemsa stain and 1 percent
eye infection and it has got relatively poor prognostic outcome. acid-fast stain to identify the organism. Calcofluor white shows
There is a history of prolonged eye illness ranging from intracellular and extracellular oval fluorescent bodies in clumps
four months to more than a year. This is essentially a diagnosis typical of microsporidia when examined under fluorescent
by exclusion. Therefore, a high index of suspicion and microscope.4 Microsporidia spores appear bright red with
thorough knowledge of the disease is often necessary. Deep characteristic band against a blue background when stained
stromal keratitis presents like any other keratitis with pain, with one percent acid-fast.4 These spores are also mild gram
redness, tearing, photophobia and marked diminution of positive in nature. Giemsa stain shows epithelial cells
vision. Clinically microsporidial stromal keratitis could mimic containing cytoplasmic inclusion bodies consistent with
suppurative or non-suppurative inflammation and microsporidia. 4 Another successful technique to isolate
vascularization of the cornea and includes differential diagnosis microsporidia spore is modified trichrome stain. Modified
of herpes simplex, mycotic or bacterial keratitis (Fig. 6.7.5.6). trichrome staining of corneal scrapes shows a typical
Generally, the eyes are treated as bacterial, fungal or even intracellular pinkish or red spherical bodies characteristic of
herpetic keratitis. microsporidia spores (Fig. 6.7.5.7).5,7
Fig. 6.7.5.7: Microsporidial spores stained Fig. 6.7.5.8: Resolved microsporidial keratitis
with modified trichrome stain
It is more difficult to isolate the organism in microsporidial successfully treated microsporidial SPK with topical
stromal keratitis. Diagnosis currently depends on morphological fluoroquinolones.7
demonstration of the organism in one or more readily Fumagillin is considered as most specific anti-
obtainable specimens. Definitive species identification is done microsporidial agent, although it is not widely available. This
by using immunofluorescence technique, electron microscopy is naturally secreted antibiotic extracted from Aspergillus. The
and PCR. The diagnosis is made either by deep corneal water-soluble form of fumagillin (known as fumidil B) is widely
scraping or corneal biopsy. Another noninvasive technique to used to treat microsporidial infection in honeybees. The
diagnose microsporidial stromal keratitis is confocal mechanism of action of fumagillin is debatable. General belief
microscopy. The spores appear as high contrast intraepithelial is that fumagillin acts by altering the DNA content or by
or intrastromal opacities. Under electron microscope the spores inhibiting the RNA synthesis in the organism. Therapeutic
show sporoplasms and tubular polar filament. dosage of topical fumagillin is every three to four hours till
the epithelial lesions resolve. Topical fluorometholone was used
TREATMENT when there was stromal infiltration with anterior chamber
There is no standardized treatment protocol for microsporidial inflammation.
keratitis. Various authors have used different treatment Surgical treatment for microsporidial SPK is well
combinations with variable results. There is also a suggestion established. This includes diagnostic and therapeutic
that microsporidial superficial punctate keratitis doesn't debridement of the affected epithelium. The debulking
warrant any treatment due to self-limiting nature of the disease. technique mechanically reduces the loads of organism.
However, this view may not be acceptable to everybody. However, this may increase the risk of stromal infiltration as
Specific drug treatment for microsporidial keratitis includes well as secondary infection.
hexamidine, itraconazole, propamidine isethionate, Treatment outcome of microsporidial SPK is often
albendazole, fluoroquinolones, benzimidazole and the more satisfactory. Most of the eyes recover well with or without
specific fumagillin. Albendazole is a broad spectrum anti- visually insequential subepithelial scar (Fig. 6.7.5.8). Persistent
helminthic and has been shown to be effective in treatment "nummular" lesions are noted in minority group of patients.
of microsporidiosis.8 There are conflicting reports regarding Recurrence is uncommon but not impossible.
the effectivity of itraconazole, which is broad-spectrum triazole Treatment of microsporidial stromal keratitis is more
antifungal.9 Joveeta et al reported complete resolution of one difficult. As previously mentioned the disease is chronic and
third of the cases in their series after treatment with indolent in nature. There is no definitive therapy available for
itraconazole.4 Another potential antimicrosporidial agent is this entity. Font et al treated their case with fumagillin 0.3
propamidine isethonate that is traditionally used to treat percent and oral albendazole without any response.10 In
acanthamoeba keratitis. In the largest reported series, Loh et al another study Venuganti et al reported that systemic
itraconazole was effective in certain patients with 3. Metcalfe TW, Doran RM, Rowlands PL, et al. Microsporidial
microsporidial stromal keratitis.11 Some cases respond to keratoconjunctivitis in patients with AIDS. Br J Ophthalmol
medical therapy temporarily, only to recur after few weeks to 1992;76:177-8.
months. Hence, it is reasonable to say that in the absence of 4. Joveeta Joseph, Sridhar MS, Murthy S, et al. Clinical microbiological
profile of microsporidial keratoconjunctivitis in southern India.
effective medical therapy it is appropriate to manage these
cases surgically. Penetrating keratoplasty helps eradicating 5. Chan CM, Theng JT, Li L, et al. Microsporidial keratoconjunctivitis
infection and resume useful eyesight. There is no report of in healthy individuals: A case series. Ophthalmology 2003;110:1420-
recurrence of infection after corneal transplantation. 25.
In conclusion, microsporidial keratoconjunctivitis is more 6. Sridhar MS, Sharma S. Microsporidial keratoconjunctivitis in a HIV-
common than expected in healthy individuals. A high index seronegative patient treated with debridement and oral itraconazole.
of suspicion is necessary to diagnose the disease. A careful Am J Ophthalmol 1003; 136:745-6.
correlation of clinical and microbiological findings would help 7. Loh RS, Chan C ML, et al. Emerging prevalence of microsporidial
to make a definite diagnosis and to treat the condition keratitis in Singapore: Epidemiology, clinical features and
management. Ophthalmology 2009;116:2348-53.
effectively. Microsporidial infection must be considered in all
8. Yee RW, Tio Fo, et al. Resolution of microsporidial epithelial
cases of atypical multifocal epithelial keratitis and culture keratopathy in a patient with AIDS. Ophthalmology 1991;98:196-
negative stromal keratitis that is refractory to conventional 201.
medical treatment. 9. Schuster FL, Visvesvara GS, et al. Opportunistic amoebae:
challenges in prophylaxis and treatment. Drug Regist Updat
REFERENCES 2004;7:41-51.
1. Ashton N, Wirasinha PA, Encephalitozoonosis (nosematosis) of 10. Font RL, Su GW, et al. Microsporidial stromal keratitis. Arch
the cornea. Br J Ophthalmol 1973;57:669-74. ophthalmol 2003;121(7):1045-47.
2. Friedberg DN, Stenson SM, Orenstein JM, et al. Microsporidial 11. Venuganti GK, Prashant G, et al. Is microsporidial keratitis an
keratoconjunctivitis in acquired immunodeficiency syndrome. Arch emerging cause of stromal keratitis? - a case series study. BMC
Ophthalmol 1990;108:504-08. Opthalmology 2005;5-19.
6.7.6 Contact Lens Related Keratitis

M Vanathi
Contact lens wear is the most common predisposing factor and adnexa.2,6,8,14,38,55 Gram-positive organisms such as
for infectious keratitis in patients with previously healthy eyes. Staphylococci and Streptococci are more commonly associated with
Contact lens induced keratitis may be of the immune or corneal ulcers in patients wearing aphakic and therapeutic
infectious type. Contact lens (CL) wearers most likely to contact lenses.1,6,8,14,38 The association of virulent gram-
experience corneal infection are those on soft contact lens negative pathogens, including Pseudomonas aeruginosa, as
wear. Contact lens-associated infectious keratitis1-16 can result causative organisms of severe keratitis has been well established
in severe ocular morbidity. It commonly occurs with among wearers of soft contact lenses.1,56,57 Extended wear
disposable soft contact lens wear,17-24 high - Dk extended- contact lens users are at particular risk of infection with
wear rigid gas permeable (RGP) CL wear,25 and plano-tinted Pseudomonas aeruginosa. Infections caused by P. aeruginosa can
contact lenses.26 Users of extended wear soft contact lenses be highly destructive to the cornea and are often difficult to
(EW-SCLs) are at particular risk to infection.3,6,13,15,25-35 treat. This is attributed to its possession of a large genome
The most important pathogens associated with contact lens containing a larger than usual number of genes devoted to
related corneal infections are Pseudomonas aeruginosa1-16,18,28,36,37 virulence, regulation of virulence, adaptation to diverse
and Acanthamoeba species. 36-54 Other pathogens include environmental conditions, and resistance to killing.58
Staphylococcus species, Streptococcus species, enteric gram-negative Although they have been described in contact lens wearers,
organisms, and the mixed flora of the eyelids, conjunctiva, infections due to fungi are relatively uncommon.1,10 Fungal
keratitis among contact lens wearers is rare, even in regions PATHOPHYSIOLOGIC EFFECTS OF
where noncontact lens-associated fungal keratitis is more CONTACT LENS WEAR
common, comprising less than 5 percent of microbial keratitis
Contact lens wear causes a wide spectrum of changes in the
among contact lens wearers.1,37,57,59-62 Fungal infections are
cornea and conjunctiva, the most important of which is an
usually more common in therapeutic contact lens wear27 or
induced hypoxia and hypercapnia.63 These lead to pathologic
the immunocompromised patients. In recent times however,
changes resulting in corneal edema, infection, or warpage in
it has been observed that the microbial spectrum of contact
susceptible patients.
lens-related keratitis may be evolving, with increasing
• Hypoxic changes occur in all patients who wear lenses
involvement of Fusarium species in nontherapeutic soft contact
overnight and the cornea usually recovers during the
lens compared with prior reports.
following day in most patients.71-73 The reduced oxygen
The fact that development of soft lenses that allow
availability and the carbon dioxide accumulation with CL
physiological levels of oxygen to reach the ocular surface
wear result in a number of metabolic changes including a
(silicone hydrogel lenses), has not significantly reduced the
reduction in the corneal epithelial metabolic rate and
risk of contact lens-related corneal infection points to the fact
accumulation of stromal lactic acid. These lead to a
that hypoxia is not required for infection to occur though it
compromised epithelial junctional integrity, resulting in
does not rule out hypoxia as a contributor to the problem.63
epithelial fragility, abrasion,76 punctate keratitis and
susceptibility to microbial invasion77
EPIDEMIOLOGY AND RISK FACTORS
• There is a change in corneal epithelial structure with extended
The incidence rates for bacterial microbial keratitis range from wear lenses that may predispose to bacterial adherence56
approximately 2/10,000 per year for rigid contact lens, 2.2 to • A more permanent effect of stromal acidosis is endothelial
4.1/10,000 per year for daily-wear soft contact lens, to 13.3 to polymegathism. More severe changes of polymegathism
20.9/10,000 per year for extended-wear soft contact lenses.64 occur with duration of wear, with PMMA lenses, and with
The risk with therapeutic contact lenses is much higher - 52/ extended wear of contact lens.19,20 Contact lens wear does
10,000 per year. Annual incidence of microbial keratitis is not seem to alter endothelial cell density significantly
estimated to be 4 to 21 per 10000 soft contact lens wearers • Contact lens have significant effects on the tear film,
depending on overnight wear.65-67 resulting in increased tear evaporation, stimulation of reflex
The most significant risk factors in contact lens related tearing, a decreased blink rate, alteration in tear-film
infections include extended wear soft contact lens, overnight osmolarity and trapped debris with tear stagnation under
wear, smoking, male sex, socioeconomic status, suboptimal a contact lens. Epithelial erosions from corneal desiccation
adherence to recommended lens wear and care regimens.68-74 manifest with coarse punctuate erosion in the central or
The risk of microbial keratitis among contact lens wearers is paracentral cornea or with nasal and temporal peripheral
about 80-fold greater than among healthy nonwearers.68 staining of the cornea adjacent to the edge of the lens
The major risk factor for microbial keratitis is overnight • Ocular surface changes induced by contact lens wear: A state of
wear of soft contact lens, the risk increasing with the number subclinical conjunctival inflammation persists even in
of nights of continuous wear. Higher risks have also been asymptomatic contact lens wearers. 75 Decrease DAF
related to lower socioeconomic status, smoking, and male (membrane associated C-regulatory protein which inhibits
patients and patients with the acquired immunodeficiency virus complement activation) leads to ulcerative and immune
infection.75 Poor hygiene and noncompliance with contact lens keratitis. It is important to note that only one percent of
cleaning and lens-case cleaning have also been rated as tear film is exchanged with soft contact lenses versus 14
significant risk factors. The age of the contact lens is predicted percent with rigid lenses. This may contribute to the greater
to be an important factor, based on several laboratory studies incidence of infectious keratitis among SCL wearers
confirming adherence of bacteria to contact lenses. The other • Contact lens wear may suppress or interfere with factors
major risk factors in the development of contact lens related that normally inactivate or remove foreign microorganisms
infectious keratitis include corneal trauma, exposure to polluted from the eye. 29 Changes in the conjunctiva and the
water, use of home made saline for disinfections, improper conjunctival flora of patients with contact lens wear,
lens care and poor compliance with contact lens cleaning increase the propensity to infection from subsequent other
solutions, overnight wear and extended wear schedules. mechanisms. After exposure, pathogenic factors play a role
in mediating bacterial infection, starting with adherence infections.76 Though daily disposable soft contact lenses are
factors. There is a higher prevalence of gram-negative rods thought to theoretically have a lower risk of infectious keratitis
compared with the microbial keratitis in cases without compared with other lens wear regimens, as risk of infection
contact lens wear.24,25 Approximately one third of contact still exists, these lenses should be prescribed and used with
lens related microbial keratitis is associated with gram- great care to minimize contact lens-related infectious keratitis.77
positive cocci, such as Staphylococci and Streptococci, but two
thirds is associated with gram-negative rods, especially Contact Lens Contamination
Pseudomonas aeruginosa. The distribution varies among the
Contact lenses themselves can act as a vector to which
different lens styles and wear patterns.26 Fungi are relatively
microorganisms adhere and get transferred to the ocular
infrequent, occurring more commonly in microbial keratitis
surface. Contact lenses can get infected with commensal
with therapeutic contact lens wear than in microbial
microorganisms of the ocular surface or the potential
keratitis with cosmetic or aphakic wear.27 Acanthamoeba
pathogens that may occur transiently on the ocular surface. In
keratitis has been associated with both hard and soft
the presence of reduced tissue resistance, these resident
contact lens, although daily wear soft contact lens have
microorganisms or transient pathogens invade and colonize
been the principal predisposing factor.
the cornea or conjunctiva to produce inflammation or
Microbial Keratitis Related to Orthokeratology infection.63 Hence, the risk of infectious keratitis increases
manifold in the presence of an abrasion in the cornea.
Orthokeratology is a clinical technique that uses reverse- Lens handling greatly increases the incidence of lens
geometry rigid gas-permeable contact lenses to alter corneal contamination. Even when removed aseptically from the eye,
shape to provide temporary reduction of refractive error. more than half of lenses are found to harbor microorganisms,
Microbial keratitis is the most severe, potential vision- almost exclusively bacteria. While coagulase-negative
threatening complication associated with orthokeratology staphylococci are most commonly cultured from worn lenses,
contact lens wear. Most reported cases include female patients approximately 10 percent of lenses have been found to harbor
from East Asia, aged between 8 and 15 years.78 The infectious Gram-negative and highly pathogenic species, even in
organisms implicated include Pseudomonas aeruginosa in 38 asymptomatic subjects.63
percent of these cases and Acanthamoeba species in 33 percent
cases.78 The peak year for occurrence of microbial keratitis as Mechanisms Enhancing Bacterial Adherence
seen on review of literature was 2001, accounting for more
than half of all reported cases.78 Overnight orthokeratology Multiple factors play a role in mediating bacterial adherence
contact lens wear has the potential complication of to the contact lens including pilli, net surface charge of bacteria,
pseudomonal keratitis.79 the biofilm, exotoxins and endotoxins. Bacteria have
mechanisms to adhere to contact lens surfaces, especially worn
Pathogenesis CLs, with components of mucin and proteins from the tear
film. The rapid production of a biofilm on the CL further
Microbial Adherence to Contact Lens/Cornea increases the bacterial attachment. The adherence of bacteria
The ability of bacteria to produce a slime envelope or biofilm on the lens surface allows the development of a glycocalyx
has been implicated in the pathogenesis of contact lens related and biofilm to form and convert adhering bacteria into
infectious ulcers. The formation of a polysaccharide biofilm replicating bacteria colonizing the lens surface with a stronger
(coating of mucin and protein) enhances adherence of attachment. The glycocalyx is a polysaccharide (slime)
Pseudomonas and Staphylococcus to the surface of the contact containing structure lying outside the outer membranes of
lens. The process of CL-related microbial keratitis and gram positive and gram negative organisms. Bacteria in the
inflammation is preceded by the presence or transfer or both, biofilm replicate at a slower rate because nutrients are less
of microorganisms from the lens to the ocular surface.63 available than in planktonic conditions and are hidden from
Detailed understanding of lens-related bioburden is important antiseptics and other destructive agents, including immunologic
in the understanding of factors associated with infectious and events. Biocides and antibiotics must be at high levels or have
inflammatory complications. Hyperoxygen-transmissible effective mechanisms to deal with the biofilm to achieve
silicone hydrogel contact lenses are associated with lesser inhibition of the bacteria within the biofilm. Bacteria within
morphological anomalies and a decreased incidence of biofilms are 20 to 1,000 times less sensitive to antibiotics than
are planktonic organisms. Organisms can also reach the CL environment. Regular and meticulous cleaning of the contact
from the conjunctival flora or other environmental sources lens case or planned replacement of contact lenses reduces
and the prior presence of a biofilm may increase the retention contact lens ulcerative keratitis.
time of these bacteria, resulting in increased colonization of
the lens surface. These biofilms may explain how compliant CLINICAL PRESENTATION
patients or patients with uncontaminated CL cases can get
infected. Contact Lens Associated
The cornea can get injured by the insertion and removal Acute Red Eye (CLARE)
process, by lens deposits or defects in the contact lens, by An acute corneal inflammation may be caused by overnight
chemical toxicity of CL disinfectants, or by lens-induced wear of soft contact lenses. This is characterized by pain,
hypoxia. Contact lens wear interferes with the normal defense usually unilateral, redness, tearing, photophobia, corneal
mechanisms, can initiate the epithelial defect and also increase infiltrates and blurred vision that suddenly appears upon
the expression of glycoprotein bacterial receptors on corneal waking. The lens is, commonly seen to be tight or immobile
epithelial cells, causing changes that further enhance the (immobile lens syndrome/tight lens syndrome). The
adherence of Pseudomonas. The first step is adherence of breakdown of debris accumulated behind the lens leads to
bacteria to the injured epithelium and to the exposed stroma. the inflammatory reaction. This condition mandates immediate
Pseudomonas adheres more avidly than other bacterial species contact lens removal with appropriate medical management
to corneal epithelial cells and reaches the anterior stroma by and anti-inflammatory therapy.
transepithelial migration and therefore evades normal host
defense mechanisms. It can spread radially and deeply within Pathogenesis: Contact lens wear associated red eye may be due
the stroma, migrating between stromal lamellae, facilitated by to varying etiologies. The inflammatory causes of CLARE
potent proteoglycan enzymes that destroy the corneal stroma. include:
CL wear modifies the mucin layer of the tear film, which • Hypoxia
normally inhibits bacterial attachment to the cornea, and this • Toxic effects from post-lens tear debris
delays the tear inflammatory response from reaching the site • Mechanical irritation from a poor-fitting lens
of corneal inflammatory response. • Dehydration of the tear lens while wearing lenses during
sleep
• Solution hypersensitivity or toxicity or a reaction to
Contamination of Contact Lens Care Systems
bacterial toxins.
About 40 to 70 percent of patients with contact lens wear Under hypoxic conditions, glucose gets converted to lactate
related keratitis are noncompliant with recommended care and lactate diffuses into the stroma and increases the osmolarity
regimens and with lens maintenance systems.36-44 Old and metabolic acidosis that results in corneal edema. A decrease
disinfecting systems in combination with extended wear in normal corneal metabolism causes tissue compromise that
constitute a significant risk for development of microbial can lead to CLARE. White blood cells migrate from the limbal
keratitis.49 vasculature and form infiltrates in the peripheral cornea. These
Contact lens case contamination results from a sterile infiltrates are often small (<2 mm) and cause little to
combination of poor hygiene and the failure of current no epithelial staining.
disinfection systems. Disinfection by chlorine is associated with Keratitis associated with contact lens wear may be
a higher contamination rate compared with chemical, hydrogen (Table 6.7.6.1):
peroxide, chlorhexidine, or heat disinfection.55 A recent • Infiltrative keratitis
outbreak of fusarium keratitis in contact lens wearers in – Sterile
Singapore and the United States, was related to use of a specific – Infective
contact lens cleaning solution use.63,77 • Ulcerative keratitis
Contamination of RGP-lens cases is associated with Patients usually present with symptoms of progressive
increasing age of the CL. The use of tap water or home made discomfort, limbal or conjunctival hyperemia, photophobia,
saline solutions is not recommended because all homemade mucopurulent exudates and decreased vision.
saline solution containers become contaminated. Other factors Sterile corneal infiltrates in contact lens users (Fig. 6.7.6.1),
influencing contamination of the lens case includes the are typically mid-peripheral, small, relatively indolent, and focal
patient's hygiene and the surrounding socioeconomic or multifocal in distribution. These infiltrates often resolve
Table 6.7.6.1: Differentiation between sterile and infectious infiltrate associated with contact lens wear
Clinical features Sterile Infectious
Onset Subacute / acute Usually acute (fungal & acanthamoeba may
be slowly progressive)
Incidence More common Less common
Contact lens More common with soft hydrophilic & More common with extended wear soft
silicon contact lenses contact lenses
Symptoms Usually mild discomfort or foreign body sensation Increasing pain, both sharp and aching
Conjunctiva Mild hyperemia with minimal / no discharge Diffuse conjunctival injection with ciliary flush,
eyelid edema, erythema & mucopurulent discharge
Size & location Usually < 1mm Usually > 1mm
of infiltrate Midperipheral/subepithelial Random or deep
Overlying corneal Usually intact or punctuate erosions Usually ulcerated. Staining present
epithelium No staining
Corneal stromal lesions None or white-gray focal or multifocal superficial Yellow-white, suppurative infiltrate with ill defined
well defined infiltrate with predilection for margins, frequently with mild stromal edema or
peripheral stroma stria. Predilection for central or superior cornea
Corneal endothelium Usually not affected Pseudogutta with some Descemet's folds.
Occasionally inflammatory plaque underlying
stromal infiltrate
Anterior chamber Clear or with minimal flare and cells Minimal to marked anterior chamber reaction with
(hypopyon may occur with or without hypopyon
stromal infiltrate)
Sterile corneal infiltrates responds rapidly to topical

corticosteroid therapy without the need for concomitant
antibiotic administration. When a patient on SCL wear
develops a midperipheral corneal infiltrate, the selection of
an appropriate therapeutic regimen rests primarily on deciding
whether the keratitis is due to an infectious or noninfectious
process. Such a decision is often difficult. Most often, the
infiltrate is treated as an infectious corneal ulcer. Indeed, many
of these infiltrates are noninfectious in origin which gets over-
treated with topical antibiotics. However, an incipient bacterial
infection may infrequently masquerade as a "characteristic"
sterile infiltrate. Bacteria have been isolated from the abnormal
Fig. 6.7.6.1: Contact lens induced immune keratitis
epithelium over a sterile infiltrate and may yield a positive
culture.
spontaneously on cessation of contact lens wear. The eye is
Contact Lens Related Microbial Keratitis
usually quiet, and the corneal tear film is usually acellular. The
overlying epithelium usually is intact but punctate epithelial Pseudomonas keratitis: Corneal ulcers due to P. aeruginosa are
erosions may be observed. usually associated with severe pain. Pseudomonas keratitis is
The clinical hallmark of untreated microbial keratitis is a a rapidly progressive suppurative process. Extensive ulceration
suppurative stromal infiltrate characterized by a dense yellow- and hypopyon are common. The involved corneal stroma is
white or gray-white infiltrate with an overlying epithelial defect necrotic with edema of the surrounding stroma along with a
on slit-lamp biomicroscopy. Stromal ulceration, stromal edema, ground-glass appearance. An immune ring infiltrate may also
and striae may be present. As a general rule, stromal infiltrates be observed. The immune ring observed in gram-negative
with an overlying epithelial defect should be considered ulcers such as those due to Pseudomonas is a result of the
infectious until proved otherwise. lipopolysaccharide endotoxin that is released when the
organism dies. This ring consists of polymorphonuclear

leukocytes within the corneal stroma that are attracted by the
alternate complement pathway and chemotaxis through
properdin activation. These ring infiltrates result from antigen-
antibody precipitates. Bacterial keratitis associated with soft
contact lens wear can appear differently. A granular epithelial
keratopathy without stromal infiltration can also occur in cases
of Pseudomonas aeruginosa infection.
Acanthamoeba keratitis: Acanthamoeba keratitis is an insidious,
chronic, progressive process. Severe pain, out of proportion,
to objective findings is a common presenting complaint.
Acanthamoeba can be established in the epithelium before
stromal involvement and a granular epithelial irregularity with
punctate or dendritiform changes are considered a sign of Fig. 6.7.6.2: Acanthamoeba keratitis with prolonged BCL wear in
early Acanthamoeba infection. A dendritiform pattern of aphakic bullous keratopathy
epithelial keratitis or disciform keratitis can occur in cases of
early Acanthamoeba keratitis, leading to the misdiagnosis of
herpes simplex virus (HSV) keratitis. Recurrent epithelial
breakdown and healing is common. A ring-shaped infiltrate,
partial or complete, (Fig. 6.7.6.2) may also be observed. Radial
keratoneuritis explains the intense pain.
Streptococcal or Staphylococcal keratitis: Though, Pseudomonas or
Acanthamoeba are organisms commonly related with contact
lens wear associated keratitis, Streptococcal or Staphylococcal
keratitis (Fig. 6.7.6.3) may be more commonly seen in these
patients at risk to develop microbial keratitis.
Fungal keratitis: Contact lens related corneal infection with fungi
is rare. Predisposing factors include improper lens care by the
refractive lens wearers and a chronic epithelial defect with
topical corticosteroid use among the therapeutic lens wearers.
Fig. 6.7.6.3: Contact lens induced infectious keratitis
Filamentous fungi were more likely to be associated with
cosmetic or aphakic lens wear, whereas yeasts were more
frequently found with therapeutic lens use. Fungal keratitis
Although, Acanthamoeba cysts and tropozoites obtained
accounts for approximately 3 percent of infections associated
from corneal scrapings can be stained with Gram-stain, as
with cosmetic or aphakic contact lenses and 12 percent of
well as with Giemsa, trichrome, periodic acid - Schiff (PAS),
infections associated with therapeutic lenses.80 Clinical
Gomori methanamine silver (GMS), and hematoxylin and
presentation is usually typical of fungal keratitis with chronic
eosin stain, Calcofluor white, a chemofluorescent vital stain,
indolent stromal infiltrate with feathery margins.
is also very useful. It binds to chitin and cellulose in the cell
walls of fungi and Acanthamoeba cysts. Yeast, fungal elements
LABORATORY EVALUATION
and Acanthamoeba cysts show bright apple-green fluorescence
Corneal scrapings for smears and culture are to be obtained ag ainst a reddish-orange background. An indirect
prior to initiation of antimicrobial therapy for infectious immunofluorescent staining technique and fluorescein-
keratitis. Specimens should be directly inoculated onto standard conjugated lectins may also be used for Acanthamoeba species
media - blood, chocolate, and Sabouraud's dextrose agar and identification, but these techniques require a fluorescent
thioglycolate broth. In contact lens wearers, culturing lens care microscope for visualization. Corneal scrapings inoculated on
solutions and the contact lens case may be helpful in a nonnutrient agar with an overlay of Escherichia coli or other
establishing the diagnosis. gram-negative organism enhances recovery. The presence of
Acanthamoeba trophozoites is indicated by a snail-tract 5. Donnenfeld ED, Cohen EJ, Arentsen JJ, et al. Changing trends in
clearing through the layer of bacteria. When direct inoculation contact lens associated corneal ulcers: an overview of 116 cases.
CLAO J 1986;12:145-9.
is not possible, an amoeba saline transport media and filter-
6. Galentine PG, Cohen EJ, Laibson PR, et al. Corneal ulcers associated
culture technique may be utilized. with contact lens wear. Arch Ophthalmol 1984;102:891-4.
7. Lindquist TD, Sher MA, Doughman DJ. Clinical signs and medical
TREATMENT therapy of early Acanthamoeba keratitis, Arch Ophthalmol
1988;106:73-7.
Management of immune infiltrates will include topical 8. Mondino BJ, Weissman OD, Farb MD, et al. Corneal ulcers
antibiotic therapy, avoidance of CL wear, and cessation of associated with daily wear and extended wear contact lens. Am J
topical steroid therapy and close monitoring. Treating physician Ophthalmol 1986;102:58-65.
has to be sure of the immune or infective nature of infiltrates 9. Moote MB. McCulley JP, Kaufman HF, et al. Radial keratoneuritis
before starting topical steroid therapy. as a presenting sign in Acanthamoeba keratitis. Ophthalmology
Antimicrobial therapy for infectious keratitis will be in 1986;93:1310-15.
10. Ormerod ID, Smith RE. Contact lens associated microbial keratitis.
appropriation to the isolated organisms, and management will
Arch Ophthalmol 1986;101:79-83.
be as in infectious keratitis. 11. Theodore FH, Jakobier FA, Jeuchter KB, et al. The diagnostic value
Topical antibiotic therapy is altered in accordance to the of a ring infiltrate in Acanthamoeba keratitis. Ophthalmology
culture sensitivity reports and clinical progress. Anti- 1985;92:1471-9.
acanthamoeba treatment is initiated in cases with positive 12. Wilson LA, Schlitzer R, Ahern D. Pseudomonas corneal ulcers
acanthamoeba cysts. The long-term maintenance of anti- associated with soft contact lens wear. Am. J. Ophthalmol
1981;92:546-54.
acanthoemba therapy is important along with close and regular
13. Chalupa E, Swarbrick HA, holden BA, et al. Severe corneal
follow-up. Replacement of the infected contact lens is infections associated with contact lens wear. Ophthalmology
compulsory. 1987;94:17-22
14. Laibson PR, Donnenfeld ED. Contact ulcers related to contact
CONCLUSION lens use. Int Ophthalmol Clin 1986;26:3-15
15. Krachmer JII, Purcell JJ. Bacterial corneal ulcers in cosmetic SCL
Optimal contact lens fitting minimizes, the tear film and corneal wearers. Arch Ophthalmol 1978;96: 57-61.
changes. Overnight wear should be avoided. Patient education 16. Cooper RI, Constable IJ. Infective keratitis in soft contact lens
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a lower relative risk of keratitis. Education and compliance 17. Serdahl ClL, Mannis MJ, Shapiro DR. Infiltrative keratitis associated
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3.
are associated with a lower risk. Homemade solutions should
18. Killingsworth DW, Stern GA. Pseudomonas keratitis associated
be not be used. Frequent lens case replacement should be with the use of disposable soft contact lenses. Arch Ophthalmol
practiced. Daily cleaning, disinfecting and weekly enzymatic 1989;107:322-3.
cleaning of the CLs should be standard practice. CL 19. Dunn JP, Mondino BJ, Weissman BA, et al. Corneal ulcers
disinfectant solutions must be simple to use and yet effective associated with disposable hydrogel contact lenses. Am. J.
against both planktonic bacteria and bacteria in a biofilm. Ophthalmol 1989;108:113-7.
20. Ficker L, Hunter P, Seal D, Wright P. Acanthamoeba keratitis
occurring with disposable contact lens wear. Am. J. Ophthalmol
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29. Adams CP, Cohen EJ, Laibson PR, et al. Corneal ulcers in patients
50. Moore MB, McCulley JP. Acanthamoeba keratitis associated with
with cosmetic extended-wear contact lenses. Am J Ophthalmol
contact lenses: Six consecutive cases of successful management
1983;96:705-9.
Br. J. Ophthalmol 1989;73:271-5.
30. Wilhelmus KR. Review of clinical experience with microbial
51. Autan JD, Starr MB, Jakobiee FA. Acanthamoeba keratitis a review
keratitis associated with contact lens wear CLAO J 1987;13:211-4.
of the literature, Cornea 1987;6:2-26.
31. Hassman G, Sugar J. Pseudomonas corneal ulcer with extended-
wear soft contact lenses for myopia. Arch Ophthalmol 1983; 52. Epsten RJ, Wilson LA, Visveswara GS, Plounde EG. Rapid
101:1549-50. diagnosis of Acanthamoeba keratitis from corneal scrapings using
32. Lemp MA, Blackman HJ. Wilson LA, Leveille AS. Gram negative indirect fluorescent antibody staining Arch Ophthalmol
corneal ulcers in elderly aphakic eyes with extended-wear lenses. 1986;101:1318-21.
Ophthalmology 1984;91:60-3. 53. Hust IW, Green WR, Metz. W, et al. Management of Acanthamoeba
33. Spoor TC, Hartel WC, Wyann P, Spoor DK. Complications of keratitis. A case report and review of the literature. Ophthalmology
continuous-wear soft contact lenses in a nonreferral population. 1984;91:1105-11.
Arch Ophthalmol 1984;102:1312-3. 54. Liesegang TJ. Contact Lens - Related Microbial Keratitis: Part-I:
34. Schein OD, Glynn RJ, Poggio EC, et al. The relative risk of Epidemiology Cornea; 1997; 16: 125-31.
ulcerative keratitis among users of daily-wear and extended-wear 55. Holland GN, Donzis PB. Rapid resolution of early Acanthamoeba
contact lenses. N Engl J Med 1989;321:773-8. keratitis after epithelial debridement. Am J Ophthalmol 1987;104:
35. Poggio EC, Glynn RJ, Schein OD, et al. The incidence of ulcerative 87-8.
keratitis among users of daily-wear ad extended-wear contact lenses. 56. Sharma S, Gopalakrishnan S, Aasuri MK, Garg P, Rao GN. Trends
Am J. Ophthalmol 1989;108:658-64. in contact lens-associated microbial keratitis in Southern India.
36. Bowden FW, Cohen EJ. Corneal ulcerations with contact lenses. Ophthalmology. 2003;110(1):138-43.
Ophthalmol Clin North Am 1989;2:267-73. 57. Koidou-Tsiligianni A, Alfonso E, Forster RK. Ulcerative keratitis
37. Schein OD, Omerod LD, Barraquer E, et al. Microbiology of associated with contact lens wear. Am J Ophthalmol 1989; 108:64-
contact Lens - related keratitis. Cornea 1989;2:267-73. 7.
38. Stern MA. Pseudomonas keratitis and contact lens wear the lens/ 58. Stover CK, Pham XQ, Erwin AL, Mizoguchi SD, Warrener P, et
eye at fault. Cornea 1990; 9 (suppl I) S 36-S 38. al. Complete genome sequence of Pseudomonas aeruginosa PA01, an
39. Jones DB. Acanthamoeba - the ultimate opportunist. Am J opportunistic pathogen. Nature 2000;406:959-64.
Ophthalmol 1986; 2:527-30. 59. Schein OD, Ormerod LD, Barraquer E, et al. Microbiology of
40. Stehr-Green JK, Bailey TM, Visvesvara GS. The epidemiology of
contact lens-related keratitis. Cornea 1989;8:281-5.
Acanthamoeba Keratitis in the United States. Am J Ophthalmol
60. Cheng KH, Leung SL, Hoekman HW, et al. Incidence of contact-
1989;107:331-6.
lens-associated microbial keratitis and its related morbidity. Lancet
41. Samples JR, Binder PS, Luibel FJ, et al. Acanthamoeba keratitis
1999;354:181-5.
possibly acquired from a hot tub. Arch Ophthalmol 1984;
61. Mah-Sadorra JH, Yavuz SG, Najjar DM, Laibson PR, Rapuano
102:707:334-6.
42. Moore MB, McCulley JP. Luckenbach M, et al. Acanthamoeba CJ, Cohen EJ. Trends in contact lens related corneal ulcers. Cornea
keratitis associated with soft contact lenses. Am J Ophthalmol 1985; 2005;24:51-8.
100: 396-403. 62. Rattanatam T, Heng WJ, Rapuano CJ, Laibson PR, Cohen EJ.
43. Cohen EJ, Buchanan HW, Laughnea PA, et al. Diagnosis and Trends in contact lens-related corneal ulcers. Cornea 2001;20:290-
management of Acanthamoeba keratitis, Am J Ophthalmol 1985; 4.
100: 389-95. 63. Szczotka-Flynn LB, Pearlman E, Ghannoum M. Microbial
44. Wilhelmns KR, Osato MS, Font RL. Rapid diagnosis of contamination of contact lenses, lens care solutions, and their
Acanthamoeba keratitis using calcofluor white Atch Ophthalmol accessories: a literature review. Eye Contact Lens 2010;36(2):116-
1986; 101:1309-12. 29.
45. Moore MB, McCulley JP, Newton C, et al. Acanthamoeba keratitis. 64. Cutter GR, Chalmers RL, Roseman M. The clinical presentation
A growing problem in soft and hard contact lens wearers. prevalence and risk factors of local corneal infiltrates in soft contact
Ophthalmology 1987;94:1654-61. lens wearers. CLAO J 1996;22:30-7.
65. Poggio EC, Glynn RJ, Schein OD, et al. The incidence of ulcerative schedule: results of a 3-month prospective study. CLAOJ
keratitis among users of dailywear and extended-wear soft contact 1994;20:225-30.
lenses. N Engl J Med. 1989; 321:779-83. 74. Schein OD, Glynn RJ, Poggio EC, et al. The relative risk of
66. Schein OD, Poggio EC. Ulcerative keratitis in contact lens wearers: ulcerative keratitis among users of dailywear and extended-wear
incidence and risk factors. Cornea. 1990;9(suppl 1):S55-S58. soft contact-lenses-a case control study. N Engl J Med 1989;321:
67. Schein OD, McNally JJ, Katz J, et al. The incidence of microbial 773-8.
keratitis among wearers of a 30- day silicone hydrogel extended- 75. Pisella PJ, Malet F, Lejeune S, et al. Ocular Surface Changes Induced
wear contact lens. Ophthalmology 2005;112:2172-9. by Contact Lens Wear. Cornea 2001;20:820-5.
68. Dart JKG, Stapleton F, Minassian D. Contact lenses and other risk 76. Bialasiewicz AA. [Infection immunology in silicone hydrogel
factors in microbial keratitis. Lancet 1991; 338:650-3.
contact lenses for continuous wear--a review] [Article in German]
69. Schein OD, Buehler PO, Stamler JF, Verdier DD, Katz J. The impact
Klin Monbl Augenheilkd 2003;220(7):453-8.
of overnight wear on the risk of contact lens-associated ulcerative
77. Su DH, Chan TK, Lim L. Infectious keratitis associated with daily
keratitis. Arch Ophthalmol 1994;112:186-90.
70. Dart J. Extended-wear contact lenses, microbial keratitis, and public disposable contact lenses. Eye Contact Lens 2003;29(3):185-6.
health. Lancet 1999;354:174-5. 78. Watt KG, Swarbrick HA. Trends in microbial keratitis associated
71. Driebe WT Jr. Present status of contact lens induced corneal with orthokeratology. Eye Contact Lens 2007;33(6 Pt 2):373-7.
infections. Ophthalmol Clin North Am 2003;16:485-94. 79. Hsiao CH, Yeh LK, Chao AN, Chen YF, Lin KK. Pseudomonas
72. Foulks GN. Prolonging contact lens wear and making contact lens aeruginosa corneal ulcer related to overnight orthokeratology. Chang
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73. Nilsson SE, Montan PG. The annualized incidence of contact lens 80. Wilhelmus KR. Review of clinical experience with microbial
induced keratitis in Sweden and its relation to lens type and wear keratitis associated with contact lenses. CLAO J 1987;13:211.
6.7.7 Atypical Mycobacterial Keratitis

Sujata Das
Mycobacterium, the only genus in the family Mycobacteriaceae, normal flora of human sputum, gastric content and ocular
contains over 50 species including M. tuberculosis and M. leprae. surface.2 They are known to cause a variety of human diseases,
Members of the other species have been termed atypical, including infections of the cornea. In 1965, Turner and Stinson
anonymous, nontuberculous bacilli. Although isolated described the first case of nontuberculous mycobacterial
infrequently from clinical specimens in the past, the relative keratitis in a case of corneal ulcer that developed four months
importance of these other mycobacterial species has after superficial injury with a foreign body.3 M. fortuitum was
progressively increased in recent years. Nontuberculous or identified as the etiological agent. The first case of corneal
atypical mycobacteria are widespread in the environment1 and infection with M. chelonae was reported by Gangadharam and
were once thought to be non-pathogenic. Historically, co-workers.4 The vast majority of ocular infections that result
classification of the nontuberculous mycobacteria has been in clinical disease have been caused by mycobacterial isolates
based on the growth and pigmentation characteristics. Early that are rapid growers, especially M. fortuitum or M. chelonae.
classification schemes divided the species of Mycobacterium Corneal infection with M. avium-intracellulare, M. gordonae and
into four groups based on pigment production, rate of growth, M. marinum have also been reported.5-7
and colony characteristics of the organisms. The four major
groups have generally been referred to as photochromogenic, PATHOGENESIS
scotochromogenic, nonchromogenic, and rapidly growing Predisposing factors are essential in the pathogenesis of
mycobacteria.1 atypical mycobacterial infection. The portal of entry for
Unlike M. tuberculosis and M. leprae, other mycobacterial nontuberculous mycobacteria in disease is not always
species are found free in the natural environment. determined. Nearly all reported cases of nontuberculous
Nontuberculous mycobacteria are aerobic, non-spore forming, mycobacterial keratitis have followed physical trauma, surgery,
non-motile bacilli, environmental saprophytes, widely or contact lens use; a breakdown in natural defenses appear
distributed in soil and water. It has been isolated from the to be an important factor in the pathogenesis of the disease.
Infection results in multiple foci of disease at various levels progresses. The presenting corneal lesion has occasionally been
within the corneal stroma. The presence of organism linear and described as dendritiform with accompanying
stimulates a mixed acute and chronic inflammatory response. epithelial ulceration. Cracked-windshield pattern of corneal
The development of granulomatous inflammation appears to infiltrate is diagnostic of atypical mycobacterial keratitis.21 In
play an important role in protecting cornea against addition to the more typical features, a broad spectrum of
nontuberculous mycobacterial keratitis.8 unusual clinical presentation such as ring stromal infiltrate22,23
and infectious crystalline keratopathy24 has been reported. In
RISK FACTORS post-LASIK infection, infiltrate is either localized or diffuse
involving the flap, interface and/or anterior stroma.
Nontuberculous mycobacteria are ubiquitous and can cause
infection when surgical instruments or clinical devices are
LABORATORY DIAGNOSTIC
exposed to contaminated water, ice or other solutions. These
PROCEDURES
pathogens are resistant to nutritional deprivation, temperature
extremes and chemical disinfectants, such as chlorine, which Ocular infection by nontuberculous mycobacteria may
contribute to their occurrence in keratitis after surgical occasionally be suspected by clinical presentation, but the
procedures. Biofilms in the pipes supplying municipal water
were found to be a frequent site for mycobacteria.
Nontuberculous mycobacteria appear to survive and grow not
only in tap water but also in distilled water.
Environmental exposure to nontuberculous mycobacteria
is the most common route of inoculation, and many patients
have a history of antecedent trauma especially those involving
foreign body.9,10 It also occurs after anterior segment surgery
including radial keratotomy,11 penetrating keratoplasty12-14 and
incisional posterior capsulotomy.15 Contact lens has also been
associated with nontuberculous mycobacterial keratitis.16
Mycobacterium species are recently emerging as leading
pathogens among reported infection after laser in situ
keratomileusis (LASIK).17-19
Fig. 6.7.7.1: Slit lamp picture showing superficial stromal
CLINICAL FEATURES infiltrate with surrounding clear cornea
Clinically, nontuberculous mycobacteria produce relatively slow

progressing keratitis. It may mimic the indolent course of
disease caused by other organisms such as fungi, anaerobic
bacteria, or herpes simplex virus. Clinical infection usually
develop two to eight weeks after the corneal trauma, but
delayed onset keratitis occurring as long as two years after
radial keratotomy has been reported. 20 It is usually
characterized by delayed onset and delayed diagnosis after
LASIK. Pain seems to be a significant presenting symptom
of post-LASIK mycobacterial keratitis.
The typical clinical features include a predisposing corneal
trauma, or surgery, such as penetrating keratoplasty, radial
keratotomy, LASIK, followed by a latent period of few weeks,
and manifesting as stromal infiltrate, which may be single or
multifocal lesions with relative paucity of suppuration Fig. 6.7.7.2: Slit lamp picture showing dense stromal abscess in
(Fig. 6.7.7.1). It may form dense stromal abscess and perforate a case of atypical mycobacterial keratitis due to Mycobacterium
(Fig. 6.7.7.2). Satellite lesion may develop as the disease fortuitum
laboratory investigation is required to confirm the diagnosis. part of the keratectomy specimen should be placed in formalin
A high index of suspicion is required while planning for for histopathological examination with hematoxylin and eosin
laboratory investigation as the routine microbiological work- (H&E) and Ziehl-Neelsen acid-fast stains (Fig. 6.7.7.5), and
up may not include the specific stain and culture media. part can be sent to the microbiological laboratory for culture
An adequate specimen must be sent for specific test, as and for antibiotic sensitivity assays. Following inoculation on
these organisms stain poorly with Giemsa (Fig. 6.7.7.3) and media, growth may take up to seven days for rapidly growing
Gram stain. Ziehl-Neelsen acid-fast stain is more specific for mycobacteria such as M. chelonae and several weeks for slowly
detection of organism. Corneal scrapings are preferred over growing mycobacteria. Antibiotic susceptibility results may take
swabs. Mycobacterium organisms are seen as bright red thin several more days.
rods with the Ziehl-Neelsen acid-fast stain (Fig. 6.7.7.4). The
small acid-fast bacilli may be easily missed if not carefully
looked for, under high magnification (x1000).
Although, the recommended culture media for isolation
of mycobacteria are Lowenstein-Jensen's (LJ) agar or
Middlebrook 7H11, they can grow well on conventional media
such as blood and chocolate agar within three to four days.
Although members of "rapid growers" may grow within seven
days, "slow growers" may take several weeks. While the culture
media are incubated for two weeks in microbial keratitis,25
prolonged incubation of the culture media, especially LJ
medium for four weeks is recommended for cases of suspected
mycobacterial keratitis.23 Cultures may be negative if the
infection is deep in the cornea, and obtaining an appropriate
specimen is difficult. These features may explain the difficulty
in obtaining a fast diagnosis in mycobacterial infections.
Fig. 6.7.7.4: Corneal scraping stained with Ziehl-Neelsen stain using
Corneal specimens for culture can be obtained by superficial 20% H2SO4 shows numerous slender, acid-fast bacilli (pink bacilli
scraping of stromal infiltrates or corneal biopsy. In cases which in blue background) suggestive of Mycobacterium sp.(x1000)
required superficial keratectomy extirpative corneal surgery, (Courtesy: Dr Savitri Sharma)
Fig. 6.7.7.3: Corneal scraping showing numerous slender,

occasionally curved, unstained bacilli along with degenerated
polymorphonuclear cell (Giemsa stain, x1000). The same smear
showed numerous acid-fast bacilli on Ziehl-Neelsen stain suggestive Fig. 6.7.7.5: Corneal button from patient with Mycobacterium sp
of Mycobacterium sp. (Courtesy: Dr Savitri Sharma) keratitis (Ziehl-Neelsen stain) (Courtesy: Dr Geeta K Vemuganti)
TREATMENT Previous studies have cautioned against the use of

corticosteroids in the management of mycobacterial keratitis.
Medical Corticosteroids may prolong and even worsen the course of
Mycobacterial keratitis is more difficult to treat than other the disease. A recent report has demonstrated that patients
types of bacterial keratitis. The length of treatment is typically with mycobacterial keratitis treated with steroids had minimal
prolonged. Nontuberculous mycobacteria are generally inflammatory cellular reaction with a large number of
organisms in histologic sections of their corneas, whereas
resistant to conventional antibiotics, but they do respond
dense inflammatory infiltrates with almost no organisms were
favorably to amikacin. Amikacin (2.5%) made from injectable
seen in specimens from patients not treated with topical
amikacin in artificial tears has been traditionally the drug of
steroids. 28 Corticosteroids should not be used in the
choice in the treatment of nontuberculous mycobacteria for
management of active mycobacterial infections, and may be
many years. Poor penetration of amikacin through an intact
used judiciously even when the infection seems inactive.
epithelium, coupled with a slow growth rate of the
mycobacterium and survival within keratocytes and Surgical
macrophages, is responsible for the resistance of these
Despite aggressive and protracted treatment, the clinical
organisms to treatment. The nontuberculous mycobacteria also
outcome of medical therapy has been unsatisfactory in many
show varying degrees of susceptibility to other drugs, including
cases. Ford et al28 reported that 55 percent of the cases of
the fluoroquinolones, aminoglycosides, tetracyclines,
keratitis due to nontuberculous mycobacteria did not respond
erythromycin, cephalosporins, sulphonamides, neomycin,
to medical therapy alone and ultimately required a surgical
clarithromycin, and vancomycin. Combination therapy with
procedure.
topical amikacin and ciprofloxacin or with amikacin and
Scrapings of the corneal surface (in superficial infiltrates)
clarithromycin has been the main stay of therapy.17,26,27
or lifting the LASIK flap and scraping the stromal bed (in
Clarithromycin, a new macrolide antibiotic, was recently deep infiltrates or when surface cultures are negative) for
found to be the only drug effective against 100 percent of all smears and cultures, irrigation of the stromal bed with an
culture isolates of both M. chelonae and M. fortuitum.28 It has antibiotic solution, or possibly amputation of the flap, should
been reported to penetrate intact epithelium.29 Clarithromycin be immediately performed in patients who have interface
has been shown to have the best minimal inhibitory keratitis.17
concentrations against the isolated Mycobacterium species Lifting of flap and irrigation may allow for better
(0.25-0.50 µg/ml) compared with amikacin and tobramycin penetration of antibiotics, as well as the removal of some of
(4 µg/ml each), ciprofloxacin (8 µg/ml), doxycycline (1-64 µg/ the microorganisms. In cases in which the flap undergoes
ml), and tetracycline (2-64 µg/ml).17 Clarithromycin was shown melting, is densely infiltrated, or when there is no significant
to achieve concentrations greater than minimal inhibitory clinical improvement, amputation of the flap should be
concentration (MIC90) for nontuberculous mycobacteria in attempted without delay. The benefit of removing the LASIK
rabbit corneas after topical application of one to four percent flap and eradicating the infection far outweighs the probable
solutions every two hours.28 Azithromycin is another macrolide scarring of the cornea.17
antibiotic that has been reported to be used in cases of M. In order to reduce or eliminate the number of infectious
chelonae keratitis following LASIK.26 A topical formulation of organisms in the cornea, extirpative keratectomy is required
2 mg/ml of azithromycin was used with topical amikacin, in severe or recalcitrant cases. This also presumably enhances
topical ciprofloxacin, and oral clarithromycin.26 Clarithromycin the antimicrobial drug penetration and improved patient
has been shown to be more effective than azithromycin comfort. If the infection fails to respond to extirpative surgery
in vitro.30 and intensive antimicrobial therapy, a Gundersen conjunctival
Fluroquinolones are the only commercially available topical flap or therapeutic keratoplasty is needed. Penetrating or
antibiotics that have shown to have activity against lamellar corneal transplantation may be an additional mode
mycobacteria. Topical ciprofloxacin has been used as single- of therapy for the very deep infections close to Descemet's
agent therapy against nontuberculous mycobacterial membrane; however, if possible, it is best to delay
keratitis.31,32 Though the fourth generation quinolones are transplantation until the infection is eradicated and the eye is
known to be more effective, a change in sensitivity pattern quiescent. Postoperatively antibiotic should be continued
should be kept in mind.33 initially. Corticosteroid should be used judiciously.
REFERENCES 18. John T, Velotta E. Nontuberculous (atypical) mycobacterial keratitis

after LASIK: Current status and clinical implications. Cornea 2005;
1. Runyon EH. Anonymous mycobacteria in pulmonary disease. Med 24(3): 245-55.
Clin North Am 1959;43(1): 273-90. 19. Fulcher SF, Fader RC, Rosa RH Jr, Holmes GP. Delayed-onset
2. Dugel PU, Holland GN, Brown HH, Petit TH, Hofbauer JD, mycobacterial keratitis after LASIK. Cornea 2002; 21(6): 546-54.
Simons KB, Ullman H, Bath PE, Foos RY. Mycobacterium 20. Matoba AY, Torres J, Wilhelmus KR, Hamill MB, Jones DB.
fortuitum keratitis. Am J Ophthalmology 1988;105(6): 661-9. Bacterial keratitis after radial keratotomy. Ophthalmology 1989;
3. Turner L, Stinston I. Mycobacterium fortuitum; as a cause of 96(8): 1171-5.
corneal ulcer. Am J Ophthalmol 1965;60:329-31.
21. Lazar M, Nemet P, Bracha R, Campus A. Mycobacterium fortuitum
4. Gangadharam PR, Lanier JD, Jones DE. Keratitis due to
keratitis. Am J Ophthalmol 1974; 78(3): 530-32.
Mycobacterium chelonei. Tubercle 1978;59(1):55-60.
22. Richardson P, Crawford GJ, Smith DW, Xanthis CP. Mycobacterium
5. Knapp A, Stern GA, Hood CI. Mycobacterium avium-intracellulare
chelonae keratitis. Aust N Z J Ophthalmol 1989; 17(2): 195-6.
corneal ulcer. Cornea 1987;6(3):175-80.
23. Huang SC, Soong HK, Chang JS, Liang YS. Non-tuberculous
6. Moore MB, Newton C, Kaufman HE. Chronic keratitis caused by
mycobacterial keratitis: A study of 22 cases. Br J Ophthalmol 1996;
Mycobacterium gordonae. Am J Ophthalmol 1986;102(4): 516-
80(11): 962-8.
21.
24. Hu FR. Infectious crystalline keratopathy caused by Mycobacterium
7. Schönherr U, Naumann GO, Lang GK, Bialasiewicz AA.
fortuitum and Pseudomonas aeruginosa. Am J Ophthalmol 1990;
Sclerokeratitis caused by Mycobacterium marinum. Am J
Ophthalmol 1989; 108(5): 607-8. 109(6): 738-9.
8. Paschal JF, Holland GN, Sison RF, Berlin OG, Bruckner DA, Dugel 25. Sharma S, Athmanathan S. Diagnostic procedures in infectious
PU, Foos RY. Mycobacterium fortuitum keratitis. Clinicopathologic keratitis. in Nema HV, Nema N (Eds): Diagnostic procedures in
correlates and corticosteroid effects in an animal model. Cornea ophthalmology. Jaypee Brothers Medical Publishers, New Delhi,
1992; 11(6): 493-9. 2002;232-53.
9. Turner L. Atypical mycobacterial infections in ophthalmology. 26. Chandra NS, Torres MF, Winthrop KL, Bruckner DA, Heidemann
Trans Am Ophthalmol Soc 1970; 68: 667-729. DG, Calvet HM, Yakrus M, Mondino BJ, Holland GN. Cluster of
10. Meisler DM, Friedlaender MH, Okumoto M. Mycobacterium Mycobacterium chelonae keratitis cases following laser in situ
chelonei keratitis. Am J Ophthalmol 1982; 94(3): 398-401. keratomileusis. Am J Ophthalmol 2001; 132(6): 819-30.
11. Robin JB, Beatty RF, Dunn S, Trousdale MD, Riffenburgh R, Rao 27. Gelender H, Carter HL, Bowman B, Beebe WE, Walters GR.
N, Smith RE. Mycobacterium chelonei keratitis after radial Mycobacterium keratitis after laser in situ keratomileusis. J Refract
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12. Aylward GW, Stacey AR, Marsh RJ. Mycobacterium chelonei 28. Ford JG, Huang AJ, Pflugfelder SC, Alfonso EC, Forster RK, Miller
infection of a corneal graft. Br J Ophthalmol 1987; 71(9): 690-93. D. Nontuberculous mycobacterial keratitis in south Florida.
13. Wunsh SE, Byle GL, Leopold IH, Littman ML. Mycobacterium Ophthalmology 1998; 105(9): 1652-8.
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22(3):178-80. Activities of four macrolides, including clarithromycin, against
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16. Bottone EJ, Cho KW. Mycobacterium chelonae keratitis: elucidation chelonae keratitis. Am J Ophthalmol 1993; 115(1): 114-115.
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6.7.8 Chlamydial Infections of the Eye

Gaurav Kumar, M Vanathi
Spectrum of chlamydial infection in the eye is large, ranging membrane protein, and these are best detected by
from trachoma, adult inclusion conjunctivitis and neonatal immunofluorescence using monoclonal antibody. Fifteen
inclusion conjunctivitis. Rarely, the eye is also involved in patients serovars of C. trachomatis have been identified A, B, Ba,
with Chlamydia psittaci and Lymphogranuloma venereum. C - K, L1 - L3.6
Trachoma remains an important cause of blindness due to All Chlamydia have a common reproductive cycle. The
infectious diseases in most parts of the developing world. It is extracellular environmentally stable infectious particle is about
probably the third most common cause of blindness worldwide, 0.3 microns in diameter known as elementary bodies (EB)7
after cataract and glaucoma.1 It has been eliminated from with a electron dense nuclei, which has equal amounts of RNA
developed countries (except Australia), and is hyperendemic in and DNA. Their membrane proteins are highly cross linked.
the underdeveloped regions, primarily Africa, Asia and the The EBs enter the epithelial cells. They appear to bind to host
Middle East.2 Current estimates indicate that there are 8 million cells via heparin bridges. The Chlamydial ligands involved in
people who are blind or have severe visual impairment from heparin binding include major outer membrane protein
trachoma, 7.6 million unoperated trichiasis cases and 84 million (MOMP) and cysteine rich protein Omc B, both of which are
with active trachoma.3 These figures were a significant reduction present on outer membrane complex. It enters through the
from the previous global estimates (1995) of 6 million blind, 10 base of microvilli. Multiple mechanisms appear to be
million trichiasis cases and 146 million with active disease.3 The functional in engulfment procedure, receptor mediated
highest prevalence of trachoma is reported from countries such endocytosis into clathrin coated pits and pinocytosis via
as Ethiopia and Sudan where the prevalence of active trachoma noncoated pits.
in children is often greater than 50 percent and trichiasis is found Lysosomal fusion is inhibited and a membrane bound
in up to 5 percent of adults.4 vacuole is formed. EB's cell membrane loses cross linking and
reorganizes into a larger reticulate body (RB)7 measuring about
STRUCTURE AND 0.5 to 1 microns in size. RB contains 4 times as much RNA as
DEVELOPMENTAL CYCLE DNA, it grows in size and divides repeatedly by binary fission.
After a certain period, reticulate body differentiate back again
Chlamydiae can be considered as gram negative bacteria that
to EB, membrane late proteins are synthesized in this period,
lack mechanisms for the production of metabolic energy and
including chlamydial outer membrane protein complex Omc
cannot synthesize ATP. For survival, they require intracellular
B, Omc A, two histones H1 like proteins Hc1 and Hc2. After
environment which is energy rich intermediates, making
24 - 48 hours entire vacuoles become fluid filled with infectious
chlamydiae, obligate intracellular parasites. Their outer cell wall
elementary bodies. The developmental cycle is complete by
resembles gram negative bacteria and contains tetrapeptide
release of these infectious EBs.8 In vitro, the chlamydial
linked matrix. Lysozyme has no effect on cell wall. Penicillin
development cycle takes between 36 and 70 hours to complete.
binding proteins occur in the chlamydial cell wall. It acts by
inhibiting transpeptidation of bacterial peptidoglycans. N-
PATHOLOGY
acetylmuramic acid appears to be absent in chlamydial cell
walls. As RNA, DNA and prokaryotic ribosomes are present Trachoma is caused by repeated infection with Chlamydiae
in chlamydiae, they are able to synthesize nucleic acid and trachomatis A, B, Ba, C. Chlamydiae have evolved several
cellular protein. mechanisms to evade the host immune response. Its
Chlamydia that infects human are divided on the basis of intracellular location protects it from antibody and they do
antigenic composition, intracellular inclusion, sulfonamide not fuse with lysosomes. Chlamydiae down regulate MHC
susceptibility and disease production into three species: C. Class1 molecules, which save it from cytotoxic T cells.
trachomatis, C. pneumoniae and C. psittac.5 Chlamydia possess Histopathological changes can be seen in the palpebral
genus specific antigens, that are heat stable 2-keto 3- conjunctiva, tarsal plate, meibomian glands and orbicularis
deoxycytonic acid as an immunodominant component. Species oculi muscle fibres. The pathological hallmark of active
specific and serovar specific antigens are mainly the outer trachoma is lymphoid follicles that have a germinal centre and
a parafollicular region dominated by lymphocytes. Diffuse inflammatory thickening of the conjunctiva. The key sign of
inflammatory exudate is also present, which consists of T cells, active trachoma is characteristic tarsal follicle 0.5 - 2.0 mm in
B cells, plasma cells, dendritic cells, macrophages and diameter, and is slightly raised. In early infections phases, there
polymorphonuclear leucocytes. Children with active infection could be epithelial keratitis and anterior stromal infiltrates with
have upregulated cytokines interleukin 1 , interleukin 12p40, corneal neovascularization (vascular pannus). Pannus is more
inteleukin 10, interferon and matrix metalloproteinase 9 (MMP common in upper limbus. A unique characteristic of trachoma
9).9 Upper tarsal conjunctiva show hyperemia and follicular is lymphoid follicles at limbus, which after resolution leaves a
reaction. Ocular bacterial infections play an important role in depression called Herbert's pit. Uncommonly bacteriologically
pathogenesis and spread of disease. sterile pannus ulcer can also occur, which are shallow, oval
Trachomatous cicatrization of eyelid tissues occurs as a epithelial defects parallel to the limbus, beyond the tip of pannus.
result of the submucosal inflammation leading to fibroblasts With time trachomatous scarring begins. Initially it appears
hyperproliferation and new tissue formation. Subepithelial as small stellate scars, which later form a dense basket wave
avascular and fibrous membrane appears clinically as a white pattern. A thick band of scar tissue appears in upper lid near
firm scar. The intimate relationship of subepithelial, contractile lid margin called Arlt's line Scarring leads to eyelid thickening
fibrous membrane to the posterior, slightly concave surface at the mucocutaneous junction, conjunctivalization,
of tarsus and the arrangement of its vertically oriented collagen meibomian gland atrophy, goblet cell deficiency and dry eye.
fibres in parallel layers, can cause buckling of the atrophic Trichiasis and entropion in the presence of dry eye leads to
tarsal plate or posterior displacement of mucocutaneous recurrent corneal erosions, ulceration, scarring and
junction which leads to entropion and trichiasis. 10 opacification of cornea (Figs 6.7.8.1A and B).
Histopathological section shows secondary amyloidosis and
LABORATORY DIAGNOSIS
destruction of accessory lacrimal glands and ducts, goblet cells
and meibomian glands. These changes result in dry eye and Microscopy: This is the oldest and most widely used method for
further ocular surface change. chlamydial detection. Conjunctival scraping stained with
Giemsa stain show mature inclusion bodies which appear as
CLINICAL FEATURES dark purple masses — Halberstaedter and Prowazek body in
There are two different phases of the disease: the cytoplasm of epithelial cells. Acridine orange and iodine
a. One which occurs during childhood due to active are alternative stains. Common sources of misdiagnosis of
Chlamydial infection and cytoplasmic inclusion bodies include pigment granules, keratin,
b. The second is the late cicatricial phase, occurring as the nuclear extrusions, goblet cells, eosinophilic granules and other
sequelae of repeated infection. bacteria. Microscopy requires trained technicians, is time-
In children, acute chlamydial infection presents as follicular consuming, and is probably the least sensitive method for
conjunctivitis with diffuse infiltration and papillary diagnosis.11
hypertrophy. In very young children follicles are not formed Cell Culture: This is the gold standard in identifying the agent.
and the presentation is with papillar y reaction and Efficient isolation, transport and early plating is required. For
Figs 6.7.8.1A and B: Conjunctival scarring (A), trichiasis and entropion (B), in healed trachoma
transport, enriched sucrose phosphate transport medium is infection is chronic and due to this, large percentage of the
used with strict cool chain maintenance. It is inoculated on population may have a high titer in endemic areas.
McCoy cells or He La cells. This specimen is centrifuged into Polymerase chain reaction: This is highly sensitive method. It
monolayer to aid cellular infection. Determining culture amplifies DNA from very little amount of sample. Assays
positivity, requires Giemsa staining for identification of based on PCR are part of the group of nucleic acid
inclusion bodies. Culture takes around 3 to 6 days. amplification tests. This detects the plasmid common to all
Direct fluorescent antibody: This process is used to detect specific Chlamydia as target gene.
molecules on cells. The reagent labeled with fluorescent dye PCR is ideally suited to the detection of DNA of fastidious
binds to specific protein, which is visible on fluorescent and noncultivatable infectious agents because it does not rely
microscope. A direct fluorescent antibody test, Syva Microtrack on the presence of viable organisms in the sample. The first
(Syva, PaloAlto, California) uses labeled antibody to detect bacterium for which a PCR-based detection method was
species specific epitope in MOMP. One advantage of this published was C. trachomatis.
technique is that the specimen could be transported to A number of different nucleic acid sequences have been
laboratory at ambient temperature. Usually 5 to 10 elementary used as targets in PCRs for the detection of C. trachomatis.
bodies, is taken as threshold for positive result, but has been These include the chlamydial cryptic plasmid (pCT), omp1,
found to be varied with different studies. coding for MOMP, the gene coding for 16S rRNA, and omp2,
Enzyme immunoassay: This detects antigen and antibodies by coding for OmcB. With the exception of pCT, all of these
producing enzyme triggered color change. Samples are taken targets are sequences found on the C. trachomatis chromosome,
by conjunctival swab. It is then put in detection buffer and is which includes two complete rRNA operons and single copies
placed on solid phase support (such as microtitre plate well), of omp1 and omp2. PCR directed at plasmid genes or omp1
to which antibodies that bind chlamydial antigens are attached. is thought to be both sensitive and specific for the diagnosis
This antigen antibody complex are detected by applying an of C. trachomatis infection. Mahoney et al12 estimated that
enzyme linked second antibody to it. A colorless substrate plasmid-based PCRs are between 10 and 10,000 times more
converts into coloured substance after detection with the sensitive than PCRs directed against C. trachomatis chromo-
enzyme added. So, antigen antibody linked with enzyme is somal genes. This is probably at least partly attributable to the
detected as color change. presence of multiple copies of the plasmid per chlamydial
Enzyme immunoassay detects chlamydial liposaccharide cell. This does not correlate well with clinical severity. It is
as antigen, which shares epitopes with a number of other used mostly in hypoendemic area.
species (Staph aureus, H. aegyptus, klebsiella species). So conjunctival Lab diagnosis Specificity Sensitivity
infection with any of the organism will cause false positive Cell culture 100% 65 - 85%
result. Direct immunofluorescence 81 - 99% 80 - 99%
ELISA 97 - 98% 85 - 97%
Nucleic acid probe: This method uses nucleic acid hybridization PCR 95 - 100% 88 -100%
to detect chlamydiae. The Gen-probe Pace 2 system (San
Diego) was approved by FDA for assessing endocervical, male GRADING AND CLASSIFICATION
urethral and conjunctival specimen. Trachoma is a common disease, many grading system came
The specimen collected with Dacron swabs can be stored to standardize the diagnosis and grade the disease for field
at 2 to 25°C for upto 7 days. A chemical luminescent - labeled survey and to describe the disease problem. The first was the
single stranded DNA probe that is complimentary to MacCallan’s stages of trachoma13, and other important ones
chlamydial ribosome is used. The sample is heated so that include, the modified WHO system or FPC system by Dawson
cells are lysed and rRNA is released. The labeled DNA combine in 198114 and the WHO simplified system in 1987.15
with the organisms RNA, forming a heat stable DNA RNA
hybrid. The presence of a luminescent DNA RNA hybrid is MacCallan Classification
measured in luminometer. The whole procedure takes 2 to 3 The original MacCallan’s classification, based on A F
hours. The sensitivity and specificity are high. The results may MacCallan’s extensive study of the disease in Egypt, where
be affected by excess mucus and blood. this disease has been endemic since ancient times, divided the
Serology: Detection of antibody is mostly done by complement clinical presentations of trachoma into 4 stages. In addition
fixation. Micro IF test is also used in serum, tears and other to the 2 subdivisions of Stage II, there were two more sub-
fluids of secretory surfaces. It is not very helpful as Chlamydia divisions incorporating the added complications of spring
catarrh and gonococcal conjunctivitis to the acute follicular P3 - for pronounced papillae, conjunctiva thickened and
reaction, characteristic of trachoma. 13 opaque, normal vessels on the tarsus are hidden over
This classification has clinical relevance even today and is more than half of the surface.
summarized below: Conjunctival scarring (C) is graded as:
Stage I (Incipient trachoma): Small conjunctival folllicles and diffuse C0 - for no scarring on the conjunctiva;
infiltration give the conjunctiva a velvety appearance. There is C1 - mild, fine, scattered scars on the upper tarsal con-
no conjunctival discharge or scarring. junctiva or scars on the other parts of the conjunctiva;
C2 - moderate, more severe scarring but without shortening
Stage II (Established trachoma): The conjunctiva becomes or distortion of the upper tarsus and
thickened and roughened but without scaring and a progressive C3 - severe scarring with distortion of the upper tarsus.
pannus may be seen. Two sub-stages are grossly seen:
A. Follicle predominant: Larger follicles are the predominant Trichiasis/entropion (T/E) is scored as:
sign T/E0 - no trichiasis or entropion,
B. Papillary predominant: Diffuse papillary infiltration T/E1 - lashes deviated towards the eye but not touching
predominates, obscuring the follicles. the globe
T/E2 - lashes touching the globe but not rubbing on the
Stage III (Cicatrising trachoma): Follicles are present with varying cornea, and
degrees of conjunctival cicatrisation. T/E3 - lashes constantly rubbing on the cornea.
Stage IV (Healed trachoma): The disease is completely arrested Corneal scarring (CC) is scored as:
with conjunctival scars and no follicles are present. This stage CC0 - no scarring,
is non-contagious. CC1 - minimal scarring or opacity not involving the visual
axis and with clear central cornea,
WHO Classification CC2 - for moderate scarring or opacity involving the visual
axis, with the pupillary margin visible through the
In the modified WHO system,14 active infection is more opacity, and
precisely defined. Zones are defined by two imaginary lines CC3 - for severe central scarring or opacity, with the
on the everted tarsal surface, approximately parallel with the pupillary margin not visible through the opacity.
upper tarsal border and curve upward towards their lateral
(Reproduced from the classification of trachoma, with the permission of the World
extremities. (Zone 1 includes the entire upper tarsal border Health Organization, from Guide to Trachoma control in programmes for the
and adjacent lateral tarsal surface; zone 2 occupies the area prevention of blindness, Dawson CR, Jones BR, Tarizzo ML (Au), WHO
between zones 1 and 3 and extends to the lateral quarters of Publication, 1981, copyright notice March 2011.)
the lid margin; zone 3 includes the tarsal conjunctiva adjacent The WHO simplified system15 was designed to simplify
to the central half of the lid margin and, at its center, covers the previous system.
just less than half the vertical extent of the tarsal surface). The WHO simplified system uses the following
The upper tarsal follicles (F) are graded as: criteria:
F0 - no follicles, • TF (Trachomatous inflammation, follicular): The presence
F1 - follicles present but not more than five in zones 2 and of five or more follicles in the upper tarsal conjunctiva.
3 together, These follicles must be at least 0.5 mm in diameter in the
F2 - follicles more than five in zones 2 and 3 together but central part.
less than five in zone 3, and • TI (Trachomatous inflammation, intense): Pronounced
F3 - five or more follicles in each of the three zones. inflammatory thickening of the upper tarsal conjunctiva
that obscures more than half of the normal deep tarsal
Upper tarsal papillary hypertrophy and diffuse infiltration (P) vessels
are graded as: • TS (Trachomatous conjunctival scarring): The presence
P0 - absent papillae, normal appearance; of scarring in the tarsal conjunctiva
P1 - for minimal, individual vascular tufts (papillae), • TT (Trachomatous trichiasis): At least one eyelash rubs
prominent, but deep subconjunctival vessels on the on the eyeball. Evidence of recent removal of in-turned
tarsus not obscured; eyelashes should also be graded as trichiasis.
P2 - for moderate, more prominent papillae and normal • CO (Corneal opacity): Easily visible corneal opacity over
vessels appear hazy even when seen by the naked eye; the pupil. The opacity is dense enough to obscure, at least,
and part of the pupil margin when viewed through the opacity.
The presence of follicular or intense trachomatous Antibiotic: Antibiotic used for prophylaxis and treatment is
inflammation represents active disease. Azithromycin 20 mg/kg, maximum 1gm single oral dose or 1
(Reproduced from the classification of trachoma, with the permission of the World percent tetracycline eye ointment twice daily for six weeks.
Health Organization from A simple system for the assessment of trachoma and WHO recommends mass community treatment.
its complications, Thylefors B, Dawson CR, Jones BR, West SK, Taylor HR et
WHO recommendation for antibiotic treatment for
al, Bull World Health Organ. 1987; 65(4): 477–83, copyright notice March
trachoma:
2011.)
• Determine the district-level prevalence of TF in 1 to 9-
TREATMENT year-old children
– If prevalence is 10 percent or more, mass treatment
Medical management: Main aim in trachoma management is to with antibiotic throughout the district
decrease sequelae of chlamydiae infection. The primary – If prevalence is less than 10 percent, assessment at the
prevention strategies are very important in achieving this goal. community level in areas of known disease
In active infection, topical 1 percent tetracycline ointment • In assessment at the community level:
twice daily for 6 weeks or a single oral dose of azithromycin – In communities in which the prevalence of TF in
20 mg/kg is advocated. Azithromycin as a macrolide class of 1 to 9 year-old children is 10 percent or more - mass
antimicrobial, acts on the 50S ribosomal subunit of chlamydiae. treatment with antibiotic
It is a well tolerated and safe drug for mass treatment. – In communities in which the prevalence of TF in
Azithromycin as compared with tetracycline ointment, was 1 to 9 year-old children is 5 percent or more, but less
found to be equally effective and had 20 percent less fever than 10 percent - targeted treatment should be
and headache episodes and 40 percent less diarrhea and considered
vomiting episodes.16 For older children with severe intensity – In communities in which the prevalence of TF in
disease, oral erythromycin, tetracycline or doxycycline given one to nine year-old children is less than five percent
twice daily can be used. Azithromycin is not used in pregnancy - antibiotic distribution is not recommended
and in children < 6 months of age. The duration for which treatment is to given, is not clearly
defined. A mathematical model antibiotic treatment for
Surgical management: Surgery in trachoma patients is done to trachoma control suggests that for hyperendemic regions
correct the inturning of lashes. Bilamellar tarsal rotation has (>50%), mass antibiotic treatment may be required twice a
been found to be the best surgery in all randomized control year and for regions with moderate prevalence (<35%), annual
trails. One of the common indication for keratoplasty is treatment is possibly sufficient.19
trachomatous corneal opacity in developing countries. There The current WHO recommendation advises three annual
is high rate of failure of surgery because of poor ocular surface rounds of mass treatment to be given initially. After this, the
and corneal vascularization due to repeated infection. community should then be re-assessed to see whether the
prevalence of active disease has dropped sufficiently to
SAFE strategy: The alliance for the global elimination of
discontinue treatment.
trachoma by 2020 (GET 2020) has adopted the safe strategy
as the main action against trachoma. Facial Cleanliness: It is one of the SAFE strategy. By washing
S - Tertiary prevention - Surgery away potentially infectious ocular secretion, the transmission
A - Secondary prevention - Antibiotic of C. trachomatis to others can be interrupted.
F - Primary prevention - Facial cleanliness
E - Primordial prevention - Environmental improvement Environment Changes: Eye seeking flies are common in
endemic countries, and the fly most commonly found in
Surgery: The aim of trachoma is to limit damage from inturning contact with eyes is Musek Sorbens, which preferably breeds
of lashes. WHO recommends the bilateral tarsal rotation on human feces. Lack of proper toilets, has been associated
procedure17 for anyone with trichisis, regardless of number with increased risk of trachoma. Recommended
and position of eyelashes touching the globe. Failure of environmental sanitary intervention undertaken to reduce
surgery, is the main problem as this is a ongoing process and trachoma include provision of water latrines, refuse dumps,
after one year, failure rates, have been reported to be between spray to control flies, animal pens away from human
5 to 40 percent.18 Azithromycin used at the time of surgery households and health education to improve personal and
improved outcome. environmental hygiene.
CHLAMYDIA PSITTACI subepithelial opacities similar those of epidemic

keratoconjunctivitis. The clinical course may last 3 to 12
The natural host of Chlamydia psittaci are birds and mammals.
months. In acute phase, patient typically present with redness,
It spreads when person inhales the organism present in dried
mucopurulent discharge and matting of lashes. Later, the
feces or respiratory secretions of infected birds. Pneumonia
follicles become less prominent. In more advanced cases,
is most frequent presentation also called bird's fancier lung.
corneal vascularization, keratitis and conjunctival scarring may
Ocular involvement is rare, and presents as subacute follicular
occur. Laboratory evaluation of the conjunctival smear stained
conjunctivitis. The follicles are present in both upper and lower
with Giemsa Stain and culture with McCoy cells can be done.
palpebral conjunctiva, as well as bulbar conjunctiva. Subepithelial
PCR can be used for this purpose but gold standard is culture.
keratitis and pannus is also reported. Lymphnodes may also be
enlarged. To diagnose the case as psittacosis, the history of Treatment: AIC should be looked as systemic disease with ocular
exposure to birds or mammals is required. involvement, thus systemic therapy is required. The
A patient is said to have confirmed case if compatible recommended regimen is a three week course of oral tetracycline,
symptoms are present and laboratory confirmation is by one 250 mg or 500 mg 4 times a day. The single dose of Azithromycin
of the three methods: can also be used. Topical therapy is used as supportive therapy.
a. C. psittaci cultured from respiratory secretions; Sexual partners should be treated simultaneously.
b. Antibody against C. psittaci is increased four fold or greater
by complement fixation (CF) or microimmunofluorescence NEONATAL INCLUSION CONJUNCTIVITIS
(MIF).
Chlamydiae is common cause of ophthalmia neonatorum
c. Immunoglobin M is detected against C. psittaci by MIF.
(Table 6.7.8.1) . Neonatal inclusion conjunctivitis (NIC) usually
A probable case of psittaci is defined as either:
appears 5 to 19 days after birth, but earlier infection can occur
i. Clinically compatible illness that is epidemiologically
when placental membrane ruptures before delivery. It is
linked to a confirmed case, or
acquired during passage from birth in the vaginal delivery, it is
ii. An antibody titre of at least 32 by CF or MIF in at
very uncommon in cesarean section.
least one serum specimen after the onset of symptoms.
Chlamydia accounts for 40 percent of cases of ophthalmia
PCR is also used in diagnosis.
neonatorum. Other causes include Neisseria gonorrhoea, other
It is treated with oral tetracycline for prolonged period,
bacterial infections, HSV and chemical toxins. Neisseria is the
optimum duration is still not known.
most important cause of its sight threatening sequelae.
NIC is caused by the D-K serovars. Intrapartum
ADULT INCLUSION CONJUNCTIVITIS
chlamydiae is known to cause pneumonia, otitis media as well
This is caused by D-K serotypes of Chlamydiae trachomatis. These as infections of the nasopharynx, rectum or vagina.21 An
serotypes usually cause urogenital infections. Adult inclusion infected mother may transmit infection to the child in
conjunctivitis (AIC) is the ocular manifestation of chlamydial 50 to 75 percent of cases, with the chances of NIC being 30
urogenital infection. AIC is uncommon, occurs in about 0.3 to 50 percent in infected cases. 22 Neonatal chlamydial
to 2 percent of patients with urogenital disease.20 As compared conjunctivitis is characterized by a bilateral swelling of the
to trachoma, AIC is more common in developed countries. It lids, hyperemia and infiltration of conjunctiva and purulent
spreads via direct inoculation, infectious discharges to the eye discharge. Follicular conjunctivitis does not occur, keratitis has
by fingers, fomites or orogenital sexual practices. Once it was been reported in some cases.
a common cause of 'swimming pool conjunctivitis', which
occurred mostly due to inadequately chlorinated swimming
Table 6.7.8.1: Neonatal conjunctivitis
pools.
Infection occurs 5 to 14 days after inoculation and presents Etiology Time of onset discharge
as acute follicular conjunctivitis with preauricular Chemical 1- 48 hours Mucopurulent
lymphadenopathy on the side of the involved eye. It starts Neisseria gonorrhoeae 1 - 2 days Purulent
unilaterally but bilateral involvement usually develops. As Bacterial
compared to adenoviral conjunctivitis it has a more chronic (Staphylococcus,
course if left untreated and follicles are more common in lower Streptococcus, Hemophilus) 2 - 5 days Mucopurulent
palpebral conjunctiva and fornix. Corneal involvement includes Viral 3 - 15 days Mucoid
epithelial keratitis, marginal and central infiltrates and Chlamydial 5 - 14 days Mucopurulent
Timing of infection after birth helps in diagnosis. trachoma group of organisms in the genus Chlamydia Jones, Rake
Microbiological data is essential to rule out other causes. and Stearns, 1945. Int. J. Syst. Bacteriol 1966;16:223-52.
6. Caldwell HD, J Schachter. Antigenic analysis of the major outer
Gram stain, swabs and culture are to be done. Neisseria
membrane protein of Chlamydia spp. Infect. Immun 1982;35:1024-
gonorrhoea infection is to be looked for. Culture is the gold 31.
standard but PCR is commonly used widely in recent times. 7. Ward ME. The immunobiology and immunopathology of
Prophylaxis is best to avoid this problem. Previously silver chlamydial infections. APMIS 1995;103:769-96.
nitrate was used, but in recent times, erythromycin and 8. Jawetz E, MelnickJL, Adelberg EA (Eds). Medical Microbiology.
tetracycline is used for this purpose as silver nitrate causes 22nd Edition. McGraw Hill.
9. Burton MJ, Bailey RL, Jeffries D, Mabey DC, Holland MJ. Cytokine
redness. When diagnosis is confirmed it should treated with and fibrogenic gene expression in the conjunctivas of subjects
systemic drugs as there are high chances of pneumonia. from a Gambian community where trachoma is endemic. Infect
Current recommendation is oral erythromycin 50 mg/kg/day Immun 2004;72:7352-6.
in four divided doses for 10 to 14 days.23 Amoxicillin 500 mg 10. Lewallen S, Courtright P. Anatomical factors influencing
orally thrice daily for seven days can be used if there is any development of trichiasis and entropion in Trachoma. Br. J
Ophthalmol 1991;75:713-4.
intolerance to erythromycin.
11. Schachter JJ, Moncada CR, Dawson J, Sheppard P, Courtright ME,
Said S, Zaki SF, Hafez, A Lorincz. Nonculture methods for
OCULAR LYMPHOGRANULOMA diagnosing chlamydial infection in patients with trachoma: a clue
VENEREUM (LGV) to the pathogenesis of the disease? J. Infect. Dis. 1988;158:1347-
52.
LGV is a sexually transmitted disease. It caused by serovars 12. Mahony JB, KE Luinstra, JW Sellors, MA Chernesky. Comparison
L1-3. It rarely affects eye. It accounts for 2 to 10 percent of of plasmid- and chromosome-based polymerase chain reaction
genital ulcers. It infects macrophages compared to other assays for detecting Chlamydia trachomatis nucleic acids. J. Clin.
serovars which infect squamocolumnar cells. Microbiol 1993;31:1753-8.
In eye, it manifests as Parinaud's oculoglandular syndrome. 13. MacCallan AF. The epidemiology of trachoma. Br. J. Ophthalmol
1931;15:369-411.
It is characterized by massive infiltration of conjunctiva,
14. Dawson CR, Jones BR, Tarizzo ML. Guide to trachoma control in
papillary hyperplasia without follicles. Keratitis can occur. programs for the prevention of blindness. World Health Orga-
Massive, tender posterior cer vical and preauricular nization, Geneva, Switzerland 1981.
lymphadenopathy. 15. Thylefors B, Dawson CR, Jones BR, West SK, Taylor HR. A simple
The diagnosis of LGV is based on clinical grounds which system for the assessment of trachoma and its complications. Bull.
are confirmed by organism culture and cell typing. Lymph W.H.O. 1987;65:477-83.
16. Bailey RL, Arullendran P, Whittle HC, et al. Randomised controlled
node is the best source for specimen. Culture, is positive in trial of single- dose azithromycin in treatment of trachoma. Lancet
one third of the cases. Other diagnostic tests used are serology, 1993;342:453-6.
immunofluorescence and PCR. Along with clinical 17. Reacher M, Foster A, Huber J. Trichiasis surgery for trachoma: the
presentation, a complement fixation antibody titer of greater bilamellar tarsal rotation procedure (WHO/PBL/93.29). Geneva:
than 1:64 is diagnostic of LGV.24 World Health Organisation, 1993. http://whqlibdoc.who.int/hq/
1993/ WHO_PBL_93.29.pdf (accessed Oct 19, 2007)
Treatment choices include doxycycline (100 mg) twice daily
18. Bog H, Yorston D, Foster A. Results of community-based eyelid
for three weeks erythromycin 500 mg 4 times/day for three surgery for trichiasis due to trachoma. Br J Ophthalmol 1993; 77:
weeks azithromycin 1 gm every week 3 weeks. 81-83.
19. Lietman T, Porco T, Dawson C, et al. Global elimination of
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[see comments]. Nat Med 1999;5:572-6.
1. Resnikoff S, Pascolini D, Etya'ale D, et al. Global data on visual 20. Stenberg K, Maardh PA. Genital infection with Chlamydial
impairment in the year 2002. Bull World Health Organ 2004;82:844- trachomatis in patients with chlamydial conjunctivitis: Unexpected
51. results, Sex Transm Dis 1991;18:1-4.
2. Polack S, Brooker S, Kuper H, et al. Mapping the global distribution 21. Workowski KA, Levine WC. Sexually transmitted diseases treatment
of trachoma. Bull World Health Organ 2005;83:913-9. guidelines 2002, Morbidity Mortality Weekly report 51:RR6, 2002.
3. Thylefors B, Negrel AD, Pararajasegaram R, et al. Global data on 22. Hammerschlag M. Chlamydial trachomatis in children. Paediatr Am
blindness. Bull World Health Organ 1995;73:115-21. 1994;23:349-53.
4. Berhane Y, Worku A, Bejiga A. National Survey on Blindness, Low 23. Bunti DM, Rosen T, Lesher JL, et al. Sexually transmitted diseases:
Vision and Trachoma in Ethiopia. Federal Ministry of Health of bacterial infections, J Am Acad Dermatol 1999;25:287-99.
Ethiopia, 2006. 24. Joseph AK, Rosen T. Laboratory techniques used in the diagnosis
5. Page LA. Revision of the family Chlamydiaceae rake (Rickettsia- of chancroid, granuloma inguinale and lymphogranuloma
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Chapter 6.8
DISEASES OF THE OCULAR SURFACE
6.8.1 Diseases of the Conjunctiva

M Vanathi
ANATOMY epithelium of the conjunctiva located behind the row

The conjunctiva is the transparent vascularized mucous of the Meibomian gland openings.
membrane covering the anterior surface of the eyeball and ii. The tarsal conjunctiva is the lining of the tarsus and is
posterior surface of the eyelids, serving to secrete mucus which firmly adherent to it.
forms an important part of the tear film and defensive iii. The orbital conjunctiva is that portion extending from
functions. It contains immunocompetent cells that are involved the tarsal conjunctiva to the fornix.
in (i) synthesizing immunoglobulins and (ii) initializing and The forniceal conjunctiva is that part extending between
mediating immune reactions.1 the palpebral and the bulbar conjunctiva. Salient features of
this include: The superior fornix which is the deepest, located
Gross Anatomy 8 to 10 mm behind the limbus and is situated at the level of
The conjunctiva is primarily composed of 3 sections: the orbital rim; The inferior fornix is 8 mm from the limbus
i. Palpebral conjunctiva that covers the posterior surface while the lateral fornix is 14 mm from the limbus; Medially is
of the eyelids; present the caruncle and the plica semilunaris (which is the
ii. Bulbar conjunctiva coats the anterior portion of the rudimentary third lid).
eyeball; and The bulbar conjunctiva consists of two parts:
iii. Conjunctival cul-de-sac or the fornix, which is the • The scleral part extending from the conjunctival fornix to
transition portion, forming the junction between the the limbus is readily separable from the underlying Tenon's
posterior eyelid and the eyeball. capsule with which it is loosely attached by the
The palpebral conjunctiva is moderately thick and mobile subconjunctival tissue. The conjunctiva, sclera and the
while the bulbar conjunctiva is very thin. Within the bulbar Tenon's capsule are firmly adherent 3 mm from the limbus.
conjunctiva are goblet cells, which secrete mucin which is an • The limbal part comprises a ring 3 mm wide at the junction
important component of the pre-corneal tear layer that of the conjunctival and corneal epithelium.
protects and nourishes the cornea. The palpebral sebaceous glands (Meibomian and Zeiss)
The palpebral conjunctiva consists1 of: secrete the superficial lipid layer of the tear film.
i. The mucocutaneous junction which is the transition The conjunctival glands are involved in the tear secretion
between the keratinizing stratified squamous epithelium (Fig. 6.8.1.1). There are two groups of accessory lacrimal glands
of the lids and nonkeratinizing stratified squamous (serous and mucous) depending on the type of secretion.
• The epithlelium at the eyelid margin which is the transition

between the epidermis (keratinizing stratified squamous
epithelium) and nonkeratinizing stratified squamous
epithelium with flattened superficial cells.
• The tarsal and bulbar conjunctival epithelium is a stratified
squamous epithelium with more or less cylindrical
superficial cells with the morphology resembling the
forniceal conjunctival epithelium.
• The forniceal conjunctiva consists of cylindrical superficial
epithelial cells.
• The limbal conjunctival epithelium is the transition zone
between the conjunctival and corneal epithelia and is
comprised of stratified epithelium with flattened superficial
epithelial cells.
Limbal epithelial stem cells (SC) are located at the limbal
basal layer, along which several other cell types are found to
Fig. 6.8.1.1: Conjunctival glands occur (Fig. 6.8.1.2). These include the early transient amplifying
cells (eTAC), melanocytes (M), and Langerhans’ cells (LC).2
Serous Glands The eTAC are said to be destined for progeny production by
differentiating into late TACs (lTAC) located at the corneal
• The Krause's glands located in the deep conjunctival tissue
basal layer, then into suprabasal post-mitotic cells (PMC), and
of the superior fornix and numbers about 40 in the
finally into superficial terminally differentiated cells (TDC).
superior fornix and 8 in the inferior fornix. These are
The limbal basement membrane (BM) that separates the
similar to the orbital lacrimal gland tissue
histopathologically. epithelium from the underlying stroma has several unique
• The Wolfring's glands number about two to five situated components. The subjacent limbal stroma contains
along the upper edge of the tarsus in the upper lid and mesenchymal cells (MC), which may also serve as niche cells.
about two along the lower edge of the inferior tarsus. Because the limbal stroma is highly innervated and
vascularized, the respective role of nerves (N) and blood
Mucous Glands vessels (BV) in the niche remains to be defined.
Mucus is secreted by the goblet cells of the conjunctival Diseases of the conjunctiva are discussed under the
epithelium and by other glandular structures such as the following headings:
Henle's glands (in the upper edge of the superior tarsus and (A) Autoimmune fibrosing conjunctivitis
are composed of goblet cells).
(B) Non-autoimmune fibrosing conjunctivitis
(C) Allergic conjunctivitis
Histology of the Conjunctiva
(D) Infections of the conjunctiva
The conjunctival epithelium comprises a single layer of basal (E) Other diseases of the conjunctiva.
cells, variable layers of intermediate cells and superficial cells
with variable shapes. Also seen in the epithelial layers are (A) AUTOIMMUNE FIBROSING
melanocytes (in the basal layer) and immunocompetent cells CONJUNCTIVITIS
(esp the Langerhans’ cells). Neutrophils and lymphocytes are
usually present only in the conjunctival epithelium and The major conditions causing autoimmune cicatrizing
substantia propria, whereas both mast cells and plasma cells conjunctivitis include:
are present in the substantia propria but not the epithelium. i. Conjunctivitis associated with autoimmune bullous
Basophils and eosinophils are not usually found in either tissue. dermatoses
The conjunctival epithelium consists of between two and ii. Ocular cicatricial pemphigoid (OCP)
8 to 10 layers of cells according to the location. The four iii. Presumed drug induced OCP
distinct morphological components include:1 iv. Pemphigoid.
Diseases of the Ocular Surface 565
Fig. 6.8.1.2: Diagrammatic representation of the limbal stem cell niche
Autoimmune fibrosing conjunctivitis3-5 has been known (e.g. face, neck, scalp) occurs in approximately 25 percent of
by different names such as ocular pemphigus, essential patients with OCP.
shrinkage of the conjunctiva, benign mucous membrane The main cause of autoimmune fibrosing conjunctivitis is
pemphigoid, and at present is commonly referred to as ocular cicatricial pemphigoid, with the mean age at diagnosis being
cicatricial pemphigoid (OCP).3 The differentiation and the 6th decade of life, though pediatric cases have also been
classification of autoimmune bullous cutaneous pemphigoid known to occur.3 Female predominance is noted in patients
is a well recognized entity. Pemphigus is characterized by diagnosed with OCP with the female-to-male ratio estimated
intradermal bullae secondary to acantholysis while pemphigoid to be 1.5:1 to 3:1.11
is characterized by subepidermal blisters with the cleavage Other autoimmune bullous conditions include
occurring at the dermal-epidermal zone within the basement epidermolysis bullosa acquisita, dermatitis herpetiformis,
membrane junction.3 Autoimmune fibrosing conjunctivitis can which can affect younger patients.
occur in isolation or in association with other mucocutaneous
autoimmune conditions. Pathogenesis
Ocular cicatricial pemphigoid (OCP) is considered as one
of the subsets of mucous membrane pemphigoid (MMP). Coexistence with autoimmune conditions, detection of
MMP is a group of systemic autoimmune diseases circulation of autoimmune antibodies to the basement
characterized by T-lymphocyte dysregulation, with production membrane zone or the intracellular substance of conjunctival
of circulating autoantibodies directed against a variety of epithelium, presence of immune deposits in the conjunctiva,
adhesion molecules in the hemidesmosome-epithelial response to immunomodulatory drugs point to the
membrane complex, and the production of proinflammatory autoimmune mechanisms that underlie the pathogenesis of
cytokines and immune system activation markers. OCP can this condition. 3,7-11 The immune mechanism underlying
cause skin and other mucous membrane lesions (oral mucosa, autoimmune conjunctivitis is type II antibody mediated
pharynx, larynx, trachea, esophagus, vagina, urethra, anus), in cytotoxicity. Conjunctival inflammatory infiltrate is usually
addition to its characteristic involvement of the conjunctiva mononuclear and nonspecific with an increased level of all
causing chronic cicatrizing conjunctivitis. inflammatory mediators been observed in the conjunctival
The incidence of autoimmune conjunctivitis is not clear.3-6 epithelium and chorion of cases of autoimmune fibrosing
Incidence is estimated between 1 in 8,000 and 1 in 46,000 conjunctivitis. In cicatrizing pemphigoid, the fibrosing
ophthalmic patients.3-11 It is likely that early stages of OCP conjunctivitis is characterized by relentless progression of
are not reflected in these estimates because of difficulties in cicatrization in the absence of treatment and at times even
making the correct diagnosis depicting that the true frequency with control of inflammation. The pathogenesis of this
of the disease is probably higher. Oral lesions occur in 75 to progressive fibrosis is considered to be multifactorial and is
100 percent of patients with OCP. Skin involvement still unclear.3 Detection of circulating autoantibodies is rare
in ocular cicatricial pemphigoid and epidermolysis bullosa but trichiasis, distichiasis, and keratinization cause corneal
common in bullous pemphigoid.3 Target antigens identified epitheliopathy, persistent corneal epithelial defects, stromal
in autoimmune conjunctivitis have been found to be ulcers, corneal scarring, neovascularization, and even
represented by epitopes of numerous molecules composing perforation.
the junction complex between epithelium and chorion in Multiple antigens in the BMZ of squamous epithelia serve
subepithelial autoimmune conditions and desmosome epitopes as targets for a spectrum of autoantibodies observed in OCP.
in intraepithelial autoimmune conditions. 3 An altered Molecular definition of these autoantigens facilitates the
immunoregulation, with production of autoantibodies directed classification and characterization of subsets of OCP.11 Sera
against the beta 4 subunit of alpha 6 beta 4 integrin, and, from patients with OCP have been shown to recognize beta 4
reportedly, in some instances, against alpha 3, beta 3, or gamma integrin, which is a 205-kDa protein, also known as CD104.
2 subunits of laminin 5 has been described.11 A subset of patients with clinical features similar to OCP also
A genetic predisposition has also been found with a has been shown to have autoantibodies against epiligrin, which
significant association with DQw7 gene (DQb1*0301) with is identified as laminin 5, a ligand for alpha 6 beta 4 integrin,
cicatricial pemphigoid.3 HLA-DR4 antigen has also been found and autoantibodies to the alpha 6 integrin subunit.
to be associated with OCP.3 HLA-DR2 has been found to be OCP probably forms a spectrum of several different
associated with epidermolysis acquisita and with dark diseases associated with different target antigens, different
pigmented patients.3 triggers, and different therapeutic responses.
In some patients, systemic practolol therapy and topical
antiglaucoma drugs, such as pilocarpine, timolol, epinephrine, Clinical Presentation
humorsol, idoxuridine, and phospholine iodide, have also
Cicatrizing conjunctivitis is commonly a bilateral condition
reported to trigger the onset of OCP. The ter m
characterized by ocular irritation symptoms such as foreign
pseudopemphigoid or drug-induced pemphigoid has been
body sensation, burning sensation, itching, photophobia,
used for these cases. It is however unclear if these cases,
lacrimation, pain, mucus discharge and conjunctival hyperemia.
associated with medication use are identical to OCP.
The symptoms of the patients may not be in accordance to
Elucidating the molecular level changes,11 the initial trigger
the severity. The evidence of subconjunctival fibrosis is seen
is thought to be a process by which the OCP antigen undergoes
initially in the inferior and superior tarsal conjunctiva.
a conformational change that provides antigenic stimulation.
Perivascular white lines are the initial clinical presentations
This signal leads to B-cell clones generation that produce
which are then seen to progress to fornix foreshortening with
antibodies against antigens situated at the basement membrane
zone (BMZ), initiating a type II Gell and Coombs symblepharon and ankyloblepharon in advanced cases.
hypersensitivity reaction. The antibodies, immunoglobulin G Destruction of goblet cells, obliteration of the lacrimal
(IgG), immunoglobulin A (IgA), and/or immunoglobulin M gland orifices as a result of the ongoing fibrosis process results
(IgM) bind to the antigen and initiate complement activation. in dry eye syndrome. Cicatricial entropion and trichiatic lashes
Circulating autoantibodies are difficult to demonstrate by secondary to the conjunctival fibrosis also occurs. Corneal
classic indirect immunofluorescence technique in patients with morbidity such as (punctate keratitis, epithelial defects,
OCP. Specialized radioimmunoassay and immunoblot ulcerations, microbial infections, perforation, stromal scarring,
techniques allow the circulating autoantibodies to be seen in xerosis) occurs as a result of the dry eye sequelae, cicatricial
all patients with OCP who have active conjunctivitis.11 entropion and trichiatic lashes, leading to vision loss. Other
The inflammatory mediators that are produced induce commonly associated co-morbidity conditions include chronic
migration of lymphocytes, eosinophils, neutrophils, and mast glaucoma in these cases. Conjunctival hyperemia secondary
cells to the BMZ. The separation of the epithelium from the to inflammatory mediators such as cytokines (tumor necrosis
underlying tissues within the BMZ is due to the direct cytotoxic factors, interleukins) and histamine serves a good marker
action or the effect of lysosomal proteolytic enzymes. for the ongoing inflammatory activity. The conjunctival
Fibroblast activation secondary to inflammatory cytokine hyperemia may be graded from 0 to 4 depending on the
influences, with collagen production and subsequent severity in the quadrants to help in assessment and
cicatrization, is the end result in the conjunctiva. Progressive treatment.12 Blisters on the ocular surface are rarely seen, as
fibrosis causes profound tear insufficiency, meibomian gland the commonly observed lesions are usually the postbullous
dysfunction, and mucin deficiency. Symblepharon formation, corneal erosions.3
Staging of OCP Definitive diagnosis of OCP is made by demonstration

12,13 of linear deposition of immunoreactants (e.g. IgG, IgA,
The staging of OCP has been elaborated as follows:
complement component C3 or C4) at the BMZ of biopsy
Stage I—Conjunctival subepithelial fibrosis.
specimen of inflamed conjunctiva using immunofluorescent
Stage II—Conjunctival fibrosis along with lower fornix
or immunoperoxidase technique. Experienced laboratory
foreshortening.
technicians are required to process conjunctival tissue to obtain
II A: 0–25%
II B: 25–50% the highest possible diagnostic yield and sensitivity. A negative
II C: 50–75% or inconclusive biopsy result can occur due to poor biopsy
II D: 75–100% technique or poor handling of the specimen.
Stage III—Conjunctival fibrosis along with fornix Histopathology: Hematoxylin and eosin staining show the
foreshortening and symblepharon formation conjunctival infiltration with neutrophils, macrophages, and
(percentage of lower lid affected) Langerhans’ cells. Goblet cells may be decreased or absent in
III A: 0–25% patients with advanced OCP. Patients with active OCP have
III B: 25–50% excess mucus production and strands of mucus like material
III C: 50–75% in the inferior fornix.
III D: 75–100% Scanning and transmission electron microscopy study
(The number of symblephara observed at the lower fornix demonstrates presence of mucus on the surface of the
is recorded in Arabic numerals) conjunctiva, even though goblet cells are not seen. Giemsa
Stage IV—Conjunctival fibrosis with ankyloblepharon. stain results show that the total mast cell number and ratio of
Stage I is characterized by chronic conjunctivitis with mild connective tissue mast cells to mucosal mast cells are
conjunctival and/or corneal epitheliopathy with subepithelial
significantly higher than in normal conjunctiva.
conjunctiva fibrosis, best seen at the tarsal conjunctiva as fine,
The deposition of IgG, IgA, C4, or C3 is highlighted by
white striae. Stage II is characterized by cicatrization with
fluorescein or rhodamine-labeled antibodies, which are directed
conjunctival shrinkage, distorted anatomy, and foreshortening
against immunoglobulins and complement components. The
of fornices. Stage III is characterized by the presence of
diagnostic sensitivity of immunofluorescence alone is
symblepharon. Subepithelial scarring alters the orientation of
approximately 50 to 52 percent. Immunoperoxidase technique
lashes, causing aberrant lash growth. In addition, cicatricial
is required when immunofluorescence study findings are
entropion may occur. Stage IV is the end stage, consisting of
negative, but the clinical presentation strongly suggests OCP.
a dry eye with keratinization of the cornea and
The immunoperoxidase technique is approximately 1,000 times
ankyloblepharon, which immobilizes the globe. Profound
more sensitive than immunofluorescence. 11 Immuno-
keratopathy can develop secondary to eyelid disorders, tear
peroxidase can detect deposition of immunoreactants at the
insufficiency, and corneal exposure. Corneal epitheliopathy,
BMZ in smaller amounts. The diagnostic sensitivity of
persistent epithelial defects, stromal ulceration, and
immunoperoxidase is 83 percent, an increase of 31 percent
neovascularization may be present. The cornea may become
compared to immunofluorescence technique.11
completely scarred, vascularized, and keratinized.
Investigations Treatment
Diagnosis of OCP is based on clinical presentation and Medical Management
immunohistochemical studies of the conjunctiva, which can No topical agent is effective in stopping the progressive
reveal pathognomonic features of the disease. fibrosing OCP activity. Subconjunctival steroid injections or
Conjunctival biopsy of the bulbar conjunctiva, preferably subconjunctival injections of mitomycin C have been
in an inflamed region close to the limbus may be taken. Biopsy attempted temporarily for slowing disease progression, while
of the forniceal conjunctiva is avoided as it may precipitate fornix systemic therapy takes effect.
foreshortening. The sample is subdivided to be sent for: Adjuvant treatment with topical lubricants to allay dry eye
i. Histological examination symptoms is useful. The use of topical cyclosporine and
ii. Immunofluorescence and immunoenzymatic studies tacrolimus ointment has also been described to aid in the
iii. Immunoelectron microscopy. control of surface inflammation.
Control of OCP requires the use of long-term use of Methotrexate: This has a chemical structure analogous to that
systemic immunomodulators. Current guidelines for using of folic acid and prevents conversion of dihydrofolate to
chemotherapy in treating OCP are as follows:11 tetrahydrofolate by competitive and irreversible binding to
• For mild-to-moderate inflammation: Diaminodiphenyl- enzyme dihydrofolate reductase. Tetrahydrofolate is an
sulfone (Dapsone) is a first-line agent, provided the patient essential cofactor in production of 1-carbon units critical to
is not glucose-6-phosphate dehydrogenase deficient. synthesis of purine nucleotides and thymidylate. Partially
Methotrexate may also be considered first-line therapy. reversible competitive inhibition of thymidylate synthetase
When therapeutic response is unsatisfactory, or use of occurs within 24 hours after methotrexate administration,
dapsone is contraindicated, or if the patient cannot tolerate resulting in inhibition of DNA synthesis, DNA repair, RNA
the drug, mycophenolate mofetil or azathioprine can be synthesis, and cell division at specific stages of the cell cycle.
substituted. If inflammation persists, cyclophosphamide By inhibiting DNA synthesis in immunologically
can be used sequentially. competent cells, methotrexate acts as an immunosuppressive
• For severe inflammation: Cyclophosphamide initially, and agent. Both B and T cells are affected, and primary and
systemic prednisone added with rapid taper for a limited secondary antibody responses can be suppressed when
period of time (3 months). administered during antigen encounter. Dosage: Adult—2.5
• Patients with active conjunctival inflammation refractory to 7.5 mg/week PO/IV/IM single dose or divided, increased
to chemotherapy or patients who do not tolerate the gradually according to clinical response (not to exceed 25 mg/
spectrum of immunosuppressive drugs can be treated with week, pediatric dose—5 to 15 mg/m2/week PO/IM single
intravenous immunoglobulin or a combination of dose or 3 divided doses with 12 hours interval).
intravenous immunoglobulin and rituximab infusions. Azathioprine: The prodrug metabolized in liver to active
The goal of pharmacotherapy is to reduce morbidity form, 6-MP, which interferes with purine metabolism and
and to prevent complications. Combination therapy in a ultimately with DNA, RNA, and protein synthesis. It
stepladder regimen is needed in many cases to improve disease suppresses both B and T lymphocytes and is effective in
control.11-15 suppressing mixed lymphocyte reaction in vivo and
Some of the commonly used immunosuppressants are recirculating T lymphocytes that are in the process of homing.
elaborated here. It can also suppress development of monocyte precursors and
Dapsone: Recommended as first-line agent for treatment of thus participation of K cells (derived from monocyte
OCP if inflammatory activity is not severe, disease is not precursors) in antibody-dependent cytotoxicity reactions.
rapidly progressive, and patient is not glucose-6-phosphate Dosage is to be reduced by 25 percent if allopurinol is
dehydrogenase deficient. A response usually is observed within administered concomitantly, as allopurinol interferes with
4 weeks of initiation of therapy. Dapsone has both metabolism of 6-MP. Dosage is 2–3 mg/kg PO qd or divided
antimicrobial and anti-inflammatory activity. Mechanisms by doses in adults (pediatric dose of 2 to 5 mg/kg/d; maintenance
which it influences inflammatory and immune systems are not dose—1 to 2 mg/kg/d).
clear. It is believed to mediate anti-inflammatory effects in Cyclophosphamide: This belongs to nitrogen mustard
cicatricial pemphigoid by a variety of mechanisms. Evidence family of alkylating agents. The prodrug is converted in vivo
suggests that dapsone stabilizes lysosomal membranes, by hepatic microsomal cytochrome P-450 mixed function
decreasing release of contents, and interferes with oxidase system into its active metabolites, phosphoramide
myeloperoxidase halide-mediated cytotoxic system of mustard and 4-hydroxy-cyclophosphamide. These act
neutrophils, may inhibit Arthus reaction and adjuvant-induced through nucleophilic substitution reactions resulting in
arthritis in a manner similar to that of corticosteroids and formation of covalent cross linkages (alkylation) with DNA,
indomethacin. It is given as 25 mg orally for 1 week initially in thereby mediating their major immunosuppressive activity.
adults. May be increased to 50 mg bid with dose adjustments Both B- and T-cell function are depressed. It is advisable to
based on clinical response and drug tolerance (not to exceed take total daily dose in morning and maintain adequate oral
150 mg/day). A slow taper to maintenance level once fluids throughout rest of day, in an effort to induce frequent
inflammatory process is under control is advisable. (Pediatric voiding, and thereby risk of hemorrhagic cystitis from
dosage: 1 mg/kg divided twice daily, and not to exceed 100 prolonged contact of bladder mucosa with
mg/d). cyclophosphamide metabolites is minimized.
Intravenous administration of cyclophosphamide offers recommended in adults is 5 mg/kg as single IV infusion at

certain advantages over oral administration and is useful as it: week 0 and week 2, and then q4week thereafter (may increase
• Permits rapid induction in patients with severe ocular dose up to 10 mg/kg).
inflammatory involvement. Etanercept (recombinant human TNF-alpha receptor
• Avoids prolonged bladder exposure, allowing larger doses, protein fused with Fc portion of IgG1 that binds to TNF-
and frequent dosing in patients with hemorrhagic cystitis alpha, thereby neutralizing the effects of TNF-alpha),
induced from oral intake. monoclonal antibodies—daclizumab (humanized monoclonal
• Induces only transient neutropenia, making intercurrent antibody that specifically binds to and blocks interleukin-2
infections less likely. (IL-2) receptor on surface of activated T cells), rituximab
Dosage:1-2 mg/kg/d PO/IV in adults with infusions repeated (genetically engineered chimeric murine/human monoclonal
q3-4 weekly, depending on clinical response and leukocyte antibody directed against the CD20 antigen found on the
count. surface of B lymphocytes), IV Immune globulin (pooled
immunoglobulin G (IgG) immunoglobulins from the plasma
Mycophenolate mofetil: This has been shown to be useful
of approximately a thousand or more blood donors, acts by
in moderate OCP. It is well tolerated. Dosage: 500 mg/d PO
modulation of complement activation; suppression of
initially, increasing up to 1000 mg PO bid over 2 months
idiotypic antibodies; saturation of Fc receptors on
(pediatric: 600 mg/m2 PO bid; to a maximum of 1000 mg
macrophages; and suppression of various inflammatory
PO bid over 2 months).
mediators, including cytokines, chemokines, and
Systemic steroids: Though systemic corticosteroids can metalloproteinases) are some of the other newer reported
control the activity of the disease, they are not as effective as therapy administered for OCP.
other immunosuppressive drugs. The doses of systemic steroid
required have been shown to be very toxic with tapering of Surgical Management
systemic steroids always being associated with recurrence of
Ocular surgical procedures are to be performed when the
disease activity, suggesting the requirement of high doses for
inflammation is completely under control, and systemic
extended periods of time. Corticosteroids are not to be used
corticosteroids should be used perioperatively, when the
as a sole agent. Their use is reserved for severely inflamed
procedure involves the conjunctiva or the cornea. Once the
eyes that do not readily respond to immunosuppression alone.
inflammation is suppressed, such procedures as marginal
When administered, corticosteroids should be used for a
rotation of the eyelid, mucous membrane grafting, retractor
limited period of time, preferably not more than 3 months.
plication, fornix reconstruction, or cataract extraction can be
Prednisone acts as an immunosuppressant that decreases
performed without significant danger of excessive
inflammation by reversing increased capillary permeability and
postoperative inflammation and cicatrization.
suppressing PMN activity. Dosage: 1 mg/kg/d PO
administered during the first week of therapy and tapered every Epilation: Aberrant lash growth that produces damage to
week by 10 mg and therapy is discontinued within 8 to 12 the ocular surface is common in OCP. Epilation of the
weeks. trichiatic lashes and destruction of the follicles helps preventing
further irritation of the ocular surface and removes factors
Sulfasalazine: Sulfonamide derivative with anti-inflammatory
that mimic immunologically driven conjunctival inflammation.
properties decreases inflammatory response and systemically
Mechanical epilation has a temporary effect, and the lashes
inhibits prostaglandin synthesis. Dosage of 0.5–1 g/d PO with
that regrow are more harmful than the original lashes. Gas
increase weekly to maintenance dose of 2 g/d PO divided bid.
permeable scleral contact lenses can be used to protect the
It may be increased to 3 g/d if response is not satisfactory, after
ocular surface from injury by aberrant lashes.
12 weeks of treatment (not to exceed 4 g/d).
In case of trichiasis or distichiasis, permanent destruction
Immunomodulators interfere with cytokine actions
of the lash follicles is ideal.
responsible for inflammation.
Punctual occlusion along with preservative free ocular
Infliximab: This is a chimeric IgG1k monoclonal antibody lubricants, topical mild steroids and topical cyclosporine is
that neutralizes cytokine TNF-alpha and inhibits its binding helpful. Meibomian gland dysfunction is to be treated with
to TNF-alpha receptor. It reduces infiltration of inflammatory warm compresses and lid massages with eyelid hygiene, with
cells and TNF-alpha production in inflamed areas. Dosage or without systemic tetracycline therapy.
Lid surgery: Entropion surgery is avoided in patients with Complications

OCP because of the interference with the conjunctiva.11
Ocular complications of OCP include the following:
Recently, several cases of lower lid entropion have been treated
• Corneal epithelial defects
successfully with a retractor plication technique. The procedure
• Corneal stromal ulcers
is repeatable in case of undercorrection, with the conjunctiva
• Corneal perforation
remaining intact during the surgery, which can avoid the
• Endophthalmitis
exacerbation of conjunctival inflammation. • Glaucoma.
Tarsorrhaphy can be used in case of lagophthalmos,
corneal hypoesthesia, or corneal epithelial defects. Systemic Complications
Fornix reconstruction with amniotic membrane
transplantation or autologous oral mucosa can be used to Two types of lesions can occur. The most common lesion is a
reconstruct the conjunctival fornices in patients with OCP. vesiculobullous er uption, similar to that of bullous
Ocular surface reconstruction procedures such as mucous pemphigoid, which rupture spontaneously and heal without
membrane grafting reconstructs the anatomy of fornices and significant scarring. The second type of lesion is an
provides nonkeratinizing epithelium with goblet cells supplying erythematous localized plaque that evolves into recurring
mucous production to the ocular surface. These are not to be bullae, which can rupture and leave scars (i.e. Brunsting-Perry
performed in patients with severe keratoconjunctivitis sicca, dermatitis). Patients with OCP may present with skin lesions
advanced OCP, or active conjunctival inflammation. The long- and lesions on other mucous membranes (e.g. nose, mouth,
term beneficial effect of this procedure is seen in approximately esophagus, pharynx, larynx, urethra, vagina, anus). Oral
one-third of the patients only. involvement is the most common. Scarring of mucosa in the
nose and the mouth can be debilitating. Nasopharyngeal
Corneal surgery: Corneal procedures providing a satisfactory involvement can manifest as ruptured vesicles of the nasal
long-term visual outcome in OCP patients is very limited. As mucosa along with discharge, crusting, and epistaxis. Patients
corneal transplantation on a dry eye with impaired lid function with tracheolaryngeal lesions may present with hoarseness,
and limbal stem cell deficiency has a very poor prognosis, dyspnea, and laryngeal stenosis. Aphonia can occur secondary
corneal grafting in patients with advanced OCP should be to vocal cord involvement. Laryngeal stenosis and tracheal
avoided. This procedure should only be performed in case of scarring with mucous accumulation may lead to fatal
corneal perforation. asphyxiation. Progressive desquamative gingivitis results in
In patients with advanced corneal damage from OCP, bone loss and dental extraction. Pharyngeal scarring can cause
keratoprosthesis may be the only feasible alternative for visual painful swallowing with subsequent malnutrition and weight
rehabilitation. Necrosis of the tissue surrounding the loss. Patients suspected of having OCP must be examined for
prosthesis is the major problem limiting the long-term the presence of dysphagia and difficulties in breathing. Pain
outcomes. This process can lead to aqueous leak, retinal on defecation or rectal bleeding can manifest as a result of
detachment, infection, and extrusion of the prosthesis. Recent rectal involvement. Esophageal involvement is typically silent,
advances in keratoprosthesis along with lifelong use of topical though progressive scarring associated with esophageal
antibiotics have improved the outcome. inflammation results in esophageal strictures, which may
Cataract surgery: The need for cataract surgery is common produce dysphagia, and sometimes choking with attempted
in patients with OCP. Cataract surgery performed on patients swallowing of food leading to death from asphyxiation.
with OCP is followed by increased conjunctival inflammation,
Conclusion
rapid progression of keratopathy, and conjunctival scarring,
if the disease is not medically controlled. Poor outcome of Multidisciplinary approach is required seeking consultations
cataract surgery is associated with chemotherapy intolerance, with an appropriate specialist in case of skin involvement or
and presence of any preoperative conjunctival inflammation. involvement of other mucous membranes. Patients who have
Use of perioperative systemic steroids is necessary in patients difficulty swallowing or breathing require an immediate
who are on systemic immunosuppressive therapy and in those endoscopic examination looking for esophageal webs, as these
patients whose inflammation is currently in remission without patients are at risk of asphyxiation. Patients receiving
taking any immunosuppressive agents. chemotherapy may require regular consultations with a
chemotherapist. Patients may also require referral to an ear, 5. The conjunctiva. In: Cornea: Fundamentals, Diagnosis and
nose, and throat specialist for laryngoscopy in case of recent Management. Krachmer, Mannis, Holland. Vol I. 2nd Edition
Elsevier Mosby 2005, pg 557-719.
onset of hoarseness, which may be caused by laryngeal stenosis 6. Ciurtin C, Cojocaru VM, Arama S, Stoica V. Epidemiology of
and tracheal scarring. These patients are in a medical emergency ocular involvement in autoimmune diseases. Rom J Intern Med
because of the risk of mucous accumulation and subsequent 2008;46(3):243-7.
fatal asphyxiation. 7. Demers PE, Robin H, Prost C, Toutblanc M, Hoang-Xuan T.
As relapses are common in approximately one-third of Immunohistopathologic testing in patients suspected of ocular
cicatricial pemphigoid. Curr Eye Res 1998;17(8):823-7.
the cases, lifelong follow-up care is mandatory. Patients who 8. Bernauer W, Broadway DC, Wright P. Chronic progressive
relapse commonly regain disease control readily on institution conjunctival cicatrisation. Eye (Lond) 1993;7(Pt 3):371-8.
of therapy and do not deteriorate to more advanced 9. Rashid S, Dana MR. Cicatrizing and autoimmune diseases. Chem
cicatrization. Immunol Allergy 2007;92:195-202.
10. Eschle-Meniconi ME, Ahmad SR, Foster CS. Mucous membrane
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11. Foster CS, Sainz De La Maza M. Ocular cicatricial pemphigoid
1. Kantelop B, Creuzot Gorcher. Anatomy in inflammatory diseases review. Curr Opin Allergy Clin Immunol 2004;4(5):435-9.
of the conjunctiva. T Hoang-Xuan, C Baudouin, and C Creuzot- 12. Tauber J, de la Maza, Maite S, Foster CS. Systemic chemotherapy
Garcher. New York: Georg Thieme Verlag 2001;3-6. for ocular cicatricial pemphigoid. Cornea 1991;10(3):185-95.
2. Wei Li, Y Hayashida, Ying-Ting C, SCG Tseng. Cell Research 13. Foster CS. Cicatricial pemphigoid. Trans Am Ophthalmol Soc
2007;17;26-39. 1986;84:527-663.
3. H Robin, T Hoang-Xuan. Fibrosing conjunctivitis in inflammatory 14. Sami N, Letko E, Androudi S, et al. Intravenous immunoglobulin
diseases of the conjunctiva. T Hoang-Xuan, C Baudouin, and C therapy in patients with ocular-cicatricial pemphigoid: a long-term
Creuzot-Garcher. New York: Georg Thieme Verlag 2001;73-86. follow-up. Ophthalmology 2004;111(7):1380-2.
4. Smolin and Thoft’s The cornea. Smolin G, Foster CS, Azar DT, 15. Saw VP, Dart JK, Rauz S, et al. Immunosuppressive therapy for
Dohlman CH. 4th Edition. Lippincott Williams and Wilkins ocular mucous membrane pemphigoid strategies and outcomes.
2005,305-347. Ophthalmology 2008;115(2):253-261.e1.
(B) NONAUTOIMMUNE FIBROSING and widespread small blisters that arise on erythematous or
CONJUNCTIVITIS purpuric maculae that are different from classic targets of
The major cause of non-autoimmune cicatrizing conjunctivitis, erythema multiforme. However, Stevens-Johnson syndrome
Stevens-Johnson syndrome is discussed here in detail. and toxic epidermal necrolysis (TEN) are thought to be severity
variants of the same disease, which differ from erythema
Stevens-Johnson Syndrome multiforme.4 Stevens-Johnson syndrome and toxic epidermal
necrolysis are characterized by identical clinical signs and
Erythema multiforme major/Stevens-Johnson syndrome/
symptoms, identical treatment approach, and identical
Toxic epidermal necrolysis is a complex immunological
prognosis. Patients with 90 percent skin detachment and
syndrome characterized by acute blistering of the skin and at
diagnosed with toxic epidermal necrolysis, may have none or
least two mucous membranes. In 1860, Ferdinand von Hebra1
first described erythema multiforme (EM) as a self-limited only mild ocular involvement with excellent prognosis while
cutaneous disease characterized by multiform skin lesions. with 10 percent skin detachment may have severe ocular
Stevens-Johnson syndrome came into recognition following involvement with blinding consequences.5
the description of reporting of an extraordinary, generalized There seems to be a female predominance in the
eruption with continued fever, inflamed buccal mucosa, and occurrence of SJS with the patients affected being in the age
severe purulent conjunctivitis by Stevens and Johnson in range from 10 to 30 years.6
1922.2,3 Erythema multiforme or Stevens-Johnson syndrome Causes of conjunctival cicatrization are not limited to
as it is more commonly known, is divided into two categories: autoimmune diseases, such as ocular cicatricial pemphigoid, a
erythema major multiforme and erythema multiforme minor. severe disease associated with poor ocular prognosis. Other
Erythema multiforme describes typical target lesions of raised well-known causes include thermal and chemical burns,
edematous papules, with or without mucosal involvement. It postinfectious conjunctivitis, and Stevens-Johnson syndrome.7
has been proposed to restrict the terminology of Stevens- Ocular rosacea and atopic keratoconjunctivitis are also
Johnson syndrome to characterize mucous membrane erosions described as under diagnosed causes of conjunctival fibrosis.7
Though several classifications have been reported, the Drug induced: Drugs causing SJS include:5
simplest one can be as follows:8 • Antibiotics: Penicillins, sulfa antibiotics, fluoroquinolones.
Stevens-Johnson syndrome—A minor form of Toxic • Anticonvulsants: Phenytoin, carbamazepine, valproic acid,
epidermal necrolysis (TEN) with less than 10 percent body barbiturates. (Most anticonvulsant-induced SJS commonly
surface area (BSA) detachment. occurs within the first 60 days of use).9
Overlapping Stevens-Johnson syndrome/toxic epidermal • NSAIDs: Cyclooxygenase-2 (COX-2) inhibitors.
necrolysis (SJS/TEN)—Detachment of 10 to 30 percent BSA. • Anti-gout medication: Allopurinol.
Toxic epidermal necrolysis—Detachment of more than • Antidepressants.
30 percent BSA. • TNF-alpha antagonists such as infliximab, etanercept, and
adalimumab.
Causes
Malignancy related: Various carcinomas and lymphomas
Various etiologic factors such as infection, vaccination, drugs, have been reported with the occurrence of SJS.
systemic diseases, physical agents, food, etc. have been
implicated as causes of Stevens-Johnson syndrome. 5,8-10 Idiopathic: Stevens-Johnson syndrome (SJS) is idiopathic in
Whites with human leukocyte antigen (HLA)-Bw44 appear to 25 to 50 percent of cases.
be more susceptible to develop Stevens-Johnson syndrome.10
Japanese study quotes that individuals with the HLA-A*0206 Immunopathogenesis
allele are prone to develop Stevens-Johnson syndrome-related The pathophysiology of acute SJS involves an idiosyncratic,
ocular complications.10 Certain HLA alleles are said to be delayed hypersensitivity reaction. Certain groups of patients
associated with an increased probability of developing Stevens- appear more susceptible to develop Stevens-Johnson syndrome
Johnson syndrome upon exposure to specific drugs (patients than the general population. The slow acetylators, patients
with HLA-A29, HLA-B12, and HLA-DR7 have been who are immunocompromised, and patients with brain
associated with sulfonamide-induced Stevens-Johnson malignancy on radiotherapy with concomitant antiepileptics
syndrome while HLA-A2 and HLA-B12 has been more are thought to be at an increased risk.10 The slow acetylators
frequently seen in Stevens-Johnson syndrome-induced by are incapable of achieving complete detoxification of reactive
NSAIDs, and HLA-B*5801 allele was found to be associated drug metabolites. Such metabolites can act as haptens that
with Stevens-Johnson syndrome incited by allopurinol).10 interact with host tissues rendering them to be antigenic.13,14
Studies on HLA class II molecules in patients with ocular Antigen presentation and production of tumor necrosis
manifestations secondary to Stevens-Johnson syndrome factor alpha (TNF-alpha) by the local tissue dendrocytes
revealed that the HLA-DQB1*0601 allele was strongly culminates in recruitment and augmentation of T-lymphocytes’
associated with Stevens-Johnson syndrome with ocular proliferation and enhances the cytotoxicity of the other
disease.11,12 immune effector cells.15 The activated CD8+ lymphocytes
The four main etiologic categories described include: induce epidermal cell apoptosis through various mechanisms
• Infectious (such as release of granzyme B and perforin). Apoptosis of
• Drug-induced the keratinocytes occurs as a result of ligation of their surface
• Malignancy-related death receptors with the appropriate molecules. This triggers
• Idiopathic. the activation of the caspase system leading to DNA
Infectious: Viral diseases reported to be linked to the etiology disorganization and cell death.16
of SJS include herpes simplex virus (HSV), AIDS, Coxsackie Activated T-cells can release soluble Fas ligand and
viral infections, influenza, hepatitis, mumps, interferon-gamma, which induces Fas expression by the
Lymphogranuloma venereum (LGV), rickettsial infections, and keratinocytes.8 Once apoptosis ensues, the dying cells further
variola. Bacterial etiologies include group A beta hemolytic produce more chemokines resulting in the inflammatory
Streptococci, Diphtheria, Br ucellosis, Mycobacteria, process, causing extensive epidermal necrolysis.
Mycoplasma pneumoniae, tularemia, and typhoid. 5 It is to be noted that the ocular findings in chronic SJS are
Coccidioidomycosis, dermatophytosis, and histoplasmosis are secondary to severe keratoconjunctivitis sicca occurring as a
the fungal etiologies while malaria and trichomoniasis have result of the initial damage incurred. Hence prompt optimal
been reported as protozoal causes.5 In children, Epstein-Barr management of SJS at the onset, will result in better prognosis
virus and enteroviruses have been identified. and lesser ocular morbidity.17
Clinical Presentation Table 6.8.1.1: Classification and grading of ocular involvement
Acute presentation of ocular SJS includes corneal epithelial Corneal complications Score 0 Score 1 Score 2 Score 3
defect with neovascularization and surface conjunctivalization. Superficial – Sparse Patchy Coalescent
punctate <1/3 1/3–2/3 >2/3
Patient presents with red eye, tearing, pain, photophobia keratopathy
blepharospasm, severe grittiness and foreign body sensation, Epithelial defect – <1/4 1/4–1/2 >1/2
decreased vision, lid edema and burning sensation. Other Loss of palisades – <1/2 of >1/2 of Total loss
systemic lesions involving the skin, mucosal lesions (involving of Vogt circum-
ference
circum-
ference
the mouth, esophagus, pharynx, larynx, anal region, trachea, Conjunctivalization – <1/4 1/4–1/2 >1/2
vagina and urethra) may also be present.18 Corneal – Confined Extending Extending
Severe eye involvement in chronic ocular Stevens-Johnson neovascularization to peri- upto into central
phery pupillary cornea
syndrome presents with corneal neovascularization and margin
conjunctivalization of the ocular surface. The complications Opacification Clear Partial Iris details Complete
noted in chronic SJS are: obscuration poorly obscura-
of iris visible tion of iris
• Corneal complications: Superficial punctate keratopathy, details details
epithelial defect, loss of the palisades of Vogt (POV), Keratinization – <1/4 1/4–1/2 >1/2
conjunctivalization, neovascularization, opacification, Conjunctival Score 0 Score 1 Score 2 Score 3
keratinization. complications
• Conjunctival complications: Hyperemia, symblepharon Hyperemia – Sectoral Diffuse Significant

formation. engorge-
ment of
engorge-
ment of
engorge-
ment of
• Eyelid complications: Trichiasis, mucocutaneous junction conjunc- conjunc- conjunc-
tival tival tival
involvement, meibomian gland involvement, punctal vessels vessels vessels
damage. Symblepharon – Only <1/2 of >1/2 of
A new method for grading the extent and severity of ocular conjunc- corneal corneal
tival surface surface
involvement in patients with SJS has been recently elaborated surface involved involved
(Table 6.8.1.1).19 involved
Eyelid Score 0 Score 1 Score 2 Score 3

complications
Classification and Grading
Trichiasis – <1/4 1/4–1/2 >1/2
of Ocular Involvement
Mucocutaneous – Mild Moderate Severe
junction irregularity irregularity irregularity
Conjunctival: Hyperemia, symblepharon. involvement
Meibomian gland Clear Yellowish Cheesy Inability to
Corneal: SPK, epithelial defect, loss of POV, conjunctivalization, involvement oily fluid white material express
expressed fluid expressed any fluid
neovascularization, opacification, keratinization. expressed
Eyelid: Trichiasis, mucocutaneous junction involvement, Punctal damage – Iatrogenic

punctal
Either
Superior/
Both
Inferior/
meibomian gland involvement, punctal damage. occlusion Inferior Superior
occluded occluded
13 components: Grade of 0–3 is assigned depending on the
severity, with an overall total score of 39 (Table 6.8.1.1).19 Ocular examination (Figs 6.8.1.3A to C) includes evaluating
for lid complications (trichiasis, distichiasis, meibomian gland
Pattern of ocular involvement has been described as follows dysfunction, mucocutaneous junction involvement, blepharitis,
(Flow chart 6.8.1.1):15 entropion), conjunctival involvement (hyperemia, papillae,
• Mild/Moderate SJS follicles, keratinization, subepithelial fibrosis, conjunctival
• Severe SJS shrinkage, foreshortening of fornices, symblepharon,
• SJS–OSF (ocular surface failure) ankyloblepharon) and corneal complications (superficial
• SJS–RI (recurrent inflammation) punctate keratitis, epithelial defect, stromal ulcer,
• SJS–S (scleritis) neovascularization, keratinization, limbitis, conjunctivalization,
• SJS–MMP (mucous membrane pemphigoid). stromal opacity, perforation).
Flow chart 6.8.1.1: Natural history of progression of ocular disease

following onset of SJS/TEN (SJS = Stevens-Johnson’s Syndrome;
TEN = Toxic Epidermal Necrolysis) (Reproduced from The natural
history of Stevens-Johnson’s Syndrome: Patterns of chronic ocular
disease and the role of systemic immunosuppressive therapy. De
Rojas MV et al (Au). British Journal of Ophthalmology 2007, Volume
91, page 1048-53. Copyright notice February 2011 with permission
from BMJ Publishing Group Ltd)
Mild ocular manifestations such as lid edema or erythema,

conjunctival injection or chemosis resolve early. Moderate
lesions such as conjunctival membrane or pseudomembrane,
corneal erosion, or epithelial defect manifestations may require
more prolonged therapy but eventually resolve. Severe
manifestations include severe ocular inflammation or vision
threatening diseases such as conjunctival fornix foreshortening,
symblepharon, corneal infiltrate or ulceration that require
continuation of ophthalmologic treatment and lead to the
chronic nature of the ocular morbidity.
Chronic ocular complications of SJS lead to corneal
damage (Figs 6.8.1.4A to D). The severity of ocular involve-
ment correlates significantly with the final visual outcome.20
Laboratory Investigations
Serum levels of tumor necrosis factor (TNF)-alpha, soluble
interleukin 2-receptor, interleukin 6, and C-reactive protein
are typically elevated in patients with Stevens-Johnson
syndrome (SJS). None of these serologic tests are used
routinely in diagnosing and managing Stevens-Johnson
syndrome.
Skin biopsy is the only diagnostically helpful laboratory
study.
Histopathologic findings: Conjunctival biopsy shows
subepithelial plasma cells and lymphocyte infiltration.
Perivascular lymphocytes with predominant helper T cells are
seen. Immunohistology of the conjunctiva shows HLA-DR
positive cells in the substa ntia propria, vessel walls, and
epithelium. In the epithelium, HLA-DR is presented by Figs 6.8.1.3A to C: Acute SJS showing conjunctival hyperemia,
Langerhans cells, macrophages, and activated T cells. corneal erosion and pseudomembranes
Figs 6.8.1.4A to D: Chronic SJS showing dry eye with conjunctival hyperemia, cicatrization, early symblepharon,
lid margin thickening and keratinization and corneal opacification
Immunoreactant deposition in vessel walls, comprised of modalities have been advocated for the treatment of Stevens-
immunoglobulin and complement components, is another Johnson syndrome. Plasmapheresis, immunosuppressive
prominent feature. therapy, and intravenous immunoglobulin (IVIg) have all been
On transmission electron microscopy, the conjunctiva of advocated with variable results. The safety of systemic
patients with episodic conjunctival inflammation show corticosteroids in the treatment of Stevens-Johnson syndrome
squamous epithelial metaplasia, vascular basement membrane is controversial. Accepted current approach for corticosteroid
zone disruption, reduplication, and thickening. use suggests an early use of short-term (4–7 days), high-dose
intravenous corticosteroids.17,21 The other immunosuppressive
Management
agents (cyclosporine, azathioprine, or cyclophosphamide) in
Acute SJS: the acute phase are not very useful as they take weeks to exert
Systemic management: Patients with acute SJS need inpatient a suppressant effect on the immunological reactions of the
intensive care for supportive systemic management and acute phase. 12,22,23 Immunosuppressive therapy is of
symptomatic relief. importance in the management of the chronic ocular surface
Given the current scenario of incomplete understanding inflammation occurring in selective cases. 12 Intravenous
of the pathogenetic mechanisms of SJS, several therapeutic immunoglobulins block Fas receptors on the surface of
keratinocytes, thereby blocking Fas-Fas ligand mediated

apoptosis. However their beneficial role in the management
of SJS and the doses required are not clear.24
The main aim in pharmacotherapy of SJS patients is to
decrease morbidity and prevent complications. Persistent and/
or recurrent ocular inflammation mandates the use of short-
term systemic corticosteroids either alone or in conjunction
with long-term immunosuppressive therapy, in order to reduce
severity of conjunctival inflammation and cicatricial changes,
in order to improve visual prognosis by way of reducing
damage to ocular surface. The dosages of the various
therapeutic agents include:
Prednisone: 5–60 mg/day orally, with dose adjustments in
accordance to the severity of the condition and response
(pediatric—1–2 mg/kg/day in divided doses).
Methylprednisolone: 10–250 mg IV, repeated 4–6 hourly with
total dose not exceeding 1.5 g/24 hours (pediatric—0.5–2 mg/
kg/day).
Cyclosporine: Initial 14–18 mg/kg/day PO 4–12 hours before
organ transplantation with maintenance dose of 5–15 mg/
kg/day PO in two divided doses. (pediatric does is as in adults).
Cyclophosphamide: 500-750 mg/m2 PO (pediatric dose is as in
adults).
IV immune globulins: Adult—2 g/kg IV over 2–5 days.
Treatment of acute ocular manifestations involves
aggressive lubrication of the ocular surface with other
supportive measures and antibiotic therapy. Topical steroids
help to decrease inflammation and to be used with caution
after resolution of corneal lesions. With chronic inflammation
and progressive cicatricial changes, topical steroids, antibiotics,
and ocular surface lubrication remain the mainstay of therapy.
Surgical management in acute phase includes
symblepharon lysis, tarsorrhaphy for exposure keratopathy,
maintenance of ocular integrity with amniotic membrane
grafting, tissue adhesives, lamellar grafts, and therapeutic
penetrating keratoplasty in cases of perforation. Visual
rehabilitation in patients with visual impairment can be
considered once the eye has been quiet for at least 3 months.
Treatment of chronic ocular manifestations: Cases with
mild chronic superficial keratopathy secondary to mild to
moderate keratoconjunctivitis sicca require long-term
lubrication. In addition a permanent lateral tarsorrhaphy may
be of help.
The visual rehabilitation in patients with extensive ocular
involvement, that has resulted in severe dry eye syndrome with
posterior lid margin keratinization, limbal stem cell deficiency, Figs 6.8.1.5 A to C: Ocular surface in chronic SJS
Figs 6.8.1.6A and B: Note the ocular surface is better in a chronic SJS patient compliant to treatment and follow-up
persistent epithelial defects with subsequent corneal 2. Stevens AM, Johnson FC. A new eruptive fever associated with
neovascularization, and corneal opacification with surface stomatitis and ophthalmia. Reports of two cases in children. Am J
Dis Child 1922; 24:526-33.
conjunctivalization and keratinization, is difficult to treat. The
3. Thomas BA. The so-called Stevens-Johnson syndrome. BMJ
removal of keratinized plaques from the posterior lid margins, 1950;1:1393-7.
along with mucous membrane grafting, is effective in 4. Roujeau JC. Stevens-Johnson syndrome and toxic epidermal
determining the future success of corneal surgeries.25 necrolysis are severity variants of the same disease which differs
Limbal stem cell transplantation and amniotic membrane from erythema multiforme. J Dermatol 1997;24(11):726-9.
grafting with superficial keratectomy for removing 5. Parrillo SJ. Stevens-Johnson syndrome and toxic epidermal
conjunctivalized or keratinized ocular surface may be done necrolysis. Curr Allergy Asthma Rep 2007;7(4):243-7.
6. Pushker N, Tandon R, Vajpayee RB. Stevens-Johnson syndrome
subsequently. Lamellar or penetrating keratoplasty for visual in India—risk factors, ocular manifestations and management.
rehabilitation might be done in selective cases. Best approach Ophthalmologica 2000;214(4):285-8.
in management will be to maintain useful vision rather than 7. Faraj HG, Hoang-Xuan T. Chronic cicatrizing conjunctivitis. Curr
perform allografts in a scenario of chronic SJS. Long term Opin Ophthalmol 2001;12(4):250-7.
use of gas permeable scleral contact lenses may be necessary 8. French LE. Toxic epidermal necrolysis and Stevens Johnson
to protect the ocular surface and improve visual acuity. Long- syndrome: our current understanding. Allergol Int 2006;55(1):9-
16.
term management requires frequent treatment of trichiatic
9. Mockenhaupt M, Messenheimer J, Tennis P, et al. Risk of Stevens-
lashes and/or eyelid margin repair for distichiasis or entropion. Johnson syndrome and toxic epidermal necrolysis in new users of
Keratoprosthesis may be required for visual rehabilitation when antiepileptics. Neurology 2005;64(7):1134-8.
multiple surgical interventions have failed. 10. Letko E, Papaliodis DN, Papaliodis GN, Daoud YJ, Ahmed AR,
Long-term follow-up of cases of chronic SJS requires Foster CS. Stevens-Johnson syndrome and toxic epidermal
the treating physician to look out for ocular complications necrolysis: a review of the literature. Ann Allergy Asthma Immunol
2005;94(4):419-36; quiz 436-8, 456. Review.
(Figs 6.8.1.5 and 6.8.1.6) such as chronic cicatrizing
11. Power WJ, Saidman SL, Zhang DS, Vamvakas EC, Merayo-Lloves
conjunctivitis, corneal epithelial defects, corneal stromal JM, Kaufman AH, Foster CS. HLA typing in patients with ocular
ulcers, corneal perforation, and endophthalmitis. About 27– manifestations of Stevens-Johnson syndrome. Ophthalmology
50 percent of patients with SJS are seen to progress to severe 1996;103(9):1406-9.
ocular disease. 12. Khalili B, Bahna SL. Pathogenesis and recent therapeutic trends in
Stevens-Johnson syndrome and toxic epidermal necrolysis. Ann
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1. Von Hebra F. Acute exanthema und hautkrankheiten. In: von Hebra intravenous immunoglobulin therapy in the treatment of
F, ed. Handbuch der Speciellen Pathologie und Therapie. Erlangen: autoimmune mucocutaneous blistering diseases. Arch Dermatol
Verlag von Ferdinand Enke 1860;198-200. 2003;139(8):1051-9.
14. Assier-Bonnet H, Aractingi S, Cadranel J, Wechsler J, Mayaud C, 20. Di Pascuale MA, Espana EM, Liu DT, Kawakita T, Li W, Gao YY,
Saiag P. Stevens-Johnson syndrome induced by cyclophosphamide: Baradaran-Rafii A, Elizondo A, Raju VK, Tseng SC. Correlation
report of two cases. Br J Dermatol 1996;135(5):864-6. of corneal complications with eyelid cicatricial pathologies in
15. De Rojas MV, Dart JK, Saw VP. The natural history of Stevens- patients with Stevens-Johnson syndrome and toxic epidermal
Johnson syndrome: patterns of chronic ocular disease and the role necrolysis syndrome. Ophthalmology 2005;112(5):904-12
of systemic immunosuppressive therapy. Br J Ophthalmol 21. Sotozono C, Ueta M, Koizumi N, et al. Diagnosis and treatment
2007;91(8):1048-53. of Stevens-Johnson syndrome and toxic epidermal necrolysis with
16. Foster CS, Fong LP, Azar D, Kenyon KR. Episodic conjunctival ocular complications. Ophthalmology 2009;116(4):685-90.
inflammation after Stevens-Johnson syndrome. Ophthalmology 22. Hynes AY, Kafkala C, Daoud YJ, Foster CS. Controversy in the
1988;95(4):453-62. use of high-dose systemic steroids in the acute care of patients
17. Araki Y, Sotozono C, Inatomi T, Ueta M, Yokoi N, Ueda E, with Stevens-Johnson syndrome. Int Ophthalmol Clin
Kishimoto S, Kinoshita S. Successful treatment of Stevens-Johnson 2005;45(4):25-48.
syndrome with steroid pulse therapy at disease onset. Am J 23. Kardaun SH, Jonkman MF. Dexamethasone pulse therapy for
Ophthalmol 2009;147(6):1004-11, 1011.e1. Epub 2009 Mar 14. Stevens-Johnson syndrome/toxic epidermal necrolysis. Acta Derm
18. Ukponmwan CU, Njinaka I, Ehimiyen ET. Ocular complications Venereol 2007;87(2):144-8.
of Stevens-Johnson syndrome and toxic epidermal necrolysis. Trop 24. French LE, Trent JT, Kerdel FA. Use of intravenous
Doct 2010;40(3):167-8. immunoglobulin in toxic epidermal necrolysis and Stevens-Johnson
19. Sotozono C, Ang LP, Koizumi N, Higashihara H, Ueta M, Inatomi syndrome: our current understanding. Int Immunopharmacol
T, Yokoi N, Kaido M, Dogru M, Shimazaki J, Tsubota K, Yamada 2006;6(4):543-9.
M, Kinoshita S. New grading system for the evaluation of chronic 25. Wall V, Yen MT, Yang MC, Huang AJ, Pflugfelder SC. Management
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Ophthalmology 2007;114(7):1294-302. Surf 2003;1(4):192-201.
(C) ALLERGIC CONJUNCTIVITIS Atopic Conjunctivitis

The clinical profiles of allergic conjunctivitis may be described Atopic keratoconjunctivitis (AKC) was initially described by
as follows: Hogan as a bilateral conjunctivitis occurring in association
• Atopic keratoconjunctivitis with patients with atopic dermatitis.2 Foster later elaborated
• Giant papillary conjunctivitis the occurrence of AKC in the absence of atopic dermatitis.3
• Seasonal conjunctivitis (hay fever conjunctivitis) AKC is commonly associated with concomitant eczema,
• Perennial allergic conjunctivitis asthma, and family history of atopy. Individuals with atopy
• Vernal keratoconjunctivitis often have environmental allergies, allergic asthma, rhinitis,
• Contact conjunctivitis. and atopic dermatitis or eczema and may also manifest food
Initially all allergic subtypes of conjunctivitis were allergies, urticaria, and nonhereditary angioedema. Atopic
considered (as suggested by Coombs and Gell1) to be a result keratoconjunctivitis is more prevalent in men than in women.
of classical type I IgE-mediated hypersensitivity reaction at Patients commonly affected are in the age group ranging from
the conjunctival level. Recent clinical observations, however, the teens to the 5th decade of life.
suggest that other tissues of the eye (the lids with their high
Clinical features: Patients with AKC present with complaints
content of mast cells, the tear film with its immunoglobulins,
of severe pruritis, burning sensation, tearing, ropy discharge
and the cornea) are also involved in the ocular allergic reaction.
and photophobia. The complaints are chronic with seasonal
New discoveries regarding the pathogenesis of ocular allergies
exacerbations though the severity is much more than that seen
indicate the participation of the entire ocular surface in allergic
in perennial or seasonal allergic conjunctivitis. Lid edema with
diseases. This is due to tissue contiguity and complex
induration may be seen. An extra lid fold (Dennie's line/
interaction between these tissues through cell-to-cell
Dennie-Morgan folds–secondary to chronic eye rubbing),
communications, chemical mediators, cytokines, and adhesion
Hertoghe sign (loss of lateral eyebrows) may be seen. Bulbar
molecules. It is also possible that the neural and endocrine
conjunctiva is chemotic and congested. Trantas dots (clusters
systems influence the ocular allergic response.
of necrotic eosinophils, neutrophils, and epithelial cells),
Investigations: Include laboratory workup, IgE assay, skin tests, gelatinous nodules and epithelial cysts may be seen in the
conjunctival allergen tests, impression cytology. limbus. Tarsal conjunctiva shows papillary reaction.
Decreased vision and blindness results from chronic for GPC include, suture induced irritation, extruding scleral
superficial punctate keratitis, persistent epithelial defects, buckles and ocular prosthetic wear. Papillae greater than 0.3
corneal scarring or thinning, and symblepharon formation.4 mm in diameter are seen in the upper tarsal conjunctiva, with
Chronic use of topical steroids commonly results in steroid symptoms of itching, coated CLs, CL intolerance, decreased
induced cataract, glaucoma and corneal infections. Herpes visual acuity, conjunctival congestion and increased mucus
simplex keratitis and a higher incidence of keratoconus is also discharge which are characteristic of GPC.11
seen in AKC patients. Conjunctival biopsy can help Allergic symptoms accompany papillary changes in the
differentiate atopic keratoconjunctivitis (AKC) from cicatricial ocular tarsal palpebral conjunctiva as part of an immuno-
pemphigoid in advanced cases which shows excessive globulin E (IgE)-mediated hypersensitivity reaction.
eosinophils, mast cells, and goblet cells while basement
membrane antibodies or complement components are seen Clinical features: Patients with GPC usually have intolerance
in cicatricial pemphigoid. to contact lens wear, complaining of increased mucus at the
Pathophysiology: Type I and Type IV hypersensitivity reactions inner canthus at the time of CL removal. Symptoms include
are responsible for the inflammatory changes of the increased mucus discharge, increasing discomfort to CL wear,
conjunctiva and the cornea in AKC. Immunoglobulin E (IgE) redness, itching and decreased vision at times. Examination
is the serum mediator of the exuberant responses and increased reveals giant papillae in the upper tarsal conjunctiva along with
tear and serum IgE levels are seen during disease exacerbations. conjunctival injection. Soft contact lens wear is associated with
Increase in circulating B cells is also seen. a higher incidence of GPC compared to rigid lenses.
Silicone hydrogel lenses tend to induce more local giant
Management: Prophylactic treatment to reduce disease papillary conjunctivitis while hydrogel lenses cause more
exacerbations5 includes use of topical mast cell stabilizers generalized giant papillary conjunctivitis reactions. Heat
(Cromolyn sodium 4%, Lodoxamide tromethamine 0.1%,
sterilization, poor cleaning, rough contact lens edges, and
Nedocromil sodium 2%) and antihistamines (Olopatadine
extended wearing times predispose to GPC. Increased
hydrochloride 0.1%, Ketotifen fumarate 0.025%, Azelastine
frequency of contact lens replacement, rigorous cleaning,
hydrochloride 0.05%, Epinastine hydrochloride 0.05%).
peroxide disinfection, and decreased wear times help to reduce
Treatment of acute exacerbations includes intensive short-
GPC.
term topical steroids therapy with gradual tapering in
The symptoms and signs of GPC vary according to the
proportion to the severity of the presentation. Topical 0.05
percent or 2 percent cyclosporine suspended in oil (4–6 times severity.11 Preclinical signs of GPC include mild conjunctival
per day) might be a useful adjunct therapy when there is a hyperemia, with fine papillary reaction associated with no or
need to decrease steroids or administer steroid sparing minimal symptoms or mild mucus production with or without
treatment.6 Systemic cyclosporine to induce remission and lens coating. Mild GPC presents with mild hyperemia, partial
continued on maintenance doses has also been described in loss of vascular pattern of conjunctiva, 0.3–0.5 mm sized
refractory cases.7 T lymphocyte immunomodulators, such as papillae associated with mild mucus production, coated CL,
tacrolimus (systemic/topical ointment instillation), have been early CL intolerance features of increased CL awareness and
reported to be successful in refractory cases.8,9 decreased wearing time. Moderate GPC patients have moderate
Other treatments required include cataract surgery with conjunctival hyperemia with early subconjunctival scarring
IOL implantation, management of steroid induced glaucoma, distorting the normal vascular pattern, with papillae sized 0.5
keratoplasty in cases with corneal scarring, and plasmapheresis mm or larger. Discomfort on CL wear associated with mucus
in patients with high IgE levels. production, coated CL and excessive lens movement may also
In most cases, management of systemic allergy results in be seen. Severe GPC is characterized by significant hyperemia
significant alleviation of ocular symptoms. Reduction or of the conjunctiva with papillae greater than 0.75 mm and
elimination of inciting environmental allergens is necessary such patients are unable to wear their contact lenses showing
for optimal prophylaxis. severely coated lenses with mucus production.
Pathophysiology: Mechanical irritation and/or antigenic stimulus

Giant Papillary Conjunctivitis
of the tarsal conjunctiva of the upper lids, possibly by the
Giant papillary conjunctivitis (GPC) was first described by contact lens surface or edge or deposit is supposed to trigger
Spring10 in association with contact lens wear. Other causes mast cell degranulation and typical secondary inflammatory
cascade. This leads to conjunctivitis and further tissue changes white, capped scars of the giant papillary lesions may be
and increasing inflammatory markers in the tears. observed for a long period of time. Frequent monitoring of
patients for activity, patient education on the chronic nature
Histopathological changes: In GPC, degranulating mast cells are
of the disease and its symptoms is important.
found in the epithelium, with eosinophils and basophils found
to be infiltrating the epithelium and substantia propria.
The predominant mast cell (of the normal skin subtype) Seasonal and Perennial
with both tryptase and chymase is found to occur in GPC Allergic Conjunctivitis
while in VKC the predominant mast cell subtype is that with Seasonal allergic conjunctivitis or conjunctivitis associated with
only tryptase, which is T lymphocyte dependent (as found in hay fever is the most common form of allergic conjunctivitis
the lung).12 Other associated findings include: noted to present with a seasonal onset of symptoms in
• Increased density of inflammatory cells association with airborne pollens and antigens. The patients
• Increased levels of tear histamine, IgE, IgG, IgM, may present with only ocular symptoms but associated nasal
complement factors (C3, factor B and C3 anaphylotoxin), or pharyngeal symptoms may be present. Family history of
increased lactoferrin, neutrophilic chemotactic factor, atopy might be present. Patients complain of increased tearing,
leukotriene, and eokine, decreased decay-accelerating factor ocular itching with associated hyperemia of the conjunctiva.
(DAF) which has an inhibitory role on C3 amplification in A milky conjunctival involvement has been described11 due
the complement cascade.13-17 to the edema. Severe cases might present with lid edema and
• Membranous epithelial cells (M cells) (that are involved in upper tarsal conjunctival papillary hypertrophy (Fig. 6.8.1.7)
the binding, uptake, and translocation of antigens in The signs and symptoms are typically noted to be seasonal
mucosa associated lymphoid tissue) have been found to occurring in the summer months.
hyper-proliferate. 18 This along with the increased Perennial allergic conjunctivitis is similar to seasonal allergic
lymphocytes lead to the conjunctival changes in GPC. conjunctivitis but is chronic in nature occurring all through
Management: Contact lenses need to be discontinued in the year. The signs and symptoms tend to be less severe.
patients with CL wear associated GPC. Topical steroids along Common airborne allergens are implicated to be responsible
with mast cell stabilizers and antihistamine medications will for perennial allergic conjunctivitis.10 Pathophysiology involved
also be required. Anti-inflammatory topical medications may in seasonal and perennial allergic conjunctivitis is a type I
also be useful in mild cases.19 Better CL care and hygiene, hypersensitivity reaction. Management includes identification
frequent lens replacement, changing the CL lens design or of the possible allergen and its elimination from the patients
material can also be helpful. In mild-to-moderate GPC, patients environment. Topical vascoconstrictors (such as naphazoline,
may continue contact lens wear with change in contact lens
design and materials and care regimens and education. Use of
non-preserved chemical disinfectants such as hydrogen
peroxide and enzymatic treatments is also beneficial. In
moderate to severe GPC, CL wear is to be discontinued for
three to four weeks along with medications. In the event of
the patient responding with resolution of papillary reaction
and hyperemia and improved corneal status, refitting with rigid
gas permeable lenses may be considered along with a frequent
lens replacement regimen. If the GPC is seen to recur, use of
topical mast cell stabilizer is to be started six times a day, along
with a new contact lens. The topical medications may be
tapered in accordance to the response to treatment. It is to be
noted that therapeutic effect can be observed by improved
CL tolerance, decreased ocular itching, and hyperemia of the
tarsal conjunctivae, and decreased inflammation of the giant
papillae, and mucus in the tears. Lids of some patients may Fig. 6.8.1.7: Upper tarsal conjunctival
return to normal appearance, while in others, residual small, hyperemia with papillary hypertrophy
and tetrahydrozoline hydrochloride) with or without topical predominant form).11 A mixed form can also occur with a
antihistaminics usually helps to alleviate symptoms. Topical combination of both tarsal and limbal lesions.
steroids may be required in severe cases. Chronic cases may Signs include the presence of giant papillae hypertrophy
need supratarsal steroid injections to control the upper tarsal with the typical cobblestone appearance of the upper tarsal
inflammatory reactions. conjunctiva or at the limbus, the presence of aggregates of
epithelial cells and eosinophils at the limbus (Trantas’ dots),
Vernal Keratoconjunctivitis and marked conjunctival hyperemia (Figs 6.8.1.8A to D).
Corneal shield ulcers (Togby's ulcers) are mainly located in
Vernal keratoconjunctivitis (VKC) is a bilateral, seasonal,
the upper paracentral cornea. Subconjunctival fibrosis,
external ocular inflammatory disease of unknown cause.11,20,21
symblepharon, and conjunctival keratinization can develop in
VKC is a seasonal atopic disease in young children (more
severe chronic cases. Cornea involvement is due to superficial
common in boys), which occasionally becomes severe and leads keratopathy, or the presence of corneal shield ulcers (seen to
to shield ulcers and other complications. It primarily affects occur in approximately 3–11%) and neovascularization.22-24
children, may be related to atopy, and has environmental and Blepharitis, eczema or lid maceration may also be present.
racial predilections. Although usually self-limiting, vernal Cataract and steroid-induced glaucoma are the major ocular
keratoconjunctivitis can result in severe corneal morbidity due complications.
to its associated potentially blinding corneal complications.
Patients with VKC present with intense itching, tearing, Immunopathogenesis: A complex non-IgE dependent
photophobia, and mucous discharge. Large cobblestone pathogenic mechanism has been thought to be responsible
papillae are usually seen in the superior tarsal conjunctiva and for VKC. VKC is no longer considered to result only due to a
limbal conjunctiva. The most common signs are giant papillae, Type I IgE mediated hypersensitivity reaction. A Th2-mediated
superficial keratitis, and conjunctival hyperemia. reaction and allergic inflammation of conjunctiva with mast
Though patients with VKC frequently have a family or cells, eosinophils and mast cells has been implicated.22 It is
medical history of atopic diseases, such as asthma, rhinitis, now postulated that the pathogenesis of VKC is characterized
and eczema, a positive skin test or RAST (radioallergosorbent by a Th2 lymphocyte alteration, while the exaggerated IgE
test) is not a common association thereby confirming that it response to common allergens is an inconsistent and, possibly
is not solely an IgE-mediated disease.21 The pathogenesis of a secondary event. Th2 lymphocytes cause hypersecretion of
VKC is now considered to be multifactorial, with the IgE (interleukin 4, IL-4) and for differentiation and activation
interaction of the immune, nervous and endocrine systems. of mast cells (IL-3) and eosinophils (IL-5).20,25 Histamine
release from the mast cells and basophils results in the
Clinical features: VKC typically affects boys in their first immediate inflammatory reaction and the recruitment of
decade of life as a chronic bilateral inflammation of the inflammatory cells (lymphocytes and eosinophils). This leads
conjunctiva characterized by hyperemia, chemosis, to release of other toxic cell mediators (such as eosinophil
photophobia, and filamentous and sticky mucous discharge. cationic protein, EDN/EPX) with corneal epithelial damage.20
Approximately 23 percent of patients have a perennial form These inflammatory and epithelial cells possibly induce
of VKC from time of disease onset with more than 60 fibroblast proliferation and collagen production producing the
percent having additional recurrences during the winter. 21 characteristic conjunctival findings. Other mediators said to
It has been observed that in about 16 percent of the cases, be involved in VKC are eosinophilic mediators and substances
the seasonal (vernal) form evolves into a chronic, perennial derived from the metabolism of arachidonic acid
inflammation after a mean of 3 years from disease onset, (prostaglandins and leukotrienes). The biological activities of
implying that the longer the duration of the disease, the leukotrienes on the conjunctiva perhaps contribute to the
more likely that it would evolve into a chronic form of the presence of the characteristic symptoms observed in VKC,
disease. 20 Itching, photophobia, burning, and tearing are such as mucus secretion, conjunctival hyperemia, and
the major ocular symptoms. Conjunctival hyperemia chemosis.21 Substance P and nerve growth factor are certain
subsequent to exposure to nonspecific stimuli, may also be neural factors that have also been implicated in the
seen. pathogenesis of VKC, and the overexpression of estrogen
The characteristic clinical hallmark of the disease are giant and progesterone receptors in the conjunctiva of VKC patients
papillae (cobblestone appearance) present in the upper tarsal has introduced the possible involvement of sex hormones in
conjunctiva (tarsal predominant form) or at limbus (bulbar VKC pathogenesis.21
Figs 6.8.1.8A to D: Vernal keratoconjunctivitis showing palpebral and limbal lesions
Management: VKC is usually easily diagnosed by the typical, detect steroid responders and steroid induced glaucoma.
characteristic signs and symptoms. Laboratory investigations Topical mast cell stabilizers and topical antihistamines are also
such as total and specific IgE determination, as well as skin effective in reducing signs and symptoms of the disease, but
tests are not considered useful as more than 50 percent of may have to used in conjunction with topical steroids in the
patients with VKC are negative. In case of a diagnostic acute phases of exacerbations of the disease. Use of
dilemma, a conjunctival scraping can be helpful in unpreserved solutions may reduce the risk of hypersensitivity
demonstrating the presence of eosinophils infiltrating the to preservatives that are frequently superimposed in these
conjunctival epithelium.21 VKC usually becomes quiescent or patients. Nonsteroidal anti-inflammatory agents may also be
subsides by puberty. In some cases however, its severity grade beneficial.
is higher and may be observed to persist beyond puberty. Such Following control of the acute phase of the disease, topical
cases are seen to have significant ocular surface changes steroids are to be gradually tapered and discontinued and long-
resulting in visual debility. term maintenance therapy with topical mast cell stabilizers
Symptomatic treatment to control ocular surface along with intermittent antihistamine and NSAIDs will be the
discomfort and inflammation is generally achieved with mainstay in the management of VKC. Cyclosporine A (CsA)
cautious topical steroid therapy. Topical steroid preparations formulations of 0.5 to 2 percent ophthalmic emulsions in olive
are the most effective therapy for moderate to severe form of or castor oil, used four times daily, may be used as an alternative
VKC, with frequent and careful monitoring being required to to steroids in severe forms of VKC, in order to decrease
frequency of steroid use in steroid dependent cases. CsA is initial phases of presentation. Complex immune mechanisms
effective in controlling ocular inflammation, by blocking Th2 are responsible for the allergy inflammation of the diseases.
lymphocyte proliferation, and IL-2 production. It also inhibits Treatment of chronic forms of ocular allergies mandates
histamine release from mast cells and basophils and, by collaborative efforts between the ophthalmologist and the
reducing IL-5 production, brings about decrease in recruitment allergist or immunologist.
and inflammatory effect of eosinophils on the conjunctiva.21
CsA is also said to be responsible for the reduction of REFERENCES
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Aspects of Immunolog y. Chap. 13. Blackwell Scientific
to effect decrease in generalized hyper-reactivity may not be
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Ocular examination is usually sufficient for making differential
7. Hoang-Xuan T, Prisant O, Hannouche D, Robin H. Systemic
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9. Miyazaki D, Tominaga T, Kakimaru-Hasegawa A, Nagata Y,
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• Specific tests to assess ocular allergic inflammation (such 10. Spring TF. Reaction to hydrophilic lenses. Med J Aust
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Conjunctival provocation tests have been employed to Brown and Company, Boston 1994;347-63.
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nonspecific conjunctival hyperreactivity, and to evaluate cells; distribution of MCT and MCTC in vernal conjunctivitis and
sensitivity to therapeutics. giant papillary conjunctivitis. J Allergy Clin Immunol 1990;86(1):34-
Differential cytokine levels in tear samples (using 40.
13. Donshik PC, Ballow M. Tear immunoglobulins in giant papillary
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Allergy Clin North Am 2008;28(1):59-82, vi. Ophthalmol 2001;49(4):241-5.
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23. Cameron JA. Shield ulcers and plaques of the cornea in vernal 28. Hodges MG, Keane-Myers AM. Classification of ocular allergy.
keratoconjunctivitis. Ophthalmology 1995;102:985-93. Curr Opin Allergy Clin Immunol 2007;7(5):424-8.
(D) INFECTIONS OF THE CONJUNCTIVA viral infections in the pathogenesis of this disease. A large
range of treatment options are available reflecting the difficulty
(This has been covered in the Section 6.7—Infections of the Cornea and
involved in preventing recurrence of the disease.
the External Eye)
Epidemiology: Pterygia tends to occur in hot and dry climatic
(E) OTHER DISEASES regions with a higher risk in populations of regions within 30
OF THE CONJUNCTIVA degrees of latitude. A high risk prevails in outdoor workers
exposed to sunlight, especially those working in the setting of
Other diseases of the conjunctiva discussed here includes
highly reflective surfaces.8,9
pterygium and nutritional disease of the eye.
Etiopathogenesis
Pterygium
The etiopathogenesis of pterygium has not been fully
Pterygium (Fig. 6.8.1.9) is a disease of the ocular surface that
understood. Recent studies have reported significant progress
is associated with chronic UV exposure and is characterized
towards understanding the mechanisms involved in its
by proliferation, inflammatory infiltrates, fibrosis, angiogenesis
pathogenesis.3 It has been observed that certain signaling
and extracellular matrix breakdown. The word pterygium is
derived from the Greek word ‘pteryx’, which means wing. This
condition is a common ophthalmic disease. Pterygium is seen
in all countries of the world but its prevalence rates are higher
in the tropics than in temperate latitudes with the equatorial
countries having a higher prevalence rate1 (commonly referred
to as the “pterygium belt”).2 Pterygium is characterized by
excessive fibrovascular proliferation on the exposed ocular
surface, thought to be caused by increased ultraviolet light
exposure from climatic factors and aggravated by microtrauma
and chronic inflammation from environmental factors.3-7
Though the mechanism(s) contributing to the occurrence
of pterygium is incompletely understood, recent research
points to evidence implicating stem cell failure, a genetic
component, anti-apoptotic mechanisms, cytokines, growth
factors, extracellular matrix remodelling (through the actions
of matrix metalloproteinases), immunological mechanisms and Fig. 6.8.1.9: Pterygium
pathways, activated by UV light result in induction of mediators chronicity and a stable position. This fibrovascular lesion of
responsible for the growth of pterygium.3 Chronic UV the ocular surface can sometimes have an aggressive clinical
exposure is a widely accepted etiological factor in the behavior threatening vision.
pathogenesis as this concept is supported by epidemiological Pterygium is commonly seen to occur on the nasal side.
data, ray tracing models and histopathological changes that The possible explanation for this is the increased actinic
share common features with UV damaged skin.10 exposure in this region secondary to ultraviolet light reflection
Genetic studies also implicate hereditary factors.10-13 from the nose. Also, the anterior part of the eye acts as a lens,
Epithelial mesenchymal transition, bone marrow progenitor with light incident on the temporal cornea being focused across
cells, and neuronal signals are also thought to play a the anterior chamber onto the nasal limbus. The peak light
contributory role in the pathogenesis of pterygium.10-13 Recent power density at the nasal limbus calculated by computer-
evidence suggests that pterygium is a proliferative lesion rather assisted optical ray tracing techniques was found to be 20 times
than degenerative condition. Its occurrence is strongly the power density of the incident light temporally.16,17
correlated with exposure to ultraviolet radiation of solar light. Pterygium symptoms include blurring, irritation,
Molecular genetic alterations reported in association with lacrimation, and foreign body sensation. Significant
pterygium include loss of heterozygosity (LOH), point astigmatism may be induced either with or against the rule.18
mutations of proto-oncogenes, such as K-ras and alterations Corneal astigmatism in an eye with pterygium is the result of
in the expression of tumor suppressor genes, such as p53 or cumulative effect of a naturally occurring astigmatism and that
p63.13 Certain other observations noted to be associated in due to the pterygium. The possible mechanisms explaining
pterygium include the frequent detection of HPV DNA, ocular this is due to the following reasons:19,20
surface changes such as the overexpression of various proteins, i. The tractional force of contractile elements within the
including defensins and phospolipases D, as well as the up- pterygium lead to mechanical distortion and flattening
regulation of growth factors.13 of the cornea;
ii. The localized pooling of tears at the head of the
Histopathology: Histopathological evaluation reveals that the
pterygium is also thought to lead to corneal flattening.
pterygium is composed of loose fibrous connective tissue with
Several studies 20-35 have dealt with the issue of pterygium
fibrovascular ingrowth and destruction of the Bowman's layer.
induced corneal astigmatism and have recommended a critical
Degenerating collagen results in hyalinization of the
size for surgery before a significant degree of astigmatism
subepithelial connective tissue. Eosinophilic granular material
occurs.
and concretions are also present. Significant amount of
Pterygium induced with-the-rule corneal astigmatism is
pterygium tissue comprises of abnormal elastic fibers. These
hemimeridional on the side of the pterygium resulting in a
fibers stain as elastin but do not degrade with elastase and
localized flattening of the cornea central to the leading apex.
hence have been called elastotic. These fibers have been found
The common types of astigmatism induced by a pterygium
to be elastic fiber precursors and abnormal maturational forms
include with-the-rule astigmatism mainly, followed by against-
in states of degeneration.14 Numerous fibroblasts found in
the-rule and oblique astigmatism. The extension and total area
the vicinity of the elastodysplasia indicate a probable actinic
of pterygium have a better correlation with corneal astigmatism
induced damage that resulted in the formation of abnormal
than the width.22,23,35 Extension, total area, and to a lesser
tissue.
degree, the width, form important parameters in pterygium
assessment. Corneal astigmatism always is higher than in the
Signs and Symptoms
normal control eyes in unilateral cases.
Pterygium, a wing-shaped encroachment on the cornea by the Before encroaching upon the visual axis, pterygia typically
conjunctiva, in the interpalpebral region of the conjunctiva, induce with-the-rule astigmatism, which can be visually
which may be atrophic, stationary or progressive. Commonly significant. The induced amount of regular and irregular
located in the nasal region, pterygium is composed of:15 astigmatism is proportional to its size.33,36 Pterygium size is
• A body connecting to the bulbar conjunctiva; an important predictor for both the amount of induced corneal
• A head that proceeds anteriorly on to the cornea; and astigmatism and the timing for surgical intervention. Pterygium
• A cap at the leading edge. has been suggested to contribute to corneal astigmatism20-35
Stocker's line of iron deposition may be found central to of > 2 D when its extension is > 2.2 mm, its width is > 5 mm,
the leading edge where the tear flow is abnormal, indicating or its total area is > 6.25 mm2. Early surgical intervention can
therefore reduce effects of corneal morbidity due to pterygium however, no consensus regarding the ideal treatment for the
induced corneal distortion and visual disturbance arising from disease. Comparability between studies is limited by the fact
the encroachment of the pterygium into the visual axis. The that the study definitions of various studies vary widely.
total area and extension of pterygium constitute the critical As bare sclera excision is associated with a high recurrence
factors in inducing astigmatism, with length > 2.25 mm can rate, pterygium excision is often combined with conjunctival
lead to corneal astigmatism of 2 D.23 Early surgical intervention autograft, mitomycin C, beta-irradiation or other adjunctive
has also been recommended when the pterygium size is 1.0 therapies to reduce recurrence rates. Conjunctival autografting
mm from the limbus or > 16 percent of the corneal radius.26 and mitomycin C application are the most commonly used
Thus while there exists a general agreement on the fact that methods for preventing recurrences. Mitomycin C and beta-
increasing extent of the pterygium into the cornea induces irradiation should be used judiciously because of the potential
astigmatism, a consensus on the critical size of primary pterygia long-term risk of sight-threatening complications. Additional
for surgical intervention is still not clear. It is generally agreed clinical trials should be performed to evaluate the relative
upon that the finding where, the pterygium induces visually
significant central with-the-rule astigmatic changes which may
not be apparent by subjective refraction may be used to help
identify those patients who may benefit from surgical
intervention.37
Indications for treatment of pterygium include:37
• Proximity to the visual axis resulting in diminution of vision
• Encroachment of the visual axis
• Significant astigmatism leading to visual debility
• Restriction of ocular movements
• Atypical appearance such as possible dysplasia
• Symptomatic growth
• Cosmetic concerns.
More than 50 percent of pterygium recurrences have been
found to occur by 4 months after excision and nearly all (97%)
by the first year.38 Many factors play a pivotal role in recurrence
including fibroblastic activity, inflammation and Fig. 6.8.1.10: Conjunctival autograft with human fibrin glue
vascularization. Post excision recurrence rates vary widely. fixation after pterygium excision
Pterygium morphology grading 39 that is commonly
followed is:
T1 : Atrophic and transparent form with clearly visible
episcleral vessels
T2 : Intermediate form with partially visible episcleral vessels
T3 : Fleshy and opaque form with totally obscured episcleral
vessels.
Treatment
Pterygium management has traditionally involved surgery,
often enhanced by the use of antimetabolites. Therapeutic
options for pterygium have been described based on the
mechanisms that perpetuate its growth. At present, there are
a wide variety of surgical methods40 (Figs 6.8.1.10 and 6.8.1.11),
but very few clinical guidelines on the optimal treatment of
primary or recurrent pterygium. The primary aim is to excise Fig. 6.8.1.11: Pterygium excision with conjunctival limbal
the pterygium and prevent its recurrence. There is currently, autograft with suture fixation
efficacies and long-term safety of the various treatment enough tissue might not be available for harvesting conjunctival
modalities. autografts from the same eye or from the fellow eye. Such
Recent advancements in the understanding of molecular scenarios demand use of other tissue sources such as the
and biochemical events underlying pterygium pathogenesis amniotic membrane.82 Pterygium excision with closure using
may enable the use of less invasive treatment methods. amniotic membrane grafting is also widely practiced.83-89
Several surgical approaches have been attempted in the Amniotic membrane grafts by their characteristics of
management of pterygium41-45 with all procedures being epithelialization facilitation, anti-infammatory effects (due to
classified in accordance to the method of excision of the inhibition of fibroblast's chemokine expression 90,91 and
pterygium and the method of closure of the defect created. epithelial interleukin-1 expression) and prevention of
Following excision, the resulting defect may be left exposed neovascularization (due to vascular endothelial growth factor
as in bare sclera excision46 or closed using the adjacent (VEGF) inhibition). Recent studies have compared the
conjunctival tissue as in primary closure44,46-48 or by employing recurrence rates between conjunctival autografts and amniotic
a pedicle flap,46,49 or by transposition of the pterygium head.49 membrane grafts in both primary and recurrent pterygium.92
Other methods of closure include: The reported recurrence rates vary greatly among different
• With a conjunctival autograft (CAG)47,50-56 surgical procedures and among different groups performing
• With the conjunctival limbal autograft (CLAG)44,55-58 similar procedures. The amount of subconjunctival tissue
• Rotational autografts59 removal, type of suture used and postoperative treatment—
• With other tissue sources such as buccal mucous membrane all influence the rate of recurrence. Conjunctival autografts
grafts, amniotic membrane grafting,60 lamellar/penetrating achieve better results and are better in preventing recurrence
keratoplasty,44,61,62 or sclerokeratoplasty.63 than AMGs in pterygium surgery.83,92
The other techniques include yttrium-aluminium-garnet An adequate post-operative regimen of topical
(YAG) laser treatment64 and Barraquer's polishing technique.65 corticosteroid is associated with a lower pterygium recurrence
Use of adjuvants (such as the fibrin glue) to fixate the rate.93
tissues used to close the defect is gaining popularity involving Grading of conjunctival inflammation83 in pterygium
lesser postoperative pain, and lesser surgery time and lesser recurrence is:
recurrence rate as well (5.3%).66 • Grade 1—Normal
Without covering the defect, adjunctive treatment such as • Grade 2—Fine episcleral vessels present but no fibrous
β radiation,47,67,68 thiotepa44 mitomycin C,54,69-74 5-fluoro- tissue
uracil,75 cyclosporine A76 or daunorubicin77 is used with the • Grade 3—Fibrovascular tissue reaching the limbus
aim to achieve a lesser recurrence rate. It is to be remembered • Grade 4—Fibrovascular tissue invading the cornea.
that these adjunctive treatments are associated with
Medical management: Early stages of pterygium may be
complications71,72,78,79 such as:
managed with refractive correction. Topical lubricants may be
• Poor epithelial healing,
helpful. Associated inflammation may warrant use of topical
• Superficial punctate keratitis,
anti-inflammatory therapy.
• Late-onset scleral ulceration
• Microbial infection Surgical management:
• Glaucoma
Excision of pterygium: Excision techniques described include
• Endophthalmitis.
the following:
The aggressive nature of recurrences, increased size and
• Avulsion technique94,95 (initial dissection of the body from
speed of regrowth, higher incidence of symblepharon serve
the underlying sclera and avulsion of the head of the
as a reminder to exercise caution, to the treating physician.
pterygium by grasping it with a broad forceps and applying
Conjunctival autografting has been widely adopted in the
countertraction to assist shearing it off from the cornea).
management of pterygium with a reduced recurrence
• Superficial keratectomy (sharp dissection starting at the
rate.51,55,80,81 However concerns remain over issues revolving
head, to achieve better smoothness and clarity of the
around whether conjunctival autografts are to be reserved for
cornea).
recurrent pterygia because of the risk of compromising the
normal ocular surface architecture which might affect the Closure Methods:
outcome of glaucoma filtering surgery if required later.51 While • Bare scleral closure: This technique involves removal of the
dealing with pterygia with increased width, multiple heads, pterygium excision of some bulbar conjunctiva nasally,
leaving the defect to heal from the surrounding conjunctiva. Complications of Pterygium Surgery
This is the quickest method and other adjunctive
Intraoperative:
postoperative therapy such as mitomycin, beta irradiation • Corneal/scleral thinning following extensive dissection or
and thiotepa might be used along with this. Recurrence excessive cautery
rates range to as high as 80 percent in this technique. • Medial rectus muscle injury
• Simple conjunctival closure: This technique involves excision • Bleeding
of the pterygium with minimal conjunctival tissue removal • Globe perforation
and closure of the conjunctival defect with sutures leaving • Damage to canalicular system
very little or no bare sclera. Recurrence rates range from • Reverse application of conjunctival graft.
45 to 70 percent in this method.
Postoperative:
• Sliding conjunctival flaps: This technique involves closing the • Recurrence
defect after pterygium excision using inferior/superior • Corneal/scleral necrosis (Figs 6.8.1.12 to 6.8.1.14)
conjunctival sliding flaps. Reported recurrence rates range • Endophthalmitis
from 1 to 5 percent with minimal complications such as
flap retraction and cyst formation.
• Conjunctival autografts: This involves closure of the defect
with free conjunctival autograft from the superotemporal
limbus. Reported recurrence rates range from 2 to 40
percent. This technique involves a longer surgical time and
greater ocular surface disruption. This is the most widely
performed and accepted method in recent times.
• Lamellar corneal transplants: Few studies have reported the
pterygium excison and closure of bare sclera with lamellar
sclera or cornea. Recurrence rates range from 6 to 30
percent. This method involves a more complex surgical
method with risk of infectious disease transmission and is
not widely practiced.
• Other methods: Other described methods include:
– Pterygium removal with transposition of the head of
the pterygium
– Split skin grafts
– Cautery
– Excimer laser treatment
– Conjunctival autorotation grafts
– Limbal conjunctival autografts and
– Amniotic membrane grafts.
Adjunct therapies in pterygium management include:
• Use of intraoperative mitomycin application (0.2 mg/ml
for three minutes)
• Postoperative mitomycin (0.4 or 0.2 mg/ml four times daily
for 4–14 days)
• Postoperative thiotepa drops (1:2000 three hourly for six
weeks)
• Postoperative beta irradiation (15 Gy in either single or Figs 6.8.1.12A and B: Scleral melt following pterygium excision
divided doses). (A) and upon healing (B)
• Scleritis
• Keratitis
• Inclusion cyst
• Pyogenic granuloma
• Dellen
• Persistent astigmatism
• Persistent epithelial defect.
Nutritional Eye Disease

Vitamin A deficiency (VAD) is a systemic disease affecting
cells and organs throughout the body with resultant changes
in epithelial architecture that have been termed “keratinizing
metaplasias.”96 The main cause of nutrition related ocular
morbidity in developing nations is due to VAD that occurs
Fig. 6.8.1.13: Corneal melt following pterygium excision due to dietary insufficiency as a result of malnutrition. Acute
VAD is commonly seen to occur in poor socioeconomic
children due to acute infections such as measles, which presents
with severe pneumonia and diarrhea. Bottle fed babies, feeding
with dilute cow’s milk, improper weaning practices are some
of the common associations known to precipitate acute VAD
in developing nations. Other reasons for VAD include
congenital liver disease and phenylketonuria. In developed
countries, VAD occurs due to alcoholism, liver disease,
malabsorption and self imposed dietary restrictions. The
WHO and UNICEF recommend vitamin A supplementation
in management of measles cases in populations among whom
vitamin A deficiency is known to be a problem or measles
case-fatality rates exceed 1 percent.96
Vitamin A Metabolism
Vitamin A, or retinol, is a fat-soluble vitamin occurring in the
liver (fish liver), egg yolk and dairy products.
Carotenoids, provitamin A precursors, that can be
converted to retinol in the intestine are found in green leafy
vegetables, red palm oil, yellow fruits, etc. Carotenoids are
biologically less active than retinol, with their dietary sources
being less efficiently processed and absorbed from the gut
(approximately six times as much provitamin-β-carotene (by
mass) as retinol must be ingested to obtain an equivalent effect).
The ingested retinol is absorbed in the small intestine,
transported to the liver, and stored as retinyl palmitate
(Fig. 6.8.1.15). It is circulated in the bloodstream as retinol
along with a carrier protein, retinol-binding protein (RBP),
(the complex being termed as the holo-RBP) and in the serum,
the RBP-retinol complex combines with transthyretin, (a large
Figs 6.8.1.14A and B: Corneal melt with perforation and iris
protein also synthesized in the liver).
prolapse following pterygium excision for which corneal patch graft For utilization in the target cells (such as retinal
has been performed photoreceptors, epithelial linings throughout the body), retinol
is extracted from the serum. In the event of excess vitamin A Children with borderline, marginal intake tend to have
intake beyond requirements (180 to 450 μg/day of retinol or limited liver reserves, with any sudden decrease in intake, (due
its equivalent), it is stored in the liver with the liver reserves to change in diet, impaired absorption as in gastroenteritis, or
being released to maintain serum retinol at a normal level (well sudden increase in metabolic demand as in febrile conditions
above 0.7μ mol/liter or 200 μg/liter). notably measles or growth spurt) results in acute VAD
Chronic vitamin A deficiency depletes liver stores with precipitating blinding xerophthalmia, sepsis and death. In the
resultant low serum retinol levels, thereby impairing cellular scenario of high liver retinol reserves, it might take several
function, and resulting in abnormal differentiation (e.g. months for this to occur. Severely malnourished, protein-
xerophthalmia) and other physiological consequences and deficient children synthesize RBP at a much reduced rate with
clinical manifestations of deficiency (e.g. anemia, impaired low serum retinol levels, and hence even with sufficient liver
resistance to infection). The duration of inadequate intake reserves, may present with VAD. Storage of retinol and
required to precipitate clinical vitamin A deficiency state synthesis of RBP is also poor in diseased liver.
depends on: Under carefully controlled conditions of depletion,
• The amount of vitamin A (or precursor) ingested; physiological consequences of vitamin A deficiency, such as
• The extent of pre-existing liver stores; and impaired dark adaptation or abnormal conjunctival epithelial
• The rate at which vitamin A is being utilized by the body. differentiation (determined by impression cytology), generally
Fig. 6.8.1.15: Schema of vitamin A metabolism (This figure has been reproduced with the permission of the World Health Organization
from vitamin A deficiency and its consequences - A field guide to their detection and control. Alfred Sommer (Au), 3rd edition, WHO
Publication, 1995, page 4. Copyright notice March 2011; WHO website URL: http://www.who.int/nutrition/publications/micronutrients/
vitamin_a_deficiency/9241544783/en/; accessed on the 9th March, 2011)
begin to occur at levels below 1.0 μmol/liter, and with xerosis in a child less than six years of age is considered a
xerophthalmia manifestations are seen to occur, especially strong sign of VAD. Majority of nasal Bitot’s spots in children
below 0.7 μmol/liter or 200 μg/liter). They tend to be more less than six years tend to resolve with treatment compared to
frequent and of higher severity at levels below 0.35 μmol/ those in children over 10 years of age.97
liter.96 Among vitamin-A-deficient populations, children with The best way to differentiate between active and inactive
measles, respiratory disease, diarrhea, or significant protein- lesions is the response to vitamin A therapy. Active conjunctival
energy malnutrition should be suspected of being deficient xerosis and Bitot’s spots resolve within 2 to 5 days of vitamin
and treated accordingly. Uncomplicated, gradual depletion of A therapy. Most will disappear within 2 weeks, but temporal
vitamin A stores results in xerophthalmia of increasing severity, lesions tend to persist, in shrunken form, for months.96
manifesting as night blindness, conjunctival xerosis and Bitot’s Removal of Bitot’s spots does not help as they tend to reform
spot, corneal xerosis, and corneal ulceration/keratomalacia. usually. It is to be noted that severe ocular morbidity can occur
Classification of xerophthalmia
even in the absence of signs of xerosis and the sequence may
not be followed in all cases.97
XN Night blindness
X1A Conjunctival xerosis Corneal xerosis: Lack of normal corneal lustre with dryness,
X1B Bitot’s spots superficial punctate keratitis commonly seen in the inferior
X2 Corneal xerosis
X3A Corneal ulceration Keratomalacia < 1/3 corneal surface and inferonasal region of the cornea progressing to involve
X3B Corneal ulceration Keratomalacia ≥ 1/3 corneal surface the entire corneal surface is seen.
XS Corneal scars Corneal changes commence even before they become
XF Xerophthalmic fundus
apparent on observation. Early cases of corneal xerosis present
(This table has been reproduced from the Table on Classification with punctate lesions on slit-lamp biomicroscopy only, while
of Xerophthalmia, with the permission of the World Health in more severe disease the punctate lesions become numerous,
Organization from Vitamin A deficiency and its consequences—A
field guide to their detection and control, Alfred Sommer (Au), 3rd
spreading upwards over the central cornea, and the corneal
edition, WHO Publication, 1995, page 8, copyright notice March stroma becoming edematous. Thick, keratinized plaques
2011; WHO website URL: http://www.who.int/nutrition/publications/ resembling Bitot’s spots may form on the corneal surface, in
micronutrients/vitamin_a_deficiency/9241544783/en/; accessed on
the 9th March, 2011)
the interpalpebral zone. With treatment, these corneal plaques
(One international unit (IU) of vitamin A = 0.3 mg of retinol, 0.55 peel off, sometimes leaving a superficial erosion. Corneal
mg of retinyl palmitate/0.6 mg of b-carotene/1.2 mg of other xerosis responds within 2–5 days to vitamin A therapy, with
provitamin A carotenoids); (Biochemical criteria for VAD: Plasma
the cornea regaining its normal appearance in 1 to 2 weeks.96
≤ vitamin A 10 μg/dl)
The ocular presentations of vitamin A deficiency include:96,97 Corneal ulceration and keratomalacia: Corneal ulceration in
VAD is seen classically as round or oval "punched-out" defects,
Conjunctival xerosis: The temporal interpalpebral part of the in the setting of a xerotic cornea. More than one ulcer might
conjunctiva is commonly involved in xerosis with features of be present, with most being confined to the periphery of the
dryness, lack of wettablity, thickening, wrinkling, and cornea, especially its inferior and nasal aspects. The ulceration
pigmentation. Xerotic areas stain with lissamine green or Rose may be shallow, but is commonly deep. Deep ulcers tend to
Bengal dye. Conjunctival epithelium undergoes change to perforate and heal with peripheral adherent leucoma
keratinized squamous epithelium. Conjunctival xerosis is a formation. Superficial ulcers often heal with scarring.
“soft sign” in VAD diagnosis, but is reliable when it is noted Keratomalacia is characterized by rapidly progressive,
to extend into the inferior palpebral conjunctival region. localized melt involving entire corneal thickness. It begins as
Conjunctival xerosis commonly occurs in preschool children. an opaque, gray lesion and in severe diseases is seen as
Bitot’s spots: Bitot’s spots appear as light-gray plaques with sloughing necrotic stroma resulting in a large ulcer or
foamy surface, in the temporal or nasal interpalpebral bulbar descemetocele, with perforation and heals as a dense, white,
conjunctiva, and are frequently bilateral and represent areas adherent leukoma.
of conjunctival keratinization, acanthotic thickening and loss Secondar y infection might also occur. Conjunctival
of goblet cells (signs of xerosis). The foamy appearance is congestion may occur secondary to corneal ulceration. In cases
due to the combination of bacteria (Corynebacterium xerosis) of acute VAD presenting with corneal melts, conjunctival
and mucus and keratin. Bitot’s spots along with conjunctival xerosis may not be seen and may precede the appearance of
night blindness. Keratomalacia due to vitamin A deficiency as severely malnourished. History of a recent precipitating
an important cause of preventable corneal opacification has a episode of pneumonia, measles, gastroenteritis, or tuberculosis,
reported percentage varying between 8 percent and 27.3 is common, and the mortality is high if untreated.
percent.98
Corneal scars (Fig. 6.8.1.16) are seen in cases of healed Treatment
corneal ulcerations and may be varying density scars (nebula,
The frequency of vitamin A administration depends on the
macula, leukoma), staphyloma, descemetocele, or phthisis bulbi
condition being treated. Xerophthalmia is a medical emergency
(due to perforation with extrusion of intraocular contents).
with a high risk of corneal destruction and blindness, and/or
Night blindness: Retinol is essential for the elaboration of sepsis and death. Effective therapy requires:
rhodopsin in the rods which are the sensory retinal receptors • Prompt recognition of affected children with active disease;
responsible for vision in dim light conditions. Vitamin A • Immediate administration of massive doses of vitamin A;
deficiency affects rhodopsin production, impairs rod function, • Concomitant treatment of underlying systemic illnesses
hence produces night blindness. Night blindness is generally and protein-energy malnutrition; and
the earliest manifestation of vitamin A deficiency. It becomes • Prevention of recurrence.
evident in cases with mild affection only after photic stress. Prompt administration of massive amounts of vitamin A
Night blindness responds rapidly, usually within 24 to 48 hours, is essential. Oral administration is preferred as it is safe, cheap,
to vitamin A therapy. and highly effective.
Xerophthalmic fundus: The small white retinal lesions described Treatment Schedule for Xerophthalmia
in some cases of vitamin A deficiency are accompanied by
constriction of the visual fields and disappears within 2 to 4 Timing Dosage
Immediately upon diagnosis 66 mg of retinyl acetate or
months in response to vitamin A therapy.
110 mg of retinyl palmitate
General pattern of xerophthalmia: The prevalence of milder (2 lakh IU) orally
manifestations of xerophthalmia (night blindness and vitamin- Next day 66 mg of retinyl acetate or
A-responsive Bitot’s spot and conjunctival xerosis) increases 110 mg of retinyl palmitate
from the age of 2 to 8 years. Malnutrition, is usually mild. (2 lakh IU) orally
Children suffering from severe forms of VAD with corneal Within 1–4 weeks 110 mg retinyl palmitate/66
involvement are younger (often 1–4 years of age), and more whenever mg retinyl acetate (200,000
clinical deterioration IU) oral.
occurs,
Every 2–4 weeks, in the
presence of persistent
kwashiorkor.
Other Considerations:
• Children 6–11 months of age/< 8 kg body weight should
receive half the dose
• Children < than 6 months: one-quarter of the dose
• Intramuscular injection of 55 mg water-miscible retinyl
palmitate (1 lakh IU) is given in children with severe
stomatitis who cannot swallow/severe persistent vomiting/
gastroenteritis/severe malabsorption (as in cystic fibrosis)
that prevents an adequate response. (Oil-miscible
preparations are not to be given by injection as they are
poorly absorbed from the injection site).
Fig. 6.8.1.16: Corneoiridic scarring due to healed Very large doses of vitamin A are teratogenic, particularly
keratomalacia with perforation early in pregnancy, and treatment of xerophthalmia in women
of reproductive age mandates, modification of the standard Estimated mean requirement and safe levels of intake for vitamin A99
regimen. Mean requirement Recommended safe intake
For night blindness or Bitot's spots, 55 mg retinyl palmitate Group (mg RE/day) (mg RE/day)
(10,000 IU vitamin A) should be administered daily for 2 days.96 Infants and children
0–6 months 180 375
For breast fed infants with VAD, vitamin A therapy may be 7–12 months 190 400
administered to the mothers. Proper weaning advice is also to 1–3 years 200 400
4–6 years 200 450
be given. Treating physician should be aware of hyper- 7–9 years 250 500
vitaminosis induced benign intracranial hypertension which Adolescents
manifests with incessant crying and vomiting in infants. 10–18 years 330–400 600
Vitamin A rich diet (fish and animal livers, fish-liver oil, Adults
egg yolk, dairy products, etc) or β-carotene (lightly cooked Females
19–65 years 270 500
green leafy vegetables, red palm oil, and red-, yellow-, and 65+ years 300 600
orange-colored fruits, such as papaya and mango), with Males
Pregnant women
300
370
600
800
addition of small amount of edible oil to enhance the Lactating women 450 850
absorption of β-carotene, is to be advised. (The following conversion factors are used to calculate comparable values
as mg:
High risk groups: All cases of measles in populations in 1 IU retinol = 0.3 mg retinol
which VAD is known to occur, or where measles case-fatality 1 IU β-carotene = 0.6 mg β-carotene
1 IU retinol = 3 IU β-carotene)
rates exceed 1 percent, should receive the same initial treatment
as xerophthalmia.96 Children with severe, complicated, life-
Surgical management: Optical iridectomy may suffice to
threatening measles and all children with measles who are
restore useful vision in cases with peripheral adherent
under 2 years of age should be considered for vitamin A
leukomas, especially in the developing nations where the
therapy even if they do not come from a “high-risk”
demand for donor tissue is high and patient compliance to
population.96 (The official WHO/UNICEF recommendation
follow-up after keratoplasty is not optimal. Severe corneo-
for treating measles is a single dose rather than two successive
iridic scars will require optical penetrating keratoplasty.
doses).
Therapeutic corneal grafting may be required to restore the
Children affected with severe protein-energy malnutrition
tectonoid integrity of the eye in cases of severe keratomalacia,
or illness (chronic or recurrent diarrhea, lower respiratory
but success of keratoplasty in keratomalacia is not very
disease, acute otitis) and hailing from communities in which
encouraging.98
VAD is prevalent, should receive vitamin A therapy appropriate
to their condition and age. The underlying illness requires
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28. Ozdemir M, Cinal A. Early and late effects of pterygium surgery 50. Said A, Fouad ARA, Mostafa MSE, et al. Surgical management of
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51. Kenyon KR, Wagoner MD, Hettinger ME. Conjunctival autograft 70. Hayasaka S, Noda S, Yamamoto Y, et al. Postoperative instillation
transplantation for advanced and recurrent pter ygium. of low-dose mitomycin C in the treatment of primary pterygium.
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52. Lewallen S. A randomized trial of conjunctival autografting for 71. Frucht-Pery J, Ilsar M, Hemo I. Single dosage of mitomycin C for
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53. Singh G, Wilson MR, Foster CS. Long-term follow-up study of 1994;13:411-3.
mitomycin eye drops as adjunctive treatment for pterygia and its 72. Rachmiel R, Leiba H, Levartovsky S. Results of treatment with
comparison with conjunctival autograft transplantation. Cornea topical mitomycin C 0.02 percent following excision of primary
1990;9:331-4. pterygium. Br J Ophthalmol 1995;79:233-6.
54. Starck T, Kenyon KR, Serrano F. Conjunctival autograft for primary 73. Cano-Parra J, Diaz-Llopis M, Maldonado MJ, et al. Prospective
and recurrent pter ygia: surgical technique and problem trial of intraoperative mitomycin C in the treatment of primary
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55. Allan BD, Short P, Crawford GJ, et al. Pterygium excision with 74. Mahar PS. Conjunctival autograft versus topical mitomycin C in
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57. Figueiredo RS, Cohen EJ, Gomes JA, et al. Conjunctival autograft postoperative recurrence of pterygium. Yan Ke Xue Bao
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Ophthalmic Surg Lasers 1997;28:99-104. 77. Dadeya S. Kamlesh Intraoperative daunorubicin to prevent the
58. Rao SK, Lekha T, Mukesh BN, et al. Conjunctival autograft for recurrence of pterygium after excision. Cornea 2001;20:172-74.
primary and recurrent pterygia: technique and results. Indian J 78. Tarr KH, Constable IJ. Late complications of pterygium treatment.
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59. Jap A, Chan C, Lim L, Tan DT. Conjunctival rotational autograft 79. Dougherty PJ, Hardten DR, Lindstrom RL. Corneoscleral melt
for pterygium. An alternative to conjunctival autografting. after pterygium surgery using a single intraoperative application
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60. P Luanratanakorn, T Ratanapakorn, O Suwan-apichon, RS Chuck. 80. Alaniz-Camino F. The use of postoperative beta radiation in the
Randomised controlled study of conjunctival autograft versus treatment of pterygia. Ophthalmic Surg 1982;13:1022-5.
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2006;90(12):1476-80. on pterygium recurrence in a controlled trial comparing conjunctival
61. Laughrea PA, Arentsen JJ. Lamellar keratoplasty in the management autografting with bare sclera excision. Arch Ophthalmol
of recurrent pterygium. Ophthalmic Surg 1986;17:106-08. 1997;115:1235-40.
62. Busin M, Halliday BL, Arffa RC, et al. Precarved lyophilized tissue 82. Solomon A, Pires RTF, Tseng SCG. Amniotic membrane
for lamellar keratoplasty in recurrent pterygium. Am J Ophthalmol transplantation after extensive removal of primary and recurrent
1986;102:222-27. pterygia. Ophthalmology 2001;108:449-60.
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Ophthalmol 1992;1:114-16. conjunctival autografts, amniotic membrane grafts, and primary
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application of Er:YAG laser for the treatment of pterygium. 84. Shimazaki J, Shinozaki N, Tsubota K. Transplantation of amniotic
Ophthalmic Surg Lasers 2000;31:8-12. membrane and limbal autograft for patients with recurrent
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66. Koranyi G, Seregard S, Kopp (Eds). Cut and paste: a no suture, 86. Shimazaki J, Kosaka K, Shimmura S, et al. Amniotic membrane
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15. patients with complicated pterygium. Hunan Yi Ke Da Xue Xue
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23. Organization 2004.
6.8.2 Tear Film Dysfunction—Dry Eye Disease

Rakhi Kusumesh, Shweta S Agarwal, Geetha Krishnan Iyer, M Vanathi
Dry eye disease (Fig. 6.8.2.1) is a common multifactorial eye increased with age, male sex, current smoking history,
problem with increasing worldwide prevalence. The study of ophthalmic surgeries, contact lens wear and with coexisting
dry eye disease is a rapidly expanding field which requires the ocular conditions like meibomian gland dysfunction,
ophthalmologist to stay abreast with not only newer pterygium, blepharitis, and conjunctival disease. Dry eye disease
management modalities but also diagnostic challenges that is more frequently found in patients with arthritis, thyroid
mimic, coexist and aggravate dry eye. It is a disorder that affects dysfunction and poor general health.1
all age groups thereby causing considerable impact on the
health sector both in terms of manpower and finances, due
to the loss in quality of life.
EPIDEMIOLOGY
The prevalence of dry eye has not been determined accurately
due to the lack of a single definition of the condition as well
as the variability of criteria included in several studies. However,
the large number of studies carried out in various countries
estimate the prevalence of dry eye disease to be between 5-34
percent. The Beaver Dam Study demonstrated an incidence
of dry eye of 13.3 percent that significantly correlated with
patient age.1 Dry eye was apparently higher in women (14.7%)
than men (11.7%).2 Approximately, 4.3 million Americans
suffer from dry eye disease and up to 7-10 million self-medicate
with artificial tear substitutes.3 Being a heterogeneous group
of conditions with multifactorial etiologies, prevalence varies Fig. 6.8.2.1: Slit-lamp biomicroscopic
with the many subcategories of the disease. Prevalence of dry picture of dry ocular surface
DEFINITION PATHOPHYSIOLOGY
In 1995, the National Eye Institute defined dry eye4 as: “a Changing Concepts Over the Years
disorder of the tear film due to tear deficiency or excessive
evaporation, which causes damage to the interpalpebral ocular • Aqueous tear deficiency
surface and is associated with symptoms of ocular discomfort”. • Mucin-deficient dry eye
This definition is more clinically oriented with not much • Concept of ocular surface as a biological continuum
emphasis on the pathogenetic mechanisms or the events that • Meibomian gland dysfunction
occur in response to dry eye. • Hormonal imbalance
Keeping in pace with the progress in the understanding • Inflammation—Although the exact place of inflammation
and knowledge of the pathophysiology of dry eye over the in the cascade of events is not clear, its role in the
years, and its impact on the visual function, the Dry Eye pathogenesis is unmistakable.
Workshop (DEWS) in 2007 decided to improvise the definition
Factors in the Pathogenesis
as follows:5 “Dry eye is a multifactorial disease of the tears
of Dry Eye Disease
and ocular surface that results in symptoms of discomfort,
visual disturbance and tear film instability with potential • Genetic predisposition
damage to the ocular surface. It is accompanied by increased • Systemic autoimmune disorder
osmolarity of the tear film and inflammation of the ocular • Viral infections affecting lacrimal gland (Epstein-Barr,
surface.” cytomegalovirus, human immunodeficiency virus,
The term Lacrimal Functional Unit (LFU),6,7 implicates hepatitis C)
the integrated system comprising the lacrimal glands, ocular • Neurotrophic keratitis
surface (cornea, conjunctiva), eyelids, the meibomian and • Hormonal insufficiency:
accessory lacrimal glands, and the sensory and motor nerves – Age related
that connect them. This gives a more unified concept that – Menopause
explains the pathophysiology of ocular surface disorders. – Androgen insufficiency
The overall and ultimate function of this unit is to maintain • Age related atrophy of lacrimal gland
the clarity of the cornea and thereby the quality of the • Insufficiency of spread of tears (conjunctivochalasis)
image projected onto the retina. The definition of dry eye • Iatrogenic
could therefore also be framed as: “A disorder whereby – LASIK
dysfunction of the lacrimal functional unit causes an – Contact lens
unstable tear film which in turn promotes ocular surface – Medications—systemic/topical
inf lammation, epithelial disease and symptoms of • Video display terminal
discomfort.” • Environmental stress.
On the basis of pathophysiology and clinical presentation,
the DELPHI panel suggested that the term dry eye does not Causes for Ocular Surface
reflect all the events occurring in the eye and hence Damage in Dry Eye Disease
recommended dysfunctional tear syndrome (DTS) as a more Traditionally, the tear film has been described as three layered,
appropriate term for this disease.7,8 namely—the innermost mucin, aqueous in between and the
However, the term dry eye is so embedded in medical outermost lipid layer.10 However, this concept has been revised
literature and lay writing that the term DTS has been replaced substantially with the new concept of the tear-ocular surface
by dry eye disease (DED).9 structure being that of a metastable tear film consisting of an
Considering dry eye as a sole deficiency of one of the aqueous gel with a gradient of mucin content decreasing from
components of the tear film trivializes the complexity of the the ocular surface to the undersurface of the outermost lipid
condition and its impact on the ocular surface health. layer. This system forms a finely regulated, interdependent
zone of interaction, changes in any one of which inevitably • Patient related

leads to breakdown in the other, leading to a vicious cycle of – Visual effects, rapid tear breakup time leading to
damage.4 The causes for ocular surface damage are: increased blink rate and degradation of image
1. Unstable tear film (due to): – Symptom related, subjective distress ultimately leading
– Mucin deficiency (cicatricial conjunctival disorders). to ocular fatigue.
Loss of the mucin layer leads to the shearing off of
the epithelial cells causing ocular surface irritation and CLASSIFICATION
inflammation in case of persistence of the pathology.
– Evaporative loss due to lipid deficiency (meibomian The International Dry Eye Workshop (DEWS) recently
gland dysfunction) developed a 3-part classification of dry eye, based on etiology,
– Mechanical cause leading to inadequate spread of tears. mechanisms and disease stage.7
2. Hyperosmolarity of tears: Chronic hyperosmolar stress The classification system, which is updated as an
leads to dessicative damage of the ocular surface. etiopathogenic classification by the DEWS Subcommittees,
Hyperosmolar tears act as toxic agents towards the formulated by the National Eye Institute (NEI)/Industry Dry
conjunctival and corneal epithelia both by direct osmotic Eye Workshop Report in 1995, distinguishes 2 main categories
mechanism and by mediated inflammatory activity. (or causes) of dry eye states, as follows: an aqueous deficiency
3. Blink-related microtrauma: The shearing effect caused state and an evaporative state. 4
by the movement of the upper lid over the cornea in the Deficient aqueous production can be further classified
presence of decreased lubrication causes exfoliation of as follows:
cells with exposure of the deeper layer of cells devoid of Non-Sjögren syndrome
microvilli leading to instability of tear film. • Primary lacrimal gland deficiencies
4. Loss of corneal sensation: In the normal state, subthreshold – Idiopathic
sensory input from the ocular surface modulates secretory – Age-related dry eye
activity via the efferent sympathetic and parasympathetic – Congenital alacrima (e.g. Riley-Day syndrome)
innervation of the lacrimal and meibomian glands. The – Familial dysautonomia.
individual is usually unaware of the nerves sensing the • Secondary lacrimal gland deficiencies
environment. A suprathreshold sensory event makes the – Lacrimal gland infiltration
individual painfully aware of the nerves being activated. – Sarcoidosis
This is due to a number of involuntary reflexes being – Lymphoma
activated which include reflex lacrimation, a cardiovascular – AIDS
reflex, the blink reflex and the Bell's phenomenon, which – Graft vs host disease
are all nonsuppressible and serves to protect the eye from – Amyloidosis
potential danger. The heightened sensation seen in – Hemochromatosis
punctate corneal epitheliopathy due to tear breakdown is – Lacrimal gland infectious diseases
probably due to the disruption of the tight junctions in – HIV diffuse infiltrative lymphadenopathy syndrome
the apical cell layer of the epithelium that allows greater – Trachoma
access of the environmental stimuli to the sensory nerve – Systemic vitamin A deficiency (xerophthalmia)—
endings. Thus, under stressful conditions, the otherwise Malnutrition, fat-free diets, intestinal malabsorption
intact neural loop, gets disrupted. from inflammatory bowel disease, bowel resection or
5. Inflammation: Either primary as a part of the underlying chronic alcoholism
disorder or secondary to all above mentioned factors, – Lacrimal gland ablation
inflammation ultimately forms the most important – Lacrimal gland denervation.
causative and resultant factor. • Lacrimal obstructive disease
– Trachoma
Final Outcome of Dry Eye Disease – Ocular cicatricial pemphigoid
• Ocular surface related – Erythema multiforme and Stevens-Johnson syndrome
– Punctate epitheliopathy – Chemical and thermal burns
– Erosions – Endocrine imbalance
– Epithelial defect. – Postradiation fibrosis.
• Medications—Antihistamines, beta-blockers, phenothiazines, – Hypersecretory—Meibomian seborrhea

atropine, oral contraceptives, anxiolytics, antiparkinsonian – Hyposecretory—Retinoid therapy
agents, diuretics, anticholinergics, antiarrhythmics, topical – Obstructive—Simple, primary or secondary to local
preservatives in eye drops, topical anesthetics, and disease (e.g. anterior blepharitis), systemic disease (e.g.
isotretinoin. acne rosacea, seborrheic dermatitis, atopy, ichthyosis,
• Reflex hyposecretion—Reflex sensory block and reflex psoriasis), syndromes (e.g. anhidrotic ectodermal
motor block dysplasia, ectrodactyly syndrome, Turner syndrome),
– Neurotrophic keratitis—Fifth nerve/ganglion section/ and systemic toxicity (e.g. 13-cis retinoic acid,
injection/compression polychlorinated biphenyls); or cicatricial, primary or
– Corneal surgery—Limbal incision (e.g. extracapsular secondary to local disease (e.g. chemical burns,
cataract extraction), keratoplasty, refractive surgery (e.g. trachoma, pemphigoid, erythema multiforme, acne
PRK, LASIK, RK) rosacea, VKC, AKC).
– Infective—Herpes simplex keratitis, herpes zoster • Low blink rate
ophthalmicus – Physiological phenomenon, such as during
– Topical agents—Topical anesthesia performance of tasks that require concentration (e.g.
– Systemic medications—Beta blockers, atropine-like working at a computer or a microscope)
drugs – Extrapyramidal disorder, such as Parkinson disease
– Chronic contact lens wear (decreasing dopaminergic neuron pool).
– Diabetes • Disorders of eyelid aperture and eyelid/globe congruity
– Aging – Exposure (e.g. craniostenosis, proptosis, exophthalmos,
– Cranial nerve VII (CN VII) damage high myopia)
– Multiple neuromatosis – Lid palsy
– Ectropion
Sjögren syndrome – Lid coloboma.
• Primary [no associated connective tissue disease (CTD)] • Drug action (e.g. Accutane)
• Secondary (associated CTD)
– Rheumatoid arthritis Extrinsic causes
– Systemic lupus erythematosus • Vitamin A deficiency
– Progressive systemic sclerosis (scleredema) – Development disorder of goblet cells
– Primary biliary cirrhosis – Lacrimal acinar damage.
– Interstitial nephritis • Topical drugs and preservatives (surface epithelial cell
– Polymyositis and dermatomyositis damage)
– Polyarteritis nodosa • Contact lens wear
– Hashimoto thyroiditis • Ocular surface disease (e.g. allergy).
– Lymphocytic interstitial pneumonitis Classification of dry eye on the basis of mechanisms
– Idiopathic thrombocytopenic purpura includes tear hyperosmolarity and tear film instability.
– Hypergammaglobulinemia For a classification of dry eye on the basis of severity,
– Waldenstrom macroglobulinemia the Delphi Panel Report8 was adopted and modified as a third
– Wegener granulomatosis. component of the DEWS (Table 6.8.2.1).
Evaporative loss can be further classified as follows: DIAGNOSTIC TESTS

Intrinsic causes The tear film integrity and the health of the ocular surface are
• Meibomian gland disease extremely important in maintaining optical clarity of the
– Reduced number—Congenital deficiency, acquired cornea. Dry eye diseases could threaten the corneal clarity thus
meibomian gland dysfunction resulting in visual impairment and surface breakdown.
– Replacement—Distichiasis, distichiasis lymphedema Currently, there are no uniform criteria for diagnosis of dry
syndrome, metaplasia eye, combination of diagnostic tests are used to asses
– Meibomian gland dysfunction symptoms and clinical signs. Recognition of the underlying
Table 6.8.2.1: Dry eye classification based on severity

Dry eye severity level 1 2 3 4
Discomfort, severity Mild and/or episodic; Moderate episodic or Severe frequent or Severe and/or disabling
and frequency occurs under chronic, stress or constant without stress and constant
environmental stress no stress
Visual symptoms None or episodic Annoying and/or activity- Annoying, chronic and/or Constant and/or possibly
mild fatigue limiting episodic constant, limiting activity disabling
Conjunctival injection None to mild None to mild Mild to moderate Marked
Conjunctival staining None to mild Variable Moderate to marked Marked
Corneal staining None to mild Variable Marked central Severe punctate erosions
(severity/location)
Corneal/tear signs None to mild Mild debris, decreased Filamentary keratitis, Filamentary keratitis,
mucus meniscus mucus clumping, mucus clumping, increased
increased tear debris tear debris, ulceration
Lid/meibomian glands MGD variably present MGD variably present Frequently present Trichiasis, keratinization,
symblepharon
TFBUT (sec) Variable ≤10 ≤5 Immediate
Schirmer score Variable ≤10 ≤5 ≤2
(mm/5 min)
(Reproduced with permission from "The definition and classification of dry eye disease: Report of the Definition and Classification sub-
committee of the International Dry Eye Workshop.” Ocular Surface 2007;5:163-178)
condition is therefore of paramount importance. This requires received in the past should be noted as also the perceived
a thorough history taking and examination. A number of response of the patient to the prescribed medications.
questionnaires are available for evaluation of dry eye disease a. Patient symptoms: Dry eye symptoms remain an important
symptomatology, including severity, effect on daily activities parameter of dry eye examination, although symptoms
and quality of life. alone are inadequate for differential diagnosis of dry eye,
because the same symptoms can be experienced with a
HISTORY TAKING range of ocular surface conditions and tear film disorders.11
Patients will use a myriad of terms to describe their
History taking is often ignored in an ophthalmic evaluation symptoms—dryness, grittiness, burning, itching, foreign
for various reasons and especially due to the misplaced reliance body sensation, redness, tiredness, inability to keep the
on the ability of the slit-lamp biomicroscope to detect the eye open and tearing. Tearing can be associated with dry
cause of the patient's problem. However, history taking forms eye states, though paradoxical, due to the reflex tearing.
an integral part of the ocular examination in dry eye and often Drying of the ocular surface due to a decreased afferent
helps in revealing associated conditions that could aggravate secretion stimulates the afferent receptors on the ocular
the ocular problem. Most types of dry eye are more common surface leading to reflex secretion from the lacrimal glands
in women, especially postmenopausal. Diseases with a poor and thus causing tearing. Also, it is important to look into
prognosis such as Stevens-Johnson syndrome associated tear the diurnal periodicity. Patients with moderate dry eye tend
dysfunction usually have an abrupt onset of signs and to have more symptoms as the day progresses due to the
symptoms. Leading questions help ascertain if the condition decreased evaporation during sleep. In patients with
has progressed. Dry eye states with an underlying immune immune related dry eye, the lacrimal gland functioning is
disorder generally tends to progress relentlessly, while others subnormal on awakening. On the contrary, patients who
such as ocular cicatricial pemphigoid have a characteristic complain of symptoms primarily in the morning generally
chronic recurrent pattern. Any treatment that the patient has have meibomian gland inflammation that tends to accrue
secretions along the closed lid margins through the night CLINICAL TESTS TO EVALUATE THE
and cause maximal symptoms on awakening. A careful and LACRIMAL FUNCTIONAL UNIT
thorough clinical history is extremely useful in classifying
the etiologies of disease and directing potentially significant Tear Secretion Assessment
treatment modalities.
Schirmer's Test
b. Occupational and medical histor y: The occupational
environment of the patient forms an important aspect of Schirmer's test, originally described in 1903, remains the most
history taking. Conditions that increase evaporation from commonly used technique for assessing tear secretion. It is
the ocular surface such as constant exposure to low performed by placing a standardized sterile commercially
humidity air conditioned environment, extremely hot and available 35 × 5 mm folded (Whatman 41) filter paper strip
dry surroundings, exposure to dust or chemical fumes over the lid margin at the junction of the medial two-third
should be noted. A number of drugs could aggravate the and lateral one-third of the lower lid. Aqueous tear production
dry eye state. A few of these include antitussives, is measured by the millimeters wetted during the test period,
antihypertensives, antihistamines, decongestants and usually 5 minutes.
antidepressants. Schirmer’s 1: < 5 mm at 5 minutes is considered abnormal.
c. Associated systemic disorders: A number of systemic Schirmer’s 2: Is perfor med as above along with nasal
diseases can be responsible for or aggravate the dry eye stimulation using a cotton tipped applicator. A value of < 10
state. Quite often, the ophthalmologist may be the first to mm at 5 minutes is considered abnormal.
diagnose an underlying systemic disorder that presents with Abnormality in both tests is indicative of lacrimal gland
dry eye. Rheumatoid arthritis is one of the common causes dysfunction affecting both the normal and reflex tear
of dry eye and history of joint stiffness—especially secretion.
morning stiffness should be asked for. Immune Schirmer's 3: It was originally described similar to Schirmer's
dysfunctional states can alter the other secretory glands 1 along with retinal stimulation by looking at the sun and is
resulting in dry mouth and/or poor oral hygiene. no longer performed.
Meibomian dysfunction due to seborrheic dermatitis Jones basal tear secretion:12 Is performed similar to Schirmer's
(dandruff) is a common cause of tear film alteration. 1 but with application of anesthetic drop prior to placement
d. Importance of rapport building: Although history taking of the strips.
primarily serves to try and detect the presence, the severity
and associated risk factors for a dry eye, it has another Phenol Red Thread Test
important purpose. Dry eye is a relatively chronic condition
Hamano in 1982 invented phenol red thread (PRT) tear test.13
for which there is no specific cure. Since the disorder also
It consists of a cotton thread impregnated with pH indicator
has an important psychological component, it is vital for
phenol red that is inserted into the temporal side of the lower
the patient to develop trust and confidence in the treating
conjunctival sac for 15 seconds. When thread is wetted with
physician. The history taking process is a good opportunity
tears, phenol red turns from yellow to bright orange and the
for the clinician to develop a rapport with the patient. This
process also helps the physician assess the profile of the length of thread wetted measures aqueous tear production.
patient, his expectations from the treatment, and his Normal values are 9-18 mm of wetting. This test is more
understanding of the disease process. It is extremely repeatable and reliable than the Schirmer's test.14
important for the patient at the outset to clearly understand
Tear Volume Assessment
the nature of the disease, the scope of the treatment and
the symptom relief that is possible.
Tear Meniscus Height
e. All patients should be questioned regarding the use of
contact lenses. Contact lens patients should always be The lower meniscus is examined for its height, regularity, width
questioned the length of time contact lenses are worn, the and curvature. The normal tear meniscus height is 0.1-0.3 mm.
type of contact lenses and the cleaning solutions, whether The presence of mucin/debris and foam in the tear film along
the patient sleeps with the contact lenses and the timing the eyelid margin is suggestive of inflammation and meibomian
of symptoms relating to contact lens usage. gland dysfunction respectively.
Reflective meniscometry projects black and white stripes, Tear Function Index (TFI)
and measures the curvature of the lower tear meniscus, from
This test is similar to the Schirmer test with anesthesia, but
which meniscus volume can be approximately calculated.
involves the addition of 10 drops of 0.5 percent fluorescein.
Radius of tear meniscus curvature is directly proportional to
Five minutes after instillation, the length of the wetted portion
tear meniscus volume, and if the radius is less than 0.25 mm,
is measured and the intensity of dye staining is compared to
it indicates hyposecretory dry eye.15
the standard strip colors. The TFI value is equal to the value
Other noninvasive method to visualize the tear meniscus
of the Schirmer test with anesthesia divided by the TCR. The
include optical coherence tomography, strip meniscometry, and
tear clearance rate is proposed as a simple and useful way to
a device Tearscope Plus using interference phenomena.16-18
estimate basal tear turnover and tear flow, and measure tear
drainage indirectly. This can be calculated with tear
Tear Clearance Assessment
fluorophotometry after applying one drop (2%) of fluorescein
Tear Clearance Test and collecting the specimen. The decay of tear fluorescein is
recorded over a period up to 30 minutes. It shows a biphasic
The fluorescein clearance test (FCT) is a dynamic tear curve that allows calculation of tear clearance rate. Patients
functional test to reveal basic tearing, reflex tearing and tear who have aqueous tear deficiency (ATD) and delayed tear
clearance simultaneously. FCT is performed as follows: clearance will have a low TFI value.20-21
After applying one drop of 0.5 percent proparacaine to
each eye, the inferior fornix is carefully dried with tissue paper. Evaluation of Tear Film Stability
An aliquot of 5 µl of fluorescein 0.25 percent (or, dye
impregnated strips can be used) is applied in the inferior Tear Break-up Time
conjunctival cul-de-sac without directly touching the An unstable tear film is the hallmark of dry eye. Invasive and
conjunctival surface. The patient is asked to blink normally. noninvasive techniques are available to assess the stability.
Schirmer's testing is carried out for 1 minute at the end of 10, Tear film stability measured by the tear break-up time
20 and 30 minutes respectively. At the end of the 30 minutes, (TBUT) test may be the most important and practical test for
i.e. the last test, Schirmer strip is inserted after nasal stimulation diagnosing dry eye. It is performed by placing fluorescein in
with cotton tipped applicator. Clearance is defined as normal the lower conjunctival sac using a fluorescein-impregnated strip
if the dye cannot be detected at the 20-minute interval. wetted with nonpreserved saline, asking the patient to blink,
The FCT allows one to determine the following three important and measuring the interval between a complete blink and the
tear dynamic functions, i.e. basal tear secretion, reflex tear secretion first randomly appearing dry spot in the precorneal tear film.
under nasal stimulation and tear clearance at the same time. This test should be performed without topical anesthesia and
Its clinical applications are: without holding the lids. Tear break-up may be initiated by
1. To determine aqueous tear deficiency (dry eye) with higher the rupture of the mucous layer at its thinnest spots, allowing
accuracy. the aqueous to come in contact with exposed patches of
2. To differentiate dry eye into with or without reflex tearing. epithelium.22 Despite being widely applied for both clinical
Sjögren syndrome or primary lacrimal gland diseases are and research purposes, TBUT has been considered to be
characterized by the loss of reflex tearing, thus helping inaccurate and not reproducible.23
establish the severity of dry eye.
3. To guide physicians to perform punctal occlusion with Noninvasive Tear Break-up Time
plugs or permanent cauterization.
An alternative method reflects a regular pattern off the corneal
4. To determine subclinical DTS as a cause of ocular
surface and measures the time for it to distort or breakup
irritation, medicamentosa and other ocular surface
following a blink. Because no instillation of fluorescein is
disorders.
required, this test is known as the noninvasive break-up time
(NIBUT). Xeroscope, the Keeler tearscope, Placido-based
Fluorophotometry
computerized videokeratoscopy can be used for determining
Fluorophotometric techniques can also be used to quantitate the NIBUT. A value of > 10 sec is considered normal for
tear secretion and volume but is expensive and technique lacks both TBUT and NIBUT, reflects tear film instability, whereas
standardization.19 less than 5 seconds is a marker of definite dry eye.24
The tear breakup pattern for tear lipid deficiency tends to Different grading schemes for ocular surface dye staining
be linear on the inferior and central cornea compared with a have been proposed as follows, but a universal grading scheme
more random circular breakup pattern over areas of punctate is yet to be finalized.
epitheliopathy for aqueous tear deficiency. a. van Bijstervald staining: It uses rose-bengal staining of
Tear film stability analysis system: This records the consecutive the conjunctiva and cornea. It evaluates the staining on
topographic images every second for 10 seconds, thus deriving the scale of 0-3 in 3 areas, the nasal and temporal triangular
several quantification indices. There are two parameters, TMS- areas of conjunctiva and the cornea with a maximum score
BUT is a measure of the time it takes for the ocular surface to of 9. A score of greater than 3 is considered abnormal.26
change its refractive power by 0.5 diopters after each blink. TMS- b. Oxford scheme grades the conjunctiva and cornea together
BUA represent the area where the break-up time is less than or using fluorescein and rose-bengal or lissamine green stain.
equal to 5 seconds. In dry eye patients, a gradual increase in SRI It was developed to quantify epithelial damage in case of
and SAI, reduction in TMS-BUT and higher values of TMS- dry eye, uses a chart with a series of panels labeled A-E in
BUA have been reported.24,25 order of severity (absent, minimal, mild, moderate,
Lipid Layer Assessment severe).27
c. The NEI workshop grading system: It uses fluorescein to
Meibomian gland dysfunction (MGD): Biomicroscopic
grade the cornea and rose-bengal for conjunctiva. A score
recognition of pathological signs such as ductal orifice
of > 3 out of 15 and >3 out of 18 is considered abnormal
metaplasia (white shafts of thickened meibum in the orifices),
for the cornea and conjunctiva respectively.26
reduced expressibility of meibomian gland secretions,
Though no specific grading system can be considered
increased turbidity and viscosity of the expressed secretions
superior to the other, the aim is to remain consistent in
and dropout of glandular acini aids in diagnosis of MGD.
technique and grading over time.26
Ocular Surface Damage Assessment
(2) Impression Cytology: It has been useful in the
(1) Diagnostic Dye Staining: The use of dyes such as investigation of many aspects of dry eye disease such as:
fluorescein, rose-bengal, and lissamine green helps in • Pathophysiology of dry eye (degree of squamous
assessing the: metaplasia)
• Integrity of the ocular surface epithelium • Monitoring clinical trials (to evaluate efficacy of treatments)
• Protective status of the precorneal tear film. • Associating dry eye disease with other systemic conditions.
Fluorescein dye: Fluorescein staining occurs when there is (3) Tear Osmolarity: In patients with dry eye, the impaired
cellular membrane disruption or cell-cell junction loss and balance between tear secretion, evaporation and clearance
therefore is useful in assessing the intactness of the epithelial leads to an increase in tear osmolarity, which is considered
barrier. Pseudostaining may occur when fluorescein dye pools one of the major sources of discomfort, ocular surface
in indented, but healthy epithelium. damage and inflammation.
Rose-bengal dye: It not only stains devitalized epithelial cells Its cut-off value is 315.6 mOsmol/L between healthy and
but also healthy epithelial cells which are not protected by a dry eyes.28
normal mucin layer. Therefore, it has a unique property of
(4) Tear protein assays.
evaluating the protective status of the preocular tear film. This
dye is irritating so it is better to use a topical anesthetic prior (5) Corneal sensitivity: Cochet-Bonnet esthesiometer, uses
to using rose bengal dye. Rose bengal stains the conjunctiva a monofilament nylon which is extendable from 0-60 mm.
more intensely than the cornea but in severe cases of dry eye, When applied perpendicularly to the corneal surface with
it can stain the entire cornea. a bending angle of 5 degrees, this thread exerts pressures
Lissamine green: Lissamine green is a synthetic organic acid from 11-200 mg/mm2 correlating inversely with the length
dye that stains the ocular surface similar to RB without causing of the filament. Two noncontact esthesiometers have also
stinging. It detects dead or degenerated cells and causes less been described: the gas esthesiometer and the noncontact
irritation. It does not stain healthy conjunctival epithelium. esthesiometer.
Interpretation of ocular surface staining is based on two In routine clinical practice, a cotton wick can be used
factors: intensity and location. to assess the presence, or absence of corneal sensation.
Management Viscosity agent used in artificial tears include

carboxymethylcellulose, polyvinyl alcohol, propylene glycol and
The foremost objectives in caring for patients with dry eye
hydroxypropyl-guar. High viscosity agents tend to cause
disease are to improve the patient's ocular comfort and quality
blurring of vision, therefore low viscosity agents are generally
of life, and to return the ocular surface and tear film to the
preferred for mild to moderate dry eye. Preservatives in the
normal homeostatic state. Although symptoms can rarely be
artificial tears retard the growth of microbial organisms but
eliminated, they can often be improved, leading to an
also usually have toxic effects on the ocular surface. The most
improvement in the quality of life.
commonly employed preservatives are benzalkonium chloride,
There is a wide variety of phar macologic and
chlorobutanol, thimerosal and chlorhexidine, the most toxic
nonpharmacologic approaches to the management of dry eye
of which is benzalkonium chloride. Benzalkonium chloride is
disease. These approaches are best described within categories
the most frequently used preservative in topical ophthalmic
that include avoidance of exacerbating factors, eyelid hygiene,
preparations, as well as in topical lubricants. Preferred
tear supplementation, tear retention, tear stimulation, and anti-
preservatives include sodium chlorite which degrades to
inflammatory agents.
chloride ions and water upon exposure to UV light after
instillation and sodium perborate which is converted to water
Avoidance of Exacerbating Factors
and oxygen on contact with the tear film. Tear substitutes
Environmental modifications such as humidification, with preservatives are usually well tolerated in mild dry eye,
avoidance of wind or drafts and avoidance of dusty or smoky but if more frequent use is necessary, preservative free tear
environments may ameliorate dry eye symptoms. Lifestyle or substitutes are recommended.36
workplace modifications may be helpful, for example, taking In general, ointments do not support bacterial growth and,
regular breaks from prolonged reading or computer use, and therefore, do not require preservatives. Gels containing high
lowering the computer monitor below eye level so that the molecular weight crosslinked polymers of acrylic acid
gaze is directed downward.5,29-31 Increasing blink frequency29 (carbomers) have longer retention times than artificial tear
or fast blinking exercises31 have also been recommended. If solutions, but have less visual blurring effect than petrolatum
feasible, medications that exacerbate disease should be ointments.
discontinued.29 Although artificial tears can improve symptoms and
objective findings, there is no evidence that they can resolve
Eyelid Hygiene the inflammation that accompanies dry eye.
The conventional treatment of meibomian gland dysfunction Tear Retention
consists of warm compresses, lid hygiene, topical and systemic
Lacrimal outflow occlusion slows tear clearance, and is
antibiotic, topical steroids and artifical tears.
indicated in patients with aqueous-deficient dry eye. The
presence of ocular surface inflammation needs to be identified
Tear Supplementation
as inflammation can worsen following punctal occlusion, as
Ocular lubricants or artificial tears are mainstay of dry eye occlusion of tear outflow would prolong contact of the
treatment. These products differ with respect to number of abnormal tears containing proinflammatory cytokines with
variables, electrolyte composition, osmolarity or osmolality, the ocular surface. Therefore, treatment of inflammation
and presence or absence of preservatives and compatible before plug insertion has been recommended. The lacrimal
solutes. In theory, the ideal artificial lubricant should be puncta can be occluded by thermal method, by implanting
preservative-free, contain potassium, bicarbonate and other plugs or by surgical methods.
electrolytes and have a polymeric system to increase its 1. Punctal occlusion: The aim of punctal occlusion is to retard
retention time.32-34 Physical properties should include a neutral tear clearance in an attempt to treat the ocular surface of
to slightly alkaline pH. Osmolarities of artificial tears have patients with deficient aqueous tear production. Punctal
been measured to range from about 181 to 354 mOsm/L.35 plugs are divided into the following types:
Colloidal osmolarity also varies between tear products, • Absorbable: Made of collagen or polymers. The
influences water transport across the ocular surface occlusion duration ranges from 7-180 days.37 The plugs
epithelium.5 Higher artificial tear viscosity increases the dissolve by themselves or may be removed by saline
retention time and may help to protect the ocular surface. irrigation.
• Nonabsorbable: Made of silicone or hydrophilic 3. Salivary gland autotransplantation: Salivary submandibular

acrylic, are intended to be permanent. Contraindications gland transplantation is capable of replacing deficient
to the use of punctal plugs include allergy to the materials mucin and the aqueous tear film phase. Such surgery is
used in the plugs to be implanted, punctal ectropion capable of substantially reducing discomfort, but often
and pre-existing nasolacrimal duct obstruction, which has no effect on vision.44
would presumably, negate the need for punctal occlusion.
The most common complication of punctal plugs is Anti-inflammatory Therapy
spontaneous plug extrusion and more troublesome Based on the concept that inflammation is a key component
complications include internal migration of a plug, of the pathogenesis of dry eye, the efficacy of a number of
biofilm formation and infection,38 and pyogenic anti-inflammatory agents for treatment of dry eye disease has
granuloma formation. been evaluated. These include:
2. Moisture chamber spectacles: They reduce tear evaporation 1. Topical cyclosporine: Topical cyclosporine is currently the
by increasing humidity around the eye. only pharmacologic treatment that is FDA approved
3. Contact lenses: They are used in severe dry eye or when specifically for dry eye. Cyclosporine is disease modifying
other therapies have failed, to help retain the tear film and/ agent. It reduces conjunctival IL-6 levels, decreases
or promote ocular surface healing. activated lymphocytes in the conjunctiva, reduces
4. Tarsorrhaphy: It is done to narrow the palpebral aperture, conjunctival inflammatory and apoptotic markers, and
decreasing evaporation. If partial closure fails, complete increases conjunctival goblet cell numbers.45-48
closure may be indicated.39 2. Corticosteroids: Although topical corticosteroids are
effective, they are generally recommended only for short-
Tear Stimulation: Secretagogues term use because prolonged use might result in adverse
Several potential topical pharmacologic agents may stimulate effects including ocular infection, glaucoma and cataracts.
aqueous secretion, mucous secretion or both. The agents However, corticosteroids may differ in their propensity to
currently under investigation are diquafosol (one of the P2y2 cause these complications.
receptor agonists), rebamipide, gefarnate, ecabet sodium 3. Oral tetracyclines: Tetracyclines are used in dry eye
(mucous secretion stimulants) and 15(S)-HETE (MUC1 primarily for their anti-inflammatory rather than
stimulant). antibacterial actions. Mechanisms may include decreased
Two orally administered cholinergic agonists, pilocarpine matrix metalloproteinase activity and decreased production
and cevilemine, have been evaluated in clinical trials and found of proinflammatory cytokines such as interleukin (IL)-1
to be marginally beneficial.5 and tumor necrosis factor-alpha.5
Biological Tear Substitutes Essential Fatty Acids
1. Autologous serum tears: Autologous serum tears have They benefit dry eye in two ways: By reducing inflammation
biochemical and mechanical properties similar, but not and by altering the composition of meibomian lipids. There
identical, to those of normal aqueous tears.40 They are are at least two EFA nutritional supplements marketed
unpreserved but can be stored frozen for 3 to 6 months, so specifically for DED: one containing omega-3 fatty acids from
that blood donation is required 2 to 4 times a year.41 flax seed and fish oil and another containing a blend of omega-
Autologous serum tears are effective in improving symptoms 3 and omega-6 fatty acids from cod liver oil. Omega-6 fatty
and signs of severe or refractory dry eye. Autologous serum acids are precursors for arachidonic acid and certain
treatment is usually well tolerated and most patients report proinflammatory lipid mediators (PGE2 and LTB4). In
improvement of discomfort sensation. Although contrast, certain omega-3 fatty acids (e.g. EPA found in fish
uncommon, some patients may experience increased oil) inhibit the synthesis of these lipid mediators and block
discomfort, slight epitheliopathy, bacterial conjunctivitis or production of IL-1 and TNF-alpha. Higher omega-6:omega-
eyelid eczema, according to some reports.42 3 ratio was associated with significantly greater DED risk.49
2. Autologous platelet rich plasma: Platelet-rich plasma contains
Environmental Strategies
high numbers of platelets that produce growth factors. They
induce mesenchymal and epithelial cells to migrate and Factors that may decrease tear production or increase tear
proliferate. Platelet-rich plasma has a lubricating effect.43 evaporation, such as the use of systemic anticholinergic
medications (e.g. antihistamines and antidepressants) and FUTURE ADVANCES

desiccating environmental stresses (e.g. low humidity and air
There have been tremendous advances in the treatment of
conditioning drafts) should be minimized or eliminated. Video
dry eye and ocular surface disease in the last two decades.
display terminals should be lowered below eye level to decrease
There has been a commensurate increase in knowledge
the interpalpebral aperture and patients should be encouraged
regarding the pathophysiology of dry eye. This has led to a
to take periodic breaks with eye closure when reading or
paradigm shift in dry eye management from simply lubricating
working on a computer. A humidified environment is
and hydrating the ocular surface with artificial tears to strategies
recommended to reduce tear evaporation. This is particularly
that stimulate natural production of tear constituents, maintain
beneficial in dry climates and high altitudes.50-52
ocular surface epithelial health and barrier function and inhibit
The International Dry Eye WorkShop (DEWS)
the inflammatory factors that adversely impact the ability of
Subcommittee members reviewed the Delphi Panel (the Dry
ocular surface and glandular epithelia to produce tears.
Eye Preferred Practice Patterns of the American Academy of
Preliminary experience using this new therapeutic approach
Ophthalmology and the International Task Force Delphi Panel
suggests that quality of life can be improved for many patients
on Dry Eye) approach to the treatment of dry eye and modified
with dry eye and that initiating these strategies early in the
it.5,8
course of the disease may prevent potentially blinding
Treatment recommendations are based on disease severity
complications of dry eye. It is likely that future therapies will
of DED:
focus on replacing specific tear factors that have an essential
• Level 1
role in maintaining ocular surface homeostasis or inhibiting
– Education and environmental/dietary modifications
key inflammatory mediators that cause death or dysfunction
– Elimination of offending systemic medications
of tear secreting cells. This will require additional research to
– Preserved artificial tear substitutes, gels and ointments
identify these key factors and better diagnostic tests to
– Eyelid therapy (for MGD).
accurately measure their concentrations in minute tear fluid
• Level 2— If level 1 treatment is inadequate, the following is
samples. Furthermore, certain disease parameters may be
to be added:
identified that will identify whether a patient has a high
– Nonpreserved artificial tear substitutes
probability of responding to a particular therapy. Based on
– Anti-inflammatory agents
the progress that has been made and the number of therapies
 Topical corticosteroids
in the pipeline, dry eye therapy seems to be evolving in the
 Topical cyclosporin A.
right direction.
– Topical/systemic omega-3 fatty acids
– Tetracyclines (for MGD) REFERENCES
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6.8.3 Immunological Diseases of the Eye

Geetha Krishnan Iyer
IMMUNOLOGY OF THE CORNEA, specificity. The antigen first must be processed and recognized.
SCLERA AND OCULAR SURFACE Once an antigen has been recognized, the adaptive immune
system creates an army of immune cells specifically designed
Humans have three lines of defense against infection. The to attack that antigen. Adaptive immunity also includes a
physical barrier of our skin and mucosal surfaces provides "memory" that makes future responses against a specific
our first line of defense. This effectively protects us from antigen more efficient.1
numerous pathogens found in our immediate surroundings.
Should this primary line of defense be invaded, the immune
CELLS OF INNATE IMMUNE SYSTEM
system (next two lines of defense—innate and adaptive
immunity) takes over to offer protection, which comprises of Phagocytes
cells in the bone marrow, thymus, and the lymphatic system
of ducts and nodes, spleen, and blood. Although sub-divided into two main types, namely neutrophils
Anything that causes an immune response is called an and macrophages, they both share the same function - to
antigen. An antigen may be harmless, such as grass pollen, or engulf microbes (phago—I eat, Latin).
harmful, such as the flu virus. Disease-causing antigens are
called pathogens. The immune system is typically divided into Neutrophils
two categories--innate and adaptive--although these
Microscopically, these cells possess a characteristic, salient
distinctions are not mutually exclusive.
feature—a multilobular nucleus. As such, these cells have been
Innate immunity refers to nonspecific defense mechanisms
referred to as polymorphonuclear leukocytes (PMNs) and have
that come into play immediately or within hours of an antigen's
appearance in the body. These mechanisms include physical a pivotal role to play in the development of acute inflammation.
barriers such as skin, chemicals in the blood, and immune In addition to being phagocytic, neutrophils contain granules
system cells that attack foreign cells in the body. The innate and can also be classed as one of the granulocytes. The granules
immune response is activated by chemical properties of the contain acidic and alkaline phosphatases, defensins and
antigen. Innate (natural) immunity does not require a previous peroxidase—all of which represent the requisite molecules
encounter with a microorganism or other invader to work required for successful elimination of the unwanted microbe(s).
effectively. It responds to invaders immediately, without
Macrophages
needing to learn to recognize them.
Adaptive immunity refers to antigen-specific immune Macrophages (termed monocytes when in the blood stream)
response. The adaptive immune response is more complex have a horseshoe-shaped nucleus and are large cells. Properties
than the innate and displays a high degree of memory and of macrophages include phagocytosis and antigen presentation
to T cells. Unlike neutrophils (which are short-lived cells), infected by a virus; and second, to augment the T cell response
they are seen in chronic inflammation as they are long-lived to other virally-infected cells.
cells.
Mast Cells and Basophils
Mononuclear Phagocytic System
Morphologically, mast cells and basophils are very similar in
The cells comprising the monocyte phagocytic system are tissue that both contain electron dense granules in the cytoplasm.
bound and, as a result, are further sub-divided depending on Basophils are so-called owing to the fact that their granules
their location. stain with a basic dye. Unlike mast cells, which are present in
close proximity to blood vessels in connective tissue, basophils
PHAGOCYTOSIS—THE PROCESS reside in the circulation. Both cell types are instrumental in
initiating the acute inflammatory response. Degranulation is
Phagocytosis is the process by which cells engulf
achieved either by binding to components of the complement
microorganisms and particles. Firstly, the phagocyte must move
system or by cross-linking of the IgE antibody which results
towards the microbe under the influence of chemotactic
in the release of proinflammatory mediators including
signals, e.g. complement. For the process to continue, the
histamine and various cytokines. The former induces
phagocyte must attach to the microbe either by recognition
vasodilation and augments vascular permeability whilst the
of the microbial sugar residues (e.g. mannose) on its surface
latter are important in attracting both neutrophils and
or complement/antibody, which is bound to the pathogen.
eosinophils.
Following attachment, the phagocyte's cell surface invaginates
and the microbe becomes internalized into a phagosome. The Dendritic Cells
resultant phagosome fuses with multiple vesicles containing
O2 free radicals and other toxic proteins known as lysosomes Dendritic cells consist of Langerhans’ and interdigitating cells
to form a phagolysosome. The microbe is subsequently and form an important bridge between innate and adaptive
destroyed. immunity, as the cells present the antigenic peptide to the T
helper cell (adaptive immunity). Such cells are therefore known
Opsonization ("to make tasty" - Greek) as professional antigen presenting cells (APCs).
Opsonins are molecules, which enhance the efficiency of the Eosinophils

phagocytic process by coating the microbe and effectively
Eosinophils (so called because their granules stain with eosin)
marking them for their destruction. Important opsonins are
are granulocytes that possess phagocytic properties. Despite
the complement component C3b and antibodies.
the fact that they represent only 2-5 percent of the total
leukocyte population, they are instrumental in the fight against
Natural Killer (NK) Cells
parasites that are too big to be phagocytosed.
NK cells are also known as "large granular lymphocytes"
(LGLs) and are mainly found in the circulation. They comprise Molecules of the Innate Immune System
between 5-11 percent of the total lymphocyte fraction. In
addition to possessing receptors for immunoglobulin type G There are many molecules, which work in concert with the
(IgG), they contain two unique cell surface receptors known cells of the innate immune system and which also foster close
as killer activation receptor and killer inhibition receptor. functional links with their adaptive counterpart. The three
Activation of the former initiates cytokine ("communication") major molecules are:
molecules from the cell whilst activation of the latter inhibits • Complement
the aforesaid action. NK cells serve an important role in • Acute phase proteins (APP)
attacking virally-infected cells in addition to certain tumor cells. • Interferons (IFNs)
Destruction of infected cells is achieved through the release
Complement
of perforins and granyzymes from its granules, which induce
apoptosis (programmed cell death). NK cells are also able to The complement system represents a large group of
secrete interferon-γ (IFN-γ). This interferon serves two independent proteins (denoted by the letter C and followed
purposes: first, to prevent healthy host cells from becoming by a number), secreted by both hepatocytes (liver cells) and
monocytes. Although these proteins may be activated by both Some of these substances, including some cytokines,
the adaptive immune system (classical pathway) or innate promote inflammation. Inflammation, with redness and
immune system (alternative pathway), the nomenclature is swelling, occurs because the substances attract immune cells
derived from the fact that the proteins help ("complement") to the affected tissue and, to get the immune cells there, more
the antibody response. Activation of complement via the blood flows to the tissue and more fluids enter the tissue. The
microbe itself is known as the alternative pathway. The classical purpose of inflammation is to contain the infection so that it
pathway requires the interaction of antibody with specific does not spread. Then other substances produced by the
antigen. The C3 component is the pivotal serum protein of immune system help the inflammation resolve and damaged
the complement system. Binding of the antigen to C3 results tissues heal. Although inflammation may be bothersome, it
in two possible sequelae. In either case, C3 component indicates that the immune system is functional. However,
becomes enzymatically converted to C3b. The bacterial cell excessive or long-term (chronic) inflammation can be harmful.
wall can either remain bound to C3b and become opsonized
(since phagocytes have receptors for C3b) or act as a focus CELLS OF ADAPTIVE IMMUNE SYSTEM
for other complement proteins (namely C5, 6, 7, 8 and 9).
The latter form the membrane attack complex (MAC), which There is a great deal of synergy between the adaptive immune
induces cellular lysis. system and its innate counterpart. The adaptive immune system
The functions of the complement system may be comprises two main types of leukocyte known as B and T
summarized as follows: lymphocytes. Before describing these important cell types, it
• Opsonization is necessary to be acquainted with both the primary and
• Lysis (destruction of cells through damage/rupture of secondary lymphoid organs and tissues in the body. The bone
plasma membrane) marrow represents the dominant site for hemopoiesis
• Chemotaxis (directed migration of immune cells) (production of blood cells and platelets). Although most of
• Initiation of active inflammation via direct activation of the hemopoietic cells mature in this region, T lymphocytes do
mast cells. so in the thymus. In the thymus, premature T cells undergo a
It is important that complement is regulated to protect process of positive and negative selection whereby the former
host cells from damage and/or their total destruction. This is are allowed to progress to maturity whilst the latter are marked
achieved by a series of regulatory proteins, which are expressed for termination via apoptosis.
on the host cells themselves.
Lymphocytes
Acute Phase Proteins
These serum proteins are synthesized by hepatocytes and are Morphologically, there are three types of lymphocytes: T, B
produced in high numbers in response to cytokines released and NK cells. However, only T and B lymphocytes exhibit
from macrophages. memory and specificity and, as such, are responsible for the
unique quality of the adaptive immune system.
Interferons (IFNs)
T-cells
IFNs are a group of molecules, which limit the spread of
viral infections. There are two categories of IFNs, namely type T-cells are produced in the thymus. There, they learn how to
I and type II. Type I IFNs maybe subdivided further into IFN- distinguish self from nonself. Only the T cells that ignore self
α and β. IFN-γ is the sole type II interferon. Type I IFNs are antigen molecules are allowed to mature and leave the thymus.
induced by viruses, proinflammatory cytokines and endotoxins Without this training process, T cells could attack the body's
from gram-negative bacterial cell walls. Their presence remains cells and tissues.
vital for the successful eradication of an invading virus by the Mature T cells are stored in secondary lymphoid organs
innate immune system. (lymph nodes, spleen, tonsils, appendix, and Peyer's patches
Type II IFN, IFN-γ, is produced by T Helper cells and in the small intestine). These cells circulate in the bloodstream
NK cells and is able to augment both the antigen presenting and the lymphatic system. After they first encounter a foreign
properties together with the phagocytic properties of the APCs or abnormal cell, they are activated and search for those
(e.g. macrophages and dendritic cells). particular cells.
There are different types of T cells: • Secondary immune response: But thereafter, whenever B cells
• Killer (cytotoxic) T cells attach to particular foreign or encounter the antigen again, memory B cells very rapidly
abnormal (for example infected) cells because they have recognize the antigen, multiply, change into plasma cells,
encountered them before. Killer T cells may kill these cells and produce antibodies. This response is quick and very
by damaging their cell membrane and injecting enzymes effective.
into the cells or by binding with certain sites on their surface
called death receptors. This binding triggers reactions Antibodies
within the foreign or abnormal cell that lead to death. Antibodies have two roles to play:
• Helper T cells help other immune cells. Some helper T • to bind antigen and
cells help B cells produce antibodies against foreign • to interact with host tissues and effector systems in order
antigens. Others help activate killer T cells to kill foreign to ensure removal of the antigen.
or abnormal cells or help activate macrophages enabling There are five different types (known as isotypes) of
them to ingest foreign or abnormal cells more efficiently. antibody in the human immune system—namely IgM, IgG,
• Suppressor (regulatory) T cells produce substances that IgA, IgE and IgD. In addition, there are four subclasses of
help end the immune response or sometimes prevent IgG (IgG1-4). The basic antibody unit consists of a
certain harmful responses from occurring. glycosylated protein consisting of two identical heavy and two
• Sometimes T cells, for reasons that are not completely identical light, polypeptide chains. The region which binds to
understood, do not distinguish self from nonself. This the antigen is known as the Fab region, while the constant
malfunction can result in an autoimmune disorder, in which region, Fc, not only determines the isotype but is the region
the body attacks its own tissues leading to autoimmune responsible for evoking effector systems, e.g. mast cell
disorders. activation.
IgG, is a kind of antibody that works efficiently to coat
microbes, speeding their uptake by other cells in the immune
Humoral System
system.
When first exposed to an antigen, low levels of antibodies are IgM is very effective in killing bacteria.
produced in about a week. However, a second exposure to IgA concentrates in body fluids—tears, saliva, and the
the same antigen produces a much faster response, and at a secretions of the respiratory and digestive tracts—guarding
magnitude of higher level. The ability of the antibody to bind the entrances to the body.
antigen also increases dramatically in the secondary response. IgE, whose natural job probably is to protect against
The memory of the antigen and the stimulated response is parasitic infections, is responsible for the symptoms of allergy.
the basis for success in destroying pathogens. IgD remains attached to B cells and plays a key role in
initiating early B cell responses.
The term immune complex refers to the combination of
B Lymphocytes
antigen and antibody.
B cells are formed in the bone marrow and have particular
sites (receptors) on their surface where antigens can attach. Major Histocompatibility Complex (MHC)
The B-cell response to antigens has two stages:
Major histocompatibility complex (MHC) are cell surface
• Primary immune response: When B cells first encounter glycoproteins classified as class I (also termed human leukocytic
an antigen, the antigen attaches to a receptor (membrane antigen [HLA] A, B and C), found on all nucleated cells and
bound antibodies), stimulating the B cells to divide. Some class II (termed HLA, DP, DQ and DR), found on all antigen
B cells change into memory cells, which remember that presenting cells (APCs). MHC molecules are the sine qua non
specific antigen, and others change into plasma cells. Helper of T cell induced immunity. Clinically, there is a strong
T cells help B cells in this process. Plasma cells produce association between HLA and certain systemic and ocular
antibodies that are specific to the antigen that stimulated diseases.
their production. After the first encounter with an antigen, T cells only recognize an antigen if it is carried on the
production of enough of the specific antibody takes several surface of a cell by one of the body's own major histocomp-
days. Thus, the primary immune response is slow. atibility complex, or MHC molecules.
Regulation of the immune response requires the Regulation: The immune response must be regulated to prevent
participation of the MHC. The cellular system recognizes the extensive damage to the body. Regulatory (suppressor) T cells
MHC to regulate both B-cell and T-cell responses. help control the response by secreting cytokines (chemical
messengers of the immune system) that inhibit immune
The Immune Response responses.
A successful immune response to invaders requires recognition, Resolution: Resolution involves confining the invader and
activation and mobilization, regulation, and resolution. eliminating it from the body. After the invader is eliminated,
most white blood cells self-destruct and are ingested. Those
Recognition: To be able to destroy invaders, the immune that are spared are called memory cells. The body retains
system must first recognize them. That is, the immune system memory cells, which are part of acquired immunity, to
must be able to distinguish between nonself (foreign) and self remember specific invaders and respond more vigorously to
antigens. The immune system can make this distinction because them at the next encounter.
all cells have identification molecules on their surface.
Microorganisms are recognized because the identification Immune Tolerance
molecules on their surface are foreign. In people, identification
Immune tolerance is the tendency of T or B lymphocytes to
molecules are called the major histocompatibility complex
ignore the body's own tissues. Maintaining tolerance is
(MHC). Each person has an almost unique combination of
important because it prevents the immune system from
human leukocyte antigens. Each person's immune system
attacking its fellow cells. Failure to do so can, in some cases,
normally recognizes this unique combination as self. A cell
lead to the development of autoimmune diseases.
with molecules on its surface that are not identical to those
Tolerance occurs in at least two ways—central tolerance
on the body's own cells is identified as being foreign. The
and peripheral tolerance.
immune system then attacks that cell. Such a cell may be a
Central tolerance occurs during lymphocyte development.
microorganism, a cell from transplanted tissue, or one of the
Very early in each immune cell's life, it is exposed to many of
body's cells that has been infected by an invading
the self molecules in the body. If it encounters these molecules
microorganism or altered by cancer.
before it has fully matured, the encounter activates an internal
Some white blood cells, e.g. B cells (B lymphocytes), can
self-destruct pathway, and the immune cell dies. This process,
recognize invaders directly. But others, [T cells (T
called clonal deletion, helps ensure that "self-reactive" T cells
lymphocytes)], need help from other cells of the immune and B cells, those that could develop the ability to destroy the
system, called antigen presenting cells. These cells ingest an body's own cells, do not mature and attack healthy tissues.
invader and break it into fragments. The antigen fragments Because maturing lymphocytes do not encounter every
from the invader are combined with HLA molecules as they molecule in the body, they must also learn to ignore mature
are assembled in the antigen presenting cell and moved to the cells and tissues. In peripheral tolerance, circulating
cell's surface. T cells that come into contact with the antigen lymphocytes might recognize a self molecule but cannot
presenting cell then learn to recognize the invader's antigen respond because some of the chemical signals required to
fragments. T cells are then activated and can begin fighting activate the T or B cell are absent. So-called clonal anergy,
the invaders that have that antigen. therefore, keeps potentially harmful lymphocytes switched off.
Activation and mobilization: White blood cells are activated Peripheral tolerance may also be imposed by a special class of
when they recognize invaders. For example, when the antigen regulatory T cells that inhibits helper or cytotoxic T-cell
presenting cell presents antigen fragments bound to HLA to a activation by self antigens.
T cell, the T cell attaches to the fragments and is activated. B
cells can be activated directly by invaders. Once activated, white OCULAR IMMUNE PRIVILEGE
blood cells ingest or kill the invader or do both. Usually, more Immune privileged sites are defined as places within the body
than one type of white blood cell is needed to kill an invader. where foreign tissue grafts experience extended (often
Immune cells, such as macrophages and activated T cells, indefinite) survival, whereas similar grafts placed in
release substances that attract other immune cells to the trouble conventional sites are promptly rejected. Immune privileged
spot, thus mobilizing defenses. The invader itself may release tissues differ from conventional tissues in that grafts prepared
substances that attract immune cells. from the former experience extended (often indefinite) survival
when placed at conventional sites, whereas nonprivileged tissue Manifestations of Ocular

grafts placed in conventional sites are promptly rejected. Immune Privilege
The rationale for ocular immune privilege2 is as follows:
Immune privilege manifests itself in three distinctive ways that
All organs and tissues, even those with special
can be measured experimentally through:
physiologic needs and those unable to regenerate
• The existence of an anti-inflammatory and immuno-
themselves, require immune protection against pathogens.
suppressive microenvironment
As immune protection against pathogens can damage vital
• The extended survival of allogeneic allografts
tissues in an innocent bystander manner, immune privilege
• Induction of tolerance to eye-derived antigens.
is regarded as an evolutionary adaptation that enables local
protection to be provided by immune effectors that do not
Anterior Chamber Associated
disrupt specialized tissue functions or cause the loss of
Immune Deviation (ACAID)
tissue incapable of regeneration. Immune privilege is
achieved by dynamic interactions between the immune An operational definition of ACAID holds that antigenic
system and specialized tissues. In the case of the eye, where material placed in or arising from the anterior chamber of the
a precise microanatomy and clear media must be maintained eye elicits a deviant form of systemic immunity, which includes
for light images to fall accurately on the retina, immune T cells (Tc) and B cells (non-Complement fixing) that eliminate
privilege allows for immune protection of the eye in a pathogens and virulence factors in the absence of inflammation,
manner that is larg ely devoid of immunog enic excludes effector CD4– T cells (Th1 and Th2) and B cells (that
inflammation. There are numerous sites in the body secrete complement-fixing antibodies) that eliminate pathogens
whereby tissue may be grafted with minimal risk of via immunogenic inflammation, and includes regulatory T cells
rejection. Such regions include, inter alia, the testis, thyroid, that suppress induction and expression of immunogenic
lens, anterior chamber, cornea, iris and ciliary body. inflammation secondary to Th1/Th2 cells.
Although many factors are now known to contribute to It is now clear that ACAID can be induced by diverse
the immune privileged status of the anterior chamber, most types of antigens (soluble, cell-associated, viral, tumor-specific,
haptenic, autologous, allogeneic). Unlike most other forms
can be assigned to one of the following unique features of
of experimentally induced unresponsiveness, ACAID can be
this site:
generated in naive and presensitized individuals, and when it
• The blood-ocular barrier in the tissues surrounding the
is present, it is long-lasting, dominant, and resistant to
chamber
termination.
• The absence of blood vessels in the cornea and specialized
The ACAID-inducing signal (AIS) is an F4/80– monocyte
vascular endothelial cells of the vessels within the iris
that bears antigenic epitopes but not native antigen itself and
stroma
its source is probably the eye itself.
• Absence of lymphatic drainage from the anterior chamber The eye-derived antigens are captured by indigenous APCs
(with the minor exception of the uveoscleral pathway), and are carried, presumably across the trabecular meshwork,
which ensures that contents of the anterior chamber are via the blood to the spleen, where the subsequent steps in
drained directly into the venous circulation ACAID development take place which indicates the need for
• Soluble immunomodulatory factors in aqueous humor an intact camero-splenic axis for ACAID to be activated.
(AqH) that are released from the cells and tissues Immune privilege within the eye is an evolutionary
surrounding the anterior chamber and secreted by the adaptation designed to protect the eye from sight-destroying
ciliary body inflammation. The strategies used, some of which are known
• Cell surface immunomodulatory factors that are and described above, are effective at limiting inflammation
constitutively expressed on parenchymal cells (pigment and modifying innate and adaptive immunity. As inflammation
epithelium, corneal endothelium), which line the anterior and immunity are important mechanisms for protecting against
chamber invading pathogens, there are likely to be risks associated with
• Tolerance promoting antigen presenting cells (APCs) in the eye-dependent alterations. Some of these risks and some
iris stroma and (perhaps) in the trabecular meshwork and of the benefits are described below.
outflow pathways (ACAID). • The perils of loss of ocular immune privilege
Together, these features make it possible for the multiple – Allogeneic corneal grafts are no longer protected from
manifestations of ocular immune privilege to exist. immune rejection;
– Intraocular tumors elicit immune responses of a vigor The following interact as part of the activated immune
and type that destroy the tumor but also cause phthisis; network, which can lead to scleral destruction: immune
– Irretrievable damage to the visual axis (corneal stroma, complex vessel deposition in episcleral- and scleral-perforating
endothelium, lens, vitreous) occurs secondary to acute capillary and postcapillar y venules (inflammatory
viral infection or pathogen-associated intraocular microangiopathy) and cell-mediated immune responses. The
inflammation; and autoimmune nature of scleritis also is supported by the
– Autoimmunity to strong ocular antigens is triggered, frequent association with systemic autoimmune disorders and
leading to anterior or posterior uveitis and glaucoma by the favorable response to immunosuppressive therapy.
secondary to intraocular inflammation.
• The perils of maintaining ocular immune privilege Immunopathology and the Eye
– Innate and/or adaptive immune elimination of
intraocular tumors may not be possible; Immunopathology encompasses both pathology as a result
– Acute retinal necrosis secondary to new or recurrent of an over-active immune system (hypersensitivity and
herpes virus infection of the anterior segment is a autoimmunity) together with that acquired through an
serious risk, as virus-specific ACAID is induced individuals inability to fight off infection, namely
transiently, rendering the retina vulnerable to direct viral immunodeficiency. The classification system pertaining to
toxicity. hypersensitivity reactions will be described and the anterior
segment manifestations for each subtype will be highlighted.
Conjunctival Immunology
Hypersensitivity
The conjunctival associated lymphoid tissue (CALT)3,4 is part
of the more general mucosa-associated lymphoid tissue The term hypersensitivity refers to the process whereby the
(MALT). Langerhans’ cells and lymphocytes exist within the adaptive immune response overreacts to a variety of infectious
conjunctival epithelial layer. Neutrophils, lymphocyte’s IgA and and inert antigens resulting in damage to the host tissue. Four
IgG, dendritic cells and mast cells, reside in the substantia types of hypersensitivity reactions exist as expounded by PHG
propria. It is noteworthy that eosinophils and basophils are Gell and Robin Coombs in 1963.1
not present in the healthy conjunctiva. Langerhans’ cells and • Type I reactions (i.e. immediate hypersensitivity reactions)
dendritic cells present the antigenic peptide to the conjunctival involve immunoglobulin E (IgE)-mediated release of
T helper cells. Following antigenic presentation, the T cells histamine and other mediators from mast cells and
secrete the cytokine IFN-γ which serves to promote antigen basophils.
elimination by macrophages. This is the delayed-type • Type II reactions (i.e. cytotoxic hypersensitivity reactions)
hypersensitivity (DTH) response and is characteristic of involve immunoglobulin G or immunoglobulin M
conjunctival pathology such as phlyctenulosis. antibodies bound to cell surface antigens, with subsequent
complement fixation.
Scleral Immunology • Type III reactions (i.e. immune-complex reactions) involve
circulating antigen-antibody immune complexes that
There exists only a small number of immune cells in the sclera
deposit in postcapillary venules, with subsequent
compared to the conjunctiva since it is relatively avascular. In
complement fixation.
its resting state, IgG appears to be present in large amounts.
• Type IV reactions (i.e. delayed hypersensitivity reactions,
However, a sclera under stress, may become immunologically
cell-mediated immunity) are mediated by T cells rather than
active as a result of migrating cells from the overlying episcleral
by antibodies.
and underlying choroidal vasculature.
An autoimmune dysregulation in a genetically predisposed
Type I Hypersensitivity: Allergy
host is presumed to cause scleritis. Inciting factors may include
infectious organisms, endogenous substances, or trauma. The Allergies may affect approximately 17 percent of the
inflammatory process may be caused by immune complex- population. The term atopic is used to describe those
related vascular damage (type III hypersensitivity) and individuals who possess a genetic predisposition to allergy.
subsequent chronic granulomatous response (type IV Allergies may occur to otherwise innocuous antigens (known
hypersensitivity). as allergens) and infectious agents, e.g. worms.
Type I hypersensitivity exists in two phases, the sensitiz- Type IV Hypersensitivity:

ation and effector phases. Delayed-type Hypersensitivity (DTH)
Ocular correlates: The following anterior segment conditions The term DTH has been used to describe such a reaction
are due, if not only in part, to type I hypersensitivity: owing to its prolonged time-scale relative to the other
• Seasonal allergic conjunctivitis (type I) hypersensitivity types. Although DTH can be transferred by
• Giant papillary conjunctivitis (type I and IV) T cells that have been previously sensitized by an antigen, it
• Vernal keratoconjunctivitis (VKC) (type I and IV) cannot be transferred in serum. The sequence of events leading
• Atopic keratoconjunctivitis (AKC) (type I and IV). to DTH begins with initial presentation of the antigen peptide
to T cells by APCs (e.g. Langerhans’ cells). The primed T cell
Type II Hypersensitivity: Cytotoxic migrates to the site of antigenic entry whereby it releases pro-
inflammatory mediators such as TNF. The release of these
This classification of hypersensitivity involves either IgG or cytokines facilitates blood flow and extravasation of plasma
IgM antibodies, which may induce cellular lysis due to the contents to the area. The activation of CD4+ T helper and
involvement of the classical complement pathway (as seen in CD8 cells results in the release of IFN-γ and, as a consequence,
blood transfusion reactions) or recr uit and activate enhances macrophage activity in that area. Resolution of DTH
inflammatory cells via complement. The components of is dependent on the efficacy with which such phagocytes can
complement include the C5a, which serves to attract remove the offending antigen. Recalcitrant infectious agents
inflammatory cells to the site of interest. The hypersensitivity result in a chronic DTH that causes the chronically activated
reaction is a result of the excessive amount of extracellular macrophages to fuse together and form multinucleated giant
mediators released by the inflammatory cells to antigens that cells. In an attempt to contain the infectious agent,
are too big to be completely phagocytozed. macrophages may undergo further interconnections to
resemble an epithelial layer. Owing to the similarity to this
Ocular Manifestations: layer they are referred to as epitheloid cells.
• Mooren's ulcer Both epitheloid and multinucleated giant cells secrete
• Cicatrical pemphigoid. factors that induce fibrosis resulting in granuloma formation.
Thus granulomata are the hallmark of chronic inflammation.
Type III Hypersensitivity: Immune Complex Damage and loss of function of the neighbouring tissues
Large pathogens with multiple antigenic sites have several frequently ensues until the agent is removed either chemically
antibodies bound to them forming immune complexes. or surgically.
Normally, these complexes are removed by the mononuclear Ocular Manifestations:
phagocytes in the liver and spleen with no adverse sequelae. • Ocular allergies (VKC, AKC, GPC)
However, persistence of immune complexes does occur • Idiopathic uveitis
in certain individuals leading to their deposition in tissue. As a • Sympathetic ophthalmia
consequence of the latter action, complement may be activated • Phlyctenulosis.
thus paving the way for inflammatory cells to enter the
deposition site. Since blood vessels (which filter plasma at high Type V Hypersensitivity
pressure and exhibit a great deal of tortuosity) are more
susceptible for immune complex deposition, the ciliary body This relatively new category encompasses the concept of
is particularly vulnerable to this type of hypersensitivity autoantibodies binding to hormone receptors that mimic the
reaction. hormone itself. This results in stimulation of the target cells.
Examples include thyrotoxicosis.
Ocular Manifestations:
• Uveitis (Crohn's disease) Autoimmunity
• Peripheral corneal lesions associated with rheumatoid
arthritis The ability to react against self-antigens is known as
• Stevens-Johnson syndrome autoimmunity. However, a significant number of people exist
• Sjögren's syndrome. who harbor autoantibodies and yet remain asymptomatic. The
corollary of this is that the presence of autoreactive cells per se Primary systemic vasculitis (PSV) is a disorder without
is not sufficient to trigger autoimmune disease. In fact, previously identified conditioning disease entity.
autoimmune disease is a result of breakdown of one of the Secondary systemic vasculitis (SSV) follows or accompanies
immunoregulatory mechanisms. Furthermore, autoimmune given diseases such as:
disease may be classified as either being organ specific (e.g. • Infections
insulin dependent diabetes mellitus, Grave's disease) or non- • Neoplasias
organ specific (e.g. Sjögren's syndrome, ankylosing spondylitis). • Other autoimmune disorders such as connective tissue
It is important to realize that the causes of autoimmune diseases (Sjögren's syndrome).
diseases are multifactorial. The main predisposing factors are
age, gender, infection and genetics. Primary Systemic Vasculitis (PSV)
Summary Vasculitis of Large Size Vessels
The cornea and conjunctiva and their supporting tissues are Giant cell (temporal) Granulomatous arteritis of aorta or
replete with mechanisms to regulate inflammation and preserve arteritis, e.g. large arterial branches with preference
corneal clarity and ocular surface homeostasis during Horton's disease of extracranial parts of carotid artery,
perturbation by pro-inflammatory insults. temporal artery.
Understanding general and, in specific, ocular immunology, Frequently associated with rheumatic
is of prime importance in comprehending pathophysiology polymyalgia.
of immunological corneoscleral disorders as well as the Takayasu's arteritis Granulomatous arteritis of aorta and
management protocols with their rationale. major branches.
Pulseless disease, claudication.
IMMUNOLOGICAL DISORDERS
OF THE CORNEA Vasculitis of Medium Size Vessels
Ocular surface manifestations of immunological disorders Polyarteritis nodosa Systemic necrotizing arteritis of
include: (classical) medium size or small arteries without
• Dry eye (Sjögren's syndrome) vasculitis of arterioles, venules, or
• Scleritis and/or episcleritis capillaries and without glomerulo-
• Corneal melt (peripheral ulcerative keratitis, sclerosing nephritis.
keratitis, keratolysis). Kawasaki's disease Arteritis of medium size arteries
These immunological disorders could be broadly classified frequently associated with a muco-
as: cutaneous lymph node syndrome.
i. Systemic vasculitides Coronary arteries frequently involved,
ii. Mooren's ulcer occasionally also aorta and veins.
iii. Other immunological disorders (dermatomyositis, Primary CNS Small and medium size muscular
relapsing polychondritis, sarcoidosis, graft vs host vasculitis arteries; severe headache, progressive
disease). dementia, multifocal CNS
symptomatology.
SYSTEMIC VASCULITIDES Thromboangiitis Small and medium sized arteries
Systemic vasculitides comprise a large group of inflammatory obliterans, and veins; thrombosis associated
diseases with a suggestive or proven immunopathogenesis Buerger’s disease with cigarette smoking (not generally
involving blood vessels of various sizes and affecting various accepted as entity)
organ systems. They are, thus, not one well-defined entity but
rather a collection of different diseases. Although systemic Vasculitis of Small Size Vessels
vasculitides are predominantly systemic diseases, some can Wegener's disease Granulomatous inflammation
initially remain localized for periods of time. They are classified involving the respiratory tract, with
according to the involved vessel size which is associated with necrotizing vasculitis of small and
distinct clinical pathologies and prognosis.5,6 medium size vessels including
capillaries, venules, arterioles and to 58 percent of patients, including proptosis due to orbital
arteries. involvement, scleritis with or without peripheral ulcerative
Frequently with necrotizing keratitis (PUK), PUK alone, uveitis, and vasculitis.7,8 Orbital
glomerulonephritis. involvement and scleritis (Figs 6.8.3.1A and B) are the most
Lymphomatoid Polyclonal lymphoproliferation with common ophthalmic manifestations. However, PUK can be
granulomatosis lymphocytic vasculitis. an initial clinical manifestation and the presenting or only sign
May progress to T-cell non-Hodgkin's of the disease.7,8 Prompt diagnosis is imperative because the
lymphoma, cough, dyspnea. initiation of immunosuppressive therapy, such as
cyclophosphamide, can be both sight and life saving.7,8 A
Churg-Strauss Eosinophilic granulomatous
careful review of systems may disclose a history of upper or
syndrome inflammation of the respiratory tract
lower respiratory signs or symptoms (epistaxis, sinusitis,
with necrotizing vasculitis of small
rhinorrhea, hoarseness, dysphagia, cough, or pleurisy), a history
and medium size vessels.
of microscopic hematuria, arthralgias, or skin lesions as the
Usually asthma and blood eosinophilia.
result of the underlying vasculitis process. The work-up should
Microscopic Necrotizing vasculitis of small vessels include a hematologic and serologic survey, including serum
polyangiitis (capillaries, venules, arterioles) with ANCA analysis. ANCAs are serum antibodies directed against
(microscopic small or minimal "immune depots" components of primary granules of normal monocytes and
panarteritis) in situ.
Occasionally necrotizing arteritis of
small, medium size and large arteries.
Frequently necrotizing
glomerulonephritis.
Frequently pulmonary capillaritis.
Schoenlein-Henoch's Vasculitis of small vessels (capillaries,
purpura venules, arterioles) with predomi-
nantly IgA immune deposits in situ.
Usually involved are skin, intestines,
glomeruli.
Arthritis or arthralgia may accompany.
Essential Vasculitis of small vessels
cryoglobulinemic (capillaries, venules) with deposits of
vasculitis cr yoglobulins in situ and
cryoglobulins in serum.
Skin and glomeruli are frequently
involved (check for HCV infection).
Cutaneous Isolated leukocytoclastic angiitis of
leukocytoclastic the skin without systemic vasculitis or
angiitis glomerulonephritis
(there are also forms with systemic
involvements of lungs, kidneys,
musculoskeletal system).
Behcet's syndrome Oral, intestinal and genital ulcers,
uveitis, thrombophlebitis.
Wegener's Granulomatosis
Wegener's granulomatosis is a rare multisystem granulomatous
necrotizing vasculitis with upper and lower respiratory tract Figs 6.8.3.1A and B: Scleral melt in Wegener's granulomatosis
and renal involvement. Ocular involvement may be seen in up (Courtesy: Dr M Vanathi)
neutrophils. ANCA testing has been demonstrated to be an Sjögren’s syndrome can be diagnosed in patients who have
extremely sensitive, specific marker for systemic Wegener’s no sicca symptoms if three out of the four objective criteria
granulomatosis or a closely related group of vasculitides.9 In are fulfilled. The criteria are as follows:
general, ANCA titers tend to parallel the extent and severity 1. Ocular symptoms
of Wegener's granulomatosis and fall with the remission of – Dry eyes for more than three months
disease. – Foreign-body sensation
– Use of tear substitutes more than three times per day.
Polyarteritis Nodosa 2. Oral symptoms
Classic polyarteritis nodosa (PAN) is a rare multisystem disease – Feeling of dry mouth
characterized by necrotizing vasculitis of small and medium- – Recurrently swollen salivary glands
sized muscular arteries. The systemic manifestations may be – Frequent use of liquids to aid swallowing.
protean, with various constitutional symptoms. Multiple organs 3. Ocular signs
may be involved, including kidney, skin, bone marrow, central – Schirmer test performed without anesthesia (<5 mm
nervous system, lungs, heart, gastrointestinal and genital tract.10 in 5 min)
Choroidal vasculitis is the most common ophthalmic – Positive vital dye staining results.
manifestation. Other ophthalmic findings include PUK, 4. Oral signs
conjunctival lesions, scleritis, choroiditis, retinal vasculitis, optic – Abnormal salivary scintigraphy findings
atrophy, papilledema, exudative retinal detachment, central – Abnormal parotid sialography findings
artery occlusion. The clinical characteristics of the PUK – Abnormal sialometry findings (unstimulated salivary
associated with PAN are similar to Mooren's ulcer.10 Serologic flow <1.5 mL in 15 minutes).
tests for hepatitis B surface antigen (HBsAg) should be 5. Positive minor salivary gland biopsy findings.
obtained because approximately 50 percent of patients with 6. Positive anti-SSA or anti-SSB antibody results.
PAN are seropositve. Therapy with local medical and surgical Secondary Sjögren’s syndrome is diagnosed when, in the
strategies may temporarily retard progression of the ulcer until presence of a connective tissue disease, symptoms of oral or
control with systemic prednisone and cyclophosphamide is ocular dryness are present in addition to criterion 3, 4, or 5
achieved. above.
Application of these criteria has yielded a sensitivity of
Sjögren’s Syndrome 97.2 percent and a specificity of 48.6 percent for the diagnosis
Sjögren's Syndrome is a chronic inflammatory disorder of of primary Sjögren syndrome; for secondary Sjögren
probable autoimmune nature characterized by infiltration of syndrome, the specificity was 97.2 percent and the sensitivity
the exocrine glands, particularly the salivary and lacrimal glands, 64.7 percent.13
by lymphocytes and plasma cells. The classic signs of the Systemic Lupus Erythematosus
Sjögren's syndrome, therefore, include enlargement of the
parotid glands with mucosal dryness manifest by dry mouth The ophthalmic manifestations of systemic lupus
(xerostomia) and dry eyes (xerophthalmia).11 erythematosus (SLE) are protean. They range from lesions of
the eyelid14 and secondary Sjogren’s syndrome15 to sight-
Primary Sjögren’s syndrome occurs in the absence of other threatening disorders such as retinal vascular disease and neuro-
underlying rheumatic disorder. ophthalmic involvement. Diagnosis is based on a combination
Secondary Sjögren’s syndrome is associated with other of clinical and laboratory criteria. Antibodies to nuclear antigen
underlying rheumatic disease, such as: (ANA) are found in most patients with SLE but are not
• Systemic lupus erythematosus (SLE) necessary for diagnosis when other pertinent laboratory tests
• Rheumatoid arthritis (RA) are positive and classic features of the disease are present.
• Scleroderma. However, antibodies to double-stranded DNA (ds DNA) are
According to the American-European Consensus criteria nearly unique to patients with SLE.
(as modified by Tzioufas and Voulgarelis12), diagnosis of
primary Sjögren’s syndrome requires four of six criteria given Rheumatoid Arthritis
below; in addition, either criterion number 5 or criterion Approximately 25 percent of patients with rheumatoid arthritis
number 6 must be included. (RA) will have ocular manifestations.
Dr y eye syndrome, is the most common ocular (PIP) joints, metacarpophalangeal (MCP) joints, wrist,
manifestation of RA and has a reported prevalence of 15 to elbow, knee, ankle, and metatarsophalangeal (MTP) joints.14
25 percent.16,17 3. Arthritis of hand joints: At least one area swollen (as
Corneal disease in patients with RA can be an isolated defined above) in a wrist, MCP or PIP joint.
complication, but it is most commonly associated with 4. Symmetric arthritis: Simultaneous involvement of the
keratoconjunctivitis sicca or a form of anterior scleritis. The same joint areas (see 2 above) on both sides of the body
spectrum of disease may include keratitis, sclerosing keratitis, (bilateral involvement of PIPs, MCPs, or MTPs is
and peripheral or paracentral ulcerative keratitis.16-19 The most acceptable without absolute symmetry).
common ocular presentations include keratoconjunctivitis 5. Rheumatoid nodules: Subcutaneous nodules, over bony
sicca, marginal thinning and ulceration and diffuse anterior prominences, or extensor surfaces, or in juxta-articular
scleritis. The drying effects of keratoconjunctivitis sicca lead regions, observed by a physician.
to devitalized epithelial cells and punctate epithelial erosions. 6. Serum rheumatoid factor : Demonstration of abnormal
Keratitis associated with scleritis may be acute or sclerosing. amounts of serum rheumatoid factor by any method for
Acute keratitis has been identified in 30 to 70 percent of
which the result has been positive in <5 percent of normal
patients with scleritis or episcleritis-associated RA.16,18 It is
control subjects.
marked by an inflammatory cell infiltrate that may result in
7. Radiographic changes: Radiographic changes typical of
corneal scarring, ulceration, or melting.16
RA on posteroanterior hand and wrist radiographs, which
Sclerosing keratitis is a chronic process marked by an area
must include erosions or unequivocal bony decalcification
of opacified and vascularized cornea that progresses toward
localized to or most marked adjacent to the involved joints
the visual axis. This area of opacification may be more evident
with fluorescein staining. Peripheral and paracentral ulcerative (osteoarthritis changes alone do not qualify).
keratitis can occur in association with, or in the absence of, Treatment of rheumatoid arthritis: Disease modifying anti-
scleritis and are marked by corneal thinning in the juxtalimbal rheumatoid drugs (DMARD) include: methotrexate,
cornea (peripheral) or the central (paracentral) cornea.16,17 leflunomide, sulfasalazine, azathioprine, cyclosporine A,
Without treatment, perforation and visual loss may occur. Care sodium aurothiomalate, D-penicillamine, hydroxychloroquine,
must be taken when prescribing steroids to prevent further combination therapy with short term steroid, NSAIDs, anti-
thinning of the cornea. It is important that the patient receive TNF α treatment (infliximab-chimeric monoclonal antibody,
a thorough ocular examination with frequent slit-lamp follow- etanercept-recombinant TNF receptor fusion protein,
up evaluations. Typically, topical steroids, immunosuppressive adalimumab-human monoclonal anti-TNF alpha antibody).
therapy, surgical intervention, or a combination of the above Rituximab is a selective, B-cell depleting, biological agent for
will be required to preserve vision. Surgical options include
the treatment of refractory RA. The chimeric monoclonal
ulcer debridement, conjunctival resection, corneal graft,
antibody, targeted against CD20, is being promoted as a therapy
application of tissue adhesives, sclerectomy, and scleral patch
for patients who fail to respond to other biologics and in
graft.16,17,20
combination with methotrexate (MTX), rituximab is effective
Diagnosis of Rheumatoid Arthritis and well tolerated, when used to manage RA.
For classification purposes, a patient is said to have RA if he Scleroderma

or she has satisfied at least four of the following seven criteria.
Criteria 1 to 4 must have been present for at least six weeks. Systemic sclerosis is a generalized disorder of connective tissue
Designation as classic, definite, or probable RA is not to be characterized by degenerative and inflammatory changes that
made.21,22 subsequently lead to fibrosis. The skin, blood vessels,
1. Morning stiffness: Morning stiffness in and around the esophagus, and synovium along with certain internal organs
joints, lasting at least 1 hour before maximal improvement. are affected. The most frequent ocular finding is
2. Arthritis of 3 or more joint areas: At least 3 joint areas keratoconjunctivitis sicca, which may be seen in as many as 70
simultaneously have had soft tissue swelling or fluid (not percent of patients.23 Peripheral keratitis unrelated to dry eye
bony overgrowth alone) observed by a physician; the may be seen. Specific antinuclear antibodies have been
possible joint areas are right or left proximal interphalangeal identified in scleroderma.
Other Immunological Disorders nodules of the pupillary border (Koeppe nodules), conjunctival
granulomas, band keratopathy, posterior synechiae, cataract
Dermatomyositis formation, secondary glaucoma, retinal hemorrhage, retinal
Dermatomyositis (DM) is an idiopathic inflammatory neovascularization, cystoid macular edema, venous occlusion,
myopathy (IIM) with characteristic cutaneous findings.24,25 optic disc swelling, optic nerve infiltration, compressive optic
neuropathy, proptosis and extraocular muscle palsy may also
Relapsing Polychondritis be seen.25
Relapsing polychondritis (RP) is a severe, episodic, and Pathogen.esis: Ocular sarcoidosis is a heterogeneous disease
progressive inflammatory condition involving cartilaginous having varied presentations and severities with a strong
structures, predominantly those of the ears, nose, and influence by genetic susceptibility. 30,31 Sarcoidosis is
laryngotracheobronchial tree. Ocular manifestations include characterized by the presence of noncaseating (non-
decreased visual acuity, conjunctivitis, episcleritis, scleritis, rarely necrotizing) granulomas in the affected organs or tissue
PUK, diplopia, and eyelid swelling.26,27 systems. What causes these granulomas is not known, but
current knowledge of the immunology of this disease centers
Sarcoidosis on a CD4+ T-helper type 1 cell response. Immunologic
sequences leading to the formation of sarcoid granulomas
Sarcoidosis is characterized by noncaseating epithelioid are mainly responsible for the immunopathogenesis of ocular
granulomas that may affect any organ system. The disease inflammation seen in patients with sarcoidosis. Studies
most commonly involves granuloma formation in the lungs. underscore that lymphocytes interact with macrophages. Some
Other commonly involved organ systems include the lymph postulate that CD4+ T-helper 1 cells, along with macrophages,
nodes (especially the intrathoracic nodes), skin, eyes, liver, heart, produce a cascade of cytokines and chemotactic factors which
nervous, musculoskeletal, renal, and endocrine systems.28 result in tissue changes and granulomatous lesions that affect
Signs and symptoms: Sarcoidosis is a systemic granulomatous many tissues and allow for the multisystem, multisymptom
disease of unknown etiology. Patients affected with sarcoidosis nature of this disease. The clinical features of sarcoidosis
may present with a debilitating, febrile illness with cough and mimic those of rheumatologic diseases, with increasing reports
dyspnea, fatigue, bilateral hilar lymphadenopathy (diagnosed of coexistent autoimmune disease; however, no one has
on plain film radiograph), erythema nodosum, alveolitis, acute decisively determined an association.
polymyositis, arthritis, musculoskeletal anomalies, lacrimal or Management: Management of ocular sarcoidosis depends on
salivary gland infiltration or sarcoid nodules of the skin. It the signs and symptoms of sarcoidosis. Uveitis is to be
commonly occurs in young adults in their 2nd to 4th decade aggressively managed with topical steroids and cycloplegics.
of life with a predilection for women and black racial In recalcitrant cases, periocular sub-Tenon steroid injections
predominance.28 Patients diagnosed with systemic sarcoidosis of triamcinolone may be required every three to four weeks.
have nearly 20 percent incidence of ocular involvement.29 The Antimetabolites such as methotrexate and cyclosporine A have
most prevalent ocular sign is unilateral, anterior, granulomatous been used effectively in patients intolerant to steroids.
uveitis. Less common presentations include unilateral Primary care physician is required to manage systemic
nongranulomatous uveitis, bilateral intermediate uveitis, and disease. Diagnosis of sarcoidosis is through clinical (laboratory
bilateral chronically smoldering low-grade granulomatous tests and biopsy) and radiologic evidence. Up to 90 percent
ocular inflammation (Lofgren's syndrome).28 of patients with ocular sarcoid have abnormal chest
The common clinical ocular findings associated with radiographs. Lung biopsy by tracheobronchial fiber optic
sarcoid uveitis include decreased or hazy vision, pain, techniques can be diagnostic in most cases. Biopsy of an
photophobia, lacrimation, conjunctival injection, cells and flare enlarged, potentially infiltrated lacrimal gland or conjunctival
in the anterior chamber, granulomatous iritis with large granuloma is an acceptable alternative and can be handled by
“mutton fat” keratic precipitates scattered over the back surface most general ophthalmologists.29
of the corneal endothelium, iritis spill-over leading to anterior
vitritis, true vitritis with white exudative debris in the region Graft Versus Host Disease
of the ora serrata (snowball or snowbank retinopathy) with Graft versus host disease (GVHD) occurs when
retinal vasculitis (candle wax drippings) and phlebitis (venous immunologically competent cells are introduced into an
sheathing).30 Nodules of the iris stroma (Busacca nodules), immunoincompetent host. GVHD refers to both the
immunologic insult and the resultant consequences to the Ocular complications after HSCT: Among the common ocular
organ affected. Both allogeneic and autologous hematopoietic problems following HSCT, dry eye is recognized as the most
cell transplantation can lead to GVHD besides other causes frequent complication and is closely correlated with GVHD.
such as solid organ transplants, blood transfusions, and Even with the recent improvements in the systemic
maternal-fetal transfusions.32 Acute GVHD occurs within the management of HSCT patients, the incidence of ocular
first 100 days of transplantation. It comprises of triad of complications after HSCT remains high. Hence there is a need
dermatitis, enteritis, and hepatitis. Chronic graft versus host for early recognition of the ocular involvement and the
disease (cGVHD) is a more pleiotrophic syndrome and potentially severe ocular problems in HSCT patients. This
develops after 100 days. This consists of an autoimmune necessitates intensive ophthalmic and systemic monitoring.
syndrome that targets multiple organs. The skin is commonly Ocular complications may be subdivided into two groups
the earliest organ to be affected in GVHD. It presents 3-14 depending on whether they occur by day 100 (in the acute
months after hematopoietic stem cell transplantation (HSCT) phase or early complications) or after day 100 (in the chronic
in approximately 20 percent of matched sibling transplants phase or late complications).34,35 Ocular complications after
and in 40-60 percent of matched unrelated donor recipients.
HSCT have been enumerated in Table 6.8.3.1.35
Sites most commonly involved are skin, mouth, liver,
gastrointestinal tract, lung, and eye.33
Pathogenesis: Chronic GVHD results from a reaction of Table 6.8.3.1: Ocular complications after HSCT
immunocompetent donor marrow cells with recipient tissues
Acute phase Chronic phase
and affects the skin, gastrointestinal tract, liver and other tissues
such as the eye (Fig. 6.8.3.2). Inflammatory process in graft- Pseudomembranous conjunctivitis Dry eye
Corneal ulcer Meibomian gland dysfunction
versus-host disease is induced by donor T lymphocytes reaction
Episcleritis Retinal hemorrhage
against recipient's tissue alloantigens. In the ocular tissue, these
Secondary choroidal detachment Aseptic conjunctivitis
antigens present in the lacrimal gland, conjunctiva, other tissues Secondary glaucoma Lagophthalmos
activate T lymphocytes which proliferate and differentiate, Cytarabine-induced keratitis Corneal thinning
along with other inflammatory mediators and destroy cells of Corneal thinning Corneal melting
the host's tissue compromising their function.33 Herpes simplex virus infection Nasolacrimal obstruction
Dry eye associated with chronic GVHD is one of the major Prolonged corneal ulcer
Calcerous corneal deg-
late complications after allogeneic HSCT. It has a significant
eneration
impact on the patients' quality of life with the potentiality to Iritis
progress to blindness. The pathogenic process of dry eye Optic disc edema
associated with chronic GVHD is not clear and is believed to Cotton wool spots
Cataract
be traditional alloreactivity to recipient tissues.
Fig. 6.8.3.2: Pathogenesis of GVHD

Early complications after HSCT : Pseudomembranous Pathogenesis of Dry Eye

conjunctivitis occurring in the acute phase of HSCT recipients Associated with cGVHD
is related to acute GVHD and decreased survival has been
The pathogenesis of cGVHD35 was originally explained as
noted in patients with conjunctival involvement. Conjunctival an alloimmune response to the recipient cells by donor
involvement is a marker for severe systemic involvement in lymphocytes. Chronic GVHD is a multiorgan inflammatory
GVHD. Clinical findings in conjunctival GVHD consist of disorder that resembles a mixture of GVHD and autoimmune
pseudomembrane formation due to conjunctival epithelial loss. disorders. Acute GVHD affects primarily the skin, liver, and
Corneal ulcers and pseudomembrane formation with donor gastrointestinal tract. In severe cutaneous GVHD, bullae
T cells infiltrate has been observed. Mononuclear cells formation and desquamation occur; in acute GVHD of the
expressing natural-killer markers within the conjunctival liver, cholestatic-type damage to bile ducts is seen.
epithelium with characteristic histopathologic features of acute Gastrointestinal involvement of GVHD results in extensive
GVHD. The major finding of GVHD in the cornea and loss of intestinal epithelium. In the early phase of chronic
conjunctiva is keratinization, along with associated epithelial GVHD, the predominant features are lymphoplasmacytic
thinning in some cases. Herpes simplex keratitis can occur as infiltration involving epithelium and glands. These
an infectious complication occuring during the first month inflammatory changes cause widespread fibrosis, stenosis,
after HSCT as a result of virus reactivation. Cytarabine induced obliteration, and atrophy of the involved tissue, such as liver,
keratitis can also occur. lung, intestine, and skin. Chronic GVHD shows extensive
destruction of tubuloalveolar glands and ducts, leading to sicca
Late ocular complications after HSCT: Dry eye associated
syndrome of salivary and lacrimal glands. Immuno-
with chronic GVHD is the most frequent ocular
histochemistry studies show prominent fibrosis and an increase
complication after HSCT (40-60%) followed by meibomian
in stromal fibroblasts of the lacrimal glands. Infiltration of
gland dysfunction (48%) and retinal hemorrhage (3.5-
mononuclear cells around a medium-sized duct and a markedly
20%). 35 Severe dry eye resembling Sjögren’s syndrome
fibrotic interstitium, as well as irregular cell loss of the margin
progresses rapidly after the onset of symptoms in the
of lobules, have been described. The histopathologic findings
majority of these patients. Administration of
in chronic GVHD that are different from Sjögren’s syndrome
immunosuppressant drugs for GVHD prophylaxis is usually include more CD34+ fibroblasts, excessive fibrosis in the
completed by about 180 days after HSCT, and chronic extracellular matrix, and multilayered basal lamina of ducts,
GVHD frequently develops during tapering or shortly after lobules, and vessels. These findings indicate that stromal
discontinuation of immunosuppression. The median time fibroblasts are actively involved in the pathogenic process of
from HSCT to diagnosis of dry eye tends to coincide with chronic GVHD in the lacrimal gland by producing excessive
the time when chronic GVHD is frequently observed. These extracellular matrix components.
facts suggest that an alloimmune process contributes
actively to the pathogenesis of dry eye after HSCT. INVESTIGATIONS FOR
Meibomian gland dysfunction is frequently associated with IMMUNOLOGICAL DISORDERS
severe dry eye related to chronic GVHD. The evaluation A thorough medical history and examination is mandatory, as
of meibomian gland function is helpful for the diagnosis is comprehensive laboratory investigation. This investigation
of dry eye associated with chronic GVHD. Retinal may include:
hemorrhag e is related to GVHD vasculopathy, • Complete blood count with evaluation of the differential
cytomegalovirus retinitis, or recurrence of leukemic count, platelet count, erythrocyte sedimentation rate
diseases. Lagophthalmos, corneal thinning, corneal melting, • Rheumatoid factor (RF): Positive RF findings are typically
nasolacrimal obstruction, chronic dacryocystitis, and found in most patients with Sjögren’s syndrome, even when
calcareous corneal degeneration, optic disc edema, and they do not have RA. A diagnosis of RA is to be considered
cotton wool spots have all been reported as other late if the patient has symmetric polyarticular synovitis.36
complications after HSCT. Cataract after HSCT usually • Complement fixation
develops within 3.5 years. Cataract is caused by a • Antinuclear antibodies (ANA): ANAs are typically present
combination of pretreatment with antimitotic agents, in patients with Sjögren’s syndrome.
exposure to radiation during the conditioning process, and • Antibodies to Sjögren’s syndrome antigen A (SSA/Ro) and
prolonged use of systemic steroids. Sjögren’s syndrome antigen B (SSB/La): Antibodies against
SSA/Ro are found in approximately 50 percent of patients Procedures

with the disease (75% of patients with primary Sjögren’s • Minor salivary gland biopsy37
syndrome and 15% of patients with secondary Sjögren’s – Currently, this is the best single test to establish a
syndrome). Thus, the absence of anti-SSA/Ro antibodies diagnosis of Sjögren syndrome.
does not eliminate the diagnosis of primary or secondary – In this procedure, an incision is made on the inner lip,
Sjögren’s syndrome. Antibodies against SSA/Ro are and some minor salivary glands are removed for
present in 50 percent of patients with SLE and are examination.
sometimes found in healthy individuals. Thus, the presence – At least 4 salivary gland lobules should be obtained
of antibody against SSA/Ro cannot establish a diagnosis for analysis.
of Sjögren’s syndrome. Titers of these antibodies do not – While this is the most definitive test, performing it is
reflect disease activity. More recent enzyme-linked not absolutely necessary. Patients with Sjögren’s
immunosorbent assay tests for antibodies to SSA/Ro and syndrome are essentially treated symptomatically and
SSB/La are more sensitive than previous tests. Other observed for the development of other rheumatic
investigations include: disorders or lymphoma. This can be initiated without
– Antineutrophil cytoplasmic antibody (ANCA) performing a biopsy.
– Circulating immune complexes – Biopsy can also help in the differential diagnoses
– Liver function tests because noncaseating granulomas of sarcoidosis can
– VDRL and fluorescent treponemal antibody be found.
absorption (FTA-ABS) tests
– Blood urea nitrogen and creatinine Histologic Findings
– Serum protein electrophoresis
– Urinalysis Although pathologists use different classification systems, the
– Chest roentgenogram. characteristic findings of minor salivary gland biopsy in a
person with Sjögren’s syndrome include the following:38
• Focal aggregates of lymphocytes, along with plasma cells
Imaging Studies
and macrophages
• Sialography • More than one focal aggregate is seen per 4 mm2.
– In this test, radiopaque material is injected into the • T cells, predominantly CD4+ cells, are present
salivary glands. Sialography is useful to exclude the • Normal acini are replaced by lymphocytes
presence of obstructions or strictures, but the diffuse • Focal aggregates are seen in almost all glands
sialectasis of Sjögren’s syndrome is seen in various • Ten percent of the lymphocytes are CD5+ B cells that
other diseases and is therefore not specific. produce immunoglobulin M and immunoglobulin G
– Oil-based contrast medium may not be adequately antibodies, often with a monoclonal or oligoclonal pattern
cleared in patients with Sjögren’s syndrome and, • Large foci are present, possibly showing germinal centers
consequently, may damage adjacent tissues and lead to • Epimyoepithelial islands are uncommon in the minor
a chronic granulomatous reaction. Performing this salivary gland but can be seen in the major salivary glands.
procedure with oil-based contrast should be avoided, Additional testing is done as indicated by the review of
especially during episodes of acute swelling. systems and physical examination.
• Salivary scintigraphy: In this technique, the uptake and Other immune conditions include the following:
secretion of sodium pertechnetate technetium Tc 99m is
a gauge of the salivary flow rates and can provide an SCLERITIS
objective measurement of salivary gland dysfunction. (Refer to the section on Diseases of Sclera also)
However, the finding of low flow rates is not specific to The prevalence of scleritis in the general population is
Sjögren’s syndrome. estimated to be 6 cases per 100,000 people, but has been
Positive findings on either sialography or scintigraphy fulfill described in between 0.2 percent and 6.3 percent of patients
a criterion for objective evidence of Sjögren’s syndrome by with RA and up to 7 percent of those with Wegener's
the American-European Consensus Group.36 granulomatosis.39,40
Clinical History in Scleritis

The chief complaint of patients with scleritis is pain that
responds poorly to analgesics. The pain is described as dull,
aching, or boring and may be severe and constant. Because
the extraocular muscles insert into the sclera, the pain typically
worsens with eye movement. The pain often awakens patients
from sleep and is typically worse in early morning. The pain
can spread to the periorbital region, brow, forehead, temple,
ear, or jaw, and may be disproportionate to the clinical findings.
Up to 20 percent of patients with scleritis have little or no
pain.41 The absence of pain is observed in three settings:
1. Milder disease (e.g. diffuse anterior or nodular scleritis as
opposed to the necrotizing type)
2. Patients already on immunosuppressive medications at the Fig. 6.8.3.3: Acute anterior scleritis (diffuse) showing the
time when their symptoms begin violaceous hue (Courtesy: Dr M Vanathi)
3. Scleromalacia perforans, a rare complication of advanced
RA.
Other complaints may include tearing, photophobia, and
decreased vision. Patients with anterior scleritis usually notice
eye redness. Patients with posterior scleritis may complain of
ptosis and swelling of the periorbital tissue.
Clinical Findings in Scleritis

Patients with anterior scleritis (Figs 6.8.3.3 to 6.8.3.7) present
with a red eye. However, in some cases, the redness is located
beneath the lid and may be easily overlooked without a focused
eye examination. The redness has a violaceous hue that is best
seen in natural sunlight. Slit-lamp examination reveals scleral
edema and dilatation of both the superficial and deep episcleral
vessels. The eye in patients with scleritis is tender to palpation. Fig. 6.8.3.4: Diffuse anterior scleritis (Courtesy: Dr M Vanathi)
Ocular erythema persists after the application of topical
phenylephrine. Approximately 25 percent of patients have
bilateral disease at presentation. Scleritis ultimately becomes
bilateral in about 50 percent of patients.39-41
Classification of Scleritis
The Watson and Hayreh classification of scleritis37 divides
the disorder into anterior and posterior types based upon
the anatomic distribution of disease. Anterior scleritis is
further subdivided into diffuse, nodular, necrotizing with
inflammation, and necrotizing without inflammation
(scleromalacia perforans). Although these forms of scleritis
correspond roughly to different degrees of severity, it is
unusual for a case of scleritis to evolve from one type to
another, e.g. from diffuse anterior scleritis to necrotizing
scleritis. Fig. 6.8.3.5: Recurrent anterior scleritis (Courtesy: Dr M Vanathi)
Systemic disorders have been described in up to 45 percent

of patients with diffuse anterior scleritis, most commonly RA.44
Nodular Anterior Scleritis

Nodular scleritis is the second most common clinical
presentation of anterior scleritis, accounting for approximately
20 percent of scleritis cases.43,46 Patients with nodular scleritis
present with a firm, immobile, and tender nodule that typically
is found close to the limbus. Similar to diffuse anterior scleritis,
progression to other forms of scleritis is uncommon.46 A
systemic disease is diagnosed in 40-50 percent of patients.46
Necrotizin.g Anterior Scleritis

with Inflammation
Fig. 6.8.3.6: Scleral thinning in a case of recurrent anterior
scleritis (Courtesy: Dr M Vanathi) Necrotizing scleritis is the most serious clinical presentation
of anterior scleritis. This condition has an older age of onset
compared to the other types of scleritis and a higher
proportion of patients (50-80%) have an underlying systemic
disease. 45 The two diseases most often associated with
necrotizing anterior scleritis are Wegener's granulomatosis and
RA.45 Necrotizing scleritis typically requires therapy with
glucocorticoids and/or immunosuppressive drugs to control
the disease.43 Patients present with typical signs of anterior
scleritis combined with areas of white sclera surrounded by
edema and congestion. The areas of white sclera represent
capillary closure of the episcleral vasculature, with infarction
and necrosis of the underlying sclera. Involvement of adjacent
ocular structures, including the cornea, ciliary body, and
trabecular meshwork is observed with secondary corneal
ulceration, uveitis, or increased intraocular pressure.43 After
Fig. 6.8.3.7: Anterior nodular scleritis (Courtesy: Dr M Vanathi)
resolution of scleritis with appropriate treatment, there is
thinning of the sclera with translucency, and the choroid often
Diffuse Anterior Scleritis
is seen through the sclera. Despite such thinning, rupture of
Diffuse anterior disease, the most common clinical the globe is rare.
presentation of scleritis, occurs in approximately 60 percent
of patients.42,43 Although the onset of disease is insidious, Scleromalacia Perforans (Necrotizing Anterior
ocular inflammation may involve a substantial proportion or Scleritis without Inflammation)
all of the anterior sclera at presentation. The normal radial Scleromalacia perforans, also known as necrotizing anterior scleritis
pattern of the episcleral vessels is lost and one may see beading without inflammation, is a rare but severe form of scleritis that
and tortuosity of the vessels. Signs of corneal inflammation tends to involve both eyes and presents without redness, pain, or
such as peripheral corneal infiltrates or mild corneal thinning edema. Often there is thinning and atrophy of the episclera and
may be present.43,44 Frank corneal ulceration is not typical as loss of the episcleral vasculature. Localized areas of yellow-white
it is more common in necrotizing scleral disease (described infarcted tissue are seen. Such areas are demarcated clearly from
below). Progression to nodular or necrotizing scleritis has been surrounding tissue. Thinning may become so pronounced that
observed, but is uncommon.45 the choroid is covered by conjunctiva alone. Given the lack of
Resolution of the ocular inflammation in diffuse anterior typical symptoms, patients often present with discolored sclera
scleritis may leave a bluish gray hue caused by rearrangement or blurred vision secondary to astigmatism due to scleral thinning.
of the scleral collagen fibers. This does not represent scleral The classic patient with scleromalacia perforans is an elderly
thinning, which is an uncommon sequela of anterior scleritis. woman with longstanding RA.44
Complications of Scleritis aggressive, pulse methylprednisolone can be administered

intravenously for three days. The role of depot glucocorticoid
Scleritis can be associated with significant eye morbidity. Visual
treatment is controversial, given the potential risk for scleral
loss can result from a number of complications including
perforation with this therapy.
uveitis, cataracts, corneal melts, glaucoma, and posterior
Immunosuppressive drug therapy is instituted under
segment disease. Other less common complications include
several clinical circumstances:
scleral thinning and globe rupture with minor trauma.
i. For necrotizing scleritis, which usually requires
cyclophosphamide plus glucocorticoids from the outset
EPISCLERITIS
of treatment.
Episcleritis refers to inflammation of the superficial vessels ii. When other types of scleritis are not controlled by one
within the episclera. Ocular erythema in episcleritis is limited month of high dose glucocorticoids.
usually to only a sector of the eye and is not associated with iii. When more than 10 mg/day of prednisone is required
pain, vision changes, or discharge. Examination reveals to maintain disease control.
episcleral injection, which is more likely to be bright red than iv. Occurrence of glucocorticoid-related adverse effects.
deeply violaceous in color. The vessels involved in episcleritis A variety of glucocorticoid-sparing agents have been used
are more superficial than those in scleritis, have a radial pattern, in the treatment of scleritis. Cyclophosphamide (up to 2 mg/
and can be moved with a cotton tip applicator. Furthermore, kg/day) is the drug of choice for patients with necrotizing
palpation of the area does not result in pain. Phenylephrine scleritis and in patients with scleritis associated with a systemic
blanches the episcleral vessels in episcleritis but will not do so vasculitis such as Wegener's granulomatosis. The justification
in scleritis. The condition tends to be self-limited but for use of an alkylating agent in such cases is the high risk of
intermittently recurrent. Episcleritis is less likely to be progressive ocular damage, extraocular vasculitic lesions, and
associated with a systemic autoimmune condition than death. For patients with non-necrotizing scleritis who require
scleritis.43 Ocular complications are also less likely in episcleritis. a glucocorticoid-sparing agent, first-line treatment typically
Treatment is not necessary unless the redness is consists of methotrexate (up to 25 mg/week), azathioprine
bothersome to the patient. Therapy includes nonsteroidal anti- (up to 200 mg/ day), or mycophenolate mofetil (1 gram twice
inflammatory drugs (NSAIDs). Topical glucocorticoids may daily). Depending on severity of disease, treatment typically is
be given in recurrent cases. The importance of correctly continued for one to two years after control of inflammation.
diagnosing and distinguishing between scleritis and episcleritis Possible second-line agents for scleritis include calcineurin
is based on the potential ocular and systemic complications inhibitors (cyclosporine A or tacrolimus), infliximab, or
associated with scleritis. Studies have shown that patients with rituximab.51-55 However, none of these agents has been studied
RA-associated scleritis have more widespread systemic disease rigorously to date. In some cases of necrotizing anterior
and a higher mortality rate than those without scleritis. scleritis or scleromalacia perforans, surgical therapy is required
to address extensive scleral thinning and avoid globe rupture.
TREATMENT OF SCLERITIS Scleral grafting surgery may be performed with donor sclera,
A step-ladder approach typically is utilized in the treatment periostium, or fascia lata. Simultaneous efforts to control the
of scleritis. 47-55 The first line therapy in treating non- underlying inflammation with medical therapy are essential
necrotizing scleritis that is not caused by an infection is an when surgery is required. The treatment of scleritis with
NSAID. Two NSAID drugs have been shown to be effective: immunosuppressive medications is associated with the
flurbiprofen 100 mg three times daily and indomethacin 25- potential for treatment-related morbidity and mortality.
50 mg three times daily. If one NSAID does not relieve the Patients on high-dose glucocorticoids and other
pain and inflammation, another may be tried. immunosuppressive agents require careful monitoring, with
Systemic glucocorticoids are used in three general settings: frequent clinic visits and hematological work-up.
i. When NSAIDs prove ineffective.
ii. In cases of necrotizing anterior scleritis. PERIPHERAL ULCERATIVE KERATITIS
iii. In cases of posterior scleritis. (The readers may also refer to the section on Diseases of the Limbus for
The usual starting dose is 1 mg/kg/day (maximum of 60 more details)
mg/day) followed by a tapering schedule based on clinical Peripheral corneal ulceration is a potentially devastating
response. In patients whose disease appears particularly disorder consisting of a crescent-shaped destructive
inflammation at the margin of corneal stroma that is associated – Systemic: RA, SLE, RP, sarcoidosis, progressive systemic
with an epithelial defect, presence of stromal inflammatory sclerosis, rosacea, WG, PAN, giant cell arteritis,
cells, and progressive stromal degradation and thinning. inflammatory bowel disease, metabolic conditions, and
Commonly referred to as peripheral ulcerative keratitis (PUK), nutritional deficiencies.
it can quickly produce progressive necrosis of the corneal – Local: Mooren's ulcer, marginal keratitis, blepharitis (e.g.
stroma, leading to perforation and blindness.56 staphylococcal infection, rosacea), contact lens use,
chemical injury to the eyes, trauma, surger y,
Pathophysiology neurotrophic and neuroparalytic causes,
keratoconjunctivitis sicca, Terrien marginal
The peripheral cornea has distinct morphologic and
degeneration, pellucid marginal degeneration, and
immunologic characteristics that predispose it to inflammatory
furrow degeneration.
reactions. Unlike the avascular central cornea, the peripheral
• Infectious conditions
cornea is closer to limbal conjunctiva and derives part of its
– Systemic: Shigella species, tuberculosis, syphilis,
nutrient supply from the limbal capillary arcade, a source of
hepatitis, HIV, gonococcus, Salmonella species, and
immunocompetent cells, for example, macrophages,
bacillary dysentery.
Langerhans’ cells, lymphocytes, and plasma cells.57,58 Any
– Local: Herpes simplex keratitis, varicella-zoster keratitis,
inflammatory stimulus in the peripheral cornea that is caused
bacterial keratitis, fungal keratitis, and Acanthamoeba
by invasion of microbial organisms (bacteria, virus, fungi, and
species.
parasites), immune complex deposition (in systemic immune
• Masquerade conditions: Malignancy—Leukemia.
diseases), trauma, malignancy, or dermatologic conditions may
produce local and systemic immune responses, resulting in
neutrophil recruitment and complement activation (both MOOREN'S ULCER
classic and alternative pathways) in both tissue and vessels.59 Mooren's ulcer is a painful, relentless, chronic ulcerative
Activated complement components can increase vascular keratitis that begins peripherally and progresses
permeability and further generate chemotactic factors for circumferentially and centrally. Mooren's ulcer is, by definition,
neutrophils (e.g. C3a, C5a). Neutrophils, in turn, infiltrate the idiopathic occurring in complete absence of any diagnosable
peripheral cornea and release proteolytic and collagenolytic systemic disorder that could be responsible for the progressive
enzymes, reactive oxygen metabolites, and proinflammatory destruction of the cornea. It also is strictly a peripheral
substances (e.g. platelet-activating factor, leukotrienes, ulcerative keratitis (PUK), with no associated scleritis. Absence
prostaglandins), causing dissolution and degradation of the of scleritis is of substantial importance, since many of the
corneal stroma. 57-59 In addition, the inflamed limbal misdiagnosed cases had the peripheral ulcerative keratitis
conjunctiva itself is capable of producing collagenase, which (PUK) in association with adjacent scleritis, necrotizing or
contributes to stromal degradation.60 otherwise. Its exact pathophysiology remains uncertain,
In summary, the major pathophysiologic mechanism of although a growing body of evidence indicates that it is an
PUK is a result of degradation and tissue necrosis of corneal autoimmune disease directed against a specific target molecule
stroma produced by degradative enzymes, which are released in the corneal stroma, probably triggered in the genetically
primarily by neutrophils attracted into the area by diverse susceptible individuals by one of several possible
stimuli. provocateurs.67
Mooren's ulcer is a rare disorder, typically seen in healthy
Causes adult men with no evidence of systemic disease (Fig. 6.8.3.8).
The etiologies for developing PUK are multiple and extensive. There are two clinical types of Mooren's ulcer.68 The first,
Connective tissue and vasculitic diseases are the major risk limited type, is usually unilateral, with mild to moderate
factors. Other disorders that can cause PUK include systemic symptoms, generally responds well to medical and surgical
and local infectious conditions, as well as local degenerative treatment. This type is believed to occur in older patients and
disorders. is known as typical or benign Mooren's ulcer. In contrast, the
The differential diagnosis of PUK is outlined below:61-66 second type is bilateral, with relatively more pain and generally
• Noninfectious conditions a poor response to therapy and is known as atypical or
thickness. As the end stage of the process approaches, the

patient may experience sudden relief from the excruciating
pain that has been present throughout the course of the
disease. Iritis sometimes is associated with Mooren's ulcer.
Hypopyon is rare unless secondary infection is present.
Glaucoma and cataract may complicate the process.
Perforation has been noted in up to 36 percent cases, often
associated with minor trauma to the weakened cornea.
Diagnosis of PUK: Mooren's ulcer is idiopathic, it is a diagnosis
of exclusion. Infectious etiologies should be excluded by
appropriate cultures, because microbial keratitis can rapidly
progress and are usually amenable to antibiotic therapy.
Mooren's ulcer is easily distinguished from the
noninflammatory corneal degenerations, such as Terrien's or
Pellucid marginal degeneration, in which the epithelium
Fig. 6.8.3.2.8: Mooren’s ulcer (quiescent) in a young adult male
remains intact and pain is absent. The presence of Mooren's-
like ulcer requires an extensive search for occult and potentially
lethal systemic diseases.
Management Of PUK: A step-wise approach to the
malignant Mooren's ulcer. The benign type is 25 percent
management of Mooren's ulcer, is outlined as follows:
bilateral and the malignant type 75 percent time bilateral.69,70
1. Topical steroids
Usually bilateral progressive form of this disease occurs in
2. Conjunctival resection/recession
older individual. 3. Systemic immunosuppressives
Clinical features: Patients with Mooren's ulcer usually complain 4. Additional surgical procedure
of redness, tearing, and photophobia, but pain is typically the 5. Rehabilitation.
outstanding feature. The pain often is incapacitating and may The overall goals of therapy are to arrest the destructive
well be out of proportion to the inflammation. There may process and to promote healing and reepithelialization of the
also be a complaint of decreased visual acuity, which may be corneal surface.72-77
secondary to associated iritis, central corneal involvement, or Initial therapy should include intensive topical steroids,
irregular astigmatism due to peripheral corneal thinning. On consisting of prednisolone acetate or prednisolone phosphate
examination, the disease may be noted to begin with several 1 percent, hourly in association with topical cycloplegics and
patchy, peripheral stromal infiltrates that then coalesce, more prophylactic antibiotics.64-67 If epithelial healing does not occur
often in the medial and lateral quadrants than in the superior within 2 to 3 days, the frequency of topical steroid application
and inferior ones. An epithelial defect and a shallow furrow can be increased to every half hour. Once healing occurs, the
then develop in this area. frequency can be reduced, and tapered slowly over a period
Generally, there is involvement of the limbus, in contrast of several months. Such management, especially in unilateral,
to some other forms of PUK, such as that seen with benign form, has met with good results. Some authors have
rheumatoid arthritis or staphylococcal marginal disease.71 The advocated oral pulse therapy (60 to 100 mg daily of oral
ulcerative process first spreads circumferentially and then prednisone) when topical therapy is ineffective after 7 to 10
centrally to involve the entire cornea eventually. The anterior days or in cases where topical steroids may be dangerous
one-third to one-half of the stroma is involved, because of precariously deep ulcer or infiltrate. Topical
characteristically with a steep, overhanging edge. Healing and tetracycline or medroxyprogesterone may be used for
vascularization then follow, with the disease slowly running anticollagenolytic properties of each. A therapeutic soft contact
its course over 4 to 18 months. lens or patching of the eye may be beneficial at this stage.
Portions of the ulcer may be quiescent while others are Also, any concomitant eye disease, such as acne rosacea,
active. The end-stage result is typically a scarred, vascularized meibomitis, blepharitis, dry eye, or eyelid abnormalities should
cornea that may be thinned to less than half of its original be treated.72
If the ulcer progresses despite the steroid regimen, to prevent dislodging of the glue. When a perforation is too
conjunctival resection should be performed. Under topical and large for tissue adhesive to seal the leak, patch graft will be
subconjunctival anesthesia, this consists of conjunctival necessary. In case of larger peripheral perforations, peripheral
excision to bare sclera extending at least 2 clock hours to either crescentic lamellar or full thickness keratoplasty may be
side of the peripheral ulcer, and approximately 4 mm posterior performed. Rarely conjunctival flaps or even penetrating
to the corneoscleral limbus and parallel to the ulcer. The keratoplasty may be necessary. It should be emphasized that
overhanging lip of ulcerating cornea may also be removed. the prognosis of corneal graft in the setting of acute
Tissue adhesive and a therapeutic soft contact lens may be inflammation in patients with Mooren's ulcer is very poor.
beneficial. Multiple resections may be necessary. The rationale Once the active ulceration has ceased and the remaining cornea
of this procedure is that the conjunctiva adjacent to the ulcer has been completely opacified, because of the immune system's
contains inflammatory cells that may be producing antibodies remarkable memory, surgical attempts at visual rehabilitation
against the cornea and cytokines which amplify the in Mooren's ulceration should be done only with concurrent
inflammation and recruit additional inflammatory cell. immunosuppression since attempts at penetrating keratoplasty
Cryotherapy of limbal conjunctiva has been advocated and often are associated with recurrence and graft failure.77,78
may have a similar effect. Mooren's ulcer although a distinct clinical entity, remains
Those cases of bilateral or progressive Mooren's ulcer that a diagnosis of exclusion. One should always look for associated
fail the preceding therapeutic attempts will require systemic scleritis, limbal involvement, corneal sensation, associated
cytotoxic chemotherapy to stop progressive corneal blepharitis and keratitis, lipid deposition, ulcerated corneal
destr uction. The most commonly used agents are epithelium and stroma, to rule out other causes of peripheral
cyclophosphamide (2 mg/kg/day), methotrexate (7.5 to 15 ulcerative keratitis, including infections, collagen vascular
mg once weekly) and azathioprine (2 mg/kg/day). The degree diseases and degenerative processes.
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vascular disease. Int Ophthalmol Clin Winter 1998;38(1):21-32. 78. Aronson S, Elliott J, Moore T, O'Day D. Pathogenic approach to
64. Gregory JK, Foster CS. Peripheral ulcerative keratitis in the collagen therapy of peripheral corneal inflammatory diseases. Am J
vascular diseases. Int Ophthalmol Clin Winter 1996;36(1):21-30. Ophthalmol 1970;70:65-90.
Chapter 6.9
MISCELLANEOUS CONDITIONS
OF THE CORNEA
R Revathi, Sowmyalatha Maskabil
CORNEAL FOREIGN BODIES after blast injuries (Fig. 6.9.3) or as ophthalmia nodosum after
insect injuries (Fig. 6.9.4).
Cornea being the most exposed part, often receives foreign
bodies from the environment.1 Usually a small object flying
in high speed gets lodged within or on the cornea. Protective
lid closure reflex and the Bells phenomenon renders the • Small perforations with prolapsed iris (Fig. 6.9.5)
inferior and temporal parts of the cornea, the most common • Pigmented slough on a fungal corneal ulcer.
locations for a foreign body to lodge.2 Often recurrent episodes
are occupational hazards. People working in lathes, construc- Management
tion sites, quarries are more prone for this problem.1 Single inert foreign bodies can be left. Superficial foreign
The common foreign bodies includes: bodies are removed at slit-lamp microscope after applying
• Wind blown dust topical anesthetic using moist cotton tipped applicator or fine
• Insect fragments gauge disposable needle.
• Glass fragments
• Thorn
• Metallic fillings
Inert substances like glass, sand and certain minerals are
well tolerated and may remain within the stroma for long
periods. However, minerals like metals, vegetable matter and
insect parts are poorly tolerated. They incite toxic or immune
reactions, leading on to focal edema, inflammatory cellular
reaction, vascularization and necrosis (Fig. 6.9.1). The toxins
and enzymes released from the insect stings are responsible
for intense localized necrotic lesions, diffuse corneal edema
and anterior chamber inflammatory reaction. Early removal
of these foreign bodies is imperative to arrest these reactions
(Figs 6.9.2A and B). An infectious reaction should also be
considered. A highly toxic reaction caused by the glue used in
the sticker bindis is unique in India. This substance can cause
localized corneal melts.
Careful gonioscopic evaluation of anterior chamber is
required to rule out retained glass particles in iris and the angle.
Multiple foreign bodies embedded within the stroma are seen Fig. 6.9.1: Insect sting with diffuse corneal edema
Miscellaneous Conditions of the Cornea 633
Fig. 6.9.2A: Bee sting with localized necrotic reaction Fig. 6.9.3: Multiple corneal foreign bodies after blast injury
Fig. 6.9.2B: Lesion completely healed Fig. 6.9.4: Multiple insect hairs embedded in stroma in a patient with
after removal of the sting history of ocular bee sting injury (Courtesy: Dr M Vanathi)
When an iron foreign body is present for more than a Corneal Necrosis Associated
few hours, an orange brown rust ring results (Coats ring).3 with Old Foreign Body
They are more easily removed 72 to 96 hours after initial
removal of foreign body using a fine needle/spud or dental Occasionally patients may present with corneal necrosis
burrs.3,4 surrounding the foreign body with descemetoceles or
Removal of deeply embedded foreign body requires perforations. These foreign bodies are easily lifted off the
microsurgical procedures with local or general anesthetic as cornea. Small defects may close spontaneously with patching
indicated. the eye. However, if this simple measure fails tissue adhesive
Therapy following removal of corneal foreign body and bandage soft contact lenses will be needed. Large defects
includes topical antibiotics, cycloplegia and application of firm may require lamellar keratoplasty or penetrating keratoplasty.
pressure patch.5 Re-examination on the following day is usually Topical antibiotics and cycloplegics are required. Frequent
indicated. follow-up examinations are mandatory.
Fig. 6.9.5: Pigmented limbal foreign body mimicking iris prolapse

Fig. 6.9.6: Reis-Bucklers dystrophy
RECURRENT CORNEAL EROSIONS elements between basement membrane, Bowman's membrane

and superficial stroma.
This is a highly symptomatic clinical condition where a poorly
Increase gelatinases (MMP-2, MMP-9) action which
adherent corneal epithelium often gets eroded spontaneously.
affects basement membrane collagen and adhesive molecules
It is characterized by:6
like fibronectin and laminin is also noted in RCE.7,8
• Acute attack of ocular pain at the time of awakening
Nocturnal physiological edema of the corneal epithelium
• Photophobia and lacrimation lasting for few hours to days
aggravates the loosening of the epithelium which will get
till the epithelium heals.
pealed off readily on opening the eye lids.
Precipitating factors Clinical Signs
• Trauma: Superficial shearing trauma to the corneal Acute stage: Localized roughening or edema of the epithelium
epithelium with finger nail, paper edge or plants. or true abrasions, seen best after full pupillary dilation, in
• Pre-existing abnormal corneal epithelial, basement retroillumination.
membrane and Bowman’s membrane adhesion complex Sometimes the epithelium heals with subepithelial punctate
as in epithelial basement membrane dystrophies such as white pearl like lesions. In between attacks a superficial faint
map dot–finger print, Reis-Bucklers dystrophy or stromal grey scar will mark the area of erosion. A careful examination
dystrophy like lattice dystrophy (Fig. 6.9.6). of the contralateral eye is important to diagnose dystrophic
• Diabetes mellitus changes.
• Chronic ocular surface inflammation
• Meibomian gland dysfunction Differential Diagnosis
• Ocular cicatricial pemphigoid.
Post-traumatic erosions are usually uniocular and localized Lagophthalmos causing localized epithelial damage due to
but dystrophic RCE are usually bilateral and develop in exposure keratopathy is easily confused with RCE.
multiple corneal locations.
Management
Pathology
In acute phase: Patching the eye with antibiotic ointment for
The cause of recurrent corneal erosions (REC) is poor lubrication as well as prophylaxis against secondary infection
adhesion between the epithelium and Bowman's layer due to till epithelium heals.
defective basement membrane and adhesive components like Preservative free lubricants at day time and 5 percent
fibronectin, adhesin, hemides-mosomes and anchoring sodium chloride eye ointment at bed time for a long period
promotes proper regeneration of hemidesmosomes and Punctate subepithelial infiltrates are gray or white well
epithelial attachments, will prevent future attacks.9 circumscribed spots located in the most superficial layers of
Severe Cases: Therapeutic bandage contact lenses (BCL) - the stroma. Histologically the infiltrates consists of leucocytes
Extended wear with high DK value soft lenses can be helpful. in the superficial stromal fibers and sometimes in the
Since soft lenses worn longer period of time are notorious to Bowman's membrane itself. These lesions do not stain with
attract infecting agents caution is to be exerted in patient either fluorescein or Rose Bengal dye.
selection, while prescribing this mode of therapy. Patient
education in proper lens maintenance and frequent monitoring Causes of SPK by Location
are imperative.
Diffuse and Random
In recalcitrant recurrent disease: Anterior stromal micropunctures,
done using 25 gauge needle aim at creating a firm adhesion The causes of SPK include:13,14
between the epithelium and the underlying stroma.10 The • Viral keratoconjunctivitis/keratitis
resulting punctate scars will not interfere with visual acuity. • Thygeson's SPK
Epithelial debridement (esp. in severe secondary basement • Severe VKC
membrane disorder causing RCE): After applying topical • Dry eye
anesthetic agent, the entire loose epithelium is debrided using • Toxic keratitis
cotton tipped applicator or a surgical cellulose sponge. • Contact lens wear.
Sometimes a diamond burr is used. Topical antibiotics and
BCL are advised for at least 6 weeks till the new basement Localized Lesions
membrane is formed. Patients will be symptom free for 1 to
1. Linear arrangement: Mechanical abrasions due to trichiasis
2 years.
or foreign bodies lodged in the tarsal conjunctiva.
Phototherapeutic keratectomy using excimer laser is an alternative
2. Central (interpalpebral):
modality for treatment of patients with recalcitrant recurrent
– Dry eye syndrome
erosions. Associated conditions like blepharitis are to be treated
with hot fomentation and oral Doxycycline 100 mg per day. – Radiation keratopathy
Systemic conditions like diabetes mellitus have to be controlled. – Exposure keratopathy.
3. Superior:
SUPERFICIAL PUNCTATE KERATITIS – Trachoma
Superficial punctate keratitis is a descriptive terminology for – Molluscum contagiosum or verruca of upper eye lid
the morphological changes in the corneal epithelium and – Vernal keratoconjunctivitis
adjacent tissues caused by various pathologies.11,12 Three major – Superior limbic keratoconjunctivitis
morphological types distinguished on slit-lamp are: – Contact lens induced keratoconjunctivitis.
• Punctate epithelial erosions—PEE 4. Inferior:
• Punctate epithelial keratitis—PEK
– Dry eye syndrome
• Punctate subepithelial keratopathy—SEK.
– Inclusion conjunctivitis
Punctate epithelial erosions are erosive lesions seen as depressions
– Staphylococcus blepharokeratoconjunctivitis
brilliantly stained with fluorescein dye, caused by desquamation
– Ocular rosacea
of epithelial cells. Patients present with irritation, foreign body
sensation, photophobia and lacrimation. – Reiters syndrome
– Entropion/trichiasis of lower lid
Punctate epithelial keratitis is discreet grey or white, elevated
lesions that stain well with Rose Bengal dye. They can be fine – Nocturnal lagophthalmos
or coarse and scattered. Histologically characterized by altered – Exposure keratopathy.
epithelial cells with intracellular edema and infiltrates contain Symptoms of SPK include blurred vision, photophobia,
primarily polymorphonuclear leucocytes and subsequently foreign body sensation and tearing.
lymphocytes. Salient features of most common causes of SPK include:
Adenoviral keratoconjunctivitis (Epidemic keratoconjunctivitis/ injury due to external noxious agent is suggested by analyzing
pharyngoconjunctival fever): Viral infection caused by adenovirus structural changes seen in deeper epithelial layers in affected
is characterized by acute follicular conjunctivitis, preauricular areas.15-17
lymphadenopathy and pseudo membranous conjunctivitis in
severe cases. Diffuse corneal SPK develop by second week Epithelial Keratitis in Contact Lens Wearers
(Fig. 6.9.7). It is caused by direct infection and multiplication Linear arcuate lesions due to poor fitting or fine diffuse SPK
of adenovirus in corneal epithelial cells. The keratitis evolves which is attributed to hypoxia and toxic reaction to lens care
into subepithelial infiltrates by third week. These immune products.
reactions may last for months to years.
Other viral infections caused by Herpes simplex, Zoster Treatment of SPK
varicella, myxovirus, New castle virus can also present with
Treatment of most of these conditions including viral
SPK. SPK associated with molluscum contagiosum and
keratoconjunctivitis is symptomatic with preservative free
verrucae are thought to be caused by toxic effects of virus
topical lubricants. Only herpetic viral lesions respond to
particles.
antiviral agents. Molluscum and verrucae need removal of
the primary lesions.
Thygeson's SPK
Topical steroids have a marked suppressive effect in
It is differentiated from other types of epithelial keratopathy conditions like Thygeson's SPK and SEK following viral
by 5 features: conjunctivitis.
• Chronic bilateral coarse discrete granular gray dot like Topical cyclosporin A is also advocated for long-term
opacities with raised centers (Fig. 6.9.8) use in Thygeson's SPK.18
• Long duration with remissions and exacerbations Soft contact lens wear also found to be effective in
• Eventual healing without scars Thygeson's SPK.19
• Lack of response to systemic or topical antiviral or Mechanical factors like lid abnormalities should be
antibiotics corrected surgically.
• Symptomatic response to low dose topical steroids.
The exact nature of underlying pathology is not clear. A IRIDOCORNEAL ENDOTHELIAL
viral etiology was suspected but not proved. Crops of coarse, SYNDROME
stellate lesions occur in different locations in each episode. It Iridocorneal endothelial syndrome (ICE) is a clinical entity
typically lasts for months or even years. A immune mediated which manifests as three subgroups with varying degrees of
Fig. 6.9.7: SPK in adenoviral keratoconjunctivitis showing Fig. 6.9.8: Thygeson's coarse SPK
microdendrite formation
corneal edema, iris abnormalities and secondary angle closure

glaucoma without pupillary block. The three clinical variants
are:
• Chandler's syndrome
• Essential iris atrophy
• Iris nevus syndrome/Cogan-Reese syndrome.
ICE syndrome is usually unilateral, nonfamiliar, most
commonly seen in middle aged females (male: female—1:2
to 1:5) and occurs in Caucasians more often than Blacks.20
Pathogenesis
ICE syndrome involves an abnormal clone of endothelial
cells that develop epithelium like characteristics of
desmosomes, microvilli, tonofilaments and proliferation.
These abnormal endothelial cells are dysfunctional, which
leads to corneal edema. Furthermore, the corneal endothelium
produces a membrane that covers the angle and anterior Fig. 6.9.9: Corneal edema with iris abnormalities
surface of the iris. The membrane on the iris surface contracts,
and results in peripheral anterior synechiae, glaucoma,
corectopia, stretch holes and iris nodules. Ischemia may be a
secondary phenomenon producing melt holes.
The stimuli for the epithelialization of these endothelial
cells are unknown. Though some postulate abnormal
proliferation of neural crest cells or a fetal rest of epithelial
cells, electron micrographic studies suggested herpes simplex
virus. Histopathological examination of eyes with ICE shows
thin abnormal corneal endothelium and Descemet’s membrane
separated by a thick accumulation of collagen.21-23
Clinical Presentations
Diagnosis of ICE syndrome is made when 2 of 3 main clinical
features are present in one eye:
• Abnormal corneal endothelium
• Peripheral anterior synechiae
• Iris changes.
Fig. 6.9.10: Corectopia and polycoria
Chandler's Syndrome
The corneal endothelial changes are prominent resulting in

Iris holes which occur away from the direction of pupillary
corneal edema. It can be a bilateral manifestation also. The
displacement are caused due to traction and called as stretch
border between normal and abnormal endothelium can be
holes. Melt holes occur without corectopia and stretching are
seen by careful slit-lamp biomicroscopic examination using
thought to be ischemic in nature.
specular reflection (Fig. 6.9.9)
Peripheral anterior synechiae (PAS) are most commonly
broad based located, anterior to Schwalbe's line and result
Essential Iris Atrophy
in corectopia towards the synechiae (Fig. 6.9.11). These PAS,
This clinical variant is dominated by corectopia and progressive lift the iris off the surface of the lens and produce ectropion
dissolution of the iris. The iris dissolution begins as a patchy uveae and corectopia. As PAS becomes more extensive IOP
atrophy of stroma to full thickness holes (Fig. 6.9.10). rises.
• Posterior polymorphous dystrophy
• Fuch's dystrophy
• Iris abnormalities like iridoschisis and malignant melanoma
• Developmental disorders like Reigers syndrome and
aniridia
• Neurofibromatosis and anterior uveitis with nodules (most
of these conditions are bilateral).
Management
Clinical intervention varies with dominant features of the
various subtypes and duration of disorder.
Corneal edema may respond to topical hyperosmotic
solution or ointment or soft contact lens. In many cases if
IOP improves, corneal edema reduces
Fig. 6.9.11: Peripheral anterior synechiae Penetrating keratoplasty is indicated if vision is reduced
significantly or causes pain from bullous keratopathy or
Cogan-Reese Syndrome secondary infectious keratitis.
This can be differentiated by the occurrence of pigmented Glaucoma: Medical management has generally found to be
lesions of the iris or pedunculated iris nodules. They are islands inefficient over long-term. If the entire angle is covered by
of normal iris pinched by the contracting endothelial the membrane or sealed by synechiae, clinician must rely on
membrane. Other features include heterochromia and β adrenergic antagonists, α adrenergic agonists and carbonic
ectropion uvea. anhydrase inhibitors.
Iris dissolution is very mild, as is the corneal edema and As a general rule medical treatment fails because the
severity of angle closure glaucoma. condition is progressive. Filtering surgery is often required
though it fails after 2 to 5 years, perhaps related to proliferation
Symptoms and Signs of ICE Syndrome of a membrane over the internal opening of the scelerostomy
even when adjunctive use of antimetabolite therapy. In such
Symptoms and signs of ICE syndrome include the following:
cases, repeat trabeculectomy with MMC application or other
• Intermittent blurred vision and change in the appearance shunt operations can be attempted. Immunotoxin has been
of iris/pupil. shown to inhibit proliferation of endothelium in tissue culture.
• Halos around lights and photophobia seen in patients with Perhaps antiviral therapy may play some role if the presence
corneal edema of viral particles can be confirmed and positively identified.
• Conjunctival hyperemia and pain is seen in cases of
corneal edema and increase in IOP. REFERENCES
• Varying degrees of iridocyclitis with KP. 1. Hamill MB. Mechanical injury. In Krachmer JH, Mannis MJ,
Holland EJ, (Ed): Cornea, Vol 1, Philadelphia, 2005, Mosby, Ch
Specular microscopy: Clinical specular microscopic examination 100.
of this group of disorders shows characteristic ICE cells. 2. Kaye-Wilson LG. Localisation of corneal foreign bodies. Br Med
The cells do not show the normal hexagonal appearance of J 1992;76:741-2.
endothelial cells and become more rounded with increased 3. Zuckerman B, Lieberman TW. Corneal rust ring. Arch Ophthalmol
intracellular granularity and a dark spot. It has been shown 1960;63:254-64.
that the corneal endothelial changes are the earliest in this 4. Weaver JH. A needle for corneal foreign body removal. Trans Am
Acad Ophthalmol Otolaryngol 1971;75(3):660-61.
clinical entity and marked endothelial changes were seen with
5. Hulbert MFG. Efficacy of eyepad in corneal healing after corneal
minimal anterior synechiae. The clinically uninvolved foreign body removal. Lancet 1991;337:643.
contralateral corneas of these patients have also shown to 6. Wood TO. Recurrent erosions. Trans Am Ophthalmol Soc
have these abnormal cells.24,25 1984;82:851.
7. Aietken DA, Beirouty ZA, Lee WR. Ultrastructural study of the 16. Connell PP, O'Reilly J, Coughlan S, Collum LM, Power WJ. The
corneal epithelium in the recurrent corneal erosion syndrome. Br role of common viral ocular pathogens in Thygeson's superficial
J Ophthalmol 1995;79:282. punctate keratitis. Br J Ophthalmol 2007;91(8):1038-41.
8. Kenyon KR. Recurrent corneal erosion: pathogenesis and therapy. 17. Tabery HM. Corneal surface changes in Thygeson's superficial punctate
Int Ophthalmol Clin 1979;19(2):169. keratitis: a clinical and noncontact photomicrographic in vivo study in
9. Kenyon KR, Wagoner MD. Therapy of recurrent erosion and the human cornea. Eur J Ophthalmol 2004;14(2):85-93.
persistent defects of the corneal epithelium. In: Focal points: 18. Reinhard T, Sundmacher R. Topical cyclosporin A in Thygeson's
Clinical Modules for Ophthalmologists. San Fransisco: American superficial punctate keratitis. Graefes Arch Clin Exp Ophthalmol
Academy of Ophthalmology 1991; 9:9. 1999;237(2):109-12.
10. McLean EN, MacRae SM, Rich LF. Recurrent erosion. Treatment 19. Forstot SL, Binder PS. Treatment of Thygeson's superficial
by anterior stromal puncture. Ophthalmology 1986;93:784-8. punctate keratopathy with soft contact lenses. Am J Ophthalmol
1979;88(2):186-9.
11. Diamante GG, Leibowitz HM. Superficial punctate keratopathy.
20. Shields MB. Progressive essential iris atrophy, Chandlers syndrome
In: Leibowitz HM, Waring GO, (ed): Corneal disorders: clinical
and the Iris neavus syndrome: a spectrum of disease. Surv
diagnosis and management. Philadelphia, 1998, WB Saunders, Ch
15.
21. Portis JM, et al. The corneal endothelium and Descemet's membrane
12. Brooks AM, Grant G, Gillies WE. The influence of superficial
in the ICE syndrome. Trans Am Ophthalmol Soc 1985;83:316.
epithelial keratopathy on corneal epithelium. Ophthalmology 22. Levy SG, et al. Pathology of ICE syndrome: the ICE cell. Invest
1989;96:704. Ophthalmol Vis Sci 1995;36:2592.
13. Jones BR. Differential diagnosis of punctate keratitis. Int 23. Detection of herpes simplex viral DNA in the ICE syndrome.
Ophthalmol Clin 1962;2:591. Arch Ophthalmol 1994;112:1601.
14. Hardten DR, Doughman DJ, Holland EJ, Gothard TW. Persistent 24. Neubauer L, Lund OE, Leibovitz HM. Specular microscopic
superficial punctate keratitis after resolution of chlamydial appearance of the corneal endothelium in iridocorneal endothelial
follicular conjunctivitis. Cornea 1992;11:360. syndrome. Arch Ophthalmol 1983;101:916.
15. Darrell RW. Thygeson's superficial punctate keratitis: natural 25. Hirst LW, Quigley HA, Stark WJ, Shields NB. Specular microscopy
history and association with HLA-DR3. In: Darrell RW (ed): of irido-corneal endothelial syndrome. Aust J Ophthalmol
Viral diseases of the eye. Philadelphia, Lea & Febiger 1985:312. 1980;8(2):139-46.
Chapter 6.10
CORNEAL SURGERY
M Vanathi
6.10.1 Penetrating Keratoplasty

6.10.1.1 Penetrating Keratoplasty:
Indications and Technique
Penetrating keratoplasty (PK) (Fig. 6.10.1.1.1) is the procedure Penetrating keratoplasty1-6 can be classified into:
of corneal transplantation comprising of replacement of the a. Optical-performed for obtaining a clear visual axis for
full thickness host corneal tissue is replaced with a full thickness visual rehabilitation
donor corneal tissue. b. Therapeutic-to eliminate corneal infection
The aspects discussed in this section include basics in penetrating c. Tectonic-to provide tectonic support
keratoplasty, post PK glaucoma, corneal graft rejection, corneal d. Cosmetic-to improve appearance of eyes with a whitish
graft infection, high-risk corneal grafting, pediatric keratoplasty, corneal scar.
corneal patch grafts and alternatives to keratoplasty. Zirm performed the first successful human penetrating
corneal transplantation in 1905. Advances in microsurgical
techniques, instrumentation including microscopes and
sutures, improved tissue preservation methods, better
understanding of endothelial function and ocular surface
disease and immunology, and availability of newer and potent
antibiotics and anti-inflammatory agents has revolutionized
the corneal grafting in recent times. Today, corneal
transplantation procedures, besides being performed for
visual rehabilitation are being increasingly done for refractive
indications also.
INDICATIONS
Clinical indications (Figs 6.10.1.1.2 to 6.10.1.1.6) for optical
Fig. 6.10.1.1.1: Penetrating keratoplasty penetrating keratoplasty include:
Corneal Surgery 641
Fig. 6.10.1.1.2: Pseudophakic bullous keratopathy Fig. 6.10.1.1.5: Post infectious keratitis corneo-iridic scar
Fig. 6.10.1.1.3: Corneal dystrophy Fig. 6.10.1.1.6: Corneal opacity
• Pseudophakic/aphakic corneal decompensation

• Stromal corneal dystrophies
– Granular dystrophy
– Lattice dystrophy
– Macular dystrophy
– Schnyder central crystalline dystrophy
– Central cloudy dystrophy.
• Primary corneal endotheliopathies
– Fuch's endothelial dystrophy
– Congenital hereditary endothelial dystrophy
– Posterior polymorphous dystrophy
– Iridocorneal endothelial syndromes.
• Corneal ectasias and thinning
– Keratoconus
Fig. 6.10.1.1.4: Fuch's endothelial dystrophy – Keratoglobus.
• Congenital corneal opacity

– Peter's anomaly
– Sclerocornea
– Congenital glaucoma/buphthalmos.
• Acquired corneal scars
– Postviral keratitis
– Post infectious keratitis
– Healed keratomalacia
– Post-traumatic corneal/corneo-iridic scars.
• Non-infectious ulcerative keratitis
– Post rheumatoid corneal melt
– Exposure keratopathy
– Immune corneal melts secondary to systemic
Fig. 6.10.1.1.7: Severe corneal ulcer with
vasculitides, keratoconjunctivitis sicca stromal necrosis and perforation
– Moorens's ulcer.
• Corneal degenerations
• Failed corneal grafts
Indications for Therapeutic keratoplasty (Figs 6.10.1.1.7
and 6.10.1.1.8) include:
• Non-healing infectious keratitis
• Infectious keratitis with perforation
• Post chemical injury with corneal melt.
Tectonic indications include clinical conditions where
keratoplasty is required to either reconstruct the ocular surface
as in case of corneal perforations or to strengthen the cornea
as in cases with corneal melts with thinning/ectasias, post
chemical injury corneal damage.
Changing trends in corneal transplantation have seen a
shift towards lamellar keratoplasty, with preference for
endothelial keratoplasty for corneal pathology limited to the Fig. 6.10.1.1.8: Perforated ulcerative keratitis with
endothelium when rest of the corneal tissue is normal and extrusion of lens and vitreous prolapse
anterior lamellar keratoplasty in cases with anterior stromal
disease and normal endothelium. • Aphakic/pseudophakic corneal edema and bullous
Description of outcomes after corneal grafting surgery keratopathy
has been elaborated in four major categories by Buxton et al.2 • Inactive herpetic keratitis
Anatomical success in a corneal grafting is achieved upon • Macular stromal dystrophy.
obtaining a clear and thin graft, while functional success refers
Group 3: Fair prognosis with expected success rate of 50 to 80
to achievement of significant visual improvement (of atleast
percent
two or more lines of Snellen's visual acuity) postoperatively. • Active microbial keratitis
Group 1: Excellent prognosis with expected success rate of > • Active herpetic keratitis
90 percent • Congenital hereditary endothelial dystrophy
• Keratoconus • Corneal grafts in young children
• Central/paracentral corneal scars • Mild chemical injury
• Stromal dystrophy-granular, lattice • Moderate keratoconjunctivitis sicca.
• Early central Fuch's endothelial dystrophy.
Group 4: Poor prognosis with expected success rate of < 50
Group 2: Very good prognosis with expected success rate of percent
80 to 90 percent • Severe chemical injury
• Advanced Fuch's endothelial dystrophy • Radiation injury
Corneal Surgery 643
• Ocular cicatricial pemphigoid spectrum antibiotics are usually given by most corneal surgeons
• Stevens-Johnson's syndrome for preoperative prophylaxis. Appropriate lid care
• Neuroparalytic disease preoperatively to treat any blepharitis is mandatory as
• Congenital glaucoma periocular flora constitute the common source for
• Epithelial downgrowth endophthalmitis. Instillation of five percent povidone-iodine
• Anterior segment mesodermal dysgenesis solution into the eye at the time of surgical preparation also
• Multiple failed grafts. reduces the incidence of postoperative endophthalmitis.
PREOPERATIVE EVALUATION Intraocular Pressure Control

General systemic evaluation for cardiopulmonary fitness, Achieving good lid and extra ocular akinesia is a pre-requisite
control of hypertension and diabetes, any other systemic to reduce IOP elevations due to muscle contractions
diseases, associations, details of systemic medications, allergy intraoperatively. Use of ocular compression helps to further
tendencies. Fitness for general anesthesia in indicated cases is reduce positive vitreous pressure during surgery. A Honan's
to be done.1-3 The patient's social and economic status should balloon compression at 30 mm Hg for 30 minutes is useful.
also be taken into consideration. It is imperative to assess the Use of preoperative mannitol may be considered to lower IOP
patient’s willingness to compliance to long-term follow-up and intraoperatively.
treatment.
Proper patient counseling and education is vital to ensure Anesthesia
proper understanding of the condition the patient is suffering
Penetrating keratoplasty1-3 can be safely performed in an
from and the expected outcome of the corneal grafting surgery
outpatient surgical department under monitored anaesthesia.
and the need to understand the risks associated with keratoplasty.
Peribulbar anesthetic block with or without lid block using
long acting anesthetic agents such as bupivacaine or
Ocular Evaluation
combination of bupivacaine and lidocaine is usually preferred.
• Ocular history of present and past illness and ocular General anaesthesia is indicated in pediatric cases, patients at
surgeries an increased risk for choroidal hemorrhage or other
• Visual acuity considerations such as apprehensive patient, mental
• Detailed ocular examination of the eye and the ocular impairment, deafness, aphasia or language barriers.
adnexa including slit lamp biomicroscopy to obtain vivid
understanding of the underlying pathology, details of Pupil Dilatation
corneal vascularization, tear film status evaluation,
intraocular pressure, presence of cataract, intraocular lens Constricting the pupil with two percent pilocarpine
stability, need for intraocular lens exchange, potential preoperatively may be done to reduce lens damage during
postoperative visual acuity assessment, and ultrasonic trephining in phakic patients. Pupil dilatation with mydriatics
posterior segment evaluation. In cases where details of is required when cataract surgery is planned along with the
the anterior segment are not visible, anterior segment penetrating keratoplasty.
optical coherence tomography evaluation or ultrasonic
biomicroscopy of the anterior segment will be required. Surgical Procedure
Electrophysiological tests to evaluate posterior segment Globe Exposure
may also be required.
• Tests to ensure general systemic fitness for administration Appropriate sized lid speculum with proper positioning is
of systemic postoperative steroids, immunosuppressants imperative to minimize pressure on the lids which might
and antivirals, etc. in indicated cases. produce undue increase in IOP during surgery and globe
distortion. Lateral canthotomy may help on patients in tight
SURGICAL TECHNIQUE orbit. Bridle sutures of superior and inferior recti or corneal
traction suture may be applied.
Preoperative Preparation
Anti-infective Agents Scleral Fixation Ring
Preoperative antibiotics help to reduce the risk of The scleral fixation ring helps to maintain scleral support once
endophthalmitis associated with intraocular surgery. Broad the eye is opened if scleral rigidity is insufficient. A scleral
fixation ring is secured on to the globe with four interrupted

7-0 vicryl (or 5-0 dacron sutures) with partial thickness scleral
bites. Care is to be taken to avoid deep scleral bites while placing
the sutures. The sutures are left long so as to enable them to
be clamped on to the drape or may be cut close as preferred
by the surgeon. The size of the fixation ring is chosen such
that its diameter is slightly less than the interpalpebral fissure
size. Too large a ring may transmit undue pressure on to the
globe.
Corneal surgeons may prefer the use of scleral fixation
rings in pediatric and aphakic/pseudophakic cases. Most, avoid
its use in phakic penetrating keratoplasty where globe collapse
is unlikely and also to avoid the associated globe distortion
and astigmatism. Fig. 6.10.1.1.9: Inferior decentered penetrating
keratoplasty in a case of corneo-iridic scar
Host Cornea Marking

increases with larger donor graft size as the host graft junction
The donor cornea graft is to be centered on the host cornea
moves closer to the host limbus. Donor graft of the same size
or the pupillary axis which is usually slightly nasal. The optical
as that of host trephine size is considered in cases of
axis is marked by the surgeon using gentian violet or marking
keratoconus in order to decrease postoperative myopia.
pen. A stained 8 or 12 prong radial marker may be used to
mark the corneal surface by most surgeons to aid in placement
Donor Cornea Trephination
of sutures for better alignment and symmetry.
In cases of optical penetrating keratoplasty, after selection of
Trephine Sizing appropriate trephine size for host and donor corneas, the
donor corneal tissue is prepared. The donor corneoscleral
An epithelial mark is placed on the cornea by gentle pressure button is placed on the Teflon block, endothelial side up, with
using the trephine of the desired size. The mark is readily meticulous attention to proper centration and is cut by
visualized on drying the corneal bed with cellulose sponge. punching from the endothelial side using the trephine of the
Selection of host trephine size depends on various factors appropriate size. Donor corneal tissue may be submerged in
which include: storage media or alternatively coated with ocular visco-elastic
a. Host cornea size such as viscoat to enable optimal endothelial protection. An
b. Host corneal pathology optimal cut aims at perpendicular cut edges with minimal
c. Rejection risk. trauma to the donor endothelium.
For host cornea diameter of 11.5 mm or less, the host
trephine size is taken as 7.5 mm or 7.75 mm and for host Host Cornea Trephination
cornea diameter of 12.5 mm or more, 8.25 mm or 8.5 mm The recipient bed preparation is done by host corneal
trephine size may be chosen. trephination either with suction trephines or with hand held
The donor trephine size is usually 0.25 mm larger than disposable trephines. While using hand held disposable
the host trephine size as current surgical technique utilize donor trephines, care must be taken to ensure proper perpendicular
corneal tissue cut from the endothelial side (donor corneal positioning of the trephine on the cornea. Suction trephine
tissue cut from the endothelial side is 0.25 mm smaller than a systems such as the Hessberg-Baron or Hanna trephine
same sized cut from the epithelial side). systems enable performing uniformly perpendicular cuts with
Consideration on graft decentration/large size of the less tilting. Filling the anterior chamber with visco-elastic
donor grafts may be required in therapeutic keratoplasty through a self sealing side stab incision may be preferred by
situations, eccentrically placed/large cones in keratoconus cases some surgeons prior to trephining. After obtaining adequate
or in peripheral cornea ectasias as in pellucid marginal suction (in case of suction trephines), the trephine is
degeneration. Large sized grafts and graft decentration (Fig. continuously rotated allowing its sharp edges to penetrate into
6.10.1.1.9) is commonly associated with high degrees of the host corneal tissue up to 90 percent depth or till anterior
postoperative astigmatism. The risk of immune rejection also chamber is entered. While trephining up to 90 percent depth,
Corneal Surgery 645
the anterior chamber entry is performed using a sharp blade. – Anti-torque

Preoperative pupillary constriction using miotics may be – No torque.
considered to prevent inadvertent damage to the lens. The c. Combined (interrupted and continuous combined).
host cut is then completed with beveled corneoscleral scissors, Care is taken to obtain equally distributed optimal suture
taking care to visualize the both blades of the scissors tips at tension. All suture knots are to be buried to avoid suture
all times while completing the cut. A slight upward pressure induced irritation and giant papillary conjunctivitis. It is
of the host tissue also helps to prevent inadvertent iris damage imperative to ensure proper wound apposition to avoid surface
during cutting. Any tag of tissue remaining is trimmed using a healing problems and astigmatism arising from misalignment.
Vannas scissors. A perfect perpendicular cut helps in reducing
postoperative astigmatism. In recent times, trephination Tight sutures lead to:
utilizing femtosecond laser provides better tissue alignment • epithelial healing problems
and centration. • cheese wiring and loss of wound integrity
• flat corneal graft
Donor Tissue Placement on Recipient Bed • astigmatism.
After filling the anterior chamber with visco-elastic, the Vascularization in host corneal bed, multiple failed grafts,
prepared donor corneal button is placed on the recipient inflammatory conditions, pediatric grafts, therapeutic grafts
window and rotated carefully into optimal position. Care is are indications for interrupted suturing. Interrupted sutures
taken to avoid contact of the endothelium with iris surface or are placed using 10.0 monofilament nylon with a 160° curved
with instruments. spatulated 6 mm needle. Nylon, in view of it’s elasticity, strength
and biocompatibility in the cornea is the most preferred suture
Suturing of Donor Corneal Tissue material for keratoplasty. Most surgeons prefer a 3-1-1 closure
Placement of cardinal sutures: The first cardinal suture is adjusting the tension before the second throw is done to secure
placed at the 12 O'clock position using 10.0 monofilament the suture knot. Some surgeons use 2-1-1 closure knot while
nylon interrupted suture. The suture is placed at approximately some use slip knots to allow for adjustment of suture tension.
90 percent tissue depth. Additional visco-elastic material may In interrupted suture wound closure, 16 interrupted sutures
be injected into the anterior chamber. The second cardinal are applied. More interrupted sutures may be required in
suture is placed at 180° away, at the 6 O'clock position. This pediatric grafts and larger grafts to obtain water tight closure.
suture is the most critical to ensure proper graft alignment and Rapid wound healing in pediatric grafts cause differential
for subsequent astigmatism and hence is to be carefully placed wound healing along the graft host junction necessitating early
such that there is an equal distribution of tissue on either sides. suture removal in some areas compared to the others and hence
The 3 O'clock and 9 O'clock sutures are then placed and tied. continuous sutures are not advisable in pediatric grafts.
The anterior chamber is kept filled with visco-elastic till the Interrupted and combined suturing allow selective suture
completion of the four cardinal sutures. Thereafter, it may be removal of interrupted sutures for control of astigmatism
maintained with BSS. The remaining suturing is then completed. without compromising wound integrity. Combined continuous
The knots are rotated and buried on the donor side. and interrupted suturing is commonly performed using 8 or
Subconjunctival steroids and antibiotics may be given at 12 interrupted sutures along with a single continuous suture.
the end of surgery. The corneal surgeon may prefer a lateral The bites of the continuous suture are placed in between the
tarsorrhapy in cases with anticipated surface healing problems. interrupted sutures such that the superficial part of the
Some corneal surgeons prefer to place a bandage contact lens continuous suture approximates the wound across the
in situ at the end of the surgery. A patch and shield are secured interrupted suture. This also facilitates easy removal of the
on with adhesive tape. interrupted suture when required, without jeopardizing the
continuous suture.
Suturing Techniques Continuous suturing techniques enable adjusting suture
There are a variety of suturing techniques: tension in the early postoperative period in order to control
a. Interrupted sutures astigmatism. Their ease of placement and removal also makes
b. Continuous/running suturing (single continuous or double them more advantageous. Single continuous sutures are to be
continuous) done meticulously, as even a single irregular bite can cause
– Torque severe astigmatism.
Use of surgical keratometer at the end of suturing helps extraction of the cataract and IOL implantation depending
to check for astigmatism. This is to be performed after removal on density of the corneal opacity.
of the scleral fixation ring and optimal anterior chamber
reformation. Astigmatism can be decreased by adjusting COMPLICATIONS OF PENETRATING
segments of the continuous suture from the flat axis towards KERATOPLASTY
the steeper axis or by replacing offending sutures in case of Complications in penetrating keratoplasty1-5 may be subdivided
interrupted sutures. into:
Suture adjustments with continuous suturing technique i. intraoperative complications
may be done at two to four weeks in the outpatient office set ii. postoperative complications.
up or in the operating room. With acceptable astigmatism with
sutures in place, they may be left in situ as long as visual Intraoperative Complications
rehabilitation is achievable. In combined continuous and
Intraoperative complications may be related or unrelated to
interrupted suturing, the interrupted sutures may be removed
the surgical technique.
early for astigmatic control. Indications for suture removal
include loose interrupted sutures, tight interrupted sutures
Intraoperative Complications-Related
inducing steepening of the corneal curvature, vascularized
to the Surgical Technique
sutures, broken sutures, sutures with mucus tags and infection.
Scleral Perforation: Scleral perforation during the time of
Postoperative Medications placement of bridle sutures of the recti or at the time of
placement of the scleral fixation ring can occur.
Postoperative medications include oral analgesics,
Careful suture placement using partial thickness bites with
antiglaucoma agents and systemic antibiotics if necessary.
rounded rather than cutting needles can help to alleviate this
Topical medications include frequent instillation of steroids,
antibiotics and lubricants which are subsequently tapered in problem. In the event of scleral perforation noticed at the
due course of the postoperative period during follow-up. time of recti bridle sutures, eye is to patched following
cryotherapy and followed up closely postoperatively.
Penetrating Keratoplasty Scleral perforation due to sutures for scleral fixation ring
and Cataract Surgery occurs in the region of the pars plana and may produce
bleeding into the angle. Though this is usually self limiting,
The assessment of the lens status is important in every case
postoperative retinal periphery assessment is recommended.
of keratoplasty. It is prudent to remove a cataractous lens
simultaneously whenever an optical keratoplasty (triple Problems Related to Trephination:
procedure) is done. In cases with significant corneal guttata i. Due to improper sizing of trephines: Inadvertent use of
changes, decision to perform cataract surgery alone is made smaller size trephine for donor cornea will lead to
when there is no associated stromal edema and/or central difficulty in suturing the donor tissue onto the recipient
pachymetry is lesser than 0.6 mm1 and cataract surgery is to bed and securing water tight closure. Postoperative flat
be performed using an optimal ocular visco-elastic device such corneal curvature and hyperopia might result. Angle
as viscoat. The need to perform cataract surgery and corneal compression due to tight sutures also leads to rise in
transplantation either simultaneously or in separate sittings is postoperative intraocular pressure.
to be considered carefully. The main advantages in ii. Due to eccentric trephination: Eccentric trephination may
simultaneous procedure are performance of a single procedure occur as a result of improper centration of the trephine
only, and lesser risk of endothelial damage of the graft, from on the host cornea leading to increased astigmatism and
a subsequent cataract surgery. The disadvantage lies in the risk of rejection. Improper placement of the donor
difficulty in calculation of the intraocular lens power. Cataract corneoscleral button on the teflon block, inadvertent
surgery is to be done in an eye with corneal graft after atleast slippage of the donor tissue, or improper placement of
three months of keratoplasty for stabilization of corneal manual disposable trephines at the time of punching
refractive power. Refractive power stabilization occurs after from the endothelial side will result in an eccentric donor
complete suture removal of the graft. Combined cataract and tissue cut.
corneal grafting surgery can be performed either as iii. Due to improper trephination: Damage to the donor button
phacoemulsification with IOL implant first followed by may occur due to partial trephine cut requiring re-
keratoplasty or as keratoplasty with open sky extracapsular punching and resulting in significant endothelial damage.
Corneal Surgery 647
Inadvertent dropping of donor tissue before or after iridodialysis or synechiolyis at the angle in cases of therapeutic
trephination will also severely damage the donor keratoplasty for severe microbial keratitis. Mild hemorrhage
endothelium and increase the risk of microbial can be ignored while severe bleeding might get controlled only
contamination. Prior preparation of the donor corneal with rapid restoration of intraocular pressure by suturing the
button before preparing the recipient bed will enable donor tissue into place. Use of cellulose sponges soaked in
postponement of surgery in such instances. 1:1000 dilutions adrenaline might help. Intraocular bleed that
iv. Irido-lenticular damage: Full thickness trephination of the trickles into the vitreous may take several weeks to resolve.
host cornea, either in one region or 360° will result in
Vitreous Loss: Posterior capsular dehiscence with vitreous
damage to the iris tissue or the lens. Achieving proper
loss may complicate combined surgery involving penetrating
globe hypotony, inflating anterior chamber with visco-
keratoplasty and cataract extraction with lens implantation.
elastics prior to host bed trephination, partial thickness
Decreasing positive vitreous pressure with good preoperative
trephination followed by blade entr y, pupillary
and intraoperative hypotony will greatly serve to reduce this
constriction with miotics, will help to prevent this
complication. In the event of posterior capsular rupture,
complication. In the event of this rare complication,
adequate anterior vitrectomy and peripheral iridectomy are
repair of damaged iris tissue and lens extraction with
mandatory before placement of the intraocular lens either in
intraocular lens implant is to be performed.
the capsular bad or in the sulcus.
Retained Descemet's Membrane: Improper anterior Increased vitreous loss may be encountered in cases of
chamber entry after trephination of the host cornea may result aphakic/pseudophakic bullous keratopathy. Adequate anterior
in placement of the corneoscleral scissors anterior to the vitrectomy in such cases will reduce postoperative cystoid
Descemet's membrane while completing the trephine cut. This macular edema and endophthalmitis.
will result in inadvertent retaining of the host Descemet's Inadvertent lens damage may occur in inexperienced hands.
membrane leading to postoperative double chamber formation Preoperative intraocular lens power calculation is helpful in
and subsequent clouding and failure of the graft. Retained the event of inadvertent lens damage necessitating cataract
Descemet's membrane is difficult to visualize and has to be surgery.
carefully identified and dissected out. In the event of a
perforated Descemet's membrane permitting perfusion of Intraoperative Complications- Unrelated
aqueous humor to the graft endothelium, the donor graft may to the Surgical Technique
remain clear. Retained Descemet's membrane is more likely
to occur in congenital hereditary endothelial dystrophy and Expulsive Choroidal Hemorrhage: The incidence of
aphakic/pseudophakic bullous keratopathy where the cornea expulsive hemorrhage in penetrating keratoplasty has been
is edematous and the Descemet's membrane is thick. Careful reported to range from 0.45 to 3.3 percent. Inflammed eyes,
postoperative evaluation and early intervention to remove the trauma, myopia, glaucoma, and advanced age are significant
membrane or YAG laser opening may be considered to risk factors associated with the occurrence of expulsive
maintain the health of the donor graft. hemorrhage. Good preoperative hypotony with ideal
anaesthesia and akinesia, ocular massage, achieving adequate
Endothelial Damage: Donor endothelial damage, besides vitreous detergence, control of pre-existing glaucoma, systemic
that due to improper trephination of donor tissue and hypertension control will help reduce the possibility of
improper tissue handling, may also occur due to iris, lenticular expulsive hemorrhage. Slow globe decompression during entry
or intraocular lens touch during surgery, when the anterior of the anterior chamber is strongly recommended. Occurrence
chamber is not optimally reformed. Increased instrumentation
of choroidal detachment during the open sky phase of
in the anterior chamber during surgery can also lead to
keratoplasty will be seen as dark shadows or appearance of
endothelial decompensation. Such decompensation of the
brown masses in the red reflex. This may imply that an
donor endothelium culminates in primary graft failure with
expulsive hemorrhage is imminent. Sudden extrusion of
the donor graft failing to recover in the postoperative period.
intraocular contents or hemorrhage that slowly leads to
Intraocular Hemorrhage: Bleeding into the anterior chamber extrusion of the intraocular contents followed by frank
may occur in cases of visualized corneo-iridic scars (post- bleeding is indicative of expulsive hemorrhage. Management
infectious or post-traumatic), during intraocular lens comprises of wound closure with the thumb or finger and
explantation in cases of pseudophakic bullous keratopathy, immediate posterior sclerotomy via a stab incision in the
conjunctival in the inferotemporal quadrant in order to allow

the blood contents to egress. Multiple sclerotomies may be
necessary. It is imperative to achieve wound closure as soon
as possible. Closure with routine 10.0 monofilament nylon
sutures may not suffice and 6.0 silk sutures may be required.
In the event of unsalvageable damage, evisceration might be
the only option left.
Postoperative Complications
Immediate Postoperative
Wound leak: Wound leak in the early postoperative period
leads to a shallow or flat anterior chamber with low intraocular
pressure. If the anterior chamber remains formed in the
Fig. 6.10.1.1.10: Persistent epithelial defect
presence of wound leak, a pressure patch or bandage contact
lens might help to tamponade the leak.
• Persistent epithelial defect (Fig. 6.10.1.1.10)
• Postoperative inflammation
• Suture related infiltrates
• Suture induced vascularization (Fig. 6.10.1.1.11)
• Raised intraocular pressure
• Pupillary block
• Anterior synechiae formation
• Choroidal detachment/hemorrhage.
Late postoperative complications inherent to penetrating
keratoplasty include:
• Post-PK astigmatism
• Graft infection
• Graft rejection
• Post-PK glaucoma.
Fig. 6.10.1.1.11: Suture induced vascularization
Postkeratoplasty Astigmatism
Advances in microsurgical techniques along with optimal
eyebanking facilities have resulted in achievement of better scars, herpetic scars associated with peripheral thinning,
success rates in keratoplasty in recent times. Post keratoplasty keratoconus
astigmatism is one of the most common problems in successful ii. Peripheral corneal ectasias of the host cornea such as
grafts. Average post-PK astigmatism usually ranges around four pellucid/marginal degeneration, sclera ectasias
to five diopters. The causes of postkeratoplasty astigmatism iii. Aphakic bullous keratopathy.
are multifactorial. Factors such as pre-existing corneal pathology, Postkeratoplasty astigmatism may be higher in cases such
graft related factors, trephination technique, wound thickness as keratoconus which have high pre-existing astigmatism.
disparity, wound healing, epithelial irregularities, suture related Preoperative conditions of corneal ectasias such as pellucid/
factors, etc. contribute to astigmatism in the corneal graft. Terrien's marginal degeneration, large eccentric cones in
Preoperative, intraoperative and postoperative factors that keratoconus will also be associated with high postoperative
contribute to post-PK astigmatism are briefly elaborated here. astigmatism. Vascularization of the host bed will also influence
Preoperative factors or host factors that may result in high astigmatism as a result of differential wound healing along
postoperative astigmatism following keratoplasty include: the graft host junction. Higher astigmatism may also be related
i. Increased preoperative astigmatism of the host cornea to instability of the corneo-limbal ring in aphakic patients
in conditions such as vascularized severe-corneoiridic which affects the accurate placement of the cardinal sutures.
Corneal Surgery 649
Intraoperative factors or graft related factors that meridian if the scleral fixation of the IOL is more than two to
contribute to post keratoplasty astigmatism include: three mm from limbus or steepening perpendicular to the axis
of the haptic meridian if the fixation is 0.75 mm from the
Trephination technique: Trephine tilt will result in uneven
limbus. However, this may be modified once the corneal
distribution of remaining tissue leading to irregular
sutures are removed.
astigmatism. Care is to be taken to ensure proper perpendicular
placement of the trephine to avoid undue tilt. Anterior Suture related factors: Suture technique, suture placement,
trephination of the host cornea leads to ballooning of corneal depth and length of the suture, proximity to the visual axis
tissue into the trephine causing a larger than expected host greatly influence the final astigmatism in a corneal graft. Suture
opening resulting in ovalization of the recipient window, with technique is an important factor in determining astigmatism
resultant astigmatism. Punching of the donor corneal button during the suture-in period postoperatively. Running sutures
from the endothelial side with 0.25 mm oversized trephine without interrupted sutures result in lesser irregular astigmatism
compensates for this ovalization. Uneven, irregular and oval than interrupted or combined suture techniques. Suture
trephination of the tissues will all result in greater amount of placement plays a critical role in the amount of postoperative
astigmatism. Eccentric trephination due to inadvertent astigmatism. Proper placement of cardinal sutures is imperative
eccentric placement of the trephine will cause flattening in to avoid unequal tissue distribution of the donor tissue. Radial
the axis of displacement. placement of the sutures is also essential to void irregular
Use of blunt trephines, damaged corneal blocks will also astigmatism. Marking of the cornea aids in radial suture. The
enhance residual astigmatism. Damaged trephine block, poor length and depth of sutures also affect postoperative
technique, pressure on the globe due to bridle sutures, lid astigmatism. Maintaining optimal and equal tension in all the
speculum, and fixation ring will be associated with poor 16 interrupted sutures is essential in decreasing astigmatism.
trephination resulting in higher postoperative astigmatism. Use Sutures which are too tight or loose tend to affect astigmatism
of suction trephine systems such as Hanna, Hessburg-Baron significantly. Performing optimally timed suture adjustments
help in achieving perpendicular cuts and reduce the amount in form of either suture rotations in grafts with continuous
of astigmatism postoperatively. Presence of narrow palpebral suturing, or suture replacements in grafts with interrupted
fissure, filtration blebs or irregular corneal surface may be sutures help to manage astigmatism effectively.
associated with inadequate suction. Use of intrasurgical keratometer can help to minimize
Graft size, placement and graft-host junction apposition: astigmatism postoperatively by enabling optimal suture
Graft diameters in the range of 7.0 mm to 8.5 mm are usually adjustment at the end of the surgery.
not associated with high astigmatism. Larger graft diameters
Others
tend to be associated with lesser astigmatism and small sized
grafts will be associated with higher astigmatism. Undersizing • Increased intraocular pressure in the early postoperative
of the graft in keratoconus to decrease postoperative myopia period will also contribute to higher astigmatism.
in keratoconus may lead to increased postoperative astigmatism
• Impaired wound healing can affect postoperative
due to the increased tension of the sutures to achieve wound
astigmatism.
closure. Wound apposition may also be poor in the regions of
peripheral ectasias. Eccentric placement of the graft will result • Epithelial irregularities resulting in surface irregularities,
in greater amount of postoperative astigmatism. persistent epithelial defects produce higher astigmatism
Graft host junction mal-alignment, disparity in the shape postoperatively.
of the donor and recipient corneas, disparity in tissue thickness
at the graft host junction will also result in increased astigmatism. Post keratoplasty corneal topography
Increased disparity in the host-donor graft size will result patterns that have been described include:
in higher amounts of postkeratoplasty astigmatism. Small size
1. Oval: The ratio between the shortest and longest diameter
of graft will be associated with higher astigmatism. Graft host
of the chosen color zone is less than two-thirds.
junction mal-apposition, disparity in tissue thickness at the
graft host junction will also result in increased astigmatism. 2. Regular astigmatic pattern: The principal meridians lie
Use of posterior fixated intraocular lenses (IOL) will result at right angles to each other and the arms of the bowtie
in astigmatism with early postoperative steepening in the haptic are symmetrical. An angle between the two arms of the
bowtie pattern of less then 20° is defined as regular or advance post graft series) may be used to correct higher
astigmatic pattern. astigmatism.
a. Regular symmetric bowtie: The principal meridians lie at High astigmatism in the corneal grafts may be managed
right angles to each other. The angle between the axis by astigmatic correction procedures after all sutures have been
of the two halves of the bowtie is less than 20°. The removed. Incisional keratotomy, wound revisions with or
ratio between the width of the lobes is two thirds or without suture enhancement, wedge resection, laser ablations
more or the power difference between the two lobes is (surface ablations, single stage of sequential excimer laser insitu
more than 1 D when measured 1.5 mm from the center. keratomilieusis) includes options for correction of
b. Regular asymmetric bowtie: The principal meridians lie at postkeratoplasty astigmatism. Regrafts have also been
right angles to each other. The angle between the width advocated for high levels of astigmatism in corneal grafts.
of the lobes is less than 20°. The ratio of the difference
between the width of the lobes is less than two thirds REFERENCES
or the power difference between the two lobes is less
1. Krachmer JH, Mannis MJ, Holland EJ. Penetrating Keratoplasty.
than 1 D when measured 1.5 mm from the center. In: Cornea Volume III. Surgery of Cornea and Conjunctiva. 2nd
c. Irregular astigmatism pattern: The angle between the two Edition. Mosby St Louis, Missouri 2005;1413-1655.
steepest semimeridian is greater than 20°. This is further 2. Bright Bill FS, McDonell PJ, McGhee CNJ, Farjo AA, Serderavic
subclassified into steep, flat, localized steep and triple O. Techniques in corneal transplantation. In: Corneal Surgery.
pattern. Theory, Technique and Tissue. Fourth Edition. Mosby Elsevier
2009;273-604.
3. Mayben M, Boisjoly H. Penetrating Keratoplasty. Foster CS, Azar
Management DT, Dohlman CH. In Smolin and Thoft's The Cornea. Scientific
Selective suture removal aided by corneal topography helps in foundations and Clinical Practice. Fourth Edition. Lippincott
Williams & Wilkins. Philadelphia 2005;1021-42.
the management of post keratoplasty astigmatism in the early
4. Price FW, Price MO. Adult keratoplasty: has the prognosis improved
and intermediate postoperative period. in the last 25 years? Int Ophthalmol 2008;28(3):141-6. Review.
Mild astigmatism may be amenable to optical correction 5. Al-Swailem SA. Graft failure: II. Ocular surface complications.
with glasses. Contact lenses (routine rigid gas permeable lenses Int Ophthalmol 2008;28(3):175-89. Review.
6.10.1.2 Post Penetrating

Keratoplasty Glaucoma
Glaucoma following penetrating keratoplasty (PK) is an Risk Factors for Post-PK Glaucoma
important cause of failure and irreversible visual loss due to • In optical keratoplasty scenario:
optic nerve head decompensation. Post PK glaucoma (Fig. – Aphakic and pseudophakic bullous keratopathy
6.10.1.2.1) is defined as an elevated intraocular pressure greater – Adherent leucoma
than 21 mm Hg after keratoplasty, with or without associated – Previous keratoplasty
visual field loss or optic nerve head changes.1-7 Irvine and – Post traumatic cases
Kaufman 1 in 1969, first reported the high incidence of – Pre-existing glaucoma
increased intraocular pressure (IOP) following PKP. The – Combined PK and cataract extraction
reported incidence of glaucoma following keratoplasty ranges – Performance of vitrectomy during PK
from 9 to 31 percent in the early postoperative period and 18 – Mesodermal dysgenesis
to 35 percent in the late postoperative period.8 – Irido-corneal-endothelial syndrome.
Corneal Surgery 651
– Viscoelastic induced
– Outflow reduction due to trabecular collapse
– Pre-existing peripheral anterior synechiae
– Wound leak with angle closure
– Operative technique causing compression of angles
– Pupillary block
– Malignant glaucoma.
Intermediate onset
– Inflammation
– Vitreous in anterior chamber
– Hyphema
– Steroid induced
– Ghost cell
– Graft Rejection.
Fig. 6.10.1.2.1: Corneal graft decompensation in post Late onset

penetrating keratoplasty glaucoma – Primary open angle glaucoma
– Ghost cell
– Epithelial ingrowth
• In therapeutic keratoplasty scenario:
– Steroid induced
– Significant anterior segment inflammation—
– Rejection/inflammation sequelae
preoperative/postoperative
– Pupillary block
– Perforated corneal ulcers
– Malignant glaucoma
– Severe corneal ulcers with scleral involvement
– Progressive synechial closure.
– Multiple intra-operative intraocular procedures
The etiopathogenesis of post PK glaucoma is
multifactorial.8-16 Increased postoperative inflammation due
Reported Incidences of Post PK
to various reasons such as increased manipulation in the
Glaucoma in Indications for PK8
anterior chamber (synechiolysis, pupilloplasty, multiple
Viral keratitis 20-75% intraocular procedures, such as lens extraction and vitrectomy)
Aphakic bullous keratopathy 20-70% result in elevated intraocular pressure. Retained visco-elastic
Peters anomaly 60% is another important cause for increased IOP in the early
Aniridia with scarring 56% postoperative period. Distortion of the angle along with the
Trauma 9-55% collapse of the trabecular meshwork also contributes to
Pseudophakic keratoplasty 18-53% intraocular pressure elevation. The trabecular meshwork
Ulcerative disease 50% remains supported anteriorly by the Descemet's membrane
Corneal regraft 45-50% and posteriorly by the ciliary body lens structure. Loss of
Fuchs dystrophy 0-37% trabecular meshwork support in aphakic patients due to the
Acanthamoeba keratitis 36% absence of the lens posteriorly, is aggravated by full thickness
Keratoconus 0-12% trephining leading to incision of the Descemet's membrane
CHED and ICE syndromes 0-3% and the resultant loss of anterior support. Both these factors
lead to partial trabecular collapse and obstruction of aqueous
Etio-pathogenesis outflow. Angle distortion may also occur due to tissue
compression as a result of tight suturing, long suture bites,
Mechanisms of Increased Intraocular Pressure
large graft size.
after Penetrating Keratoplasty
Prolonged use of topical steroid therapy also contributes
Early onset to rise in intraocular pressure.
– Pre-existing glaucoma Late post PK glaucoma occurs due to angle closure
– Inflammation secondary to formation of peripheral anterior synechiae. A
– Hyphema floppy atrophic iris may also lead to a higher incidence of
peripheral anterior synechiae formation, which can be high measurements over a corneal scar. While measuring IOP
prevented by iris suturing or iridoplasty. with Goldmann applanation tonometer which is standardized
for a corneal thickness of 520 microns, overestimation of IOP
Investigations in Post PK Glaucoma may occur due to increased graft thickness. Newer indentation
Corneal astigmatism and or graft edema result in errors in tonometers for pressure measurements over the lid that are
tonometry recordings thereby enhancing the diagnostic recently available need to be evaluated further.
difficulty. Poor media clarity and corneal distortion also
Management
prevents optic nerve evaluation and the decreased visual
acuity precludes visual field assessment in these patients. The management of post keratoplasty glaucoma includes
Preoperative assessment of the anterior segment of the medical and surgical options.8,19-21
eye, with the aid of diagnostic tools, such as ultrasound Appropriate management of pre-existing glaucoma goes a
biomicroscopy (UBM) or anterior segment OCT, help to long way in ensuring success of the subsequent keratoplasty and
provide details of the angle status.17 control of intraocular pressure postoperatively. Higher incidences
Following PK, corneal thickness alterations, refractive of graft failure are noted following surgical interventions for
changes and postoperative astigmatism also do not allow for glaucoma control following penetrating keratoplasty.
an accurate postoperative measurement of the intraocular Use of short sutures with optimal suture tension, equal
pressure. Gonioscopy may be performed to view the site and suture bites on either side of the graft host junction, decreased
extent of goniosynechiae or PAS. Postoperative angle graft size, oversizing of donor grafts (especially in corneo-
evaluation with UBM/anterior segment OCT helps in iridic and aphakic recipient beds) include some of the surgical
analyzing the angle of eyes with a failed graft where anterior measures that have been adopted to reduce intraocular
segment details are not discernible. The extent of irido-corneal pressure.8 Goniosynechiolysis, iridoplasty in cases of a floppy
adhesions, location of IOL, phakic/aphakic status, anterior iris and optimal visco-elastic removal at the end of surgery
chamber depth, angle width and corneal thickness can be may also help to control intraocular pressure elevation.8
determined with this technolog y. 17 Stereoscopic disc
Topical steroids are to be used prudently in the
photographs at the first examination and serial follow-up visits
postoperative period to control inflammation and prevention
are required to detect and document progression of the
of formation of peripheral anterior synechiae formation. Short
glaucomatous optic neuropathy.
acting cycloplegics keep the pupil mobile and prevent pupillary
Intraocular pressure measurements in the early
block glaucoma. Long term use of steroid therapy can lead to
postoperative period, and IOP, optic disc changes, and
secondary steroid induced open angle glaucoma.
progressive visual field changes in the late postoperative period
form the basis for diagnosis of post PK glaucoma.
Medical Management
Intraocular pressure evaluation in the early postoperative
period, when the corneal surface is irregular, can be measured Topical antiglaucoma therapy with beta adrenergic blockers
with the Mackay-Marg tonometer, the pneumatic applanation (timolol 0.5%, betoxolol 0.5%), alpha 2 adrenergic agonists
tonometer, the Tono-Pen, or recently the Dynamic Contour (brimonidine 0.1%), prostaglandin analogs (latanaprost,
tonometer which measures IOP, independent of the corneal travoprost, bimatoprost) and carbonic anhydrase inhibitors
thickness. Goldmann applanation tonometry is possible in (acetazolamide, methazolamide) remain the mainstay in medical
cases with intact epithelium and regular mires formation on management of post PK glaucoma.
applanation. Marked corneal astigmatism causes an elliptical Beta adrenergic blocking agents act by decreasing aqueous
fluorescein pattern. To obtain an accurate reading with the humor production. In addition to systemic side effects, corneal
Goldmann applanation tonometer, the clinician should rotate complications include superficial punctuate keratitis, corneal
the prism so that the red mark on the prism holder is set at anesthesia, damage to the ocular surface and dry eyes.
the least curved meridian of the cornea (along the negative Adrenergic agents can cause superficial punctate keratitis, dry
axis).18 Alternately, two pressure readings, taken 90° apart, can eyes, allergic reactions and caution is to exercised in their use
be averaged. The accuracy of applanation tonometry is reduced in aphakic and pseudophakic patients as they can produce
in certain situations, such as corneal edema, presence of scars, cystoid macular oedema. Brimonidine tartrate 0.2 percent or
blood staining, or any condition that thickens or alters the 0.15 percent with purite preservative can be used (TDS as
cornea. False low readings will be obtained in presence of monotherapy and BD as combination therapy). It's side effects
corneal epithelial edema and stromal edema and erroneous include allergic blepharoconjunctivitis. Alpha adrenergics
Corneal Surgery 653
such as apraclonidine 0.5 percent is a potent vasoconstrictor synechiae, which have been present for less than one year.
and is useful both to prevent anterior chamber bleeding Laser hyaloidotomy may be indicated if ciliary block glaucoma
during surger y and to treat resultant IOP spikes is suspected.
postoperatively from such a bleed. Miotics have little effect
Trabeculectomy: Conventional trabeculectomy is usually not
in the presence of angle closure cau sed by peripheral anterior
effective due to dense perilimbal scarring and fibrosis with an
synechiae and are no longer recommended as they induce
increased risk of failure. In aphakic eyes, vitrectomy is also
uveitis by breaking down blood aqueous barrier and
required to prevent vitreous from blocking the trabeculectomy
consequently graft rejection and the increased risk of retinal
ostium. Antimetabolites such as mitomycin-C (0.2–0.4 mg
detachment in aphakic eyes.
applied for one to four min subconjunctivally or sub-sclerally)
Topical use of carbonic anhydrase inhibitors (Dorzolamide
either intraoperatively or as postoperative subconjunctival
2% and Brinzolamide 1%) are not recommended on a long
injections (5 mg of 5 Fluoro-uracil (FU) in 0.1 cc for 7–10
term basis as they block the carbonic anhydrase enzyme in
days) must be used in these patients to inhibit the fibroblastic
the corneal endothelium and may lead to graft decompen-
response. The reported success rate in intraocular pressure
sation. Systemic carbonic anhydrase inhibitors are very useful
control with trabeculectomy with mitomycin C in patients with
as a short term therapy in the early postoperative period to
post-keratoplasty glaucoma is 67 to 91 percent and of graft
control the intraocular pressure. Long-term use is limited by
failure is 12 to 18 percent.8
serious side effects such as tinnitus, nausea, gastrointestinal
disturbances, paresthesias, fatigue, depression, anorexia, weight Glaucoma drainage devices: The use of glaucoma drainage devices
loss, nephrolithiasis and blood dyscrasias. is effective in glaucoma control in post-PK glaucoma with a
Prostaglandin analogs can also be used to decrease IOP by reported success rate of 71 to 96 percent. It has been reported
increasing uveoscleral outflow and can be used in conjunction to be associated with a high incidence of graft failure (10–51%).
with beta blockers. They can cause cystoid macular edema in The risk of graft rejection may be increased after glaucoma
patients with aphakic and pseudophakic patients and shunt surgery increases as the drainage tube may provide a
recurrence of herpetic infection has also been reported. The conduit for retrograde passage of inflammatory cells into the
toxic effect of preservatives such as Benzalkonium Chloride anterior chamber. The presence of underlying chronic
(BAC 0.01%) present in topical antiglaucoma medication, on inflammation, extensive peripheral synechiae, multiple previous
the corneal epithelium, prompts the use of preservative free surgeries, ongoing endothelial loss, complications associated with
formulation. In cases of steroid responsive glaucoma, the dose glaucoma drainage devices (such as anterior chamber shallowing
of steroid drops may be tapered to the minimum required. Less with iris graft endothelial touch) lead to graft failure. Other
potent topical steroids that have a lesser tendency to increase complications include conjunctival erosion, prolonged hypotony,
IOP (such as topical fluorometholone, loteprednol and tube endothelial touch, tube obstruction, tube failure, retinal
rimexolone) may be considered. detachment, tube plate extrusion, epithelial down growth and
infection.
Surgical Management
Cyclodestructive procedures: Cyclodestructive procedures such as
Surgical management options for post-PK glaucoma include:8 cyclocryotherapy, transscleral cyclophotocoagulation with
• Laser interventions Nd:YAG, diode or krypton laser are the other procedures for
• Trabeculectomy with antimetabolites refractory post-keratoplasty glaucoma.
• Glaucoma drainage devices
Cyclocryotherapy: The glaucoma cryoprobe is placed for one
• Cyclodestructive procedures
minute, 1.5 mm behind the corneoscleral limbus. Six total
Laser interventions: Argon laser trabeculoplasty (ALT) is possible burns are made with equidistant spots involving the inferior
only in eyes with open angle with clear grafts and moderately 180° or 270° circumference of the globe at a temperature of
elevated IOP (20–25 mm Hg) on glaucoma medications. –60°C to –80°C. Two to three clock hours of the superior
Complications include postoperative IOP spikes and uveitis quadrant of the globe is to be left un-treated to allow for a
which can trigger graft rejection. Diode laser trabeculoplasty future filtering surgery procedure. The treatment may be
and selective laser trabeculoplasty may also be done. repeated if indicated. Complications include uveitis, immediate
Nd:YAG laser iridotomy may be done for a pupillary block. rise in IOP, graft failure, corneal decompensation, macular
Gonioplasty may be useful in cases with peripheral anterior edema and phthisis bulbi.
YAG laser cyclophotocoagulation involves use of 15 evenly spaced 7. Goldberg DB, Schanzlin DJ, Brown SI. Incidence of increased
burns, placed 1 to 1.5 mm from the limbus for 180° with a intraocular pressure after keratoplasty. AM J Ophthalmol
Nd:YAG laser. The recommended mean energy level is 4.1 to 9.3 1981;92:372-7.
8. Dada T, Aggarwal A, Minudath KB, Vanathi M, Choudhary S,
joules. Gupta V, Sihota R, Panda A. Post-penetrating keratoplasty
In diode laser cyclophotocoagulation, a semiconductor diode laser glaucoma. Indian J Ophthalmol 2008;56(4):269-77.
with a wave length of 810 nm and power settings with the 9. Zimmerman TJ, Olson RJ, Waltman S, et al. Transplant size and
elevated intraocular pressure, post keratoplasty. Arch Ophthalmol
diode laser are 1750 to 2000 mW, with a two-seconds exposure
1978;96:2231-3
time, is used. It has low scleral transmission than the Nd:YAG 10. Irvine AR, Kaufman HE. Intraocular pressure following
laser (1064 nm) but greater absorption by melanin. An initial penetrating keratoplasty. Am J Ophthalmol 1969;68:835-44.
power setting of 1500 mW is increased or decreased by 250 11. Sekhar GC, Vyas P, Nagarajan R. Post penetrating keratoplasty
mW increments until it is 250 mW, below that producing an glaucoma. Indian J Ophthalmol 1993;41:181-4.
audible popping sound. 12. Simmons RB, Stern RA. Elevated intraocular pressure following
penetrating keratoplasty. Trans Am Ophthalmol Soc 1989;87:79-
Trans pupillary argon laser photocoagulation of the ciliary process 91.
can reduce IOP in direct proportion to the number of ciliary 13. Reinhard T, Kallmann C, Cepin A. The influence of glaucoma
processes ablated. Using a Goldmann three-mirror lens for history on graft survival after penetrating keratoplasty. Graefes
visualization, laser is set at 50 µm to 100 µm spot size for Arch Clin Exp Ophthalmol 1997;235:553-7.
14. Yamagami S, Suzuki Y, Tsuru T. Risk factors for graft failure in
duration of 0.1 to 0.2 second and with a power of 1000 mW.
penetrating keratoplasty. Acta Ophthalmol Scand 1996;74:584-8.
Hemostasis is obtained with repeated application of the laser 15. Figuerido RS, Araujo SV, Cohen EJ. Management of coexisting
with larger (200 µm) spot size, 0.2 second duration and lower corneal disease and glaucoma by combined penetrating keratoplasty
power (250 mW). Ciliary processes are ablated one at a time. and trabeculectomy with mitomycin C. Ophthalmic Surg Lasers
Proper visualization of the ciliary processes requiring widely 1996;27:903-9.
dilated pupil and specialized contact lens are the main limiting 16. Perl T. Disparate diameter grafting. Astigmatism, intraocular
factors. Endoscopic cyclophotocoagulation has also been pressure and visual acuity. Ophthalmology 1981;88:774-81.
17. Dada T, Aggarwal A, Vanathi M, Gadia R, Panda A, Gupta V,
described in post-PK glaucoma management.
Sihota R. Ultrasound biomicroscopy in opaque grafts with post-
penetrating keratoplasty glaucoma. Cornea 2008;27(4):402-5.
REFERENCES 18. Schimdt T. The use of the Goldmann applanation tonometer. Trans
1. IrvineAR, Kaufman HE. Intraocular pressure following penetrating Ophthalmol Soc UK 1959;79:637-50.
keratoplasty. Am J Ophthalmol 1969;68:835-44. 19. Kirkness CM, Steele AD, Ficker LA. Coexistant corneal disease
2. Foulks GN. Glaucoma associated with penetrating keratoplasty. and glaucoma managed by either drainage surgery and subsequent
Ophthalmology 1987;94:871-4. keratoplasty or combined drainage surgery and penetrating
3. Karesh JW, Nirankari VS. Factors associated with glaucoma after keratoplasty. Br J Ophthalmol 1992;76:146-52.
penetrating keratoplasty. Am J Ophthalmol 1983;96:160-4. 20. Rapuano CJ, Schimdt CM, Cohen EJ. Results of alloplastic tube
4. Wilson SE, Kaufman HE. Graft failure after penetrating shunt procedures before, during, or after penetrating keratoplasty.
keratoplasty. Surv Ophthalmol 1990;34:325-56. Cornea 1995;14:26-32.
5. Chien AM, Schimdt CM, Cohen E. Glaucoma in the immediate 21. Ayyala RS, Pieroth L, Vinals AF. Comparison of mitomycin C
postoperative period after penetrating keratoplasty. Am J trabeculectomy, glaucoma drainage device implantation and laser
Ophthalmol 1993;115:711-4 neodymium YAG cyclophotocoagulation in the management of
6. Kirkness CM, Moshegov C. Post keratoplastyglaucoma. Eye intractable glaucoma after penetrating keratoplasty. Ophthalmology
1988;@:19-26. 1998;105:1550-6.
6.10.1.3 Corneal Graft Rejection

Penetrating keratoplasty (PK) is the most widely practiced human material, higher optical quality microscopes and better drugs to
organ transplantation and has evolved from its primitive form suppress postoperative inflammation. Graft related problems
to the present day surgery due to improved eye banking and immune graft rejection form the most important cause for
procedure, technical improvements availability of good suturing emergency presentation of keratoplasty patients.
Corneal Surgery 655
Graft rejection is an immunological process resulting in Pathophysiology

reversible or irreversible damage to the grafted cornea. It
comprises of a sequence of complex immune responses which Mechanism of Rejection1-11
involve the recognition of the foreign histocompatibility Corneal grafts have a higher success rate as compared to other
antigens of the corneal graft by the host immune system forms of organ transplantation. The low incidence of graft
leading to the initiation of the immune response cascade. An rejection in keratoplasty, despite human leucocyte antigens
efferent immune response is mounted by the host immune (HLA) matching of donor and recipient not being done as a
system against these foreign antigens culminating in rejection. routine in several keratoplasty centers, is impressive. The
The risk of rejection is more in "high-risk recipient corneal normal cornea is an immunologically privileged site and the
beds which are heavily vascularized or presensitized. immune privileged status of the eye is maintained by multiple
Irreversible immune rejection of the transplanted cornea is mechanisms which include the lack of blood vessels, lack of
one of the major causes of corneal graft failure. lymphatics, blood eye barrier, relative paucity of mature antigen
presenting cells (APC) in the central cornea, presence of
Definition immunomodulatory factors in aqueous humor and the
Graft rejection was first described by Paufique et al in 1948, constitutive expression of CD 95 L (Fas Ligand) within the
later by Maumenee (1951) and elaborated further by eye. 1-4 This privilege can be lost by inflammation and
Khodadoust and Silverstein in 1969.1 Corneal graft rejection neovascularization.
is a specific immunologically mediated process, that maybe Corneal graft rejection is primarily a cell mediated response
reversible/irreversible, in which a graft having been clear for controlled by the CD4+ T cell. Inflammation and trauma
at least two weeks, suddenly succumbs to graft edema in induces vessels and lymphatics growth into the cornea.
conjunction with anterior segment inflammatory signs. Inflammatory stimuli attract antigen presenting cells (APC)
Corneal graft rejection is defined as a complex immune- into the central corneal stroma where they frequently remain.
mediated process resulting in decompensation of the Major histocompatibility complex antigen expression on
transplanted cornea. It is characterized by one of the following: corneal cells is up regulated by local production of pro
1. Development of epithelial and or endothelial rejection line inflammatory cytokines especially as a result of viral infection
and stromal rejection line or graft rejection.
2. Recent unilateral anterior chamber reaction with keratic The recognition of the foreign histocompatibility antigens
precipitates. on the cells of the corneal allografts by the host immune system
3. Increase in corneal thickness (edema) in a previously clear leads to the initiation of the immune cascade-afferent immune
compact graft with visible aqueous cells. response arm resulting in host sensitization followed by a
Other characteristic features include: efferent immune response arm, which comprises of specific
• The process usually starts at three weeks or more in a immune response against these antigens, producing
successful clear graft decompensation of the graft tissue.
• The inflammatory process is limited primarily to the graft HLA are glycoproteins located on the cell surface. Their
• The process starts at graft margin nearest to the most structure is determined by four genes on chromosome 6 (HLA-
proximal blood vessel A, B, C and D). Class I (HLA-A, B, C) antigens are expressed
• There is movement of the inflammatory reaction towards on all nucleated cells of the body including the corneal
the center to involve the entire graft. epithelium, stromal keratocytes and endothelium. Class II
(HLA-DR, DQ, DP) antigens are selectively found on B-
Incidence
lymphocytes, macrophages, Langerhans’ cells and interstitial
Reported incidence of corneal graft rejection varies from 2.3 to dendritic cells. Interferon gamma (IFN-gamma) and
68 percent.1 About, 12 percent of graft rejection, in good inflammatory reaction increase expression of Class II antigens.
prognostic keratoplasty cases and 40 percent in complicated These donor antigens in the process of host sensitization
cases culminate in graft failure.1 The frequency of episodes of get processed by antigen presenting cells (APC) of the host
graft rejection is lower in normal risk keratoplasty as compared or the donor cornea at or near the graft-host interface. The
to high-risk keratoplasty eyes. Endothelial rejection rates are processed antigens are externalized on the APCs and presented
high in grafts placed in vascularized beds. to the host immune system in conjunction with HLA II and
interleukin 1 (IL-1). Donor class I antigens get recognized by Risk Factors

host cytotoxic T cells (CD8+) and the donor class II antigens
The risk factors for occurrence of corneal graft rejection
get recognized by helper T (Th or T-helper) cells (CD4+).
include:1,5-12
Once sensitized the host mounts an immune response against
the foreign antigen which can manifest in many ways. The Donor Factors
host is apparently sensitized within a week but it is the ability
of the effector cells to reach the graft that manifests in the Donor factors mainly relate to the antigenic load of the donor
rejection phenomenon. The host response mounted against depending upon the HLA and ABO compatibility between
the foreign antigen comprises of the efferent arm of the the donor and host. Other donor factors influencing graft
rejection cascade. The activated Th cells release IL-2, IFN- rejection include the method and duration of storage of the
gamma, macrophage activation factor (MAF), migration donor cornea and nature of donor button cutting (strength
inhibition factor (MIF) and several other lymphokines and of APC in the donor button). Pretreatment of donor tissue
cytokines. IL-2 further stimulates activation and proliferation with ultra violet radiation may reduce the chances of
of other T and B lymphocytes. IFN-gamma induces expression development of rejection. Storage of corneal tissue may reduce
of class II antigens which are potent stimulators of the the frequency of allograft rejection, especially in high-risk
rejection response. Cytotoxic T lymphocytes are the primary patients. However, in the Colloborative Corneal
effector cells which mount an attack on the cells bearing the Transplantation Studies (CCTS) evaluation12, donor corneal
foreign antigen. B cells produce antibodies against the foreign preservation characteristics were not reported to have
antigen which attracts non-specific inflammatory cells such significant influence on graft outcome. Influenza vaccination
as the macrophages, natural killer cells antibody dependent precipitating a bilateral graft rejection and rejection following
cell mediated cytotoxic cells (ADCC) and complement vaccination can also occur.
activation. Thus sets in the immune mediated complex cascade
of cellular events which need to be controlled early and Host Factors
aggressively in order to protect the graft function. Vascularization of the host cornea prevails as the most
Anterior chamber associated immune deviation (ACAID) important factor. The host bed may be classified as low risk,
is another active regulatory process that requires time to develop medium risk and high-risk depending upon the degree of
and may be insufficient to prevent active sensitization to foreign vascularization. The degree of vascularization may be defined
alloantigen. FAS positive mononuclear cells infiltrating the as the number of quadrants of vascularization rather than the
anterior segment rapidly become apoptotic but may still cause a total number of blood vessels. Deep stromal vascularization
degree of damage before they die. Corneal lymphangiogenesis of the host cornea of two or more quadrants classify as high-
(CL) is always less extensive than hem-angiogenesis and CL is risk cornea. As per the CCTS definition, the host recipient
correlated to the degree of hemangiogenesis. Corneal blood bed is considered as high-risk if the vascularization of two or
vessels allow influx of immune effector cells, CL provides an more quadrants is seen extending at least two mm into the
exit route for antigenic material and APCs from the graft to the stroma or a previous graft rejection in the affected eye.12
regional lymph nodes. This induces alloimmunization and A previously rejected graft has a significant predisposition
subsequent graft rejection. Therapeutic inhibition of CL and to graft rejection as the host is presensitized, resulting in a
interference with APC uptake into lymphatic vessels might mounted immune response.
enhance transplant survival. Ocular surface diseases such as severe dry eye, severe
Lymphocytotoxic antibodies, especially directed against chemical burns, radiation burns, ocular pemphigoid, Stevens-
donor class I HLA antigens following corneal transplantation Johnson syndrome and neuroparalytic disease are also
in high-risk patients, are associated with immune graft rejection associated with poor prognosis for the corneal graft survival.
and can be an indicator of allograft rejection. The role of Inflammation due to active keratitis (bacterial, viral or
CD4 (+) T cells as effector cells in corneal allograft rejection fungal) also predisposes to decreased graft survival rates.
is poorly understood. Corneal allograft rejection results in a Young patients and bilateral graft have more chances of
series of interactions between different classes of antigen graft rejection due to active immune system. Post immunized
presenting cells, cytokines and leukocytes. The presence of patients and patients with high T4/T8 ratio also run high-risk
donor-derived Langerhans cells in the corneal allograft doubles of graft rejection. Graft rejection was found to be in association
the incidence of rejection. with risk factors like atopic dermatitis and clinically manifest
Corneal Surgery 657
tear insufficiency. An increased incidence of graft rejection Classification

has been noted to occur inferiorly, probably relating to the Corneal graft rejection can be classified as:
presence of certain factors present in the tears. It has been • Epithelial rejection
postulated that the bathing of the inferior corneal surface, • Chronic stromal rejection
particularly, the inferior graft-host interface increases the risk • Hyperacute stromal rejection
of rejection occurring at this site. • Chronic focal rejection or endothelial rejection.
The CCTS group has identified young recipient age, the
number of previous grafts, history of previous anterior Clinical Features
segment surgery, preoperative glaucoma, quadrants of anterior
synechiae, quadrants of stromal vessels, a primary diagnosis Epithelial Rejection
of chemical burn, and blood group ABO incompatibility as
In epithelial rejection the eye is generally quiet, asymptomatic
strong risk factors for graft failure.
or may be mildly inflamed. Reported incidences of epithelial
Herpetic eye disease is also considered a significant high- rejection range between 10 to 14 percent. Epithelial rejection
risk for corneal grafting and greater use of postoperative manifests as a linear pattern from the periphery of the graft,
antiviral prophylaxis in the presence of previous herpetic often close to the site of vascularization of the graft host
corneal pathology may be beneficial. junction, with gradual progression towards the center. It appears
Suture loosening, preoperative and postoperative corneal as an elevated undulating line with positive staining with
vascularization are perhaps the most important risk factors fluorescein or Rose Bengal dye. It usually subsides in six to ten
for immunologic graft reactions occurring in approximately days but may also last several weeks. Though epithelial rejection
14 percent of patients after allogenic penetrating keratoplasty. is usually self limiting (the donor epithelium is replaced by host
It has also been proposed that pilocarpine therapy epithelium within a weeks time), it usually heralds the onset of
diminishes corneal allograft immune privilege and enhances other types of rejection. It may also be associated with persistent
graft rejection by the mechanisms that may include induced epithelial defect or epithelial ring presentation.
intraocular inflammation and altering of anterior chamber
associated immune deviation. Chronic Stromal Rejection
Excimer laser phototherapeutic keratectomy can also
This represents low grade rejection process with risk of
trigger a corneal graft rejection episode.
development of other form of severe rejection. Its incidence
Intra operative factors: Large/eccentric graft, iris adhesion at graft varies from 2.4 percent to 15 percent. This presents as sub-
host junction, penetrating graft, previous anterior segment epithelial infiltrates, six weeks to 21 months postoperatively either
surgical reconstruction, bilateral graft also contribute to alone or in association with epithelial and endothelial rejection.
triggering immune rejection of the graft. Large sized graft They are best seen with diffuse direct illumination as white ovoid
being closer to the limbus elicits an earlier immune response. lesions approximately 0.2 to 1 mm in diameter either in or
immediately below Bowman's layer, in the donor tissue.
Post operative factors: Corneal epithelial breach due to exposed
suture knots, loose suture, entropion and trichiasis are some of Hyperacute Stromal Rejection
the predictive factors during post operative period that may give
rise to irritation leading to subsequent ulceration and corneal This type of rejection is usually seen simultaneously with or
vascularization, thus predisposing to graft rejection. Formation immediately following endothelial rejection. It presents as
of synechiae at the graft host junction, release of postoperative sudden onset of peripheral full thickness stromal haze in a
previously clear graft, usually adjacent to an area of
synechiae, suture removal may all induce graft rejection.
vascularization. An abscess like picture of the graft without
Pediatric age group: The active immune system of children makes any hypopyon, confined to the limits of the graft is seen, in
them more prone for graft rejection. Besides this, suture related the early stages. Ciliary congestion is present. This haziness
problems are more frequent in children. Rapid wound healing rapidly spreads to the corneal center within a very short time
leads to earlier suture loosening, aggregation of mucus leading (24–48 hours) and may be associated with loss of epithelium.
to infection, suture induced erosions, all of which predispose The stromal rejection differs from that of other types by
to vascularization and graft rejection. the following:
a. The migration of rejection band is away from the Endothelial rejection is an emergency, mandating early
vascularized part of the graft. presentation to facilitate initiation of treatment.
b. Progress of the rejection is followed by growth of vessels Rejection in corneal regrafts has the following
into the stroma. characteristics:1
c. It mimics the clinical picture of corneal abscess in heavily • It may occur within first two weeks of grafting as the host
vascularized cornea. is already presensitized
d. The haze may invade adjacent host cornea in proximity to • Higher risk of graft failure exists despite treatment, with
the vascularization. high chances of recurrences in subsequent grafts too
Mild form is amenable to medical therapy, while the severe • Involvement of the margin of the recipient bed (previously
one responds poorly to treatment. In severe form of rejection rejected graft) adjacent to the graft may be seen
the epithelium falls off leaving a persistent epithelial defect • Absence of "K" line despite intensive anterior chamber
for a long time. This may lead to total stromal haziness, stromal reaction is seen characteristically
necrosis, descemetocele and perforation. • Prolonged corticosteriod therapy will be required in the
management of rejection in regrafts.
Chronic Focal Rejection
Chronic focal rejection or the endothelial rejection is the most
symptomatic and devastating type with reported incidence rates
varying between 2 percent to 44 percent.1 Endothelial rejection
is more common in young individuals with more active immune
system. Patients present with pain, redness and decreased
vision. The average period of onset has been in months and
may occur even after 35 years. It has a direct correlation with
the degree of vascularization. It has been observed that larger
size/eccentric grafts are more prone for endothelial rejection,
possible due to the proximity of the graft to the limbal blood
vessels and existence of greater numbers of antigenic
Langerhans’ cells in the peripheral cornea which express class
II antigens.
Endothelial allograft rejection (Fig. 6.10.1.3.1) may also
be of the reversible or irreversible type depending upon the Fig. 6.10.1.3.1: Endothelial graft rejection presenting with KPs,
graft response to management. The rejection is reversible when differential graft edema, Descemet's membrane folds
the corneal graft responds to corticosteroid therapy with
reduction of edema, restoration of clarity and resolution of
inflammatory signs. It is irreversible when endothelial
decompensation sets in, resulting to graft failure (Fig.
6.10.1.3.2), despite management measures.
On examination, the eye shows conjunctival hyperemia,
anterior chamber reactions, keratic precipitates and graft edema.
The anterior chamber reaction may be mild to moderate in
nature. The KPs can be diffusely scattered or lined up in a chain
like configuration on the graft endothelium forming the
pathognomonic endothelial rejection line of Khodadoust. The
lines, starts at the periphery of the graft at the point of corneal
vascularization and moves towards the center of the graft.
Stromal edema and Descemet's membrane folds can be diffuse
or segmental. Generally these folds are between the graft edge
and endothelial rejection line. The presentation at times could
be a combined stromal and endothelial rejection. Fig. 6.10.1.3.2: Graft failure due to irreversible immune rejection
Corneal Surgery 659
MANAGEMENT OF GRAFT REJECTION Reduction of Antigenic Load of Donor Tissue

Management of graft rejection includes: 1,5-8,13-20 Intraoperative factors influencing reduction of the donor
• Prevention antigenic load include:
• Treatment. a. Proper graft centration as Langerhans’ cells that express
class II antigens are primarily located in peripheral cornea.
Prevention b. Removal of the donor epithelium to reduce the risk of
1. Preoperative measures to minimizing antigenic difference rejection as the epithelium acts as a source of class I and
between the host and the donor tissue. class II antigens. However, epithelial debridement is now
2. Intraoperative factors consist of adopting meticulous not considered to contribute to help in prevention of
surgical technique including avoiding decentration of the allogenic rejection.
recipient bed trephination, optimal suturing and good graft c. Exposure of the donor tissue to ultraviolet light is believed
host apposition. to reduce the rate of rejection by prevention of activation
3. The postoperative measures include controlling or of cytotoxic T cells. Depletion of Langerhans’ cells could
alleviating the host immune response to the foreign donor also be a possible mechanism.
tissue. Need for optimal postoperative care and close d. Depletion of local macrophages from the donor corneal
button prevents graft rejection and has been described to
follow-up of keratoplasty patients for timely interventions
be achieved by sub conjunctival injection of clodromate
in terms of suture management are of utmost importance
liposomes which alters delayed type hypersensitivity
in decreasing suture related vascularization and rejection.
(DTH).
e. Establishing anti lymphangiogenic strategies: As
Minimizing Antigenic Differences
lymphangiogenesis helps in the exit of antigen-presenting
Between Host and Donor
cells and antigen material from the corneal graft to the
Disparity between donor and recipient major histocompa- regional lymphnodes inducing alloimmunization leading
tibility antigens remains the major cause of concern. to graft rejection, regulating anti lymphangiogenic strategies
Mismatches at either class I or class II loci lead to a higher in corneal transplantation. This is still experimental.
frequency in corneal graft rejection. The risk of graft rejection f. Organ cultured stored cornea : It is believed that the organ
is further increased in patients with vascularized graft beds cultured stored corneas take up the serum proteins from
and in presensitized persons. The CCTS has elaborated the the cultured medium, thus increasing the antigenic load.
effectiveness of histocompatibility matching in high-risk On the other hand there is reported evidence of reduction
corneal transplantation. It was found that: of Langerhans’ cells and dendritic cells bearing class II
antigens which could be effective in minimizing the risk
1. HLA-A, -B or HLA-DR antigen matching does not
of rejection.
substantially reduce the likelihood of corneal graft failure.
g. Endothelial cell transplantation is a promising aspect
2. A positive donor-recipient crossmatch does not
towards minimization of graft rejection.
dramatically increase the risk of corneal graft failure.
h. Gene therapy of donor corneas ex vivo, while in storage
3. ABO blood group matching, may be effective in reducing
prior to implantation, and the relative isolation of the
the risk of graft failure.
transplanted cornea from the circulation is considered to
Corneal allograft rejection is mainly mediated by the TH1- decrease the risk of potential rejection.
type immune response, which leads to a delayed-type i. Pre-treatment of the graft with hyperbaric oxygen and also
hypersensitivity reaction. The suppression of the TH1-type use of heterologous antibody treated corneal button are
immune response and MHC matching together is found to have known to reduce antigenicity.
a beneficial effect in promoting allograft survival in humans. Other aspects of historical mention, include:
The fact that several centers worldwide are performing i. Preservation of donor cornea in recipients serum
keratoplasty without HLA matching goes to prove that the ii. Pretreatment with anti-lymphocyte serum
importance of the role of major histocompatibility complex iii. Pretreatment with succinylated anti-lymphocytic
matching in corneal graft rejection is debatable. globulin.
Suppressing the Host's Immune Response for two months, thrice daily for two months, twice daily for
three months and once daily for four more months or life
Immunosuppression of the host can be achieved by:
long as preferred by some corneal surgeons.
i. Preoperative reduction in host bed vascularization may
Treatment regime in acute rejection consists of hourly
be achieved by i) irradiation; ii) argon laser therapy; iii)
instillation of topical steroids till the rejection process gets
topical corticosteroids; iv) tectonic keratoplasty; v) stem
arrested or reversed. This is to be complimented with systemic
cell transplantation in accordance to the etiology of the
steroid therapy in form of pulse steroid dosage. Systemic
recipient disease.
steroid are to be continued per oral after the initial pulse
ii. Immunosuppressive therapy with preoperative and
therapy. Maintenance and tapering of systemic steroids will
postoperative use of drugs such as corticosteroids, is
depend on the time of postoperative presentation of the
widely practiced. Immunosuppression with oral
rejection episode, severity of the graft rejection and the
azathioprine, topical and systemic corticosteroid, topical
response to the therapy.
and systemic cyclosporine, systemic mycophenolate
Systemic corticosteroids in addition, reduce the number
mofetil is followed in high-risk keratoplasty. Rapamycin
of circulating T cells and inhibit their proliferation. Systemic
and 15 Deoxyspergualin are still in experimental stage
administration either by "oral" or "intravenous" route should
of evaluation. Newer immunosuppressives such as anti-
always be along with the topical corticosteroids. In acute graft
CD154 monoclonal antibodies, anti T monoclonal
rejection, higher doses of 60 to 80 mg daily are recommended
antibodies, neutralizing antibodies against vascular
and tapered off when the graft begins to recover and is usually
endothelial growth factor, leflomide is under
cured by six to eight weeks.
experimental evaluation.
Intravenous pulse corticosteroid therapy is given with IV
methyl prednisolone (500 mg in 150 ml of IV fluid). Though
Management
the exact mechanism by which pulse therapy reverses rejection
Management of corneal graft rejection consists of (a) early process is not exactly known, it has been supposed to cause a
detection and (b) aggressive therapy.1, 5-8 It is mandatory to fore transient lymphopenia which is maximal at four to six hours
warn the patients with corneal graft to report at the onset of and lasts up to 48 hours. The T lymphocytes get affected by
the early symptoms and signs of graft rejection such as this to a greater extent than B cells, with a resultant depletion
decreased vision, pain and redness and reduction in visual acuity. of the helper cells. Delayed hypersensitivity, skin test, primary
and secondary antibody responses return to normal by 48
Corticosteroids hours after the pulse therapy.
The anti-inflammatory effect of the pulse therapy lasts
Current practices in the management of corneal graft rejection
for four to seven days. The beneficial effect of an additional
still hold corticosteroids, in form of systemic or topical therapy,
pulse over single pulse therapy is doubtful. In high-risk grafts,
as the gold standard in the treatment of acute graft rejection
current therapy has been reported to be less effective in
because of their numerous properties. Various routes of
reversing graft rejection. The combined effect (i) inhibition
administrations have been advocated with their merits and
of the proliferation; (ii) temporary removal of re-circulating
demerits.
T- lymphocytes from the blood and eye, and (iii) suppression
The pharmacotherapeutic effects of steroids include
of inflammation serve to help in the management of graft
blockage of prostaglandin synthesis by inhibiting phospholipase
rejection. Pulse therapy is also beneficial in preventing
A2 and the lipo-oxygenase pathways, decrease of both cellular
and fibrinous exudation, inhibition of chemotaxis and subsequent rejection episodes. Graft survival following
phagocytosis, restoration of capillary permeability, stabilization treatment of a rejection episode with local corticosteroid
of the lysosomal membranes of polymorphonuclear cells treatment alone is good in those patients without other risk
(PMN) and inhibition of graft vascularization. factors for graft failure.
Topical steroid therapy for prevention and management
Cytotoxic Agents
of corneal graft rejection varies from center to center.
Treatment with topical corticosteroids for prevention in high- Azathioprine is a phase specific cytotoxic agent which inhibits
risk grafts consists of preoperative instillation of four times a purine synthesis. As this inhibits cell replication during a
day for one week. Post operative instillation comprises of specific phase of the cell cycle it is helpful in early phase of
hourly for three days, two hourly for 15 days, four times daily rejection but not in late phase. Azothioprine is given at a dose
Corneal Surgery 661
of 1-2 mg/kg/day orally along with topical corticosteroids. is between 120 ng/ml and 150 ng/ml. Elevated serum urea and
Simultaneous use of azathioprine and corticosteroid, besides creatinine, hypertension, gum hyperplasia, increased sweating,
being effective in early stage of corneal graft rejection also backache, nausea, feeling unwell, oral candidiasis, cramps, and
reduces the need of systemic corticosteroids thus reducing paresthesia of the extremities are the commonly occurring side
the systemic complications of high dose corticosteroid. During effects. Recommended dosage is 15 mg/kg/day for two days
maintenance, investigations such as complete blood counts followed by 7.5 mg/kg/day for two days and then adjusted to
and liver function test are mandatory. Further, due to the side maintain trough blood levels of 100-200 µg/l for six months
effects of the drug such as bone marrow suppression, anemic after reversal of acute rejection episode. Owing to its variable
thrombocytopenia, leucopenia, hepatocellular necrosis, GI absorption, blood level monitoring, liver function and renal
tract toxicity, increased risk of neoplasia and alopecia, use of function tests are mandatory.
azothioprine, for prevention of corneal graft rejection is Combined methyl prednisolone and CsA therapy: Systemic steroid
limited. therapy may be used in conjunction with CsA. Combined
Cyclosporine A (CsA) is a powerful immunosuppressive agent intravenous pulse methylprednisolone and oral CsA in the
derived from the fungus tolypocladium inflatum gans. Like treatment of acute corneal graft rejection is safe and effective
azathioprine, it also acts at the early stages of antigenic in reversing the rejection process and may also protect the
sensitization. It is an immunomodulator and works on T cells graft from subsequent episodes of allograft rejection.
by binding to the intracellular peptide-cyclophilin. It inhibits
antigen presentation and thus lymphokine production. By Newer Immunoregulatory Agents
virtue of its anticyclophilin activity, cyclosporine reduces FK-506 (Tacrolimus) is derived from fungus Streptomycetes
production of interleukin-2 (IL-2), thus limiting the activation tsukybaensis. FK-506 which is highly lipophilic in nature is
of CD4+ and CD8+ T cells. said to 10 to 100 times more potent than CsA with similar
Topical CsA is prepared either in olive/castor oil as two percent mechanism of action. While CsA binds to the immunophilin
solution or in artificial tear as one percent solution. It is - cyclophilin (CyP), FK-506 binds to a separate immunophilin,
prescribed five times a day along with the topical corticosteroid FK-506 binding protein (FKBP). It is effective in prevention
drop in high-risk patients both pre and post operatively. Blood of allograft rejection at a dose of 0.16 mg/kg/day. It does
CsA level after topical therapy is negligible which is much below not produce systemic side effects. FK-506 has been extensively
than systemic therapeutic level. Therefore, it does not necessitate used in preventing immune rejection for human organ
monitoring of blood cyclosporine A levels. But, monitoring of transplantation. FK-506 has been found to be effective in
renal and liver function is required. Topical cyclosporine 0.5 prevention of rejection in patients with high-risk corneal and
limbal grafts.
percent is effective in eyes with satisfactory preoperative corneal
transplantation beds, whereas it has been reported to have only Rapamycin is more potent than CsA and FK-506. It binds to
beneficial effects in eyes with poor preoperative corneal FK-506 binding protein (FKBP) and inhibits the
transplantation beds. Cyclosporine-treated grafts have been immunophilim activity. It also interferes with the IL-2 induced
found to contain significantly fewer infiltrating T lymphocytes signals. It suppresses T cell activation at the level of lymphokine
indicating that the topical application of cyclosporine actively production. It is lipophilic in nature and allows better corneal
inhibits the entry of T cells into the grafts. Topical cyclosporine penetration.
treatment is effective in reducing the risk of allograft rejection 15-deoxyspergualin (DSG) is derived from bacillus Laterosporus.
in high-risk patients. Its application is however associated with Its mechanism of action is different from that of CsA, FK-506
significant ocular surface irritation. and Rapamycin. It inhibits both lymphocytes and monocytes. It
is however associated with a number of side effects.
Systemic CsA use is used to prevent rejection in high-risk patients.
Mycophenolate mofetil (MMF) has been shown to be a safe and
Its main action is on the afferent limb of the immune response.
effective immunosuppressive agent following renal
The advantages of systemic CsA include specific
transplantation.
immunomodulation and no ocular surface complications. It also
possesses some inhibitory influence on the efferent limb, i.e. by
Other Newer Immunosuppressants
inactivating cytotoxic T lymphocytes. To be effective in corneal
graft rejection, blood level of CsA of 200 ng/ml is required but Experimental animal studies on co-administration of the new
to minimize the systemic side effects a target level of blood CsA macrolide immunosuppressant RAD and mycophenolate
mofetil in corneal transplantation, shows promising highly CONCLUSION

synergistic effect. Although therapy with CsA allows superior
Meticulous preoperative patient selection, patient education
graft survival, its use is limited because of a wide range of
and interaction between the treating corneal surgeon and
side effects.
patient, pre and post operatively are important parameters for
Oral immunization as a strategy for enhancing corneal
both prevention and management of graft rejection reaction.
allograft survival has also been experimented upon. Tissue
Inflammation, whether occur ring before corneal
cultured C3H corneal epithelial and endothelial cells were
transplantation or subsequently, profoundly influences the
administered orally in animal experiments. Oral administration
predisposition to graft rejection. Though HLA matching may
of donor specific cells was found to be successful in enhancing
be beneficial, it still requires reassessment. The use of systemic
corneal graft survival.
Vascular endothelial growth factor (VEGF), a potent immunosuppressive agents in high-risk corneal transplantation
permeability-increasing factor and angiogenesis-mediating is widely practiced and topical glucocorticosteroids remain the
factor, is reported to be strongly produced from the infiltrative drugs of choice to prevent or reverse rejection episodes. The
cells into the graft. Anti-VEGF antibody significantly ultimate goal in tackling corneal graft situations should be to
suppresses the acute rejection and hence the inhibition of prevent the occurrence of an immune rejection episode.
VEGF by topically applied neutralizing antibody is a new
potential therapeutic strategy for the treatment of corneal REFERENCES
transplantation. 1. Panda A, Vanathi M, Kumar A, Dash Y, Priya S. Corneal graft
Gene therapy in corneal graft rejection modulations is rejection. Surv Ophthalmol 2007;52(4):375-96.
being extensively investigated. Local gene therapy-mediated 2. Prendergast DG, Easty DL. Immunological aspects of corneal
expression of the immunomodulatory cytokine IL-10 has the graft rejection. Immunol Lett 1991;29:73-6.
potential to reduce the incidence of corneal graft rejection 3. Strelein JW. Immunological non responsiveness and acquisition
and to prolong corneal allograft survival. of tolerance in relation to immune privilege in the eye. Eye
1995;9:236-40.
New insights into the molecular mechanisms of
4. Alldrege C, Krachmer JC. Clinical types of corneal Transplant
corticosteroid-mediated actions have lead to studies on new
Rejection. Arch Ophthalmol 1981;99:599-604.
substances, such as selective glucocorticoid receptor agonists
5. Smolin G, Goodman D. Corneal graft rejection. Int Ophthalmol
(SEGRA), in keratoplasty. Clin 1988;28:30-6.
6. Dahlgren MA, Krachmer JH. Rejection: Clinical forms, diagnosis
OUTCOME OF CORNEAL GRAFTS and treatment. In: Brightbill FS, McDonnell PJ, McGhee CNJ,
Farjo AA, Serdarevic O (Eds). Corneal Surgery: Theory, Technique
Graft prognosis is dependent on varied factors such as pre
and Tissue. 4th Ed. Mosby Elsevier 2009, p. 537-544
operative case selection, preoperative measures for donor, intra
7. Mabou M, Boisjoly H. Penetrating keratoplasty. In: Foster CS, Azar
operative approach, early detection, type of rejection and mode DT , Dolhman CH (Eds). Smolin and Thoft’s Cornea: Scientific
of management. Visual outcome and graft survival after Foundations and Clinical Practice. 4th Ed. Lippincott, Williams
corneal transplantation is also greatly influenced by type of and Wilkins, Philadelphia, 2005, p. 1021-1042
graft rejection. 8. Foulks GN. Diagnosis and management of corneal allograft
Successful treatment outcome has been reported in 76 rejection. In: Krachmer JH, Mannis MJ, Holland EJ. Cornea, Vol
percent of grafts with endothelial rejection.1 Rejection episode 1, Elsevier Mosby 2005, p. 1541-1550
has been found to be reversible in 50 percent of vascular and 9. Casey TA, Mayer DJ. Rejection in Corneal grafting, principles and
66 percent of avascular recipient corneal beds.1 The prognosis practice, Saunders 1984;309-24.
for repeat grafts for cases with failed grafts due to rejection 10. Arensten JJ, Corneal transplant allograft reaction-Possible
predisposing factors. Trans Am. Ophthalmol Soc. UK 1983;81:361-
greatly depends on the state of vascularization of the recipient
402.
bed as against the previous occurrence of rejection episode.
11. Braude LS, Chandler JW. Corneal allograft rejection. The role of
High-risk patients (vascularized cornea and previously rejected the major histocompatibility complex. Surv Ophthalmol
graft) are more prone for graft rejection than normal risk 1983;27:290-305.
patients. In patients undergoing repeat grafts, even a non- 12. The collaborative corneal transplantation studies (CCTS).
vascularized repeat rejected graft is more prone for rejection Effectiveness of histocompatibility matching in high-risk corneal
than a vascularized non rejected graft. transplantation. The Collaborative Corneal Transplantation Studies
Corneal Surgery 663
Research Group. [No authors listed] Arch Ophthalmol 16. Hill JC, Ivery A. Corticosteroids in corneal graft rejection. Double
1992;110:1392-403. vs single pulse therapy. Cornea 1994;13:383-8.
13. Coster DJ, Williams KA. The impact of corneal allograft rejection 17. Hill JC. Systemic cyclosporine in high-risk keratoplasty: short long
on the long-term outcome of corneal transplantation. Am J term therapy. Ophthalmology 1994;101:128-33.
Ophthalmol 2005;140:1112-22. 18. Hill JC. Immunosuppression in corneal transplantation. Eye
1995;9:247-53S.
14. Banerjee S, Diek AD. Recent developments in the pharmacological
19. Hill JC. High-risk Corneal grafting. Br J Ophthalmol 2002;86:945.
treatment and prevention of corneal graft rejection. Expert Opin 20. Reis A, Reinhard T, Voiculescu A, Kutkuhn B, Godehardt E,
Investig Drugs 2003;12:29-37. Spelsberg H, Althaus C, Sundmacher R. Mycophenolate mofetil
15. Bartels MC, Doxiadis II, Colen TP, Beekhuis WH. Long-term versus cyclosporine A in high-risk keratoplasty patients: a
outcome in high-risk corneal transplantation and the influence of prospectively randomised clinical trial. Br J Ophthalmol
HLA-A and HLA-B matching. Cornea 2003;22:552-6. 1999;83:1268-71.
6.10.1.4 Corneal Graft Infection

Infectious keratitis following corneal transplantation (Fig. Bullous keratopathy, postinfectious corneal scars,
6.10.1.4.1) remains a cause of concern as it is one of the inadequate management of infectious keratitis, pediatric
leading causes of graft failure.1-3 Incidences of graft infection grafts, poor ocular surface mainly predispose to graft
vary widely with relatively high occurrence in the developing infections. The majority of the graft infections usually occur
countries. Incidence rates of post penetrating keratoplasty within the first year of keratoplasty. Suture-related problems
infectious keratitis in the developed countries varies between and persistent epithelial defect in the corneal graft are the
1.76 to 7.4 percent1 while incidence rated in developing most common risk factors predisposing to graft infection.
countries has been reported to upto 11.9 percent.1 It is to be Identification of the predisposing risk factors and timely
noted that the recurrence of herpetic keratitis in corneal grafts management play a crucial role in the prevention of
is high with a reported incidence of 1.2 per 1000 person-years occurrence of graft infection.
of herpetic keratitis in the graft after penetrating keratoplasty Though the timing of occurrence of graft infection after
which is 14.2 times the incidence rate of herpetic keratitis in keratoplasty can vary, most graft infections have usually been
the normal population.1 The incidence of herpetic keratitis noted to occur within the first year of corneal transplantation.
in corneal grafts done for viral keratitis was found to be 18 Hence intensive follow-up in the first year of keratoplasty
percent.1 especially in patients with predisposing risk factors such as
ocular surface problems, dry eye, acne rosacea, blepharitis,
chemical burns, and herpetic etiology. Early postoperative
infection, especially in therapeutic keratoplasty is due to
recurrence of host disease. Corneal donor infections and
intraoperative contamination, may also contribute to graft
infection. Persistent epithelial defect is one of the most
important of all causes for predisposition to graft infection.
In the late postoperative period, suture related infection due
to loose or broken sutures leads to the occurrence of post
keratoplasty infection, especially in pediatric grafts. The long-
term use of steroids further predisposes to graft infection.
Predisposing Factors for Graft Infections

There are many factors that may predispose to occurrence of
corneal graft infection.1-17 These include:
Fig. 6.10.1.4.1: Microbial keratitis following keratoplasty • suture related problems (Fig. 6.10.1.4.2)
• persistent epithelial defect (Fig. 6.10.1.4.3)

• recurrence of herpes simplex keratitis
• ocular surface disorders including dry eye (Fig. 6.10.1.4.4)
• graft failure
• use of soft contact lens
• lid abnormalities.
The common sources of microbial keratitis following
keratoplasty are:
• donor tissue contamination
• incomplete excision of infected recipient tissue
• infection from organisms acquired from the environment.
Donor-related Factors
Infectious keratitis and endophthalmitis following Fig. 6.10.1.4.2: Loose sutures with early infectious infiltrate
transplantation occur as a result of donor tissue contamination
at various stages of tissue processing. Donor globe
decontamination with povidone-iodine five percent as the
preferred agent, greatly reduces the chance of occurrence of
graft infection.
Host-related Problems
Ocular surface disorder: A healthy ocular surface is favorable for
good epithelial healing and tears resurfacing. Disorders of the
ocular surface predispose to delayed epithelialization, persistent
epithelial defects compounding the risk factors for graft
infection. Hence all attempts should be made to improve the
ocular surface environment with tear substitutes, punctal
occlusion, and/or lid surgery as indicated prior to penetrating
keratoplasty.
Fig. 6.10.1.4.3: Persistent epithelial defect
Recurrence of previous infection: Inadequate debulking of diseased with early suture infiltrates
host tissue may result in recurrence of the previous infection
in the graft especially in grafts for therapeutic management
of microbial keratitis. Recurrence of viral infections in the
graft also predisposes to graft infection.
Topical steroids therapy: Majority of post-keratoplasty keratitis do
receive long term topical steroids without any complications.
However long term topical steroid therapy, may serve as a risk
factor for graft infection, in the setting of other associated
factors such as suture related problems or ocular surface
disorders. Frequent application of topical steroids in high-risk
groups may impair the defense and healing mechanism of the
host. Hence it is commonly preferred to continue topical
antibiotic prophylaxis as long as the sutures are in and with the
use of frequent topical steroids in graft patients.
Use of contact lenses: The role of bandage contact lenses in the Fig. 6.10.1.4.4: Corneal graft infection in
development of infectious keratitis after keratoplasty remains an eye with poor ocular surface
Corneal Surgery 665
controversial. Use of bandage contact lenses as a routine closely watched. Prolonged retention of corneal graft sutures is
following keratoplasty is preferred by most surgeons in recent also associated with spontaneous suture erosion through the
times to enhance patient comfort in the immediate epithelium, development of suture infiltrates, suture loosening
postoperative period and epithelial healing. However in the or breakage. Suture induced corneal erosions when the sutures
wake of higher incidence of infections reported with use of persist for a longer period of time, are more prone to get
soft contact lenses, adequate caution is to be exercised in their infected. Hence the importance of prompt removal of these
postoperative use with recommended frequent follow-ups. problem sutures is mandatory. Some surgeons also consider
Some surgeons prefer to reserve their use for eyes that have early suture removal to alleviate the problem of suture related
developed persistent epithelial defect and discontinue them graft infections, especially in patients where long term follow
as soon as there is complete healing of the epithelial defect. up compliance may be a problem. The exact timing
During the period of use of therapeutic contact lens recommended for suture removal remains controversial with
prophylactic antibiotic should be used to prevent the varying individual preferences among corneal surgeons and most
occurrence of any infection. Systemic diseases, such as diabetes preferring to do suture removal either in the presence of
mellitus, may increase the risk of development of infectious significant suture induced astigmatism, suture induced erosions
keratitis following keratoplasty. or suture incited vascularization.
Socioeconomic status: In developing nations, lower socioeconomic Suture removal may also serve as a precipitating factor in
status, poor living conditions and inadequate hygiene are the development of graft infection or rejection. It is routinely
associated with increased odds of graft infection. recommended to administer a short course of topical
antibiotics after suture removal to reduce the risk of
Problems Related to the Graft introduction of microorganisms during suture removal.
Persistent epithelial defect: Persistent epithelial defect is the most Graft edema: Decompensating grafts may predispose to the
common risk factor predisposing to graft infection with development of graft infection in the presence of edematous
the odds for graft infection increasing to threefold.1 Delayed epithelium, use of topical steroids and therapeutic contact
postoperative epithelial healing may occur due to lenses.
intraoperative trauma, suture related problems, tear film Recent rejection: Immune reaction of the host against the donor
abnormalities, ocular surface disorders, or the effect of tissue has been implicated for the recurrence of herpetic
topical medications (especially with preservatives). keratitis in the graft and for the reactivation of herpetic virus
Suture related: Suture related problems such as loose suture, sterile present in the sensory ganglia in the latent phase resulting in
infiltrates, secondary infections, corneal ulcerations, wound newly acquired HSV keratitis after penetrating keratoplasty
dehiscence, and allograft rejection may complicate the (Fig. 6.10.1.4.5).1
postoperative course of a keratoplasty. Loose sutures, exposed
suture knots, broken suture ends (due to late degradation of CLINICAL PRESENTATION
the sutures) tend to allow for mucus accumulation and invasion Corneal graft infection may present as a peripheral keratitis
of microorganisms thereby acting as a nidus for colonization with or without ulceration in cases of suture
of pathogens. As these serve to predispose to the occurrence related infections and are usually small in size at the onset.
of post-keratoplasty graft infection, emphasis should be placed Central and paracentral keratitis/ulcerations occur more
on prompt removal of loose sutures, exposed knots or broken commonly in the presence of predisposing factor such as an
sutures. Suture related problem have a 3.6-fold odds of epithelial defect. Stromal infiltration and anterior chamber
developing graft infection compared with cases that did not inflammation may be associated. Central ulcers tend to be
have suture-related problems.1 Continuous sutures may have a larger. In elderly patients, most graft ulcers tend to present
greater risk of infection, as, unlike continuous sutures, in the inferior part of the cornea as a result of ocular surface
interrupted sutures can be selectively and easily removed in the disorder, particularly tear film insufficiency and exposure
event of any suture related problem or at the onset of any suture keratitis, which predispose to epithelial defects and
related infection. Increase manipulation of corneal graft sutures subsequent microbial invasion.
in terms of resuturing for wound dehiscence or suture Herpetic keratitis after keratoplasty may present as a classic
replacements in the immediate postoperative period for loose dendritic keratitis or as non-healing large epithelial defects.
sutures are potential hazards for graft infections and have to be This may occur along with an allograft rejection reaction with
Fig. 6.10.1.4.5: Recurrent viral keratitis in a corneal graft
localized stromal edema and endothelial precipitates, it is • Confocal microscopic imaging may be helpful in
difficult to differentiate between graft rejection and herpetic early cases identifying the agent of corneal infection and
keratouveitis. thereby enabling institution of prompt and appropriate
Presence of a Khodadaust line and differential stromal treatment
edema is suggestive of graft rejection. Though the incidence
of graft infection with endophthalmitis or panophthalmitis is Treatment
not very common it may occur early or late after penetrating
Medical Therapy
keratoplasty, often with disastrous consequences.
Intensive empirical topical fortified antibiotics (cefazolin 5% and
Causative organisms: Microbial organisms isolated in corneal tobramycin 1.3%), in accordance to the results of microbial
graft infection show a geographical variation.4-17 Gram- evaluation should be promptly commenced. Vancomycin (5%)
positive cocci (coagulase negative Staphylococcus and and the newer generation fluoroquinolones (levofloxacin,
Staphylococcus aureus) are the most common bacteria that have gatifloxacin, and moxifloxacin) can serve as alternative therapy.
been reported to cause post keratoplasty corneal ulcer, The newer generation of topical ophthalmic fluoroquinolones
whereas Asper gillus species have been found to offers several advantages such as an enhanced spectrum coverage
be commonest fungus reported in graft infection. Other and potency for Gram-positive cocci and possibly atypical
Gram-positive cocci that have been reported in corneal graft mycobacterial species, with improved penetration into the anterior
infection include Streptococcus pneumoniae, Streptococcus viridans, segment, and lesser propensity to promote the development of
and other alpha hemolytic Streptococci. Pseudomonas aeruginosa resistance. The success of medical management of graft infection
is the most common among Gram-negative organisms largely depends on the size and severity of the ulcer at presentation,
causing graft infection. Staphylococcus and Streptococcus sensitivity of the organisms to the chosen antimicrobial therapy
pneumoniae are the most common isolates causing pediatric and compliance to treatment.
graft infections. Management of herpetic infections of the graft includes
topical acyclovir three percent along with systemic antiviral
MANAGEMENT therapy. Systemic acyclovir therapy is also beneficial in the
prophylaxis against recurrence of herpetic keratitis after
Investigations
penetrating keratoplasty for healed viral keratitis.
• Smear examination of the corneal scrapings for Gram staining The role of long-term prophylactic antibiotic in preventing
and KOH wet mount evaluation should be performed graft infection is controversial as graft infections that ultimately
• Corneal scrapings should also be inoculated into blood, occur may involve bacterial strains resistant to the prophylactic
chocolate agar and Sabauraud's agar for bacterial and fungal antibiotic. The risk of emergence of antibiotic resistant flora
cultures should also receive careful consideration.
Corneal Surgery 667
Surgical Treatment
Non-healing large graft ulcers will need therapeutic
keratoplasty. Repeat keratoplasty for optical rehabilitation will
be required for healed ulcers resulting in significant scarring
and graft failure.
INFECTION FOLLOWING
LAMELLAR GRAFTS
Most of the predisposing factors for graft infection in
lamellar grafts are similar to that of penetrating keratoplasty
such as persistent epithelial defect, suture abscess.1,13 There
may be a delay in diagnosis of infection in lamellar grafts,
especially in the early stages, because an infiltrate may
develop in the interface and may remain unnoticed. Post-
lamellar keratoplasty (LK) microbial keratitis requires
aggressive management with intensive topical treatment Fig. 6.10.1.4.6: Infectious crystalline
modification according to culture results. keratopathy in a corneal graft
Infectious crystalline keratopathy (ICK) has a
characteristic appearance of crystal like deposits infiltrate in
the corneal epithelium and/or in the corneal anterior stroma replacement of the lamellar graft when infection is restricted
(Fig. 6.10.1.4.6). Clinical presentation is with symptoms of to the donor tissue or therapeutic penetrating keratoplasty
pain, decreased vision or photophobia. Infectious crystalline when the host bed is also involved. Optical keratoplasty will
keratopathy commonly occurs due to bacterial infection. The be required later for cases with significant residual scarring.
infection may result de novo or following surgical procedures,
like refractive surgery and corneal transplants, or corneal CONCLUSION
trauma. Though Streptococcus viridans is the most common Post keratoplasty infection is a serious vision-threatening
organism to cause crystal deposits in the cornea, other complication resulting in scarring, graft failure, or
microorganisms such as Staphylococcus epidermidis, Streptococcus endophthalmitis. Visual prognosis in eyes with post-
pneumoniae, Haemophilus, Enterococcus, and Candida can also keratoplasty graft infection is poor even after optimal therapy
cause ICK. 1 Atypical mycobacteria and fungi such as and there is a high rate of graft decompensation Optimal
Alternaria can also cause ICK, especially in eyes undergoing donor tissue processing, careful preoperative patient selection,
refractive surgery. Chronic corticosteroid use as in post good intraoperative sepsis, close postoperative monitoring and
keratoplasty eyes and topical anesthetic abuse eyes are at follow-up with adequate patient education play in major role
particular risk. in preventing graft infection. Identification of patients with
These infections, characteristically tend to be low grade risk factors for graft infection can also help in preventive
indolent infections in the interface stroma. The low level of management. Early reporting of graft patients in the event of
mitotic activity of the microbes which are enveloped in a any graft morbidity can help alleviate the severity of the
biofilm, relative inaccessiblity of the topical medication to condition. Hospitalization may be required to ensure optimal
the infection site pose problems to the early healing of these treatment.
infections. Microbial investigations to identify the organisms
must be performed. Intensive fortified topical antibiotic REFERENCES
therapy (cefazolin 50 mg/ml or vancomycin 50 mg/ml) is
required. When the organism has not been identified, a broad- 1. Vajpayee RB, Shar ma N, Sinha R, Agarwal T, Singhvi A.
Infectious keratitis following keratoplasty. Surv Ophthalmol
spectrum antibiotic is used. Treatment of infectious
2007;52(1):1-12. Review.
crystalline keratopathy may be required to be continued for
2. Shar ma, N, Prakash G, Vajpayee RB. Post Keratoplasty
weeks or even months. Raising the lamellar flap for antibiotic Infections. In Brightbill FS, McDonnell PJ, McGhee CNJ,
wash may be required in chronic cases. Infections after LK Farjo AA, Serderavic O. Corneal Surgery. Theory, and Tissue,
not responding to antimicrobial therapy will need Technique. Fourth Edition. Mosby Elsevier 2009;471-6.
3. Jeng BH, Oxford KW, Aboot RL. Infections after penetrating 10. DJ Harris, RD Stulting, GO Waring, et al. Late bacterial and fungal
keratoplasty. In Krachmer JH, Mannis MJ, Holland EJ. Cornea. keratitis after corneal transplantation. Spectrum of pathogens, graft
Volume II. Surgery of Cornea and Conjunctiva. Second Edn survival, and visual prognosis. Ophthalmology 1988;95:1450-7.
2005;1551-64. 11. M Lamensdorf, LA Wilson, GO Waring III, HD Cavanagh.
4. YA Akova, M Onat, F Koc, et al. Microbial keratitis following Microbial keratitis after penetrating keratoplasty. Ophthalmology
penetrating keratoplasty. Ophthalmic Surg Lasers 1999;30:449-55. 1982;89(Suppl):124.
5. 4 SA Al-Hazzaa, KF Tabbara. Bacterial keratitis after penetrating 12. AB Leahey, RL Avery, JD Gottsch, et al. Suture abscesses after
keratoplasty. Ophthalmology 1988;95:1504-8. penetrating keratoplasty. Cornea 1993;12:489-92.
6. AK Bates, CM Kirkness, LA Ficker, et al. Microbial keratitis after 13. N Sharma, V Gupta, M Vanathi, et al. Microbial keratitis following
penetrating keratoplasty. Eye 1990;4:74-8. lamellar keratoplasty. Cornea 2004;23:472-8.
7. KP Cheng, DA Hiles, AW Biglan, et al. Risk factors for 14. CS Siganos, A Solomon, J Frucht-Pery. Microbial findings in suture
complications following pediatric epikeratoplasty. J Cataract Refract erosion after penetrating keratoplasty. Ophthalmology
Surg 1992;18:270-9. 1997;104:513-6.
8. CG Christo, J van Rooij, AJ Geerards, et al. Suture-related 15. H Tavakkoli, J Sugar. Microbial keratitis following keratoplasty.
complications following keratoplasty: a 5-year retrospective study. Ophthalmic Surg 1994;25:350-60.
Cornea 2001;20:816-9. 16. J Tixier, T Bourcier, V Borderie, et al. [Infectious keratitis after
9. LP Fong, LD Ormerod, KR Kenyon, et al. Microbial keratitis penetrating keratoplasty]. J Fr Ophthalmol 2001;24:597-602.
complicating penetrating keratoplasty. Ophthalmology 17. RB Vajpayee, SK Boral, T Dada, et al. Risk factors for graft infection
1988;95:1269-75. in India: a case-control study. Br J Ophthalmol 2002;86:261-5.
6.10.1.5 High-risk Corneal Grafting

Corneal grafting in high-risk recipient beds remains a challenge. recipient cornea with two or more quadrants of deep
The immune privilege afforded by the absence of antigen vascularization, or one in which a graft had previously been
presenting cells in the donor tissue, avascularity of the recipient rejected (Fig. 6.10.1.5.1). For a vascularized cornea to qualify
tissue and, anterior chamber associated immunodeviation as high-risk, the two stromal blood vessels are required to be
(ACAID) help to maintain clear corneal allografts without present, at least six clock hours apart. Two quadrant deep
supplemental immunosuppressive regimen in "normal" risk vascularization is less at risk than in which, all four quadrants
cases of keratoplasty.1 Primary low-risk corneal transplants
have the highest success rate (90%) and lowest rejection rate
(11–18%). High-risk corneal grafts are those in conditions in
which the cornea loses its immune-privileged status, resulting
in its susceptibility to immunological rejection induced failure.
Eyes under high-risk have been defined as having at least two
quadrants of stromal vascularization and/or a history of
previous graft rejection. 2 Herpes simplex virus keratitis
(HSVK), chemical injury, large sized grafts, HLA-A and HLA-
B incompatibility, previous failed corneal graft/s, decreasing
age of recipient, glaucoma, and peripheral anterior synechiae3
have also been considered as other risk factors. The risk of
graft failure has been found to vary substantially even within
a high-risk population.2 Assigning a numerical value to each
of the risk factors help to compute a risk score to distinguish
between patients at the higher and lower ends of the risk scale.4
In the Collaborative Corneal Transplantation Study 5 Fig. 6.10.1.5.1: Case of failed graft due to immune rejection
(CCTS) "high-risk" was defined as corneal grafting on the showing deep quadrant vascularization (high risk recipient bed)
Corneal Surgery 669
are heavily vascularized. It has been observed that the incidence medications can help to improve graft survival especially in
of rejection increases with both the number of quadrants the bilaterally blind patients. Studies report improvement with
vascularized and with the total number of vessels crossing both short and long term systemic CsA in high-risk
the proposed graft/donor junction.6 Graft rejection in a keratoplasty.12 Some degree of immunological privilege has
previously grafted eye relates more to the number of blood been considered to be re-established, indicating that CsA can
vessels in the cornea than to the number of previous grafts.7 eventually be safely withdrawn.10 Few authors have found no
Recipient corneas can be divided into low, medium, and high- statistical benefit from the use of systemic CsA, possibly due
risk depending on the number of quadrants of vascularization to variations in criteria for high-risk and inclusion of other
(avascular, 1–2 quadrants, and 3+ quadrants respectively).8 factors such as chronically inflamed eyes.13 Intensive topical
Considerable correlation exists between the risk score and corticosteroid therapy decreases inflammation, thereby
rejection episodes. Reported failure rates of corneal grafts vary lowering the local population of immunologically active cells
between 60 and 90 percent in "high-risk" recipient eyes.9-11 and also reducing the expression of class 2 antigens in the
The clonal expansion of graft-specific lymphocytes occurs recipient cornea. Long-term results of the use of systemic
in lymphoid tissues. With topical steroids not reaching these mycophenolate mofetil (MMF) and tacrolimus for the
secondary lymphoid organs, and the effect of systemic steroids prevention of rejection has been seen to be effective in patients
not seeming sufficient to interfere with the clonal expansion with high-risk corneal grafts.
of activated T cells, it is essential to administer systemic
immunosuppressives in order to achieve clear graft survival in CYCLOSPORINE
high-risk keratoplasty cases. Considering that corneal
Cyclosporine A is a powerful immunosuppressive agent derived
transplantation is not a life-saving procedure, the profile of
from the fungus tolypocladium inflatum gans. It also acts at
side-effects is of paramount importance when choosing an
the early stages of antigenic sensitization. It is an immuno-
immunosuppressive medication. Various immunosuppressive
modulator and works on T cells by binding to an intracellular
agents have been tried with relative safety and efficacy for
peptides cyclophilin. It inhibits antigen presentation and thus
prolonging graft survival in patients with high-risk keratoplasty
lymphokine production. By virtue of its anticyclophilin activity,
especially in those patients who are bilaterally blind. When
cyclosporine reduces production of interleukin-2 (IL-2), thus
immunosuppressive therapy is to be considered in high-risk
limiting the activation of CD4+ and CD8+ T cells.
corneal grafting cases, appropriate caution should be exercised
Cyclosporine A (CsA), is a very potent prophylactic agent for
in its use, with particular attention to side effects, proper patient
preventing corneal allograft rejection and is used in some
selection and information before instituting treatment.
specialized centers after high-risk keratoplasty. Although
Obtaining an informed consent is mandatory in all cases.
Treatment plan protocols call for exclusion of patients with a therapy with CsA allows superior graft survival, its use is limited
history of malignant disorders, serological evidence of HIV because of a wide range of side effects (diabetogenicity, arterial
or HbsAg, systemic infections that requires therapy at the time hypertension, hyperlipidemia, nephrotoxicity). Apart from this
of entry, active peptic ulcer disease, inadequate contraceptive for CsA to be effective, the daily dose should be adjusted to
measures, pregnancy, or patients aged 18 years or below. keep blood levels between 120 to 150 ng/ml, which leads to
Corneal surgeons dealing with high-risk cases need to expensive and labor intensive laboratory drug monitoring. The
devise appropriate treatment regimens to enhance graft C(2) serum level of CsA is now not considered to provide
survival. Intensive topical corticosteroid therapy is beneficial. helpful information about the prognosis of the corneal grafts
The addition of systemic corticosteroid has not been shown but may be used for CsA treatment monitoring.
to add much benefit. With availability of systemic CsA, and
Treatment Schedule
other lesser toxic alternatives, immunosuppression has now
become more acceptable. The adoption of appropriate After baseline evaluation including clinical history, blood pressure,
treatment regimens a few days before surgery should be total blood count, blood urea, creatinine, electrolytes, and liver
considered to optimize the local corneal environment before function tests, oral cyclosporine A is given as daily dosage starting
grafting. The use of tissue typing in high-risk vascularized immediately after surgery in a loading dose of 10 to 15 mg/kg/
corneas is still controversial but can be considered. No day10,12-18 (Table 6.10.1.5.1). Thereafter, cyclosporine A blood
consensus exists on one single therapy for all these grafts and levels are to be monitored and measured biweekly to ascertain
devising therapeutic regimens, sometimes with multiple therapeutic levels of approximately 200 ng/ml. Blood pressure,
complete blood cell count, serum creatinine and liver functions Topical CsA is prepared either in olive/castor oil as two
are to be evaluated every two to four weeks. Patients are to be percent solution or in artificial tear as one percent solution. It
followed on a regular basis every day for the first postoperative is prescribed five times a day along with the topical
week, weekly in the first month, and then monthly. Cyclosporine corticosteroid drop in high-risk patients both pre- and post-
is given for 12 months unless significant side effects occur. The operatively.19-24 As blood cyclosporine A level after topical
dose of CsA is to be adjusted to the whole blood trough levels therapy is negligible, monitoring of blood cyclosporine A levels
with a target range of 120 to 150 ng/ml. During the early is not required. However, monitoring of renal and liver
postoperative period, blood CsA levels and blood chemistry are function is required.
to be estimated twice weekly. With stabilization of the CsA levels
Side Effects
the frequency of the tests may be reduced. The advantages of
systemic CsA include specific immunomodulation and no ocular Elevated serum urea and creatinine, hypertension, gum
surface complications. hyperplasia, increased sweating, backache, nausea, feeling
Table 6.10.1.5.1: Drugs useful in high risk corneal grafting

Drugs Type Dose Mechanism of action Side effects
Cyclosporine Immunophilline binding 10-15 mg/kg/day to It binds to intracellular Nephrotoxicity, hepatotoxicity,
drug from fungus maintain trough protein called cyclophilin, anorexia lethargy, viral
tolypocladium levels of 120-150 ng/ml1 this inactivates calcineurin infection, hypertension,
which is necessary for hirsutism, gum hyperplasia,
response of helper T cell tremor and seizures
to antigenic stimuli and
production of IL-2, thus
being highly T cell specific
Mycophenolate Immunomodulator 1 gm twice daily for Reversibly inhibits the Vomiting, diarrhea, electrolyte
mofetil (morpholinoethyl ester 12 months2 denovo formation of disturbances, hepatotoxicity
of mycophenolic acid) guanosine nucleoside by and exacerbation of atopic
inhibiting the enzyme dermatitis
inosine monophosphate
dehydrogenase thereby
inhibiting purine
bisynthesis of T&B cells
Tacrolimus Macrolide antibiotic from 2 gm/day on day of It binds to specific cytosol Hypertension, headache,
(FK 506) fungus Streptomyces surgery and then protein FK 506 binding malaise, GIT disturbances,
tsukubanesis adjusted to lower end protein and inhibits the paraesthesia, pancreatitis,
of range of whole blood T cell mediated signal folliculitis, reversible increase
tacrolimus level between transduction required for in serum creatinine, insomnia,
1-12 mg/l3 transcription of IL-2 and diabetes, increased frequency
other lymphokines of epileptic episode and
lymphopenia
Rapamycin Macrolide product of Once daily to attain It binds to FK binding Headache, swelling of
(Sirolimus) Streptomyces blood trough levels protein which inhibits extremities, gastritis,
hygroscopicus of 4-10 ng/ml4 calcineurin, inhibiting vomiting, diarrhoea, weight
response to IL-2 and gain, insomnia, fever, rash,
thereby blocks tremor
activation of T&B cells
IL-1 receptor – 20 mg/ml/ Topical drops Promotes corneal allograft Studied in animal models
antagonist in 0.2% Na hyaluronate survival in large part by
vehicle preventing activity of
recipient Langerhans’ cells
and thereby preventing
these cells from inducing
systemic allosensitization.
It down regulates CD-11b+ve
monocytic cell appearance
in corneal stroma
Corneal Surgery 671
unwell, oral candidiasis, cramps, bone marrow toxicity, and oral steroids in preventing acute rejection following high-
hirsutism and paresthesia of the extremities are the commonly risk corneal transplantation.14 Mycophenolate mofetil
occurring side effects. represents a promising alternative therapeutic option in
These side effects are rare when the drug blood level is patients who are at high-risk for corneal graft failure.
well monitored and kept at low therapeutic levels of
approximately 200 ng/ml. The use of CsA in solid organ TACROLIMUS
transplantation has been associated with an increased risk of
Tacrolimus (FK-506) is a macrolide antibiotic isolated from
lymphoproliferative disorders that has been attributed to the
the soil fungus Streptomyces tsukubaensis, with potent immuno
long duration of therapy and the use in conjunction with other
suppressive activity, 10 to 100 times more potent than CsA.
immunosuppressive drugs. The mechanism was thought to
The mechanism of action of tacrolimus is similar to
be secondary to the impairment of the organ recipient's
cyclosporine. While CsA binds to the immunophilin,
immune surveillance system, and recent evidence points to
cyclophilin (CyP), tacrolimus binds to a specific cytosol protein:
the direct stimulatory effect of CsA on malignant cells via a
FK-506 binding protein (FKBP) and inhibits the T cell
TGF-β related mechanism. This calls for a stringent
receptor-mediated signal transduction required for
reconsideration on our indications for its use in ocular
transcription of interleukin two and other lymphokines.
conditions. Considering the high frequency of side effects and
the cost of CsA the benefit of CsA over conventional therapy Treatment Schedule
in preventing rejection episodes and subsequent graft failure
is only moderate. Baseline evaluation includes clinical history, blood pressure,
total blood count, blood urea, creatinine and electrolytes, and
MYCOPHENOLATE MOFETIL liver function tests. Oral tacrolimus is to be initiated at a dose
of 2 mg/day (1 mg twice daily) on the day of surgery, and is
MMF, (morpholinoethylester of mycophenolic acid) has widely to be further adjusted (2–8 mg/day) aiming for a whole blood
approved safety and efficacy in combination with CsA tacrolimus trough level between 1 and 12 mg/l along with
following kidney transplantation. Unlike CsA, mycophenolic monitoring clinical signs 4,27 (Table 6.10.1.5.1). The
acid does not interfere with IL-2 pathways. It reversibly inhibits recommended levels are the lower end of the range between
the de novo formation of guanosine nucleosides by inhibiting 1 and 12 mg/l for grafts that do not show any signs of
the enzyme inosine monophosphate dehydrogenase. As T and vascularization or rejection, at the middle of the range for
B cells are predominantly dependent on the de novo synthesis grafts that have vascularization or rejection features.4, 27 Trough
of guanosine nucleosides, the purine biosynthesis of these levels are to be measured 12 hours after the last dose of
cells is selectively inhibited. tacrolimus and are not to be allowed to rise above 12 mg/l in
MMF is to be given in a dosage of 2 g (1 g twice daily). order to prevent toxicity.
Routine blood samples need to be taken every two to four
weeks to check for drug toxicity. Patient follow ups are done Side Effects
at weekly intervals in the first postoperative month, bi-weekly
for two months and monthly for three months and every three The common side effect of tacrolimus include hypertension
months thereafter during which laboratory assessments were or exacerbation of pre-existing hypertension, headaches,
performed. The need for blood level adapted dosing for MMF malaise and gastrointestinal disturbances, paresthesia,
remains controversial. All data concerning efficacy and safety pancreatitis, folliculitis, reversible increase in serum creatinine,
of this drug are from clinical trials with a fixed daily dose of 2 insomnia, diabetes, increased frequency of epileptic episodes
g or 3 g.14,25,26 Some centers adopt a fixed dosing of 2 g MMF and lymphopenia.
per day with blood level measurements reserved to special
situations (for example, pediatric patients, treatment failure, GENERAL CONSIDERATIONS
adverse events).14,25,26 AND OUTCOME
Lesser postoperative visits, reduced cost and logistics of Systemic immunosuppression may be recommended for 12
postoperative immunosuppression as a result of the omission to 18 months postoperatively or until suture removal,
of monitoring drug titers are advantages with MMF usage. It whichever is later. Patients with clear grafts in their only seeing
has been shown that MMF in combination with a short eye may be given the option of continuing therapy indefinitely.
postoperative course of oral steroids is just as effective as CsA Those patients with rejection episodes while on
immunosuppressive, the drug is to be continued for a period of immune graft rejection is limited in heavily vascularized,
of one year after the last rejection episode. Those with repeated keratoplasties and the conjunctive use of systemic
graft rejection episodes after discontinuing systemic and topical corticosteroid may be beneficial. Rumelt et al16
immunosuppression, may be counseled for further treatment found that once the immune rejection occurs the regraft fails
for one year. Patients who are unable to tolerate the required despite continuation of systemic cyclosporine A and extensive
dose may be given the option of changing over to an topical and systemic corticosteroids, in contrast to Hill's
immunosuppressive agent with a different side effect profile study.18 It has been postulated that vascularized corneas behave
or using combination treatment. Patients who do not opt for like other vascularized organs, but due to their smaller size,
commencing systemic immunosuppressive therapy again or they may be more affected by immune rejection limiting the
change in the nature of immunosuppressive agent may be effect of cyclosporine A. It is to be noted that repeated corneal
managed with steroids or topical cyclosporine. However, the grafts are more prone to develop postoperative complications
use of topical cyclosporine is limited by the local discomfort compared with primary grafts and the visual and graft outcome
and epithelial toxicity associated with its use.15 of eyes with regrafts may be poor even in eyes with a clear
Repeat grafts usually have extensive vascularized corneal graft due to other intraocular pathologies. Insufficient dose
bed preoperatively and a history of previous failure, sometimes and duration of CsA, and inadequately matched patients have
immune mediated. Repeat corneal transplantation is a subset also been attributed to CsA not being effective in some cases.
of high-risk condition for immune graft rejection. Rumelt The effect of topical cyclosporine A on high rejection risk
et al16 followed up 28 regrafts treated with oral cyclosporine corneal transplants is yet to be established. As allosensitization
for an average of 26.6 months and reported rejection-related following a corneal graft occurs outside the eye, at the local
failure in 32 percent and non-rejection related failure in 36 lymph nodes, topical therapy with CsA may be ineffective.
percent. They also found that six (21.4%) of 28 grafts on CsA Various groups have reported use of topical CsA.19,20 A
rejected while on treatment and another three (10.7%) failed randomized controlled study did not demonstrate improved
after treatment was stopped compared to five (42%) of 12 graft survival with topical CsA.20 Topical cyclosporine A is
control grafts that did not receive CsA. Their results showed effective in prevention of immune rejection of corneal graft in
that oral cyclosporine A seems to have a limited benefit in the humans only when combined with topical corticosteroids.21
prevention of immune graft rejection in heavily vascularized, Topical cyclosporine A treatment has been reported to be
repeated keratoplasties in humans. Only 25 percent of the beneficial in corneal transplanted eyes with no or minimal corneal
regrafts remained clear with significant improvement in visual vascularization.22
acuity; 32 percent of the regrafts had immune graft rejection, The treatment of corneal graft rejection with 0.5 percent
and ultimately all of them failed despite the continuation of topical cyclosporine is effective in eyes with satisfactory
oral cyclosporine A and the addition of topical and systemic preoperative corneal transplantation beds, whereas it has been
corticosteroids. The Kaplan-Meier analysis showed a delayed reported to have only beneficial effects in eyes with poor
failure rate of the treated group compared with the untreated preoperative corneal transplantation beds.22 The recurrence
group during the first 12 postoperative months. This was also of rejection was found to resolve by resumption of the
the average time of cyclosporine A treatment, suggesting that cyclosporine eyedrops. Topical CsA in shields or in fragments
cyclosporine A might have had effect in prevention of immune have been shown to provide a significant advance over systemic
regraft rejection and failure while being used. However, despite CsA alone, and CsA fragments also seem to be as effective as
cyclosporine A treatment, when the regrafts that failed due to shields in preventing corneal allog raft rejection. 23
causes other than immune rejection were excluded, the survival Cyclosporine-treated grafts have been found to contain
was comparable during the entire follow up period for both significantly fewer infiltrating T lymphocytes indicating that
the treated and untreated groups. the topical application of cyclosporine actively inhibits the
Hill17,18 treated patients with high-risk keratoplasties with entry of T cells into the grafts.24
oral cyclosporin A in conjunction with topical and systemic Preliminary results of a randomized multicenter trial
corticosteroids and found that a higher percentage of 88.9 estimated the ratio of high-risk corneal grafts without
percent remained clear. As the degree of corneal vasculari- immune reactions to be about 89 percent one year
zation and indications for the primary transplantations and postoperatively in patients on MMF, in contrast to only 67
their preoperative and postoperative status were not reported percent in the control group.25 Adverse effects of the drug
in this, a comparison of results is of limited value. Prevention such as gastroenterotoxicity, tachycardia, arthralgia or
Corneal Surgery 673
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3. Price MO, Thompson RW Jr, Price FW Jr. Risk factors for various
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6. Khodadoust AA. The allograft rejection reaction: the leading cause
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T. Immunosuppression with cyclosporine A and mycophenolate suppression allosensitization in corneal transplant. Archives of
mofetil after penetrating high-risk keratoplasty: a retrospective study. Ophthalmology 1998;116(10): 1351-7.
Transplantation 2005; 79:964-8. 33. Notara M, Daniels JT. Biological principals and clinical potentials
of limbal epithelial stem cells. Cell Tissue Res 2008;331:135-43.
Epub 2007 Aug 16.
6.10.1.6 Pediatric Keratoplasty

Penetrating keratoplasty in children is a highly challenging and parents, an expert corneal transplant surgeon and a devoted
demanding procedure with requirement for meticulous follow- pediatric ophthalmologist.
up and postoperative care. It is associated with a high-risk of
graft failure due to numerous complications and a poor visual INTRODUCTION
outcome with graft failure (resulting from numerous Congenital eye disorders, though infrequent, are important
complications including graft rejection, infection and others) causes of childhood blindness. It can occur in isolation or in
or failure of amblyopia therapy in clear grafts. Nonetheless, combination, or as part of a syndrome. Visual deprivation in
keratoplasty still remains the surgery of choice due to a lack the early months of life due to corneal opacification can lead
of an alternative procedure for the management of pediatric to long-term changes in the central nervous system.1
corneal stromal opacities or edema. Allograft rejection, graft Penetrating keratoplasty is required for the treatment of
infection, corneal neovascularization, glaucoma, trauma to the corneal opacification in children to prevent visual deprivation.
anterior segment, vitreous pathology, and additional surgical In order to achieve optimal visual results and avoid visual
interventions, especially those related to glaucoma deprivation amblyopia, corneal transplantation must be
management are attributed to be important risk factors leading performed in the early months of life. Penetrating keratoplasty
to graft failure. The success of penetrating keratoplasty in in children has been considered as high-risk transplantation
children calls for a careful preoperative evaluation and selection and is documented to have a higher rate of graft failure and
of patients, proper surgical technique, prompt management poor visual prognosis than adult keratoplasty. Varied success
of postoperative complications, optimal visual rehabilitation in pediatric keratoplasty can be attributed to preoperative,
and amblyopia therapy and compliant follow-up, with intraoperative and postoperative problems. Improved
integrated efforts at several levels, comprising of well motivated understanding of intraoperative and postoperative problems
Corneal Surgery 675
has resulted in achievement of better anatomical success in keratoplasty, is mandatory for achieving a successful anatomical
pediatric corneal grafts. and functional outcome.
Pediatric keratoplasty was infrequently performed and
considered unsuccessful before the mid 1970s. It was only INDICATIONS
recommended in pediatric patients with bilateral corneal
Pediatric corneal opacities were earlier classified into three
involvement. Penetrating keratoplasty in children is associated
diagnostic categories2,3
with a significantly lower success rate compared to adults. i. Congenital
Technical advances however have now lowered the age at which ii. Traumatic
keratoplasty is performed and indications have increased with iii. Acquired non-traumatic.
improvement in surgical techniques and therapies. Indications of pediatric corneal transplantation vary widely
Keratoplasty in infants and children is now considered a with the proportion of keratoplasties performed for congenital
safe and effective procedure. However the success and outcome indications ranging from 14 to 64 percent, for acquired non-
of pediatric keratoplasty is influenced by the timing of traumatic conditions 19 to 80 percent and for acquired
keratoplasty and the etiology for which it is performed. traumatic conditions 6 to 29 percent.4 Most of the available
Optimal postoperative management in terms of dedicated studies in the past had analyzed data based on these diagnostic
follow-up evaluations under anesthesia, monitoring of groups. The recent Al-Ghamdi et al's5 study on primary
postoperative medications, appropriate management of penetrating keratoplasty in children prompts the suggestion
sutures, correction of refractive error and institution of of a newer classification depending on visual prognosis
amblyopia therapy play a crucial role in enhancing the outcome patterns in pediatric keratoplasty:
of pediatric keratoplasty. A. Congenital opacities: Congenital hereditary endothelial
Special problems in corneal transplantation in children dystrophy
include: B. Congenital opacities: Non-CHED
1. Preoperative—difficulty in optimal visual acuity assessment 1. Frequently associated with glaucoma
and proper preoperative evaluation; 2. Infrequently associated with glaucoma
2. Intraoperative—increased intraoperative problems such as C. Acquired traumatic
low scleral rigidity, increased fibrin reaction and positive D. Acquired non-traumatic.
vitreous pressure during surgery; Congenital corneal opacities are present at the time of
3. Postoperative—the need for frequent examinations under birth and associated with loss of corneal transparency.
anesthesia for postoperative follow-up evaluations, Developmental influences affecting anterior segment
frequent loosening of sutures necessitating replacement/ differentiation between the sixth to the 16th week of gestation
early removal, increased risk of rejection and infections, result in congenital corneal opacities. These influences may
and the difficulties with repeated refractive error be genetic, infectious, traumatic, toxic or combination of these
assessments, timely initiation and reversal of amblyopia factors. The prevalence of congenital corneal opacities is
along with long-term compliance to amblyopia therapy. approximately 3/100,000 and with congenital glaucoma
Even with increased anatomic success of pediatric corneal included this rises to 6/100,000.6,7 The most common primary
grafts, optical success continues to remain a cause of concern cause of congenital corneal abnormalities in the developed
to corneal transplant surgeons. nations is Peters anomaly (40.3%), followed by sclerocornea
The focus of pediatric corneal grafting in the developing (18.1%), dermoid (15.3%), congenital glaucoma (6.9%),
nations is that an increasing number of the grafts are microphthalmia (4.2%), birth trauma, and metabolic disease
performed for infectious keratitis, post infectious keratitis (2.8%).8
corneo-iridic scars or keratomalacia. A combination of a
dedicated team of skilled corneal transplant surgeons, pediatric TECHNIQUE
ophthalmologist and motivated parents is critical to ensure Pediatric keratoplasty was considered contraindicated because
greater success in results of penetrating keratoplasty in infants of technical challenges due to a low scleral rigidity and forward
and children. displacement of lens-iris diaphragm.4 Though pediatric
Adopting a biphasic approach to pediatric penetrating keratoplasty is now considered to be a safe and effective
keratoplasty, (1) with measures to maintain clear graft, and (2) procedure, specific problems do exist in the management of
successful visual rehabilitation of the child following children who undergo corneal transplantation.
Preoperative Evaluation grafting in one eye with the hope of achieving better visual
and Decision Making acuity.1,16 In cases of Peter's anomaly, the extent of ocular
involvement is to be graded preoperatively. The association
An evaluation under anesthesia (EUA) is usually done prior to
of central nervous system abnormalities as a risk factor in
PK to adequately examine the anterior and posterior segment,
Peter's anomaly, warns the treating ophthalmologist to look
including A and B scans. It is also important to evaluate if
for signs of CNS problems (developmental delay, structural
corneal grafting is indicated and if so to decide on the surgical
defects, seizure disorders, fetal alcohol syndrome) as there
plan and postoperative management. A portable hand held
would be increased difficulty in examining and caring for
slit lamp evaluation preoperatively can eliminate the need for
neurologically abnormal children. Routine neurological
a separate preoperative evaluation under anesthesia. In cases examination and neuroimaging might be required in such cases.
with posterior segment pathology, electrophysiological tests The important issue considered in keratoplasty for traumatic
such as visual evoked responses and electroretinography can corneal scarring is the threat of amblyopia. It has been
help decide on the need to proceed with surgery. The decision recommended not to delay the timing of keratoplasty for
of surgery at an earlier age will depend on the laterality of the penetrating trauma in children beyond the point at which the
corneal condition and its severity, the risks of undergoing decision is made to perform the surgery.9 The optimal timing
general anesthesia for initial surgery and repeated postoperative and sequence of penetrating keratoplasty and glaucoma
evaluations under anesthesia, the associated systemic drainage implant surgery in refractory congenital glaucoma
abnormalities and metabolic conditions. patients who require corneal and glaucoma surgery is still
To achieve optimal visual results and avoid deprivation unclear. The decision to perform regrafts is difficult and is
amblyopia, corneal transplantation must be performed within made in the light of such factors as age, risk of glaucoma and
the first few months of life. This must be accompanied by risk of amblyopia. When graft failure occurs, regrafting is
immediate optical therapy when possible and appropriate required to visually rehabilitate the child. The primary cause
amblyopia therapy to optimize visual potential. Examinations for the corneal graft failure influences the outcome of the
of preverbal children under anesthesia in the preoperative regraft. When the risk of surgical complications and glaucoma
period are important in order to assess the corneal pathology outweigh the benefits of the surgery, it is perhaps wise to
in detail, assess intraocular pressure and initiate prompt avoid regrafting.
treatment if required. The commitment of parents to the long- Lamellar keratoplasty should be considered in order to
term care of the child after surgery plays a crucial role. Hence, obtain desired results in conditions such as superficial scars
proper counseling for the social, economic and psychological or limbal dermoid because of the significant lower risk of
demands on them following surgery is vital for a successive rejection and avoidance of intraocular surgery. Tectonic patch
outcome in pediatric keratoplasty. Preoperative evaluations grafts, rotational keratoplasty and optical iridectomy may also
should also include B-scan ultrasonography of the posterior be considered in selective cases of pediatric corneal
segment of the eye. opacification as an effective alternative management option
Early penetrating keratoplasty for congenital corneal to keratoplasty.
opacity may prevent deprivation amblyopia. However the
increased risk of failure, especially in neonatal and infant eyes, Anesthesia
prompts for a careful case selection in these situations. The
It is usually desirable to have an anesthetist experienced in
age of the child at surgery is a debatable risk for graft success.
pediatric anesthesia. It is imperative to be able to maintain the
Younger age at the time of surgery appears to increase the
optimal depth of anesthesia throughout the entire procedure.
risk of failure due to difficulties with intra- and postoperative
Use of a non-polarizing muscle relaxant with a peripheral nerve
management.
stimulator can help eliminate the risk of movement and
Decision regarding surgery in CHED cases is difficult.
contraction of the extraocular muscles. Hyperventilation of
Although the cornea appears hazy and no red reflex is seen,
the patient can help reduce intraocular pressure. A slightly higher
these patients seem to see much better than the actual
positioning of the head aids in lowering positive pressure.
assessment. If the patient has good fixation and the eyes are
orthophoric, surgery may be delayed. However if fixation is Preparation of Globe
lost and nystagmus develops, penetrating keratoplasty should
be performed promptly. When the child presents with Increased positive pressure during surgery is a major problem
nystagmus, it has been recommended to perform corneal in pediatric keratoplasty. After anesthesia is induced, 20 percent
Corneal Surgery 677
intravenous mannitol (0.5 gm to 1.5 gm/kg body weight over in the anterior chamber should be controlled and clots
a period of 20–30 minutes) and or digital massage may be removed, as fibrin residual can lead to formation of posterior
used to aid in achieving optimal ocular hypotony during synechia and PAS formation.
surgery. Some surgeons prefer to use preoperative Honan Though wound closure is faster with running suture,
balloon and intravenous mannitol to reduce positive vitreous interrupted single sutures for keratoplasties are usually
pressure and the possible risk of anterior displacement of the preferred in children as they allow an earlier suture removal to
lens-iris diaphragm. Preoperative mydriatics or miotics may avoid severe suture related problems. Visual outcome depends
be used depending on the procedure. The surgical table should on the primary diagnosis and on avoiding irreversible
contain all instruments necessary to deal with an unexpected amblyopia.
lens loss in the event of raised positive pressure. The surgeon One mm oversized corneal grafts have been used in
should ensure that the donor button has been punched and is keratoplasty in an attempt to increase the morphologic success
ready before anterior chamber entry. of corneal grafting in children.4 Oversizing donor corneal
A lid speculum with Flieringa ring would be helpful. Care buttons by one mm achieves adequate anterior chamber depth
should be taken to ensure that the speculum, surgeon and in pediatric cases and can help prevent postkeratoplasty
assistant do not apply pressure on the globe. A lateral glaucoma; a longer follow-up will be required to confirm these
canthotomy may be considered in cases of increased lid conclusions.
pressure and very small palpebral fissures. As pediatric eyes Larger grafts have been used in patients with keratoconus
have an increased scleral elasticity and decreased scleral rigidity, and buphthalmos.4 Failed regrafts in congenital glaucoma have
the use of Flieringa ring provides scleral support for the been found to be associated with smaller diameter of the
immature and lax infant tissue thereby preventing collapse of graft.10 Transplanted endothelial cells migrate over graft-host
sclera after host trephination. The Flieringa ring must be sewed
junction to the recipient rim; the fewer number of transplanted
with care in infants because suturing can penetrate the thin
endothelial cells in small sized grafts migrating over to the
sclera of pediatric eyes and cause retinal tears. In addition,
relatively larger sized recipient rim in buphthalmos has been
unequal placement of the fixation sutures can result in
thought to be responsible for graft failure. Adjusting the graft
irregularity of the graft recipient bed and considerable
size in each eye before surgery is required. 10 Surgery in
astigmatism.
buphthalmic eyes is more complicated as the corneas are
Trephination thinner due to ocular stretching and increased vitreous
pressure.
The recipient cornea is trephined to 70 to 80 percent depth
by using disposable suction trephines. Corneal trephination is CONCOMITANT PROCEDURES
technically demanding in younger patients due to the decreased
scleral rigidity and increased elasticity of infant tissue. Anterior Loss of crystalline lens and vitreous at the time of
chamber entry is made with an MVR blade through the incision transplantation may occur despite rigorous preventive
and chamber filled with ocular viscoelastic device to protect measures. When the posterior capsule is intact, thorough
the lens and iris from injury. The incision is then completed aspiration of cortical remains is to be done. In case of vitreous
with the corneo-scleral scissors. The donor cornea is punched prolapse, anterior vitrectomy with an automated vitreous cutter
out from the endothelial side and the graft host disparity of must be performed. Any vitreous strands adherent to the
0.2 mm to 0.5 mm is usually used by most corneal surgeons. wound or iris is to be removed to prevent vitreous adhesive
Rapid formation of peripheral anterior synechiae (PAS) and syndromes and PAS formation. Planned additional procedures
difficulty reforming the chamber are also important problems such as lens extraction, IOL implantation, synechiolysis, and
faced while performing pediatric keratoplasty. The use of 100 anterior vitrectomy may be performed as required.
U/ml of heparin solution to irrigate the anterior chamber to Performance of an additional surgical procedure at the time
prevent fibrin formation and subsequent synechia is preferred of keratoplasty is most significantly associated with decreased
by some corneal surgeons. The injection of sodium graft survival rate.4 Among the variables analyzed, corneal
hyaluronate into the angle after anterior chamber may decrease ulceration, vitrectomy-lensectomy, persistent inflammation,
the risk of PAS formation and secondary glaucoma. posterior segment anomalies, regrafts, and postoperative
Performing several peripheral iridectomies has been found to complications have been found to be significantly associated
be important in preventing synechia formation. Hemorrhage with poor visual outcome and allograft survival.4
SIMULTANEOUS KERATOPLASTY Postoperative Problems

WITH GLAUCOMA FILTERING
DEVICE IMPLANTATION • Need for frequent examination under anesthesia for
postoperative evaluations
Upon completion of the keratoplasty, a limbal based • Early suture loosening due to rapid wound healing
conjunctival flap is created in the superotemporal quadrant. requiring examinations at more frequent intervals for suture
The plate of the primed drainage device is sutured to the sclera removal/replacements in order to avoid suture related
with 8.0 nonabsorbable sutures, 8 to 100 mm posterior to the problems
limbus. The tube is cut to an appropriate length with an anterior • Timely diagnosis of problems may be affected due to lack
bevel and inserted into the anterior chamber through a 23 of communication as the children are not able to express
gauge needle track and is covered by a donor scleral patch. In difficulties early
patients younger than six months with anteroposterior • Parent motivation levels need to be very high for
diameter less than 22 mm, a pediatric sized implant might be compliance to follow-up
preferred.11 When cyclocryotherapy is required in cases of • Early optical rehabilitation with glasses/contact lens to
refractory glaucoma requiring penetrating keratoplasty, it is initiate amblyopia therapy
typically performed in two or three quadrants with two to • Meticulous postoperative long-term follow-up for
four spots in each quadrant. amblyopia management.
Problems in pediatric keratoplasty can be subdivided
into those arising in the preoperative, intraoperative and PEDIATRIC KERATOPROSTHESIS
postoperative periods.4 Use of keratoprosthesis to treat pediatric corneal opacity4,12
Preoperative Problems prompts the evolving of an alternative treatment option for
those eyes with poor prognosis for graft survival. Though
• Complete preoperative evaluation of the corneal pathology keratoprosthesis implantation helps to restore a clear visual
is usually not possible axis without extrusion or rejection and may be an appropriate
• Need for specialized investigations such as ultrabiomic-
alternative for the management of pediatric corneal opacity,
roscopic examination
keratoprosthesis in pediatric cases is to be only considered as
• IOP evaluation is usually not accurate in opaque corneas
the final resort. Keratoprosthesis may offer the possibility of
• Patient should be evaluated for systemic associations in
rapid visual rehabilitation due to high optical quality enabling
cases of congenital corneal opacities.
early amblyopia treatment.
Intraoperative Problems
• Small size of the palpebral fissure reduces the working EPIKERATOPLASTY
space available for manipulations Epikeratoplasty was being performed for providing refractive
• Excessive lowering of the intraocular pressure is to be correction of pediatric aphakia. Epikeratoplasty in children
avoided as severe hypotony prevents optimal trephination can be more successful if risk factors such as younger patient
of the recipient cornea age, microcornea, corneal endothelial cell dysfunction, mental
• Caution is to be exercised while performing the scleral retardation, and combining the procedure with cataract surgery
fixation due to the higher risk of perforation as the sclera are avoided. Complications such as residual refractive error,
is thinner in pediatric eyes epithelial defect, interface opacities, graft vascularization and
• Use of Flieringa rings with unequal placement of fixation graft infection, graft necrosis, graft haziness or opacification,
sutures may also result in increased distortion resulting in and graft dehiscence have made this procedure less desirable.
difficulty while suturing
• Need for performing associated procedures such as
Postoperative Management
lensectomy, anterior vitrectomy, glaucoma procedures, etc
is high Postoperative management of pediatric corneal grafts demands
• Increased positive pressure of vitreous with forward shift dedicated follow-up evaluations under anesthesia, monitoring
of lens-iris diaphragm due to the low scleral rigidity and of postoperative medications for frequency alterations,
increased elasticity of pediatric eyes appropriate management of sutures, close watch for rejection,
• Increased difficulty in suturing and cheese wiring due to frequent correction of refractive errors, initiation of amblyopia
the thin peripheral corneal tissue in certain cases. therapy, and ensuring compliance to long-term amblyopia
Corneal Surgery 679
therapy. Hence the need to emphasize on the biphasic approach AMBLYOPIA MANAGEMENT
of maintaining a clear graft, and reversing amblyopia, is of
The neurological basis of amblyopia is related to the concept
paramount importance in the postoperative management.
of cortical competition.4 All cortical cells are potentially
connected to both the eyes equally, provided both eyes are
Immediate Postoperative Management
functioning equally. If due to some reason one eye
Postoperative treatment regimen involves topical corticosteroid predominates, these cortical cells are stolen by the dominating
along with antibiotics and lubricants. Topical steroids are given side. The dominance of one eye over the other is usually a
more frequently in the initial postoperative period and gradually result of better visual acuity in that eye, especially if primary
tapered and changed to less potent steroids such as strabismus is not present. It is postulated that strabismic
fluorometholone over three to six months. Topical CsA 2% amblyopia is initiated as a maladaptive differentiation in the
when used in pediatric keratoplasty can help reduce frequency ocular dominance columns, whereas the non-strabismic
and duration of postoperative topical steroids. Examinations amblyopias (anisometropic and the deprivation amblyopias)
of preverbal children under anesthesia in the early may be initiated from the malfunctioning of the ganglion cell
postoperative period are important in order to assess the graft population of the amblyopic eye.14,15 Thus the non-strabismic
status, assess intraocular pressure and initiate prompt treatment amblyopias are caused by optical degradation of one retinal
if required. image while in strabismic amblyopias both retinal images are
initially clear. The total clinical picture is confusing because
SUTURE REMOVAL of secondary changes in other parts of the central nervous
system that occurs subsequently. The manifest features can
Loosening of sutures or vascularization needs urgent be due to a slower, more enduring type of change (pooling,
examination under anesthesia for suture removal. Frequent loss and re-wiring of the neurons) as well as a more transient,
EUA's during the first two months after PK in children less adaptive type of response (such as suppression of diplopia).
than six months is mandatory, until all sutures are removed Thus traditionally, mechanisms leading to amblyopia have been
and at monthly intervals for six months and less frequently divided into two basic types, those causing form deprivation
thereafter. Frequent EUA's are also required to detect problems and those resulting in abnormal binocular interaction. It is of
such as glaucoma and retinal detachment. importance to realize that the process of visual maturation
All sutures are usually removed by three months in children and development of amblyopia becomes especially significant
younger than eight years and by six months in older children. in the early period of visual development which is also called
Different centers follow their own set routines for suture the critical period, when neural plasticity makes the visual
removal in pediatric keratoplasty. An increased frequency of system vulnerable to any abnormal experience. This period is
topical steroids and antibiotics is required for a week after up to seven to eight years in humans. Once this period is over,
suture removal. Suture loosening and graft rejection can occur amblyopia is not likely to occur. This is also the period when
insidiously in young children who cannot communicate the amblyopia therapy is maximally effective as the immature visual
occurrence of discomfort and vision changes. Graft rejection system can be modulated in this period.
is supposed to occur at a more rapid phase in children due to As the visual deprivation in amblyopia is more related to
an amplified wound healing response.13 the competitive interaction between both the eyes rather than
disuse in most cases, results of treatment are better if the
REFRACTIVE CORRECTION treatment is started within the critical period of visual
maturation as then the changes in the lateral geniculate body
Refraction is done after suture removal for optical correction and the visual cortex is partially or completely reversible. The
and amblyopia therapy initiated as soon as possible. In cases keyword for the management of amblyopia is "equalization"
of potential risk of dense amblyopia, early refractive correction of visual acuity between both the eyes so that they can function
may be provisionally prescribed with frequent changes as together as a team. The modalities include a high degree of
required in an attempt to increase the effectivity of amblyopia suspicion of the condition, early detection, observation of
therapy and prevent dense amblyopia. Early refractive associated abnormal eye movements in the form of roving
rehabilitation in terms of spectacle correction or contact lenses eye movements, nystagmus, abnormal head postures, etc.
to correct residual astigmatism and contact lenses or intraocular removal of any media opacity, correction of refractive errors
lens implants for aphakia is required. and providing the worse eye a competitive advantage over the
better eye by occluding the better eye, either physically with a the cornea, persistent epithelial defects, and performance of
patch or with the help of cycloplegic drugs. Strict vigilance lensectomy-vitrectomy were factors most highly correlated with
and monitoring of therapy is important. Aggressive amblyopia poor graft survival. Postoperative shallowing of the anterior
management is mandatory for good visual outcomes in chamber and the occurrence of anterior synechia leading to
pediatric patients undergoing keratoplasty. Occlusion of the secondary glaucoma are other significant problems causing
better eye by direct patching over the skin forms the mainstay graft failure in the pediatric age group. Other factors limiting
of the treatment of amblyopia. A patch applied over the skin visual outcome include glaucoma, hemorrhage and retinal
is preferred to a patch over the spectacles as the child can complications.
easily take off the spectacles or look outside through the sides Graft rejection: Pediatric corneal transplantation has an increased
of the occluded spectacle. The principle of this therapy is to rejection rate due to a more active immune system in younger
provide a competitive advantage to the worse eye over the patients.17 Endothelial immune rejection leading to graft failure
better eye so as to eliminate the components of abnormal remains one of the main causes for graft failure in pediatric
binocular interaction and the inhibitory influences of the better corneal transplantation. Well established graft rejection in
eye on the receptive fields of the worse eye. Occlusion should children is usually irreversible.18 Increased risk of allograft
be started as soon as possible. The family should be educated rejection after bilateral keratoplasty is controversial.4 The
to recognize the fixating eye and guide the patient towards decision to perform keratoplasty in the fellow eye in bilateral
free alternation. cases is to be made by the treating surgeon. Early intervention
is to be considered for both eyes in view of providing useful
REGRAFTS vision and to avoid irreversible amblyopia in the eye that is
Repeat penetrating keratoplasty is quite often required in operated upon later. In infants with an amplified inflammatory
pediatric eyes as there is a high chance of failure of the primary response, graft rejection can occur rapidly and be less
graft with poor prognosis for visual recovery. The graft survival responsive to treatment. Early symptoms of graft rejection
is worse in eyes undergoing multiple regrafts. Repeat such as reduced visual acuity and ocular discomfort cannot be
transplantation in infants and children fail more frequently than communicated thereby resulting in delay in diagnosis and
the first transplantation. Regrafts in congenital glaucoma tend treatment and a higher degree of graft failure. Most of the
to fail earlier than primary grafts4. Rejection reversals have been reported percentages of graft rejection in pediatric keratoplasty
described to be more successful in the primary grafts compared vary between 22 percent to 43.4 percent.4
to that in regrafts.16 The increased need for regrafting, besides Topical cyclosporine (CsA) 2% is used four times a day
the high incidence of complications in pediatric corneal along with systemic steroids as a routine in pediatric
transplantation, places a high emphasis on decision making keratoplasty by some surgeons. It is then tapered over three
before attempting surgical intervention. Repeat grafts may still months to once a day. CsA is a potent immunomodulator
be indicated in infants or children in the amblyogenic age group that affects early stages of antigenic sensitization and
as even if the regraft survives for only one year, as this will subsequent proliferation of immunocompetent cells.
enhance the visual development of the child and reduce the Prolonged use of topical corticosteroids is associated with
risk of loss of vision due to amblyopia. increased risk of cataract formation, glaucoma and delayed
wound healing. Use of topical CsA eliminates these risks of
COMPLICATIONS topical steroids. While steroids induce a general ocular
Acquired corneal scars, corneal decompensation, older immunosuppression with an enhanced risk for secondary
children, and phakic eyes have the best prognosis. Corneal infection, topical CsA being a specific immunomodulator by
perforations, active inflammation or infection, and infants with nature of their action on T lymphocytes only, do not affect
multiple ocular anomalies have the worst prognosis. Children the antimicrobial arm of the immune system. Therefore, there
undergoing combined procedures have been found to have a is less risk of graft infection. Early suture removal can also be
less favorable result than those undergoing a single- or two- done with use of topical CsA as this does not delay wound
staged procedure. Complications such as cataract development, healing which is beneficial in pediatric corneal grafts as the
secondary glaucoma, epithelial defects, band keratopathy, suture related problems can be minimized.
retinal detachment, wound leakage, retrocorneal membrane, Graft infection: Bacterial keratitis after primary penetrating
and microbial keratitis make the postoperative course complex keratoplasty in children is a serious complication resulting in
often necessitating regrafting. Preoperative vascularization of graft failure and poor visual outcome. Reported incidences
Corneal Surgery 681
of graft infection vary from 10 to 50 percent in pediatric grafts.4 end of the procedure that extreme care is taken to avoid this
Graft survival prognosis becomes bleak after onset of bacterial complication. With improved surgical technique and suture
infection and hence calls for aggressive preventive measures. materials, postoperative wound leak and dehiscence is now
Most of the pediatric graft infections being attributed to suture rarely seen.
related causes, penetrating keratoplasty in children requires
Cataract: The reported rates of cataract vary between two to
frequent examinations to reduce risk of infection due to suture
seven percent with as much as 18 percent in eyes with multiple
related problems. Completion of suture removal as early as
interventions.4
possible or before six months can be considered. A continued
close follow-up is required even after removal of sutures Endophthalmitis: Reported rate of endophthalmitis following
especially in eyes with glaucoma or ocular surface disorders. pediatric keratoplasty is about two percent.4 The incidence of
Prolonged use of antibiotics until all sutures have been ocular infections (4–9%)4 following pediatric keratoplasty is
removed can perhaps decrease the risk of development of higher in cases of children undergoing multiple procedures as
graft infection in these cases. Non-compliance to follow-up, in glaucoma patients where there is a need for multiple
failure to report to the transplant surgeon after irritation due intraocular interventions.
to loose sutures is the most important risk factor for graft
Glaucoma: The incidence of post penetrating keratoplasty
infection in developing countries. Lower socioeconomic status
glaucoma has been found to be five to nine percent in cases
and long distance from the treating referral center contributes
of pediatric penetrating keratoplasty.4
to delay in diagnosis and treatment. There is a higher prevalence
of graft infection in eyes with congenital corneal opacity Retinal detachment and phthisis: Other vitreo-retinal complications
(especially in eyes with congenital glaucoma) compared to such as expulsive choroidal hemorrhage (2–3%), retinal
acquired causes. The requirement to perform multiple detachment (3–5%) and phthisis (4–13%) have also been
glaucoma and other surgical diagnostic procedures may reported in pediatric penetrating keratoplasty.4 Yang et al's19
probably explain the higher prevalence of graft infection in series have reported a relatively high rate of retinal detachments
congenital glaucoma eyes undergoing penetrating keratoplasty. (35%) and phthisis (18%) in eyes with Peter's anomaly that
Most of the reported infections of the pediatric corneal underwent multiple intraocular procedures for IOP control
graft infection are due to Streptococcus pneumoniae. In eyes with and visual rehabilitation.
endophthalmitis secondary to graft infection, Haemophilus Amblyopia: Amblyopia and its correlates (deprivation, refractive
influenzae and Streptococcus pneumoniae have been isolated from amblyopia, nystagmus and defective development of central
the vitreous.4 Frequent postoperative examinations as long as fixation) form the most important of the factors for visual
sutures are present will help in reducing risk of infections due outcome. Corneal pathology in children, which results in
to neglected sutures. In children less than six months, all sutures decreased vision has also been found to induce refractive errors
are usually removed within two months with prophylactic especially myopia due to elongation of the eye, and more so,
antibiotics coverage. Prolonged use of broad spectrum if the condition is unilateral. Even after the best surgical
prophylactic antibiotic therapy till all sutures are removed can intervention for the removal of the corneal pathology, the
also help in reducing suture related complications. associated refractive error in the operated eye and pre-existing
Persistent epithelial defect: Persistent epithelial defects (PED) in amblyopia may result in subnormal rehabilitation of the visual
pediatric corneal grafts can result in graft failure. PED resulting acuity. Aggressive treatment for amblyopia is one of the most
important factors resulting in a high optical success of the
from poor graft host junction apposition and faulty suturing,
procedure and the best visual outcomes. Prolonged corneal
early suture loosening, drug toxicity, tear and surface
graft survival can be achieved in children, but successful
abnormalities may predispose to graft infection. Prolonged
restoration of visual acuity depends upon a period of normal
epithelialization, subsequent to PED also leads to significant
visual development before the onset of corneal opacification.
graft haze compromising optical quality of vision.
Children with earlier onset of corneal opacities associated with
Wound dehiscence: Wound leak and dehiscence (2–10%),4 due to more severe ocular pathology requiring more complicated
suboptimal suturing can lead to postoperative shallowing of intervention procedures, leading to a more difficult
the anterior chamber necessitating immediate postoperative postoperative management, will be associated with a poorer
suturing under anesthesia. The surgeon should ensure at the visual outcome.
REFERENCES 10. Toker E, Seitz B, Langenbucher A, et al. Penetrating keratoplasty

for endothelial decompensation in eyes with buphthalmos. Cornea
1. Wiesel TN. Postnatal development of visual cortex and the 2003;22:198-204.
influence of environment. Nature 1982;299:583-91. 11. Al-Torbak AA. Graft survival and glaucoma outcome after
2. Stulting RD. Penetrating keratoplasty in children. In Brightbill FS
simultaneous penetrating keratoplasty and Ahmed glaucoma valve
(ed). Corneal surgery: theory, technique and tissue. St Louis: Mosby
implant. Cornea 2003;22:194-7.
1993;2:374-85.
12. Aquavella JV, Gearinger MD, Akpek EK, McCormick GJ. Pediatric
3. Stulting RD, Sumers KD, Cavanagh HD. Penetrating keratoplasty
keratoprosthesis. Ophthalmology 2007;114:989-94.
in children. Ophthalmology 1984;91:1222-30.
13. Brown SI, Salomon SM. Wound healing of grafts in congenitally
4. Vanathi M, Panda A, Vengayil S, Chaudhuri Z, Dada T. Pediatric
keratoplasty. Surv Ophthalmol 2009;54:245-71. Review opaque infant corneas. Am J Ophthalmol 1983;87:1253-64.
5. Al-Ghamdi A, Al-Rajhi A, Wagoner MD. Primary pediatric 14. Taylor D, Hoyt CS. Pediatric ophthalmology and strabismus. New
keratoplasty: indications, graft survival, and visual outcome. J York: Elsevier Saunders 2005;3:1-62.
AAPOS 2007;11:41-7. 15. Keech RV, Kutschke PJ. Upper age limit for the development of
6. Nichal KK, Naor J, Jay V, et al. Clinicopathological correlation of amblyopia. J of Pediatr Ophthal and Strab 1995;32:89-93.
congenital corneal opacification using ultrasound biomicroscopy. 16. Yang LL, Lambert SR, Lynn MJ, Stulting RD. Long-term results
Br J Ophthalmol 2002;86:62-9. of corneal graft survival in infants and children with Peters anomaly.
7. Townsend WM. Congenital anomalies of the cornea Kaufman Ophthalmology 1999;106:833-48.
HE, Baron BA, McDonald MB (eds). The Cornea. CD ROM. 17. Alldrege C, Krachmer JC. Clinical types of corneal transplant
London: Butterworth-Heinemann 1999;2. rejection. Arch Ophthalmol 1981;99:599-604.
8. Rezende RA, Uchoa UB, Uchoa R, et al. Congenital corneal 18. Beauchamp GR. Pediatric keratoplasty: problems in management.
opacities in a cornea referral practice. Cornea 2004;23:565-70. J Pediatr Ophthalmol Strabismus 1979;16:388-94.
9. Dana MR, Schaumberg DA, Moyes AL, Gomes JA. Corneal 19. Yang LL, Lambert SR, Lynn MJ, Stulting RD. Surgical management
transplantation in children with Peter's anomaly and mesenchymal of glaucoma in infants and children with Peters' anomaly: long-
dysgenesis. Multicenter Pediatric Keratoplasty Study. Ophtha- term str uctural and functional outcome. Ophthalmology
lmology 1997;104:1580-6. 2004;111:112-7.
6.10.1.7 Corneal Patch Grafts

Corneal patch grafts may (Figs 6.10.1.7.1 and 6.10.1.7.2) be • Descemetocele
performed to restore tectonic integrity of the ocular surface in • Peripheral ulcerative keratitis with severe thinning
cases of corneal/corneoscleral perforations not amenable to
management with glue application.1,2 Perforations larger than 3
mm can be managed with patch graft procedure. Restoration of
normal corneal thickness of corneas with thinning may also be
achieved with lamellar patch grafts. Patch grafts may be (i) full
thickness grafts (ii) lamellar grafts or (iii) mushroom type of grafts.2
A full-thickness corneal patch graft is performed in cases of
corneal perforation with pseudocornea formation. Mushroom
grafts may be performed for cases with corneal perforation with
or without central iris incarceration and surrounding flange of
corneal thinning at the edges of the perforation. Lamellar grafts
are useful in cases of corneal thinning without perforation or iris
incarceration.
Corneal thinning with impending perforation occurs secondary
to infection, trauma immune disease or inflammatory causes.
Indications for patch grafts include:
• Focal corneal or corneo scleral thinning/melts Fig. 6.10.1.7.1: Peripheral patch graft for post chemical injury
• Small corneal perforations corneal melt
Corneal Surgery 683
• Postinfectious keratitis focal melts

• Focal corneal melt secondary to keratomalacia
• Steroid induced corneal melts/thinning
• Post pterygium excision corneal/corneoscleral melt/
thinning.
Corneal patch grafts are effective for tectonic
reconstruction of the ocular surface.
REFERENCES
1. Soong HK, Farjo AA, Katz D, et al. Lamellar corneal patch grafts
in the management of corneal melting. Cornea 2000;19:126-34.
2. Vanathi M, Sharma N, Titiyal JS, Tandon R, Vajpayee RB.
Tectonic grafts for corneal thinning and perforations. Cornea
Fig. 6.10.1.7.2: Patch-graft with pupilloplasty 2002;21(8):792-7.
6.10.1.8 Alternatives to Keratoplasty

AUTO-ROTATIONAL KERATOPLASTY distance from the edge of this circle to the geometric center
of the cornea is determined (taken as positive if the central
Penetrating keratoplasty is the ideal choice for optimal visual
cornea was involved or negative if the opacity was within the
rehabilitation in corneal opacities. Autologous ipsilateral rotating
largest area of the clear cornea). The required trephine size is
keratoplasty is a special form of keratoplasty in cases of non-
obtained with the following equation: 1.5 × diameter of the
progressive opacification of the central area of the cornea, which
is rotated towards the limbus and the clear peripheral cornea is largest circle of clear area of cornea added to the shortest
rotated into the optical axis of the eye. Autologous rotational distance from the circle to the corneal center.
keratoplasty is considered an alternative therapeutic option in Surgical technique: Following partial thickness trephination of
patients with central corneal scars. Its advantage compared to the host cornea, anterior chamber entry is made with a MVR
allogeneic procedures is that there is no immunogenic rejection blade and filled with viscoelastic. The host corneal trephination
reaction. It can be considered as an alternative procedure to cut is completed with corneo-scleral scissors. Care is taken to
penetrating keratoplasty in a scenario in which tissue scarcity exists, gently separate iridocorneal adhesions if any. Pupilloplasty, if
as well as in cases that have a high-risk of developing immunologic required is performed to position the pupil in the center of
allograft rejection. Rotational autokeratoplasty has many advantages, the cornea. The host corneal button is rotated to bring the
such as having no immune reaction, providing easy postoperative clear cornea into the central area and the scar into the farthest
care in younger patients having susceptibility to amblyopia, and peripheral position (Figs 6.10.1.8.1A to E). Postoperative
demonstrating no vascularization of the cornea. However its medications with topical steroids and antibiotics were given
disadvantages include limitations of patient selection, residual for six to eight weeks along with topical lubricants.
postoperative astigmatism, anterior synechia, and glaucoma. The Ipsilateral rotational autokeratoplasty is a safe and effective
largest problem inhibiting its widespread use is the limitations of surgical procedure. By rotating an eccentric corneal button, the
patient selection. Rotational autokeratoplasty is usually performed scar could be displaced peripherally and clear cornea brought
for selective cases of corneal scars.1-8 Preoperative endothelial counts into the visual axis (Figs 6.10.1.8.2A and B). Though penetrating
are to be done to evaluate the status of the endothelium. keratoplasty is the ideal choice for optimal visual rehabilitation,
Calculation of the trephine size: The size of the trephine may be consideration of graft rejection in a setting of pediatric
determined based on the method described by Bourne and keratoplasty, upholds rotational autokeratoplasty as a viable
Brubaker9 or on the surgeon's judgment. According to the alternative. Ipsilateral rotational autokeratoplasty combined with
method described by Bourne and Brubaker,9 the diameter of pupilloplasty can be put to effective use for visual rehabilitation
the largest circle of clear cornea is measured. The shortest in selective cases of corneo-iridic scars especially in developing
Fig. 6.10.1.8.1A: Diagrammatic representation of corneo-iridic

scar
Fig. 6.10.1.8.1D: Trephined host cornea rotated

to bring clear area into center
Fig. 6.10.1.8.1B: Trephining of the host cornea

over the corneo-iridic scar
Fig. 6.10.1.8.1E: Final positioning and suturing

of graft with central pupilloplasty
been described for preoperative surgical planning. Bower et al

have described a simple digital imaging in preoperative surgical
planning for rotational autokeratoplasty which demonstrates
the potential for tele-ophthalmology. Bourne and Brubaker9
elaborate a method for determining the maximum clear central
corneal area that can be obtained by rotational autokeratoplasty
and the most appropriate trephine size and placement. Two
Fig. 6.10.1.8.1C: Pupilloplasty positioning in the dimensions are required to be measured either at the slit lamp
center of the visual axis area
or from photographs: the diameter of the largest circle of
clear cornea and the shortest distance from the edge of this
nations where a scarcity of donor corneal tissue prevails. It also circle to the center of the cornea. Other complex mathematical
allows for a less complicated postoperative follow-up which is modeling for preoperative calculation in rotating
suited to patients of lower socio-economic status in developing autokeratoplasty has also been described in literature.12-15
countries who have to travel long distances to tertiary care centers. Recently Afshari et al16 have reported a mathematical model
This technique can be successful only in those cases of central for most clinical instances of a rotational autograft, in which
corneal scarring with sufficient undamaged peripheral cornea and an 8 mm graft with a decentration of 0.5 mm can be effective.
where minimal interference with angle structures is required.10 They proposed that for scars that are alpha degrees from the
Careful preoperative planning ensures successful horizontal, the graft should be rotated 180–alpha degrees for
achievement of the desired effect of clearing the visual axis. optimal results. Most of these are complex methods and
Miscalculation will result in significant residual central opacity. obtaining good preoperative slit lamp photographs are not
Digital imaging11 and complex calculation9,12-16 methods have possible, such as in pediatric cases, and it has to be left to the
Corneal Surgery 685
Figs 6.10.1.8.2A and B: Rotational autokeratoplasty with pupilloplasty (B) in a pediatric corneo-iridic scar (A)
surgeon's discretion to decide on the optimal trephine sizing 5. McDonnell PJ, Falcon MG. Rotational autokeratoplasty. Eye
at the time of the surgery. After autologous rotational 1989;3(Pt 5):576-80.
keratoplasty relative annual endothelial cells loss of 1.1 percent 6. Sah WJ, Myoung YW, Hahn TW, Kim JH. Rotational
±2.6 percent has been reported.17 Endothelial cell loss in autokeratoplasty in advanced lipid keratopathy. Ophthalmic Surg
autologous grafts has been found to be significantly lower Lasers 1997;28:1020-4.
7. Naumann Go, Volker HE, Gackle D. Ipsilateral rotational
than in homologous grafts.18 Most of the published series3–5,
8 have reported moderate to good visual outcomes for autokeratoplasty. Klin Monatsbl Augenheilkd 1977;170:488-93.
8. Bobrova NF. Reconstruction of the anterior eye segment in children
rotational autokeratoplasty for corneal scars. The visual based on penetrating rotary autokeratoplasty. Oftalmol Zh
outcome in autokeratoplasty remains suboptimal as compared 1990;5:261-6.
to homologous keratoplasty due to higher amounts of 9. Bourne WM, Brubaker RF. A method for ipsilateral rotational
astigmatism as a result of persistence of the corneal opacity autokeratoplasty. Ophthalmology 1978;85:1312-6.
and eccentric placement of the grafts bringing it closer to the 10. Robinson LP. Keratoplasty following anterior segment trauma. Aust
visual axis. The cosmetic blemish due to presence of the scar J Ophthalmol 1981;9:59-62.
still remains in spite of recreating a relatively clear central visual 11. Bower KS, Mines MJ, Stutzman RD. Digital imaging to assist
axis with rotational autokeratoplasty. Delay in timing of preoperative planning for ipsilateral rotational autokeratoplasty. J
keratoplasty due to the paucity of donor corneal tissue also Telemed Telecare 2006;12:374-6.
12. Karpouzas I, Pouliquen YJ. Computerized method for rotational
remains a problem in developing countries. Therefore
autokeratoplasty. Cornea 1991;10:369-71.
rotational autokeratoplasty with pupilloplasty can be 13. Karpouzas I, Pouliquen Y. Modelling and numerical optimization
considered as an alternative to allogeneic keratoplasty for early of corneal rotation. IMA J Math Appl Med Biol 1991;8:73-82.
visual rehabilitation with the option of minimizing post- 14. Jonas JB, Panda-Jonas S. Calculation of size and location of
operative visits and eliminating immunogenic rejection. autologous ipsilateral rotating keratoplasty. Graefes Arch Clin Exp
Ophthalmol 1994;232:538-44.
REFERENCES 15. Schroeder W. [Rotation auto-keratoplasty. Preoperative calculation].
Klin Monatsbl Augenheilkd 1989;195:83-6.
1. Vasco-Posada L. Ipsilateral autokeratoplasty. Am J Ophthalmol
1967;64:717-21. 16. Afshari NA, Duncan SM, Tanhehco TY, Azar DT. Optimal size
2. Groden Lr, Arentsen JJ. Ipsilateral rotational autokeratoplasty. Ann and location for corneal rotational autografts: a simplified
Ophthalmol 1983;15: 899-901. mathematical model. Arch Ophthalmol 2006;124:410-3.
3. Ver ma N, Melengas S, Garap JA. Ipsilateral rotational 17. Birnbaum F, Reinhard T, Bohringer D, Sundmacher R. Endothelial
autokeratoplasty for the management of corneal opacities. Aust N cell loss after autologous rotational keratoplasty. Graefes Arch Clin
Z J Ophthalmol 1999;27:21-5. Exp Ophthalmol 2005;243:57-9.
4. Murthy S, Bansal AK, Sridhar MS, Rao GN. Ipsilateral rotational 18. Bertelmann E, Hartmann C, Scherer M, Rieck P. Outcome of
autokeratoplasty: an alternative to penetrating keratoplasty in rotational keratoplasty: comparison of endothelial cell loss in
nonprogressive central corneal scars. Cornea 2001;20:455-7. autografts vs allografts. Arch Ophthalmol 2004;122:1437-40.
6.10.2 Lamellar Keratoplasty

6.10.2.1 Anterior Lamellar Keratoplasty
M Vanathi
Introduction: Lamellar Keratoplasty ii. Posterior lamellar keratoplasty (PLK) (Posterior replacement
The field of keratoplasty has seen major advances in surgical of deep stromal and endothelial layers or endothelial
techniques that encourage a shift in the surgical treatment of keratoplasty (EK):
corneal disease. Though penetrating keratoplasty is still being • Deep lamellar endothelial keratoplasty (DLEK)
widely practiced for most corneal pathologies, recent times • Descemet’s stripping endothelial keratoplasty
has seen a change with penetrating keratoplasty being replaced (DSEK)/Descemet's stripping automated endothelial
by various types of lamellar techniques. Lamellar keratoplasty keratoplasty (DSAEK)
targets to replace damaged corneal tissue while retaining • Descemet's membrane endothelial keratoplasty
normal tissue (Figs 6.10.2.1.1 and 6.10.2.1.2). (DMEK)
In recent times, lamellar keratoplasty is classified as: The shifting emphasis from penetrating to lamellar forms
i. Anterior lamellar keratoplasty (ALK) (Lamellar procedure of corneal transplantation due to the advent of new techniques
replacing anterior stroma): in both anterior lamellar keratoplasty (ALK) and posterior
lamellar keratoplasty (PLK), the improved visual outcomes,
• Lamellar keratoplasty: (conventional up to the layer
use of microkeratomes, and femtosecond lasers enhanced
of stromal involvement)
lamellar keratoplasty has encouraged several corneal surgeons
• Deep anterior lamellar keratoplasty (complete
to now consider lamellar corneal transplantation for the
removal of stroma baring the Descemet's
management of a wide variety of corneal pathologies.
membrane):
♦ Manual (manual dissection, lamellar separation
ANTERIOR LAMELLAR KERATOPLASTY
with air, saline, viscoelastic)
♦ Automated (automated lamellar therapeutic
History
keratoplasty—(ALTK) Lamellar keratoplasty was first suggested in 1830 by von
♦ Hemi-automated lamellar keratoplasty (HALK). Walther.1 Von Hippel (1880)2 and Filatov (1930)3 further
Figs 6.10.2.1.1A and B: Diagrammatic representation of anterior Figs 6.10.2.1.2A and B: Diagrammatic representation of
lamellar keratoplasty: (A) Lamellar keratoplasty: (conventional up to posterior lamellar keratoplasty
the layer of stromal involvement); (B) Deep anterior lamellar
keratoplasty (complete removal of stroma baring the Descemet's
membrane)
Corneal Surgery 687
improved on it. Paufique further developed surgical techniques range from keratoconus and hereditary dystrophies, to include
in 1940.4 Hallerman5 attempted deep dissection up to the severe ocular surface disease and cases following infection and
Descemet's membrane in 1959. McCulloh6 described lamellar corneal perforation. The concept of creating a deep lamellar
keratoplasty using full thickness donor tissue, while Malbran7 bed for lamellar keratoplasty is well known. Exposing the
described peripheral lamellar dissection with central peeling in Descemet's membrane is tedious, time consuming procedure
keratoconus. Anwar8 in 1974 described deep dissection under and technically more demanding. New techniques that use air
direct visualization in a potential cleavage plane between stroma and ophthalmic viscosurgical devices to aid in baring the
and Descemet's membrane. Anwar was the first to describe deep Descemet's membrane serve to reduce the surgery time and
dissection baring the Descemet's membrane and used full improve the safety of the procedure.
thickness donor tissue after removing the donor Descemet's
membrane and endothelium, in lamellar keratoplasty. Archila9 Advantages and Disadvantages of
again described deep lamellar dissection up to the Descemet's Anterior Lamellar Keratoplasty
membrane in the 1980s. Archila used intrastromal air injection
and spatula dissection to facilitate access to the Descemet's Advantages
membrane without perforation. Price10 and Rostron11 described
• ALK is largely a non-penetrating surgery, it reduces the
similar techniques later, with Sugita 12 elaborating
risk of intraocular complications such as glaucoma, cataract
hydrodelamination and spatula delamination. The divide and
formation, cystoid macular edema, retinal detachment,
conquer technique involving dividing the corneal stroma into
endophthalmitis and expulsive hemorrhage
four quadrants in two successive layers to reach the Descemet's
• ALK retains the normal recipient endothelial layer, thereby
membrane was described by Tsubota.13 Melles14 described deep
lamellar dissection facilitated by a special semi-sharp spatula in reducing the risk of endothelial graft rejection
a closed manner. The "Big Bubble" technique of Anwar and • ALK does not require good endothelial quality donor tissue
Teichmann15 for deep lamellar dissection has gained popularity • As the integrity of the Descemet's membrane is not
in recent times. disturbed, ALK technically achieves a stronger corneal
Lamellar transplantation procedures, largely being non- wound
penetrating extraocular procedures, have several advantages, • Suture related astigmatism is lesser in ALK procedures.
such as reduced risk of incidence of intraocular complications
like glaucoma, cataract formation, retinal detachment, cystoid Disadvantages
macular edema, endophthalmitis and expulsive hemorrhage, • ALK is technically more demanding and time consuming.
reduced risk of graft rejection, and early suture removal.16-21 • Suboptimal visual acuity compared to PK due to interface
Despite the distinct advantages of ALK surgery such as the problems, lamellar dissection regularity, and residual
preservation of the normal host endothelium and need to use scarring.
non-optical grade corneas, penetrating keratoplasty still
remains the most common procedure, as lamellar corneal Indications for Lamellar Keratoplasty
surgery is more technically demanding, time consuming, and
the resultant interface irregularity and haze arising from manual The various indications for lamellar keratoplasty include:22
lamellar dissection results in suboptimal visual outcomes. • Optical
Recent improvements in the surgical techniques of corneal Anterior stromal opacities of varied etiology
lamellar dissection and advances in instrumentation such as – Congenital (Dermoid)
microkeratome-assisted lamellar corneal transplantation have – Acquired
contributed to improved optical quality of vision with lamellar ♦ Post-traumatic (Multiple corneal foreign bodies,
corneal surgeries. As endothelial cell counts and graft survival post-chemical injury scars, contact lens induced
rates in penetrating keratoplasty decline in long-term, opacities, healed/repaired post-traumatic scars)
unnecessary replacement of healthy endothelium in anterior- ♦ Post inflammatory/infective (Trachomatous
stromal disorders does not seem logical. keratopathy, healed superficial keratitis)
Deep anterior lamellar keratoplasty is now being considered ♦ Degenerative (Recurrent pterygium, keratoconus,
as the first choice of surgery for a wide range of diseases pellucid marginal degeneration, Terriens degene-
affecting the corneal stroma while the endothelium is relatively ration, spheroidal degeneration, Salzman nodular
healthy. The indications for deep anterior lamellar keratoplasty degeneration, band shaped keratopathy)
♦ Dystrophies (Epithelial and stromal dystrophy) Surgical Procedure

♦ Neoplastic (Ocular surface squamous neoplasia)
• Tectonic Preoperative Preparation
– Corneal stromal melts as in Descemetocele, post- The preoperative preparations for lamellar keratoplasty are
rheumatoid corneal melts, Mooren's ulcers similar to that of penetrating keratoplasty except that lowering
• Therapeutic of intra-ocular pressure and pupillary dilatation is not required
– Infective keratitis limited to the anterior corneal layers unless a concurrent phacoemulsification is planned.
• Refractive
– corneal ectasias and degenerations such as keratoconus, Surgical Technique
pellucid marginal degeneration
– post LASIK keratectasia Globe Exposure
– post PRK scarring Appropriate sized lid speculum with proper positioning is
– irregular astigmatism. imperative to minimize pressure on the lids which might
• Ocular surface reconstruction produce undue increase in IOP during surgery and globe
– Large lamellar transplantation/limbal segmental or distortion. Lateral canthotomy may help the patients in tight
annular grafts either alone or in combination with orbit. Bridle sutures of superior and inferior recti are preferred
limbal conjunctival grafts/amniotic membrane grafts by some surgeons.
for ocular surface inflammatory diseases such as
Stevens-Johnson syndrome, chemical injury. Host Cornea Marking
Types of Lamellar Keratoplasty The donor cornea graft is to be centered on the host cornea
or the pupillary axis which is usually slightly nasal. The optical
Inlay Lamellar Keratoplasty axis is marked by the surgeon using gentian violet or marking
• Conventional lamellar keratoplasty (involving central pen.
cornea) A stained 8 or 12 prong radial marker may be used to
• Segmental (for lesions not involving the visual axis) mark the corneal surface by most surgeons to aid in placement
• Key hole (for lesions involving both peripheral/pupillary of sutures for better alignment and symmetry in anterior
area) lamellar keratoplasty.
• Annular/Crescentic (for lesions involving only the
Sizing and Trephination
peripheral cornea).
The size of the opacity is measured with a measuring caliper
Onlay Lamellar Keratoplasty to decide the trephine size. The trephine is preset to the
• Epikeratoplasty for keratoconus requisite depth in accordance with the depth of stromal
involvement. Partial thickness trephination of the host cornea
Preoperative Assessment bed is then carried out.
1. Detailed slit lamp biomicroscopic evaluation of the corneal Stromal Dissection

pathology to assess depth of stromal involvement is to be
done. Lamellar dissection of the stromal tissue can be carried out:
2. Preoperative assessment as in penetrating keratoplasty, of • Manually with the lamellar dissector/crescent knife or
lid and ocular adnexa, precorneal tear film, rule out facilitated by use of air, BSS, or viscoelastics, either alone
presence of infection/inflammation, posterior segment or by a combination
evaluation and intraocular pressure is mandatory. General • Automated—using the automated microkeratome as in
systemic evaluation may be required in cases to be operated ALTK.
under general anesthesia. Anterior lamellar keratoplasty traditionally consists of
3. Pachymetry and anterior segment optical coherence manual dissection of the stromal layers with the use of lamellar
tomography indicating depth of involvement of the dissectors. A smooth lamellar dissection is often difficult to
corneal pathology is recorded. obtain in manual dissection and deeper dissection carries the
Corneal Surgery 689
risk of perforation. Hence the resultant visual outcome in of the Descemet's membrane has also been described.31,32
manual lamellar dissection commonly remains compromised However it deserves to be mentioned that the cleavage plane
due to irregularity or residual scarring. of separation is supposed to occur not between the stroma
and the Descemet's membrane but between the banded and
Manual Lamellar Dissection non-banded part of the Descemet's membrane.33
The advantage of deep lamellar keratoplasty over that of
The manual lamellar dissection methods8 include:
standard lamellar keratoplasty is the elimination of the graft-
Closed Dissection host stromal interface, and the associated resultant haze and
irregularity. This provides for achieving better visual outcomes
After the desired depth trephination, a stromal pocket is made and faster visual rehabilitation. The visual outcomes of deep
with the help of a Paufique knife at the incision site. The lamellar keratoplasty have been found to be comparable to
intralamellar dissection is carried out with the help of a standard penetrating keratoplasty with the endothelial cell loss
Desmarre's lamellar dissector/crescent knife. The lamellar also being reported to be equal to that of penetrating
corneal dissector is introduced through the pocket while lifting keratoplasty.
up the anterior lip of the flap with a Pierse Hoskin's forceps
Viscodissection: Viscoelastic material is injected slowly into the
and the dissection is continued by gentle side to side movement.
stromal pocket which allows the separation of the Descemet's
The lamellar dissector is held parallel to the posterior stromal
membrane from the rest of the posterior stroma. The cannula
bed in order to prevent perforation. The surgical field is kept
is slowly advanced into the created space with continued
dry to facilitate dissection and detect any inadvertent
viscoelastic injection till the complete lamellar visco-separation
perforation. The method of closed lamellar dissection provides
is achieved.
a smoother separation but is more difficult as direct
visualization is not possible. Hydrodelamination: Saline solution may also be injected into the
stromal pocket to help obtain lamellar dissection with this
Open Dissection process being termed hydrodelamination as described by Sugita
et al.12 It remains to be noted that besides being a more
In open lamellar dissection, the edge of the separated anterior
technically demanding procedure, the rate of perforation is
lamellar tissue is held retracted with the help of the forceps during
supposed to be as high as 39 percent even with experienced
dissection enabling direct visualization of the area of separation.
surgeons.30
Additional techniques have been described to facilitate
lamellar dissection enabling safer approaches to removal of Air dissection: Anwar big bubble technique: In recent times the most
the deeper stromal layers. This form of lamellar dissection widely practiced approach to achieve deep lamellar separation
reaching the deeper posterior stromal layers is termed deep is by deep stromal air injection.8,9 The big bubble technique15
lamellar keratoplasty (DLK). These techniques involve the use involves using a 27 or 30 gauge needle attached to an air filled
of deep stromal injection of air, 8,9,11,23,24 saline 12,25 or syringe. The needle is inserted bevel down into the corneal
viscoelastics.12,26-29 The force of the injecting substances into stroma at the entry site for two to four mm at an angle until it
the stroma creates a plane of least resistance. If the plane is is in the deep stroma and approaches the posterior stromal
sufficiently posteriorly directed, it will enter the plane between and Descemet's membrane interface. Air injection then causes
the stroma and the Descemet's membrane, facilitating lamellar rapid separation of the Descemet's membrane forming a
dissection baring the Descemet's membrane, with this circular air pocket that is seen as a silvery bubble with a clearly
procedure being termed deep anterior lamellar keratoplasty defined circular edge. Persistent air injections further widen
(DALK). DALK or maximal depth lamellar keratoplasty the separation baring the Descemet's membrane up to the
involves removal of the entire corneal stroma baring the trephination edge. Perforation rates with this technique are
Descemet's membrane thus resulting in elimination of the lower (9%). 22 This has been further modified with by
graft-host stromal interface and the associated problems of performing a manual lamellar dissection of the anterior stroma
scarring and irregularity, resulting in enhanced visual outcomes up to a depth of 50 to 60 percent stromal thickness before
and rapid visual rehabilitation. attempting advancement of the needle into the deep posterior
Careful manual peeling technique is also used by some stroma for air injection.22 This allows for better depth
surgeons.30 Use of tryphan blue to aid in better visualization perception, thereby reducing the risk of perforation.
Automated Lamellar Keratoplasty rejection, with optical results similar to penetrating keratoplasty
(PK). However, many surgeons so not prefer DALK as the
Microkeratome first surgery of choice as the surgery is more technically
The advent of advanced microkeratome systems allows for demanding and also takes a longer time to perform in
a much superior smooth surface than manual method in comparison to a standard PK. Though DALK is more time
anterior lamellar keratoplasty. It however is not suitable in consuming when host stromal tissue is removed layer by layer
thin and ir regular cor neas as in cases of advanced until Descemet’s membrane is bared, it is beneficial to patients
keratoconus. Indications for ALTK include anterior stromal with healthy endothelium.
dystrophies with lesions largely limited to the anterior Lamellar dissection of host stromal tissue close to the
stromal layers, moderate forms of keratoconus and post Descemet's membrane, termed 'deep lamellar keratoplasty' was
PRK haze. first introduced by Archilla9 in 1984, who also described the
use of intrastromal air injection to facilitate host tissue removal.
Surgical Procedure In recent times, DALK has gained popularity due to
improvements in the surgical techniques, and the availability of
For anterior lamellar keratoplasty, the ALTK procedure
new surgical instruments and devices such as viscoelastics that
involves anterior lamellar corneal dissection of the recipient
have helped to improve surgical success and reduce surgery time.
cornea using the microkeratome. With the aid of the artificial
anterior chamber, the microkeratome is used to cut the donor
Indications of Deep Anterior
lamellar graft to match the recipient stromal bed, which is
Lamellar Keratoplasty
then sutured into position on the recipient bed.
• Keratoconus
Postoperative Care • Hereditary dystrophies
• Ocular surface disease
Postoperative care involves frequent use of topical steroids
• Infectious diseases.
and antibiotics, tapered gradually along with tear supplements.
Early suture removal may be performed for suture loosening
Keratoconus
and refractive rehabilitation of these cases.
DALK can be performed in all cases of corneal scars that do
DEEP ANTERIOR LAMELLAR not involve the corneal endothelium. The most common
KERATOPLASTY indication for DALK is keratoconus patients, who benefit most
retaining from preserving their own endothelium as these
The technique of deep anterior lamellar keratoplasty (DALK)
patients are relatively young, run the risk of g raft
(Fig. 6.10.2.1.3) can largely avoid the risk of endothelial
decompensation eventual to immunological rejection after PK.
Reported incidences of immunological rejection in
keratoconus patients following PK is as high as 20 percent.
The relative risk of secondary glaucoma in steroid responders
can be avoided with DALK, since topical steroids can be
discontinued early in the postoperative period. Keratoconus
patients with scars due to acute hydrops are not good
candidates for DALK since a central scar results in a break in
Descemet's membrane, and deep scarring limits visual recovery.
Hereditary Dystrophies
Most of the hereditary dystrophies including Avellino
dystrophy, granular dystrophy and lattice dystrophy are good
indications for DALK. As the Descemet's membrane is sturdier
in older patients as compared to the younger keratoconus
patients, the success rate of DALK is also better. Lamellar
Fig. 6.10.2.1.3: Deep anterior lamellar keratoplasty dissection to remove superficial stroma prior to exposure of
Corneal Surgery 691
Descemet's membrane will be required in eyes with dense

opacification.
DALK is indicated for most hereditary dystrophies, except
macular dystrophy in which the deeper stromal layers and the
endothelium are invariably involved.
Ocular Surface Disease

Conditions such as, trachomatous keratopathy, Stevens-Johnson
syndrome, ocular cicatricial pemphigoid, and ocular surface
chemical injuries, present with severe ocular surface disease along
with limbal stem cell deficiency. The residual stromal scarring
prevents effective visual rehabilitation in these situations even
after attempts of ocular surface reconstruction techniques such
as limbal transplantation or cultivated limbal epithelial
transplants (Fig. 6.10.2.1.4A). It is discouraging to note that Fig. 6.10.2.1.4A: Post ex-vivo cultured limbal stem cell
the poor outcome of PK in these eyes and the high immune transplant in a case of chemical injury
rejection reported in limbal transplant patients with either
simultaneous or secondary PK. For these reasons, DALK in
these eyes (Figs 6.10.2.1.4B and C) is a more preferred choice
than standard PK.
Therapeutic deep anterior lamellar keratoplasty: DALK in cases with
small corneal perforations and infectious disease limited to
anterior corneal layers help to achieve both tectonic integrity
and optical rehabilitation.
Surgical technique of DALK: Though DALK can be performed
under both general and local anaesthesia, it is to be noted
that the bare Descemet's membrane may not be able to
withstand sudden increase in vitreous pressure during the
course of the surgery, and hence surgeons generally prefer
to perform DALK under general anesthesia, especially those
in their learning curves for the surgery.
The 'classical' technique for DALK by lamellar dissection
involves, removal of host tissue, layer by layer until the deep
stroma or the bare Descemet's membrane is exposed. As
visualization of stromal fibers becomes difficult when the
amount of tissue becomes minimal, injection of irrigation fluid
causes swelling of stromal fibers which can then be manipulated
with fine forceps. The process of stromal fibers removal is time
consuming and demands surgical precision and expertise, making
DALK a specialized form of keratoplasty.
Techniques such as intra-stromal air injection or segmental
removal of host stroma help to improve baring of the
Descemet's membrane. Recent revolutionary techniques have
dramatically decreased surgery time with improved success.
Melles et al,14 in 1999 injected air into the anterior chamber,
to create a mirror reflex to guide surgical instruments into the
space between Descemet's membrane and the posterior Figs 6.10.2.1.4B and C: DALK in the same patient
stroma. The difference in refractive index between air and Management of Descemet's membrane perforation will
corneal tissue creates a reflex of the surgical knife, and the depend upon the size and location of the defect. Small self
distance between the instrument and reflex helps to judge the limiting perforations may be easily managed by air injection
amount of residual stromal tissue. into the anterior chamber at the end of surgery, or
Viscosurgical devices also aid in lamellar dissection up to postoperatively at the slit lamp. The air bubble affords
the level of the Descemet's membrane. It is imperative to tamponade to seal the perforation against aqueous inflow.
adequately irrigate the viscoelastic material, as any residual Once optimal apposition has been achieved, it is rare for an
viscoelastic will cause a double anterior chamber that will occurrence of a double anterior chamber in the absence of
mandate a surgical intervention. trauma. Larger tears that extend from rim to rim or along the
The 'big bubble' technique of Anwar and Teichman15 in circumference of the trephine excision are more difficult to
2002, involves use of pneumatic pressure to detach Descemet's manage. Air tamponade might suffice in relatively small flap
membrane by injecting air into the deep stroma with a 30G tear (horseshoe type). However, for larger macroperforations
needle, putting to effective use the loose adhesion between where Descemet's membrane usually tends to curl-up with
Descemet's membrane and posterior stroma. The air injected the endothelium facing inwards, an anchoring suture (10-0 or
into the supra-Descemet's space results in a dome-shaped 11-0 nylon) to directly suture the tear edge to the donor stroma
detachment of Descemet's membrane that can be identified will be required. The sutures may be removed if pseudoanterior
by a ring under the surgical microscope, creating the big bubble. chambers do not occur.
Remaining stromal tissue can then be removed to expose the
Pseudoanterior chambers: Breaks in Descemet's membrane
Descemet's membrane, which is characteristically smooth when
predispose to pseudo-anterior chambers or double chambers.
all of the stromal tissue is removed. The donor graft tissue,
Pseudoanterior chambers can occur in cases without any
after removing the endothelial cells by either mechanical
apparent complications. They may result due to occult breaks
debridement, or stripping of Descemet's membrane using
that may not have been apparent during surgery. Double
forceps is then sutured onto position on the bared Descemet's
chambers may also occur due to retained viscomaterial.
membrane.
Shallow double chambers may be self-limited and resolve
Confirmation of the big bubble separation of the
in a few weeks. Long standing ones will require surgical
Descemet's membrane becomes difficult as significant amount
intervention by injection of air or surgical gases into the
of intrastromal air, above the bubble obscures the visualization
anterior chamber.
of the circular bubble edge. The "small bubble test"34 have
been recently devised to aid in the confirmation of having
COMPLICATIONS OF
achieved the big bubble. Air bubble injected into the anterior
LAMELLAR KERATOPLASTY
chamber, if seen in the periphery of the anterior chamber
infers that the periphery is the highest point of the anterior I. Intra-operative Complications
chamber and that the central big bubble has been achieved, as
this produces a posterior convexity protruding into the central Intraoperative complications inherent to lamellar keratoplasty
anterior chamber. include:
1. Irregular lamellar bed: Irregular lamellar dissection of
Surgical Complications: the host gives rise to astigmatism and poor optical quality
• Descemet's membrane perforation of vision. As achieving smooth lamellar separation is
• Pseudo-anterior chambers. difficult by manual dissection, special methods of
Descemet's membrane perforation: Descemet's membrane dissections such as the big bubble technique or automated
perforation or tears have been reported to occur in microkeratome assisted anterior lamellar keratoplasty.
approximately 10 to 30 percent of cases. Its occurrence varies Irregular lamellar bed also leads to significant interface
in accordance to the indication for the sugery and the patient haze compromising refractive outcome of the procedure.
age. There is a higher incidence of Descemet's membrane 2. Perforation of the posterior stroma/Descemet's
rupture in keratoconus eyes either due to the younger average membrane: Inadvertent micro/macroperforation of
age or an intrinsic property of the disease. Use of viscoadaptive cornea may occur during lamellar dissection. As discussed
viscoelastic may offer additional protection of the Descemet's earlier, perforation risk remains high in deep lamellar
membrane during surgical maneuvers of the overlying stroma. keratoplasty and deep anterior lamellar keratoplasty
Corneal Surgery 693
procedures, even with experienced surgeons. Thin host occur. Corneal dystrophy lesions may also reappear in the
corneas as in advanced keratoconus, inexperienced donor lamellar graft.
surgeons or corneal surgeons in their learning curve of 4. Graft Rejection: Rejection is less common in a lamellar
lamellar procedures are more likely to encounter keratoplasty as the host endothelium is preserved but never
perforation. In the event of a perforation, the anterior the less it may still occur.
chamber may be reformed with air and lamellar dissection 5. Graft vascularization: Corneal vascularization into the
may be continued manually if the situation permits, from lamellar bed might occur especially in cases with ocular
an area diagonally opposite to the site of perforation. The surface pathologies such as trachomatous keratopathy,
operating surgeon may also anticipate a double chamber chemical burns and Stevens-Johnson syndrome.
in the early postoperative cases in such cases of perforation.
In the event of too large a perforation of the posterior REFERENCES
bed, conversion to a full thickness penetrating keratoplasty
will be essential. It is pertinent to always proceed for deep 1. Muhlbauer FX. Uber transplantation der Cornes, Gekronte
Preisscrift. Munich. Jos. Lindauer, 1840. Abstract in
lamellar surgery with availability of good optical grade
Zeis: Schmidt CC (ed): Jahrbiicher der in und auslandischen
donor cornea for penetrating keratoplasty in the event of
gesammten Medizin Leipzig, Otto Wigaband, 1842; 267-8.
perforation. 2. von Hippel A. Eine neue Methode der Hornhauttransplantation.
Microperforation might commonly occur during Al-brecht v. Graefes Arch Ophthalmol 1888; 34:108.
suturing due to the needle edge. These usually are not 3. Filatov VP. Transplantation of the cornea. Arch Ophthalmol 1935;
troublesome and may lead to mild anterior chamber 13:321-3.
shallowing but tend to resolve subsequently. 4. Paufique L, Charleux J. Lamellar keratoplasty. In: Casey T, ed.
3. Graft-host malapposition/edge ir regularity: Corneal grafting. New York: Appleton-Century-Crofts, 1972: 121-
76.
Malapposition of the host-donor corneal tissue might
5. Hallerman W. Verschiedenes uber keratoplastik. Klin Monatsbi
occur due to improper sizing of tissue. Edge irregularity
Augenheilkd 1959;135:252-9.
arises in cases of microkeratome cuts as the edge is not 6. McCulloch C, Thompson GA, Basu PK. Lamellar keratoplasty
perfectly perpendicular. This may be tackled with adoption using full thickness donor material. Tans Am Ophthalmol Soc 1963;
of hemi-automated anterior lamellar procedure in which 61:154-80.
the trephine is used to cut grafts of appropriate size after 7. Malbran E. Lamellar keratoplasty in keratoconus. In: King JH.
the donor automated cuts on the donor cornea and the MsTigue JW, eds. The Cornea-World Congress. London/
host corneal lamellar dissection is performed manually. Washington DC, Butterworths, 1965:511-8.
4. Interface debris: Interface debris due to fibers, bleeding, 8. Anwar M. Technique in lamellar keratoplasty. Trans Ophthalmol
Soc UK 1974;94:163-71.
etc. may occur. The interface is to be thoroughly washed
9. Archila EA. Deep lamellar dissection of the host tissue with
in such cases, to avoid persistence as this would enhance intrastromal air injection. Cornea 1984-85;3:217-8.
interface irregularity and haze. 10. Price FW, Jr. Air Lamellar keratoplasty. Refrac Corneal Surgery
1989;5:240-3.
II. Post Operative Complications 11. Chau GK, Dilly SA, Sheard CE, Rostron CK. Deep lamellar
keratoplasty on air with lyophilized tissue. Br J Ophthalmol 1992;
1. Persistent epithelial defect: Poor epithelialization of the 76:646-50.
graft might occur in cases with wound/edge problems, 12. Sugita J, Kondo J. Deep lamellar keratoplasty with complete removal
suture related problems or eyes with ocular surface of pathologic stroma for vision improvement. Br J Ophthalmol
pathologies. 1997;81:184-8.
2. Infection: Graft infection due to various causes such as 13. Tsubota K, Kaido M, Monden Y, et al. A new surgical technique
suture related, lid adnexal abnormalities, poor ocular for deep lamellar keratoplasty with a single running suture
surface, prolonged topical steroid, poor hygiene can be a adjustment. Am J Ophthalmol 19987;126:1-8.
14. Melles GRJ, Lander F, Reitveld FJR, et al. A new surgical technique
potential vision threatening problem. Activation of
for deep stromal anterior lamellar keratoplasty. Br J Ophthalmol
herpetic infections may also occur after lamellar graft 1999;83:327-33.
surgery. 15. Anwar M. Teichmann KD. Big-bubble technique to bare the
3. Recurrence of the primary pathology: Recurrence of Descemet's membrane in anterior lamellar keratoplasty. J Cataract
a herpetic lesion (HSV) in the donor lamellar graft can Refract Surg 2002;28:398-403.
16. Ehrlich MI, Phinney RB, Mondino BJ, et al. Techniques of lamellar 27. Shimmura S, Shimazaki J, Omoto M, et al. Deep lamellar
keratoplasty. Int Ophthalmol Clin 1988;28:24-9. keratoplasty (DLKP) in keratoconus patients using viscoadaptive
17. Arentsen JJ. Lamellar grafting. In: Brightbill FS, ed. Corneal Surgery: viscoelastics. Cornea 2005;24:178-81.
Theory, Technique and Tissue. 2nd ed. St Louis: Mosby; 1996:416-72. 28. Manche EE, Holland GN, Maloney RK. Deep lamellar
18. Alio JL, Shah S, Barraquer C, et al. New techniques in lamellar keratoplasty using viscoelastic dissection. Arch Ophthalmol
keratoplasty. Curr Opin Ophthalmol 2002;13:224-9. 1999;117:1561-5.
19. Melles GRJ, Remeijer L, Geerards A, et al. The future of lamellar 29. Wylegala E, Tarnawska D, Dobrowolski D. Deep lamellar
keratoplasty. Curr Opin Ophthalmol 1999;10:253-9. keratoplasty for various corneal lesions. Eur J Ophthalmol 2004;
20. Teichmann KD. Lamellar keratoplasty-a comeback? Middle East J 14:462-72.
Ophthalmol 1999;7:59-60. 30. Coombes AG, Kirwan JF, Rostron CK. Deep lamellar keratoplasty
21. Benson WH, Goosey JD. Lamellar keratoplasty. In : Krachmer JH, with lyophilised tissue in the management of keratoconus. Br J
Mannis MJ, Holland EJ, ed. Cornea Vol III. Surgery of the cornea
Ophthalmol 2001;85:788-91.
and conjunctiva: Therapeutic and reconstructive procedures. St.
31. Wylegala E, Tarnawska D, Dobrowolski D. Deep lamellar
Louis: Mosby; 1997:1833-42.
keratoplasty for various corneal lesions. Eur J Ophthalmol 2004;
22. Tan DT, Mehta JS. Future directions in lamellar corneal
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transplantation. Cornea 2007 Oct; 26(9 Suppl 1):S21-8.
32. Hirano K, Sugita J, Kobayashi M. Separation of corneal stroma
23. Anwar M, Teichmann KD. Deep lamellar keratoplasty: surgical
techniques for anterior lamellar keratoplasty with and without and Descemet's membrane during deep lamellar keratoplasty.
baring of Descemet's membrane. Cornea 2002;24:373-83. Cornea 2002; 21:196-9.
24. Caporossi A, Simi C, Licignano R, et al. Air-guided manual deep 33. Muraine MC, Collet A, Brasseur G. Deep lamellar keratoplasty
lamellar keratoplasty. Eur J Ophthalmol 2004;14:55-8. combined with cataract surgery. Arch Ophthalmol 2002;120:
25. Amayem AF, Anwar M. Fluid lamellar keratoplasty in keratoconus. 812-5.
Ophthalmology 2000;107:76-9. 34. Parthasarathy A, Por YM, Tan DT. Using a "small bubble
26. Melles GRJ, Remeijer L, Geerards AJM, et al. A quick surgical technique" to aid in success in Anwar's "big bubble technique" of
technique for deep, anterior lamellar keratoplasty using visco- deep lamellar keratoplasty with complete baring of Descemet's
dissection. Cornea 2000;19:427-32. membrane. Br J Ophthalmol 2008 Mar;92(3):422.
6.10.2.2 Posterior Lamellar Keratoplasty

Conventional surgical management of corneal endothelial preoperative status, a predictable and stable corneal power
decompensation is penetrating keratoplasty, which is faced by with high optical quality, a healthy donor, a tectonically stable
a prolonged recovery time and increased visual rehabilitation globe, safe from injury and infection, and a surgical technique
time due to a high degree of postoperative astigmatism.1 In that can be quickly and easily acquired.3
an attempt to alleviate the problems related to conventional
penetrating keratoplasty, Melles et al2 reported the use of History
endothelial keratoplasty in a patient with pseudophakic bullous Posterior lamellar keratoplasty (PLK) was first described by
keratopathy. They called this technique "Posterior lamellar Melles in 1998.4 This technique involves creation of a corneal
keratoplasty" which involves replacement of the diseased pocket originating at the limbus. The central posterior lamellae
posterior corneal layers and the endothelium with donor are excised using a specially designed trephine and a posterior
corneal tissue while the host anterior corneal stroma is retained. donor graft is slid into position through the same pocket. No
This serves to replace the dysfunctional host endothelium with suturing of the posterior graft is performed. This involves
healthy donor endothelium, thereby resulting in regression of high surgical skills and complicates the performance of other
the epithelial and stromal edema in patients with endothelial intraocular procedures that may be required at the time of the
decompensation such as bullous keratopathy and Fuch's penetrating keratoplasty surgery. Busin et al5 successfully
corneal dystrophy. The ideal goal of endothelial transplantation reported the use of endokeratoplasty (EKP) for surgical
would be to obtain: a smooth surface topog raphy treatment of diseased endothelium. EKP involves creation
postoperatively without significant change in astigmatism from of a hinged anterior corneal flap of 9.5 mm diameter by means
Corneal Surgery 695
of a microkeratome, substitution of the underlying central • Descemet membrane breaks due to birth trauma after
posterior stroma, Descemet's membrane and endothelium (6.5 forceps delivery
mm diameter) with a donor button of 7 mm diameter and • Congenital hereditary endothelial dystrophy.
suturing the anterior corneal flap back into position over the
donor cornea. The technique of PLK was further adopted by Comparison of DSEK vs DSAEK
Terry and Ousley6 as the deep lamellar endothelial keratoplasty
(DLEK). This involves obtaining a posteriolamellar donor DSEK
tissue by manual dissection (Fig. 6.10.2.2.1). The host posterior • Manual dissection has an increased risk of donor tissue
corneal lamella is dissected using specially designed trephines perforation
through the stromal pocket and replaced with the prepared • Manual dissection does not yield a smooth anterior surface
donor tissue. DLEK is superior to traditional penetrating of the donor posterior lamella
keratoplasty in terms of producing a normal predictable • Adhesion of the posterior lamellar lenticule is better due
corneal topography with endothelial survival as good as or to the greater tissue thickness and irregular anterior
even better than that of penetrating keratoplasty.7,8 The deep surface
stromal interface haze precludes optimal visual acuity • Anterior stromal stab incisions are not required to provide
achievement in DLEK. The creation of the stromal dissection for interface fluid regress
plane for the recipient deep lamellar pocket in DLEK is • Donor lenticule dislocation is lesser
problematic as it is manual. Femtosecond laser is now capable • More time consuming
of performing all the surgical dissection and incisions necessary • Visual recovery is slower.
for DLEK surgery.9 The next modification of PLK was
Descemet's stripping endothelial keratoplasty (DSEK).10,11 In this DSAEK
procedure, instead of performing a lamellar dissection, the
host Descemet's membrane is peeled off using specially • Microkeratome dissection reduces the risk of donor tissue
designed strippers. This is easier to perform as compared to perforation
DLEK leaving a smooth recipient interface onto which the • Microkeratome dissection yields a posterior donor lamellar
donor tissue can be applied. While this may give better visual of superior optical quality
results, there exists a higher propensity to postoperative • Adhesion of the posterior lamellar lenticule is not as easy
dislocations. The present incarnation of PLK is termed as in DSEK, as the donor posterior stromal lenticule is
Descemet's stripping and automated endothelial keratoplasty (DSAEK) thinner and has a smooth anterior surface
(Figs 6.10.2.2.2A to D) described by Price and Price.12 In this • Anterior stromal stab incisions are required to allow for
the DSEK procedure was further modified by using the the interface fluid to flow out in order to enhance donor
mechanical microkeratome of the ALTK system to obtain button adhesion
the donor posterior lamella in order to achieve more consistent • Donor lenticule dislocation is more
donor tissue quality. • Less time consuming
• Visual recovery is more rapid.
Indications
DSEK/DSAEK Procedure
All conditions where corneal transplantation is required to
treat endothelial dysfunction, with no scarring of the anterior DSAEK essentially involves a technically demanding procedure,
corneal layers, will form primary indications for posterior using a microkeratome to prepare the posterior lamellar donor
button, which is used to exchange the diseased host endothelium
lamellar keratoplasty. These include conditions such as:
through a 5 mm scleral tunnel incision. With respect to the
• Fuchs endothelial dystrophy donor tissue selection for DSEK, any donor tissue with a good
• Pseudophakic bullous keratopathy endothelial cell count and a good scleral rim is preferred. With
• Aphakic bullous keratopathy respect to use of pediatric donor tissue for DSEK, pediatric
• Failed graft donor tissue may be very flaccid and would give an unpredictable
• Iridocorneo endothelial syndrome cut on the Moria microkeratome system. For such cases, it is
• Argon laser iridotomy induced bullous keratoplasty preferable to use the manual dissection.
Fig. 6.10.2.2.1: DLEK surgery
Figs 6.10.2.2.2A to D: DSAEK surgery
A 5 mm corneo-scleral tunnel incision is made and

paracentesis ports are constructed. The host Descemet's
membrane and endothelium is scored and stripped using a
Descemet's stripper. The donor endothelial button comprising
of Descemet's membrane and endothelium is prepared (Flow
chart 6.10.2.2.1) either by manual dissection (DSEK) or using
an automated microkeratome (DSAEK), which is then inserted
into the host anterior chamber either by "push" or "pull"
techniques. The donor button is positioned into place, the corneo-
scleral tunnel incisions are sutured and adhesion achieved by
complete air tamponade of the anterior chamber for an hour.
Burping of the bubble is done after an hour to release some air
from the anterior chamber. Flow chart 6.10.2.2.1:Donor preparation
Corneal Surgery 697
Surgical steps in DSAEK

1. The surgical procedure includes making a standard sclera
or corneal tunnel to enter the anterior chamber.
2. A 7 to 8 mm mark is made using a trephine on the cornea.
This helps in guiding the descemetorrhexis.
3. Descemetorhexis is performed using a reverse Sinskey
hook. This process can be assisted by improving the
visibility by using air, trypan blue or chandelier illumination
Fig. 6.10.2.2.3A: Long Kelmann-McPherson forceps
system.13 In case phacoemulsification is to be done as a
combined surgery, first the phacoemulsification is
completed and then descemetorhexis is carried out. Having
scored the Descemet's membrane, the diseased Descemet's
membrane can be peeled off using a forceps or a
Descemet's stripper or using an automated irrigation and
aspiration cannula. After the removal of the Descemet's
membrane, few surgeons prefer to scrape the edges of
the scored area. This helps in improving the adhesion of
the graft to the stroma.14 Fig. 6.10.2.2.3B: Goosey single point fixation forceps
4. Methods of insertion of the donor lenticule: A number of
methods have been devised to insert the lenticule in the anterior
chamber:
The taco fold was the commonly used initial technique
for the donor lenticule insertion. This involved folding the
donor lenticule into a 60:40 taco fold followed by insertion
using a noncoapting forceps (Figs 6.10.2.2.3A to C). This
was however associated with high complication rates
related to the difficulty in unfolding in the anterior chamber
and eventual trauma to the endothelial cells. A modification
Fig. 6.10.2.2.3C: Ogawa single point fixation forceps
of the technique was using a Hitch suture which is a 10-0
monofilament nylon suture that is passed through the graft
loop made on one side of the graft.15 The suture is passed The sheet glide described in the cataract surgery has
on the 40 percent fold which is placed inferiorly and the also been described for donor lenticule insertion.18 The
lenticule is unfolded using a Sinskey hook that pulls on donor lenticule is placed on healon smeared sheet glide
the suture. with the endothelial side down and inserted into the
However, due to the high endothelial cell loss of up to anterior chamber using either needle push through or
34.3 percent associated with the forceps technique, other forceps pull through technique. The endothelial damage
non-traumatic techniques for the donor lenticule insertion by this method is nine percent. Recently, a number of
are followed by certain surgeons.16 The first step towards devices have been developed which act as both carrier and
this was the development of the Busin glide for the donor injector systems for insertion of the donor lenticule into
insertion.16 Busin glide consists of a specialized instrument the anterior chamber. The latest among these is the Tan's
that can load and carry the lenticule with the endothelial endoglide which is specially designed to avoid any
side up and helps in inserting the lenticule using the pull endothelial surface rubbing against each other with
through technique using a specialized forceps. Use of Busin reported endothelial cell loss of only five percent.
glide for insertion of donor lenticule is associated with an 5. Anterior chamber air tamponade: After insertion of the
endothelial cell loss of up to 25 percent.16 donor lenticule into the anterior chamber it is important
Another technique involved the use of cartridge for to secure the donor into position to allow adequate
the insertion of the donor lenticule. This further decreased apposition with the stroma of the host. This is achieved
the endothelial cell loss to nine percent.17 using air tamponade. Many surgeons believe in complete
air fill only for a period of seven to ten minutes followed further intervention which might enhance endothelial
by partial air removal, in order to prevent any undue damage.
increase in intraocular pressure and related optic nerve 3. Air bubble tamponade in the anterior chamber to facilitate
damage. This is followed by watertight closure of the donor lenticule adhesion can result in postoperative
wound. A few surgeons also prefer to place venting pupillary block and secondary angle closure glaucoma.
incisions, around four to five incision in order to drain 4. Primary graft failure.
out any fluid from the interface. Major reported complications of DSAEK22,23 include:
Postoperative treatment includes frequent doses of • Posterior graft dislocations (mean, 14%; range, 0%–82%)
topical steroids and antibiotics. Antiglaucoma medications • Endothelial graft rejection (mean, 10%; range, 0%–45%)
may be added as per need. • Primary graft failure (mean, 5%; range, 0%–29%)
• Iatrogenic glaucoma (mean, 3%; range, 0%–15%).
Non-Descemet's Stripping • Average endothelial cell loss
Endothelial Keratoplasty At 6 months: 37 percent
Recently, Kobayashi A et al19 suggested that not stripping the At 12 months: 42 percent.
Descemet's membrane provides a better and smoother interface
with comparable dislocation rates. Histopathological studies20 Intraoperative Complications
on the corneas undergoing keratoplasty following failed DSEK • Inversion of the donor lenticule: Rarely during the insertion,
have proved that even in areas with retained host Descemet's the donor tissue may be inverted24 and may lie with the
membrane, the adhesion of the donor lenticule is equally good. endothelial side lying at the stromal side of the tissue. This
Thus, adhesion of the donor to the host stroma does not appear is corrected by flipping the lenticule in the anterior
to involve significant scarring or keratocyte proliferation. chamber.
Contrary to previous assumptions, retained DM does not
appear to hinder graft adhesion, raising the possibility that The Advantages of DSAEK vs PK
removal of DM may be unnecessary for endothelial
transplantation. DSAEK
New Triple Procedure • The 5 mm scleral entry incision in DSAEK results in a

structurally stronger globe
Phacoemulsification with DSEK/DSAEK has become the • The scleral wound may be left sutureless or closed with
new triple procedure. In cases of Fuchs endothelial dystrophy minimal suturing
with cataract, phacoemulsification with simultaneous DSEK
• Ocular surface topography is not altered and retains the
has become the procedure of choice. The combined surgery
corneal innervation
has similar dislocation rates, with no iatrogenic graft failures,
• Rapid refractive rehabilitation
a rapid visual recovery and similar rates of endothelial cell
• Repeat surgery is less invasive and can be easily performed
loss.21 Special considerations22 during the combined surgery
• Requires learning new surgical skill
includes, use of viscocohesive viscoelastics during the
• Significant manipulation of the posterior stromal lenticule
phacoemulsification, small anterior capsulorhexis [~ 4 mm]
to facilitate stabilization of the 6-mm optic IOL, complete (dissection, folding and implantation into the anterior
removal of viscoelastic after descemetorhexis, IOL power more chamber) results in greater endothelial damage than PK
myopic by 1.25 D, to compensate for post-DSAEK hyperopia. • Postoperative donor dislocation may occur in up to 30
percent of the cases
Complications of DSEK • Air bubble induced pupillary block may occur.
Complications Inherent to DSAEK Surgery Penetrating Keratoplasty

1. Increased handling of the posterior stromal donor tissue • Full thickness wound in penetrating keratoplasty results
(dissection, folding and insertion into the anterior chamber) in a weaker wound
enhances the likelihood of increased endothelial cell loss. • 16 interrupted sutures of PK and the associated suture
2. Postoperative dislocation of the posterior lamellar disc can related problems remain
occur in upto 30 percent23 cases with necessitation of • Ocular surface topography is altered
Corneal Surgery 699
• Considerable time also taken for re-innervation of the full 12. Price FW Jr, Price MO. Descemet's stripping with endothelial
thickness graft in PK keratoplasty in 200 eyes: early challenges and techniques to enhance
• Visual rehabilitation is slow donor adherence. J Cataract Refract Surg 2006;32:411-8.
13. T Inoue, Y Oshima, C Shima, Y Hori, N Maeda, Y Tano. Chandelier
• Repeat surgery is more invasive
illumination to complete Descemet stripping through severe hazy
• No new skill involved
cornea during Descemet-stripping automated endothelial
• Endothelial damage risks are low keratoplasty. Journal of Cataract and Refractive Surgery
• Intraoperative risks associated with open globe surgery. 2008;34,6,892-6.
14. Terry MA, Shamie N, Chen ES, Hoar KL, Friend DJ. Endothelial
Outcome of Posterior keratoplasty: a simplified technique to minimize graft dislocation,
Lamellar Keratoplasty iatrogenic graft failure, and papillary block. Ophthalmology
2008;115:1179-86.
The results of the use of precut tissue are comparable with
15. Vajpayee RB, Agarwal T, Jhanji V, Sharma N. Modification in
that during the surgery. Visual recovery has been found to be Descemet's stripping automated endothelial keratoplasty: "Hitch
faster with microkeratome assisted tissue dissection of donor suture" technique. Cornea 2006;25:1060-62.
tissue compared to manual dissection.26 Femtosecond assisted 16. Bahar I, et al. Busin glide vs forceps for the insertion of the donor
dissection of the tissue gives a more predictable cut and planar lenticule in Descemet stripping automated endothelial keratoplasty.
configuration with a center to periphery ratio of lenticule close Am J Ophthalmol 2009;147:220-6.
to 1, which helps in avoiding any refractive surprises and post 17. Kuo AN, Harvey TM, Afshari NA. Novel delivery method to
operative hyperopia in cases where DSEK/DSAEK is reduce endothelial injury in descemet stripping automated
endothelial keratoplasty. Am J Ophthalmol 2008;145:91-6.
combined with phacoemulsification and IOL implantation.27
18. Jodhbir S, Mehta et al. Comparison of donor insertion techniques
for Descemet stripping automated endothelial keratoplasty. Arch
REFERENCES
Ophthalmol 2008;126(10):1383-8.
1. Binder PS. Controlled reduction of postkeratoplasty astigmatism. 19. Kobayashi A, et al. Non-Descemet stripping automated endothelial
In: Brightbill FS, ed. Corneal surgery: Theory, Technique and Tissue. keratoplasty for endothelial dysfunction secondary to argon laser
St Louis: Mosby 1986;326-32. iridotomy. Am J Ophthalmol 2008;146:543-9.
2. Melles GRJ, Lander F, Beekhuis WH, Remeijer L, Binder PS. 20. Matthew C Caldwell. The histology of graft adhesion in Descemet
Posterior lamellar keratoplasty for a case of pseudophakic bullous Stripping with Endothelial Keratoplasty. Am J Ophthalmol
keratopathy. Am J Ophthalmol 1999;127:340-1. 2009;148:277-81.
3. Terry MA. Endothelial keratoplasty: clinical outcomes in the two
21. Terry MA, Shamie N, Chen ES, Phillips PM, Shah AK, Hoar KL,
years following deep lamellar endothelial keratoplasty. Trans Am
Friend DJ. Endothelial keratoplasty for Fuchs' dystrophy with
Ophthalmol Soc 2007;105:530-563
4. Melles GR, Egglink FA, Lander F, et al. A surgical technique for cataract: complications and clinical results with the new triple
posterior lamellar keratoplasty. Cornea 1998;17:618-26. procedure. Ophthalmology 2009;116:631-9.
5. Busin M, Arffa RC, Sebstiani A. Endokeratoplasty as an alternative 22. Koenig SB, Covert DJ. Early results of small-incision Descemet's
to penetrating keratoplasty for the surgical treatment of diseased stripping and automated endothelial keratoplasty. Ophthalmology
endothelium. Ophthalmology 2000;107:2077-82. 2006;114:221-6.
6. Terry MA, Ousley PJ. Endothelial replacement without surface 23. W Barry Lee. Descemet's stripping endothelial keratoplasty: safety
corneal incisions or sutures: topography of the deep lamellar and outcomes: a report by the American Academy of
endothelial keratoplasty procedure. Cornea 2001;20:14-8. Ophthalmology. Ophthalmology 2009;116(9):1818-30.
7. Terry MA. A new approach for endothelial transplantation: deep 24. Hashemi H, Shamshiri M, Mehravaran S. Flipping the inverted
lamellar endothelial keratoplasty. Int Ophthalmol Clin 2003;43:183- donor disk in Descemet stripping automated endothelial
93. keratoplasty. Cornea 2009;28(2):214-6.
8. Terry MA. Endothelial replacement: new surgical strategies. In: 25. Price MO, Baig KM, Brubaker JW, Price FW Jr. Randomized,
Krachmer J, Mannis M, Holland E, eds. Cornea: Surgery of the prospective comparison of precut vs. surgeon-dissected grafts for
cornea and conjunctiva, 2nd ed. St Louis: Mosby-Year book 2004.
Descemet stripping automated endothelial keratoplasty. Am J
9. Terry MA, Ousley PJ, Will B. A practical femtosecond laser
Ophthalmol 2008;146:36-41.
procedure for DLEK endothelial transplantation Cadaver eye
26. Yian Jin Jones. Comparison of the femtosecond laser (IntraLase)
histology and topography. Cornea 2005;24:453-9.
10. Melles GR, Wijidh RH, Nieuwendal CP. A technique to excise the versus manual microkeratome (Moria ALTK) in dissection of the
Descemet's membrane from a recipient cornea (Descemetorhexis). donor in endothelial keratoplasty: initial study in eye bank eyes.
Cornea 2004;23:286-8. Cornea 2008;27:88-93.
11. Price FW Jr, Price MO. Descemet's stripping with endothelial 27. Takeshi Ide, et al. Descemet stripping automated endothelial
keratoplasty in 50 eyes: a refractive neutral corneal transplant. J keratoplasty tissue preparation with femtosecond laser and contact
Refract Surg 2005;21:339-45. lens. Cornea 2010;29:93-8.
6.10.3 Ocular Surface Reconstruction with

Amniotic Membrane Grafting
M Vanathi
OCULAR SURFACE RECONSTRUCTION AMNIOTIC MEMBRANE

TRANSPLANTATION
Reconstruction of the ocular surface might be achieved by:
• Conjunctival autografts Brown1 used rabbit peritoneum to promote healing and
• Conjunctival limbal autografts or allografts prevent spread of necrosis of ocular surface in acute burns,
• Amniotic membrane grafting which led to Sorsby et al's2,3 use of chemically processed, dry
• Mucous membrane grafting. amniotic membrane as a patch for treating acute ocular burns.
The various indications for ocular surface indications Ocular surface reconstruction with amniotic membrane trans-
include: plantation (AMT) has been widely advocated by Kim and
Tseng in 1995.4,5 Amniotic membrane enhances growth and
Conjunctival Autograft differentiation of conjunctival epithelial cells6 and is reported
to inhibit subconjunctival scar tissue formation.7 Amniotic
• Pterygium membrane is considered to be a favorable substrate for ocular
• Fornix reconstruction surface reconstruction.8-16
• Post excision of conjunctival lesions.
Characteristics of Amniotic Membrane
Conjunctival Limbal Autograft/Allograft
Amniotic membrane is the inner membrane of the foetal
• Limbal stem cell deficiency membranes. It consists of a thick continuous basement
– Chemical injury membrane and an avascular stromal matrix that contains a
– Thermal burns. high concentration of basic fibroblast growth factor,17
• Contact lens keratopathy basement membrane components18-20 and several trophic
• Persistent epithelial defect factors. Recent evidence indicates AM has anti-inflammatory
• Stevens-Johnson syndrome antiproteocytic21,22 and antimicrobial activity.23,24 The stromal
• Ocular cicatricial pemphigoid. matrix of the AM contains protease inhibitors, 25 anti-
inflammatory proteins.26 It suppresses TGF-β signaling and
Amniotic Membrane Grafting proliferation and myofibroblast differentiation of human
corneal and limbal fibroblasts. 27,28 It is avascular and
• Post chemical injury symblepharon release antiangiogenic. It does not express histocompatability antigens
• Immune melts of cornea/sclera and has antibacterial properties. It facilitates epithelial cell
• Post pterygium excision migration, reinforces adhesion of basal epithelial cells,
• Conjunctivochalasis diminishes their apoptosis and promotes their differentiation.
• Post-ocular surface squamous neoplasia excison
• Limbal dermoid Wound Healing Features
• Post-conjunctival lesions excision. of Amniotic Membrane
AMT effects rapid healing and reduction of ocular
Mucous Membrane Grafting
inflammation due to the following mechanisms:
• Bilateral extensive post chemical injury symblepharon • The AM provides a new basement membrane, which forms
• Ocular cicatricial pemphigoid a substrate for enhancing adhesion and growth of epithelial
• Stevens-Johnson syndrome. progenitor cells, including stem cells.
Corneal Surgery 701
• AM also exerts an antiinflammatory effect. The expression • Other indications of AM use

of 1L-α and 1L-β is markedly suppressed when human – Stem cell cultures.
epithelial cells are cultured on the AM stromal matrix.29
• AM stromal matrix has a direct anti-scarring effect Preparation of Amniotic Membrane
secondary to its suppression of TFG-β signaling and
AM is the innermost semitransparent layer of the foetal
myofibroblast differentiation.
membranes and is separated from the placenta. The human
• All these act in combination to restore the micro-
placenta is obtained following an elective cesarean delivery
environmental conditions conducive to the growth of the
from a consenting donor tested negative for HIV, hepatitis B
epithelial progenitor cells.
and C and syphilis. AM is prepared as elaborated here.32-34
• AM is also thought to promote nerve regeneration by
Under a laminar flow hood the placenta is cleaned of blood
maintaining nerve growth factor signalling.30
clots with sterile saline solution containing 50 µg/ml of
Thus effective restoration of stromal thickness to normal amphotericin B. The AM is separated from the chorion by
or near normal levels in deep corneal ulcerations using AM blunt dissection and flattened on to nitrocellulose membrane
transplantation (AMT) has made it an alternative option, in
of appropriate size with the epithelium-basement membrane
management of corneal ulcerations especially in the developing
surface up. This is stored at –70°C in a sterile vial containing
countries where there is shortage of corneal tissues. Penetrating
DMEM (Dulbecco's Modified Eagle Medium) and sterile
keratoplasty can be performed subsequently after resolution
glycerol (sterilized by autoclaving) in a ratio of 1:1 (vol/vol)
of ocular surface inflammation and improvement in ocular
along with 3.3 percent L-glutamine, 25 µg/ml gentamicin, 50
surface wettablity.
units/ml penicillin 100 µg/ml ciprofloxacin and 0.5 mg/ml
Indications for Amniotic amphotericin B. The vial is thawed at room temperature for
Membrane Transplantation 10 minutes or at 4°C for 30 minutes. The membranes can be
used for upto six months after preparation but the cellular
Preserved AMT has been used in the management of viability is found to be reduced by more than 50 percent in
persistent epithelial defects with and without stromal thinning two months. Damage of AM cells due to cryopreservation
and perforation (neurotrophic keratopathy), herpetic infection, results in decreased levels of AM associated of growth factors.
autoimmune diseases, shield ulcer, infectious keratitis and in Upon thawing, before transplantation, the surgeon should
extensive infectious scleral and corneo-scleral ulcers. AMT ensure the epithelial side of the AM is identified by its stickiness
combined with glue may also be used for treating small corneal to the tip of the cotton swab.
perforations. Common indications include31 the following:
• AMT in the presence of stem cell deficiency AMT Surgical Technique
– Ocular chemical injury.
Amniotic membrane overlay: A single layer or multilayered AM with
• AMT in the absence of stem cell deficiency
stromal side down is placed over the epithelial defect trimmed at
– Corneal epithelial defects
the edges and secured to the cornea with 10.0 nylon suture with
– Corneal/Corneoscleral ulcers
buried knots. This is performed in cases with non-healing epithelial
– Bullous keratopathy.
ulcerations with minimal or no stromal thinning. It is also useful
• AMT for conjunctival reconstruction
in the effective management of persistent epithelial defects of
– Pterygium
the cornea and in acute chemical injury.
– Conjunctivochalasis
– OSSN Amniotic membrane inlay: In cases of epithelial defect/ulcerations
– Limbal dermoid associated with stromal thinning, amniotic membranes are placed
– Symblepharon stromal side down, layer by layer, filling up the stromal defect.
– Conjunctival lesions The layers are trimmed to fit the size of the ulcer defect. The
– Leaking blebs. topmost layer is fashioned to cover the area of defect and is
• AMT in ocular cicatricial diseases sutured to the cornea with 10.0 nylon suture with buried knots.
– Toxic epidermal necrolysis The underlying layers, compactly packed under the larger top
– Ocular cicatricial pemphigoid layer, may be left unsutured. A compact packing of the stromal
– Oculopalpebral and reconstructive surgery. ulceration aids in good healing.
Amniotic membrane inlay with overlay: After compact packing of The glue plug is then secured with an AMT to avoid its extrusion
the stromal ulcer defect with multiple layers of amniotic and an extended-wear bandage contact lens is applied.
membrane and sealing it with a sutured top layer of membrane, An alternative technique is the placement of an amniotic
an overlay of multilayered amniotic membrane patch covering membrane of optimal size in the anterior chamber directly
the whole cornea may be placed and sutured to the underlying under the corneal perforation lesion. The cyanoacrylate tissue
conjunctiva. Multilayered inlay with onlay grafting of amniotic adhesive can then be applied over the perforation site and
membrane helps in achieving early ocular surface stabilization sealed successfully.
in severe grades of ocular chemical injury (Fig. 6.10.3.1).
Amniotic membrane in symblepharon release: Amniotic membrane
Amniotic membrane patch technique: Amniotic membrane can be grafting with suture fixation or glue fixation achieves effective
effectively used for patching the cornea by placing basement ocular surface reconstruction in cases of symblepharon after
membrane side downwards and the stromal side up and chemical injury (Figs 6.10.3.3 and 6.10.3.4A and B).
suturing it to the surrounding perilimbal conjunctiva. This
Amniotic membrane patch technique: An amniotic membrane patch
effectively serves to act as a patch for the cornea.
technique can also be performed by placing an amniotic
Amniotic membrane for corneal perforation: Perforations lesser than membrane covering the whole cornea with the basement
2 mm in size can be treated with this technique (Fig. 6.10.3.2). membrane side facing down and sutured to the surrounding
The bottom of the perforation is closed with an appropriate conjunctiva. A bandage contact lens may be placed over the
sized amniotic membrane and multi-layer amniotic membrane membrane until total healing occurs.
graft is then placed, packing the defect. A larger sized amniotic
AMT in infectious corneal ulcers: Pathogenic microorganisms
membrane is placed uppermost to cover the whole ulcer area,
produce disease in the cornea by direct invasion, secretion of
trimmed to fit the ulcer and sutured with an interrupted 10.0
toxic products or by both. Most of the proteolytic enzyme is
nylon suture.
endogenously released by epithelial and stromal cells and
Amniotic membrane and glue in the management of corneal perforation: polymorphonuclear cells. A series of matrix-metallo-
The technique consists of using a high-viscosity sodium proteinases (MMPs) influence corneal wound healing.
hyaluronate viscoelastic material to restore anterior chamber depth Infectious ulcerative keratitis can be modified by controlling
followed by a debridement of the ulcer. The perforation site is MMP activity in tissue. MMP-2 and MMP-9 can degrade
filled with the human fibrin glue (HFG) on the corneal surface. basement membrane collagens (types IV and VII).
Fig. 6.10.3.1: Amniotic membrane inlay with overlay for ocular Fig. 6.10.3.2: Amniotic membrane inlay with overlay for
surface reconstruction in a case of corneoscleral melt in grade IV perforated neurotrophic ulcer
chemical injury.
Corneal Surgery 703
AM is reported to contain tissue inhibitors of MMP-1

and MMP-2, which can inhibit collagen destruction by MMP-
2 and MMP-9. AM contains proteinase inhibitors like α1 anti
chymotrypsin, α2 macroglobulin, α1 antitrypsin, α2 antiplasmin
and inter α1 trypsin inhibitor. It also has inhibitory effects on
various proteases in polymorphonuclear (PMN) cells.
These suggest the possibility of modulating therapeutic
effect of AMT on infectious keratitis. It also provides an
effective barrier against PMN cells in the tear film and prevents
stromal infiltration of inflammatory cells to the injured cornea,
besides its influences on wound healing. Additional
mechanisms involved may be the effect of AMT mimicking
collagen shield when the AM is presoaked in anti-infective
agents, thus providing long-term drug delivery effect. Within
48 to 72 hours of effective and appropriate antimicrobial
Fig. 6.10.3.3: Amniotic membrane grafting (inlay with onlay and
fornix formation) with symblepharon ring in situ for ocular surface therapy, progression of the keratitis is halted in bacteria induced
reconstruction corneal ulceration. When the pathogen activity is suppressed
and clinical signs indicate improvement of the lesion, amniotic
membrane graft can be applied safely and effectively. AM graft
has also been found to be effective in promoting conjunctival
re-epithelialization and reducing scleral melts and inflammation
in extensive infectious scleral and corneoscleral ulcers.
Amniotic membrane transplantation (AMT) has been used as
adjunctive therapy to promote wound healing and prevent
perforation in bacterial keratitis.
AMT in HSV-1 necrotizing keratitis: Stromal herpes simplex virus
keratitis (HSK) is an immune-mediated disease. After reactivation
from latency in the trigeminal ganglion, herpes simplex virus
(HSV) antigens are expressed and corneal antigens exposed.
CD4+ T cells are the principal mediators of the inflammatory
response. The corneal damage is caused by proinflammatory
molecules and reactive radicals. Neutrophils, T cells and
macrophages contribute to tissue destruction in the cornea.
AMT has been found to promote epithelialization and reduce
stromal inflammation and ulceration in HSV-1 keratitis in the
animal model study. The healing process in necrotizing herpes
keratitis may be promoted by AMT.
AMT in other conditions: Amniotic membrane grafting helps in
effective ocular surface stabilization in various conditions such
as following pterygium excision, dermoid excision and excision
of ocular surface squamous neoplasia (Fig. 6.10.3.5).
Advantages of AM grafting
The thick basement membrane of the amniotic membrane
facilitates epithelial migration and reinforces the adhesion of
basal epithelial cells causing rapid epithelization. It also
Figs 6.10.3.4A and B: Amniotic membrane grafting with fibrin promotes epithelial differentiation and prevents epithelial
glue fixation after symblepharon release with keratectomy apoptosis.
(SJS) or ocular surface pemphigoid. Symblepharon release

with reconstruction in cases with keratoconjunctivitis sicca
in SJS is effectively done with buccal mucosa grafts with
fornix reformation. Large areas required to be reconstructed
will necessitate ex vivo cultured mucosal grafts. Mucus
membrane graft is also useful for cases of SJS where
significant lid margin keratinization might be excised and
reconstructed with mucosal grafts.
REFERENCES
1. Brown AL. Lime burns of the eye: use of rabbit peritoneum to
prevent severe delayed effects. Arch Ophthalmol 1941;26:754-69.
2. Sorsby A, Symons HM. Amniotic membrane grafts in caustic burns
of the eye. Br J Ophthalmol 1946;30:337-45.
3. Sorsby A, Haythorne J, Reed H. Further experience with amniotic
membrane grafts in caustic burns of the eye. Br J Ophthalmol
Fig. 6.10.3.5: Multilayered AMT for ocular surface 1947;131:409-18.
reconstruction after OSSN excision 4. Kim JC, Tseng SCG. Transplantation of preserved human amniotic
membrane for surface reconstruction in severely damaged rabbit
corneas. Cornea 1995;14:473-84.
Preserved AM expresses mRNAs for several growth 5. Dua HS, Azuara-Blanco A. Amniotic membrane transplantation.
factors and contains several growth factor proteins that might Br J Ophthalmol 1999;83:748-52.
benefit epithelialization. In a deep stromal ulcer, abundant 6. Meller D, Tseng SCG. Conjunctival epithelial cell differentiation
release of inflammatory cytokines and proteolytic enzymes on amniotic membrane. Invest Ophthalmol Vis Sci 1999;40:878-
by stromal keratocytes and inflammatory cells induces more 86.
rapid dissolution of the AM necessitating multiple grafting. 7. Tseng SCG, Li DG, Ma X. Suppression of transforming growth
factor-beta isoforms. TGF-B receptor type II, and myofibroblast
Fixation of AM in AMT can be facilitated with either
differentiation in cultured human corneal and limbal fibroblast by
human fibrin glue or sutures. Histopathological evaluation has amniotic membrane matrix. J Cell Physiol 1999;179:325-35.
revealed that the integration of the transplanted amniotic 8. Tsubota K, Satake Y, Ohyama M et al. Surgical reconstruction of
membrane35 into the host cornea can be either superficial, the ocular surface in advanced ocular cicatricial pemphigoid and
intrastromal, intraepithelial or subepithelial. Amniotic Stevens-Johnson syndrome. Am J Ophthalmol 1996;122:38-52.
membrane graft causes less vascularization on healing and is 9. Lee SH, Tseng SCG. Amniotic membrane transplantation for
persistent epithelial defects with ulceration. Am J Ophthalmol
relatively easy to perform. It provides more acceptable
1997;123:303-12.
cosmesis, does not disturb healthy conjunctiva and acquires 10. Tseng SCG, Prabhasawat P, Lee SH. Amniotic membrane
progressive transparency with time leading to improvement transplantation for conjunctival surface reconstruction. Am J
in visual acuity. Hence AMTs are more advantageous than Ophthalmol 1997;124:765-74.
conjunctival graft. They produce less tissue inflammation 11. Prabhasawat P, Barton K, Burkett G, et al. Comparison of
compared to tissue adhesives. Performing multilayer AMT conjunctival autografts amniotic membrane grafts and primary
successfully manages small corneal perforations and help to closure for pterygium excision. Ophthalmology 1997;104: 974-85.
12. Shimazaki J, Yang H, Tsubota K. Amniotic membrane
avert an emergency tectonic keratoplasty. An optical PKP can
transplantation for ocular surface reconstruction in patients with
be performed later in a more favorable setting with a better chemical and thermal burns. Ophthalmology 1997;104:2068-76.
outcome of vision. 13. Tsen SCG, Prabhasawat P, Barton K, et al. Amniotic membrane
transplantation with or without limbal allografts for corneal surface
Limbal stem cell transplantation has been described in the section on
reconstruction in patients with limbal stem cell deficiency. Arch
limbal stem cell deficiency. Ophthalmol 1998;116:431-41.
14. Azuara-Blanco A, Pillai CT, Dua HS. Amniotic membrane
Mucous Membrane Grafting transplantation for ocular surface reconstruction. Br J Ophthalmol
1999; 83:399-402.
Ocular surface reconstruction with buccal/labial mucosa 15. Honavar SG, Bansal AK, Sangwan VS, et al. Amniotic membrane
is performed in cases with extensive ocular surface injury transplantation for ocular surface reconstruction in Stevens-
due to chemical/thermal burns, Stevens-Johnson syndrome Johnson syndrome. Ophthalmology 2000;107:975-9.
Corneal Surgery 705
16. Tsai RJF, Li LM, Chen JK. Reconstruction of damaged corneas 26. Hao Y, Hui Kang D, Hwang D, et al. Identification of
by transplantation of autologous limbal epithelial cells. N Engl J antiangiogenic and antiinflammatory proteins in human amniotic
Med 2000;343:86-93. membrane. Cornea 2000;19:348-52.
17. Shinozaki M Shoda A, Shimazaki J. Detection of basic fibroblast 27. Tseng SCG, Li D, Ma X. Suppression of transforming growth
growth factor from amniotic membrane. Invest Ophthalmol Vis factor beta isoforms, TGF-β receptor type II and myofibroblast
Sci 1995;36:131-8. differentiation in cultured human corneal and limbal fibroblasts
by amniotic membrane matrix. J Cell Physiol 1999;19:325-35.
18. Lwebuga-Mukasa JS, Thulin G, Madri JA, et al. An acellular human
28. Lee S, Li D, Tan DTH, et al. Suppression of TGF-b signaling in
amniotic membrane model for in-vitro culture of type II
both normal conjunctiva fibroblasts and pterygiual body fibroblasts
pneumocytes. The role of the basement membrane in cell
by amniotic membrane. Curr Eye Res 2000;20:325-34.
morphology and function. J Cell Physiol 1984;121:215-25. 29. Solomon A, Rosenblatt M, Monroy DC et al. Suppression of
19. Modesti A, Scarpa S, Dórazi G, et al. Localization of type IV and interleukin α and interleukin α in the human corneal epithelial
V collagens in the stroma of human amnion. Prog Clin Biol Res cells cultured on the amniotic membrane matrix. Br J Ophthalmol
1989;296:459-63. 22001;85;444-9.
20. Behzad F, Jones CJ, Aplin JD. The role of intergrin alpha 6 beta 4 30. Tonhani A, Grueterich M, Tseng SC. The role of NGF signalling
in hemidesmosomes of human amnion (abstract). Biochem Soc in human limbal epithelium expanded by AM Culture. Invest
Trans 1991;19:381S. Ophthalmol Vis Sci 2002;43:987-94.
21. Na BL, Hwang JH, Kim JC, et al. Analysis of human amniotic 31. Bouchard CS, John T. Amniotic membrane transplantation in the
membrane components as proteinase inhibitors for development management of severe ocular surface disease: indications and
of therapeutic agent for recalcitrant keratitis. Trophoblast Res outcomes. Ocul Surf 2004;2(3):201-11.
1999;13:453-66. 32. Riau AK, Beuerman RW, Lim LS, Mehta JS. Preservation,
22. Kim JS, Kim JC, Na BK, et al. Amniotic membrane patching sterilization and de-epithelialization of human amniotic membrane
for use in ocular surface reconstruction. Biomaterials
promotes healing and inhibits proteinases activity on wound healing
2010;31(2):216-25. Epub 2009 Sep 24. Review.
following acture corneal alkali burn. Exp Eye Res 2000;70:329-37.
33. Dekaris I, Gabri é N. Preparation and preservation of amniotic
23. Talmi YP, Sigler L, Inger E, et al. Antibacterial properties of human
membrane. Dev Ophthalmol 2009;43:97-104.
amniotic membranes. Placenta 1991;12:285-8. 34. Alió JL, Abad M, Scorsetti DH. Preparation, indications and results
24. Svinarich DM, Gomez , Romero R. Detection of human defensins of human amniotic membrane transplantation for ocular surface
in the placenta. Am J Reprod Immunol 1997;38:252-5. disorders. Expert Rev Med Devices 2005;2(2):153-60.
25. Na BK, Hwang JH, Shin EJ, et al. Analysis of human amniotic 35. Resch MD, Schlötzer-Schrehardt U, Hofmann-Rummelt C, Sauer
membrane components as proteinas inhibitors for development R, Kruse FE, Beckmann MW, Seitz B. Integration patterns of
of therapeutic agent of recalcitrant keratitis. Inverst Ophthalmol cryopreserved amniotic membranes into the human cornea.
Vis Sci 1998;39:S90. Ophthalmology 2006;113(11):1927-35.
6.10.4 Surgical Instruments

in Corneal Transplantation
For any surgical procedure, appropriate instruments are 3. Straight Tissue Forceps
essential for achieving excellent results. In corneal
transplantation, the microsurgical instruments that minimizes
tissue trauma are important for a successful outcome. Major
advances in the microsurgical instruments along with, the
routine use of surgical microscope have revolutionized the
suturing techniques. Over the last few decades many
4. Mini Curved Iris McPherson Vannas Scissors
modifications even though subtle have taken place specifically
aimed at improving the quality of outcomes after penetrating
keratoplasty. For instance, to improve the refractive outcome,
there have been a number of modifications to the design of
trephines in order to create perfect regular wounds.
The basic instruments for penetrating keratoplasty would
include: 5. Micromini Troutman Katzin Corneal Transplant
1. Preparation of the recipient bed and corneal button Scissors (Right and Left)
i. Trephines
ii. Cutting blocks
iii. Artificial anterior chamber maintenance systems.
2. Microsurgical instruments for ophthalmic surgery
i. Specific for cor neal transplantation such as
corneoscleral scissors and intraoperative keratometers
ii. General instruments used in anterior segment surgery
including speculum, forceps, scissors and needle
holders.
A typical corneal transplantation tray would consist of the
following:
1. Barraquer Wire Speculum 6. Spring Action Curved Iris Scissors
7. Curved Needle Holder Without Lock

2. Iris McPherson Tying Forceps
Corneal Surgery 707
8. Suture Placement Marker used because of the relative ease of use as well as being
inexpensive especially in many developing countries. In case
of handheld trephines without the handle, the blade is
positioned manually by aligning to the center. There are no
cross hairs for aiding in centering. With a handle, it allows the
theoretical advantage of more stability. In addition, it offers
9. PK Cutting Block
the advantage of fitting an internal obturator with or without
10. Trephine System
a calibrated nut for presetting the depth of trephination. This
11. Sinskey Lens Manipulating Hook
has the advantage of preventing an accidental entry into the
anterior chamber. Significant disadvantages include, obturator
distorting the cornea if it touches the apex before the blade,
causing irregular cut can be a problem especially in keratoconus
12. Air Injection Cannula 30G patients. With the obturator it also obscures the surgeons view
and also necessitates the purchase of many different handles
to accommodate different blades. In addition, oversizing of
the donor is essential as the donor button is punched from
the endothelial side inducing more myopia.
Using a Vacuum System

Corneal Trephine Systems
Vacuum based systems offer the advantage of stabilization
Trephines are integral part of corneal button preparation of the globe, reduces the chances of overcutting or
and have undergone significant change in design and quality undercutting due to any tilt and unequal pressure on the globe.
over the years. A trephine is a circular scalpel blade used They are particularly useful in soft and perforated globes as in
alone or with a handle that when rotated, produces a circular therapeutic keratoplasty for perforated corneal ulcers or in
corneal incision. Von Hippel introduced the concept of cases with corneal thinning.
round trephine and the subsequent modifications have all One of the popular trephine systems introduced in 1980s,
been based on the underlying basic principle, circular is the Hessburg-Baron vacuum trephine (Fig. 6.10.4.2). It
incisions produce the most favorable refractive outcome. consists of an outer body with a 16 compartment suction
A variety of trephines have been developed over the years ring attached to a 6 ml syringe for providing fixation and
in an attempt to produce the perfect cut donor and recipient
buttons. Trephines are available in different sizes varying
from 5 to 17mm depending on the different systems. Two
different systems exist (Table 6.10.4.1):
Handheld Trephines
The handheld trephines also can be used with or without a
handle. Castoviejo handheld trephine (Fig. 6.10.4.1) developed
in the 1930s was the popular trephine in the 1970s. It is widely Fig. 6.10.4.1: Catroveijo hand held trephine system
Table 6.10.4.1: Trephine systems

Trephine system Type Vacuum attachment Sizes Comment
Castroviejo Hand-held None 4–16 mm
Barron Vacuum Outer ring of trephine body 6–9 mm
Hanna Vacuum Outer ring of trephine body 7–11 mm
Krumeich Vacuum Separate suction ring
Lieberman Vacuum Outer ring of trephine body Single cutting diamond blade
Fig. 6.10.4.2: Hessburg-Barron vacuum trephine Fig. 6.10.4.3: Barron donor cornea punch
stability during trephination. The inner wall of the vacuum choosing the different trephine systems, the surgeons need to
chamber is slightly recessed to account for the anterior corneal consider the surgical skills and comfort of use with these
curvature and 16 markers on the outer ring may be inked thus systems as well as the cost of these systems.
helping with accurate suture placement. The inner trephine In corneal transplantation, preparation of the donor button
blade assembly consisting of the blade, cross hair for centering is as important as that of the recipient bed for a successful
and four plastic spokes for turning the blade. A calibrated outcome. Preparation of the donor button consists of a separate
mechanism allows for advancement of the trephine by 0.25 system that includes the cutting blocks and donor punching
mm for each complete 360-degree turn. system. Different punching systems exist all with the aim of
Hanna trephine system also has similar syringe driven producing a donor button with minimal endothelial damage
vacuum outer chamber for adequate globe stabilization. The while achieving a uniform cut with minimal tissue distortion.
eight suction holes attached to an inner blade unit prevent Most of these systems utilize punching from the endothelial
corneal vaulting. As with Hessburg-Baron system, accurate side, while those utilizing the artificial anterior chamber system
centering is possible with the help of fenestrated obturator. uses trephination from the epithelial side.
The Hanna Trephine System includes a vacuum trephine
and punch for performing penetrating keratoplasty. It consists Donor Corneal Punch
of premounted single-use blades of diameters from 7.00 to One of the most popular systems used is the Iowa punch system
9.00 mm in .25 steps and 9.00 to 10.50 in 0.50 steps and which has a central platform with an integrated piston assembled
designed for limbal base suction, controlled trephination depth, to the neck of the platform. A donor punching system that utilizes
vertical, uniformly shaped trephination and accurate centration. a spring coil can fit different sized trephines 6.25 to 9 mm. Donor
It also has the advantage that trephination depth can be cutting blocks with or without vacuum can be placed on the
adjusted, which prevents accidental entry and damage of platform for preparation of donor buttons.
anterior chamber structures. The Troutman punch system is still popular in many
In the Krumeich trephine system, a separate Barraquer developing countries, mainly due to the ease of use and being
style suction ring with a cross hair device for centering exists less expensive. This consists of a base-plate, a piston carrier, a
with a clear obturator, which controls the trephining depth in piston handle that fits the carrier, trephines and 18 mm Teflon
100-micron increments. block. Each handle fits specific sized trephines and is available
A single point cutting using a diamond blade is the unique in 3 different sizes (5–7 mm, 7–9 mm, 9–11 mm).
feature of the Lieberman system. It allows for cutting of a round The Barron donor cornea punch (Fig. 6.10.4.3) consists
or oval button perpendicular to the visual axis. While the outer of a trephine system housed on top, which fits on to the nylon-
suction ring holds the trephine to the limbus using a vacuum cutting block. Four stainless steel guideposts align with four
mechanism, the single point diamond knife produces the desired corresponding holes in the cutting block. The unit also has a
incision with the help of two cutting inserts. This offers the plastic ring that protects the blade during shipment. The cutting
theoretical advantage of prevention of unequal or irregular cuts at block has four small holes that can be inked to identify the
different stromal depths. The donor cornea however needs to be quadrants for cardinal suture alignment. These are available
incised using the same system with an attached artificial chamber. in different sizes, with blade diameters ranging from 6.0 mm
One of the biggest problems with evaluation of different to 9.5 mm
trephine systems has been the paucity of literature in this field Rothman-Gilbard corneal punch is a nonspring loaded
or studies comparing the different systems. Hence when system that utilizes eight marking-suction holes to fix the
Corneal Surgery 709
tissue in position during trephination. These eight holes Corneal Microsurgery Instruments
also correspond in location to the meridians of an eight-
Scissors
blade radial keratotomy marker. Together when used, this
system has the advantage of facilitating alignment of Commonly used scissors found in the PKP tray include the
meridians on donor and host tissues. In addition, this aids Westcott scissors, Vannas scissors and the corneoscleral scissors.
in radial placement of equidistant sutures from the wound The corneoscleral scissors (Troutman) (Fig. 6.10.4.4) are the
margin. most specific for PK and is one of the instrument that is
In the Lieberman donor punch, instead of the surgeon's indispensive to the transplant surgeon. The blades are curved
aid, gravity from a weighted head is used to trephine the corneal with the lower blade inside the upper blade for creating beveled
button. Excellent trephination can be achieved when using incisions. In addition, the shorter radius of curvature and
the smaller blades (7–8 mm). angulation allow making precise shorter cuts in a circular fashion.
The vacuum based systems used for trephining the A simple Westcott scissors (Fig. 6.10.4.5) is useful for
recipient bed can also be used for donor trephining with the cutting the sutures used to secure Flieringa ring in case of
additional use of artificial anterior chambers. The chamber high myopes or in cases with low scleral rigidity. Other uses
allows the donor corneoscleral cap to be anatomically include removing dense pannus or in the removal of dense
positioned epithelial side up and maintain adequate pressure papillary membranes or iris fixated lenses. Vannas scissors
similar to intraocular pressure, while lamellar dissection or full comes in different sizes and designs. At least one straight and
thickness trephination can be performed from the epithelial curved ones are usually found in every PK instrument tray.
side. One of the commonly used systems is the Barron artificial Vannas scissors (Fig. 6.10.4.6) are most useful in working
anterior chamber. This has a base that holds the tissue retainer inside the anterior chamber. Some of the common instances
and has dual ports with pinch clamps to inject or aspirate where Vannas is useful include like trimming wound edges,
viscoelastic, balanced salt solution (BSS) or air. A tissue retainer for pupilloplasty, creating an iridectomy and removing pupillary
for securing the donor cornea tissue and a positive-action membranes.
locking ring that holds the tissue retainer securely against the
base completes the anterior chamber system. Donor buttons Needle Holder
with diameter up to 12.5 mm can be prepared using this system
Needle holders are available in different sizes and design.
and can hold donor cornea tissue having a scleral rim diameter
In the corneal tray, one fine and one larger nosed standard
of 14 mm to 18 mm. Advantages include epithelial side
needle holder are the ones usually found. Some surgeons
trephination, minimal endothelial injury and similar stromal
prefer the hockey stick configuration, as it is easy to work
wound profile of donor/recipient beds.
in deep-set eyes. Few important tips need to be remembered
Recent advances have resulted in the use of femtosecond
while choosing needle holders. Fine tipped delicate curved
lasers for donor and host trephination. Newer trephination
ones are ideal for passing sutures in the cornea in different
techniques such as profiled trephinations (top hat and
meridians. In addition, non-locked ones are ideal to prevent
mushroom profiles) have been proposed for better wound
any tissue distortion. One also needs to keep in mind that
closures. Preliminary studies show that femtosecond assisted
these fine needle holders should not be used to place larger
keratoplasty produces precise trephination cuts of superior
sutures as in anchoring sutures of Flieringa ring.
wound strength and stability to that of manual trephination.
Forceps
Trephining Blocks
The 0.12 forceps is one of the most important instruments
Cutting blocks used for support of the corneal button are found in corneal transplantation tray. Different designs exist
quite essential for adequate stabilization of the corneal button such as the straight Bonn corneal forceps (Fig. 6.10.4.7), curved
and to ensure central round wound edges. Both vacuum aided Bonn corneal forceps or the curved Colibri style (Fig. 6.10.4.8).
and compound-curved concave well approximating the corneal All of these consist of fine 1×2 teeth 0.12 mm high, which
peripheral curves are significant advances in the recent years. permit atraumatic grasp of corneal tissue or the 10-0 nylon
Some of the blocks feature central vents and marking aids for sutures. It also comes with a grooved platform for better grasp.
identification of the quadrants and placement of cardinal The curved shaft and angulation of around 100 degrees in
sutures. These blocks are usually made of teflon, nylon or some of the models improve the grasp and offers an
polycarbonate. unobstructed view of the operating field. The length of these
Fig. 6.10.4.4: Troutman corneal scissors
Fig. 6.10.4.9: Flieringa ring
Fig. 6.10.4.5: McPherson-Westcott scissors A number of other instruments that are routinely used
include the cyclodialysis spatula, Sinskey hooks, and 30G
cannulas for performing different procedures. The cyclodialysis
spatulas are particularly useful for synecheolysis and releasing
adhesions. Similarly the cannulas are useful in injection of
viscoelastics and BSS into the anterior chamber through the
side port incisions. Every tray in addition should contain
Fig. 6.10.4.6: Vannas scissors
Flieringa ring (Fig. 6.10.4.9). This is useful in cases with low
scleral rigidity with a tendency for globe collapse.
Intraoperative Keratometers
Intraoperative keratometers are used to assess the corneal
curvature intraoperatively and to aid in preventing suture
induced astigmatism. Most of the commercially available
keratometers are based on the placido technology and are
Fig. 6.10.4.7: Bonn corneal forceps attached to the surgical microscope. In addition, various hand-
held systems are also available for qualitative measurement of
the astigmatism. In general, the tighter the suture, oval rings
are observed with the axis of shortest diameter reflecting the
steepest meridian.
In short, only a few of the instruments that are used in
corneal transplantation are unique for the procedure such as
the corneoscleral scissors. Most of the instruments are the
same as those used in other anterior segment surgical
Fig. 6.10.4.8: Colibri curved forceps procedures such as cataract surgery. Over the years many subtle
modifications have been made to some of the instruments in
forceps varies from 70 to 110 mm. The longer ones are design even though they serve the same purpose. There are
particularly useful in manipulating tissues inside the anterior several options available and in the end selection is mostly
chamber. The straight forceps can also be substituted for the based on personal choice. However, each surgeon should
tying forceps along with curved needle holders to economize choose the ones that they are comfortable with based on their
the time during surgery. prior experience and surgical training.
Corneal Surgery 711
6.10.5 Keratoprosthesis
Keratoprosthesis, as the name implies is an artificial cornea ophthalmologists like Cardona,8 Choyce, 9 Dohlman, 10
(kerato = cornea; prosthesis = artificial substitute). Barraquer, Strampelli,11 Singh, Worst12 and Pintucci13 to add
Keratoprosthesis surgery is indicated in cases with corneal considerable body of knowledge in this difficult field.
blindness with good visual potential for which conventional
treatment with penetrating keratoplasty is not favorable. Design and Materials
Keratoprostheses are made of clear plastic with excellent Keratoprosthesis restores sight to an eye with damaged
tissue tolerance and optical properties. They vary in design, cornea by means of a special tube that acts as a "periscope"
size and even the implantation techniques may differ across from the eye to the outside world. The keratoprosthesis
different treatment centers. It is indicated in severe cases extends both inside the eye and outside into the
of chemical burns (Fig. 6.10.5.1), end stage Stevens-Johnson environment. The tube passes out of the eye either
syndrome (Fig. 6.10.5.2), chronic inflammation, advanced through the eyelids or between the fused lids. The tube is
dry eye; ocular cicatricial pemphigoid (Fig. 6.10.5.3) and ordered to a specific optical power to help restore the
repeated graft failure (Fig. 6.10.5.4). Although early visual patient's sight, but the patient may have to wear refractive
recover y is f avor able, the percentag e of severe correction for clear vision. It provides patients with just
complications, such as extrusion, is extremely high in spite a type of tunnel vision. The extent of the visual field
of the number of devices and surgical techniques described increases with increasing diameter and decreases with
in the literature. Techniques for implanting a synthetic increasing length of the optical cylinder.
corneal replacement (keratoprosthesis) offer hope to this
Keratoprosthesis designs usually consist of an optical
disparate group of patients, who are often blind for many
cylinder and a supporting flange. Devices usually consist
years.
of a porous outer skirt element (Dacron for the Pintucci
keratoprosthesis and autologous tooth for the Strampelli
History
keratoprosthesis) joined to a rigid polymethylmethacrylate
The use of an artificial cornea to treat corneal blindness lens. These devices are initially implanted beneath the
was first conceptualized by Pellier de Quengsy in 1789. 1 facial skin, to allow the porous skirt to integrate with
He tried to restore vision in a completely opaque cornea autologous fibroblasts, before being transferred to the eye,
by fitting a silver rimmed glass window in the eye. In 1853, to ensure biocompatibility. Autologous buccal mucosal
Nussbaum2 performed experiments in rabbit eyes and graft is sutured over the ocular surface. This is fenestrated
implanted a quartz crystal implant into the cornea to restore over the lens element to allow a pathway for light to focus
vision. Improvement in keratoprosthesis design and on the retina, restoring vision. A wound healing reaction
insertion were continued in human eyes by Heusser (1859),3 to implantation of the keratoprosthesis device weaves new
Von Hippel (1877),4 Dimmer (1889),5 Salzer (1895).6 These collagen through the porous skirt to integ rate the
primitive keratoprosthesis were replete with complications keratoprosthesis with the surrounding scleral tissue.
like formation of retroprosthetic membrane, necrosis, The materials used for the optical cylinder include
infection and extrusion of the prosthesis. PMMA (Choyce, Boston keratoprosthesis), dacron
Various attempts in search of a successful (Pintucci keratoprosthesis), polycarbonate (Champagne
keratoprosthesis were made, but nothing fruitful could be cork keratoprosthesis), Hydroxy-apatite (Leon-Barraquer
achieved till the 1950s. Research in this field gained keratoprosthesis), hydrogel (AlphaCor keratoprosthesis)
momentum when Stone and Herbert7 noted that PMMA and polyurethane (Seoul keratoprosthesis). The clinical
(poly methylmethacrylate) splinters embedded in the corneas results of a very large number of different implants
of pilots of World War II were well tolerated. This led to indicate that polymethylmethacrylate (PMMA) has been
experiments showing that PMMA discs could be retained in the most widely used material for optical cylinders, and
the corneas of rabbits. Soon, genuine contributions regarding it has never been reported as a cause of failure. 14-15 The
technique, materials and follow-up were published by many supporting flange of the keratoprosthesis is usually made
Fig. 6.10.5.1: A case of severe chemical burns with severe dry Fig. 6.10.5.3: A case of ocular cicatricial pemphigoid where
eye and keratinization keratoplasty has a poor prognosis
Fig. 6.10.5.2: End stage Stevens-Johnson syndrome Fig. 6.10.5.4: Eye showing evidence of multiple graft failure
up of methacrylate, teflon, dacron mesh, polycarbonate, are only indicated in eyes with some residual tear function
tooth and bone (as in osteo-odonto keratoprosthesis), and are classified as wet eyes.
cartilage (as in chondro keratoprosthesis) or nail (as in A variety of modifications have been introduced over
onycho keratoprosthesis). The keratoprosthesis devices the years to various keratoprosthesis designs, but a single
have been classified into non-penetrating, penetrating piece, flexible, ideal keratoprosthesis without accompanying
and perforating type depending on the design (Table complications that would serve as an epithelialized donor
6.10.5.1). They are also described as collar button shaped button is the need of the hour.
devices and stem with skirt devices. There are some
keratoprosthesis which are suitable for severe dry eyes Indications
w i t h a b s e n t t e a r f u n c t i o n l i ke os t e o - o d o n t o - Broadly, keratoprosthesis surgery is indicated in patients with
keratoprosthesis-OOKP (Fig. 6.10.5.6) and Boston bilateral corneal blindness who have little or no chance of
keratoprosthesis Type II. T he Champagne Cork, success with a standard corneal graft (Table 6.10.5.2). A detailed
Pintucci, Boston Type I and AlphaCor keratoprosthesis ophthalmic and psycho-social assessment of the patient is a
Corneal Surgery 713
must. Patient selection involves stringent criteria. They are Table 6.10.5.1: Classification of keratoprosthesis designs
indicated in medical conditions like non-inflammatory 1. Non-penetrating (Intralamellar) (Fig. 6.10.5.5A)
conditions (graft failure with chronic edema, corneal 2. Penetrating
dystrophy), graft failure following herpes simplex keratitis, • anterior
zoster, infectious keratitis, trachoma, ocular cicatricial • posterior (Fig. 6.10.5.5B).
3. Perforating
pemphigoid (OCP), chemical burns and Stevens-Johnson • Intralamellar (Fig. 6.10.5.5C).
syndrome (SJS). • Anterior
Keratoprosthesis can be divided into temporary and – Cardona through and through keratoprosthesis
– Ceramic keratoprosthesis
permanent, depending on the indication. A temporary
– Dohlman keratoprosthesis
device is used intra-operatively to aid in visualization and – Type-I: for wet eyes
is removed following surgery. The indications include severe – Type-II: for dry eyes
ocular trauma for anterior and posterior segment – Osteo-odonto-keratoprosthesis
– Boston KPro (I and II)
reconstr uction, cataract extraction, modified triple – Champagne-cork keratoprosthesis.
procedure, vitreoretinal surgery in cases of corneal opacity • Posterior
or ocular trauma and combined penetrating keratoplasty – Nut and Bolt keratoprosthesis (Fig. 6.10.5.5D).
and vitreoretinal surgery. The examples include Eckardts
keratoprosthesis, Landers Foulk and Landers wide field if the patient is a good candidate for the keratoprosthesis
lenses. Permanent keratoprosthesis are used to treat patients surgery. Parameters to be noted include visual acuity, accuracy
with severe corneal disease where corneal transplantation of light projection, intraocular pressure, evaluation of blink
is inappropriate or has repeatedly failed. and tear mechanism, signs of chronic inflammation, whether
the patient is phakic, pseudophakic or aphakic, optic nerve
Preoperative Assessment head cupping, ultrasound B-scan and A-scan. Oral cavity
assessment for OOKP surgery is essential.
It is essential that the eye to be undergoing keratoprosthesis
surgery, be free from initial insult of injury, physical or
Keratoprosthesis Types
chemical, active inflammation or infection. Intraocular pressure
and Surgical Procedure
should be adequately controlled with no evidence of
glaucomatous damage to the optic nerve head. A good visual Many types of the keratoprostheses have been developed and
potential must be elicited with the aid of light projection, implanted in patients over the past two decades with variable
pupillary responses, ultrasonography of the posterior segment long-term success. These include the osteo-odonto-
and electrodiagnostic tests. Prior to surgery, a detailed history keratoprosthesis (OOKP), Dohlman-Doane keratoprosthesis
should be taken to assess the corneal condition and determine (now known as the Boston KPro), the Pintucci KPro, and the
Fig. 6.10.5.5: Types of keratoprosthesis designs: (A) Non-penetrating (Intralamellar);

(B) Penetrating posterior; (C) Perforating; (D) Nut and Bolt keratoprosthesis
Fig. 6.10.5.6: Basic principle and architecture of osteo-odonto-keratoprosthesis
Table 6.10.5.2: Indications of keratoprosthesis the grafted buccal mucosa. Fornix reconstruction may be needed
before initiating keratoprosthesis surgery in some cases. The
• Bilateral blindness
• Severe, debilitating corneal disease where keratoplasty is first stage involves the reconstruction of the ocular surface by
unfavorable the ophthalmologist and fashioning of osteo-odonto-lamina
• Evidence of good retinal function with the optical cylinder by the dental surgeon. Buccal mucosal
• Normal intraocular pressure
• No current intraocular inflammation graft is harvested taking care to avoid injuring the parotid duct
• Adult, well motivated patient prepared for regular follow-up opening (Fig. 6.10.5.9). The graft is trimmed of excess fat and
and fully aware of associated risks of keratoprosthesis. soaked in cefuroxime solution before suturing onto the ocular
surface (Fig. 6.10.5.10). The preparation of osteo-odonto-
AlphaCor artificial cornea (previously known as the Chirila
lamina involves drilling of a hole through the dentine of the
KPro).
canine tooth, wherein the crown of the harvested tooth is used
as a handle (Figs 6.10.5.11 and 6.10.5.12). The root and
Osteo-odonto-keratoprosthesis (OOKP)
surrounding bone is worked into a lamina with dentine on one
OOKP combines a synthetic optic with a biological haptic side and bone on the other. The PMMA optical cylinder is
(Fig. 6.10.5.7). It is based on the principle of using the cemented in the hole and the whole complex is then placed in
patient's own tooth to form a biological niche to support the submuscular space of the lower eyelid of the other eye.18
PMMA optic (Fig. 6.10.5.8) to restore sight in patients with The second stage involves retrieval of the osteo-odonto-
severe, keratinized ocular surface disease. This lamina (Fig. 6.10.5.13) from its sub-muscular pocket and
keratoprosthesis was first introduced by Benedetto Strampelli reflection of the buccal mucosal graft. Flieringa ring is sutured
in 196411 and later modified by Falcinelli16 and Christopher in place and the center of the cornea is marked, trephined,
Liu.17 It is indicated in recurrent graft failure, end stage SJS, the diameter of which corresponds to that of posterior part
OCP, chemical burns, dry eyes and trachoma and of the optical cylinder. Total iridectomy, lens extraction and
contraindicated if oral hygiene is poor, mucosal disease is anterior vitrectomy are performed before the keratoprosthesis
present or in the presence of other dental problems. Oral is sutured onto the cornea and sclera.18
assessment includes clinical examination of the state and Electron beam tomography can be used to monitor the
presence of canine tooth, state of the buccal mucosa and thickness and structure of the OOKP laminae in vivo. Through
radiological examination of the tooth. this technique, significant thinning of the lamina can be picked
OOKP surgery is performed in two stages spaced two to up early and also allows closer follow-up of this group of
four months apart. This allows soft tissue to grow around the patients to look out for signs of aqueous leakage, optic
osteo-odonto-lamina and ensures adequate vascularization of extrusion and consequent endophthalmitis.19
Corneal Surgery 715
Boston Keratoprosthesis acuity outcomes of greater than 20/40 in 23 percent of patients

and greater than 20/200 in 57 percent of patients. Failure for
The Boston Keratoprosthesis is an "artificial cornea" that can
visual acuity to improve from the Boston Keratoprosthesis
be used in severe corneal opacity or after corneal transplant
was attributed to underlying ocular disease such as advanced
failure or when such a transplant would be unlikely to succeed.
glaucoma, macular degeneration, or retinal detachment.21 The
Hence, this procedure helps patients whose conditions are the
Boston Type II Keratoprosthesis is similar in design to the
most difficult to treat. The Boston Keratoprosthesis has been
Type I and is reserved for patients with extreme dry eyes,
under development since the 1960s and has gradually been
symblepharon, SJS and OCP where there are no fornices to
perfected. It received FDA clearance in 1992. It is the most
support the device.
commonly used keratoprosthesis in the United States.20
The keratoprosthesis is made of clear plastic with excellent
There are two types of Boston Keratoprosthesis: Type I
tissue tolerance and optical properties. It consists of two parts
and Type II. Type I Keratoprosthesis is more commonly used
but when fully assembled, it has the shape of a collar button.
and is indicated in eyes with reasonable blink and tear
The device is inserted into a corneal graft, which is then sutured
production mechanism. The Multicenter Boston Type 1
into the patient's cloudy cornea (Fig. 6.10.5.14). If the natural
Keratoprosthesis Study (MBTKS), a prospective case series
lens is in place, it is also removed. The one-step surgery is
of 141 cases from 17 centers with an average follow-up of 8.5
relatively simple. General anesthesia is recommended. The
months, reported retention rates of 95 percent with visual
device is incorporated into a corneal graft which is then sutured
into the patient's cornea like a standard graft. Visual
improvement is usually seen on the first postoperative day.
The Boston Keratoprosthesis is known for long-term (many
years) stability and safety. Its optical system can provide
excellent vision if the rest of the eye is undamaged.21
Pintucci Keratoprosthesis
It was introduced by Pintucci in 1979 with dacron tissue as
the supporting element with the aim of significantly reducing
the complication rate. It has proved to be a useful modality
of treatment for bilaterally corneally blind Asian patients.22
The Dacron mesh is fixed to a medical grade PMMA optical
cylinder (5.5 mm long and 3.5 mm wide). The spaces between
Fig. 6.10.5.7: Osteo-odonto-keratoprosthesis: biological the filaments allow biological colonization of surrounding
haptic and synthetic optic
Fig. 6.10.5.8: A case with OOKP cylinder in situ Fig. 6.10.5.9: OOKP Surgery Stage 1A showing harvesting and
implantation of buccal mucous membrane graft
Fig. 6.10.5.12: Preparation of osteo-odonto lamina involves

Fig. 6.10.5.10: Buccal mucosa in situ following stage I OOKP. drilling of a hole through the dentine of the canine tooth
Fig. 6.10.5.11: OOKP Surgery Stage 1B showing removal of Fig. 6.10.5.13: OOKP Surgery Stage 2-Retrieval and
canine tooth for OOKP lamina implantation of OOKP lamina
tissue. The main characteristics of dacron tissue are softness is marked with gentian violet. General anesthesia with nasal intubation
and pliability, thus preventing aseptic corneal necrosis by is preferred. The keratoprosthesis is introduced upside down with
mechanical stress; it is chemically inert, and therefore not the optical cylinder vertical in the inferior orbito-palpebral sulcus
subject to reabsorption; it can be autoclaved; is easily cut pocket. The orbicular muscle is sutured with 8.0 Dexon and the skin
into the desired shape; and it can be sutured.23 In this way with 6.0 black silk. In severe dry eye, the lacrimal puncta are closed
the colonized dacron tissue plays a trophic and a mechanical with diathermy. A free labial mucosa graft is dissected and sutured
role. When healed, it becomes fully integrated with the on the cornea. Antibiotic ointment is instilled and lids closed.
surrounding tissues both biologically and mechanically, and The second stage is performed after about two months.
also acts as a barrier to microbial contamination. Before The colonized keratoprosthesis is removed from the lower lid
surgery, examination of the conjunctiva and lids is very and the cornea is partly exposed by dissecting the oral mucous
important because reconstructive plastic surgery is often graft. The cornea is trephined with a Franceschetti trephine.
necessary prior to the main surgery, as in cases of trichiasis, The optical cylinder is placed and the colonized Dacron tissue
lagophthalmos, etc. is sutured. During follow-up, the dacron tissue must be
The surgical technique to implant a Pintucci keratoprosthesis examined carefully for erosion through the surrounding tissues,
consists of two stages. In the first stage, the central part of the cornea loosening, aqueous leaks and infection. The most common
Corneal Surgery 717
complication, especially in extremely dry eyes, is the oral shape of the KP creates a "valve" on the cornea, ensuring a
mucous necrosis.24 watertight situation (Fig. 6.10.5.16). The "equatorial" scleral
fixation keeps the valve around the trephined hole. The steel suture
AlphaCor Artificial Cornea fixation on the equatorial sclera takes care of preventing extrusion
(Figs 6.10.5.17A and B). The structural organization of the device
This device is indicated in cases with Stevens-Johnson
ensures a wider visual field. It has been successfully used worldwide
syndrome, severe inflammation and in severe dry eyes. It is
as well as in India.25
contraindicated in herpes simplex keratitis. It consists of a
biocompatible, flexible one-piece artificial cornea made up of
Seoul-type Keratoprosthesis (S-KPro)
opaque, high water content, flexible hydrogel PHEMA sponge
that encourages bio-integration with host tissue. The central This keratoprosthesis consists of an optic portion made of
optic core is transparent and provides a clear optic with a polymethyl methacrylate (PMMA), a skirt of polypropylene
refractive power in situ similar to human cornea. It is available or polyurethane, and haptics of monofilament-polypropylene
separately for aphakic eyes (AlphaCor-ATM) and phakic/ (Prolene). The main difference between the conventional
pseudophakic eyes (AlphaCor-PTM). The prosthesis is inserted keratoprosthesis and S-KPro is the method of fixation to the
after peritomy and intrastromal lamellar dissection of the eyeball. In the case of S-KPro, the skirt is anchored to the
cornea. The posterior surface of the optic is in direct cornea, and the polypropylene haptics are anchored to the
communication with the anterior chamber and the anterior sclera to improve stability.
surface of the optic is covered with the anterior corneal lamella
and conjunctival flap, with the skirt being within the lamellar Postoperative Management
pocket. The second stage consists of opening the anterior
The success rate of keratoprosthesis surgery can be improved
covering layers about 12 weeks post-implantation.
with pharmacological intervention. A life-long regimen of daily
drops of antibiotics is prescribed to prevent infection. The
Champagne Cork Keratoprosthesis
patient should be seen the following day, after one week, two
(Singh-Worst Kpro)
weeks, one month and every month for the first half year, and
The main characteristic of this device is the fixation of the device then every two to three months. The prescription regimen
to the healthy and stable sclera instead of the diseased cornea. It should be individualized depending on the patients' condition.
has a polycarbonate structure with a dual fixation principle. It is Postoperative medication usually includes fluoroquinolone and
better suited for vascularized corneas (Fig. 6.10.5.15) like post vancomycin drops (14 mg/ml) once or twice daily.
SJS, OCP, chemical burns and severe dry eyes. The anti-conical Prednisolone acetate one percent is prescribed as needed. The
patient should be told about the importance of compliance
of medication.
Complications
Keratoprosthesis surgery is associated with a large number of
complications especially in the first year after surgery. However,
the patient is never free from potential complications and
requires frequent and close monitoring and follow-up.
Complications need to be identified early and treated promptly
to ensure a favorable outcome, if possible. Care of the
keratoprosthesis patient imposes a significant time burden on
the corneal surgeon, and hence should be undertaken
judiciously, both on the part of the corneal surgeon and the
patient.
The lack of adequate integration between the optic and
Fig. 6.10.5.14: A case showing implantation of Boston its surrounding skirt, and between the skirt and the host tissue,
keratoprosthesis underlies the reason for most of the complications associated
Fig. 6.10.5.15: Severely vascularized cornea
Fig. 6.10.5.16: A case with Singh-Worst keratoprosthesis in situ
with different types of keratoprosthesis. The problems of melt

and extr usion are the most common complications
encountered. Necrosis of tissue around the keratoprosthesis
is noted. Unless treated, this can lead to subsequent tissue
breakdown melt, aqueous leak, infection, or retinal detachment.
Certain measures reduce the risk of occurrence of these events.
The use of collagenase enzyme-suppressing medication also
lowers the incidence of this complication. In some cases,
however, necrosis still occurs, typically beginning around the
edge of the cornea adjacent to the optical stem. If identified
early, various repair mechanisms can be attempted to halt the
process. A thin slice of donor corneal tissue with a central 3
mm trephined opening and a radial cut can be slipped under
the anterior plate and sutured in place. This reinforces the
base of the keratoprosthesis and allows for further stabilization Figs 6.10.5.17A and B: Singh-Worst keratoprosthesis
Corneal Surgery 719
of the device through early vascularization, which is a favorable pneumoniae, Staphylococcus aureus and Staphylococcus epidermidis are
sign. Skin retraction away from the plastic stem of the common in Stevens-Johnson syndrome and OCP. Moderate
keratoprosthesis can lead to subsequent leakage, infection, and incidence of endophthalmitis is reported in chemical burns
extrusion. Repeated skin revisions may be necessary in the and low incidence in non-cicatrizing conditions.26
initial postoperative period, but subsequently, fibrosis may Glaucoma is a common complication of keratoprosthesis
occur around the base of the keratoprosthesis stem to provide surgery and is one of the more common direct causes of
stability. eventual blindness in many patients. Its pathogenesis is multi-
Post operative inflammation can lead to formation of factorial and may be associated with prolonged uveitis giving
retroprosthetic membranes and blurring of vision. This usually rise to trabecular meshwork blockage by inflammatory cells
resolves after one or two months. Long-term uveitis is rare or by the development of peripheral anterior synechiae.
but can result in persistent development of membranes and Preexisting glaucoma is another precipitating factor. One of
even retinal detachment. The use of corticosteroid in the early the major difficulties with these patients is monitoring
postoperative period is recommended in these patients. The intraocular pressure postoperatively and digital palpation of
use of corticosteroids in these patients should be done the globe is the only method useful in these cases. The
cautiously and under strict supervision, as they inhibit wound morphology of the optic nerve head can be assessed using
healing and may lead to the formation of tear fistulas and the 90-D lens or direct ophthalmoscopy, and disc photography
secondary infections, particularly in patients with Stevens- can be used at repeated intervals. Visual fields should be
Johnson syndrome. In addition to topical steroids, occasional monitored on a frequent basis and can also be used to assess
peribulbar injections of 40 mg of triamcinolone may be glaucoma damage. Systemic carbonic anhydrase inhibitors are
instituted. Retroprosthetic membranes may be managed by the mainstay of treatment. Bearing these difficulties in mind
creating a small opening with Nd:YAG (neodymium:yttrium in both the postoperative monitoring and treatment of
aluminum-garnet) laser. The back plate of the keratoprosthesis glaucoma, Ahmed valve glaucoma shunts may be a viable
has a laser ridge that keeps the membrane away from the stem. option in intractable cases.
In some patients, a dense retroprosthetic membrane may not
be amenable to Nd:YAG laser treatment surgical opening with CONCLUSION
vitrectomy cutting instrument may be required.
Keratoprosthesis surgery is more demanding than standard
The other posterior segment complication associated with
keratoplasty. Successful outcome requires strict patient
keratoprosthesis surgery is sudden vitritis with drastic
compliance, frequent follow-up and dedicated physician time.
reduction of vision and this is usually sterile in nature. This
However, in cases where further keratoplasty appears vain,
condition can be treated with peribulbar triamcinolone and
keratoprosthesis can be most gratifying. Developments in
prophylactic antibiotics only. Retinal detachment is an
biomaterials technology and bio-integration could make the
uncommon complication. It may be rhegmatogenous in nature
goal of ideal keratoprosthesis a reality.
and is probably associated with peripheral retinal breaks. In
some patients, tractional retinal detachment may occur, REFERENCES
particularly after chemical burns and is usually secondary to
occurrence of inflammatory vitreoretinal membranes and 1. Pellier de Quengsy G. Precis au cours d'operations sur la cbirurgie
des yeux, Paris, 1789, Didot.
postoperative uveitis. This condition has a grim prognosis and
2. Nussbaum N. Cor nea Ar tificialis, ein Substitut fur die
treatment is usually not successful. Transplantatio Cornea. Deutsbe Klinik 1853;34:367.
Postoperative infection is uncommon in the early 3. Heusser J. Die Einheilung einer Cornea artificials. Oesterr Ztscbr
postoperative period, but endophthalmitis can occur at any Pract Med 1860;26:424.
stage after surgery. It is a rare complication in patients who 4. von Hippel A. Eine neue Methods der Hornhauttransplantation.
adhere to the prescribed prophylactic antibiotics regimen. Early Arch Ophthalmol 1888;34:108.
detection and treatment of tissue melts can help reduce this 5. Dimmer F. Zwei Falle von Celluoidplatten der Hornhaut. Klin
Monaltsbl Augenb 1891;26:104.
complication. Nonetheless, some patients present with a
6. Salzer F. Uber den Kunstilichen Hornhautersatz. Wielsbaden 1898.
fulminant endophthalmitis without an obvious source of 7. Stone W, Herbert E. Experimental study of plastic material as
leakage around the keratoprosthesis with a poor final outcome. replacement for cornea. Preliminary report. Am J Ophthalmol
Endophthalmitis has been reported to be sterile in 70 percent 1953;36:68-73.
cases and infectious cases with pathogens like Streptococcus 8. Cardona H. Keratoprosthesis. Am J Ophthalmol 1962;54:284.
9. Choyce DP. Evolution of choice two-piece multistage perforating 19. Fong KC, Ferrett CG, Tandon R, Paul B, Herold J, Liu CS. Imaging
keratoprosthesis technique in 135 eyes (1967-1980). In: Trevor of osteo-odonto-keratoprosthesis by electron beam tomography.
Roper editor: Vlth Congress of European Society of Br J Ophthalmol 2005;89(8):956-9.
Ophthalmology, New York, 1981, Grune & Stratton. 20. Dohlman CH, Waller SG, Netland PA. Keratoprosthesis surgery.
10. Dohlman CH, Schneider HA, Doane MG. Prosthokeratoplasty. In: Linquist TD, Lindstrom RI, eds. In: ophthalmic surgery update.
Am J Ophthalmol 1974;77:694. 4th ed. Vol V-L. Chicago: Mosby Year Book, 1996:1-32.19. Maskati
11. Strampelli B. Keratoprosthesis with osteodontal tissue. Am J QB.
Ophthalmol 1963;89:1029-39. 21. Zerbe L Brian, Belin W Michael, Ciolino B Joseph, et al. Results
12. Worst JGF. Twenty-three years of keratoprosthesis research: present from the multicenter Boston Type 1 keratoprosthesis study.
state of art. Refract Corneal Surg 1993;9:188. Ophthalmology 2006;113:1779-84.
13. Pintucci S, Pintucci F. Keratoprosthesis avec un nouveau support 22. Maskati BT. Asian experience with the Pintucci keratoprosthesis.
haptique a la colonization tissulaire pour oeil sec. Ophthalmologie Indian J Ophthalmol 2006;54:89-94.
1988;2:157. 23. DeBakey ME, Crawford ES, Morris GC, Cooley DA. Patch graft
14. Polack FM. Corneal optical prostheses. Br J Ophthalmol 1071; angioplasty in vascular surgery. J Cardiovasc Surg 1962;3:106-41.
55:838-43. 24. Pintucci S, Pintucci F, Cecconi M, Caiazza S. New Dacron tissue
15. Fyodorov SN, Moroz ZI, Zuev VK. Keratoprostheses. London: colonizable keratoprosthesis: clinical experience. Br J Opthalmol
Churchill Livingstone, 1987:7-54. 1995;79:825-29.
16. Falcinelli G, Barogi G, Taloni M, et al. Osteoodonto- 25. Andel Van MV, Worst J, Singh I. Artificial corneas for the third
keratoprosthesis: present experience and future prospects. Refract world? The best efforts for the worst cases: the first clinical trials of
Corneal Surg 1993;9:193-4. low cost "champagne cork" keratoprosthesis of PMMA, glass/
17. Liu CSC, Scisio A, Smith GT, et al. Indications and technique of stainless steel and polycarbonate in 102 corneal blind patients in
modern osteo-odonto-keratoprosthesis (OOKP) surgery. Eye Amritsar, Punjab. An Inst Barraquer, (Barc.)28(suppl):177-179(1999).
News 1998;4:17-22. 26. Nouri M, Terada H, Alfonso EC, Foster CS, Durand ML, Dohlman
18. Liu C, Paul B, Tandon R, et al. The osteo odonto keratoprosthesis. CH. Endophthalmitis after keratoprosthesis: incidence, bacterial
Seminars in Ophthalmology 2005;20:113-28. causes, and risk factors. Arch Ophthalmol 2001 Apr;119(4):484-9.
Chapter 6.11
EYE BANKING
An eye bank is a non-profit organization with an aim to acquire enables safe transportation of material and increases the
and provide donated human eye tissue for corneal duration of storage, so that an efficient use of donor cornea
transplantation procedures in addition to providing vital tissue can be made. Introduction of the MK medium by McCarey
for research and education. It also stores and preserves human and Kaufman in 1974 was a significant development, heralding
corneal tissue for future use. The eye bank also holds the a revolution in corneal preservation.5 This medium proved to
responsibilities of ensuring the safety and efficacy of donor be reliable for storage of donor cornea at 4°C for at least
corneas together with fair and equitable distribution of three to four days, allowing for elective planning of corneal
transplantable corneas. All these services are provided in an surgery. Kaufman et al (1985) presented K-Sol as a storage
environment of stringent quality assurance standards with method viable for up to ten days.6 In 1991, Optisol™ (Bausch
focus not merely on the quantity of tissue provided but also & Lomb) was developed as a storage medium that lasts up to
on the quality of tissue and quality of service offered. 14 days.7 Capella and Kaufman developed the basic method
of cryopreservation in 1965. 8 The first successful
Historical Perspective transplantation using a cryopreserved human donor tissue was
reported by East Cott in 1954. The specular microscope
The idea of replacing dysfunctional cornea originated in the
developed by Stocker (1953) revealed the vital role, endothelial
18th century. Corneal transplantation was the first successful
cells play in corneal transparency.9
organ transplantation ever done in history. Edmund Zirm
performed the first successful corneal transplant in 1906.1
Medical Perspective
VP Filatov is considered as the father of modern eye
banking. In 1937, he showed that cadaver tissue stored at 4°C The process of corneal transplantation begins with corneal
could be used as donor material.2 This ultimately led to the donation. The selection of donor corneal tissue is influenced
establishment of eye banks for the collection and storage of by the potential for transmission of disease to the recipient
tissue. He pioneered the usage of donated, cadaveric cornea and also by the quality or potential efficacy of the tissue.
and highlighted the importance of protecting the intraocular Standards and guidelines for donor selection were initially
tissues while trephining the host tissue. He also propagated developed by the Eye Banking Association of America who
the use of direct suturing. The first eye bank was set up in produced their first set of Medical Standards in 1980. A
New York in 1959 by Townley Paton,3 and the Eye Bank rigorous review process has ensured that these Medical
Association of America (EBAA) was founded in 1961.4 This Standards continue to evolve as new knowledge and insight
organization laid down the standards for obtaining, develops. A list of absolute contraindications for the use of
preservation, storage and usage of donor tissue. donor tissue is included in Table 6.11.1. These contra-
The preservation of donor cornea is responsible for the indications are designed to reduce the potential for:
outcome of surgery to a great extent. A preservation 1. Viral transmission of disease
procedure, besides ensuring the endothelial viability, also 2. Transmission of bacterial or fungal infections
3. Transmission of malignant disease assessment reveals no contraindication to donation, acquisition

4. Any corneal pathology that poses a risk to the success of of donor tissue can be carried out. Tissue can be retrieved for
the surgery. transplantation either by performing an enucleation, i.e. surgical
Eye banks must have consistent policies for the removal of the whole eye or by an in-situ corneo-scleral
examination and documentation of a prospective donor's excision (i.e. globe retained in the orbit).10 The retrieval
available medical records, medical history and details regarding procedures for both of the techniques are given in detail in
the cause of death with emphasis on medications, laboratory Section III H8.340 under Donor Ocular Tissue Recovery.11
reports (especially microbiology, serology and hematology Donor eye enucleation is technically easier and requires less
reports), and noting the amount and time of any transfusions. time to perform than in-situ corneo-scleral excision. Corneal
An important factor to note is the length of time the cornea endothelium quality in enucleated eyes deteriorates in 24 to
has been ischemic (death enucleation time). An individual, who 36 hours, which can be prolonged only on preservation of
is qualified either by profession, education or training, should excised corneo-scleral buttons in tissue culture medium.
take legal permission from the next of kin. Though both the methods yield comparable results in terms
Once it has been determined that a consented donor meets of endothelial quality, microbial contamination, graft clarity,
medical and social history screening criteria, and the physical and postoperative median visual acuity at the end of three
months,12 many eye banks recommend enucleation of whole
Table 6.11.1: Contraindications for the donor eyes and corneo-scleral excision in the eye bank
use of donor tissue for keratoplasty laboratory. The equipment and supplies required for tissue
1. Death of unknown cause collection are given in Table 6.11.2. During enucleation, the
2. Death from central nervous system disease of unestablished prime considerations are to minimize manipulation of tissues
diagnosis
3. Creutzfelt-Jacob disease or a risk factor
surrounding the eye in order to preserve donor appearance,
4. Subacute sclerosing panencephalitis to prevent touching or distortion of the cornea and thus
5. Progressive multifocal leukoencephalopathy minimize any cell loss (epithelial and endothelial), and to reduce
6. Congenital rubella bacterial contamination.
7. Reyes syndrome
8. Active viral encephalitis or encephalitis of unknown origin Corneal evaluation begins with a gross examination of
9. Active septicemia (bacteremia, fungemia, viremia) the corneas in situ. A simple penlight examination can reveal
10. Active bacterial or fungal endocarditis epithelial defects (drying, erosion, sloughing), corneal edema
11. Active viral hepatitis
12. Rabies
with associated haze and striations due to folding of
13. Active leukemias Descemet's membrane, abnormal corneal shape, blood or
14. Active disseminated lymphomas (Hodgkin's disease, cloudiness in the anterior chamber, corneal scars or infiltrates,
Malignant non-Hodgkins lymphoma, Burkitt's lymphoma, arcus senilis, and any signs of conjunctivitis and discharge.
Mycosis fungoides, Multiple myeloma, Macroglobulinemia,
Heavy Chain disease) The slit-lamp enables a more accurate observation of the
15. High risk for HIV infection cornea, revealing earlier stages of pathology that are visible
16. Hepatitis B surface antigen positive donors grossly. The first part of the examination is a low to medium
17. HTLV-I or HTLV-II infection
18. Hepatitis C seropositive donors
power examination of the total cornea at approximately
19. HIV seropositive donors 20 to 30 degrees angle of incidence and moved to scan the
20. HIV or high risk for HIV infection entire cornea. In this way, major defects can easily be identified
21. Retinoblastoma, malignant tumors of the anterior ocular and then examined at a higher power to determine their nature
segment
22. Active ocular or intraocular inflammation and extent. The stroma is examined for overall clarity, amount
23. Congenital or acquired disorders of the eye which would of edema and stromal folds. Stromal folds are associated with
preclude a successful outcome for the intended use corneal edema. The amount of corneal edema, and thus the
24. Prior intraocular surgery or anterior segment surgery
(Refractive corneal procedures, Laser photoablation surgery)
severity and number of folds, will depend on time since donor
25. Behavioral and or social issues, i.e. homosexual or other high death, temperature, integ rity of the epithelium and
risk sexual behavior within the last five years, intravenous endothelium. A specular reflection of the endothelial layer
drug use for non medical reasons within the last five years, can be observed in a small area of the endothelial reflex. The
exposure to infectious disease within the last year by contact
with an open wound, needle stick, or mucous membrane or condition of the corneal endothelium is central to evaluating
tattooing or piercing within the last 12 months using shared the suitability of corneal tissue for penetrating keratoplasty,
instruments. as it is primarily the layer responsible for the maintenance of
Eye Banking 723
Table 6.11.2: Equipment and supplies for the tissue collection

1. General supplies
a. Donor information sheet, consent forms, etc
b. Pen-light—for gross examination of eyes
c. Insulated container with water ice and special foam to transport the tissue
d. Supplies for blood collection
e. Non sterile preparatory gloves
f. Broad spectrum antibiotic solution
g. Eye protection (safety goggles), shoe covers
h. Disinfectant solution
i. Eye caps/prosthesis
j. Biohazard disposable bag
k. Gauze and cotton pads
l. Two small closed stainless containers for gauze pads soaked in 70 percent alcohol in one and 5 percent betadine in the other.
2. Autoclaved and sterile materials: All materials must be autoclaved at 270° F for one hour. The kit should have the date of preparation
along with the initials of the person preparing it. The kit may include the following materials:
a. Sterility maintenance covers on barrier drape. A double holed drape facilitates procedure on both eyes.
b. Protective biohazard apparel-surgical gown (preferably moisture impermeable) cap, mask, etc.
c. Cotton tipped applicators or hemostats to open the eyes.
d. Sterile balanced salt solution or 0.9 percent sterile saline to irrigate the eyes.
e. Two sterile hemostats separately wrapped to hold the gauze pads.
f. Sterile gloves.
g. 8–10 pieces of gauze.
h. Two eye jars with eye cages and a piece of 2" × 2" gauze. Eye jars should be labeled left and right.
i. Cotton balls or gauze to pack the orbits with surgical equipment.
3. For enucleation procedure
a. Solid blade eyelid speculum—one
b. Toothed (suturing) forceps—one
c. Conjunctival scissors—one
d. Muscle hook—one
e. Hemostats—two
f. Enucleation or optic nerve scissors—one
g. Allis forceps—one
h. Surgical tray—one
i. Test tubes or plain vials
j. Needle holder
k. Sutures
l. Enucleation spoon.
4. For corneal excision (autoclaved)
a. Solid blade eyelid speculum—one
b. Toothed forceps—two
c. Conjunctival scissors—one
d. Iris forceps—one
e. Hemostats—two
f. Right and left Castroviejo scissors—one each
g. Surgical tray—one
h. Disposable syringes with 21 G needle—5 ml and 10 ml
i. Test tubes or plain vials
j. B.P. blade handle and surgical blades no. 11 and 15.
Blood samples are taken from the donor that is serologically tested for human immunodeficiency virus 1 and 2, Hepatitis B surface antigen
and Hepatitis C virus. The best sites for post mortem blood collection are the femoral vein, subclavian vein, heart or the jugular vein. The
tubes containing 5 to 10 ml of blood should be kept upright till the time the serum is separated. The tissue is then processed and stored
in a preservative medium (Figs 6.11.1A to D).
corneal turgor and transparency. Specular microscopy microscopy is mostly used by eye banks using hypothermic
determines the endothelial cell density, cell pleomorphism and storage of corneo-scleral buttons. The majority of eye banks
polymegathism and identification of corneal guttata. These using organ culture storage methods usually prefer other
changes reflect the current well-being of the endothelium as methods of endothelial evaluation. These include phase
well as being indicative of its functional reserve.13 Specular contrast microscopy and transmitted light microscopy often
Fig. 6.11.1A: Processing kit Fig. 6.11.1B: Cleaning and disinfection of donor eye
Fig. 6.11.1C: Removal of corneo-scleral rim from whole globe Fig. 6.11.1D: Transfer of donor button to preservative media
accompanied by trypan blue intravital staining of the removal mechanism of the cornea at 4ºC. This helped in
endothelial layer. maintenance of corneal detergence and extended the storage
Various methods have been used for the storage of donor time to two to three days. Over the years the
cornea for keratoplasty. The methods have been classified in M-K formulation has been improved by the addition of
terms of duration of storage as (a) short-term, (b) intermediate the more stable HEPES (4-(2-hydroxyethyl)-1-
term (c) long-term and (d) very long-term. For short term piperazineethanesulfonic acid) buffer and the replacement of
storage, two techniques are used: Moist-chamber storage and the penicillin streptomycin antibiotics to gentamicin which
M-K medium. Filatov 2 first described the use of moist has a greater spectrum against gram-negative bacteria.14
chamber storage of whole eyes at 4ºC. Although the moist- The development of the intermediate-term corneal storage
chamber technique has been in use since many years, its main medium has facilitated a better maintenance of the donor
drawback is that the tissue viability is maintained only for cornea and flexible surgical scheduling. In the mid-eighties
around 24 hours of storage. This is because the endothelium 2.5 percent chondroitin sulfate was added to the basic M-K
of the cornea, when stored as a whole globe, is subjected to formulation. The resultant solution, K-Sol, successfully
the toxic build up of metabolic waste and necrotic tissue in extended the storage time to seven to ten days. However, one
the stagnant aqueous humor. McCarey and Kaufman modified of the problems with media containing chondroitin sulfate is
an existing tissue culture medium, TC 199, by adding dextran that it may cause corneal swelling. An improved solution,
as an osmotic agent to compensate for the inactivity of water Dexsol, overcame this problem by the addition of dextran to
Eye Banking 725
the formula. Optisol, the latest commercially available storage younger, better corneal tissue resulting in more optical and
medium is better than dexsol in maintaining better endothelial successful grafts.
cell morphology and thinness of the cornea. It can store cornea
for seven to ten days between 2 to 6ºC. Optisol is now usually Administrative and
available as OptisolGS that contains both gentamicin and Technical Perspective
streptomycin to give broad antimicrobial coverage. Modern eye banks have developed into professional operations
Organ Culture is a medium term storage method using with highly trained staff and certified technicians, round the
storage temperatures between 31ºC and 37ºC. This technique clock coverage and growing public interaction. The eye bank
provides preservation of up to 35 days. This extended storage should run smoothly technically and financially and have strong
time enables matching of high-risk recipients with tissue typed public relations and professional education programs. The
donor cornea and aids in better functional assessment of the main key to a successful eye banking program is its effective
cornea. These advantages have made organ culture method public communication. The eye bank should have facility and
as the preferred method of corneal storage across Europe, specific manpower to receive round the clock telephone calls.
UK and New Zealand. Kaufman and Capella15 reported
successful preservation of donor corneas for periods up to
one year by cryopreservation. In the future, an ideal method
for corneal cryopreservation will need to be developed using
different cooling rates, and cryoprotectants.
Hospital Cornea Retrieval Program

There are broadly two ways of overcoming the acute global
shortage in quality corneas. One is by encouraging voluntary
donation while the other is by exploring newer sources for
cornea procurement. Voluntary eye donation is a result of
realization of one's social responsibility towards the corneal
blind. Eye Donation Counselors (EDCs) directly motivate the
family members of the deceased for an eye donation.
The Ramayamma International Eye Bank initiated the
Hospital Cornea Retrieval Program (HCRP) in 1990 to
concentrate on deaths that occur at hospitals and encourage
eye donations using a combined method of motivation and
grief counseling. The HCRP focuses on hospitals to retrieve
corneal tissue because of several inherent advantages with the
setting (Fig. 6.11.2). Availability of medical history, availability
of tissues from younger individuals, reduction in time interval
between death and corneal excision and cost effectiveness are
some of these. Trained counselors are stationed in multi-
speciality hospitals where they counsel and motivate a family
to pledge the eyes of their deceased relation, and contribute
to the worldwide effort to reduce corneal blindness. The LV
Prasad Hospital Cornea Retrieval Program recorded a high
yield of donor tissues recovered through the HCRP. Of the
3,932 tissues collected between 1991 and 2000, 56 percent
was achieved through the motivational approach of EDC.
Hospital Cornea retrieval program is a revolution in eye
banking that has remarkably increased the availability of Fig. 6.11.2: Hospital eye donation protocol
The staff should be accessible to meet public courteously the training and certification of eye bank technicians and the
during office hours. accreditation of eye banks. The focus on technicians clearly
For an eye bank setup, a minimum area of 600 sq. ft is recognized their important role in the transfer of corneas from
required which accommodates a serology lab, tissue processing donors to recipients. These medical standards broadly include
lab, evaluation storage and shipping laboratory.16 An eye bank statement of purpose, outline of the organization of an eye
should have communication facilities, access to equipment such bank, medical directors and their qualifications, eye bank
as slit-lamp, refrigerators for storing blood samples, tissues technicians and their qualifications and training, laboratory
and storage media, and laminar flow hood, surgical facilities, acceptability of donor tissue, record keeping of donor
instruments, sterilization facilities, serology laboratory, tissue, enucleation procedures, inspection of donor tissue and
preservation media and appropriate transportation system. lastly certification and recertification of eye banks and eye
Each eye bank should have a policy manual with details of all bank technicians.
the policies and functions. Record keeping, tracking, quality
assurance and performance, confidentiality in all aspects should Legal Perspective
be accounted for in all eye banks. The need for documenting,
storing and retrieving vast amount of data mandates the use Laws governing organ or tissue procurement all over the world
of a computer. Each eye bank should have custom made have incorporated one of the two general approaches. One
software necessary to store eye donors and recipient records, approach requires voluntary consent prior to tissue removal
eye pledge details, the results of tissue screening and general by the decedent before death or the survivors in legal
correspondence. The eye bank technicians must be familiar possession of the body after death. The second approach
with the procedures and policies of the eye bank and should presumes consent and allows tissue removal in the absence of
be aware of aseptic techniques of enucleation, tissue handling, prior objections. The approach in each country is to a large
and corneal excision and preservation procedures. extent determined by its need for organs, legal and social
Eye banks should establish and document a just, equitable heritage and the public support for such laws. The choice of
and fair system of distribution. A proper networking of eye law and its enthusiastic application by health care workers in
banks is essential for completion of this function. turn, influence the success of efforts to develop a sufficient
Documentation of distribution (time and date of requests supply of corneas.17
and delivery of eye tissue) should be available at all times. There are 160 countries where it is legal to procure
Access to tissue for patients with corneal blindness should be cadaveric eyes.18 Countries with 'voluntary consent' or 'opt-
provided without regard to sex, age, religion, race, creed, color in' structure depend heavily on the surviving family consent
or caste of the recipient. In distributing the tissue to the to facilitate eye donation. Most Asian countries including India
receiving surgeon, the entire medical history of the donor with have legal "Opt-in" system.17 Some countries including USA
details of the tissue should be described. have refined "mandated choice consent" and "Routine Inquiry
laws".19 Individuals are required under "mandated choice
Medical Standards in Eye Banking consent" to indicate along with some other state requirements
Quality consciousness is fundamental to the success of corneal like Income Tax return filing or driver's license, if they will
transplantation. It should be followed by all eye banking want to be listed by choice as voluntary eye donors. Under the
organizations in order to achieve acceptable levels of quality, provisions of 'Routine inquiry' health care workers are
expertise and ethics in dealing with eye tissue for mandated to compulsorily ask for cadaveric eye donation
transplantation as well as to define minimum standards of (Routine Inquiry Law, 1986, USA). These legal provisions have
practice in the procurement, storage and distribution of helped improve procurement of voluntary donor corneas.
corneal tissue. These medical standards and regulations are The available laws can be grouped along a spectrum based
intended to assure the highest possible standards of safety on the level of consent needed. At one end of the spectrum,
and efficacy for donor cornea, while maintaining an adequate reflecting customs and heritage, the surviving family has
donor pool. controlling authority to donate a deceased person's cornea.
In order to improve the safety of eye banking, regular At the other end, unless an objection is registered prior to
reviews and improvements in the standards and certification death, corneas can be removed as needed. Geographically,
of eye banks and eye bank personnel for the purpose of Asian and Latin American countries are concentrated in the
ensuring the quality of eye tissue is essential. When medical former group while Continental European nations constitute
standards were formulated in the late 1970s, the plan included most of the 'presumed consent' nations.
Eye Banking 727
National Perspective Program (HCRP), in India. ORBIS has provided support to

various institutions in setting up the international training and
Blindness continues to be one of the major public health
resource center for eye banking and corneal transplantation.
problems in Asia and Latin America. According to the World
This project endeavors to promote and increase eye donations
Health Organization, there are about ten million blind and
in India, while strengthening eye banking systems and
visually disabled people in India alone. Of these, nearly 2.5
procedures through training and research.
million persons are corneal blind, a large proportion of which
In a developing country like India, the eye banking system
is reversible and curable. The wide disparity and paucity of
must be effective and financially relevant. A 3-tier structure
donor human eyes in India is reflected by the fact that at least
has been proposed by Dr. G N Rao to address this issue
250,000 patients need corneal grafts and not more than 2000
(Fig. 6.11.3). An integrated system involving a three-tier
corneal grafts are being transplanted in the whole country in
community eye banking pyramid based on the infrastructure
a year.
and manpower at all levels. The three-tiers proposed were eye
In 1993, there were 166 eye banks in India, of which
donation centers, eye bank and eye bank training centers. The
approximately 27 eye banks collected more than 50 eyes per
top tier comprises of 5 Eye banking training centers (EBTC)
year and 6413 corneal grafts were done as reported by 104 eye
which would be responsible for tissue harvesting, processing
banks.20 Social organizations like Lions, Rotarians and Red
and distribution, creating public awareness as well as training
Cross have made productive efforts in the eye donation
and skill up-gradation of eye banking personnel. The middle
program.21 Since 2004, various associations and organizations
tier would comprise of a strong network of 45 Eye Banks,
such as National Program for Control of Blindness (NPCB),
(organizations which would comply with all the regulations
Eye Bank Association of India (EBAI) and ORBIS
stipulated by Govt. of India/EBAI) and these would cater to
International have been active in providing strategies to
a population of 20 million each. These Eye Banks would be
strengthen eye banking initiatives in the country. The strategies
closely linked with 2,000 Eye Donation Centers—EDC (ratio
include education, preventive measures, sustainable source of
of 1:50 suggested), each of which would cater to a population
donor cornea (wherein Hospital Cornea Retrieval Program
ranging from 50,000 to 100,000. The Eye Donation Centers
plays an important part) and community participation. The
will be regulated and funded by the Eye Banks themselves.
blue-print for eye banking in India would be a reality only
The EDC should provide public and professional awareness
with the nongovernmental-government partnership. The
of eye donation, coordinate with donor families and hospitals
Government of India supports eye banks through recurring
to motivate eye donation, to harvest corneal tissue, and collect
and non-recurring grants for operational and infrastructure
blood for serology and to ensure safe transportation of tissue
costs respectively. The government and nongovernment
to the parent eye bank.
organizations have joined hands to deliberate and evolve
policies for accreditation, review progress of implementation,
recommend for funding, develop plan of action, medical
standards and guidelines, identify training institutes, develop
training courses and training material.14
The Eye Bank Association of India (EBAI) was established
in 1989 with the objective to improve the quality of eye bank
services in the country and to coordinate all eye banks from a
national level. It also aids in providing training for eye bank
technicians so as to increase tissue quality and quantity. EBAI
stresses on the importance of registration, networking,
availability of resources and information, education and
communication.
Orbis International identifies corneal blindness as a priority
prog ram area in its global prog ram inter ventions.
Strengthening eye banking and its management services at all
levels has been one of the primary goals for ORBIS in India.
ORBIS has been supporting corneal blindness, including eye Fig. 6.11.3: 3-tier pyramid structure proposed for efficient eye
banking projects such as the Hospital Cornea Retrieval banking system
The key to the success of this road map will be widespread and presumed consent are actively followed upon and
HCRP, favorable legislations, public awareness, medical guidelines be devised for simplification of the registration
standards, accreditation and continuous training programs for processes.
the personnel involved in eye banking. The road map
culminated in three action plans—immediate, intermediate and International Perspective
long-term. In 1961, Eye Bank Association of America (EBAA) was
The plan was implemented in a phased manner— constituted by ten member eye banks in the United States of
immediate, intermediate and long-term. The immediate plan America to establish and certify uniform standards and
of one year, called for accreditation, establishment of medical
promote the various objectives of eye banks.4 The first medical
standards and the 3-tier model for community Eye Banks by
standards on eye or tissue banking were developed by EBAA.
the Government, while the Eye Banks, EBAI concentrated
The EBAA works closely with the Congress and the federal
on HCRP projects, improving public awareness and provision
agencies as well as international agencies, such as the World
of funding. The intermediate 3-year plan was reserved for
Health Organization (WHO) to promote fair and balanced
amendments in legislations to facilitate eye banking. The long-
policies to promote donation and eye banking. The EBAA
term plan spanning six years called for EBAI, Government
has promoted programs for training and certification of eye
and Eye Banks to complete nation wide network by December
bank technicians, for developing written policy and procedure
2008, all Eye Banks to comply with required standards and
manuals for the day-to-day operation of an eye bank, for the
EBAI to assume a monitoring role of all eye bank functions.
accreditation of individual eye banks, and for the frequent
By 2006, cornea collection should be 30,000, which would
evaluation and revision of the EBAA Medical Standards
gradually increase to 50,000 by 2008, 100,000 by 2012, and
document, all of which help ensure the quality and quantity
150,000 by 2015 and touch 200,000 by 2020.22
of the corneal supply. There are approximately 88 accredited
In India, legislation was first passed by the then Bombay
state in 1957 to regulate eye donation.23 The Transplantation eye banks in the US. Accreditation of eye banks was the first
of Human Organs bill which includes corneal transplantation attempt by a transplant organization to monitor the activities
in its purview, enacted in 1994, did not help eye donation of its members for the purpose of assuring the quality of eye
significantly. 24 Transplantation of Human Organs Act tissue. During the year 2004, the member eye banks of EBAA
(THOA) provides for the regulation of removal, storage and collected about 46,841 eyes of which about 32,106 corneas
transplantation of human organs for the therapeutic purposes were used for transplantation. The major source of this tissue
and prevention of commercial dealings in human organs for was hospitals.27
matters connected therewith or incidental thereto.25 A special The European Eye Bank Association (EEBA) is a
provision for removal of corneas was included in the technical-scientific organization for eye banks in Europe and
Amendment Bill of the Transplantation of Human Organs comprises of individual members from over 80 eye banks
and Tissues, 2008.26 The THO Act in section 3, currently located in some 22 European countries.28 Founded in 1989
provides that organs shall be removed by a registered medical with the simple objective of sharing information on eye
practitioner only. During the national consultation, it was banking, the Association is today the leading pan-national
pointed out that this stipulation was actually hampering the association in Europe dedicated to the advancement of eye
eye donation program and was, therefore, suggested that for banking and an authoritative reference point for eye banks
the removal of corneas, a trained eye technician could do the which work according to quality standards. The Association
job. This suggestion has been accepted and it is proposed establishes and maintains an agreed set of medical and
that in Section 3, after sub section (4), a new sub section 4-A technical standards, promotes the collection of data on eye
shall be inserted to provide that a technician possessing such bank activities including eye donor selection and procurement,
qualifications and experience may be allowed to perform relevant research and development, education and training in
enucleation. eye banking, and maintains linkage with national and
Model eye banking in India can be achieved only when international corneal transplant communities and relevant
HCRP is encouraged in all private and government hospitals, bodies. More than 14,000 human donor corneas are processed
medical standards are made uniform and mandatory for all annually in the European eye banks.29 Organ culture is the
eye banks and EDC, amendments to laws like required request preferred storage method in European eye banks and the
Eye Banking 729
donor tissue undergoes screening for microbial contamination 7. Kaufman HE, Beuerman RW, Steinemann TL, Thompson HW,
and positive serology (hepatitis, HIV, etc) as well as optional Varnell ED. Optisol corneal storage medium. Arch Ophthalmol
1991;109:864-8.
HLA typing and matching 8. Capella JA, Kaufman HE, Robbins JE. Preservation of viable
corneal tissue. Arch Ophthalmol 1965;74:669-73.
The Future 9. Stocker FW. The endothelium of the cornea and its clinical
implications. Trans Am Ophthalmol Soc 1953;51:669-786.
Eye banking in the present times has been a result of well- 10. Lane SS, et al. Whole globe enucleation versus in situ corneal
established medical standards which are continually evaluated, excision. Cornea 1994;13:305-9.
reviewed and internationally disseminated. Improved corneal 11. Standards of Eye Banking in India. NPCB INDIA 2009;48-51.
storage techniques, and comprehensive corneal evaluation 12. Jhanji V, Tandon R, Sharma N, Titiyal JS, Satpathy G, Vajpayee
through the combined use of slit-lamp and specular RB. Whole globe enucleation versus in situ excision for donor
microscopy combined with ongoing eye bank procurement corneal retrieval—a prospective comparative study. Cornea
2008;27(10):1103-8.
programs have led to scheduled elective corneal transplant 13. Laing RA. Specular microscopy of donor corneas. In: Brightbill
surgery with safe, efficacious tissue. In the future it may be FS, Editor: Corneal surgery: Theory, technique and tissue. Edition
possible for eye banks to enhance corneal epithelial and 2. St Louis, Mosby-Year Book 1993;575-86.
endothelial viability through the manipulation of growth 14. Waltman SR, Palmberg PF. Human penetrating keratoplasty using
factors. Similar manipulation could conceivably provide an modified M-K Medium. Ophthalmic Surg 1978;9:48-50.
opportunity to decontaminate the tissue of infectious agents 15. Kaufman HE, Capella JA. Preser ved corneal tissue for
transplantation. J Cryosurg 1968;1:125-9.
including bacteria, viruses and prions. Such tissue engineering
16. Facilities, Equipment and maintenance. Standards of Eye banking
techniques may also be able to modify the immune rejection in India 2009 by NPCB, DGHS, MOHFW, India 2009;1-2.
and wound healing responses of donor corneas, or indeed 17. Saini JS, Reddy MK, Jain AK, Ravindra MS, Jhaveria S, Raghuram
provide the ability for in vitro "growth" of the corneal L. Perspectives in eye banking. Indian J Ophthalmol 1996;44:47-
endothelium. Confocal microscopy could provide an additional 55.
means of evaluating the cornea prior to transplantation. 18. Lee PP, Yang JC, M Donnel PJ, et al. Worldwide legal requirements
Whatever the future holds, eye banks must continue to for obtaining corneas 1990. Cornea 1992;11:102-7.
19. Andersen KS, Fox KM. The impact of routine inquiry law on
provide a service that ensures the safety and efficacy of donor
organ donation. Health Att 1988;7:65-78.
tissue and ensures fair and equitable distribution of 20. Statement of the Minister of state of health and family Welfare,
transplantable tissue. This must be achieved at all times Dr. C. Silvera in Rajya Sabha dated 27th April, 1995. India.
maintaining the self-esteem and confidentiality of the donor, 21. Kalevar V. Eye banking in India. Indian J Ophthalmol
the dignity of the donor's family and the dignity of the 1989;37:110-1.
prospective recipient. 22. Pinto S. The Dawn of Eye Banking in India NPCB INDIA
Newsletter 2004;1(8).
REFERENCES 23. Atri AP. Human Organs Transplantation Act 1994 and its effect
on eye donation. Punarjyoti, News letter of Eye Bank Association
1. Zirm EK. (V. Graefe's Archiv Fur Ophthalmologie, 1906) Eine of India, February, 1995.
erfolgreiche totale keratoplastik (A successful total keratoplasty). 24. Griffith NF. The promise of 'international eye banking'.
Refractive and Corneal Surgery 1989;258-61. Ophthalmology 1990;14:205-10.
2. Filatov VP. Transplantation of cornea from preserved cadaver eyes. 25. Draft Notification regarding Transplantation of Human Organs
Lancet 1937;1:1395-7. Act, 1994.
3. Paton D. The founder of the first eye bank: R. Townley Paton, 26. Transplantation of Human Organs Rules amendment 2008.
MD. Refract Corneal Surg 1991;7:190-4. 27. Eye Bank Association of America, 1994 statistics, ARVO news
4. Brightbill FC (Ed). Corneal surgery. Theory, Technique and tissue. letter, summer 1995; 21.
2nd Edn. St. Louis 1993. 28. Jonesa G, Ponzina D, Pelsb E, Maasb H, Tulloc AB, Claerhoutd I.
5. McCarey BE, Kaufman HE: Improved corneal storage. Invest European Eye Bank Association In Eye Banking. Dev Ophthalmol
Opthalmol 1974;13:165-73. Basel, Karger 2009;43:15-21.
6. Kaufman HE, Varnell ED, Kaufman S, Beuerman RW, Barron 29. Pels L, Mass H, Tullo A. European eye bank association directory.
BA. K-Sol cor neal preser vation. Am J Ophthalmol 8th edn. Amsterdam: Netherlands Ophthalmic Research Institute
1985;100:299-300. 2000.
Chapter 7.1
INCISIONAL KERATOREFRACTIVE
SURGERY
Refractive errors occur when the light rays after refraction

through the optical media are not accurately focused on the
retina. The optical system of the eye can be considered a
combination of two-lens systems with an effective refractive
power of 64D.1 The cornea accounts for two-thirds of the
refractive power (42D) while the lens accounts for the rest.
In subjects with myopia, either the corneal curvature is too
steep or more often as is the case, there is an increase in the
axial length of the eyeball. This results in focusing of the
light rays after refraction in front of the retina. Refractive
errors for centuries have been corrected with either spectacles
or contact lenses. However, surgical corrections for refractive
error have come into vogue about four decades ago as many
patients desire clear vision without relying on optical devices.
In general, this can be achieved by techniques performed on
either one of the two refractive systems, the cornea or the
lens.2 Lens extraction with intraocular lens implantation is
one approach to correct significant refractive error. On the
other hand, since two-thirds of the refractive power lies with Figs 7.1.1A and B: Effect of radial incision on paracentral cornea
the cornea, alterations to the corneal curvature also can achieve
the same goal. Since the 1970s, till the advent of excimer
laser, one of the popular surgical procedures aimed at epikeratoplasty where a small donor cornea was reshaped
flattening the paracentral cornea for patients with low to and sutured to the anterior corneal surface within the
moderate myopia has been radial keratotomies.3 By making epithelium.6 The basic tenet underlying all these procedures
multiple radial incisions in the peripheral cornea, flattening is is to change the shape of the cornea to alter its optical
induced in the paraxial cornea to reduce the effective refractive property (Table 7.1.1). Similarly, incisional keratotomy can
power of the optical system (Figs 7.1.1A and B).2-4 Other also be done for the correction of astigmatism, where
methods to achieve the same goal is lamellar procedures, tangential or arcuate incisions (arcuate keratotomy) are placed
wherein removal or addition of tissues can be done to alter in the mid-peripheral cornea.7 This flattens the steeper
the anterior curvature of the cornea. Barraquer advocated meridian and steepens the axis 90 degrees away. However,
corneal reshaping or keratomileusis, wherein a small piece of with the advent of excimer laser in 1995 and the new era of
corneal tissue is removed thereby altering the corneal shape.5 refractive surgical procedures such as photorefractive
Werblin and Kaufman had a modified variation, keratotomy and LASIK where incisional refractive procedures
734 Refractive Surgery
Table 7.1.1: Incisional keratorefractive procedures for Likewise introduction of centrifugal incisions as against the
different types of refractive errors centripetal incisions proposed by the Russian studies have
Refractive error Surgical technique resulted in less postoperative complications.4
Myopia Radial keratotomy
Astigmatism Arcuate keratotomy Principles: Corneal Coupling
Transverse keratotomy Any surgical incision placed on the cornea, results in a change
Limbal relaxing incision of the corneal curvature. This induces a flattening in the axis
Postpenetrating keratoplasty Relaxing incisions of incision and steepening 90 degrees away depending on a
astigmatism
number of factors.7,15 Based on Gauss’s law for a perfectly
Wedge resection
elastic dome any change in one axis, results in an equal or
comparable change in the opposite axis. The degree of changes
have become less popular and are largely obsolete for that occur after an incision can be described as a coupling
refractive error correction in myopia.8 However, despite the ratio which is an important concept in refractive surgery.
advances made with LASIK and wave front technology, Coupling is the ratio of flattening or steepening that occurs
astigmatic keratotomy has an important role in the correction in the axis of incision to that at 90 degrees away. Although
of astigmatism following cataract surgery (limbal relaxing cornea is not a perfectly elastic sphere, the concept of coupling
incisions) and following penetrating keratoplasty (arcuate helps predict or calculate the magnitude of changes that occurs
keratotomy). after incisional keratotomies.16
Sphere from plus cylinder refraction
____________________________________________
RADIAL KERATOTOMY FOR Coupling ratio =
CORRECTION OF MYOPIA Sphere from minus cylinder refraction
For any incisional refractive surgical procedure, this ratio
History
serves as a guideline to the magnitude of the topographical
Schiotz first observed in 1885 that flattening of the cornea changes required at both axes to correct any refractive error.
occurred in the incised meridian.8 Studies from Dutch literature The sign of the ratio of the sphere indicates whether steepening
document the first studies on incisional keratotomy. In 1890, (plus sign) or flattening (minus sign) is required. For example,
Lans, the Dutch ophthalmologist, while working with rabbits a ratio of 2:1 indicates that correction of the refractive error
noticed flattening and induced astigmatism with partial requires a procedure that flattens or steepens twice the amount
thickness corneal incisions.9 In the 1940s, Sato, the Japanese induced in the axis 90 degrees away. In case of a negative
ophthalmologist used posterior corneal incisions in keratoconus sign of the sphere it indicates flattening is required and vice
patients to correct myopic astigmatism.10 Using a especially versa.7
designed knife he induced ruptures of Descemets membrane Different types of incisions produce unique coupling
to cause flattening. However his long-term results were not effects (Table 7.1.2). Radial incisions flatten the cornea along
good as most of his patients developed endothelial loss and the axis of incision and 90 degrees away.15 The coupling
late onset corneal edema.9 Further advancements were made ratio is 1:1 and if symmetrical does not cause astigmatism.
in the 1970s by the Russian ophthalmologists, Fyodorov and Tangential incisions flatten the axis of surgical incision and
Durnev who introduced the concept of non-perforating radial steepen the axis 90 degrees away.17 On the other hand, paired
incisions and optical zones for correction of myopia and transverse incisions produce a coupling ratio of 1:1 with
astigmatism.11 Considering the increased number of incisional flattening of the axis of incision and steepening 90 degrees
keratotomy procedures in the United States in the late 1970s, away without any change in the overall spherical equivalent.18
the National Institute of Health undertook the Prospective Circumferential incisions may result in more effect than linear
Evaluation of Radial Keratotomy study (PERK) for assessing tangential incisions and produce a 2:1 flattening-steepening
the safety, predictability and efficacy of radial keratotomy.12 coupling ratio. Radial and tangential incisions can be combined
Further refinements in instrumentation, nomograms and use to produce larger effect.16,19 In case of combining radial
of postoperative steroids have resulted in better surgical with tangential incisions, the steepening effect at 90 degrees
outcomes for patients with moderate myopia (less than 6.00D) can be uncoupled. In addition, depending on the optical zone
over the years.13 For reducing overcorrections and improving and length of the incisions, larger flattening-steepening effect
predictability, fewer incisions have been proposed (mini-RK).14 can be achieved.7 In trapezoidal procedures, two tangential
Incisional Keratorefractive Surgery 735
Table 7.1.2: Coupling ratios for different incisions complications. 23 The number of incisions also greatly
Incision type Coupling ratio influences the amount of refractive correction that is achieved.
Four incisions correct about 75 percent of the refractive
Radial 1:1 flat-flat
error, while with eight incisions, 90 percent of the target
Tangential 1:1 flat-steep
correction can be achieved. Other variable that affects the
Circumferential 2:1 flat-steep
amount of flattening is the age of the patient with greater
Radial and tangential 3:1 flat-flat
effect on older patients.22 Most nomograms account for about
incisions are combined with a radial incision to produce higher 0.5 to 1.00 D change with each decade.
coupling effect of upto 6:1.20 However these incisions are
Patient Selection
highly unpredictable and are no longer used in clinical practice.
Radial keratotomy is most effective and has predictable
Factors Affecting Outcome outcomes in patients with moderate myopia (less than
From all the clinical studies done to date, a number of factors 6.00D).23 As with any refractive surgical procedure, patients
affecting the surgical outcome have been established.3,4 These should have refractive stability (within 0.50D) for atleast the
include: previous two years.4 Corneal diseases including keratoconus,
i. Optical zone diameter peripheral corneal ectatic disorders, corneal scarring, and
ii. Number of incisions herpetic corneal diseases are contraindication for incisional
iii. Incision depth keratotomies.
iv. Amount of refractive error
v. Age of patient Surgical Techniques
Radial keratotomy is performed under topical anesthesia
Optical Zones using the standard operative sterile technique usually in the
The flattening effect of radial incisions on the cornea depends operative suite. An optical zone marker (3–5 mm) is used
on the relationship of the incisions to the visual axis.21 In to mark the optical zone based on the nomogram
general, incisions closer to the optical axis induce a greater recommendations. Ultrasonic pachymetry should be done
change in the net correction. In other words, the amount of to assess the corneal thickness in each quadrant. The patient
flattening depends on the diameter of the central, untreated is asked to fixate on the light of the surgical microscope
area, the optical zone. Smaller optical zones produce larger while a double pass diamond knife is used to create the
corrections and diameters more than 5 mm has minimal radial incisions. The diamond knife is usually set at 90 to
effect.22 Larger incisions induce larger amounts of flattening 100 percent of the thinnest paracentral pachymetry reading.
and correction of myopia upto 11 mm, beyond which the RK incisions, originally described and those in the PERK
effect reverses. Similarly with tangential incisions that are study were centripetal in nature and consisted of eight
closer to the visual axis, larger correction of myopia can be incisions.12 Refinements in surgical techniques has evolved
achieved. Usually optical zones less than 3 mm zones are since the PERK data were published.24 One such system is
associated with complications and are not advised. the Casebeer keratorefractive system where the surgeon
titrates the primary procedure with enhancements, depending
Centering on the initial results.25,26 Further modifications involved using
centrifugal incisions, which start from the central optical
Most surgeons place incisions based on the pupillary axis
zone to the periphery and then return back to the central
though there are surgeons who advocate the visual axis.
optical zone. Improvements in the diamond blade design
also prevented any accidental pass into the central optical
Incisions
zone. Another system that became popular was the mini-
Deeper incisions produce more flattening, but at the same RK wherein the incisions were carried out only upto a 7 mm
time can result in wound instability, unpredictable outcomes peripheral corneal zone.14 Different studies have confirmed
and carries the risk of perforation.22 Incisions in refractive that with mini-RK greater refractive stability could be
surgical procedures to achieve optimal effect should be 85 to achieved without any significant complications.14,26 The
90 percent deep for maximum flattening without any postoperative care, as with any other anterior segment
procedure include topical antibiotics, topical steroids and i. Measurement of corneal curvature with Placido based
cycloplegics. systems in smaller optical zones of post-RK corneas is
inaccurate;
Complications ii. Anterior and posterior corneal curvature are no longer
similar; and
Sight Threatening Complications iii. An underestimation of the anterior chamber depth in
Potentially fatal complications such as corneal perforation,27 post-RK corneas results in a hyperopic surprise if
infectious keratitis,28 endophthalmitis,29 incisions into the standard keratometry values are used for IOL power
corneal optical zone, retrobulbar hemorrhage,27 and traumatic calculation in these patients.
cataract,27 are rare with RK. Though traumatic rupture of
the globe has been reported as late as ten years after RK, it is Stability of Refraction and
fortunately rare. 30-32 Non-visual complications such as Refractive Changes
vascularization of the stromal scars, epithelial plug formation
and non-progressive endothelial disruption beneath the incision Diurnal Variation
are some of the complications that are commonly seen after
Fluctuation in vision due to refractive instability has been
incisional refractive surgeries.4
observed up to many years after radial keratotomy.13 Data
Visual Distortions from the PERK study showed that there was a small but
observable myopic shift of 0.31 ± 0.58D at ten years follow-
As with any refractive procedures, visual distortions and glare up and in general does not require multiple corrective lenses.24
are common postoperative complications with radial This has been attributed to changes in the corneal curvature
keratotomies. Generally, these are common with smaller optical due to local edema at the site of incisions during sleep with
zones (< than 3 mm) and associated with more than eight progressive steepening on waking up.
incisions. The incidence is highest during the first six months
after surgery, which reduces upto about four percent as the Hyperopic Shift
scar matures.33 Quality of vision is more impaired at low
illumination environmental conditions with subjective Progressive flattening is one of the well-known complications
complaints of starburst patterns and haloes due to light after radial keratotomy. The change is maximal between six
scattering effect. This is dependent on pupillary diameter and months to two years with the rate of change dropping there
can interfere with driving at night. after. In the PERK study 43 percent of the patients had
increase of at least +1.00 D or more at ten years follow-
Changes in Visual Acuity, Corneal up.24 The average rate was +0.21D per year during the first
Topography, Refraction and Problems two years, which fell down to +0.06D per year between two
in Calculation of IOL Power to ten years. Lessons from the PERK study also show that
hyperopic shift lessens with time and occurs with higher myopic
Radial keratotomy changes the corneal curvature resulting in corrections and with smaller optical zone diameters. However,
an oblate shape with central flattening and more steepening review of data from many studies in the post-PERK study
in the periphery. This results in a complex optical system with era with refinement in surgical techniques as well as
little correlation between keratometry, refraction and visual instrumentation shows that refractive instability and hyperopic
acuity. After undergoing RK, one to three percent of patients shift are no longer major concerns.13
report loss of one to two or more Snellen lines in their best-
corrected visual acuity.24,34 With the number of refractive Undercorrections and Overcorrections
surgeries on the rise every year, this also poses additional
challenges in calculating intraocular lens implant power in A number of studies have shown that undercorrections and
this population who need to undergo cataract surgery.35 Most overcorrections remains the most common obstacle to achieve
of the third generation lens formulas rely on the axial length surgical success in those undergoing incisional keratotomy.36,37
and keratometry for IOL power calculation. Determining In different series, this ranges from 3 to 17 percent and has
accurate keratometric power of the post-refractive surgery resulted in most surgeons preferring to undercorrect the
cornea is challenging due to a number of factors refractive error to account for the small hyperopic shift.4
Outcomes
Most literature on the surgical outcome of radial keratotomy
can be divided into the PERK and post-PERK eras for more
accurate comparisons as there have been many modifications
to the surgical techniques and nomograms after the PERK
study. The ten years follow-up results from the PERK study
showed that 70 percent did not need any optical correction.24
In addition, 53 percent patients achieved uncorrected visual
acuity of 20/20 and 85 percent patients had 20/40 or better
vision. In terms of predictability, 90 percent predictable
interval at four years follow-up was 4.42D, which is quite
high when compared with the results in the current excimer
laser era. In addition, as mentioned earlier, 43 percent patients
showed a hyperopic drift of 1.00D at the end of ten years
follow-up.8,24 In the post-PERK era, different studies that
used lesser number of incisions with refined nomograms have
showed much-improved outcomes with less unpredictability
as seen with the PERK trial.3,13 Using the Casebeer RK
nomogram, Werblin et al showed that out of 205 patients, 99
percent achieved uncorrected 20/40 or better visual acuity.38
Similarly in another series using mini-RK incisions (four
incisions), Lindstrom et al showed 98 percent patients
achieving 20/40 or better visual acuity in a series of 125
patients.14 Improved refractive stability, less hyperopic shift
and less overcorrection were noted in the four incision studies.
Though these studies are retrospective case series, all these
studies show remarkable similarity as regards stability of Fig. 7.1.2: Types of incisional keratotomy
results. for correction of astigmatism
INCISIONAL KERATOTOMY FOR

CORRECTION OF ASTIGMATISM Arcuate Keratotomy
For correction of astigmatism, several techniques have been
General Principles
popular including arcuate keratotomy, wherein arcuate or
tangential incisions are placed in the mid peripheral cornea at In arcuate keratotomy, incisions are placed in the steepest
the 7 mm optical zone (Fig. 7.1.2). Though unpredictable at meridian in a mid-peripheral optical zone. This flattens the
times, it has been shown to be effective and safe in reducing cornea at the site of incision and steepens 90 degrees away
clinically significant astigmatism. Alternatively, arcuate incisions without any change of spherical equivalent. These incisions
can be placed more peripherally at the limbus for correction are placed upto a depth of 95 percent of the paracentral
of astigmatism and this is typically combined with cataract corneal thickness at an ideal optical zone of 6 to 7 mm.15,39
surgery. The most popular techniques are the transverse or Incision length should not be longer than 3 mm or 120 degrees
arcuate keratotomies. As discussed earlier, transverse incisions of an arc. In general, higher correction of astigmatism can
produce a 1:1 flattening-steepening while arcuate incisions be achieved by smaller optical zones and longer, deeper or
produce more flattening in the axis of incision. Arcuate more number of incisions. Optical zones less than 5 mm are
keratotomy is more preferred as they have greater effect on associated with irregular astigmatism. Nomograms such as
astigmatism reduction due to uniform distance from the Lindstrom’s nomogram serve as guidelines to the number
optical center. and length of incisions.15,18
Instrumentation and Surgical Techniques is poor predictability with frequent under and overcorrec-
Different techniques have been described, though all of them tions.42 Factors that have attributed to poor predictability
share the same principle of placing the incision in the axis of include non-uniform depth of the incisions and lack of
steep meridian. 18,40 Using a surgical keratometer or a precision of the incisions. 43 Overcorrections are a real
topography unit to accurately decide the axis of the cylinder challenge and do require some form of surgical intervention.
is critical prior to the placement of incisions. Intra-operative Suture correction is usually recommended for over-
measurements of the cornea at the site of incisions as well as corrections after arcuate keratotomy and can achieve
the paracentral cornea should be done with an ultrasonic satisfactory results.44
pachymeter. Arcuate keratotomy marker such as Lindstrom
marker is typically used for placing the incisions. A high-quality Limbal Relaxing Incisions
micrometer knife that can be preset to different depths such, Limbal relaxing incisions (LRI) are simple effective ways of
as front-cutting diamond knife is by and large helpful for treating corneal astigmatism at the time of cataract surgery.
placing the incisions. Good visibility is essential for improving It has been well-known that placing cataract wound in the
the accuracy while placing arcuate incisions. Different axis of steeper meridian can reduce pre-existing astigmatism.
modifications are available including mechanical trephines However with the advent of newer techniques such as toric
(Hanna arcuate trephine) for placing more accurate and intraocular lenses, these surgical techniques have become less
smooth incisions at specified depths. popular than before. Similar to arcuate keratotomy, limbal
Under topical anesthesia, the patient is placed under the relaxing incisions also have a coupling ratio of 1:1 and the
surgical microscope and asked to fixate on the fixation target. spherical equivalent is unchanged. Usually, LRI are combined
The optical center is marked and the optical zone identified with phacoemulsification and intraocular lens implantation
for placing the relaxing arcuate incisions. The plus cylinder to correct preexisting corneal astigmatism.45 Curved incisions
axis of the manifest refraction is used to identify the steep are placed just anterior to the limbus and at lesser relative
axis. Based on the nomogram and corneal topography, the depth (around 600 microns, 50 microns lesser than the
magnitude of correction is adjusted. As mentioned earlier thinnest pachymetry) compared to arcuate keratotomy. As
prior to the incisions, corneal thickness at the optical zone is these incisions are further away from the visual axis, LRI
measured using intraoperative pachymetry to accurately preset correct less astigmatism as compared to the arcuate
90 percent incision depth. After the procedure, the incisions keratotomy. The instrumentation and surgical technique for
are irrigated with balanced salt solutions. Postoperative care LRI are similar in nature to that of AK. However most
includes topical antibiotics for a week. surgeons prefer back cutting diamond blades more often for
making the incisions. Sample normograms have been published
Clinical Outcomes which serve as a guide to the number and length of the
Arc-T study group results that evaluated arcuate keratotomy incision to achieve the desired degree of cylindrical
on naturally occurring astigmatism show various predictors correction.46 A number of studies have shown good clinical
that influence the outcome, including age, gender, length and outcomes for LRIs to correct astigmatism in patients
number of incisions.41 In 160 eyes of 95 patients with mean undergoing phacoemulsification. Carvalho et al showed in
preoperative astigmatism of 2.8 ± 1.2 D, there was mean 50 eyes of 37 patients, there was a significant reduction in
reduction of 1.6 ± 1.1D. In addition, single incisions were mean astigmatism from 1.93 ± 0.58 to 1.02 ± 0.60D at six
more likely to have no residual astigmatism and paired months postoperatively.45 In another series of 37 eyes of 26
incisions were more likely to have overcorrections. It was patients there was an absolute reduction of 1.72 ± 0.81D at
also noted that females were more likely to have one year follow-up.47 Common complications include under
undercorrection while males were more likely to have and over correction. Irregular astigmatism is less common
overcorrections. compared to AK.
Complications SURGICAL CORRECTION OF

REFRACTIVE ERRORS AFTER
Even though a safe procedure, rare complications that have
PENETRATING KERATOPLASTY
been reported include corneal perforation and infections.
Irregular astigmatism is more likely in cases where the optical High degree of refractive error and astigmatism forms one
zones are smaller. Another drawback with arcuate keratotomy of the major obstacles to visual rehabilitation after successful
penetrating keratoplasty.48 Surgical intervention is the only Wedge Resection

avenue if optical methods including contact lenses do not
For higher degrees of astigmatism in excess of 10D, crescentic
provide visual rehabilitation. In some instances, especially in
wedge resection is a more appropriate intervention for
the elderly population, contact lenses are poorly tolerated
refractive errors, though it is fraught with unpredictability
due to corneal surface irregularities and dry eyes.
compared to relaxing incisions. In addition it has 1:2 coupling
Some of the common surgical procedures employed
ratio (flattening/steepening) with a resultant increase in myopia
include relaxing incisions, wedge resection and arcuate
or decrease in hyperopia. Wedge resection is more invasive
keratotomy. With significant advances of excimer laser in
and requires adequate local anesthesia and akinesia. Corneal
refractive surgical procedures, photorefractive keratectomy
topography is required to identify the axis of steepening and
and LASIK has been more or less widely accepted for
ultrasonic pachymetry is performed to estimate the corneal
correction of myopia and astigmatism after corneal
thickness at the site of wedge resection. The wound at the
transplantation. Arcuate keratotomy as described earlier can
graft host junction is incised for 90 degrees and a wedge of
be performed for correction of corneal transplantation
tissues is removed by freehand dissection. About 0.1 mm of
associated astigmatism. This is usually performed on the donor
tissue removal corrects 1 to 2D of astigmatism approxi-
rather than the host tissues, so that the host tissues are not
mately.52 The wound is closed with multiple 10–0 nylon sutures
disturbed in case future transplantation is necessary.49 In
with tightness aimed at one-third to one-half overcorrection
general, in keratoplasty patients, any surgical corrections should
based on intraoperative keratoscopy. This procedure also
not be performed until all sutures are removed and refractive
requires longer post-operative visual rehabilitation period as
stability is observed.
well. Wedge resection can correct up to 20D of astigmatism,
but can be associated with irregular astigmatism from the
Relaxing Incisions multiple sutures.
Astigmatism is one of the most common refractive errors REFERENCES
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host junction can be performed that corrects 4 to 5D of 1. Katz M, Kruger PB. The human eye as an optical system. In:
Tasman W, Jaeger EA, eds. Duane’s Clinical Ophthalmology.
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you choose? I. Radial keratotomy will always have a place.
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7. Rowsey JJ, Fouraker BD. Corneal coupling principles. Int
performed in an operative suite under a surgical microscope. Ophthalmol Clin 1996;36(4):29-38.
However, larger incisions are associated with lesser 8. Choi DM, Thompson RW, Price FW. Incisional refractive surgery.
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Undercorrections are usually preferred than over-corrections. Astigmatismus durch nicht-perforirende corneawunden. Graefes
Arch Klin Exp Ophthalmol 1898;45:117-52.
Relaxing incision is combined with compression sutures placed
10. Sato T. Treatment of conical cornea (incision of Descemet’s
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Slight overcorrection of the astigmatism is usually aimed so 11. Fyodorov SN, Durnev W. Operation of dosaged dissection of
that postoperative suture removal can be done after titration corneal circular ligament in cases of myopia of mild degree. Ann
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12. Waring GO III, Moffitt SD, Gelender H, et al. Rationale for and 34. Spigelman AV, Williams PA, Lindstrom RL. Further studies of four
design of the National Eye Institute Prospective Evaluation of Radial incision radial keratotomy. Refract Corneal Surg 1989;5:292-5.
Keratotomy (PERK) Study. Ophthalmology 1983;90:40-58. 35. Hill WE, Byrne SE. Complex axial length measurements and
13. Shapiro DR. A comparison of modern incisional keratotomy and unusual IOL power calculations. Focal Points: Clinical modules
photorefractive keratectomy. Int Ophthalmol Clin 1997;37(1):65-81. for ophthalmologists. San Francisco: American Academy of
14. Lindstrom RL. Minimally invasive radial keratotomy: mini-RK. Ophthalmology; 2004, module 9.
J Cataract Refract Surg 1995;21:27-34. 36. Deitz MR, Sanders DR, Raanan MG. A consecutive series (1982–
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1983;90:148-55. Ophthalmol 1987;103:417-22.
16. Thornton SP. Astigmatic Keratotomy: a review of basic concepts 37. Damiano RE, Forstot SL. Extreme corneal flattening after radial
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38. Werblin TP, Stafford M. The Casebeer system for predictable
17. Bates WH. A suggestion of an operation to correct astigmatism.
keratorefractive surgery-one year evaluation of 205 consecutive
Arch Ophthalmol 1984;23:9-13.
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18. Lindstrom RL. The surgical correction of astigmatism: a clinician’s
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perspective. Refract Corneal Surg 1990;6:441-54.
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20. Ibrahim O, Hussein HA, El-Sahn MF, et al. Trapezoidal keratotomy naturally occurring astigmatism. J Cataract Refract Surg
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Ophthalmol 1991;109:1374-81. 41. Price FW, Grene RB, Marks RG, Gonzales JS, ARC-T. Study
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Ophthalmology 1993;100:1103-15. prospective evaluation of the predictability of arcuate keratotomy.
22. Salz JJ, Rowsey JJ, Caroline P, et al. A study of optical zone size Evolution of surgical nomogram predictability. Arch Ophthalmol
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Ophthalmol 1985;103:590-4. 42. Melles GRJ, Binder PS. A comparison of wound healing in sutured
23. Jester JV, Venet T, Lee J, et al. A statistical analysis of radial kerato- and unsutured corneal wounds. Arch Ophthalmol 1990;108:
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24. Waring GO III, Lynn MJ, Nizam A, et al. Results of the Prospective 43. Binder PS, Wasring GO. Keratotomy for astigmatisms. In:
evaluation of Radial keratotomy (PERK) study five years after Refractive keratotomy for myopia and astigmatism. Edited by
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25. Casebeer JC. The system. In: A systemized approach to 44. Alio JL, Ismail MM. Management of astigmatic keratotomy
keratorefractive surgery. Edited by Hanson GK, Boca Raton, FL. overcorrections by corneal sutures. J Cataract Refract Surg
Chiron Intraoptics 1993;3-21. 1994;20:13-7.
26. Jory W. The predictability and safety of 4-incision keratotomy for 45. Carvalho MJ, Suzuki SH, Freitas LL, et al. Limbal relaxing incisions
myopia and myopic astigmatism. Eur J Implant Refract Surg 1995; to correct corneal astigmatism during phacoemulsification. J Refract
7(1):17-9. Surg 2007;23(5):499-504.
27. Marmer RH. Radial keratotomy complications. Ann Ophthalmol 46. Wang L, Misra M, Koch DD. Peripheral corneal relaxing incisions
1987;19:409-11. combined with cataract surgery. J Cataract Refract Surg 2003;29:
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28. Beldavs RA, Al-Ghamdi S, Wilson LA, et al. Bilateral microbial
47. Bayramlar HH, Daglioglu MC, Borazan M. Limbal relaxing
keratitis after keratotomy. Arch Ophthalmol 1993;111:440.
incisions for primary mixed astigmatism and mixed astigmatism
29. Gelender H, Flynn HW, Mandelbaum SH. Bacterial endophthal-
after cataract surgery. J Cataract Refract Surg 2003;29(4):723-
mitis resulting from radial keratotomy. Am J Ophthalmol
8.
1982;93:323-6. 48. Binder PS. The effect of suture removal on postkeratoplasty
30. Bloom HR, Sands J, Schneider D. Corneal rupture from blunt astigmatism. Am J Ophthalmol 1988;105:637-45.
trauma 22 months after radial keratotomy. Refract Corneal Surg 49. Hardten DR, Lindstrom RL. Surgical correction of refractive
1990;6:197-9. errors after penetrating keratoplasty. Int Ophthalmol Clin
31. McDermott ML, Wilkinson WS, Tukel DB. Corneoscleral rupture 1997;37(1):1-35.
ten years after radial keratotomy. Am J Ophthalmol 1990;110: 50. Troutman RC, Swinger C. Relaxing incision for control of
575-7. postoperative astigmatism following keratoplasty. Ophthalmic
32. McNeill JL. Corneal incision dehiscence during penetrating Surg 1980;11:17.
keratoplasty nine years after radial keratotomy. J Cataract Refract 51. Krachmer JH, Ching STT. Relaxing corneal incisions for
Surg 1993;19:542-3. postkeratoplasty astigmatism. Int Ophthalmol Clin 1983;23:153.
33. Arrowsmith PN, Marks RG. Visual, refractive, and keratometric 52. Troutman RC. Corneal Wedge Resections and relaxing incisions
results of radial keratotomy: one year follow-up. Arch Ophthalmol for postkeratoplasty astigmatism. Int Ophthalmol Clin
1987;105:76-80. 1983;23:161-8.
Chapter 7.2
LASER REFRACTIVE SURGERY

AND PHAKIC IOLS
Mahipal Singh Sachdev, Charu Khurana, Hemlata Gupta
Refractive surgery has seen extensive advancements in An intensive examination is done to assess the status and
recent years and has evolved from a rudimentary science a suitability of the eye for any procedure and decide the best
few decades ago to an extremely sophisticated branch of technique possible to produce an optimum vision correction.
ophthalmology. Major innovations and breakthroughs have
PREOPERATIVE WORK-UP IN
helped make refractive surgery safe, precise, predictable
LASER REFRACTIVE SURGERY
and stable and improved not only vision but the quality of
life of millions of patients who have benefited from it. At The aims in preoperative evaluation include:
the same time, complications emphasize the need to exercise i. To assess the patient’s expectations
extreme caution and care, before advising any refractive ii. To generate specific refractive data for planning
procedure. A meticulous and methodical approach to pretreatment
operative evaluation, surgical techniques and follow-up is iii. To identify any risk factors involved in performing
required. refractive surgery in the patient.
Cornea is the chief refractive surface of the eye and is Patients are advised to discontinue wearing contact lenses
approximately 550 microns thick in the center and goes upto at least two to three weeks prior to preoperative evaluation.
Cycloplegic refraction is performed as part of the examination
approximately 700 microns in the periphery with an average
and hence patients are precounseled about inablility to read
power of +44 D. It is composed of five layers, epithelium
for 6 to 12 hours and advised against driving during this time
(which is made up of basal columnar cells, wing cells and
period.
surface cells), Bowman’s membrane (which is not a true
A detailed history is very important for proper patient
membrane but a condensation of the superficial stroma),
selection.
stroma which constitutes 90 percent of corneal thickness,
Descemet’s membrane (which is a true membrane), and Assessment of the Patient
endothelium.1 • Patients younger than 18 years of age, and female patients
Laser refractive surgery essentially consists of a spectrum who are pregnant or breastfeeding should not undergo
of procedures aimed at modifying the refractive power of refractive surgery.
the eye by changing the corneal curvature using lasers (PRK, • Patients involved in contact sports involving blows to the
LASIK, LASEK), incisions (RK, AK), intracorneal insertion face and eyes such as boxing and wrestling, or in
of rings, gels and changing the lenticular power using phakic occupations prone to a higher likelihood of trauma and
lenses in the anterior or posterior chamber and clear lens injuries such as the armed forces, may have refractive
extraction for high myopia. A combination of techniques surgery but it is better to offer procedures such as PRK
maybe used to correct higher refractive errors such as phakic or LASEK as alternatives to LASIK.
IOL implantation along with LASIK. This is broadly termed • It is wise to advise all patients to check the qualifying
as bioptics. refractive criteria as features such as contrast sensitivity
testing and glare disability measurement might be required, due to spasm of accommodation and latent hyperopia. The
which may be affected by refractive surgery procedures. extent of myopia and astigmatism determine the choice of
• It is good to assess the expectations of the patient before excimer laser as well as whether wavefront-guided surgery is
performing any refractive procedure. an option. In patients who have high astigmatism, axis
alignment during surgery is an important issue. A five degree
History axis misalignment results in 17 percent less effect in
astigmatism reduction. If the axis is misaligned by 30 degrees,
Contraindication to refractive surgery include patients with
there is no reduction in the magnitude of the cylinder.1
history of herpetic keratitis, keratoconus patients, and patients
on isotretinoin therapy. Relative contraindication for refractive Pupil measurements: The pupil size is measured under low
surgery includes patients with glaucoma, glaucoma suspects, light (mesopic) conditions (less than 5 lux) and may be
ocular hypertension, uveitis, and those with history of previous performed using a Rosenbaum card or a infrared
incisional keratotomy. Systemic conditions, such as pupillometer such as the Colvard Pupillometer (Oasis,
autoimmune diseases (e.g. lupus, rheumatoid arthritis), Glendora, CA). Most wavefront sensing devices measure pupil
immunodeficiency states (e.g. HIV) and diabetes prevent diameters along with aberrations to plan customized ablation
proper healing after a refractive procedure and are therefore profiles (Fig. 7.2.1). In a pupil less than 3 mm in size, high
also considered relative contraindications. If the patient has order aberrations (HOA) are greatly reduced. In eyes with
a history of keloid formation, then PRK or LASEK is to be larger pupils and dimlight conditions such as night driving,
avoided. It is also wise to avoid refractive surgery in a patient HOA may become significant. Customized ablations reduce
with cataractous lens. Patients with unstable refractive error the incidence of HOA. The average mesopic pupil diameter
are not suitable candidates for refractive surgery and it is has been reported to range from 4.0 to 8.0 mm. A proper
required that the patient’s refraction be stable for at least one preoperative pupil size assessment and analysis of the planned
year. refractive correction is useful in identifying patients at risk
of developing glare and halos after photoastigmatic refractive
Ocular Evaluation keratectomy (PARK). Larger diameter ablation zones reduce
A complete ophthalmic examination is performed. This the incidence of glare in patients with large pupils but this
includes: needs to be balanced by increased ablation depth for larger
• Examination of the ocular adnexa diameter treatments. A dark-adapted pupil diameter of more
• Visual acuity than 6 mm is a large pupil for a 6 mm diameter LASIK or
• Manifest and Cycloplegic refraction assessment PRK treatment as it allows light from the untreated cornea
• Anterior segment slit lamp examination
• Quantitative and qualitative evaluations of lacrimal
function
• Contact lens history
• Evaluation of blink reflex
• Dilated fundus examination
• Intraocular pressure
• Computerized corneal topography
• Biometry
• Pupil diameter
• Pachymetry
• Determination of the dominant eye
• Wavefront measurements.
Visual acuity and refraction: This includes recording
uncorrected Snellen visual acuity, visual acuity with present
glasses, dry manifest refraction and wet manifest refraction
(after cycloplegia with 1% cyclopentolate eye drops). Fig. 7.2.1: Pupil measurements using a wavefront analysis.
Cycloplegic refraction is important to unravel pseudomyopia Note elliptical shape of pupil (7.1 x 6.6 mm)
Laser Refractive Surgery and Phakic IOLs 743
beyond the 6 mm diameter treatment zone to create glare or efficient and accurate way to measure corneal thickness. Its
a halo effect around the viewed image. In patients with high accuracy and reproducibility is influenced by the
astigmatism and high preoperative refractive errors, the minor perpendicularity of the probe’s application to the cornea and
axis of the elliptical astigmatic treatment is smaller than the probe placement on the corneal center. It may be difficult to
ablation diameter.2 Pupil diameters more than 6 mm are usually accurately locate the same point of measurement in serial
associated with greater night vision problems and halos and examinations. Its disadvantages include:
though not a contraindication to surgery, may need • Need to use anesthetic
modification of the surgical plan. Correlation between • Contact method, may cause spread of infection or
preoperative pupil sizes and the long-term persistence of epithelial abrasion
symptoms of glare and halos is controversial and for mild to • Differences in pressure applied during measurement
moderate myopia with low astigmatism, large mesopic pupils • Lack of precision.
have not been found to be predictive of glare and halo after Optical pachymetry is considered more useful as it produces
LASIK treatment.3 detailed thickness maps at multiple locations on the cornea
The intraocular pressure (IOP) is measured using giving the exact position on the cornea using a co-ordinate
applanation tonometry (Goldmann tonometer or Pneumo- system.7 Peripheral corneal measurements and early changes
tonometer). There are several sources of error in applanation as in forme fruste keratoconus are better identified on these
tonometry, including central thickness and structural rigidity maps. The Pentacam also gives a relative pachymetry map which
of the cornea. Central thickness is related to the corneal gives a comparative difference from a normal eye pachymetry
rigidity and influences the force required to flatten the map with the thinnest point being normalized to zero.
applanated area. The Orbscan II corneal topography system (Bausch &
Lomb) provides topographic analysis and pachymetric
Relevance of IOP measurements in patients of refractive measurements of the cornea. Scanning-slit topography requires
surgery: Goldmann applanation tonometry overestimates IOP the patient to fixate for 1.0 to 1.5 seconds. The SP-2000P
in patients with thicker corneas and underestimates it in those specular microscope (Topcon Corp.) is a noncontact optical
with thinner corneas. Postoperative IOP measurements after instrument that provides pachymetric measurements and
corneal refractive surgery for myopia as well as hyperopia specular microscopy simultaneously. The central corneal
are reduced.4 The reduced IOP after excimer laser refractive thickness measurements are higher with Orbscan than with
surgery is considered to be due to false low IOP reading by ultrasonic pachymetry due to the differences between their
Goldmann applanation tonometry due to thinner post methodologies. As the Orbscan system measures the hydrated
operative cornea rather than a real decrease in IOP. In contrast mucous component of the tear film over the cornea, its readings
to Goldmann applanation tonometry, pneumotonometry is are higher than ultrasonic readings and require the use of the
said to measure IOP more reliably after laser in situ acoustic equivalent correction factor (0.92).8 If the cornea is
keratomileusis.5 Corneal ablation of approximately 90 microns unusually thick (>600 microns) or thin (less than 500 microns)
reduces Goldmann applanation tonometry readings by 3.0 as measured with ultrasonic pachymetry, then an Orbscan could
mm Hg after LASIK surg ery. This decrease equals be performed to confirm the measurements. The safety goal
approximately 0.2 mm Hg/10 µm of stromal ablation.6 Mild in LASIK procedure is to aim to have a residual corneal bed
to moderate myopic treatments of LASIK do not tend to of at least 250 microns. If the cornea is thin (less than 500
influence IOP measurement by Goldmann applanation microns), then PRK or LASEK may be preferable to LASIK.
tonometry. However, in patients with high myopia who The actual flap thickness after a microkeratome cut may vary,
undergo LASIK, nomogram adjustment or the use of a and an intraoperative pachymetry after the corneal flap is
constant correction factor may be required to calculate true fashioned, may be considered to provide a better estimate of
IOP after refractive corneal surgery. False low IOP readings the treatment ablation depth.
have the risk of delaying the diagnosis of future glaucoma in Leung et al found that scanning slit topography tends to
patients who undergo refractive surgery. This is of particular underestimate corneal thickness in corneas measuring less
importance to recognize glaucoma early especially in glaucoma than 500 µm and over-estimate it in corneas more than
suspects and in steroid responders. 500 µm in thickness. 9 Most studies have found a good
Corneal thickness measurements or pachymetry is correlation between pachymetry values as measured with
crucial for refractive surgery planning and is commonly done Pentacam scheimpflug imaging, optical coherence tomography
using ultrasonic pachymetry. Ultrasonic pachymetry is an and ultrasonic pachymetry.10
Specular microscopy: This may be performed to assess the • Three dimensional topography (Astramax, LaserSight
endothelial cell morphology and density in patients who have Technologies Inc., Winter Park, Florida)
a thick cornea (>600 microns) to rule out Fuchs corneal • Slit scanning (Orbscan, Bausch and Lomb, Rochester, New
endothelial dystrophy. York)
• Scheimpflug imaging (Pentacam, Oculus Inc, Dutenhofen,
Ocular dominance: This is tested in patients undergoing
Germany)
monovision refractive surgery. It can be tested using sighting
• Very high frequency (VHF) ultrasound (Artemis, Ultralink
tests, e.g. hole in the card test, sensory tests (binocular rivalry
LLC, St Petersburg, Florida)
tests) or by assessing asymmetry in visual acuity and contrast
• High speed anterior segment optical coherence
sensitivity. Eye dominance is determined by the hole-in-the-
tomography (Visante, Carl Zeiss Meditech, Jena,
card test or by viewing a distant object through a gap between
Germany).
the outstretched hands. In patients undergoing monovision
Standard keratometry measures the corneal curvature
refractive surgery, the dominant eye is corrected for distance
on two principal meridians at points 3 and 4 mm apart at the
vision, and the non-dominant eye undercorrected to less than
center of the cornea and assumes that the remainder of the
2 diopters of myopia for near vision.
central and peripheral cornea is a perfect spherocylindrical.
Slit lamp examination: Evaluation of the anterior and However as corneal irregularities increase, these two
posterior segments of the eye is performed. Specifically, the measurements do not suffice. In such cases placido disc
presence of blepharitis/meibomitis is noted and treated prior measurement of the corneal surface helps to highlight the
to surgery to decrease the risks of infection and interface irregularities in shape.11 The placido disc mires appear widely
inflammation following surgery. The presence of superficial separated in flat areas while steeper portions show closely
punctate keratitis may be due to dry eyes. A Schirmer test is placed mires. Topographers use computerized keratoscopic
performed and patient counseling that refractive surgery may imaging to digitally reconstruct the corneal surface and
worsen the dry eye disease is to be done. A punctal plug may represent it as a color coded map. As a general rule, cooler
be placed prior to or immediately after surgery. Corneal colors such as blue represent flat areas while warm colors
epithelial basement membrane dystrophic changes increase such as red indicate steep areas. These maps portray not only
the risk of epithelial problems later and may be an indication the central region of the cornea but also the peripheral and
for PRK rather than LASIK. Clinical signs of keratoconus mid-peripheral areas where surface abnormalities may lie.
are to be looked for. The Massachusetts Eye and Ear Computerized corneal topography examination is an
Infirmary method of keratoconus classification is a useful important part of the preoperative evaluation. Corneal
method to detect keratoconus suspects. tomography (Fig. 7.2.2) is creation of three-dimensional images
from two-dimensional cross sections. The Orbscan II is a
Dilated fundus examination: This is performed by slit lamp
hybrid system which combines a projective slit scanning device
biomicroscopy to examine the central fundus and indirect
with a reflective placido technique. 12 The images are
ophthalmoscopy for the retinal periphery. If peripheral retinal
represented as color maps including a curvature map, anterior
degenerations such as lattice degeneration or atrophic retinal
and posterior elevation map and pachymetric map. Though
holes are present, retina consultation and prophylactic laser
Orbscan has been found to be accurate for corneal
may be sought.
topography in normal population, myopes and keratoconus
patients, its posterior elevation data is unreliable in patients
Corneal Topography
after refractive surgery. This is possibly related to loss of
Accurate mapping of the corneal structure, contour, surface transparency and increased scattering of light by edema.
and thickness has become increasingly important as refractive This helps to detect and differentiate irregular astigmatism,
procedures are gaining popularity for elective vision correction. due to contact lens warpage or other causes as conditions
Advancements in technology have enabled further progress with irregular astigmatism are a contraindication to LASIK.
beyond traditional keratometry by use of sophisticated imaging The average Sim K is noted and the central keratometry
systems which analyze multiple data points at both the anterior number is used to choose the diameter of the flap cut
and posterior surface of the cornea. The commonly used (9.5 mm if 41 D or less and 8.5 mm if 48 D or more). Flat
corneal topography systems include: corneas are associated with small microkeratome flaps and
free caps, and steep corneas are associated with flap anterior segment of the eye within two seconds (Fig. 7.2.3).
buttonholes. Central keratometry flatter than 35 or 36 D or Topography and pachymetry of the entire anterior and
steeper than 50 D after LASIK is associated with a decrease posterior surface of the cornea from limbus to limbus is
in quality of vision.13 Corneal topography is used to detect calculated and displayed (Fig. 7.2.4). Along with this, it measures
keratoconus and other ectasias to identify asymmetrical the anterior chamber angle, depth and volume. It also images
steepening, higher anterior and posterior elevation, who are the iris, anterior and posterior surface of the lens and
potentially at high risk for developing ectasia after LASIK. quantifies the lens densitometry.
Inferior corneal steepening, in forme fruste keratoconus, is a Posterior elevation mapping has been found to be more
topographical finding in corneas that appear normal on slit- accurate with Pentacam than with Orbscan as the Pentacam
lamp biomicroscopy. Mathematical indices to detect subtle views the cornea directly. In evaluation of keratoconus, the
keratoconus topographically have been developed. If the anterior elevation map differences between the best fit sphere
inferior-superior (I-S) value is more than 1.4, keratoconus is (BFS) and the corneal contour are studied:
to be suspected and ruled out. Inferior steepening may also • Less than +12 µm are considered normal
be due to contact lens warpage, a repeat topography is • Between +12 µm and +15 µm are suspicious
advisable after two weeks of discontinued contact lens wear. • More than +15 µm are typically indicative of keratoconus
Contact lens warpage induced steepening will decrease on Similar numbers about 5 µm higher apply to the posterior
repeat topography after discontinuation of contact lens wear. elevation maps. These are especially useful for LASIK/PRK
Wavefront analysis is performed to determine the extent of screening and to detect post surgery ectasia.
higher order aberrations and the data is used to perform The Pentacam also allows calculation of ‘Equivalent K-
wavefront-guided LASIK or PRK. Readings’ based on the “Holladay Report” to improve the
The Pentacam (Fig. 7.2.2) uses rotating Scheimpflug calculation of IOL power for patients who have undergone
imaging technology to generate a complete image of the prior refractive surgery. Normal keratometry measurement
Fig. 7.2.2: Corneal tomography image obtained with a pentacam 3D reconstruction of the anterior segment of the eye with red and green
denoting the anterior and posterior corneal surface, blue depicting the iris tissue and the lens shown in yellow
Fig. 7.2.3: Schiempflug image obtained with a pentacam. The lens densitometry is shown on the right
Fig. 7.2.4: Pentacam generated image of the corneal topography showing 4 refractive maps (clockwise from top left) the sagittal curvature, the
front elevation, the back elevation and corneal thickness maps. The data on the left provides information regarding the keratometry and
astigmatism and corneal thickness at the center of the pupil and the thinnest pachymetry values
in post-refractive surgery patients leads to erroneous IOL

calculation due to:
• Following myopic LASIK, overestimation of keratometry
reading causes under-estimation of IOL power resulting
in a hyperopic outcome
• Following hyperopic LASIK, underestimation of kerato-
metry reading causes overestimation of IOL power
resulting in myopic outcome.
This happens because most keratometers measure four
paracentral points on the corneal surface ignoring adjacent
steeper or flatter areas which have been modified by ablation Fig. 7.2.5: Effect of aberrations on the image produced in the eye
during refractive surgery. Also most keratometers are
calibrated for a corneal index of 1.3375 which assumes that system (Snell’s law) and what is actually achieved (Fig. 7.2.5).
the corneal thickness and the relationship between the anterior These differences vary from simple defocus to highly
and posterior corneal surface is constant. None of these may aberrated wavefronts. The Dutch mathematician and
be true following excimer ablation leading to inaccurate astronomer, Frits Zernike described these aberrations first
calculation. Methods which may be used to calculate the IOL using mathematical models known as Zernike’s polynomials
power after refractive surgery include: to explain the wavefront measurements of the eye (Fig. 7.2.6).
• Clinical history method The shape of the wavefront is described in the x, y and z
• Contact lens over refraction coordinates (Fig. 7.2.7). The final figure is obtained from the
• Vertexed IOL power method sum of the Zernike polynomials describing all types of
• Double keratometry adjustment deformation (Fig. 7.2.8).16 The French mathematician and
• Intraoperative autorefraction physicist Jean Baptise Fourier used sine waves to describe
• Effective refractive power calculation using the Holladay the wavefront pattern. By adding sine waves of appropriate
Diagnostic Summary. amplitude and frequency, the exact wavefront analysis is
obtained to identify and measure imperfections of the eye
Optical coherence tomography is an optical method of cross- and treat them accordingly (Fig. 7.2.9). Hartmann-Shack
sectional scanning based on reflection and scattering of light pattern is used to identify 255 spots and a wavefront map is
from structures within the cornea achieving an axial resolution obtained (Fig. 7.2.10).
of 3 to 20 µm using a non-contact technique.14 It allows a Aberrations can be divided into two groups, chromatic
precise calculation of thickness of the different corneal layers and monochromatic. Chromatic aberrations are caused by
and is especially useful in measuring LASIK flaps, corneal the difference in distribution of incident polychromatic
epithelium, intracorneal ring segments, etc. radiation throughout a medium and depends on the wavelength
Ultrasound biomicroscopy allows measurement of individual of the light that penetrates the eye. This type of aberration
corneal layers including the epithelium, corneal flaps, stroma cannot be corrected, because it depends on the composition
and can be used as a guide for free cap replacement according of the ocular structures and not their shape. Monochromatic
to the pattern of flap irregularities.15 VHF (Very High aberrations are related to a specific wavelength and include
Frequency) ultrasound scans a series of meridians in an arc spherical refractive error (defocus), cylindrical refractive
motion matched to the curvature of the cornea. errors (astigmatism), and high-order aberrations (HOA) such
as spherical aberrations and coma.
Corneal Wavefront Aberrometry Optical aberrations produced by each person’s eye are as
distinct as each person’s fingerprint. They have been classified
Refractive errors are traditionally described as a spherical as below:
error (plus or minus) with or without astigmatism. Optical Low-order aberrations include the following:
defects which significantly affect the retinal image quality • Order-zero (no order): These aberrations are characterized
beyond the spherical and cylindrical component are called by axial symmetry and a flat wavefront
aberration derived from the Latin word ‘ab-erratio’ which • First-order: These linear aberrations correspond to tilting
means going off-track or deviating. Aberration is the difference around a horizontal (x) or vertical (y) axis. They describe
that exists between an ideal image formed in a perfect optical the tilt or prismatic error of the eye
Fig. 7.2.6: Zernike’s polynomials to show various aberrations
Fig. 7.2.8: Comparison of Zernike’s analysis and Fourier analysis
• Second-order: Spherical defocus and astigmatism describe

Fig. 7.2.7: A wavefront pattern described in x, y and z co-ordinates
showing how light is moving through the visual system. The colors the spherical error and astigmatic component and its
indicate how light is progressing with areas moving ahead ‘faster’ are orientation or axis. These components are similar to
shown in red and ‘slower’ areas shown in blue. A perfect wavefront measurements found with basic refraction.
with no visual defects would appear green High-order aberrations are as follows:
Fig. 7.2.9: A Hartmann-Shack analysis of the wavefront pattern Fig. 7.2.10: Hartmann-Shack wavefront sensor
• Third-order aberrations correspond to horizontal and lens and a video recorder registers the deformation of the
vertical coma and triangular astigmatism with the base reflected pattern, analyzes it, and returns the image to a
along the x- or y-axis (trefoil) reticulum.20 Analyzing the image and comparing the aberrated
• Fourth-order aberrations include spherical aberration, retinal grid pattern with the ideal grid positioning quantifies
tetrafoil, and secondary astigmatism the optical aberrations at the level of the entrance of the
• Fifth-tenth order aberrations are important only when the pupil. The distortion of the grid pattern enables calculation
pupil is greatly dilated. of the aberrations of the optical system of the eye.
Tracey System
Wavefront Devices
This device measures an ingoing light that passes through the
The wavefront device or aberrometer is the instrument used optical system of the eye and forms an image on the retina,
to study the refractive errors and total aberrations of the measuring one ray at a time in the entrance pupil rather than
eye. The analysis of the emerging wavefront can be based on measuring all of the rays at the same time.21 This design
different principles and may be done using the Hartmann decreases the chance of crossing the rays in highly aberrated
Shack wavefront sensing device, Tscherning aberroscopy, eyes with a total scanning time of 10 to 40 ms. It processes a
optical path difference scan and ray tracing refractometry. complete refractive map of the eye and a distortion map of
the wavefront.
Hartmann-Shack System
Scanning System or Optical
Hartmann-Shack aberrometer uses a laser light source to Path Difference Scans
measure and visualize ocular aberrations. The light reflected
by the retina is divided into several light points by a lenslet This system scans a large number of points and examines
the relationship between the light source and the reflected
array.17–19 The location of each spot is captured by the video
component. 22 This diagnostic instrument combines
sensor and compared with its theoretical location in an
autorefractometry, corneal topography, and analysis of the
aberration-free system. The combined relative offsets of the
wavefront to create a single map of the corneal surface’s
points provide a wavefront aberration map (Fig. 7.2.10).
refractive power. After analysis, all the systems produce
aberrometric maps or topographical maps which describe
Tscherning System
the difference in microns between a light wavefront and a
The Tscherning system uses a frequency-doubled neodymium: reference wavefront.
yttrium-aluminum-garnet (Nd:YAG) laser emitting light at Wavefront images can be used for diagnostic and
532 nm. The incident light beam passes through a perforated therapeutic reasons:
• They are used to localize aberrations conditions of luminance and glare, it denotes the relationship
• They are used to measure all aberrations of the eye between the optical efficiency of the eye and the minimum
including 2nd order (sphere and cylinder), 3rd order (coma retinal threshold for pattern detection. Spherical and
like), 4th order (spherical aberrations) and others cylindrical refractive errors as well as higher order optical
• Combined with corneal topography systems, they are used aberrations such as spherical aberrations and coma have an
to plan customized ablations. Clinically, correction of the impact on the contrast sensitivity function of the eye.25
spherocylindrical error alone in some eyes is insufficient Wavefront guided ablations provide greater contrast sensitivity
to produce an optimal result, because some of the than standard lasik.26,27
aberrations present can cause irregular astigmatism. The
integration of the wavefront analysis and corneal Glare Acuity Testing
topography with the laser treatment plan helps to perform
Glare can be defined as the contrast lowering effect of stray
an ideal ablation which can treat almost all significant
light in a visual scene. Glare is a visual condition in which the
aberrations of the eye.
observer feels either discomfort and/or exhibits a lower
Summary: Wavefront technology allows measurement of the performance in visual tests (e.g. visual acuity or contrast
sphere, cylinder, and axis of a patient and HOA such as sensitivity). This occurs when a relatively bright source of
coma and spherical aberration. The aberrations measured light (called the glare source) is placed within the visual field.
are not just corneal but aberrations of the entire optical system. Measurement of visual function in the clinic or the laboratory
Treating these aberrations with personalized laser ablation is usually performed under ideal conditions of daytime
plans helps to provide better quality vision. (photopic) lighting and the absence of extraneous light sources.
Recommended lighting for acuity testing is in the order of
Corneal Hysteresis 160 cd/m2.
Hysteresis is a term coined by Sir James A Ewing in 1890
Types of Glare
denoting a property of physical systems to react slowly to the
forces applied to them. Corneal hysteresis is the ‘energy Direct glare: Glare produced by a source of light situated in
absorption capability’ of the cornea and is a measure of the the same or nearly the same direction as the object of fixation
viscous damping of the corneal tissue. The Corneal Response Disability glare: Glare which reduces visual performance
Analyzer from Reichert utilizes a rapid air impulse and an without necessarily causing discomfort. Disability glare refers
advanced electro-optical system to measure two applanation to reduced visibility of a target due to the presence of a light
pressure measurements, one while the cornea moves inwards source elsewhere in the field. It occurs when light from a
and the other as the cornea returns. 23,24 Due to its glare source is scattered by the ocular media. This scattered
biomechanical properties, the cornea resists the dynamic air light forms a veil of luminance which reduces the contrast
puff causing delay in inward and outward applanation events and thus the visibility of the target
resulting in two different pressure values. The difference
between these two pressure values is Corneal Hysteresis (CH). Discomfort glare: Glare which produces discomfort without
Measuring the corneal hysteresis has helped clinicians study necessarily interfering with visual performance. Discomfort
the biomechanical properties of the cornea. Low CH means glare refers to the sensation one experiences when the overall
that the cornea is less capable of absorbing the energy of the illumination is too bright (e.g. on a snow field under bright
air pulse and normal eyes exhibiting significantly lower CH sun.)
values maybe at risk for developing corneal disorders in the Indirect glare: Glare produced by an intense light source
future. Such people may be more at greater risk for situated in a direction other than that of the object of fixation.
developing post-LASIK ectasia. As such, preoperative Glare tester is an instrument for measuring the effect of
estimation of the CH has not yet become universal but may glare on visual performance. These include instruments such
soon be incorporated in LASIK work-up schedules as its utility as the Brightness Acuity Tester (BAT), Miller-Nadler Glare
becomes clearly identified. Tester, and Optec 1500 Glare Tester. The Miller-Nadler Glare
Tester consists of a glare source surrounding a Landolt C.
Contrast Sensitivity
The instrument contains 19 black Landolt C, all of the same
Contrast sensitivity testing is an important estimate of the size, 6/120 (or 20/400). Each Landolt C is presented in one
complete visual system function. Measured under varying of four orientations and from the highest to the lowest contrast
at which the subject can no longer judge in which direction patients who have –1.00 D to –3.00 D of myopia with 1.00
the letter appears. The contrast threshold is expressed in D or less of astigmatism, patients with keratoconus and in
percentage disability glare. those with keratectasia. Intacs inserts are two tiny inserts made
of polymethylmethacrylate (PMMA) with an arc length of
Brightness acuity tester (BAT) is used to test glare disability.
150 degrees. The degree of myopic correction is determined
The Brightness Acuity Tester can simulate three bright light
by the thickness of the Intacs inserts; thicker the Intacs inserts,
conditions: (1) Direct overhead sunlight; (2) Partly cloudy
greater the amount of correction achieved. Intacs inserts
day; (3) Bright overhead commercial lighting. Visual acuity
can be removed or replaced. Corneal flattening in the meridian
is measured using the low, medium or high light settings of
of the corneal incision may sometimes occur with Intacs,
the BAT. Brightness Acuity Tester (BAT) is a standardized
resulting in ‘against-the-rule’ astigmatic shift. Intacs have been
glare source of light. It is presented in a hemisphere held
used in patient with corneal ectasias. Excimer laser refractive
over one eye. The light source can subtend a visual angle
surgery procedures (LASIK and PRK) are not used in treating
of 8 to 70 degrees at a vertex distance of 12 mm. The
keratoconus patients because of poor refractive predictability
patient is asked to read a visual acuity chart through a small
and poor stability. Intacs may benefit patients with keratoconus
aperture in the hemisphere. The chart can be a low-contrast
as it does not weaken the central and paracentral cornea. It
or high-contrast logMAR visual acuity chart or for example,
causes changes in the shape and power of the central cornea
the Pelli-Robson contrast sensitivity chart.
by an arc-shortening effect. Asymmetric Intacs implantation
The vast majority of LASIK patients experience at least
can improve both uncorrected and best spectacle-corrected
some temporary glare and halos during the immediate
visual acuity and reduce irregular astigmatism in keratoconus.
recovery. This can last for weeks and is due to corneal swelling
In keratoconus, unlike in the standard myopic technique, a
and reorganization of the corneal architecture. Patients in
thicker ring segment is placed inferiorly, and a thinner segment
the healing phase need to understand that this is normal and
is placed superiorly to preferentially flatten the inferior cornea.
different from the persistent variety of night vision problems.
Intacs may also be used to alter the biomechanical properties
The definitions, differences, and methods of measurement
of the cornea for the correction of iatrogenic keratectasia
of such vision disturbances after refractive surgery are
after LASIK for myopia.
described in our article. In most cases of corneal refractive
Laser thermal keratoplasty is a thermal technique to shrink
surgery, there is a significant increase in vision disturbances
peripheral corneal collagen and thereby steepen the central
immediately following the procedure. The majority of patients
cornea. LTK may be performed in patients with +0.75 to
improve between six months and one year post-surgery.28
+2.50 diopters of hyperopia with not more than 1.0 diopters
of astigmatism. The Hyperion LTK system (Sunrise
CHOICE OF REFRACTIVE
Technologies International, Inc., Fremont, CA) is a
SURGICAL PROCEDURE holmium:YAG laser. Two concentric rings of eight spots of
The majority of refractive surgery procedures that are laser energy is applied to the periphery of the cornea to
performed for refractive correction of myopia and hyperopia gently heat the corneal collagen and steepen its shape. The
include: Laser In Situ Keratomileusis (LASIK), Photo- hyperion delivers eight simultaneous spots (0.6 mm) on the
refractive Keratectomy (PRK), Photoastigmatic Keratectomy cornea in a circular pattern; one ring at 6 mm diameter and
(PARK) and Laser Epithelial Keratomileusis (LASEK). (These one ring at 7 mm diameter for a total of 16 spots. LTK has
procedures are discussed in details in the subsequent section been reported to provide predictable refractive outcomes
and in the Lasers in Ophthalmology chapters). for low hyperopia with tendency for regression.
Incisional refractive surgical procedures, radial keratotomy The principle of Conductive keratoplasty (CK) (Refractec,
(RK) and astigmatic keratotomy (AK), are associated with Inc. Irvine, CA) is based on that of thermokeratoplasty, using
progressive hyperopic shift and structural weakening of the radiofrequency (RF) energy to reshape the cornea and modify
cornea. its refractive characteristics.29,30 CK may be performed for
Other refractive surgery procedures include intracorneal low to moderate hyperopia (between +0.75 and +3.00 diopters).
ring segments for treatment of low myopia (ICRS) and To perform the procedure, a handpiece with a Keratoplast™
conductive keratoplasty (CK) and laser thermokeratoplasty Tip delivers controlled RF energy directly to the corneal stroma
(LTK) for low to moderate hyperopia. in a ring pattern. Conductive keratoplasty creates a purse-string
Intracorneal ring segments (ICRS) or Intacs inserts effect that steepens the central cornea through a ring of
(Addition Technology, Inc., Fremont, CA) are approved for application spots around the periphery of the cornea.
REFRACTIVE SURGERY IN accurate placement of the flap on the ablated stromal

SPECIAL SITUATIONS surface making it an extremely safe, precise and predictable
procedure.
Monovision for presbyopia: Monovision is a method of presbyopic
LASIK has become increasingly popular since 1995 and
correction in which the dominant eye is usually corrected for
is now the most commonly performed refractive procedure
distance vision and the nondominant eye corrected for near.
to correct myopia, hyperopia and astigmatism. Errors ranging
This approach has been used successfully with contact lens
from –0.5 D to –12 D of myopia, +0.5 to +4 D of hyperopia
correction.
and upto 8 D of astigmatism can be treated. LASIK can also
High ametropia: Higher levels of myopia cannot be treated be used to treat residual refractive errors after PRK, RK,
with deeper excimer laser ablations as the residual corneal after cataract surgery with IOL implantation and penetrating
stromal bed is enough to prevent keratectasia and refractive keratoplasty and can be combined with other refractive
instability. Surface ablation, phakic intraocular lenses (IOLs) surgeries (bioptics and trioptics).31-34
and clear lens extraction are alternatives to LASIK for high The basic instruments required for a LASIK procedure
myopia. are the microkeratome and the excimer laser unit. A wide
Pediatric refractive surgery: Pediatric patients with considerable variety of microkeratomes are available including the
anisometropia, high ametropia, or refractive accommodative conventional mechanical keratome, disposable keratome,
esotropia who are at risk for developing amblyopia are water jets and laser keratomes.
treated with either spectacles or contact lenses, along with A microkeratome essentially consists of a fine oscillating
occlusion therapy. When this approach is unsuccessful, or blade which can penetrate the cornea at pre-determined depths
when children are not tolerant/compliant to corrective lenses to slice a smooth layer of corneal tissue. The adjustable
wear, they could, theoretically, be candidates for refractive parameters allow the surgeon to decide the depth and diameter
surgery that may help to prevent or limit the development of of the corneal flap with an accuracy of 5-10 microns. The
amblyopia. assembly, operation and maintenance of the microkeratome
system are crucial to ensure accurate and predictable resections
Refractive surgery in patients with prior corneal surgery: Refractive of corneal tissue.
anisometropia and high postoperative astigmatism in post- The microkeratome set-up includes a pneumatic suction
penetrating keratoplasty eyes may need LASIK or PRK to be ring which fixates the globe and elevates the intraocular pressure
considered as a therapeutic option, in whom conventional upto 65 mm Hg to create an even and smooth corneal flap.
optical methods of correction have failed. LASIK may be On the surface of the suction ring, there are dove-tailed grooves
performed as a staged procedure, with the microkeratome over which the microkeratome head is placed and the motor
cut done initially to remove the contractile forces in the graft, allows the blade to advance to create a hinged corneal flap. A
followed by ablation at a later stage. surgeon controlled foot-pedal ensures movement of the blade
forward till the hinge is reached after which it is reversed and
EQUIPMENTS/INSTRUMENTS USED the microkeratome removed from the eye.
IN LASER REFRACTIVE SURGERY
The excimer laser system works on the principle of
LASIK or Laser assisted in situ keratomileusis was originally ablative photodecomposition using Argon Fluoride (ArF) as
conceived by Dr Jose I. Barraquer in Bogota, Columbia in the essential gas mixture. It is a Class IV laser with a wavelength
1949 where he created a free corneal cap, froze it, sculpted of 193 nm. At this wavelength, it causes selective ablation of
the undersurface on a cryolathe and sutured it back on the corneal tissue according to preset parameters. For myopia
cornea. This was followed by automated lamellar greater ablation is done in the centre of the cornea to flatten
keratoplasty in which after making a corneal flap, a the corneal shape while in hyperopia, the peripheral tissue is
microkeratome was used to excise a disc of stromal tissue ablated to cause steepening of the cornea. The ablation
and the flap was replaced without sutures. Burrato and protocol is determined specifically for each individual patient’s
Pallikaris first combined excimer laser with microkeratome refractive error and calculated accordingly by a software
technology. Subsequent modification in technique led to program in the laser system. The lasers maybe delivered either
the current form of LASIK wherein an excimer laser is through a large beam diameter of five to seven mm or using
used to ablate the stromal bed after creating a hinged corneal the scanning technique to deliver a small spot or slit in a
flap with a very fine microkeratome blade, followed by controlled manner on the stromal bed.
The depth of tissue ablation is calculated by Munnerlyn’s to fluctuation of refractive error during pregnancy, unstable
equation35 which in a simplified way states that: tear film status and avoiding exposure of the foetus or neonate
Optic zone2 × Diopteric correction required to medicines that maybe required after the LASIK procedure.
Ablation depth (µm) = ______________________________________________________ Patients on medications such as amiodarone, isotretinoin and
3
sumatriptan should be treated with caution as these
Hence the amount of tissue that must be removed
medications may interfere with the wound healing response.
depends not only on the amount of refractive error but
Ophthalmic contraindications include active ocular disease
also on the optical zone. Both the diameter and depth of
or inflammation as in conjunctivitis, scleritis, iritis or corneal
ablation need to be optimized to attain best results. Smaller
ulcer. Severe dry eye associated with kerato-conjunctivitis sicca
optical zones cause greater degree of regression and haloes
or exposure keratitis is an absolute contraindication. Herpes
while larger zones are beneficial in reducing night vision
zoster ophthalmicus or herpetic keratitis especially if active
problems.
in the previous six months is at risk for reactivation after
All laser systems come with their recommended list of
exposure to ultraviolet radiation. Corneal ectasias seen in
safety precautions. All operating room personnel should avoid
keratoconus, pellucid marginal degeneration and keratoglobus
direct exposure to skin or eye with the primary laser beam.
also preclude LASIK surgery. Glaucoma, diabetic retinopathy
The area of potential hazard for production of photo-
and progressive retinal disease make the patient unsuitable
chemical keratitis is less than 40 cm. Safety glasses should
for a refractive procedure.
be worn within this range. Odors and fumes interfere with
laser function and should not be allowed inside the laser
room. The gas cylinders used in the laser have Fluorine, Ophthalmic Examination
Argon, Helium and Neon. Fluorine is a highly toxic gas with A complete and detailed ophthalmic examination is mandatory
a sharp odor that causes irritation to nose, eyes and throat before a patient is taken up for LASIK surgery. After a
at extremely low concentrations. Excimer lasers use < 0.25 thorough history to rule out any contraindications, the patient
percent concentration of Fluorine. Argon, Helium undergoes measurement of unaided and best corrected visual
and Neon are inert non-toxic gases with no color, odor or acuity. A dry and cycloplegic refraction is performed. The
taste. patient is examined on the slit lamp to look for any lid
Strict environmental conditions need to be maintained abnormalities, corneal scarring, opacities or conjunctival
in the laser suite for proper functioning of the laser system. disease. Any blepharitis or meibomitis must be treated to
Temperature range should not fluctuate beyond 60° to improve tear function and prevent trapping of any secretions
80° F and relative humidity should be between 35 and at the flap interface.
65 percent. A corneal topography and wavescan measurement is
performed. The corneal curvature, thickness, anterior and
REFRACTIVE PROCEDURES posterior floats are measured. Any corneal thinning, ectasia
LASIK in Myopia or early keratoconus (keratoconus forme fruste) is ruled out.
LASIK is commonly performed the world over for correction Laser Procedures
of myopia. The pre-requisites for LASIK include a minimum
age of 18 years and refractive stability (no more than a ±0.5 Laser refractive surgery is based on the principle of modifying
D change in refraction in the last 6 months). the refractive power of the cornea by ablating the stromal
tissue. Laser procedures performed using excimer lasers to
Preoperative Examination correct refractive errors are of two types:
Screening for LASIK must be done to eliminate patients who Surface Treatment Techniques
are unfit for the procedure. Contact lenses must be removed • PRK (Photo-refractive keratectomy)
for a minimum of 7 to 14 days (soft contact lenses) and • LASEK (laser-subepithelial keratomileusis)
three weeks (rigid gas permeable lenses) prior to the • Epi-LASIK.
preoperative examination. Systemic contraindications for
LASIK include auto-immune disorders, collagen vascular Lamellar Treatment Techniques
disorders, diabetes mellitus and immunocompromised states. • LASIK using the mechanical microkeratome
Pregnant and nursing women should also defer surgery due • LASIK using the femtosecond laser.
In the surface treatment techniques, corneal tissue is

ablated with an excimer laser just below the corneal epithelium.
The various techniques refer to how the corneal epithelium
is removed.
• In PRK, epithelium is removed using a laser
• In LASEK, an alcohol solution is used to abrade the
epithelium
• In epi-LASIK, a microkeratome is used to remove a
uniform sheet of epithelium
• In surface ablation, a mechanical instrument is used to
scrape off the epithelium.
The excimer laser procedure is performed. The corneal
epithelium usually grows back in a couple of days.
In lamellar laser techniques, a microkeratome or a
femtosecond laser is used to create a flap. The flap is everted
on its hinge and the stroma is exposed for laser ablation. Fig. 7.2.11: The microkeratome head placed on the suction ring
After ablation, the flap is reflected back in its original place
where adhesions form within a few hours.
Performing the Laser Procedure

Based on the refraction, corneal topography and wavescan
measurements, the laser treatment plan is made. The
information is compiled together and the ablation profile is
created keeping a residual bed thickness of atleast 250
microns. The laser technique (Figs 7.2.11 to 7.2.13) is adopted
depending on the amount of refractive error, the corneal
thickness and the ablation depth required while maintaining
the minimum bed thickness.
The ablation profile of an excimer laser corrects the
spherical and cylindrical portions of the refractive error with
lasers for myopia removing tissue from the center of the
cornea to make the cornea flatter while hyperopic ablations Fig. 7.2.12: The corneal flap being lifted up
are performed in the corneal periphery to make the central
cornea steeper. Aspheric and wavefront-guided ablation
profiles treat higher-order aberrations (HOA) of the eye and
thus improve the patient’s quality of vision.36-38
Eye trackers monitor the center of the pupil and the iris
pattern to prevent de-centered ablations and compensate for
normal saccadic eye movements. The ablation procedure stops
if the eye tracker cannot locate the pupil so that incorrect or
poorly centered ablations are not performed.39
Standard LASIK ablation parameters are available, like
the Maloney’s tables. These charts have the ablation depths
calculated based on the refractive error and treat the spherical
and cylindrical components. However, they do not treat the
higher order aberrations (HOAs) and may even induce them
especially during correction of high refractive errors. To avoid
this, customized LASIK or C-LASIK is performed, which Fig. 7.2.13: Laser ablation being performed
integrates wavefront technology with the laser treatment. on the stromal bed
Complications of Laser Refractive Surgery 3. Postoperative complications: These include displaced or

dislocated flaps.45,46 Careful alignment of the flap edge should
As with any procedure, complications can occur during or
be done and slit lamp examination performed before the
after laser refractive surgery. A complete preoperative
patient is sent home after the laser procedure. If any
evaluation, an experienced refractive surgeon and meticulous
postoperative care can prevent the occurrence of such events. displacement is noted, the flap should be immediately re-
In the event of a complication, prompt and appropriate positioned and smoothened out in the correct orientation.
interventions may prevent any long-standing visual or The patient is asked not to rub the eyes at all in the
structural damage to the eye. immediate postoperative period. Flap striae or flap folds
Complications following laser refractive surgery include may be noted in the immediate postoperative period. While
the following: macrofolds depict full thickness flap tenting in a linear
1. Flap related complications: These include thin, irregular fashion, microfolds are wrinkles in the Bowman’s
or button-holed flaps with average reported incidence of membrane or epithelial basement membrane seen most
<0.2 precent.40 Thin or button-holed flaps are seen more clearly as negative lines on fluorescein staining. They are
commonly in patients with steep corneas (>46 D) or with more common in patients with thin flaps and high errors
poor suction. Treatment consists of replacement of the where greater tissue ablation is performed. Visually
flap and applying a bandage contact lens to avoid further significant flap striae need to be removed by re-lifting the
displacement. The laser procedure should be deferred till flap and stroking it back to smoothen out the striae. Severe
the flap heals smoothly. The patient can be taken up for cases seen with fixed folds or late in the postoperative period
recutting the flap after three months after the best may need epithelial debridement and thermal ironing
spectacle corrected visual acuity (BSCVA) is obtained. followed by bandage contact lens placement to keep the
Alternatively, surface ablation procedures maybe flap stretched in place.47
performed. Irregular flaps occur with jamming or jerky 4. Epithelial ingrowth: It is usually rare, occurring in less
movement of the micro-keratome and indicate poor than one to two percent cases with an extent of not more
assembly or maintenance of the motor system. than 1 mm from the flap edge.48,49 Rarely, epithelial nests
Preoperative inspection and careful alignment and or sheets may grow into the visual axis, induce irregular
insertion of the microkeratome is essential to avoid such astigmatism and cause blurring and haloes. Treatment
complications. A free cap usually occurs in flat corneas involves early identification and removal of the epithelial
(<41D) or with de-centered placement of the suction cells. Scraping both the stromal bed and the undersurface
ring. The laser ablation should be completed, and the flap of the flap is essential to prevent recurrence.
carefully removed and replaced in the correct orientation 5. Diffuse lamellar keratitis: Also known as the sands of
on the stromal bed.41-43 Sahara, diffuse lamellar keratitis is a sterile inflammatory
2. Laser related complications: These include decentration reaction with a reported incidence of around 1.8
and irregular astigmatism. Patients with high refractive error percent.50,51 The exact etiology is unknown but is believed
may find it difficult to fixate on the fixation light leading to be caused by foreign cells introduced at the time of
to de-centered ablations. Switching off external light surgery. These include gram-negative bacterial endotoxins,
sources helps the patient to fixate on the target light. Lasers residue from the microkeratome head, glove powder etc.
using iris registration to recognize and match the eye It is characterized by pain, blurred vision, foreign body
position relative to the preoperative wavescan have lesser sensation and light sensitivity and occurs usually one to
incidence of decentrations. Postoperative, patients with six days after surgery but can occur months to years later
decentered ablations complain of glare, haloes and as well.
ghosting of images due to light scattering at the edge of • Grade I: This is mild keratitis localized at the periphery
the ablation zone. Irregular astigmatism may occur due with minimal to no symptoms. Frequent topical steroids
to decentered ablations and uneven flap healing. Central (prednisolone 1–2 hourly) should be started and patient
islands may occur when specific tissue areas are not reviewed in one to two days.
ablated resulting in central elevated areas. Patients • Grade II: Moderate infiltrates extend to the central
complain of poor vision and undercorrection. Customized cornea causing decreased vision and photophobia
lasers prevent such complications and provide better occur. Treatment includes frequent topical steroids
quality vision.44 along with oral steroids to control the inflammation.
• Grade III: Clumping of inflammatory cells which Enhancement Procedures

obscure the iris details and central infiltrates with a
Patients suffering from under and overcorrections can undergo
significant decrease in vision is seen. Along with topical
enhancements months to years later after their primary LASIK
and oral steroids, lifting the flap to brush the stromal
procedure. Flaps can usually be lifted with ease after delineating
bed and the flap underface and irrigation to remove
the flap edge carefully and reflecting it back gently. It is
all the inflammatory cells and debris is important to
important to correctly identify the plane of the previous cut
prevent permanent damage.
and note the position of the hinge in order to avoid tearing
• Grade IV: Dense white central infiltrates maybe
of the flap. Anterior segment OCT maybe helpful in
associated with corneal melting and loss of vision.
identifying the plane of the corneal flap.
The flap should be immediately lifted to scrape and
The earliest time at which enhancement procedure can
remove all the interface debris and irrigated thoroughly.
be performed should be at least three to six months after the
The infiltrate should be cultured to rule out an infective
first refractive surgery, to allow the refractive correction to
agent. A drop of steroid may be placed on the stromal
stabilize. It is important to ensure that a residual bed thickness
bed to prevent further inflammation along with topical
of 250 microns is maintained after the enhancement laser.
and oral steroids.
Surface ablation or PRK may be considered for enhancement
Identification and staging of the severity of diffuse
in patients with inadequate residual bed thickness or inability
lamellar keratitis is crucial. Early intervention in the
to lift the previous flap. Complications such as epithelial
form of dispensing topical and oral steroids and lifting
ingrowth are more common after enhancement procedures
the flap to irrigate and remove the cells is required.
due to irregularity of the re-lifted flap edge.
Infiltrates may help to prevent significant visual
loss. Attention to prevention is the key, with emphasis
EPI-LASIK
on cleaning and sterilization of the microkeratome,
avoiding build up of residue, using disposable cannulas, Epi-LASIK uses an instrument called an epikeratome to create
and wearing powder-free gloves. a flap at the level of the basement membrane maintaining its
6. Infectious keratitis: Though infectious keratitis after laser integrity and sparing the stroma. It is especially useful in
surgery is rare, it can be caused by Streptococcus pneumoniae, patients with thinner corneas. The excimer ablation is
Staphylococcus aureus, Mycobacterium chelonae, and Nocardia performed after which the thin flap may either be reposited
asteroids.52-54 Atypical mycobacteria have a predilection or removed and a bandage contact lens is placed to allow a
for the anoxic environment at the flap interface and may smoother epithelial healing (Figs 7.2.14 to 7.2.18). Use of
present two to four weeks after surgery with multiple Mitomycin C drops 0.02 percent have been recommended
dense infiltrates with feathery margins. Patients complain to reduce the chances of postoperative corneal haze. Retaining
of pain, redness and decreased vision. Early diagnosis the epithelial flap has also been known to protect the bare
and prompt intervention with aggressive antibiotics should
be started. Fourth generation fluoroquinolones and
cephalosporins are recommended. Cultures should be
performed and flap amputation or penetrating keratoplasty
maybe needed in unresponsive cases.55-56
7. Ectasia: Thinning and bulging of the cornea may occur
due to biomechanical weakening of the corneal tissue
following laser ablation. Patients with preoperative
abnormal topography, missed keratoconus forme fruste cases
missed which progresses, thin corneas, high refractive
errors, and residual corneal bed thickness < 250 microns
are the risk factors. Patients complain of decreased vision
while topography demonstrates irregular astigmatism with
a myopic shift. Corneal cross linking with riboflavin 0.1
percent and ultraviolet radiation helps to increase the tissue
rigidity and improve the biomechanical strength. Advanced
cases may need corneal transplantation.57-59 Fig. 7.2.14: The epithelial flap is created using the epikeratome
Fig. 7.2.15: The epithelial flap is lifted up gently on its hinge

Fig. 7.2.18: Postoperative week 1, note
clear cornea with no stromal haze
stromal surface and prevent influx of inflammatory cells from

tears thereby reducing the incidence of corneal haze. Epi-
LASIK is associated with faster healing and less pain than
other surface ablation procedures.
Femtosecond Laser
A femtosecond laser represents a breakthrough in ultrafast
laser science. The laser uses an infrared beam of light to
precisely separate tissue through a process called photo-
disruption by generating pulses as short as one-quadrillionth
of a second (10 -15 = femto-second). The Intralase
femtosecond laser is a 60 kHz diode pumped Nd:glass
Fig. 7.2.16: The excimer laser ablation is performed oscillator with a wavelength of 1053 nm (Fig. 7.2.19) based
upon the technology whereby focused laser pulses divide
material at the molecular level without transfer of heat or
impact to the surrounding tissue.
The Intralase femtosecond laser is used to create the
corneal flap similar to a LASIK procedure eliminating the
use and risk of a microkeratome and blade and increasing
the overall safety, precision and accuracy. The laser beam is
focused on a preprogrammed depth and position within the
cornea with each pulse forming a microscopic bubble (Figs
7.2.20 and 7.2.21). As the Intralase laser moves painlessly
back and forth, the bubbles connect to form a flap with no
trauma to adjacent tissue, the entire process taking around
20 to 30 seconds. The surgeon then lifts the flap to allow
treatment by excimer laser. Laser specifications which can be
modified to meet individual patient’s needs include flap
diameter, depth, hinge location and width and side-cut
Fig. 7.2.17: Postoperative day 1, bandage contact lens in situ architecture. Intralase laser also creates a distinctive beveled
edge flap which allows for precise re-positioning and alignment The surgical steps are highlighted below (Figs 7.2.23 to
after LASIK is completed. 7.2.29).
Intralase laser creates a corneal flap of precise size, shape The Intralase femtosecond laser has also revolutionized
and depth to micron-level accuracy 100 percent greater than other forms of corneal surgery such as corneal transplantation
that of blade-keratome and markedly reduces the risk of and intrastromal ring implantation. The femtosecond laser
blade-related flap complications such as free caps, button enables surgeons to create straight, angled and arcuate incisions
holes, incomplete or decentered flaps.60,61 Not only is the which allow faster healing and improved visual recovery in
visual acuity after Intralase better but the incidence of penetrating keratoplasty. The mushroom-shaped incision
postoperative dry eye symptoms is reduced. It also creates preserves more host endothelium than the traditional trephine
fewer high and low-order aberrations which may cause glare approach while the top-hat incision allows for transplantation
and haloes at night. The precision of the flap also reduces of large endothelial surfaces. The zig-zag incision approach
the incidence of induced postoperative astigmatism as provides a smooth transition between host and donor tissue
compared with microkeratome created flap (Fig. 7.2.22). and allows for a hermetic wound seal. Intralase enabled
keratoplasty (IEK) establishes secure grafts requiring less
suture tension and reduced incidence of astigmatism leading
to faster and better visual recovery.
The femtosecond laser is also being used in the creation
of intrastromal pockets for insertion of intrastromal corneal
ring segments in the treatment of keratoconus.62 Instead of
using a mechanical spreader, the femtosecond laser is used
to create channels at a predetermined depth with a high degree
of accuracy. The laser parameters which need to be specified
include channel depth, entry incision length and width and
Fig. 7.2.19: Wavelength spectrum channel size inner and outer diameter. The narrower the
Fig. 7.2.20: Separation of corneal lamellae by focused laser energy

Fig. 7.2.21: Creation of a cleavage plane
Fig. 7.2.22: Difference between Intralase and microkeratome flaps
channel, the greater the effect, however a narrower channel hook and the INTACS segment is carefully pushed forward
also results in increased difficulty in inserting INTACS. A into the channel with the INTACS holder till the edge lies
compromise between maximal outcome and ease of insertion within 1 mm from the entry wound. Various studies have
is achieved. The entry wound and channel creation takes 12 reported better results with femtosecond laser as compared
seconds after which the entry wound is opened with a Sinskey to mechanical group with a significant reduction in average
Fig. 7.2.23: Applanation of the corneal surface Fig. 7.2.25: Flap completed and side cut being delivered
Fig. 7.2.24: Creation of laser pocket at a predetermined depth. Fig. 7.2.26: ‘Burp’ where a condensed water
The Femtolaser assisted flap is more than 50% complete bubble appears at the cleavage plane
keratometry, spherical equivalent refraction and surface they consist of two, tiny clear crescent shaped pieces of PMMA
asymmetry index and improvement in BSCVA, UCVA and which can be inserted into the cornea (Fig. 7.2.30). For myopia,
spectacle and contact lens tolerance. INTACS work by flattening the cornea to refocus light rays
and improve vision while in keratoconus patients, INTACS
Intracorneal Ring Segments flatten the steep part of the cone and reduce vision distortions.
They are available in various sizes which are chosen according
Intrastromal Corneal Ring Segments to the refractive error and the corneal thickness of the patient.
INTACS are corneal implants which are used to change the A clear, central cornea with minimum corneal thickness
shape of the cornea and correct the refractive error in patients of 450 microns at incision site and a mesopic pupil size of
with myopia and keratoconus. Approved by the US FDA, less than 6 mm are preferred. After performing corneal
Fig. 7.2.27: Lifting the flap by delineating the edge Fig. 7.2.29: Excimer ablation being performed on the stromal bed
Fig. 7.2.28: Flap completely separated Fig. 7.2.30: Intrastromal ring implants (INTACS)
topography and refraction, the size of the INTACS and Phakic IOLs
placement is planned. The incision may be made mechanically Patients who have high refractive errors and/or thin corneas,
with a diamond knife and a tunnel created by a dissector into are unsuitable for corneal refractive surgery. For such patients,
which the ring segments are placed. Alternatively, the lenticular refractive surgery is an option. This is available in
femtosecond laser can be used for the same using the form of phakic IOLs which are implanted between the
preprogrammed parameters. cornea and lens. Also termed ‘duophakia’ or ‘artiphakia’, the
INTACS offer the advantages of leaving the central normal crystalline lens is retained and an additional intraocular
cornea undisturbed. The results are rapid and predictable lens is placed to correct the refractive error. The lens maybe
and if required, the INTACS can be removed or exchanged. fixated in the angle or enclavated to the mid-peripheral iris
The corneal asphericity is maintained with minimal adverse with a claw or placed in the posterior chamber.
effects. Possible complications include epithelial defects, The advantages of phakic IOLs are the following:
channel haze, under/overcorrections, sterile infiltrates/ • Allows the crystalline lens to retain its function
epithelial cysts, infectious keratitis and ring extrusion.63 • Predictable
• Immediately stable, because the refractive outcome + 6.0 D of calculation cylindrical. The toric ICL has the
depends less on the healing processes same overall design as the spherical ICL with the addition of
• Excellent vision even in dim light conditions a toric optic. The toricity is manufactured in the plus cylinder
• Removable and exchangeable axis, within 22 degrees. The STAAR® Visian ICL™ is made
• Easily adjustable with complementary fine-tuning corneal from a combination of copolymer and collagen called
surgeries. Collamer®. This Collamer® implantable contact lens reduces
Angle supported lenses include the Vivarte/GBR lens reflections and glare, and the collagen makes it extremely
(Zeiss-Meditec), I-CARE (Corneal, Pringy, France) and biocompatible. It is made-up of 60 percent poly-HEMA,
Kelman Duet Implant (Tekia, Irvine, CA, USA). water (36%), benzophenone (3.8%) and collagen (0.2%), it
The prototype iris fixated lens is the Artisan lens (Verisyse) attracts the deposition of fibronectin on the lens surface,
which is a one-piece poly-methyl methacrylate (PMMA) IOL. inhibits aqueous protein binding and makes the lens invisible
Available in two meniscus-shaped optic diameters of 5.0 and to the immune system.
6.0 mm, it has a fixed overall diameter of 8.5 mm and an
Calculation of power: ICL/TICL calculation and
average vaulting of 0.9 mm. Potential complications include
implantation software allows calculation of spherical and
progressive endothelial cell loss, chronic uveal inflammation,
cylindrical power, length and generates the ICL/TICL
chafing of the iris stroma at the sites of enclavement, lens
implantation diagram (Fig. 7.2.31).
displacement/decentration, pigmentary dispersion syndrome
and irregular pupil. The other phakic IOLs include the Artiflex Measurement of white-to-white diameter: In the
and Veriflex foldable iris supported lenses with a polysiloxane preoperative planning, the critical parameter in sizing the ICL
optic and rigid PMMA haptics and the Nikai lens which is a is the white-to-white (WW) measurement which can be
one-piece silicone lens with a 3.2 mm concave optic and a measured with a Pentacam, OrbScan, UBM or using calipers
frontal surface that projected anteriorly through the pupil. It (Fig. 7.2.32). In myopic eyes, to determine the overall length
is fixated behind the iris plane by two haptics and has a total (in mm) of the ICL, 0.5 mm is added to the horizontal WW
length of 8.0 mm. measurement. If the ICL is too short for the sulcus, the lens
vault may be insufficient to clear the crystalline lens, exposing
Implantable Contact Lens it to the risk of an anterior capsular cataract. If it is too long,
the lens vaults excessively, crowding the angle and possibly
The Implantable Contact lens (ICL) is a posterior chamber
causing closed angle glaucoma.
phakic IOL made of collamer which has become a preferred
modality for correction of high myopia and for patients with Vault: Ideal ICL vault is approximately 500 µm, which is
thin corneas. It was first developed in the late 1980s in Russia roughly one corneal thickness. There are concerns about high
by Dr S Fyodorov and the first implant was placed in Europe vault (1000 µm) leading to angle crowding and resulting in
in 1993. Fyodorov introduced the concept of a soft phakic angle closure or synechiae formation. High vault may also
lens in the space between the iris and the anterior surface of increase iris chaffing and pigment dispersion, resulting in
the crystalline lens.64 pigmentary glaucoma. Furthermore, low vault (125 µm) may
also cause ICL contact with the crystalline lens and increase
Indications and Pre-requisites
the risk of cataract formation over time.65,66
• When residual bed after LASIK is likely to be less than
250 µ
• When the initial corneal thickness is less than 480 µ
• Refractive error between the ages of 21 to 45
• Anterior chamber depth greater than 2.8 mm
• Stable refraction (< 0.5 D change in previous 12 months)
• No ocular pathology (glaucoma, lid pathology, etc.)
• Mesopic pupil < 6.0 mm.
Implantable contact lens is indicated for placement in the posterior
chamber of the phakic eye for correction of moderate to
high myopia ranging between –3.0 D to –20.0 D. Toric ICL
(TICL) can correct upto –3 to –23 D of sphere and + 1.0 to Fig. 7.2.31: TICL implantation diagram
of -4.00 to -15.25 diopters (D). They concluded that

implantation of ICLs is safe and effective and provides
predictable and stable refractive results in the treatment of
moderate to high myopia during a four year observation
period.
Pesando et al68 evaluated ICL in 49 hyperopic eyes of 34
patients. Preoperatively, the spherical equivalent (SE) was
between +2.75 D and +11.75 D and astigmatism was between
+0.50 D and +1.00 D. The mean postoperative SE of the
manifest refraction was +0.07 ± 0.54 D and refraction
stabilized quickly and remained stable throughout the follow-
up period. The results confirmed the long-term safety,
efficacy, accuracy, and predictability of ICL for hyperopia.
Alfonso et al73 evaluated the efficacy, predictability and safety
of myopic phakic posterior chamber ICL to correct myopia
Fig. 7.2.32: Measuring the white-to-white diameter with pentacam
associated with keratoconus. They showed that spherical
(Schiempflug image) equivalent refraction was within ±1.00 D of the desired
refraction in all cases and 84 percent of cases were within
±0.50 D. Alfonso et al suggested that phakic intraocular lens
implantation is a viable treatment for myopia and astigmatism
Peripheral iridotomy: A peripheral iridotomy is performed
after PKP in patients for whom glasses, contact lenses, or
one to two weeks before the surgery to provide an outlet for
corneal refractive surgery is contraindicated. Studies
the aqueous flow around the lens. Alternatively it may be
comparing ICL implantation with wavefront guided LASIK
performed intraoperatively after ICL implantation with a
by Igarashi et al have shown that ICL implantation induces
Vannas scissors or a vitrectomy cutter. It should be sufficiently
significantly fewer ocular HOAs than wave front guided
wide (at least 500 m), positioned superiorly (from 11 to 1
LASIK. 74 Kamiya et al compared Collamer toric ICL
o’clock) and well away from the haptics placement.
implantation and wavefront-guided laser in situ keratomileusis
Procedure: The procedure is performed under topical for high myopic astigmatism and found that all eyes in the
anesthesia. After making a 0.6 mm side port, a 3.2 mm clear ICL group and 71 percent of eyes in the LASIK group were
corneal incision is made on the steep meridian. The lens is within ±1.00 D of the targeted SE correction at six months.75
introduced with the injector and positioned behind the iris on They suggested that Toric ICL implantation was better than
a horizontal axis with a cyclodialysis spatula. To control for wavefront-guided LASIK in eyes with high myopic
potential cyclotorsion in a supine position, the zero horizontal astigmatism in almost all measures of safety, efficacy,
axis is marked preoperatively on the slitlamp. The lens is predictability, and stability. The overall complication rate with
implanted temporally and gently rotated to align the axis with ICL is low and most patients have good visual recovery. The
the cylindrical axis of the patient. Complete removal of incidence of glare, haloes and night driving problems is also
viscoelastic material is essential. Presence of residual minimal. Sanders et al 76 studied incidence of anterior
viscoelastic material behind the implant may cause subcapsular opacities and cataracts 5 years after surgery in
opacification of the crystalline lens. A miotic agent is injected the Visian implantable collamer lens FDA trial. Approximately,
and the aspiration is completed. The incision is closed by six to seven percent of eyes developed anterior subcapsular
hydrating the corneal incision. opacities at over seven years following ICL implantation but
Various studies have reported that phakic TICL only one to two percent progressed to clinically significant
implantation is a good option for the correction of moderate cataract during the same period, especially very high myopes
to high myopia,67 hyperopia,68 high myopic astigmatism, in and older patients. Visual outcome following cataract extraction
eyes with keratoconus,69,70 correction of hyperopia post radial was good. Other reported complications of ICL are pigment
keratotomy71,72 and post penetrating keratoplasy.73 dispersion77 and lens deposits, acute angle closure glaucoma,78
Kamiya et al71 studied long-term clinical outcomes of late subluxation of ICL,79 endophthalmitis80 and retinal
implantation of Visian implantable lens for moderate to high detachment. 81 ICL is a safe and effective modality for
myopia in 56 eyes of 34 patients with myopic refractive errors correction of high myopia and for patients with thin corneas,
with excellent and stable post operative results. Advancements Apart from near vision glasses, the following is the list of
in anterior segment imaging and measurement technologies treatment options for the correction of presbyopia:
such as ultrasonic biomicroscopy, optical coherence • Monovision correction (using contact lenses/monofocal
tomography and Scheimpflug imaging are now providing intraocular lenses)
valuable information about anterior segment anatomy for • Multifocal IOLs
custom-designed phakic intraocular lenses for correction of • Accommodative IOLs
moderate to high refractive errors. • Phakic multifocal IOL
• Conductive keratoplasty (CK)
BIOPTICS • Intracorneal inlays
• Multifocal LASIK
For eyes with large refractive errors, one refractive procedure
• Monovision LASIK
alone may not be sufficient to correct the entire refractive
• Anterior ciliary sclerotomy
error. Combining two or three procedures together is called
• Laser anterior ciliary sclerotomy
bioptics or trioptics respectively. Lenticular options are available
• Scleral expansion bands.
in the form of phakic IOls, toric IOLs and piggyback IOLs
while corneal options for bioptics include corneal relaxing Monovision correction: This means correcting one eye for
incisions (CRIs), anterior limbal relaxing incisions (ALRI), distance and the other eye for near so that the patient is able
laser-assisted epithelial keratomileusis (LASEK), photore- to perform all activities at near and far distance without the
fractive keratectomy (PRK), conductive keratoplasty (CK) aid of glasses. Ideally the dominant eye is corrected for distance
and intrastromal ring implants. vision and the non-dominant eye for near vision.82
Combinations for bioptics or trioptics include:
Monovision maybe obtained using contact lenses, monofocal
• Clear lens extraction with a monofocal or multifocal
IOLs, LASIK or in combination with CK.
implant combined with limbal relaxing incisions to correct
concomitant astigmatism Contact lenses: Various types and combinations of contact lenses
• Phakic IOL followed by LASIK to correct the residual are available for people with presbyopia including distance
refractive error if any CLs with glasses for near reading, CLs for near vision with
• Toric IOL in the bag, multifocal IOL in the sulcus followed spectacles for distance vision, monovision CLs, RGP bifocal
by LASIK can be used for trioptics. CLs, soft bifocal CLs, and modified monovision CLs.83 The
Refractive surgery is one of the most evolved aspects of simplest option for patients already on contact lenses would
ophthalmic science and is undergoing rapid advancements be to wear near glasses concomitantly for near work. To
each day in an endeavor to provide crystal clear vision without obtain monovision with contact lenses, one eye could be given
the aid of glasses and contact lenses. Sophisticated equipments contact lens for distance correction and the other eye contact
and technological breakthroughs have greatly contributed but lens with the near add incorporated. Distance CLs with the
at the base of all these innovations is the restless human use of glasses for near-reading provides the patient with the
mind searching for perfection. As this spirit continues, so will best binocularity at all distances. The disadvantages include
the quality of vision that can be provided to patients with the need for the patient to put on glasses for reading. Modified
minimal complications, improve. monovision involves either the combination of a bifocal CL
on one eye and a single vision CL on the other eye or the use
of two bifocal CLs with one CL correcting for distance and
REFRACTIVE SURGERY
intermediate vision and the other CL correcting for
FOR PRESBYOPIA
intermediate and near vision.
Treatment of presbyopia is a challenge for the refractive Bifocal lenses are available which can be classified as a)
surgeon as the mechanisms of accommodation are complex alternating vision and b) simultaneous vision types. In alternate
and the causes of presbyopia are not fully understood. More vision lenses, the wearer sees an object through either the
importantly, it progressively increases with age. The most distant or near vision part by moving the visual axis upward
widely used standard protocol has been the use of or downward. In simultaneous vision bifocal CL, which are
progressively hyperopic spectacles which take over the near of refractive and diffractive types, both distant and near
focus of the crystalline lens. images are formed on the retina simultaneously.84,85
Monovision with monofocal IOLs: For patients who are well- effect. The 450 micron long tip has a diameter of 90 microns
adapted to monovision contact lenses, surgical removal of and produces heat to a temperature of 65° C upto 80 percent
the crystalline lens with monofocal IOL replacement may be depth in the corneal stroma. This causes steepening of the
performed correcting one eye for distance and the other eye corneal surface and reduction of presbyopic symptoms by
for near. Since the patient may take a while to adapt to inducing myopia of 1-2 D. It has been approved by the FDA
monovision correction, a trial with monovision contact lenses for treatment of presbyopia in emmetropic and hyperopic
must be performed to gauge patient acceptance and comfort patients beyond the age of 40 years.
before surgery.86 Rings of eight evenly spaced spots of 0.6 mm diameter
Multifocal IOL implantation: A refractive or presbyopic can be placed at 6 mm, 7 mm, and 8 mm with an additional
lens exchange with multifocal IOL implantation may be second ring of eight spots at 7 mm. Thus treatments consist
considered for patients who want reduced dependence on of eight, 16, 24, or 32 spots. Using a single ring of eight spots
glasses both for distance and near. Multifocal lenses are at a 7 mm diameter gives an expected correction of 0.75 to
available as diffractive and refractive types. The diffractive 0.875 D. Adding a second ring at a 6 mm diameter gives a
type provides better near vision and contrast sensitivity and correction of 1.0 to 1.625 D. Adding a third ring at 8 mm
are less dependent on the pupil while the refractive type are gives 1.75 to 2.25 D. Finally, adding eight spots at the 7 mm
pupil dependent but provide better light transmission and diameter gives an expected correction of 2.375 to 3.00 D. A
better intermediate range vision.87,88 A combination of one-year follow-up of clinical trials showed that all CK patients
diffractive and refractive type offers best results and provides experienced some improvement in near vision. Possible after-
good vision at all ranges.89 Gunenc et al found bilateral effects are temporary and include tearing, vision fluctuation
implantation with diffractive multifocal IOL in one eye and and foreign body sensation.92 - 94
refractive multifocal IOL in the fellow eye as safe and could Anterior Ciliary Sclerotomy (ACS): Multiple incisions are
provide patients with better intermediate vision, increased made in the sclera over the ciliary muscle to increase the
depth of focus, better contrast sensitivity, and less dependence distance between the lens equator and the ciliary muscle.95
on spectacles.90 The best candidates are hyperopes and high The incisions produced accommodative amplitudes of +1.25
myopes who accept multifocal correction most readily. Halos D in young presbyopes but the effect regressed over time.
and glare are the most common complaints which gradually While some studies have shown minor improvements in
reduce over time.91 presbyopic vision, others found no improvement, but
Accomodative IOLs: The Crystalens, the Accomodative concluded that this procedure weakens the sclera significantly
1CU lens and the synchrony are some of the IOLs which so that it may rupture more easily.
work on the principle of restoring accommodation based on A variation of the procedure has been tested in Japan,96
the optic-shift principle. The Crystalens is a multipiece silicone called ACS-SEP, (Anterior Ciliary Sclerotomy with Silicone
lens with a movable optic-haptic junction that works like a Expansion Plugs). This study was done on 12 people with
hinge. When placed in the capsular bag, the ciliary body and presbyopia. The same incisions were made in the sclera but
the vitreous body pressure causes a forward shift of the this time they were filled with silicone plugs. The plugs were
optic resulting in about 0.5 to 1.5 D of accommodation which sutured in position to the exact same depth as the incision
allows the patient a better range of intermediate and near (95% of scleral thickness). Results showed 1.5D of
vision as compared to a monofocal lens. The 1CU lens is a improvement over 18 months. The plugs prevented the sclera
hydrophilic acrylic lens with a biconvex optic of 5.5 mm and from weakening.
overall diameter of 9.8 mm. Postoperative lens position shifts,
capsular opacification and fibrosis are issues that may influence Laser presbyopia reversal (LAPR): This is similar to ACS,
the long term effectivity of these lenses. but uses laser instead of surgical knife. The laser vaporizes
the tissue in eight radial lines on the sclera. This removal of
Conductive keratoplasty (CK) is a relatively new corneal
tissue thins the sclera and increases the amount of space for
steepening procedure wherein radiofrequency (RF) waves are
the ciliary muscle beneath it.
used to cause collagen shrinkage. Shrinkage of the fibrous
protein in the collagen lamellae decreases the chord length Surgical reversal of presbyopia (SRP) with scleral
of the cornea in the meridian of application. Using a expansion bands: The effect of the scleral expansion band
keratoplast tip, RF waves are delivered to discrete spots in is based on the theory of Schachar that states that the
the corneal stroma in a ring pattern to create a purse-string crystalline lens is under increased equatorial zonular tension
during accommodation.97,98 In 1992, the first scleral expansion 4. Agudelo LM, Molina CA, Alvarez DL. Changes in intraocular pressure
band procedure was performed using a plastic polymethyl after laser in situ keratomileusis for myopia, hyperopia, and
astigmatism. J Refract Surg 2002 Jul-Aug;18(4):472-4.
methacrylate (PMMA) circular band sutured to the sclera.
5. Duch S, Serra A, Castanera J, Abos R, Quintana M. Tonometry
Now a separate PMMA segment is placed in each of the after laser in situ keratomileusis treatment. J Glaucoma
4 oblique quadrants of the eye. With a worldwide experience 2001;10(4):261-5.
with the scleral expansion band procedure for the SRP 6. Vakili R, Choudhri SA, Tauber S, Shields MB. Effect of mild to
involving more than 500 eyes, mean amplitude of moderate myopic correction by laser-assisted in situ keratomileusis
accommodation of 3.25 D has been obtained. The overall on intraocular pressure measurements with goldmann applanation
tonometer, tono-pen, and pneumatonometer. J Glaucoma
response has been favorable with no change in distance
2002;11(6):493-6.
refraction, best corrected visual acuity, or axial length. 7. Shildkrot Y, Liebmann JM, Fabijanczyk B, Tello CA, Ritch R.
Common adverse effects include subconjunctival hemorrhage, Central corneal thickness measurement in clinical practice. J
transient astigmatism, fluctuating near vision, and dry eyes Glaucoma 2005;14(5):331-6.
which usually resolve in six to eight weeks.99 Safety concerns 8. Yaylali V, Kaufman SC, Thompson HW. Corneal thickness
about the procedure include the possibility of infection, measurements with the Orbscan Topography System and ultrasonic
pachymetry. J Cataract Refract Surg 1997;23:1345–50.
degradation of the implants over time, and compromised
9. Swartz, Tracy; Marten, Lisa; Wang. Ming Measuring the cornea:
blood circulation in the eye. the latest developments in corneal topography Current Opinion
in Ophthalmology 2007;18(4):325-33.
Presbyopic LASIK or monovision LASIK: This corrects 10. Lackner B, Schmidinger G, Pieh S, et al. Repeatability and
one eye for near vision and the other eye for distance vision. reproducibility of central corneal thickness measurement with
Patients who respond well to a trial of monovision contact Pentacam, Orbscan, and ultrasound. Optom Vis Sci 2005;82(10):
lenses can undergo presbyopic LASIK.100 The patients must 892-9.
learn cortical adaptation and suppression to be comfortable 11. Liu Z, Huang AJ, Pflugfelder SC. Evaluation of corneal thickness
and topography in normal eyes using the Orbscan corneal
with the quality of vision attained with monovision LASIK
topography system. Br J Ophthalmol 1999;83(7):774-8.
as at any point of time only one eye is focusing clearly. 12. Rao SN, Raviv T, Majmudar PA, Epstein RJ: Role of Orbscan II
in screening keratoconus suspects before refractive corneal surgery.
Corneal inlays: Corneal inlays are five to ten microns thick Ophthalmology 2002;109:1642-6.
intracorneal implants with a diameter of 3.8 mm and a central 13. Sugar A, Rapuano CJ, Culbertson WW, Huang D, Varley GA,
aperture of 1.6 mm. Made of polyvinylidene fluoride Agapitos PJ, de Luise VP, Koch DD. Laser in situ keratomileusis
material, they increase the depth of focus by blocking out for myopia and astigmatism: safety and efficacy: a report by the
unfocussed light.101 An intracorneal pocket is made with a American Academy of Ophthalmology. Ophthalmology
2002;109(1):175-87.
microkeratome or a femtosecond laser into which the inlay is
14. Li Y, Meisler DM, Tang M, Lu AT, Thakrar V, Reiser BJ, Huang D.
implanted at a depth of 170-200 µm. The INTRACOR and Keratoconus diagnosis with optical coherence tomography
the InVue inlays are commercially available. pachymetry mapping. Ophthalmology 2008;115(12):2159-66.
Treatment of presbyopia is still far from perfect but with 15. Schuman JS. Ophthalmic imaging and diagnostics. Ophthalmology
continued research and innovation, the day is not far when Clinics of North America 1998;11:1-490.
ageing changes in the eye will not only be reversed but may 16. Lawless MA, Hodge C. Wavefront’s role in corneal refractive surgery.
Clin Experiment Ophthalmol 2005;33(2):199-209. Review.
never occur.
17. Liang J, Grimm B, Goelz S, Bille JF. Objective measurement of
wave aberrations of the human eye with the use of a Hartmann-
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2002;134(6):808-15.
Chapter 7.3
CORNEAL CROSSLINKING
Rakhi Kusumesh, Shah Nawaz, M Vanathi
Keratoconus is a progressive, bilateral, often asymmetrical Collagen Crosslink (X-Link)

non-inflammatory corneal ectasia. It is usually diagnosed and its Biomechanics
during the second and third decades of life. The ectasia
progresses at a variable rate, although it may progress more The idea to use this conservative approach to treat keratoconus
rapidly at a younger age.1,2 Treatment options for keratoconus was conceived in Germany in the 1990s by a research group
largely involve interventions that were done for tectonic, at Dresden Technical University with the aim to slow or arrest
optical or refractive purposes. progression to delay the progression. Pilot studies on humans
Two chief mechanisms held responsible for the using riboflavin UVA were commenced in Dresden in 1998,
development of keratoconus are tissue degradation or and their results were published in 2003.9 The technique of
reduced maintenance and slippage between collagen fibrils, corneal collagen crosslinking has been used experimentally to
with no overall tissue loss.3 Yet it is a disease where the temporarily block progression of keratoconus in the
pathogenesis is poorly understood, and until recently, there refractive phase. Collagen turnover takes about two to three
has been no treatment apart from transplantation. Collagen years. Crosslinking “freezes” stromal collagen, increasing the
crosslinking treatment using riboflavin and UV light has shown biomechanical stability of the cornea.
promising results. Within the last one decade advancements Crosslinking (X-linking) of the cornea is an approach
in vision correction have found an efficient treatment for which increases the mechanical and biochemical stability of
the progression of vision loss in these patients by collagen the stromal tissue.10,11 This was followed by a number of
crosslinking (X-Link). 4,5 Tomkins and Garzozi in 2008 studies and has been proved that Collagen crosslinking with
reviewed the current information regarding strengthening the riboflavin (C3R) not only stabilize the vision loss in patients
unstable cornea by crosslinking, as well as discussed its potential with keratoconus and keratectasia but also essentially halts
benefits and downfalls.6 the process.9
Collagen X-linking (C X L) creates additional chemical
Biochemical Evaluation bonds by means of photopolymerization in the anterior
of Keratoconic Cornea stroma. As UVA light acts by absorption, selection of the
The biomechanical properties of the cornea depend on the wavelength is advisable. It has been observed that 370 nm
characteristics of collagen fibers, interfibril bonds, and their corresponds to one of the riboflavin chromophore. Riboflavin
spatial-structural disposition. Decreased mechanical stability acts as a photomediator, creating free radicals to induce new
plays a role in the protrusion of the cornea in keratoconus.7 chemical bonds. In keratoconus, the central and inferior regions
Andreassen et al.8 found that the stiffness of a keratoconic of the cornea are preferentially affected (the main region of
cornea is only 60 percent of that of the normal cornea. cone formation), since interlamellar cohesive strength is
Changes in the crosslinking pattern of collagen have been minimum in that area in normal corneas and this can be
shown to accompany biomechanical changes. strengthened by X-link.
Corneal Crosslinking 771
Table 7.3.1: Physico-chemical changes in the corneal stroma induced by collagen crosslinking
Change Observation References
Increase in Young’s modulus Altered stress—strain relationship; increase in Wollensack et al. (2003) 14
Young’s modulus by factor of 4.5 (human cornea)
Increased bending stiffness Increased resistance to bending; enhanced shape retention Wollensack et al. (2003) 14
Increased corneal surface temperature Mean increase of 2.6 o (human cornea, in vivo) Mencucci et al. (2007) 15
Increased collagen fiber diameter 12.2% increase in diameter (anterior stroma) (rabbit cornea) Wollensak et al. (2004) 16
Formation of aggregated molecules High molecular weight collagen polymer on gel electrophoresis Wollensak and Redl
(> 1000 kDa) (2008) 17
Increased shrinking temperature Increased from 70° to 75°C (porcine cornea) Spoerl et al. (2004)18
Increased resistance to swelling Reduced swelling; increased transparency (porcine cornea) Wollensak et al. (2007) 19
Resistance to enzymatic digestion Digestion time doubled (collagenase) (porcine cornea) Spoerl et al. (2004)20
There have been many studies on the effects of cross- • Nine point corneal pachymetry of 400 µm minimum
linking like stress-strain measurement, thermal studies, and • Slit-lamp evaluation to rule out any corneal scarring
enzyme digestion studies.12,13 Human studies showed an • An informed consent regarding detailed description of
increase in the length of corneas after treatment by 328.9 the nature of the treatment must be discussed with all
percent and in pigs of 81.9 percent. These have been the patients or the legal guardians (in case of patients less
presented in a tabular form in Table 7.3.1.14-20 than 18 years of age).
Method of Application
Indications
This is a 30-minute, in-office treatment and requires custom-
1. Keratoconus
made riboflavin eyedrops to be applied to the cornea, which
2. Pellucid marginal degeneration
is then activated by a UV lamp light. This is a process that
3. Iatrogenic keratectasia (post laser in situ keratomileusis)
has been shown in laboratory and clinical studies to increase
4. Prevention of keratectasia (prior to refractive surgery)
the amount of C3R in the cornea and strengthen the cornea.24
5. Bullous keratopathy
The crosslinking techniques are based broadly on the
6. Microbial keratitis
methodology developed in Dresden under strict asepsis.
7. Corneal (stromal) ulceration
Topical anesthesia of propracaine hydrochloride 0.5 percent
8. Donor tissue modification prior to keratoplasty
eye drops is administered for two minutes. The central 7.0 to
9. As an adjunct to orthokeratology.
9.0 mm of corneal epithelium is removed by mechanical
Collagen crosslinkage with riboflavin and UVA has been
debridement, with or without the assistance of alcohol, without
sequentially combined with other modalities, intrastromal ring
disturbing the sub-epithelial components. This is to ensure
segments21 and photorefractive keratectomy (PRK)22 for the
that riboflavin penetrates the stroma and that a high level of
treatment of keratoconus.
UVA absorption is achieved. As a photosensitizer, 0.1 percent
Collagen crosslinking on presumed infectious keratitis may
riboflavin solution (usually containing 20% dextran) is applied
be a promising new treatment, although this remains to be
to the cornea every five minutes for 30 minutes before
elucidated in detail in future studies and until more data are
irradiation to allow sufficient saturation of the stroma. UVA
available this treatment should only be considered in the
irradiation is commenced using a wavelength of 370 nm, at
therapy of refractive keratitis or ulceration and not in the
surface irradiance of 3.0 mW/cm2 for 30 minutes (surface
first line of defence since it may have cytotoxic side effects.
dose 5.4 J/cm2). Throughout the irradiation phase, riboflavin
solution is applied every two to three minutes ensuring that
Preoperative Evaluation23
the stromal surface is kept moist and that the stromal thickness
The important preoperative parameters are: remains above 400 microns. At the end of the procedure, a
• To know the progression of keratoconus (Progression combination of steroid and antibiotic are administered
should be defined as an increase in maximum keratometry followed by a bandage contact lens application. The eye
(K) of 1.00 diopter (D) in one year) remains patched for 24 hours. Topical antibiotics drop and
lubricating eye drops, four times a day, are continued for a topography.28,29 Given the stiffening effect that CXL has on
period of one week. Follow-up examinations are required the cornea, this treatment might be expected to lead to an
everyday until complete reepithelialization. Bandage contact overestimation of intraocular pressure when measured by
lens (BCL) is removed after full corneal reepithelialization applanation tonometry and there is some laboratory evidence
occurs. Alternatively it can be performed transepithelially.25 to support this assumption.30 A small (2 mm Hg) increase in
With the aid of the paracaine, riboflavin can penetrate the intraocular pressure measurements has been observed
cornea without removal of the epithelium called the ‘Epi-on’ clinically in one series,31,32 but not in others. Transient mild
procedure. Then, an ultra violet light is placed over the eye corneal edema occurs universally during the early
for 30 minutes to activate the riboflavin. The ‘Epi-on’ postoperative period and begins to resolve after closure of
procedure does not give the patient any pain during or after the epithelial defect. The development of mild anterior and
the procedure. More recently, femtosecond laser-created mid-stromal haze is also expected. Haze can persist for several
pocket collagen cross-linking in early keratoconus, with months31 but is rarely visually significant. The posterior limit
riboflavin has been described.26 of the corneal haze is often visible on slit-lamp examination as
Unfortunately, it is not yet possible to directly observe or a line or layer of denser haze in the deeper stroma. This
measure the increase in crosslinking that is induced by this demarcation line was described by Seiler and Hafezi who
application of riboflavin and UVA, or to accurately measure postulate that this represents the transition zone between the
the depth of the changes occurring in the cornea in vivo, treated (crosslinked) stroma and the untreated posterior layers.33
although observations that have been made using in vivo
confocal microscopy. Safety
In the pilot study, Wollensak et al34 reported that following
CORNEAL RESPONSES TO CROSSLINKING
CXL, corneal and lens transparency, endothelial cell density
The outcome measure common to most clinical studies has and intraocular pressure remained unchanged. In studies done
been the change in corneal curvature as determined by on rabbit corneas, they found that a cytotoxic dose of radiation
computerized videokeratography, an increase in corneal >0.65 J/cm2 (0.36 mW/cm2) was reached at the endothelium
curvature being a marker of progression of the keratoconus using the standard surface UVA dose of 5.4 J/cm2 (3 mW/
and a decrease being interpreted as an additional therapeutic cm2 ), when applied to corneas thinner than 400 mm.
effect of CXL. A halting of progression of ectasia following Significant necrosis and apoptosis of the endothelial cells at
CXL has been a consistent finding in all published studies 24 hours was noted at the cytotoxic dose level given above.
with very few subjects requiring a second treatment.27 A It is therefore recommended that in corneas thinner than
history of progression prior to treatment based on changes 400 µm, radiation should not be performed owing to the risk
in refraction, visual acuity or the need for contact lens refitting of endothelial injury.
is not as reliable or as objective as serial computerized Mazzotta et al35 reported epithelial regeneration in four
videokeratography. If the adopted inclusion criteria days with no damage observed in the limbus. The immediate
inadvertently permit recruitment of eyes that are, in reality, disappearance of subepithelial and anterior-midstromal nerve
stable, a lack of progression following CXL may be falsely fibers after treatment was reversed by regeneration of
attributed to the treatment. subepithelial plexus in the first month and the anterior-
Flattening of the cornea, with or without reduction in the midstromal fibers during the second and third postoperative
magnitude of the astigmatism, is usually accompanied by an months. The process is almost complete at six months
improvement in uncorrected visual acuity. Not infrequently, restoring normal corneal sensitivity. Disappearance of
improvements in visual acuity is observed without keratocytes to a depth of 340 µm occurred postoperatively.
concomitant change in simulated keratometry values. In such Confocal microscopy demonstrated a gradual repopulation
cases, the improvement has been construed to occur as a of the corneal stroma, starting between the second and third
result of reduction in the irregular component of the month and completing after six months. 36 Infrared
astigmatism. A reduction in some higher order aberrations, thermocamera measurements of the human corneal surface
particularly coma, has been demonstrated after CXL during crosslinking treatment have shown the temperature
suggesting improved symmetry and homogeneity of the to be constant during the entire procedure and remain under
anterior (and possibly posterior) corneal surface the threshold of thermal injury to corneal collagen.37,38
Applications stromal ulceration resulting from infective, traumatic or

immune-mediated corneal diseases.45 Unlike EDTA and other
Keratoconus: CXL does have a role in the management of
anti-collagenases that rely on the chelation of metal cofactors,
keratoconus which can be shown to be progressing, particularly
the resistance to collagenases afforded by CXL is thought to
in patients with less advanced disease and relatively preserved
be due to changes in the tertiary structure of the collagen
corrected visual acuity. If progression can be reliably
fibrils that impede access of proteolytic enzymes to their
documented, then early intervention is likely to be most
specific cleavage sites.
beneficial, even before the onset of visual impairment or the
development of obvious clinical signs. Donor cornea modification: As CXL is capable of depleting the
stroma of keratocytes and other antigen-presenting cells, it
Other ectatic diseases: Other ectatic conditions of the peripheral
has been suggested that pretreatment of donor corneal tissue
cornea, such as pellucid marginal degeneration, may also may prevent or reduce the severity of allograft reactions
benefit from CXL.39 provided that any risk to the limbal following penetrating keratoplasty and thereby prolong graft
stem cells is adequately addressed. survival.46
Iatrogenic keratectasia is a feared complication of corneal
refractive surgery (laser in situ keratomileusis) and mimics Complications
the behavior of progressive keratoconus. Early case reports
of the use of CXL in the management of this condition, • Corneal scarring (diffuse subepithelial opacification)47
with and without insertion of intrastromal corneal ring • Stromal haze48
segments, have been encouraging, with stabilization being • Infective keratitis49
observed in the short to medium term.40 • Diffuse lamellar keratitis (post LASIK)50
The physicochemical changes induced by collagen
Bullous keratopathy: Corneal collagen crosslinking has also been crosslinking has been exhaustively elaborated (Table 7.3.1).
suggested as treatment for corneal edema. This concept is Till date only few complications such as corneal haze47 and
supported by changes in the hydration behavior of the porcine stromal demarcation line have been reported. Of all, keratitis
cornea after CXL and the observation that stromal is a major complication. Though collagen crosslinking is a
compaction follows CXL in a similar experimental model. promising procedure for the treatment of progressive
Ehlers and Hjortdal reported a reduction in corneal thickness keratoconus the possibility of a secondary infection after the
in 10 of 11 eyes treated with CXL with the majority procedure exists because the patient is subjected to epithelial
experiencing some improvement in vision.41 debridement and the application of a soft contact lens. The
role of the UV light on the immune mechanisms of the
Microbial keratitis: The antimicrobial effects of photoactivation cornea and its effect on corneal wound healing warrant further
of riboflavin may also be harnessed to treat infections of the investigation. To overcome the problem, transepithelial
cornea. Riboflavin has a modest affinity for nucleic acid and method of application is now practiced.
its absorption of UVA leads to the oxidation of guanine bases,
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Am J Ophthalmol 2003;135:620 e 7. Parasurgical therapy for keratoconus by riboflavin ultraviolet type
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27:353-6. 36. Mazzotta C, Balestrazzi A, Traversi C, et al. Treatment of
18. Spoerl E, Wollensak G, Dittert DD, Seiler T. Thermomechanical progressive keratoconus by riboflavine UVA—induced cross-
behavior of collagen-cross-linked porcine cornea. Ophthal- linking of corneal collagen: Ultrastructural analysis by Heidelberg
mologica 2004;218:136-40. retinal tomograph II in vivo confocal microscopy in humans. Cornea
19. Wollensak G, Aurich H, Pham DT, Wirbelauer C. Hydration 2007;26:390 e 7.
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ultraviolet A. J Cataract Refract Surg 2007;33:516-21. A collagen crosslinking: in vivo thermographic analysis of the corneal
20. Spoerl E, Wollensak G, Seiler T. Increased resistance of crosslinked surface. J Cataract Refract Surg 2007;33:1005 e 8.
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23. Spoerl E, Mrochen M, Sliney O, Trokel S, Seiler T. Safety of 2009;35:1298-301.
UVA-riboflavin crosslinking of the cornea. Cornea 2007;26:385- 40. Kamburoglu G, Ertan A. Intacs implantation with sequential
9. collagen crosslinking treatment in postoperative LASIK ectasia. J
24. Hayes S, Kamma-Lorger CS. Corneal collagen crosslinking in Refract Surg 2008;24:S726-9.
bullous keratopathy. J Refract Surg 2008;24(7):S730-6. Bellini 41. Wollensak G, Aurich H, Pham DT, Wirbelauer C. Hydration
LP. New uses for collagen crosslinking J Cataract Refract Surg behavior of porcine cornea crosslinked with riboflavin and
2007;33:516-21. ultraviolet A. J Cataract Refract Surg 2007;33:516-21.
42. Corbin F 3rd. Pathogen inactivation of blood components: Current 46. Wang F. UVA/riboflavin—induced apoptosis in mouse cornea.
status and introduction of an approach using riboflavin as a Ophthalmologica 2008;222:369-72.
photosensitizer. Int J Hematol 2002;76(2):253-7. 47. Herrmann CI, Hammer T, Duncker GI. [Haze formation (corneal
43. Micelli Ferrari T, Leozappa M, Lorusso M, Epifani E, Micelli scarring) after crosslinking therapy in keratoconus.] (in German.)
Ferrari L. Escherichia coli keratitis treated with ultraviolet A/ Ophthalmologe 2008;105:485 e 7.
riboflavin corneal crosslinking: A case report. Eur J Ophthalmol 48. Mazzotta C, Balestrazzi A, Baiocchi S, et al. Stromal haze after
2009;19:295-7. combined riboflavin UVA corneal collagen crosslinking in
44. Moren H, Malmsjo M, Mortensen J, Ohrstrom A. Riboflavin and keratoconus: in vivo confocal microscopic evaluation. Clin
ultraviolet A collagen crosslinking of the cornea for the treatment Experiment Ophthalmol 2007;35:580 e 2.
of keratitis. Cornea 2009;31:31. 49. Pollhammer M, Cursiefen C. Bacterial keratitis early after corneal
45. Schnitzler E, Sporl E, Seiler T. (Irradiation of cornea with crosslinking with riboflavin and ultraviolet A. J Cataract Refract
ultraviolet light and riboflavin administration as a new treatment Surg 2009;35:588 e 9.
for erosive corneal processes, preliminary results in four patients). 50. Kymionis GD, Bouzoukis DI, Diakonis VF, et al. Diffuse lamellar
Klin Monatsbl Augenheilkd 2000;217:190-3. keratitis after corneal crosslinking in a patient with post-laser in
situ keratomileusis corneal ectasia. J Cataract Refract Surg 2007;
33:2135-7.
Chapter 8
DISEASES OF THE SCLERA
M Vanathi, Rupesh Agrawal, Sujith Vengayil, Virender S Sangwan
BASIC CONCEPTS near the muscle insertions. Direct damage to or the stretch of
these nerves is the cause for pain in scleritis.1-4
Anatomy of the Episclera and Sclera Clinically the vessels overlying the sclera are in three layers:
The episclera is the thin densely vascularized layer of 1. The superficial conjunctival plexus, mainly derived from
connective tissue overlying the sclera and situated beneath the the superior tarsal arcade.
Tenons capsule. Apart from the vessels and unmyelinated nerve 2. The superficial episcleral plexus with a distinct radial
fibers, it contains bundles of collagen. The episclera blends distribution.
with subconjunctival tissues and Tenon’s capsule 1 to 3 mm 3. The deep episcleral plexus form a network directly on the
behind the limbus and it becomes very thin and indistinct sclera.
posterior to the equator. On the other hand, sclera forms The latter two plexuses of vessels are derived from
5/6th of the outer coat of the eyeball providing firm protective perforating vessels, especially the long posterior ciliary vessels
coat for the intraocular contents, resilient enough to allow for and the anterior ciliary vessels. These layers can be easily
the variations of intraocular pressure, yet firm enough to resist distinguished at the slit-lamp with red-free light and further
distortions on movement or pressure by external forces. The distinctly with anterior segment angiography. They also explain
thickness of the sclera varies from 0.3 to 1.2 mm. It is made the difference in appearance of episcleritis from scleritis. The
up of irregularly sized collagen in criss-cross pattern in a dense superficial vessels blanch with phenylephrine ten percent but
proteoglycan matrix. If the water content is reduced to 40 the deep ones are hardly altered, a clinical test often employed
percent, then the sclera becomes translucent. The sclera is to distinguish the inflammatory patterns. The superficial plexus
formed as a condensation of mesoderm outside the choroid can be easily moved on the underlying structure in episcleritis
late in development starting from before backwards, the which can be applied clinically as yet another distinguishing
posterior pole developing beyond the fifth month of fetal life. factor from scleritis.1-4
On the other hand, episclera is a fibrotic structure formed
after the development of the sclera from a mesenchymal PATHOPHYSIOLOGY OF SCLERAL DISEASE
condensation of areolar structures of the orbit, possibly in Pathophysiology of Episcleritis
response to eye movement.1-4
Sclera has low metabolic activity. It derives its nutrition Biopsy study of both diffuse and nodular episcleritis is
from both underlying choroid as well as overlying episclera. nonspecific. The inflamed area is loaded with lymphocytes
The sclera transmits blood vessels, but retains very scant supply and few other inflammatory cells but there are no mast cells,
for its own use. Thus, sclera is dependent mainly on the plasma cells or eosinophils.5
episclera to provide a response to inflammation. Hence, scleral
Pathophysiology of Scleritis
inflammation is almost always accompanied by an overlying
episcleritis. On the other hand, episcleritis per se is very rarely The sclera, consisting of collagen and elastic connective tissue,
associated with scleritis. It is supplied with nerves particularly provides a tough protective covering around the eye.
780 Sclera
Inflammation of the sclera leads to invasion of inflammatory

cells, including T cells and macrophages, resulting in enzymatic
degradation of collagen fibrils and damage. Inflammation of
the sclera leads to ischemia and necrosis with eventual scleral
thinning and perforation of the globe. Necrotizing anterior
scleritis is a particularly destructive form of scleritis. Thus,
pathogenesis of scleritis is essentially a chronic granulomatous
reaction characterized by fibrinoid necrosis, collagen
destruction, cellular infiltration by lymphocytes, plasma cells,
macrophages and polymorphonucleocytes (PMN). This is
surrounded by multinucleated epitheloid giant cells and old
and new vessels, some of which are thrombozed, suggestive
of vasculitis. Thus, it is mostly a type III immune-complex
mediated reaction, as well as, to some extent, type IV cell
mediated delayed hypersensitivity reaction.5
Fig. 8.1: Localized superficial episcleral congestion with nodule
formation at the temporal aspect of the episclera suggestive of
CLINICAL ASPECTS IN SCLERAL DISEASE nodular episcleritis (Courtesy: Dr V Sangwan)
Clinical Features
Scleritis and episcleritis have very distinct characteristics as in to the episcleral tissues, inbetween the sclera and the
onset, pain, vasculature, ocular and systemic associations, conjunctiva. Episcleritis has a more benign course without
response to treatment and complications. This helps in any visual changes or permanent damage but recurrences may
appropriate clinical diagnosis and management.1-4 be common.1-4
EPISCLERITIS SCLERITIS
Episcleritis is a transient, self-limited disease of adults. It may Scleritis is an inflammatory disease that affects the sclera and
be simple or nodular. It is twice as common in women as in is a much more severe than episcleritis. It may be localized,
nodular, or diffuse. It may involve the anterior and/or posterior
men. Patients are commonly unaware of its presence and the
segments of the eye and manifests with redness of the eye
redness may be bought into notice after being mentioned by
and severe eye pain. Isolated posterior scleritis does not present
others. The chief complaint of patients with episcleritis is
with redness of the visible portion of the eye. It occurs most
usually ocular redness with or without irritation. The redness
often in the second to sixth decades of life is significantly
typically persists for one to three days, then resolves
more common in women and is bilateral in more than half of
spontaneously. The disease occurs most commonly in the the cases.
exposure zone of the eye, often in the area of a pinguecula, Scleritis causes significant pain, may lead to structural
and may recur in the same or different locations. More than alterations of the globe, has a risk of visual morbidity, and is
one third of patients have bilateral diseases at one time or associated with an underlying systemic immunologic disease
another. Episcleritis is generally not associated with a systemic in the majority of cases. The onset of scleritis is usually gradual,
immunologic disease. Episcleritis is diagnosed clinically by extending over several days. Most patients with scleritis develop
localizing the site of inflammation to the episclera. Inflamed severe boring (piercing) ocular pain, which may occasionally
episcleral vessels are straight and radiate posteriorly from the worsen at night and awaken them from sleep. The pain may
limbus, (Fig. 8.1) have a salmon pink color in natural sunlight, be referred to other regions of the head on the involved side.
can be moved posteriorly over the deeper sclera with a cotton The globe is often tender to touch. Clinical signs aid in
tipped applicator, and blanches with topical phenylephrine ten diagnosis of scleritis. In scleritis, the sclera assumes a violaceous
percent, unlike the deeper inflamed blood vessels in scleritis. hue in natural sunlight. It is very essential to examine the patient
Episcleral edema without underlying scleral edema may be seen with suspicion of episcleritis versus scleritis in bright sunlight.
with a thin slit-lamp beam. Episcleritis presentation may be Inflamed scleral vessels have a crisscross pattern, are adherent
similar to scleritis, but inflammation and erythema is limited to the sclera and can not be moved with a cotton-tipped
Diseases of the Sclera 781
applicator. Scleral edema with overlying episcleral edema, is Necrotizing anterior scleritis may or may not be associated
often noted on slit-lamp examination.1-4 with inflammation and is the most severe and most common
form of scleritis with vision-threatening complications and
Classification of Scleritis resultant permanent visual loss. Necrotizing anterior scleritis
This can be classified as3 with inflammation is found to frequently accompany systemic
collagen vascular disorders and is associated with extreme pain
Anterior scleritis (nodular or diffuse) along with marked damage to the sclera. Necrotizing anterior
• Non necrotizing scleritis scleritis with corneal involvement is also known as
– Nodular
sclerokeratitis (Fig. 8.4).7 Patients typically present with severe
– Diffuse
pain, out of proportion to the inflammatory signs. Most
• Necrotizing scleritis
– With inflammation commonly, a localized patch of inflammation is noted initially,
– Without inflammation with the edges of the lesion more inflamed than the center.
Posterior scleritis Severe loss of tissue may result if treatment is not intensive
(Reproduced from Scleritis and Episcleritis, Watson PG, and prompt. The sclera may have a blue-gray appearance and
Hayreh SS. British Journal of Ophthalmology 1976, Volume
60(3), page 163–191, copyright notice February 2011 with
permission from BMJ Publishing Group Ltd.)
Anterior scleritis is characterized by widespread inflammation

of the anterior sclera and may present in the diffuse or nodular
form. Diffuse anterior scleritis is the most common
presentation of anterior scleritits. Nodular anterior scleritis is
characterized by single or multiple erythematous, immovable,
tender inflamed nodules on the anterior sclera (Fig. 8.2) and
approximately 20 percent of the cases may progress to
necrotizing scleritis. In diffuse nonnecrotizing scleritis, there
is inflammation of sclera with overlying scleral edema and
violaceous hue of the sclera (Figs 8.3A and B). In cases of
nonnecrotizing scleritis, vision is often maintained unless
complications such as uveitis occur.1-4
Figs 8.3A and B: Circumscribed diffuse congestion of deep scleral

vessels with overlying edema without associated necrotic changes
Fig. 8.2: Congestion of deep scleral vessels with nodule formation suggestive of diffuse nonnecrotizing scleritis (Courtesy: Dr V
suggestive of nodular scleritis (Courtesy: Dr V Sangwan) Sangwan)
782 Sclera
Posterior scleritis is less frequent compared to anterior

scleritis, but may occur concurrently (Figs 8.6A and B). It is
usually not associated with any specific systemic disorder.
Patients present with severe pain, tenderness, proptosis, visual
loss, and occasionally restricted motility. Choroidal folds,
exudative retinal detachment, papilledema and angle closure
glaucoma secondary to choroidal thickening may develop.
Presence of T sign on ultrasound B scan, i.e. fluid in Tenon’s
sheath around the optic nerve is one of the pathognomonic
sign of posterior scleritis.1-4
CLINICAL EVALUATION
IN SCLERAL DISEASE
History Taking
Fig. 8.4: Gross necrosis of sclera and peripheral cornea with
surrounding inflammation suggestive of necrotizing sclerokeratitis
Onset
with inflammation (Courtesy: Dr V Sangwan) Details on onset of the disease including prodromal phase
and conditions preceding the onset should be elicited. Scleritis
show an altered deep episcleral blood vessel pattern after the is subacute and a more gradual onset occurs than is seen in
inflammation subsides.1-4 episcleritis.
Necrotizing anterior scleritis without inflammation
Ocular Symptoms
frequently occurs in patients with long-standing rheumatoid
arthritis secondary to formation of a rheumatoid nodule in It is imperative to be able to distinguish between the
the sclera. There is a notable absence of symptoms. conjunctival and scleral conditions, presenting to the
Necrotizing anterior scleritis without inflammation is also ophthalmologist. In conjunctivitis, episcleral vessels are rarely
called scleromalacia perforans (Figs 8.5A and B). There are inflamed. It is commonly associated with discharge and there
minimal signs of inflammation and generally no pain is no pain but discomfort. In episcleritis, there is a pricking
accompanying this type of scleritis because of destruction of dry sensation, with localized discomfort and slight ache but
nerves secondary to inflammation.1-4 no severe pain. The pain of scleral disease is severe and is
Figs 8.5A and B: Gross thinning of sclera with areas of minimal scleral inflammation suggestive of necrotising scleritis without
inflammation, also known as scleromalacia perforans (Courtesy: Dr V Sangwan)
Figs 8.6A and B: (A) Circumscribed diffuse congestion of sclera suggestive of diffuse nonnecrotizing scleritis (B) Diffuse RPE mottling
and internal limiting membrane (ILM) folds at posterior pole in a patient with diffuse nonnecrotizing scleritis suggestive of posterior
scleritis (Courtesy: Dr V Sangwan)
referred to the distribution of the trigeminal nerve, the temple syndrome. Infectious diseases associated with scleritis include
and the jaw, rather than be localized to the eye alone. Signs of syphilis, post herpes zoster ophthalmicus, tuberculosis, gout,
ocular redness may follow later. In posterior scleral disease Lyme disease, and foreign body.6
there is no redness. The duration of symptoms in scleritis History of preceding bacterial/viral infections, ocular
generally persists from months to years, whereas episcleritis injury, and surgery should be elicited. History regarding
usually resolves within weeks. conditions such as asthma, eczema, food allergy in childhood,
other conditions such as erythema nodosum, late onset asthma,
Systemic Factors skin allergies, venereal disease, parasitic infestation, thyroid
disease, bowel disorders, diabetes, and connective tissue
Most scleral disease are associated with autoimmune
disorders such as rheumatoid arthritis or systemic vasculitis
diseases.5-7 In 15 percent of cases, scleritis is the presenting
should be sought for. An increased incidence of scleritis has
manifestation of collagen vascular disorder and may precede
been reported in patients taking bisphosphonates, which are
additional symptoms by one to several months.6
commonly used in the management of osteoporosis.6
Scleritis coexists with serious systemic disease in almost
50 percent of cases with the underlying problem frequently
Progression
being a connective tissue disorder. Rheumatoid arthritis (RA)
is the underlying disease in approximately one sixth of patients A careful history not only aids correct diagnosis but also helps
suffering from scleritis, and approximately one percent of define the progress of the condition. In episcleritis, recurrences
patients with rheumatoid arthritis develop scleritis at some are common in one or both eyes. These are usually not long
point in the course of the disease. Scleritis associated with lasting, there is complete recovery in between episodes and
RA is due to the development of a rheumatoid nodule on the vision remains unaffected. In scleritis however, the pain is
sclera and this is associated with an increased risk of mortality.6 usually of the persisting kind, and the eye is never completely
Other connective tissue and autoimmune diseases seen with free of discomfort and inflammation, and vision is
scleritis include systemic lupus erythematosus (SLE), compromised.
polyarteritis nodosa (PAN), seronegative spondyloarthro- Present history includes details on the intensity, type and
pathies, ankylosing spondylitis (AS), psoriatic arthritis, reactive duration of the present condition along with visual
arthritis, Wegener granulomatosis, relapsing polychondritis, disturbances, treatment taken and details of immuno-
sarcoidosis, inflammatory bowel disease, and Sjögren suppressive regimens.3
784 Sclera
Ocular Examination (angle narrowing in acute angle-closure glaucoma, hyphema

in cases of trauma and/or bleeding disorders, hypopyon in
Ocular evaluation is to help in the determination of the site uveitis/iritis) are to be looked for. External findings associated
and depth of involvement, in order to detect scleral swelling with posterior scleritis include restriction of eye movements,
and necrosis. sensitivity to palpation, and proptosis. Fundus evaluation under
Gross examination of the ocular surface and lids helps to dilatation, may be necessary to identify posterior scleritis.
reveal most of the signs of scleral disease. Fundoscopic examination of the patient with posterior scleritis
Daylight examination is most helpful in distinguishing the may also reveal papilledema, choroidal folds, and retinal
salmon-pink appearance of episcleritis, pink infiltration of hemorrhage or retinal detachment (RD).
conjunctival lymphoma, deeper purple hue of active scleral
disease or the semitransparent blue appearance of inactive Assessment for Musculoskeletal and
scleritis. Following scleritis, the sclera shows subtle alterations Connective Tissue Involvement
in color resulting from the reorientation and replacement of SLE, RA, Reiter’s syndrome affect the young and the middle
collagen fibrils. On resolution of the inflammation, a bluish aged. Polymyalgia rheumatica, and giant cell arteritis (GCA)
gray discoloration of the sclera with vascular alterations is affect the old. RA and SLE are more common in women,
readily noticeable. In active diffuse and nodular scleritis, the while ankylosing spondylitis, Reiter’s syndrome and
deep tissue assumes a dark, dusky red hue. In the necrotizing polyarteritis nodosa are common in men. Gout is also more
type, the overlying episcleral and conjunctival vessels show common in men with its onset at around, 40 years of age
changes. Early signs of scleromalacia perforans with yellowish while in women it is postmenopausal. The patient’s
discoloration may be difficult to recognize on slit-lamp occupational and leisure activities are to be noted as
evaluation. arthropathy or soft tissue inflammation involving joints,
Evaluation of the eye by slit-lamp biomicroscopy, red free tendons and bursa, might be related to it. Genetic factors might
light, and transillumination is preferred in patients of scleritis. be present in rheumatoid arthritis, ankylosing spondylitis, gout,
Slit lamp biomicroscopic examination to assess the depth and psoriasis and hemophilia. Drug history is to be elicited as
breadth of involvement, and evaluate for diffuse or segmental addition or withdrawal of drugs may affect the underlying
involvement is essential. Site and depth of inflammation is to condition. Details on the dosage and duration of systemic
be delineated and documented on each visit. Areas of steroid therapy are also to be carefully monitored. Presence
inflammation, swelling, necrosis and thinning should be of any prodromal symptoms suggestive of connective tissue
identified. Widespread injection of the conjunctival and deep disorder is to be looked for.6
scleral vessels is characteristic of diffuse anterior scleritis.
Localized elevation of the sclera is representative of nodular INFECTIOUS SCLERITIS
anterior scleritis. Nodules in anterior scleritis are immobile,
differing from the nonmobile nodules that can be seen in Infectious scleritis8 may be bacterial, viral (Herpes zoster), fungal,
episcleritis. Scleral thinning is suggested when the uveal protozoan or parasitic. Acute infections are mostly by bacteria
pigment is seen. This is a blue-violet hue best seen in natural (Staphylococci, Pseudomonas, Proteus). Such processes usually are
lighting. Red-free filter (green light) helps to identify avascular accompanied by conjunctivitis with purulent exudate. Deep
areas of the sclera. Examination of the vascular networks bacterial infiltrates in the presence of scleral necrosis may
(conjunctival plexus, superficial episcleral plexus, and deep involve the vitreous. In these cases, gram-negative organisms
scleral plexus) helps to distinguish the layer of involvement. tend to be present. Staphylococci can also cause chronic
Besides examination of areas of exudation, granuloma infections, with the formation of granulomas or fistulas.
formation and neovascularization, evaluation should also Painful nodules, conjunctival and scleral ulcers may be seen.
include visual acuity changes, changes in the refractive status, The edges of scleritis gives important diagnostic clues, in
corneal involvement, presence of uveitis/cyclitis, choroidal infectious scleritis they may be more yellowish white as against
effusion and non-rhegmatogenous retinal detachment, the noninfectious scleritis where they are more whitish and
intraocular pressure elevation and orbital involvement. avascular. Scrapings from these edges can give clues about the
Globe perforation typically results in an abnormal shape microorganisms present. Negative scraping with non resolving
of the pupil and/or uveal or vitreous prolapse. Corneal changes nature of scleritis with high index of suspicion should prompt
may be seen in up to 50 percent of cases. Anterior chamber scleral deroofing or scleral biopsy to look for the infective
evaluation for possible narrowing, hyphema, or hypopyon, microorganism.
SURGICALLY INDUCED are other important causes. In endogenous inflammation, the

NECROTIZING SCLERITIS causative factor can be due to infectious agents including,
herpes, syphilis, and tuberculosis, though true infection of
Surgically induced necrotizing scleritis (SINS)9 is a rare
the sclera is rare. Non-specific granulomatous scleritis can
complication of ocular surgery. Most commonly seen after
occur more frequently and is seen most commonly in the
cataract surgery, it may also be seen after glaucoma, RD, squint
connective tissue disorders. Connective tissue diseases also
or even pterygium surgery, more so with multiple surgeries on
form an important causative factor.
the same eye. It may occur from a few days to a few decades
after surgery. It is consistently seen around the site of the
surgical wound on the sclera. The etiology is unknown, but Vasculitis
more than half of them have an underlying autoimmune or Vasculitis of the sclera does not occur. It is affected secondarily
metabolic disorders like diabetes mellitus and dysthyroid status. in vasculitis, associated inflammatory diseases of the uvea and
It is rarely associated with local infection. Unlike other forms panophthalmitis.
of scleritis, SINS is mostly necrotizing in nature and may even
be the initial manifestation of serious systemic disease. Thus, Metabolic
all the patients with SINS need to be investigated appropriately.
Deposition of uric acid and cystine crystals, are seen in gout
Treatment is very difficult and protracted. Systemic steroids and cystinosis respectively. No signs of inflammation are
remain the mainstay, as they do not respond to NSAIDs. Pulse detected. Homogentisic acid metabolism, altered in
intravenous methyl prednisolone therapy followed by high alkaptonuria, can lead to pigmentation of the sclera. High levels
dosages of corticosteroids and immunosuppressive agents of circulating calcium, and defects in fat metabolism can lead
form the mainstay of treatment. In severe and rapidly to depositions in the sclera. The most familiar deposition is
progressive cases, cyclophosphamide is the drug of choice. the abnormal accumulation of bilirubin as seen in the icterus
Cyclosporine is also reported to be effective. of jaundice. Lipids get deposited between the scleral fibers,
and the globe can assume a yellow appearance. Frequently
SCLERAL DEGENERATION/THINNING there are deposits of calcium also causing whitish plaques.
Scleral degenerations may be secondary to aging or diseases. Following severe inflammations of the sclera, amyloid
Conditions associated with scleral degeneration include: deposition may occur.
Progressive Myopia Tumors
Pathological myopia results in progressive thinning of the There are no known primary tumors of the sclera. Metastatic
disease resulting in secondary involvement of the sclera, are
sclera. The exact cause is not clear. Genetic predisposition,
associated with breast or lung cancer in its late stages. The
eye-rubbing and prolonged exposure to night time lighting
sclera, because of its tough fibrous structure, prevents the
are possible causative associations.
spread of intraocular tumors. Tumors which affect the uveal
tract, such as melanomas, myleomas and sarcoid, can spread
Staphyloma
through the vascular channels and nerve bundle perforations
Scleral thinning predisposes to ectasias, which occurs due to of the sclera.
scleral outward distortion. When uveal tissue is also involved,
it is referred to as a staphyloma. The location of the staphyloma Pigmented Abnormalities
may be anterior, intercalary, ciliary, equatorial or posterior.
Anterior and intercalary staphylomas may be associated with Thinning of the sclera can be seen in newborns and young
children, giving rise to a bluish tinge due to the appearance of
retinal detachment and glaucoma.
the underlying uvea and choroid through the transparent sclera.
Melanotic pigmentation of the sclera is often seen in the
Granulomatous Inflammations
pigmented races as a normal occurrence. This is usually not
Exogenous or endogenous granulomatous inflammation result congenital, as it appears following birth. Small cuffs of melanin
in scleral pathology. Infectious microbial agents cause can be seen surrounding the vascular channels. When this
exogenous inflammations affecting the sclera. Scleral band normal pigmentation is associated with a neural vascular
infections, suture related wound abscesses and foreign bodies bundle, it is known as an Axenfeld’s loop. Scleral pigmentation
786 Sclera
might also occur as a representation of intraocular disease, INVESTIGATIONS OF A PATIENT

such as malignant melanoma. Causes of blue sclera include WITH SCLERITIS
Pagets disease (osteogenesis imperfecta), Ehlers-Danlos
syndrome, alkaptonuria and other conditions such as acid The work-up of scleritis should1-4 include a complete physical
phosphatase deficiency, Al Gazali Sabrinathan Nair syndrome, examination, with attention to the joints, skin, cardiovascular
and Diamond-Blackfan anemia. and respiratory system. The following laboratory tests are
recommended:
COMPLICATIONS OF SCLERAL DISEASES • CBC with differential counts
• ESR
Episcleritis • Serum antibody screen (antinuclear antibodies, anti-DNA
• Localized stromal keratitis antibodies, rheumatoid factors)
• Dellen formation • ANCA in cases with bilateral necrotizing scleritis
• Chest X-ray to look for underlying pulmonary involvement
arising from systemic disease.
Scleritis
• Mantoux test
Non-necrotizing scleritis Necrotizing scleritis Additional laboratory tests may be indicated based on the
• Infiltrative • Infiltrative clinical findings.
Localized stromal keratitis Acute stromal keratitis B-scan ultrasonography may assist in detecting posterior
Diffuse stromal keratitis scleritis.
Sclerozing keratitis Imaging of the sacroiliac joints is prudent when ankylosing
Deep stromal keratitis spondylitis is suspected.
Acute stromal keratitis Other tests include instillation of phenylephrine, a
• Destructive • Destructive mydriatic vasoconstrictor which helps differentiate deep scleral
Peripheral corneal thinning Contact lens cornea episcleral blood vessel involvement from superficial
Ulcerative keratitis Keratolysis involvement. Superficial vessels blanch following instillation
of phenylephrine, while deeper vessels remain unaffected.
Complications1-4 are common in severe scleral disease and
may lead to visual loss. Scleral inflammation leads to structural
TREATMENT
changes resulting in the involved scleral tissue becoming
translucent and blue colored. Tissue loss occurs in severe NSAIDs are particularly effective in nodular and diffuse
necrotizing disease and transillumination helps to determine scleritis and are prescribed for at least one week. High-dose
tissue loss. In the event of tissue loss, an associated intraocular oral prednisone is used primarily in necrotizing scleritis and
pressure rise may lead to staphyloma formation, but severe non-necrotizing scleritis or in cases of recurrent/
spontaneous perforation is rare. refractory scleritis. Immunosuppressive agents are used as an
Corneal involvement is mild in episcleritis with transient adjunct when steroids alone fail to control progression of the
corneal infiltration and dellen in the adjoining cornea. Severe disease. These dr ugs have serious side effects and
or recurrent scleral disease may have associated corneal contraindications and should be prescribed with caution.
involvement in form of infiltrative keratitis or ulcers which
may be superficial, midstromal or deep stromal. Corneal Episcleritis
involvement may be confined to the periphery or may involve
the whole cornea. With exclusion of conditions such as raised uric acid levels,
Association of uveitis in anterior scleral disease is rare and gout, rosacea, atopy, herpes and rheumatoid factor, simple
is found to occur in the severe forms. Posterior scleral episcleritis generally does not require treatment since it is self-
inflammation may have associated uveal effusions, choroidal limiting and fades within a few days. Treatment with anti-
lesions and optic disc edema. Glaucoma may worsen with inflammatory agents tends to promote more frequent and
scleral disease. The orbit and muscles may get involved in scleral vigorous recurrences. Available treatment modalities include
disease but scleral involvement secondary to orbital topical or systemic steroids (controversial) and topical or
inflammation can also occur. systemic NSAID (diclofenac, ketorolac, indomethacin,
ibuprofen or piroxicam). One of the latter is usually effective, Scleritis

even though several may need to be tried in succession.
Diffuse and Nodular Scleritis
Treatment is similar in cases of nodular episcleritis, where
the attacks usually last a few weeks. If the condition persists, Systemic NSAID therapy with sustained-release indomethacin
systemic (oral) NSAID may be given (Indomethacin 75–100 75 mg bid is prescribed. In case of therapeutic failure, high
mg daily or sustained release 75 mg bid, diflunisal 500 mg bid, doses of systemic steroids is given (oral prednisone 1–1.5 mg/
kg/day) and tapered slowly every week. When the response is
naproxen 375 to 500 mg bid, ibuprofen 400 mg to 600 mg qid
unsatisfactory, methotrexate (7.5–15 mg once weekly) or
or piroxicam 20 mg qid). Recurrences are common. They cease
azathioprine (2 mg/kg/day) should be considered, particularly
eventually, unless true scleritis supervenes.
in patients with SLE. Cyclophosphamide (1–2 mg/kg/day) is
In patients with episcleritis along with connective tissue
mandatory in Wegener’s granulomatosis and in polyarteritis
disease (rheumatoid arthritis or spondyloarthropathy), where
nodosa. Subconjunctival injections of steroids are contra-
treatment failures can commonly occur, systemic immuno- indicated in necrotizing scleritis because of the risk of scleral
suppression with oral methotrexate in a dose of 7.5 mg once melting and perforation. 10 Immunosuppressive therapy
a week for a period of three to five months is advocated. prescribed in scleral disease is elaborated in Table 8.1.
Table 8.1: Immunosuppressive therapy in scleral diseases of the eye
Immunosuppressive Dosage Adverse reactions Monitor

agent
1. Glucocorticoids:
a. Methylprednisolone Adult: 1 g IV 3 times/week Hypersensitivity; viral, fungal, Hyperglycemia, peptic ulcer disease
or tubercular skin infections hypokalemia, osteonecrosis,
osteoporosis, euphoria, psychosis,
growth suppression, myopathy and
infections
b. Prednisone Adult: 60–120 mg PO/day;
gradual taper over 2–3 wk
until discontinuation
Pediatric: 2 mg/kg PO/day
2. Methotrexate Adult: 7.5–15 mg PO/week or Hypersensitivity, alcoholism CBCs monthly liver and renal function
15 mg IM/week hepatic insufficiency, blood every 1–3 months during therapy (more
Pediatric: 5–15 mg/m2 /week dyscrasias, immunodeficiency frequently during initial dosing, dose
PO/IM as a single dose or as syndromes adjustments, or when risk of elevated
3 divided doses given 12 hour methotrexate levels, e.g. dehydration)
apart
3. Cyclophosphamide Adult and pediatric: Hypersensitivity, depressed bone Hematologic profile (particularly
1–2 mg/kg/d PO marrow function neutrophils and platelets in urine
for RBCs and detection of
hemorrhagic cystitis
4. Azathioprine Adult: 1 mg/kg/d PO/IV for Hypersensitivity Increases risk of neoplasia
6–8 week; increase by hepatic and renal impairment
0.5 mg/kg every 4 week until Hematologic toxicity
response or maximum dose
of 2.5 mg/kg/d
Pediatric: Initial: 2–5 mg/kg/d
PO/IV
Maintenance: 1–2 mg/kg/d PO/IV
5. Cyclosporine Adult and Pediatric: 3–5 mg/kg Hypersensitivity, uncontrolled Renal and liver functions, may
PO bd hypertension, malignancies increase risk of infection and lymphoma
788 Sclera
Necrotizing Scleritis REFERENCES

Only early stages are amenable to medical treatment (i.e. prior 1. Watson PG, Hazleman BL, Pavesio CE, Green WR. The sclera
to the advent of necrosis, which begins as yellowish avascular and systemic disorders. Second edtion. Butterworth-Heinemann
nodules). Short-term therapy with methyl prednisone is given Elsevier limited, Philadelphia, USA, 2004.
2. Akpek EK, Thorne JE, Qazi FA, et al. Evaluation of patients with
as intravenous pulse therapy. Immunosuppressive therapy with scleritis for systemic disease. Ophthalmology 2004;111(3):501-6.
cytotoxic drugs is usually required, and the treatment of choice 3. Watson PG, Hayreh SS. Scleritis and Episcleritis. Br J Ophthalmol
for necrotizing scleritis includes cyclophosphamide (1–2 mg/ 1976;60(3):163-91.
kg/day), azathioprine (1–2 mg/kg/day) and methotrexate (7.5– 4. Okhravi N, Odufuwa B, McCluskey P, Lightman S. Scleritis. Surv
15 mg once per week). Wearing of protective goggles is advisable Ophthalmol 2005;50(4):351-63. Review.
when the sclera is thin. In all cases, consultation with a 5. Usui Y, Parikh J, Goto H, Rao NA. Immunopathology of
rheumatologist is advisable. necrotising scleritis. Br J Ophthalmol 2008;92(3):417-9.
6. Pavesio CE, Meier FM. Systemic disorders associated with
episcleritis and scleritis. Curr Opin Ophthalmol 2001;12(6):471-8.
Treatment of Infective Scleritis
Review.
Biopsy helps to identify the causative organism. Intensive 7. Galor A, Thorne JE. Scleritis and peripheral ulcerative keratitis.
Rheum Dis Clin North Am 2007;33(4):835-54, vii. Review.
antibiotic therapy, topical and systemic is usually is required in
8. Rich RM, Smiddy WE, Davis JL. Infectious scleritis after retinal
cases of infective scleritis. Acanthamoeba scleritis tends to have
surgery. Am J Ophthalmol 2008;145(4):695-9.
a poor prognosis and a prolonged refractory course 9. Gokhale NS, Samant R. Surgically induced necrotizing scleritis after
necessitating long-term topical anti-acanthamoeba therapy. In pterygium surgery. Indian J Ophthalmol 2007;55(2):144-6.
the event of any foreign body induced infective scleritis, 10. Michalova K, Lim L. Biologic agents in the management of
surgical removal along with intensive therapy is required to inflammatory eye diseases. Curr Allergy Asthma Rep 2008;8(4):339-
control the disease. 47. Review.
Chapter 9.1
GLAUCOMA: BASIC ASPECTS

AND CLASSIFICATION
Parul Sony
ANGLE OF THE ANTERIOR CHAMBER Trabecular meshwork extends between the Schwalbe`s line
anteriorly and the scleral spur posteriorly. It has varied
The angle of the anterior chamber is the peripheral recess
appearance owing to its structure and amount of pigmentation.
bound anteriorly by the corneosclera and posteriorly by
The pigmentation varies from light gray to dark brown.3
the root of the iris and the ciliary body. It has an important
Schwalbe's line is the anterior most structure in the angle
role in the process of aqueous drainage. Direct, view of
formed by the prominent end of Descemet's membrane of
the angle structures is not possible due to total internal
the cornea. It is seen as a fine ridge just in front of the
reflection which, when eliminated allows detailed
trabecular meshwork.
observation of the angle structure. The various structures
seen from posterior to anterior include the root of the
Angle: Microscopic Anatomy
iris, ciliary body band, scleral spur, trabecular meshwork
and Structure
and the Schwalbe`s line (Fig. 9.1.1).1 With gonioscopic
examination, the angle width can be graded using various These structures are (Fig 9.1.2)
systems mentioned in literature.
Scleral Spur
The ciliary body band is formed by the anterior most part
of the ciliary body that lies between the scleral spur and the Present at the posterior wall of the scleral sulcus, the scleral
root of iris. It is brown or gray in color. Its width depends on spur is formed by the inward projecting fibers of the scleral
the level of insertion of the iris root. roll, which in turn is formed by the group of fibers that run
Scleral spur is seen as a white line between the ciliary body parallel to the limbus.2 The scleral spur is composed of mainly
band and the trabecular meshwork and is formed by the collagen fibers with few elastin fibers. The scleral spur prevents
posterior portion of scleral sulcus.2 collapse of the Schlemm's canal.
Fig. 9.1.1: Anatomy of the anterior chamber angle

792 Glaucoma
Fig. 9.1.2: Microscopic anatomy of the trabecular meshwork
Schwalbe's Line 1. The uveal meshwork;

2. The corneoscleral meshwork;
The Schwalbe's line marks the termination of Descemet's
3. The juxtacanalicular meshwork or the cribriform layer.
membrane. It is seen as a discontinuous elevated white line,
The uveal meshwork is the innermost part of trabecular
and is formed by the oblique insertion of the uveal trabeculae
meshwork that merges with the ciliary body and the root of
into the limbal stroma. It lines the posterior border of a
the iris posteriorly and corneal stroma near the Schwalbe's
smooth area (50–150 microns width) called zone S formed
line anteriorly.3 It comprises of trabecular beams or bands
due to transition of trabecular endothelium to corneal
which have a central core that mainly consists of collagenous
endothelium.
fibers distributed with a few elastic fibers, and is lined by
trabecular endothelial cells resting on a thick basement
Trabecular Meshwork
membrane. These trabecular beams run mostly in radial
Trabecular meshwork is a sieve like structure consisting of fashion, and have pores and openings of 25 to 75 microns.
lamellated sheets that bridges the scleral spur converting it The corneoscleral meshwork forms the main portion of
into Schlemm's canal.3-6 It is the main structure which allows the trabecular meshwork. It extends from the scleral spur
outflow of aqueous from the eye. posteriorly to cornea anteriorly. It consists of flat interlacing
beams and plates comprising a central core made of collagen
Anterior Trabecular Meshwork and elastic fibers similar to the uveal meshwork and are lined
by a single layer of enothelial cells supported by a basement
This is the anterior most part of the trabecular meshwork
membrane. The average pore size is smaller than the uveal
that lies just posterior to the Schwalbe's line, adjacent to limbus
meshwork (5–50 microns) and may be further smaller (1–2
and has no contact with the Schlemm's canal. This is the non
microns) in the outer most part.
filtering part of the trabecular meshwork. It consists of three
The juxtacanalicular meshwork (cribrifor m layer,
to five trabecular beams covered with trabecular cells.
endothelial meshwork) is the outermost part of the trabecular
meshwork that lies adjacent to the inner wall of the Schlemm's
Filtering Trabecular Meshwork
canal.6 It consists of a network of fine fibrils, elastic like
The trabecular meshwork that lies adjacent to the inner wall fibers and elongated fibroblasts like cells arranged in layers
of the Schlemm’s canal forms the filtering meshwork. It is and embedded in homogenous extracellular matrix. This
further divided into three functionally and morphologically portion of the meshwork offers maximum resistance to the
different portions: aqueous outflow.
Glaucoma: Basic Aspects and Classification 793
CELL SYSTEM AND CELL BIOLOGY the canal open. It is covered with a single layer endothelial lining.
OF TRABECULAR MESHWORK The endothelial cells of the inner wall are elongated and spindle
The trabecular meshwork contains three basic cells: shaped and contains giant vacuoles. The outer wall cells are
1. The trabecular cells rest on a basement membrane and shorter and flatter with larger surface area and are well
cover the beams of the uveal meshwork, and plates and supported by a complete basement membrane.
strands of the corneoscleral meshwork. These cells
produce glycosaminoglycans (GAG), extracellular Intrascleral Collector Channels
glycoproteins (laminin, fibronectin and thrombospondin) The outer wall of Schlemm's canal has 25 to 35 opening for
and fibrillar material. The GAGs include mainly the the collector channels. These connect the Schlemm's canal to
hyaluronic acid and others like chondroitin, heparan, the episcleral and conjunctival veins of the limbal region.
keratan and dermatan sulfate. The main collagen These are of two types:
synthesized includes type I, III, IV, V and VI. The 1. Direct collector channels (Aqueous veins of Ascher) are
trabecular cells are highly phagocytic. They play an four to five in number and directly run from the
important role in cleaning the aqueous from particles, Schlemm's canal to the episcleral venous plexus without
cellular debris, proteins molecules, red blood cells, bacteria any intervening intrascleral veins.
and pigment granules, thus preventing the obstruction of 2. Indirect collector channels are numerous and short and
the intertrabecular pathways. They are derived from neural join the intrascleral capillary network soon after leaving
crest cells. the Schlemm's canal.
2. The cribriform cells lack any basement membrane support
and are embedded in homogenous extracellular matrix. Episcleral and Conjunctival Veins
These are derived perivascular cells, and are responsible
The collector aqueous vessels join the episcleral and
for extracellular substance.
conjunctival venous systems by several routes. The direct
3. The endothelial cells of Schlemm's canal rest on the
system drains directly into the episcleral veins, then into the
basement membrane which they themselves produce.6
cavernous sinus via the anterior ciliary and superior ophthalmic
These are mesodermal in origin and are capable of
veins. Other collector channels cross the conjunctival tissue
developing pores and vacuoles which allows aqueous
and drain into conjunctival veins in the perilimbal area. The
outflow.
conjunctival veins drain into the superior ophthalmic and
Schlemm's Canal and Collecter’s Channel facial veins via the palpebral and angular veins.
Schlemm's Canal CILIARY BODY AND

Schlemm's canal is a circular channel embedded in the scleral THE CILIARY PROCESSES
sulcus.5,7 Its diameter varies from 350 to 500 microns (Fig. The ciliary body is a part of the uveal tract. It is a triangular
9.1.3). Anterior lumen is usually collapsed and posterior lumen structure comprising the ciliary body muscle, vessels, the ciliary
is wide. The canal is not uniform in shape and size and processes and the nerve terminals.
frequently split by septa and bridges which also help to keep
Ciliary Body Muscle
Ciliary body muscle has longitudinal and the circular fibers.
The circular fibers run parallel to the limbus and are present
anteriorly and inwards. The longitudinal fibers attach the ciliary
body to the limbus at the scleral spur. The radial fibers connect
the circular and the longitudinal fibers.
Ciliary Body Vessels

The major arterial circle is the main source of blood supply
to the ciliary body. It lies near the root of the iris and is
formed by the anastmosis between the anterior ciliary arteries
Fig. 9.1.3: Microanatomy of collecter channels and Schlemm's canal and the long posterior ciliary arteries. The major arterial circle
794 Glaucoma
gives rise to the anterior and posterior ciliary process arterioles layered epithelium. The non-pigmented epithelial cells and its
that supplies the ciliary processes. various junctions form the main barrier for aqueous production.
Ciliary Processes Aqueous Humor Production
The ciliary processes are the functional unit for production Molecular Mechanism
of aqueous humor.8 Each ciliary process contains a capillary The three main processes involved in aqueous formation
network, the stroma and the epithelium. The ciliary body include:
capillaries endothelium is thin and overlies a basement • Diffusion involves transport of lipid soluble substances
membrane. The stroma surrounds the capillaries and is through the lipid portion of cell membrane across the
composed of mucopolysaccharides, proteins and collagen. concentration gradient
The ciliary epithelium is a bilayered structure with outer • Ultrafiltration is transport of water and water soluble
pigmented and inner non-pigmented epithelium. The substance across the cell membrane through the protein
pigmented epithelium has melanin granules and atypical micropores along the osmotic gradient and hydrostatic
basement membrane on the stromal side. The nonpigmented pressure
epithelium is the main site that forms the blood aqueous • Active Secretion is responsible for 80 to 90 percent of
barrier. The non-pigmented epithelium lies on a basement total aqueous secretion. It involves active transport of
membrane that is composed of glycoproteins, laminin and large size charged substances against the concentration
collagen. The cells have various intercellular junctions. The gradient with expenditure of energy. It is mediated through
main ones are the gap junction which exist between the the proteins in the cell membrane and the energy is derived
pigmented epithelium cells, the non-pigmented cells and also by hydrolysis of adenosine triphosphate (ATP).
between the pigmented and non-pigmented cells. The tight
Main steps of aqueous humor production are:
junctions exist only between the non-pigmented cells and form
• Accumulation of plasma reservoir: At the start diffusion
barrier for intermediate and high molecular weight substance
and ultrafiltration results in accumulation of most of
like proteins.8,9
plasma substance behind the tight junction of the
Innervation of Ciliary Body nonpigmented epithelium
• Active transport across the blood aqueous barrier: This
The ciliary body is innervated both by parasympathetic and
transport involve transcellular movement of cations (Na+,
sympathetic nerve fibers. The parasympathetic fibers arise
K+) and anions (HCO3– and Cl–) and other substance
from the Edinger Westphal nucleus, run via the oculomotor
across the nonpigmented epithelium
nerve and end up in the ciliary ganglion. The postganglionic
– 70 percent of Na+ is actively transported into the
fibers supply the ciliary body muscle. Stimulation of the
posterior chamber. Two main enzymes involved in
parasympathetic system releases acetylcholine that stimulates
this transport are Na + K + ATPase and carbonic
cholinergic receptors resulting in contraction of the ciliary
anhydrase. Na+ is mainly transported through this
muscle and increased conventional aqueous outflow via the
enzyme. Other transporters for Na include Na+–K+–
trabecular meshwork. The sympathetic fibers originate from
Cl+ symport and parallel Na+ –H+ antiport. Glycosides
the ciliospinal center of Budge, synapse in the superior cervical
like oubain and vanadate reduce aqueous production
ganglion and innervate the ciliary body blood vessels. Mediating
by inhibiting Na+ K+ ATPase enzyme. Potassium is
through the adrenergic receptors and with the catecholamines
mainly transported via active secretion and also via
as neurotransmitters the sympathetic system increases aqueous
diffusion. There are three types of channels for K+
humor secretion by the ciliary epithelium.
transport. Chloride ion is also actively transported
through Cl– channels.
AQUEOUS HUMOR
– Carbonic anhydrase facilitates transport of bicarbonate
Aqueous humor is an intraocular fluid derived from the plasma by mediating rapid interconversion between HCO3 and
within the capillary network of the ciliary processes.10 It is CO2. Bicarbonate further effects Na+ transport by
produced by the tip of the ciliary processes and is secreted regulating the pH for optimim active transport of Na+.
into the posterior chamber from where it flows around the – Other substances that are transported actively include
lens, through the pupil into the anterior chamber. The aqueous ascorbic acid which is transported by Na+ dependent
secretion is through the capillary wall, stroma and the double transporter, and various amino acids.
• Osmotic flow: Once various substances are actively, secreted, Adenylcyclase is an enzyme demonstrated in the epithelium
an osmotic gradient develops across the ciliary epithelium. of the ciliary body that plays a role in the synthesis of cAMP.
This gradient result in movement of water and other cAMP increases aqueous formation. The majority of
plasma constituents via diffusion and ultrafiltration. receptors in ciliary body are α-2 and β-2. The α-2 receptors
are inhibitory and their stimulation results in inhibition of
Rate of Aqueous Humor Production adenylcyclase and thus decreased aqueous production.
Stimulation of β receptors results in activation of
The rate at which the aqueous humor is produced measured
adenylcyclase and increased production of aqueous.
in microliters per minute. The normal rate is 2.68±0.064µL/
Decreased inflow of aqueous is seen in a variety of ocular
min (range 1.5–4.5 µL/min). The rate of aqueous formation
and systemic conditions including diabetes mellitus, myotonic
varies throughout the day and follows a circadian rhythm.
dystrophy, and ocular conditions like uveitis, acute phase of
The rate is low during the night, when it is almost half of,
hypotony, choroidal detachment, and retinal detachment.
that during the morning hours. Thus, β-blockers are less
Aqueous production also decreases with aging. Additionally
effective during sleep.
males have insignificantly higher rate of aqueous production
compared to females.
Measurement of Aqueous
Normal tension glaucoma and patients with ocular
Humor Production
hypertension have been shown to have normal aqueous inflow
• Methods based on measuring the rate of appearance or rates, whereas eyes with pigment dispersion syndrome have
disappearance of a substance from aqueous like been seen to have increased flow rates compared to controls.
fluorescein, radiolabelled isotopes and parahippuric acid. Intake of large amount of water over a short period (1 liter)
These techniques involve measurement of the rate of is also associated with increased inflow of aqueous due to
accumulation or dilution or decay of a given substance osmotic stress.
from the anterior chamber Exogenous pharmacologic agents which reduce aqueous
• Direct measurement of aqueous production is based on inflow are used in the treatment of glaucoma. These include
the equation. β blockers, (nonselective and selective α receptor) and carbonic
Flow = C (Po-Pv), where anhydrase inhibitors. Atrial natriuretic peptide, and seratonin
Po = IOP receptor agonists are a few other such agents which are not
Pv = Episcleral venous pressure clinically used.
C = Facility of outflow.
Aqueous Humor Characteristics
Factors Influencing Aqueous
Aqueous humor is a clear, colorless, watery solution that is
Humor Production
produced in the posterior chamber and circulates to the
Both endogenous and exogenous factors influence aqueous anterior chamber.12 It serves various functions in the eye; it
humor inflow. Aqueous production is influenced by various maintains proper intraocular pressure (IOP), it provides
complex hormonal factors. Sympathetic system and serum glucose, metabolites (electrolytes, aminoacids) and oxygen to
epinephrine are important factors which stimulates aqueous the cornea and lens, it mediates substrate for anterior chamber
production. The ciliary epithelium does not show presence immune reaction and paracrine signalling through the aqueous,
of nerve supply, but the vessels of ciliary process exhibit it provides high concentration of vitamin C, and its
dense sympathetic innervations that influence aqueous transparency aids in maintaining the optical system of the
formation.11 Topical epinephrine has been shown to stimulate eye. In addition, it also clears the anterior chamber of various
flow by 19 percent during the day and 47 percent during the substances like blood, macrophages, and inflammatory
evening. Norepinephrine has less effect than epinephrine. products.
Despite this, it is interesting to note that the circadian rhythm Aqueous humor is slightly hypertonic when compared to
is maintained even after adrenalectomy and in patients with plasma and acidic with a pH of 7.2 (Table 9.1.1). It has a
horner's syndrome with absent sympathetic innervation. volume of 0.31 ml (0.25 ml in the anterior chamber and
Exogenous corticosteriods augment epinephrine mediated 0.06 ml in the posterior chamber). It has a refractive index
stimulation of aqueous production. Hormones like of 1.336 (slightly lower than cornea). Both, its viscosity and
vasopressin increase aqueous production by enhancing the osmotic pressure, are slightly higher compared to water and
active transport of Na+ across the ciliary epithelium. plasma respectively.
796 Glaucoma
Table 9.1.1: Characteristics of human aqueous compared to the anterior chamber, whereas concentration of
humor compared to plasma sodium, chloride ions, lactate and urea is higher in the anterior
• Slightly hypertonic chamber.
• Acidic (pH 7.2 in anterior chamber)
• Marked deficit in proteins (5–10 mg/100 ml vs 6–7 gm/100 ml)
• Marked excess of ascorbate (0.96 mmol/L vs 0.02 mmol/L) Factors Affecting Aqueous
• Slight excess of Humor Composition
– Chloride
– Lactate Blood aqueous barrier is formed by the tight junctions between
– Pyruvate the nonpigmented epithelium cells of the ciliary body and
• Slight excess of
– Sodium also by the endothelium of the capillaries. These capillaries
– Glucose become leaky in inflammatory conditions and result in flare.
– Bicarbonate With the breakdown of blood aqueous barrier, the proteins
– Carbondioxide
– Urea
and antibodies come in aqueous making it plasmoid aqueous.
• Other components Increased proteins results in the Tyndall effect. The entry
– Aminoacids rate of other substances like fluorescein dye and sucrose
– Sodium hyaluronate
– Norepinephrine
also increase. The fibrinogen results in partial clotting of
– Tissue plasminogen activator aqueous.
Comprising 99.9 percent of water, aqueous contains Aqueous Humor Outflow

almost 15 times higher concentration of ascorbate compared Cellular Organization
to plasma and is markedly deficient in proteins (0.02% in
aqueous compared to 7% in plasma). Immunoglobulin (Ig) Aqueous is produced in the posterior chamber and flows to
concentration of aqueous is also low, with IgG, being the main the anterior chamber, it leaves the eye at the anterior chamber
one. Others like IgA, IgD, and IgM are usually absent. This angle passing through trabecular meshwork, Schlemm's canal
low concentration is because of the blood aqueous barrier. intrascleral channels, episcleral veins and conjunctival veins.13-15
The aqueous proteins are mainly derived from plasma, but The two main routes of aqueous outflow are the
some studies state that these are derived from intrinsic conventional (trabecular) outflow and the unconventional
glycoproteins of vitreous. In an inflammed eye with disruption (uveoscleral) outflow.
of blood aqueous barrier the protein concentration of aqueous
Unconventional Outflow
increases. The concentration of aminoacids which are actively
secreted varies in aqueous. The ratio between aqueous and Unconventional outflow is responsible for 10 to 25 percent
plasma varies from 0.08 to 3.14. Concentration of most of of the total aqueous outflow. Two pathways described for
the other electrolytes and nonelectrolytes is very close to the unconventional outflow include:
plasma, however aqueous is slightly deficient in sodium (Na), • Uveoscleral outflow is through the iris root and anterior
potassium (K), bicarbonate, carbon dioxide (CO2) and glucose, surface of ciliary body into the suprachoroidal space.14
and has slight excess of chloride, lactate, and pyruvate. From there the aqueous passes via scleral pores
Other molecules present in aqueous include glyco- surrounding the ciliary body blood vessels and nerves or
saminoglycans like sodium hyaluronate, signalling molecules directly through the collagen substance of the sclera.
like catecholamines, norepinephrine, markers for nitric oxide, Suprachoroidal pressure is 2 to 4 mm Hg lower than the
enzymes like collagenase, various growth factors and myocilin. pressure in the anterior chamber. This allows uveoscleral
The composition of aqueous does not remain constant. It drainage. This can get reversed after trabeculectomy and
show changes throughout its intraocular course. Experimental lead to choroidal effusion. The extracellular matrix of
studies have shown that composition of aqueous in the anterior the ciliary body contains various glycoproteins that play
and the posterior chamber is different; however the pH, osmotic an important role in offering resistance to this flow.
pressure and total concentration of solutes is similar. This is Prostaglandin analogs increase uveoscleral outflow,
related to the permeable vessels of the iris that allow passive whereas parasympathomimetics agents like pilocarpine are
transfer of anions and nonelectrolytes into the anterior chamber known to reduce uveoscleral outflow
aqueous. Concentration of bicarbonate ions, glucose, nonprotein • Uveovortex outflow transfers aqueous into the iris vessels
nitrogen and ascorbate is higher in the posterior chamber as and the vortex veins. This flow is contributed by the
osmotic movement of fluid into iris vessels driven by a

high concentration of proteins content of blood.
Conventional Outflow
Trabecular outflow contributes 75 to 90 percent of aqueous
drainage from the eye. The tracer studies show flow is free
uptill the juxtacanalicular meshwork and the inner wall
endothelium of the Schlemm's canal that offer maximum
resistance to aqueous outflow.13
The process of aqueous humor transport across the
trabecular meshwork is a complex one. The trabecular
meshwork endothelial cells have phagocytic properties and
have contractile filaments like vimentin and desmin. These
filaments allow contractile and motilty functions. The
trabecular meshwork extracellular matrix is continuously
remodelled (synthesized and degraded) in order to maintain
patent and low resistant outflow channels. The transport of
aqueous is transcellular. Transport of aqueous is both by
pressure dependent passive transportation and also by
activation of water channel proteins (aquaporin 1). But
primarily the outflow is passive and in response to the pressure Fig. 9.1.4: Diagrammatic representation of the vacuolation theory
gradient.
Various mechanisms have been hypothesized for the
transport of aqueous from the juxtacanalicular meshwork baseline IOP (Po) is recorded, and then a known volume
into the Schlemm's canal. of fluid is injected at known pressure (Pi).
• Vacuolation theory of transcellular transport:15 In response Flow rate
to the intraocular pressure, the connective tissue of the C=
Pi – Po
juxtacanalicular meshwork opens various vacuoles and
pores following which the fusion of basal and apical cell • Tonography is a noninvasive method to determine the C
plasmalemma creates temporary channels that allows bulk value. It is performed by using a Schiotz tonometer.
flow of aqueous into the Schlemm's canal (Fig. 9.1.4). Baseline IOP reading is recorded as Po and the change in
• Intracellular transport theory: This says that aqueous flow scale reading over 4 min period (ΔR) are used to obtain
occurs via paracellular routes between the inner wall the C value from the special tonographic table. The average
endothelial cells. C value is 0.28±0.05 µl/min/mm Hg. Most of the
• Sonderman's canal: The role of transport through glaucoma patients have reduced C value. Measurement
Sonderman's canal, which are endothelial lined channels of C value using tonography is affected by ocular rigidity;
that communicate intertrabecular spaces with the eyes with low ocular rigidity may have low C value but
Schlemm's canal is still not certain. Transport of aqueous normal Po, whereas eyes with high C value and high Po
from the Schlemm's canal into the episcleral veins is may have high ocular rigidity, or elevated episcleral venous
through direct and indirect systems. It is unidirectional pressure or angle closure glaucoma.
and is dependent on pressure difference between the
Resistance to Aqueous Outflow
anterior chamber and intrascleral venous pressure. The
and its Molecular Mechanism
quantitative measure of outflow of aqueous is termed as
facility of aqueous outflow (C-value). It is expressed as The dynamics of aqueous outflow is a complex one, and the
the outflow in microliters per minute per millimeter of exact site and nature of resistance to aqueous outflow is still
mercury (µl/min/mm Hg). It can be measured using unknown. It is believed that most of the resistance (60–65%)
perfusion method, suction cup method or tonography. is within the trabecular meshwork, the remaining is offered
• Perfusion is restricted to experimental animals or by the sclera (25% by inner half of sclera and remaining
enucleated eyes as it involves cannulation of the eye. Initial 15% by the outer half of sclera).
798 Glaucoma
• Majority of resistance is offered by the juxtacanalicular during the past few decades. Glaucoma is a family of diseases
trabecular meshwork and the inner wall of endothelial not defined by a specific intraocular pressure but rather as
layer an optic neuropathy that can occur at any intraocular pressure
• Glycosaminoglycans (hyaluronic acid, chondrotin sulfate, depending on the optic nerve susceptibility of the individual
keratan sulfate, heparan sulfate) have been shown to person. The traditional classification of glaucoma consists
modulate the flow by changing the microenvironment of of classifying glaucoma into primary and secondary types.16
extracellular matrix and the flow channels. Enzymes that With better understanding of the underlying, predisposing
metabolize GAGs increase the outflow facility by ocular and systemic events, the classification of glaucoma
decreasing the resistance has changed and improved substantially. Two main
• Glucocorticoids have complex effect on aqueous outflow. classification systems currently used for classifying clinical
Glucocorticoids inhibit the synthesis of endogenous glaucoma are:
prostaglandins which have been shown to increase IOP • Etiologic (based on the initial events leading to glaucoma)
in higher doses by exerting direct effect on extracellular • Mechanical (based on the mechanism of outflow
matrix metabolism, and in low doses prostaglandins reduce obstruction)
ocular pressure in moderate and low concentration The etiologic or initial event classification is based on the
• Myocilin expression has also been linked to influence fact that glaucoma evolves through five different stages which
trabecular outflow in the pressure dependent pathway include; an initial sequence
• Contractile microfilaments contribute towards the of events, which cause changes in aqueous outflow system,
resistance to aqueous outflow, and the substances that which result in intraocular pressure (IOP) elevation, which lead
disrupt these microfilaments reduce the resistance to to glaucomatous changes in optic nerve head (glaucomatous
aqueous outflow optic neuropathy) and progressive visual field loss. This staging
• Sulfhydryl groups have dual effect on aqueous outflow. system has a disadvantage that it assumes that increased IOP
Some agents increase outflow facility whereas other is the only factor contributing to glaucomatous optic neuropathy;
decrease it by causing swelling of the trabecular meshwork and it ignores the pressure independent factors like vascular
• Fibrinolytic activity and presence of tissue plasminogen factors. It thus cannot explain normal tension glaucoma (NTG).
activator maintain a balance to keep the outflow system To explain entities like NTG, pressure independent factors
patent from fibrin and platelets have to be included in the five stage pathway with initial events
• Pressure dependent changes in the outflow system has leading to physical alterations (e.g. vascular and structural
been seen. Increased IOP is associated with increased factors) predisposing and leading to optic nerve atrophy and
resistance to aqueous outflow which is related to the visual field changes, thus omitting elevated IOP as one of the
collapse of the Schlemm's canal intervening stage. In depth understanding of initial events may
• Aging has been shown to be associated with decrease in allow development of a rationale for early glaucoma
the lumen size of the Schlemm's canal, narrowing of the intervention in the future. However, currently most treatment
trabecular meshwork and an increase in extracellular strategies focus only on control or reduction of one factor,
matrix, thus resulting in increased resistance to outflow the IOP.16
• Episcleral venous pressure is an important factor affecting The mechanical classification is based on the location and
IOP. An increase in episcleral venous pressure results in type of changes in the anterior chamber angle that lead to
an increase in the IOP. increased IOP and development of glaucoma.17 It divides
glaucoma into open angle mechanisms, closed angle
GLAUCOMA: CLASSIFICATION mechanisms and developmental anomalies of the anterior
Glaucoma has been traditionally defined as that level of intra- chamber angle. These are then further divided based on the
ocular pressure within the eye that produces significant and underlying etiology and specific structural alterations.
characteristic changes in the structure of the optic nerve
head and functional visual changes, most commonly those Classification of Glaucomas
associated with characteristic visual field changes. However, Based on the Initial Events
the pathophysiology, the clinical presentations, and the
management of the different types of glaucoma are so Open Angle Glaucoma
different, that often it is very difficult to have a common The initial event in this subtype is an increased resistance to
definition. Important concepts about glaucoma have evolved aqueous outflow and increased vulnerability of the optic nerve
head to a particular IOP level. This could have a genetic • Angle closure glaucoma, comprising pupillary block
basis. This group includes various glaucomas like:17 glaucoma and combined mechanism glaucoma
• Chronic open angle glaucoma or senile sclerotic glaucoma, • Developmental glaucomas, comprising primary
which is seen in the elderly population. congenital glaucoma, juvenile open angle glaucoma, and
• Normal tension glaucoma, which has normal pressures other developmental anomalies like the Axenfeld Reiger
and the optic nerve head damage, is due to pressure syndrome, Peter's anomaly and aniridia
independent factors, apoptosis being one of them. • Glaucoma associated with ocular and systemic
disorders, comprising glaucomas associated with
Pupillary Block Glaucoma disorders of corneal endothelium like the iridocorneal
endothelium syndrome, posterior polymorphous dystrophy
This subgroup of glaucoma is characterized by pupillary block
and Fuch's endothelial dystrophy; glaucoma associated
being the first event leading to the angle closure and increased
with disorders of iris and ciliary body like pigmentary
IOP. The primary angle closure glaucoma and combined
glaucoma, iridoschisis, iris cysts and plateau iris syndrome;
mechanism glaucoma are the two main subtypes of glaucoma
glaucoma associated with disorders of the lens like the
that are included in this group. Pupillary block glaucoma may
pseudoexfoliation glaucoma and glaucoma associated with
be divided into acute and subacute forms. Chronic angle
cataract like the phacomorphic glaucoma, phacolytic
closure glaucoma and creeping angle closure glaucoma are
glaucoma, phacoanaphylactic glaucoma, phacotoxic
also subtypes of this group. The combined mechanism
glaucoma and glaucoma associated with lens dislocation;
glaucoma is characterized by elevated IOP that persists after
glaucoma associated with disorders of retina, choroid and
a patent peripheral iridotomy for an angle closure component
vitreous in the form of neovascular glaucoma, ghost cell
and has normal appearing open angles. glaucoma and glaucoma associated with retinal
detachment; glaucoma associated with intraocular tumors
Developmental Anomalies
like retinoblastoma, malignant melanoma, metastasis and
of the Anterior Chamber
leukemia; glaucoma associated with elevated episcleral
A variety of developmental abnormalities in the drainage venous pressure and inflammation (keratitis and uveitis),
angle has been associated with the development of increased steroid induced glaucoma; glaucoma associated with ocular
IOP leading to glaucoma. These anomalies usually have a trauma secondary to angle recession and hyphema, and
genetic basis. The developmental anomalies include high glaucoma associated with intraocular surgery like malignant
insertion of the iris on the trabecular meshwork, incomplete glaucoma, glaucoma in aphakia and pseudophakia,
development of trabecular meshwork and Schlemm's canal glaucoma associated with epithelial and fibrous down
or broad iridocorneal adhesions. The developmental glaucoma growths, post-penetrating glaucoma and silicone oil induced
could again be primary with no other ocular or systemic glaucoma.
association or could be associated with other ocular and
systemic developmental anomalies. Classification Based on Mechanism
Classifying glaucoma based on mechanism allows better
Glaucoma Associated with understanding of the aqueous outflow obstruction and is also
Other Ocular Disorders helpful in developing a treatment strategy for controlling IOP
in each case. However, this classification presumes that
This is a large subgroup that includes various secondary
increased IOP is the basis of glaucomatous damage and
glaucomas that occur following an event that does not involve ignores the pressure independent factors; and many times
either pupillary block or increased resistance to outflow as more than one mechanism of IOP elevation is applicable.
the initial event, but includes inflammation, tumor, trauma, The advantages of using this system are two-fold a) firstly, a
or hemorrhage as the initial event or the initial pathology. It better and complete understanding of mechanism of aqueous
involves structures like the cornea, iris, ciliary body, lens, retina, outflow obstruction in comparison to knowledge of the initial
choroid or vitreous. Most of these glaucomas are acquired events; b) and secondly that currently. IOP is the only
but some have a genetic defect to begin with. modifiable factor that most treatment options focus on.
A synopsis of such a classification is: This classification classifies glaucoma into open angle
• Open angle glaucoma, comprising chronic open angle glaucoma mechanism, closed angle glaucoma mechanism and
glaucoma and normal tension glaucoma developmental anomalies of the anterior chamber angle.
800 Glaucoma
Open Angle Glaucoma Mechanism iris, trabecular meshwork or Schlemm's canal as in Axenfeld-
Reiger and Peter's anomaly.
These eyes have open angles on gonioscopy. The obstruction
A detailed synopsis of the classification of glaucoma based
to the aqueous outflow can be pretrabecular (on the anterior
on mechanisms of outflow obstruction with elaboration of
chamber site of the trabecular meshwork), trabecular (within
different clinical conditions causing the same is:18
the trabecular meshwork) or post trabecular (distal to
• Open angle glaucoma mechanism comprising
trabecular meshwork). The p r e t r a b e c u l a r m e c h a n i s m
pretrabecular mechanisms associated with presence of
glaucoma may arise from a variety of reasons like a membrane
inflammatory membranes, fibrous and epithelial
covering the angle which could be a fibrovascular membrane,
downgrowths, fibrovascular membranes and endothelial
endothelial layer, epithelial membrane or an inflammatory
layer over the trabecular meshwork as may be seen in
membrane. If trabecular meshwork itself offers increased post-penetrating glaucoma, posterior polymorphous
resistance to aqueous outflow, the glaucoma is termed as dystrophy and iridocorneal endothelial syndrome;
having a trabecular mechanism. This could be idiopathic as in trabecular mechanisms comprising idiopathic causes like
primary open angle glaucoma or secondary to clogging of the chronic open angle glaucomas and the steroid induced
meshwork by red blood cells, pigments, inflammatory cells, glaucomas, glaucomas associated with clogging of the
proteins, viscoelastic or vitreous. It could also result from trabecular meshwork in the form of hemorrhagic and
direct involvement of the trabecular meshwork, in the form ghost cell glaucoma (red blood cells), hemolytic glaucoma,
of trabecular edema, fibrosis and scarring. If Schlemm's canal phacolytic glaucoma and melanomalytic glaucoma
offers increased resistance due to collapse or scarring or due (macrophages), glaucomas associated with neoplasia in
to clogging of the canal or if the episcleral venous pressure the form of malignant tumors, neurofibromatosis, nevus
is elevated, the mechanism is posttrabecular. of Ota and juvenile xanthogranuloma, glaucomas
associated with pigment in the trabecular meshwork in
Angle Closure Mechanism
the form of pigmentary glaucoma, pseudoexfoliation
These glaucoma have IOP elevation due to appositional glaucoma, glaucoma associated with uveitis, trauma and
closure of trabecular meshwork (leading to synechial closure malignant melanoma, glaucomas due to the presence of
later) by peripheral iris which is either pulled or pushed proteins in the trabecular meshwork as may be seen in
anteriorly. The "pull mechanisms" are anterior mechanisms uveitis and lens induced glaucomas, glaucomas associated
that could be contracting fibrovascular membrane, endothelial with the presence of viscoelastic substances, α-
layer or inflammatory membrane. The "push mechanisms" chymoptrypsin and vitreous in the trabecular meshwork,
are posterior mechanisms including posterior push on the iris glaucomas associated with alterations in the trabecular
due to aqueous, lens and vitreous. This could again be with meshwork as may be seen in trabecular edema due to
or without pupillary block. The pupillary block glaucoma uveitis induced trabeculitis, scleritis and alkali burns,
results from apposition between the peripupillary iris and lens trauma (angle recession) and intraocular foreign body as
resulting in increased resistance to aqueous flow from the may be seen in siderosis and chalcosis; and post-trabecular
posterior to the anterior chamber. This results in peripheral mechanisms related to obstruction of the Schlemm's canal
bowing of the iris and closure of the trabecular meshwork. as may be noted in canal collapse and clogging subsequent
Other mechanism causing pupillary block are forward shift to obstruction by sickled red blood cells, and elevated
of lens, cataractous lens, and posterior synechiae leading to episcleral pressures as may be seen subsequent to carotid
seclusio pupillae. The “push mechanism” glaucoma without cavernous fistula, cavernous sinus thrombosis, retrobulbar
pupillary block include anterior movement of lens, iris or tumors and thyroid ophthalmopathy.
vitreous as may be seen in malignant glaucoma, plateau iris • Angle closure glaucoma mechanism comprising
syndrome, intraocular tumors; and iris and ciliary body cysts. anterior (pulling) mechanism associated with contracture
of membranes in the form of neovascular glaucoma,
Developmental Anomalies
iridocorneal endothelial syndrome and posterior
of Anterior Chamber Angle
polymorphous dystrophy, and contracture of inflam-
Developmental anomalies may lead to glaucoma which matory precipitates and posterior (pushing mechanisms)
develops at an early age (congenital or juvenile glaucoma). associated with pupillary block subsequent to lens induced
These could result from developmental defects like high mechanism as may be associated with intumescent,
insertion of iris, or incomplete development of peripheral subluxated and mobile lens, and posterior synechiae
associated with uveitis and presence of vitreous and those meshwork and Schlemm's canal as may be seen in the
not associated with pupillary block in the form of the Axenfeld Reiger syndrome, Peter's anomaly and other
plateau iris syndrome, malignant glaucoma, lens induced developmental anomalies of the angle, and iridocorneal
glaucoma, forward vitreous shift following lens extraction adhesions as may be seen in the Axenfeld Reiger syndrome
(not resulting in papillary block), following anterior shift and aniridia.
of the iris lens diaphragm as may be seen subsequent to
scleral buckling, panretinal photocoagulation, presence of Evidence Based Categorization of
intraocular tumors in the form of malignant melanoma Glaucoma (Tables 9.1.2 and 9.1.3)
and retinoblastoma, cysts of the iris and ciliary body and Definitions and classifications of any condition undergo
retrolenticular tissue contracture as may be seen in changes and modifications depending upon the relevance of
retinopathy of pre-maturity and persistent hyperplastic
Table 9.1.3: Clinical classification of glaucoma based on
primary vitreous.
evidence based categories
• Developmental anomalies of the anterior chamber
Glaucoma Suspects
angle comprising high insertion of the iris as may be
1. Disk suspects. Those who met category 1 (but not category
seen in association with congenital glaucoma, juvenile 2) disk criteria, but were not proved to have definite field
glaucoma, glaucoma associated with other developmental defects.
anomalies; incomplete development of trabecular 2. Field suspects. Those with definite field defects, but not
meeting category 1 disk criteria.
3. Those with optic disk margin hemorrhages.
Table 9.1.2: Clinical categories for diagnosis of 4. Those with an IOP ≥ 97.5th percentile.
glaucoma based on the levels of evidence 5. Those with an occludable drainage angle, but normal optic
disk, visual field, intraocular pressure, and no peripheral
Category 1 (structural 1. Eyes with CDR or CDR
anterior synechiae.
and functional evidence) asymmetry >=97.5th percentile
for the normal population or a POAG
neuroretinal rim width reduced 1. Optic nerve damage meeting any of the three categories of
to <0.1 CDR (between 11–1 evidence mentioned in Table 9.1.2.
o’clock or 5–7 o’clock) 2. No evidence of angle closure on gonioscopy.
2. Definite visual field defect 3. No identifiable secondary cause for glaucoma.
consistent with glaucoma
PACG
Category 2 (advanced 1. CDR or CDR asymmetry >=
Primary angle closure suspect
structural damage with 99.5th percentile of the normal
An eye in which appositional contact between the peripheral iris
unproved functional population
and posterior trabecular meshwork is considered possible (see
loss) 2. Visual field could not be
footnote).
performed satisfactorily by the
subject Primary angle closure (PAC)
In such cases, glaucoma was An eye with an occludable drainage angle and features indicating
diagnosed solely on structural that trabecular obstruction by the peripheral iris has occurred,
evidence such as peripheral anterior synechiae, elevated intraocular
pressure, iris whorling (distortion of the radially orientated iris
In diagnosing category 1 or 2 glaucoma, there should be no
fibers), "glaucomfleken" lens opacities, or excessive pigment
alternative explanation for:
deposition on the trabecular surface. The optic disk does not
a. CDR findings (dysplastic disk, marked anisometropia).
have glaucomatous damage.
b. The visual field defect (retinal vascular disease, macular
degeneration, or cerebrovascular disease). Primary angle closure glaucoma (PACG)
PAC together with evidence of glaucoma, as defined above.
Category 3 (Optic disk If it is not possible to examine the
not seen. Field test optic disk, glaucoma is diagnosed if: Glaucoma with secondary ocular pathology
impossible) (A) The visual acuity <3/60 and the 1. The diagnosis of secondary glaucoma is based on the
IOP >99.5th percentile, or (B) The presence of optic neuropathy, in the presence of a secondary
visual acuity <3/60 and the eye ocular pathological process. These processes may include
shows evidence of glaucoma neovascularization, uveitis, trauma,lens related glaucoma,
filtering surgery, or medical records pigment dispersion, pseudo-exfoliation, etc.
were available confirming glauco- 2. Most of the patients may fall in category 3 as the media is
matous visual morbidity. often hazy and not amenable to optic disk evaluation in these
patients (reduced visual acuity, high IOP, with a RAPD)
CDR = Cup-disk ratio; IOP = Intraocular pressure 3. The condition in usually unilateral
(Reproduced from The definition and classification of glaucoma in (Reproduced from The definition and classification of glaucoma
prevalence surveys. Foster PJ, Buhrmann R, Quigley HA, in prevalence surveys. Foster PJ, Buhrmann R, Quigley HA, et al.
et al. Br J Ophthalmol 2002;86:238–42. Copyright notice year January Br J Ophthalmol 2002;86:238–42. Copyright notice year January
2011 with permission from BMJ Publishing Group Ltd.) 2011 with permission from BMJ Publishing Group Ltd.)
802 Glaucoma
the same in different situations. Experiences of cross-sectional 3. Spencer WH, Alvarado J Hayes TL. Scanning electron microscopy
glaucoma prevalence research in Asia and Africa have of human ocular tissues: Trabecular meshwork. Invest Ophthalmol
prompted the establishment of a newer evidence based Vis Sci 1968;7(6):651-62.
4. Flocks M. The anatomy of the trabecular meshwork as seen in
classification based on the extent of structural damage seen
tangential section. AMA. Arch Ophthalmol 1956;56(5):
in glaucomatous optic neuropathy, the associated visual 708-18.
dysfunction in terms of the visual field loss and the level of 5. Fine BS. Structure of the trabecular meshwork and the canal of
intraocular pressure present.19 Schlemm. Trans Am Acad Ophthalmol Otolaryngol 1966;
This classification divides the categorization of glaucoma 70(5):777-90.
into three levels of evidence (Table 9.1.2). 6. Vegge T. Ultra structure of normal human trabecular endothelium.
Based on these levels of evidence, the different categories Acta Ophthalmol 1963;41:193-9.
of patients diagnosed as glaucoma has been classified as 7. Ashton N. The exit pathway of aqueous. Trans Ophthalmol Soc
UK 1960;80;397-407.
summarized in Table 9.1.3.
8. Morrison J, Van Burshik EM. Ciliary process microvasculature of
the primate eye. Am J Ophthalmol 1984;97:372-8.
Classification Based on 9. Raviola G, Raviola E. Intercellular junctions in the ciliary
Molecular Etiology epithelium. Invest Ophthalmol Vis Sci 1978;17:958-60.
10. Gabelt BT, Kaufman PL. Aqueous humor hydrodynamics. In
Studies have shown that glaucoma has a genetic basis. Many Kaufman PL, Alma A Eds Adler's physiology of the eye. St Louis
different genes and their mutations have been identified in Mosby 2003;230-40.
glaucoma. With increasing knowledge of genetic associations 11. Bill A the role of ciliary blood flow and ultrafiltration in aqueous
in the future, it may be possible to classify glaucoma based humor formation. Exp Eye Res 1973;16:287-91.
on molecular and genetic etiology.20 12. De Berardinis E. Tieri O. Polzella A, et al. The chemical composition
of human aqueous humor in normal and pathological conditions.
Exp Eye Res 1965;4:179-86.
SUMMARY 13. Seiler T, Wollensak J. The resistance of the trabecular meshwork
to aqueous outflow. Graefes Arch Clin Exp 1985;223(2):88-91.
The two commonly used systems of classification of 14. Bill A Philips CI. Uveoscleral drainage of aqueous humour in
glaucoma are based on etiology (initial events), and mechanism. human eyes Exp Eye Res 1971;12:275-81.
The disadvantage of these two systems are that both presume 15. Grierson I, Lee WR. Pressure induced changes in the ultra structure
increased IOP as the only causative factor for glaucoma, and of the endothelium lining's Schlemm's canal. Am J Ophthalmol
secondly that neither of these systems incorporate a genetic 1975;80:863-8.
basis for the pathogenesis of glaucoma. However, as many 16. Geijssen HC, Greve EL. The spectrum of primary open angle
causative factors leading to glaucoma are unknown, both these glaucoma I: Senile sclerotic glaucoma versus high tension glaucoma.
Ophthalmic Surg 1987;18:207-13.
classifications provide useful categorization of glaucoma.
17. Barkan O. Primary Glaucoma: Pathogenesis and classification.
The newer clinical classification system is being increasingly Am J Ophthamol. 1954;37(5):724-44.
adopted on both research and public health issues related to 18. Shaffer RN. A new classification of glaucomas. Trans Am
glaucoma. Ophthalmol Soc 1960;58:219-25.
19. Foster PJ, Buhrmann R, Quigley HA. The definition and
REFERENCES classification of glaucoma in prevalence surveys. Br J Ophthalmol
2002;86:238-42.
1. Last R. Wolff's anatomy of the eye and orbit. Philadephia: WB 20. Alward WLM. Molecular genetics of glaucoma: effects on the
Saunders, 1961. future disease classification. In: Van Buskrik EM, Shields MB, eds
2. Moses RA, Grodzki WJ Jr. The Scleral spur and sclera roll. Invest 100 years of progress in glaucoma. Philadelphia: Lippincott-Raven
Ophthalmol Vis Sci 1977;16(10):925-31. 1997;143-9.
Chapter 9.2
GLAUCOMA EVALUATION
9.2.1 Assessment of a Patient with Glaucoma

Shalini Mohan
Glaucoma is a chronic progressive optic neuropathy that results CLASSIFICATION

in damage to retinal ganglion cells and surrounding tissue
Glaucoma can be classified in two broad categories:
structures. According to the American Academy of
Ophthalmology, glaucoma is defined as ‘multifactorial optic Open Angle glaucoma: It is the most common variety of
neuropathy with characteristic visual field defects and glaucoma.1-3 In this type of glaucoma the angle of the anterior
characteristics changes in the optic nerve head.1 The most chamber is open and normal with some structural abnormality
common risk factor implicated is rise in intraocular pressure, in trabecular meshwork. The resultant improper drainage of
it is currently the only modifiable risk factor.2 Therefore, the aqueous humor gives rise to increase in intraocular pressure.
main goal of medical or surgical treatment is to lower the When the condition is not associated with any other cause,
IOP to a level that prevents or reduces further loss of retinal and thought to be hereditary, it is known as primary open
ganglion cell and subsequently the visual function. Important angle glaucoma (POAG).
considerations in the management of glaucoma patients Angle closure/Closed angle/Narrow angle glaucoma: In these group
include clinical factors, including visual field status, the optic of disorders the angle of the anterior chamber of the eye is
disk's appearance, IOP level, patients' adherence to and narrow due to apposition of the iris to the trabecular
persistence with prescribed therapy, their medical, family and meshwork resulting in poor drainage of aqueous humor and
social history, and the interaction of these factors over IOP rise. It can be secondary to some ocular or systemic
extended periods of follow-up. pathology or can be primary. Half the glaucoma patients in
Major factors at play in glaucoma evaluation include: India have primary angle closure glaucoma (PACG).4 In PACG,
i. the relationship between structural characteristics (the crowding of the anterior segment structures occur because
appearance of the optic disk and the retinal nerve fiber of shallow anterior chamber, thicker lens and smaller axial
layer (RNFL) and length of eye ball.5-7 The iris lens touch is broad so that
ii. the functional capabilities (perimetry and other clinical aqueous is not able to go from the posterior chamber to the
psychophysical tests) that are affected by glaucomatous anterior chamber completely. As age advances, increased
damage. crystalline lens thickening causes the iris lens contact to become
804 Glaucoma
Fig. 9.2.1.2: Facial hemangioma in Sturge -Weber syndrome
Fig. 9.2.1.1: Iris bombe
broader, so that aqueous accumulates in the posterior chamber.

The result is that the iris is pushed forward in a condition
known as iris bombe (Fig. 9.2.1.1). This forward bowing of
iris results into formation of adhesions between iris and
peripheral cornea, known as peripheral anterior synechia
(PAS). This further blocks the passage of aqueous humor.
Fig. 9.2.1.3: Circumciliary congestion
GLAUCOMA EVALUATION
It may be briefly considered under the following headings:
External Examination
• External eye examination
• Anterior segment examination The external examination is uneventful in a case of open
– IOP assessment angle glaucoma but sometimes few findings may reveal
– Angle evaluation obvious or subtle clues to associated glaucoma. A
i. Gonioscopy hemangioma of upper eyelid and face may be associated
ii. Ultrasound biomicroscopy (UBM) with Sturge-Weber syndrome8,9 (Fig. 9.2.1.2) and glaucoma
iii. Anterior segment-optical coherence tomography on that side of face. External examination should also include
(AS-OCT) a search for signs of trauma, proptosis, and restriction of
– Structural analysis of optic nerve head ocular movements.
i. Stereoscopic disk evaluation
ii. Optic disk imaging-stereoscopic disk photography, Anterior Segment Evaluation
Heidelberg retina tomograph, retinal nerve fiber
A detailed anterior segment examination by slit lamp
layer (RNFL) measurement by scanning laser
biomicroscope is an essential tool for glaucoma evaluation.
polarimetry (GDx), optical coherence tomography
iii. Functional analysis-visual field testing Conjunctiva: Conjunctiva shows circumciliary congestion (Fig.
a. Standard automated perimetry 9.2.1.3) in the acute stage of angle closure glaucoma and
b. Short wavelength automated perimetry (SWAP) some other types of secondary angle closure glaucoma. Dilated
c. Frequency doubling perimetry (FDP). episcleral vessels are seen in arterio-venous malformations
Glaucoma Evaluation 805
Fig. 9.2.1.4: Sentinel vessel Fig. 9.2.1.5: Enlarged cornea in buphthalmos
and the presence of a single-dilated anterior ciliary artery, a

‘sentinel vessel’ (Fig. 9.2.1.4) is an important sign of ciliary
body tumor8,9 which may sometimes present with raised
intraocular pressure and glaucoma.
Cornea: It is normal in open angle, subacute and chronic stage
of angle closure glaucoma where the rise in IOP is gradual
but corneal edema is present in the acute stage of narrow
angle glaucoma.
Stromal scars may be seen in cases of ocular trauma.
Descemet's membrane may show tears in developmental
glaucoma or buphthalmos (Fig. 9.2.1.5) due to the sudden
stretching of globe by raised IOP which heals leaving linear
scars known as 'Haab Striae'.10
Endothelial side of the cornea may show pigments and Fig. 9.2.1.6: Van Herick's grading
keratic precipitates in acute angle closure and other types of
secondary glaucomas. Krukenberg's spindle is seen in
The thinnest light beam is shown from the periphery at the
pigmentary glaucoma in which pigments are deposited at the
limbus.
back of the cornea.
The ratio of the anterior chamber width to the corneal
Anterior chamber (AC): The depth of the anterior chamber width is assessed through this orientation of the slit beam and
is normal in open angle glaucoma but it may be shallow the gradation is a direct measure of this observation. If no
in narrow angle and uveitic glaucoma. An oblique torch anterior chamber width is seen, the angle is considered to be
light examination can be done for AC depth assessment. closed and is graded as 0; if the anterior chamber width is less
When light is projected from the temporal quadrant, if than 1/4th of the corneal width, the angle is less than 10o and
the other part of the iris can be seen, the angle is deep. In its closure is considered likely, and it is graded as 1; if the
a case of shallow angle, the reflection of the convex iris anterior chamber width is 1/4th of the corneal width, the
will be seen. chamber angle is approximately 20o, its closure is considered
To assess the anterior chamber depth, van Herick's possible and it is graded as 2; if the anterior chamber width is
method11 (Fig. 9.2.1.6) of grading is followed. For this, ½ of the corneal width, the anterior chamber angle is
the patient is seated on the slit lamp and the angle between approximately between 20o and 35o, angle occlusion is
the illumination and the viewing beams is kept at 60 degrees. considered to be unlikely and it is graded as 3 while if the
806 Glaucoma
anterior chamber to the corneal width has a ratio of one or

more, the angles are open to the extent of 35o or more, closure
is considered to be very unlikely and it is graded as 4.11
The exact assessment can be done with the help of
gonioscopy which will be discussed subsequently.
Pupil: Pupillary examination is very important in glaucoma
diagnosis. Relative afferent pupillary defect can be present in
an eye with advanced glaucomatous optic atrophy. In case of
acute angle closure, the glaucoma pupil is mid-dilated and
non-reacting due to sphincter ischemia.
Iris: The color and pattern of the iris must be seen carefully.
Iris pattern is lost and looks muddy when acute angle closure
glaucoma sets in. Iris adhesions to cornea or lens known as
anterior or posterior synechiae are signs of angle closure and
inflammatory glaucoma (Fig. 9.2.1.7). Fig. 9.2.1.7: Posterior synechia in inflammatory glaucoma
Pupillary margin of the iris may show neovascular vessels
(iris neovascularization) in cases of neovascular glaucoma
(Fig. 9.2.1.8). White flaky deposits may also be seen in cases
of pseudoexfoliation syndrome. Iris naevus can be present
in naevus of Ota. Pseudopolycoria and iris atrophy can be
seen in iridocorneal endothelial syndrome.
Radial transillumination defects are seen in cases of
pigmentary glaucoma whereas transillumination defect at
pupillary margin can be seen in case of pseudoexfoliation
syndrome.
Iris stromal atrophy can be seen in cases of acute angle
closure glaucoma and iridocorneal syndrome. Pupillary ruff
atrophy is also seen in cases of angle closure glaucoma.
Lens: Glaucomaflecken is anterior subcapsular opacities seen
in cases of acute angle closure glaucoma. Swollen lens with
shallow anterior chamber is present in lens induced glaucoma. Fig. 9.2.1.8: Neovascular glaucoma
Subluxated (Fig. 9.2.1.9) or dislocated lens as in micro-
spherophakia may cause pupillary block and raised IOP.
Pseudoexfoliation syndrome may show whitish or ashen gray
rings of flakes on the anterior capsule of the lens (Fig.
9.2.1.10). Ring of pigments after breaking of synechia may
be seen in cases of inflammatory glaucoma.
Intraocular Pressure: The normal mean intraocular pressure
(IOP) in human adults is 15.5 +/- 2.6 mm Hg.12 Armaly in
1965 suggested that the IOP curve in the normal population
remains Gaussian upto 21 mm Hg but thereafter tends to
skew towards higher IOP.13 Additionally, IOP is Gaussian till
40 years and then skewed towards higher IOP. Fig. 9.2.1.9: Subluxated lens
It is proved that IOP is an important risk factor in the
neuropathy of primary open angle glaucoma (POAG). OAG.14,15 In spite of the relationship between elevated IOP
Furthermore, studies have demonstrated that reduction in and glaucomatous optic neuropathy, there is a great inter-
the level of IOP lessens the risk of nerve fiber layer loss in individual variation in the susceptibility of the optic nerve to
Fig. 9.2.1.10: Pseudoexfoliation syndrome
IOP-related damage. Data from longitudinal studies suggest

that nearly ten percent of untreated ocular hypertensives
with an IOP that is consistently 24 mm Hg or above, develop
glaucoma in five years.16
Amongst all risk factors for glaucoma, IOP remains the
only treatable risk factor. In the ocular hypertension treatment
study (OHTS), the progression of glaucoma was reduced by
half in patients with IOP consistently less than 24 mm Hg.17
IOP varies from hour-to-hour in any individual. Many
studies indicate that the circadian rhythm of IOP peaks in
the early hours of the morning.18-21 IOP often rises when a
patient assumes a supine position.22,23 When checking IOP, Fig. 9.2.1.11: Measurement by Schiotz tonometer
measurements for both eyes, the method used (Goldmann
applanation tonometry is considered the standard), and the
is used quite often due to its simplicity and easy transportability.
time of the measurement is to be recorded. A difference
It is based on the principles of indentation tonometry.
between contralateral eyes of 3 mm Hg or more indicates
greater suspicion of glaucoma. In most circumstances, the
Indentation Tonometry
measurements should be repeated on at least two to three
occasions before deciding on a treatment plan. The The Schiotz tonometer consists of three parts, footplate,
measurement should be made at different times of the day plunger and scale. A series of known weights of 5.5 mg, 7.5
to check for diurnal variation. A diurnal variation of 8 mm mg, 10 and 12.5 mg are applied to the plunger. When the
Hg or more indicates an increased risk for glaucoma whereas footplate is kept on the cornea (Fig. 9.2.1.11), the plunger
2 to 4 mm is the normal variation. Rest of the cases are indents the cornea which results in deformation of the globe.
considered borderline.24 This deformation is recorded by the scale attached to the
plunger. The reading on the scale is converted to IOP with
Tonometry the help of a nomogram known as Friedenwald
nomogram2,10,26 published after modification in 1955. The
Measurement of IOP is known as tonometry. It is of two
formula requires a constant "K" which is the coefficient of
types:
ocular rigidity. It is the measure of resistance of the eye to
1. Indentation tonometry
the distending force of the tonometer.
2. Applanation tonometry
Schiotz developed the first device that quantified Clinical technique: The patient lies supine after the procedure is
intraocular pressure (IOP) with relative reproducibility.25 It explained. Topical anesthetic drops are instilled in the eyes.
808 Glaucoma
The patient is asked to look at a fixed target (which can be b. Variable force: These types of tonometers measure the force
his own thumb. The foot plate of the tonometer is kept on that is needed to flatten a standard area of the cornea.
the cornea and the reading on the scale is read. It is then The prototype is the Goldmann applanation tonometer
correlated with the nomogram provided with the tonometer. and it is the current gold standard.38
Limitations: The “K” value or ocular rigidity is kept average Goldmann applanation tonometer: Goldmann applanation
for all the eyes. So, in eyes where ocular rigidity is high or low, tonometer (Fig. 9.2.1.12A) is mounted on a standard slit lamp.
the values become unreliable. Higher ocular rigidity is seen in It has a plastic biprism (Fig. 9.2.1.12B), which is used to flatten
eyes like high hypermetropia,27 chronic glaucoma, 28 and the cornea after anesthetizing. The prism is mounted on a
chronic vasoconstrictor therapy.26 So the recorded IOP would rod. Before touching the cornea with biprism, sodium
be higher in these eyes. Low ocular rigidity is seen in high fluorescein39 dye is instilled in the eye and cobalt blue filter is
myopia, 27 miotic therapy, 27 after retinal detachment switched on. When the observer views from the slit lamp
surgery,29,30 intravitreal injection of gas29,31 and vasodilator uniocularly, two semicircles are seen in Figures 9.2.1.13A to
therapy.26 False high readings are obtained with very thick C. The knob of the tonometer is adjusted so that inner margins
and steep corneas.2,10 Unreliable readings are found in scarred of both the semicircle meet and start pulsating. This is the
corneas with significant pathology.32,33 end point where the reading is taken.
Adequate thickness of the circles is very important as
Applanation Tonometry thicker or thinner circle may lead to falsely high or low readings
(Figs 9.2.1.13A to C).40
Applanation tonometry is based on the Imbert Fick Law which
Other Tonometer Types:
states that in an ideal, dry, thin walled sphere, pressure equals
1. Perkin's tonometer: It is a hand held tonometer based
force needed to flatten the surface (F) divided by area of
on the same principle as the Goldmann tonometer. The
flattening (A), P = F/A.2,10,28,34-36 In applanation tonometry,
advantages are that as no slit lamp is required, the IOP
3 mm diameter area of the cornea is flattened, which
can be recorded with the patient in the supine position or
minimally displaces fluid of five microliter. Therefore, IOP
when under anesthesia.38,41,42
readings are not affected by variations in scleral rigidity.37
2. Pneumatonometer: This measures the IOP by flattening
Applanation tonometry can be divided into two subtypes: the cornea with graded flow of gas against a flexible
a. Variable area: These tonometers measure the area of the diaphragm. The principle is similar to that of the Mackey-
corneas flattened by a known amount of force. The Marg tonometer, but the sensor is air pressure. It is useful
example of this type of tonometer is Maklakov for assessing the IOP in scarred, edematous corneas and
tonometer.10,28,34,35 also for assessment of IOP over soft contact lens.43
Figs 9.2.1.12A and B: (A) Applanation tonometer as slit lamp attachment and (B) the applanation bi-prism in close view
Figs 9.2.1.13A to C: (A) Semicircles as seen in applanation tonometer, (B and C) Thin and thick mires in applanation tonometer
3. Mackey-Marg tonometer: This is an electronic 7. Ocular response analyzer: This tonometer utilizes the
applanation tonometer that functions by applanating the principles of air-puff tonometry to correct the effect of
cornea with a probe which has a 1.5 mm fused quartz corneal hysteresis on the IOP measurement. The
plunger that records the IOP when pressed against the measurement of the values of compressed air required
cornea. The recording in through an attached stylus that to flatten the cornea and its rebound back to its normal
documents the pressure curve. As observation of the contour gives a measure of the biomechanical
mires on the patient's cornea is not a prerequisite for the characteristic of the cornea.50
assessment of IOP, it can be used in scarred and irregular 8. Non-corneal transpalpebral tonometer: This instrument
corneas. The Tono-pen operates on the principle of the measures the IOP through the eyelid overlying the sclera.
Mackey Marg tonometer and demonstrates an average The response of the free falling rod, rebounding against
of four to ten acceptable readings as the final IOP value. the tarsal plate, gives the measure of the IOP. Parameters
A major advantage is its portability.44,45 like thickened and abnormal eyelid may affect the values
4. Air-puff tonometer: In this, a puff of compressed air is of the IOP but these instruments are of use in children
blown through a nozzle towards the patient's cornea and and uncooperative patients.51
the IOP is measured based on the physical relationship
of the flattening of the cornea of a required measure to Gonioscopy
the amount of compressed air blown through the nozzle
as per a predetermined pressure-time characteristic curve The angle of the eye is examined by gonioscopy, which
as per the Goldmann principle. This is the physical basis requires the use of special lenses (Gonioscope).
of the noncontact tonometer (NCT).46 The need for gonioscopy arises as the rays from angle
5. Dynamic contour tonometer: It is a new digital strikes the corneal interface at more than 45 degrees which is
tonometer that provides direct transcorneal measurement more than the critical angle for this interface and therefore,
of IOP, and is sensitive enough to detect the ocular pulse the rays are totally internally reflected. Goniolens change the
amplitude (OPA) due to the patient's heartbeat.47,48 It interface refracting properties and allows visualization of the
uses the principle of contour matching instead of angle.2,10,28,34
applanation, and eliminates the systematic errors inherent Gonioscopy is performed to rule out angle-closure or
in all previous tonometers, such as the influence of secondary causes of IOP elevation, such as angle recession,
corneal thickness and rigidity. pigmentary glaucoma, neovascular glaucoma, and exfoliation
6. Rebound tonometer: This tonometer determines the IOP syndrome.
by use of a small, plastic tipped magnetized metallic probe The peripheral contour of the iris is examined for plateau
against the cornea. The rebound of this magnetized probe iris configuration, and the trabecular meshwork for peripheral
into the device due to the deceleration of the induction anterior synechiae, as well as for neovascular or inflammatory
current caused by the eye, determines the IOP. This is membranes or silicone oil, foreign body or a tumor. Schlemm's
simple, portable and cheap device, of use in children and canal may be seen if blood refluxes into the canal. This might
uncooperative patients but not much data is available indicate elevated episcleral venous pressure caused by
regarding its comparability with the Goldmann conditions such as a carotid-cavernous fistula, Grave’s
tonometer48,49 orbitopathy, or Sturge-Weber syndrome.8,9
810 Glaucoma
Indications • Koeppe: Prototype

The indications of gonioscopy can be divided into diagnostic • Barkan: Surgical
and therapeutic: • Swan-Jacob: For surgical use in children
• Layden: Premature infants
Diagnostic Indications
• Richerson-Schaffer: Koeppe lens for infants
• Narrow peripheral anterior chamber
• Thorpe: Operating room
• Evidence of
– Angle closure The Koeppe lens and the Swan-Jacob goniolens are most
– Inflammation used (Fig. 9.2.1.14). The main advantage of this type of
– Neoplastic activity goniolenses are that one can have a panoramic view of the
– Developmental anomaly whole anterior chamber and the angle structures in normal
• Classification of glaucoma spatial orientation. Both the angles can be viewed
• Extent of simultaneously and surgical procedures can be performed.
– Neovascularization
– Angle recession Advantages
• For planning of treatment • Both eyes can be visualized simultaneously
– Iris neovascularization • Good binocularity
– Laser procedures • Minimal distortion of the angle
• Panoramic view of the angle
Therapeutic Indications • Viewing angle can be manipulated by the examiner
• Argon laser trabeculoplasty
• Laser goniotomy Disadvantages
• Reopening of trabecular opening • Supine position of the patient
• Opening of sclerostomy fistula • Needs operating microscopes
• Poor details of anatomy seen.
The angle of the eye can be assessed by two methods:
1. Direct: The angle is seen directly in a lens. The various 2. Indirect: Indirect gonioscopes have a mirror in which a
examples are as follows: laterally inverted image is seen. Goldmann single or three
Fig. 9.2.1.14:Direct goniolenses

Table 9.2.1.1: Characteristics of indirect gonioscopic lens

Type of lens Angle Contact diameter Radius of curvature Comments
Goldmann single mirror 62° 14 mm 7.4 mm Easy
Goldmann three mirror 59° 13–20 mm 7.4 mm Coupling fluid
Four mirror lens (Same values 64° 9 mm 8.4 mm Indentation
for all three gonioscopes)
1. Zeiss (Separate handle)
2. Posner( Attached handle)
3. Thorpe (Finger held)
4. Sussman trabeculoplasty 59 o × 2 9 mm ALT (Argon laser trabeculoplasty)
62 o × 2
mirror (59o mirror used for gonioscopy) or the Zeiss four Table 9.2.1.2: Differences between
mirror lens (Table 9.2.1.1) are used (Table 9.2.1.2). 3 mirror and 4 mirror lenses
Type of Lens Goldman Goldman Zeiss
Advantages single mirror 3 mirror 4 mirror
• It can incorporate the advantages of slit lamp Diameter of contact 12 mm 12 mm 9 mm
magnification , controlled illumination, and stereopsis to cornea
Overall diameter 15 mm 18 mm 9 mm
• Manipulation and indentation is possible
Rim size 1.5 mm 3 mm No rim
• It allows localization of angle structures
Angle of the mirror 62° 59° 64°
• It is convenient for patients and examiners
Height 17 mm 12 mm 12 mm
Disadvantages Distance of the mirror 3 mm 7 mm
from the center
• Reflected image is seen Radius of 7.4 mm 7.4 mm 7.85 mm
• Image is inverted and of the opposite angle curvature
• Small aperture lens may cause distortion of the angle Coupling fluid Required Required Required
(following indentation)
• Cannot compare both the eyes simultaneously It might be difficult to see the Schwalbe's line in case of
• Needs co-operation of the patients a closed or a narrow angle (Fig. 9.2.1.16). For this, a very thin
beam of slit lamp is thrown onto the cornea at an angle so
Structures Seen in Gonioscopy that one can see a corneal wedge (Figs 9.2.1.17A and B). The
Structure from the root of iris onwards are (Fig. 9.2.1.15): point where the two corneal beams from the anterior and the
1. Root of iris posterior part meet is the Schwalbe's line.2,10,28,32
2. Ciliary body band: This is seen as a grayish brown band just The thumb rule is that if one can see two white lines, the
anterior to the iris, sometimes covered with filaments. line Schwalbe’s and the scleral spur, the angles are considered
3. Scleral spur: This is the anterior part of the sclera shown to be open.
as a white line between the pigmented lines of the
trabecular meshwork and the ciliary body band. If one Grading of the Angle
can see this line, it is sure that the angle is open. The angle has been graded in different ways depending upon
4. Trabecular meshwork: This has got two parts posterior, the structures seen on gonioscopy. The diagnosis, prognosis
pigmented and anterior non-pigmented part. The and management of different types of glaucoma is based on
pigmentation increases with age. It also varies with the this grading. Some of the commonly used grading systems
type of glaucoma and is more if any intraocular surgeries are:
has been performed. 1. Shaffer's grading: This system in conjunction with the Van
5. Schwalbe's line: It is the outer most structure and seen as a Herick's method of assessing the anterior chamber, grades
wedge. It corresponds to the peripheral termination of the angle into 5 grades from zero to four, with grade 0
the Descemet's membrane of cornea and usually, cannot implying an angle of 0° and imminent closure, grade 1
be seen without a gonioscope. When visible on direct indicating an angle of not more than 10°, with only
examination, it is called prominent Schwalbe's line or visualization of the Schwalbe's line and which is likely to
posterior embryotoxon, a feature of Axenfield-Rieger go into angle closure, grade 2 with an angle between 10°
anomaly. and 20° with visualization upto the trabecular meshwork
812 Glaucoma
Fig. 9.2.1.15: Angle of the anterior chamber
and which is unlikely to go into closure, grade 3 with

open angles between 20° and 35° where the scleral spur
can be visualized and grade 4 with an open angle more
than 35°, which has almost no chances of closing.11,52
2. Scheie's grading: This is the reverse of Shaffer's grading
where grade 0 indicates a widely open angle with visible
ciliary body band (CBB), grade 1 denotes an angle with
narrow CBB and no closure, grade 2 implies an angle
with no CBB seen, which may go into closure, grade 3, an
angle with obscuration of most structures including the
posterior trabecular meshwork and likely angle closure
and grade 4 angles which are gonioscopically closed.53
3. Spaeth's grading: This elaborate classification, on the same
lines as the Shaffer's classification, is based on the angle
Fig. 9.2.1.16: Narrow angle structures seen, the level of iris insertion, the iris
Figs 9.2.1.17A and B: Corneal wedge

configuration, angle width and angle recess.54 These It is appropriate to write the names of the structure visible
parameters are: in all four quadrants, when one sees with the gonioscope at
normal position with eyes looking straight with minimum
Level of iris insertion illumination and smallest possible beam that does not fall in
• A (Anterior to Schwalbe's line) the pupillary area.
• B (Just behind Schwalbe's line) The other method of documentation is making a Becker’s
• C (At the scleral spur) goniogram or Shaffer’s circular diagram (Fig. 9.2.1.19). The
• D (Deep angle CBB seen) diagram shows representation of various structures according
• E (Extremely deep angle) to structure.
The other important aspect of gonioscopy is differentiation
Angular width—10°, 20°, 30°, 40°
of true synechial angle closure to appositional angle closure.
Peripheral iris configuration (Figs 9.2.1.18A to C): There are the following two methods to differentiate it.9
• q-queer (Fig. 9.2.1.18A) a. Manipulative gonioscopy: It is done with the help of
• r-regular (Fig. 9.2.1.18B) Goldmann lenses which have a diameter greater than the
• s-steep (Fig. 9.2.1.18C) corneal diameter. The patient is asked to look towards
Figs 9.2.1.18A to C: Spaeth's grading

814 Glaucoma
Fig. 9.2.1.19: Shaffer's circular diagram
Fig. 9.2.1.21: Peripheral anterior synechia
Fig. 9.2.1.20: Manipulative gonioscopy
the mirror in which the examiner is viewing the angle

(Fig. 9.2.1.20) or the examiner moves the lens towards Fig. 9.2.1.22: Iris processes
the angle viewed.55 If examiner is viewing the superior
angle in the inferior mirror, he has to ask the patient to
look inferiorly or examiner moves the goniolens superiorly.
Difference between Iris Processes and PAS
It causes the viewing angle to open up if it is an
appositional angle closure, whereas the angle does not Iris processes PAS
open if it is closed due to synechia (Fig. 9.2.1.21). • Thin, fine, lacy • Solid and uniform
b. Indentation gonioscopy: It is done for the same purpose but • Present in the young • Present with
it can be done only with goniolenses of smaller diameter with dark iris inflammatory processes
than that of the cornea, that is the four mirror lenses.56 • Do not alter with • Do not allow the angle to
compression gonioscopy open up
The lens is pushed back towards the cornea so that aqueous • Become lacier and angle • Tenting of synechia
is pushed posteriorly into the angles and if angles are wall can be seen
closed due to apposition they will open up. • Follow concavity of angle
It is also important to differentiate between iris processes
(Fig. 9.2.1.22) and peripheral anterior synechia (PAS) (Fig. The disinfection of gonioscope is necessary to avoid
9.2.1.22) which can also be done by above two techniques of transmission of infection.57 It should be done each time the
angle examination. Other important points to differentiate procedure is done on the patient. Guidelines for disinfection
are as follows: of gonioscopes include:
• 70 percent ethyl alcohol sponge for ten seconds segment structures and evaluates them both quantitatively
• 1:10 household bleach (sodium hypochlorite) for five mins and qualitatively. It allows noninvasive in vivo imaging of
• Three percent hydrogen peroxide structural details of the anterior ocular segment at near
• One percent formaldehyde microscopic resolution.
• Ethylene oxide sterilization for operating gonioscopes. UBM P60 is available recently which has flexibility with
probe frequencies like 12.5, 20, 35 and 50 MHz.61 Depth of
penetration can vary depending on the probe frequencies.
Ultrasound Biomicroscopy (UBM)
Principle: This has the same principle as that of a B scan
This is a recent tool for assessment of anterior segment and ultrasound. It comprises a ultrasonic probe of 50 MHz in
its angle. Ultrasound biomicroscopy (UBM) is a high resolution the place of 8 to 10 MHz used in B scan ultrasound.58-60
ultrasound technique developed by Pavlin, Sherar and Foster The sound waves move inside and get reflected from the
in Toronto in the late 1980s.58-60 It is a high-frequency intraocular structures. As the frequency of the probe is very
ultrasound technology that provides exceptionally detailed high, the penetration is less and hence, it can image the
two-dimensional gray-scale images of the various anterior structures of anterior segment of the eye only.
Fig. 9.2.1.23: Normal ocular structures as seen on UBM (cornea, anterior chamber, angle, pars plana and sclera)
816 Glaucoma
Method: The examination is done with the patient in the supine Indications: The indications for UBM include (Fig. 9.2.1.25)
position,62 after local anesthetic has been applied to the eye. 1. Cornea
A sufficient palpebral fissure must be present to accommodate • Corneal edema
an eye cup (plastic or silicone) which is used to create a small • Descemet’s membrane detachment
water bath.63 Normally, one or two percent methylcellulose • Corneal dystrophy
solution is used as the coupling fluid. The probe is kept in the • PRK
water bath and started with the help of a foot paddle. Real • LASIK
time images are seen on the computer screen and images can • Keratoplasty:
be stored in the machine. – lamellar
– penetrating
Qualitative and Quantitative Examination • Corneal opacity
2. IOL-position, tilting, haptic position, presence in case of
This gives a two-dimensional gray-scale images of the following corneal opacity
structures58-65 (Fig. 9.2.1.23): 3. Trauma67
• Conjunctiva, cornea, anterior sclera 4. Angular pathology
• Anterior chamber angle structures • Glaucoma-for angle evaluation
• Ciliary body • To check patency of iridotomy68
• Anterior layers of the lens, zonules, IOL • Irido-ciliary cyst
• Pars plana • Supraciliary effusions
The software UBM pro 2000 is incorporated in the • Pupillary block
machine by which all the angle parameters58-60,66 (Table • Cyclodialysis clefts
9.2.1.3) can be measured automatically by just marking the • Angle recession
scleral spur in the image (Fig. 9.2.1.24). It has an inbuilt caliper 5. Tumors
for enabling any measurements. 6. Scleritis, episcleritis, intrascleral vessels
Fig. 9.2.1.24: UBM parameters

Fig. 9.2.1.25: UBM images of anterior segment pathologies
7. Extraocular muscles • Smaller cups may lead to artifactual widening of angles

8. Congenital glaucoma69-72: To look for stretching of ciliary • Time consuming
body along with prominent scleral spur • Operator dependent
9. Glaucoma surgeries73,74: To assess trabeculectomy and
deep sclerectomy ostium, to assess tube obstruction in Anterior Segment Optical Coherence
glaucoma drainage devices.75 Tomography (AS OCT)
The limitations of UBM include: OCT imaging in ophthalmology was done to image the
• Contact investigation—patient discomfort posterior segment with a wave length of 800 µm, which is
• Need to be done on patient in supine position incapable of scleral penetration. More recently, however, a
• Cannot be used in the immediate post op period new anterior segment OCT (AS-OCT) system was introduced
• Cannot be used in suspected open globe injuries using a longer wavelength (1310 nm).76 This allowed deeper
• Cannot be used in younger children penetration and cross-sectional imaging of the anterior
• Posterior capsule not imaged chamber, including visualization of the angle. A lateral
818 Glaucoma
Table 9.2.1.3: Quantitative parameters of UBM OCT provides high-resolution images of the anterior segment
Name Description
of the eye (Fig. 9.2.1.26) and allows a detailed qualitative and
Angle opening distance Distance between the trabecular
quantitative evaluation of the anterior chamber angle. This
(AOD) meshwork and the iris at 500 µm real-time imaging device also allows study of the dynamic
anterior to the scleral spur relationship between structures such as the peripheral iris
Trabecular-iris angle Angle of the angle recess and trabecular meshwork, thereby functioning as a light-dark
(TIA θ 1)
provocation test that is safe and repeatable. Coherent infrared
Trabecular-ciliary process Distance between the trabecular
(TCPD) meshwork and the ciliary process light from a diode laser is used whose time delay in the
at 500 m anterior to the scleral reflected light is measured from the machine. Series of axial
spur
scans are taken which give the image of anterior segment of
Iris thickness (ID1) Iris thickness at 500 µm anterior
to the scleral spur
eye. The resolution is 2 to 20 microns which is why it is
Iris thickness (ID2) Iris thickness at 2 mm from the iris
suitable for measurement of finer eye structures.78,79
root
Indications: They are the same as that for UBM except that it
Iris thickness (ID3) Maximum iris thickness near the
pupillary edge
cannot image the ciliary body and zonular abnormalities. These
Iris-ciliary process distance Distance between iris and the
are:
(ICPD) ciliary process along the line of • Angle closure glaucoma for angle assessment,
TCPD measurement of angle parameters, plateau iris, angle
Iris-zonule distance (IZD) Distance between the iris and recession glaucoma, anterior segment examination in
the zonule along the line of TCPD
opaque corneas80-86
Iris-lens contact distance Contact distance between
(ILCD) the iris and the lens • Phototherapeutic keratectomy to assess the depth of
Iris-lens angle (ILA θ 2) Angle between the iris and the corneal opacity12
lens near the pupillary edge • LASIK for CCT and to measure flap thickness, specially
for enhancement surgery87,88
• Keratoconus and INTACS for CCT and positioning of
INTACS89,90
• Assessment of IOL position in case of bullous
keratopathy
• Cysts of the anterior segment to diagnose etiology91
• Regrafts for assessment of posterior synechia
• Biometry for Phakic IOLs92
• Dry eyes for measurement of tear meniscus93
• Corneal power measurement for post LASIK patients.94
Advantages of the AS-OCT:
• Non-contact, and therefore has no disadvantage of
Fig. 9.2.1.26: Anterior segment on AS OCT indentation caused by placement of the scleral cup on
the eye (which is required to maintain the water bath in
resolution of 15 µm and axial resolution of 8 µm, enables UBM (Table 9.2.1.4). Also, there is no possibility of
corneal abrasion or punctate epithelial erosions (possible
useful applications of this new AS-OCT technology. The AS-
with UBM)
OCT has the benefits of being a rapid, non-contact method
• More physiological, as patient is imaged sitting upright.
that may be performed easily by a technician, with the patient
(Lying supine may artificially widen the anterior chamber
sitting in an upright position, and therefore being of a definite
angle as the iris-lens diaphragm moves posteriorly due
advantage over the ultrasound biomicroscopy.77
to gravity)
Principle: It is based on the principle of partial coherence • Shorter imaging time. (Patient set-up in UBM takes
interferometry.78 The infrared diode laser light of 1310 nm longer. Also, only one angle is imaged at a time with the
light used is able to penetrate sclera and limbus. The AS- older versions of the UBM)
Table 9.2.1.4: Comparison of AS OCT & UBM CCT likely influences the measurement of IOP with many
AS OCT UBM tonometers, including applanation techniques.100 Increased
Light source 1310 nm diode laser Ultrasound 50 MHz CCT beyond the mean of 545 µm causes overestimation of
frequency IOP; lower CCT translates into underestimation of the IOP.
Type Non contact Contact A thin cornea (e.g., 480 µm) may occur with glaucomatous
Axial resolution 18 50
Coupling medium Not required Required visual field loss despite normal applanation IOP because the
Field of view 16 mm across 5 mm across measurements are fallaciously low. Conversely, a thick cornea
(entire angle seen (only a part of angle (e.g., 620 µm) might be seen in an eye with high IOP, normal
in one scan) can be seen at one
time visual fields and a normal optic nerve because it results in
Ciliary body, Not well seen Well imaged false overestimation of true IOP. Ehlers et al95 extrapolated
zonules that applanation tonometry is overestimated or underestimated
Posterior capsule Well seen Not imaged
Image quality Clear grainy by approximately 5 mm Hg for every 70 µm difference in
measured CCT from mean thickness. It is also possible that
central corneal thickness may itself constitute an intrinsic
• Rapid image acquisition. (8 frames captured per second), risk (or protective) factor for glaucomatous optic nerve
allows the operator to choose best image damage independent of its ability to affect the IOP
• Requires less expertise to perform and there is less of a measurement.
learning curve for the operator Techniques for measuring CCT are conventional optical
• Target may be used to induce accommodation in the and ultrasonic technique. The ultrasonic technique consists
eye being imaged. This is useful in the evaluation of of scan ultrasound and ultrasound biomicroscopy. The other
accommodative intraocular lenses instruments with which CCT can be measured are specular
• It is more comfortable for the patient, due to non-contact microscopy, corneal topography, confocal microscopy, anterior
technique, upright position and rapid imaging acquisition segment optical coherence tomography, pentacam and ocular
• Less interoperator variability, due to non-contact response analyzer. Refer to section on corneal evaluation for
technique. further details.
Limitations:
Optic Disk and Nerve Fiber
• Not penetration of pigmented iris epithelium.
Layer Evaluation
• Ciliary body, zonules are not visualized clearly
The optic disk examination is an essential diagnostic tool for
Pachymetry glaucoma evaluation. Its examination confirms glaucoma and
also helps assess for progression of glaucoma.
Pachymetry (Greek words: Pachos = thick + metry = to This section discusses the following subheadings:
measure) is a term used for the measurement of corneal • Pathogenesis of glaucomatous optic atrophy
thickness. It is an important indicator of corneal health status • Clinical evaluation
especially with regard to corneal endothelial pump function.95 – Subjective methods
It is also a measure of corneal rigidity and consequently has – Objective methods
an impact on the accuracy of intraocular pressure (IOP) • Clinical changes of optic disk
measurement by applanation tonometry.96 The impact of • Documentation
central corneal thickness (CCT) on applanation tonometry – Disk diagrams (subjective methods)
was first discussed by Goldmann.96,97 – Disk photography
• Quantitative methods
Corneal Thickness in Normal Eyes: The normal corneal thickness
– SLP - Scanning laser polarimetry
in the central cornea varies between 0.49 mm and 0.56 mm
– SLO - Scanning laser ophthalmoscope
at the center. The mean CCT as shown by various studies is
– OCT - Optical coherence tomography
0.51 to 0.52 mm (standard deviation 0.02–0.04 mm).95
Ocular hypertension treatment study (OHTS) group
Pathogenesis of Glaucomatous Optic Atrophy
published a landmark report in 2002 that CCT was an
important independent risk factor for progression from ocular a. Mechanical theory:101,102 Muller proposed the theory
hypertension to early glaucoma.98,99 that elevated IOP led to direct compression and death of
820 Glaucoma
neurons. This is because raised IOP causes physical disadvantages of being contact lens and therefore have the
alterations of the optic nerve head due to back bowing risk of transmitting infection. The observer can have full
of the lamina cribrosa. This leads to obstruction of stereopsis, so that depth of perception is also possible. The
axoplasmic flow and axonal death. important point to keep in mind is that the image is reversed
b. Vascular theory: This theory suggested by von Jagger103 (superior neuroretinal rim will be seen inferiorly and macula
says that ischemia is responsible for interruption of short would be seen nasally). The slit lamp beam length can also be
post-ciliary arteries which blocks the axoplasmic flow.104 used to measure the disk size.107
This leads to death of neurons. 4. Hruby lens: This is a –66D lens which was used previously
but not used commonly in recent times.108 It has been
Clinical Evaluation of Optic Nerve Head described in detail in Section 12.
Careful examination of the optic nerve head and meticulous Stereoscopic viewing during slit-lamp examination
documentation is the key to glaucoma diagnosis. It can be improves the accuracy of disk evaluation, since the disk is a
done by various methods which are following: complex, three-dimensional structure. Cup to disk ratio of
1. Direct ophthalmoscope: It is the most commonly used method 0.3:1 or less is normally found in non-glaucomatous subjects.
of examination of the optic nerve head. It magnifies the But single cutoff values for the cup to disk ratio designed to
disk to 15 times than normal and therefore an enlarged distinguish between normal subjects and those with glaucoma
view of disk can be seen. As this is an uniocular are imperfect for screening, since the normal ratio varies
examination, depth perception is not possible and in cases considerably with optic disk size. Larger disk may have larger
of very large myopic disk it might be difficult to see all cup and vice versa. When the cup to disk ratio equals or
the findings. However it is useful in cases of small pupil exceeds 0.6, the probability of glaucoma increases
and for red free examination. It can be also helpful to dramatically.
measure the optic disk size. The smallest graticule of the The disk should be viewed stereoscopically with 90D lens
Welch Allyn Ophthalmoscope projects a circle of 1.5 mm to assess evidence for glaucomatous damage, including the
diameter at the optic nerve head. Therefore one can assess following:
the disk size by projecting it to retina and comparing it • Cup to disk ratio in horizontal and vertical meridians
(Gross technique).105 • Color and slope of the cup
2. Indirect ophthalmoscope: It magnifies the image five times • Appearance of the disk
and is not a very good tool for disk examination. Although, • Progressive enlargement of the cup
it can measure disk size by incorporation of a spacing • Neuroretinal rim (NRR) thickness, color, notching and
device on a condensing lens, that allows measurement of the ISNT rule and the which states that NRR is broadest
the disk images with a calipers.106 inferiorly followed by superior, nasal and temporal
3. Slit lamp biomicroscopy: As slit lamp alone cannot focus on • Evidence of nerve fiber layer damage using a red-free
retina, a lens is used which can be of following types: filter — May be focal (slit or wedge) or diffuse defect
• Presence of splinter hemorrhage (most common
• The 45D of corneal surface refraction is replaced by
inferotemporally)
an afocal plane surface
• Asymmetry between disks in the two eyes
– Contact type lens — Goldmann
• Peripapillary atrophy (possible association with the
• High power converging lens are used
– +90D lens, +78D development of glaucoma)
• The refractive power of the eye is neutralized • Congenital abnormalities of the optic nerve head
– Hruby lens — approximately -60D
Optic Disk Changes in Glaucoma
• Modern wide-angle imaging system
– Ocular Mainster wide field Early Signs
Converging lenses like + 90D and + 78D lenses are most 1. Enlargement of cup (vertically oval instead of the normal
suitable for examination of the optic nerve head. They are horizontal oval).
used in conjunction with the slit lamp so that magnification 2. Splinter hemorrhage at disk margin (Fig. 9.2.1.27)
of the slit lamp can be used as a adjunct. Goldmann lenses 3. Discrepancy in cup disk ratio (C:D) in both the eyes of
can also be used for the same purpose but they share the 0.2 or more
4. Notching of NRR It is found that cup to disk ratio is not an ideal parameter
5. Pallor of NRR to assess glaucomatous damage, as larger disk has a larger
6. Loss of ISNT rule cup and vice versa. Therefore, Spaeth et al109 devised a new
7. Retinal nerve fibre loss — seen on red free examination method to assess glaucomatous damage known as disk damage
as dark stripes/wedge shaped defects likelihood scale (DDLS) which incorporates disk size and
rim width in the evaluation of the disk. This has a high inter-
Late Signs
observer reproducibility and correlates strongly with visual
1. Enlargement of C:D ratio to 0.7 or more (Fig. 9.2.1.28)
field loss.
2. Lamellar dot sign: Optic nerve fibres pass through a sieve
like structure known as the lamina cribrosa. Due to Documentation of Optic Disk
stretching of optic nerve head these pores enlarge and
later on become slit like known as lamellar dot sign. Stereoscopic fundus photographs and disk diagrams:
Stereoscopic fundus photographs and clinical drawings are
3. Bean pot cupping: Total cupping with complete loss of NRR
required as a baseline for future comparisons. Stereoscopic
and vessels emerging from the disk margin.
photographs110 are the gold standard for recording of disk
4. Nasal shifting of vessels: Its not a reliable sign.
findings. They have following advantage:
5. Bayonetting sign: Broken vessels at the disk margins are
• Serves as a permanent record
known as bayonetting sign. When the vessels emerge from
• Better documentation is possible
the cup they follow the contour of the cup. Due to
• Disk morphometry analysis is possible
overhanging margins they get hidden under the margin
Two-dimensional photograph of optic nerve head is
and so they appear broken.
known as planimetry.
6. Baring of circumlinear vessels: Normally the vessels follow
the contour of the cup. Due to progressive enlargement Quantitative techniques: Newer imaging techniques that
of cup, there occurs a gap between the vessel and the utilize different physical properties of light for optical analysis
margin of the optic cup known as baring. can document the status of the optic nerve and the nerve
7. Pulsations of retinal arterioles: It is a pathognomonic sign of fiber layer. Sommer et al111,112 found that 88 percent of
glaucoma. ocular hypertensives who converted to glaucoma had RNFL
Fig. 9.2.1.27: Hemorrhage at disk margin Fig. 9.2.1.28: Advanced glaucomatous optic disk
822 Glaucoma
defects135 at the time when visual field defect were detected

with white on white perimetry. Sixty percent of these
converters had RNFL defects present six years prior to the
visual field defect.113 It has also been seen that RNFL
changes can occur prior to optic nerve head changes.
Therefore, these newer investigations have come up which
are able to pick up glaucoma before it appears on white on
white perimetry and it is known as pre-perimetric glaucoma.114
Furthermore, they can be used to detect changes over
time. The value of these technologies for diagnosing glaucoma
and for determining progression over time is currently under
investigation.
Fig. 9.2.1.29 : Principle of scanning laser polarimetry
Scanning laser polarimetry: Retinal nerve fiber layer
(RNFL) thickness is measured by scanning laser polarimetry
(GDx, Carl Zeiss Meditec, Inc, Dublin, CA) with polarized birefringence for each eye. In order to individually
light and is compared to normative database of aged matched compensate for the anterior segment birefringence, the specific
controls incorporated in the machine.115 axis and magnitude of the anterior segment birefringence
Principle: The RNFL is made of highly ordered parallel axon must be known.117 This is determined by first imaging the
bundles which cause RNFL to be birefringent. Birefringence eye without compensation. Once the anterior segment
is the splitting of a light wave by a polar material into two birefringence axis and magnitude values are determined, the
components. These components travel at different velocities retardation signal from the anterior segment can be
which creates a relative phase shift that is termed as compensated.
retardation. The amount of phase shift or retardation is Enhanced corneal compensation (ECC): This is a newer software
proportional to the thickness of the RNFL.115,116 to account for atypical retardation pattern (ARP) seen in
A scanning laser polarimeter is a confocal scanning laser myopes and aphakes.
ophthalmoscope with an integrated ellipsometer to measure ECC algorithm introduces a predetermined birefringence
retardation. Polarized light passes through the eye and is bias in these patterns to correct ARP to give more reliable
reflected off the retina. Because the RNFL is birefringent, readings.118
the two components of the polarized light are phase shifted
relative to each other (retarded) (Fig. 9.2.1.29). The amount Clinical interpretation of the GDx VCC printout: For
of retardation is captured by a detector, and converted into each GDx VCC scan (Fig. 9.2.1.30) an age-matched
thickness (in microns). comparison is made with the normative database and any
significant deviations from normal limits are flagged as
Anterior segment birefringence: The anterior segment (the cornea abnormal with a ‘p’ value.
and lens) of eye is also birefringent. Therefore, the total
The print out shows the following maps which are used
retardation of a subject's eye is the sum of the cornea, lens, for interpretation.
and RNFL birefringence. So, compensation of anterior
1. The Thickness Map shows the RNFL thickness in a color-
segment birefringence is necessary to isolate RNFL coded format, the color spectrum going from blue to
birefringence.
red. Thick RNFL values are warm colors like yellow,
Early scanning laser polarimeters (e.g. the GDx NFA and orange, and red while thin RNFL values are cold colors
the GDx Access), compensated for anterior segment
like dark blue, light blue, and green.
birefringence based on fixed values for the axis and magnitude 2. The Deviation Map reveals the location and magnitude of
of the anterior segment birefringence.116 But it gave fallacious
RNFL defects over the entire thickness map. For each
readings due to fixed values. So, the machine was modified, scan, the RNFL thickness at each pixel is compared to
as VCC (variable corneal compensator).
the age-matched normative database, and the pixels that
Variable corneal compensation (VCC): The GDx VCC measures fall below the normal range are flagged by colored squares
and individually compensates for anterior segment based on the probability of normality. The warm colors
Inter-eye symmetry: This measures the degree of symmetry

between the right and left eyes by correlating the TSNIT
functions from the two eyes. Values range from -1 to 1, where
values near one represent good symmetry. Normal eyes have
good symmetry with values around 0.9.
The nerve fiber indicator (NFI): The NFI is a global measure

based on the entire RNFL thickness map. It utilizes
information from the entire RNFL thickness map to optimize
the discrimination between healthy and glaucomatous eyes.
The output of the NFI is a single value that ranges from 1 to
100 and indicates the overall integrity of the RNFL.
1–30 → normal,
31–50 → borderline,
51+ → abnormal.
Serial analysis is also possible by which progression can
be assessed.
Advantages
• Does not require pupillary dilatation
• Good reproducibility
• Does not require a reference plane as in HRT
Fig. 9.2.1.30: GDx VCC printout • Can detect glaucoma on first examination
• Early detection before standard visual field
• Easy to operate
indicate more damage and cold colors indicate lesser • Comparison with age matched normative database
damage. The probability is mentioned below the map.
3. The TSNIT Map: TSNIT stands for Temporal-Superior- Limitations
Nasal-Inferior-Temporal and displays the RNFL thickness • Affected by anterior and posterior segment pathology
values along the calculation circle starting temporally and – Ocular surface disorders
moving superiorly, nasally, inferiorly, and ending temporally. – Macular pathology
In a normal eye the TSNIT plot follows the typical 'double – Cataract and refractive surgery
hump' pattern, with thick RNFL values superiorly and – Refractive errors (false positive in myopes)
inferiorly and thin RNFL values nasally and temporally. – Peripapillary atrophy (scleral birefringence interferes
The TSNIT graph shows the curve (or function) of the with RNFL measurement)
actual values for that eye along with a shaded area which • Does not measure actual RNFL thickness (inferred value)
represents the 95 percent normal range for that age. In a • Measures RNFL at different locations for each patient
healthy eye, the TSNIT curve falls within the shaded • Does not differentiate true biological change from
area. When there is RNFL loss, the TSNIT curve falls variability
below this shaded area. • Limited use in moderate/advanced glaucoma
• Requires a wider database from the Indian population
4. The TSNIT parameters are displayed in a table in the center • 4th machine prototype (cannot update earlier versions)
of the printout. The TSNIT parameters are summary
measures based on RNFL thickness values within the Confocal scanning laser ophthalmoscopy: The
calculation circle. These parameters are automatically Heidelberg Retina Tomograph is a confocal laser scanning
compared to the normative database and are quantified in Ophthalmoscopy (CSLO) system and functions for acquisition
terms of probability of normality. Normal parameters and analysis of three dimensional images of the posterior
values are displayed in green, abnormal values are color- segment. Heidelberg retinal tomography (HRT) enables the
coded based on their probability of normality. quantitative assessment of the topography of ocular structures
824 Glaucoma
along with follow-up of topographic changes. Various studies retinal surface appears dark. With the information in the
have shown that it is highly reproducible.119-125 topography image, we can quantify the three-dimensional
Principle: It is based on two basic principles (Fig. 9.2.1.31): properties of the examined structure.
• Confocal imaging The reference plane (Fig. 9.2.1.32) is defined parallel to
• Scanning tomography the peripapillary retinal surface and is located 50 microns
The laser light is focussed on the retina. The reflected posterior to the retinal surface at the papillo-macular bundle.
beam is deflected to a detector. A diaphragm is incorporated The Heidelberg Retina Tomograph operation software
in the passage of the deflected beam which cuts off automatically defines a reference plane for each individual
peripheral rays and focuses the central rays only. This eye. The distance between the reference plane and the retinal
surface is used to measure the mean thickness of the retinal
diaphragm acts as a pin hole and is conjugated to the focal
nerve fiber layer. All structures located below the reference
point of the illuminating system, and is hence known as
plane are considered to be cup; all structures located above
confocal.
the reference plane and within the contour line are considered
Two-dimensional pictures are acquired in the above
to be rim.
manner and then sequential scans are taken at varied depth
A contour line is drawn by the observer at the disk margin
known as scanning tomography. Two-dimensional optical
which calculates the reference plane. Therefore, it becomes
section images are acquired within 32 milliseconds and with a
observer dependent.125-127
repetition rate of 20 Hz. The images are digitized in frames
The Moorfield's regression analysis is software available
of 256×256 picture elements. The size of the field of view
with the HRT 2. The normative database in HRT 2 include
can be changed and set to 10° x 10°, 15° x 15°, or 20° x 20°. 349 subjects for the stereoscopic parameters and 110 subjects
A three-dimensional image is acquired as a series of 32 equally for the Moorfields regression analysis (MRA) out of which
spaced two-dimensional optical section images. The total 51 were glaucomatous subjects and 80 were normal
acquisition time is 1.6 seconds. The light source is a diode subjects.128 Disk parameters for the disk as a whole and in
laser with a wavelength of 670 nm. A 1 mm pupil diameter is six pre-defined sectors are analyzed. Linear regression analysis
sufficient to get the image. is performed on the relationship between normal disk
The result is a color coded topography image which is an parameters and optic disk area, and the normal ranges are
image of pseudocolors for better visualization. The optic defined by the 99 percent prediction intervals. These when
nerve head appears bright because it is excavated; the elevated applied to the glaucomatous group has shown that the
Fig. 9.2.1.31: HRT principle based on confocal imaging and scanning tomography
and maximum cup depth, a measure for the three-

dimensional shape of the cup, and for the mean thickness
of the retinal nerve fiber layer along the contour line.
Progression assessment: HRT has been well accepted for
progression assessment. There are three methods to assess
progression:
• Parametric description
Fig. 9.2.1.32: HRT-reference plane • Computation and analysis of topographic difference
images
neuroretinal rim area had the greatest sensitivity and specificity • Change probability maps
for detecting a glaucomatous abnormality. HRT3, a newly-enhanced version which includes the Fast
Check Glaucoma Probability Score, is generated using an
HRT printout: The HRT Printout (Fig. 9.2.1.33) shows the advanced form of artificial intelligence called a relevance
following zones: vector machine. This sophisticated analysis provides a
• Color coded topography image: Red area marks the cup, rest statistical probability of glaucoma using ethnic-specific
of the disk area is divided into a sloping (blue) and a databases (Afro-American, Caucasian & Indian).128,129 The
stable (green) neuroretinal rim software eliminates the need to draw contour lines or use
• Reflection image: This is a false color picture. The Moorfields reference planes and provides real-time feedback to assist
regression analysis divides ONH into six sectors. The neuro the operator in acquiring a quality image.
retinal rim (NRR) area in each sector is then compared Advances over HRT 2 include:
with the normal database depending on the disk size. A • Larger ethnic based normative database (Caucasian,
green tick indicates good health, yellow question marks African, Indian)
indicate borderline health and red cross indicates damaged • Provides, cup, rim, RNFL analysis with a single machine
NRR • Takes optic disk size into consideration (small, average,
• Graphs: large sized)
– Graph between the above two images is known as • Asymmetry analysis using OU database to compare one
vertical height profile and beneath topography map is eye of patient with the other
known as horizontal height profile. In these two graphs, • Glaucoma probability score (GPS) based on artificial
the red line indicates the location of the reference intelligence method (or relevance vector machine by
plane and black lines perpendicular to the height profile comparing patient's disk with corresponding healthy and
denote the borders of the disk as defined by the glaucomatous disk).
contour line
– Mean height contour graph is the graph beneath Optical coherence tomography: Tomographic techniques
reflectance image. The green line indicates retinal generate slice images of three-dimensional objects. The stratus
surface height profile along the drawn contour line optical coherence tomography (OCT) (Humphrey-Zeiss
and the rest of the lines denotes same as above graph. Medical Systems, San Leandro, CA) uses reflected light in a
Dark black line indicates the mean peripapillary retinal manner analogous to the use of sound waves in
surface height, this is then set as a zero point of the ultrasonography. The echo delay time of the light (similar to
height (z-axis) the use of sound in ultrasonography) backscattered from
• Moorfield regression analysis: This is the graph in the form of different layers in the retina is measured using an optical
columns present at the lower right hand corner. The whole interferometer, to create computerized cross-sectional images
column represents the total optic nerve head area in a of the retina and optic disk. It also gives quantitative
specific sector. The column is divided into the percentage information about the peripapillary retinal nerve fiber layer
of rim area (green) and percentage of cup area (red) thickness. The name STRATUS OCT (derived from stratum,
• Stereotactic parameters: The result of this analysis is a set of Latin for "layer") refers to its unique ability of direct cross-
stereometric parameters given at the lower left corner of sectional imaging of the layers of the retina akin to histological
the print out. The most important parameters are the section. The first optical ocular scanning device was developed
disk area, cup and rim area, cup and rim volume, mean by Huang and Fujimoto in 1991.130
826 Glaucoma
Fig. 9.2.1.33: HRT printout
Principle: It is based on the interferometer principle of through a coupler which splits it into sample and reference
Michelson 130 while the newer versions are based on arms (Fig. 9.2.1.35). The amplitude delays of the tissue
spectrometry. A low coherence light (Figs 9.2.1.34A and B) reflections from two arms are combined at the coupler and
source from diode laser of 830 nm wavelength is used. The detected by a photo diode. When output delay is matched a
infrared light from a superluminescent diode laser is passed interferometric pattern is generated which is detected and
used to form images of optic disk and retina. To derive

information from a two-dimensional picture, several
longitudinal scans are performed.
In the time domain OCT, the axial resolution increases
with widening of the optical band width of the employed
light source. The depth resolution of this technology depends
on the characteristics of the light source and is approximately
15 microns.130,131 The lateral resolution is dependent on both
wavelength and the optics of the eye and is between 30 and
50 microns. A circular scan centered on the optic disk and
the peripapillary retina acquires between 128 and 768 A-
scans in less than two seconds and uses mathematical
algorithms to determine the nerve layer thickness.132 This
information is then used to create a two-dimensional image
by performing successive axial range measurements. In the
OCT scanners currently commercially available, highly
reflective structures are shown with bright colors (red and
white), while those with low reflectivity are represented by
darker colors (black and blue). Those with intermediate
reflectivity appear green.
It has 16 scans protocols for glaucoma and retina patients.
Four scans are important from the glaucoma point of view:
1. RNFL scan
2. Fast RNFL scan
3. Optic disk scan
4. Fast optic disk scan
The RNFL thickness measurements (Fig. 9.2.1.36) along
the circular scan made around the optic disk are on the vertical
axis, and the temporal, superior, nasal, and inferior quadrants
Figs 9.2.1.34A and B: Principle of OCT are on the horizontal axis. Circular diagrams show quadrant
Fig. 9.2.1.35: Principle of OCT

828 Glaucoma
and clock-hour RNFL thickness averages. The average RNFL

thickness is also shown. Though normative database is not
available for statistical significant change but changes in the
RNFL can be studied over time in the same patient. The
graphs indicate the RNFL thickness along the nasal, superior,
temporal, and inferior quadrants for each eye separately and
together on the bottom graph. Circular diagrams show
quadrant and clock hour thickness averages.
The optic disk scan (Fig. 9.2.1.37) measures the amount of
optic nerve fiber at the optic nerve head. It takes six radially
acquired cross-sectional line scans. One measure is the cross-
sectional area of the nerve fiber above the cup. The other
measure is the minimum distance between the retinal pigment
epithelium and the RNFL surface. This analysis measures
the disk diameter by tracing a straight line between the two
reference points. It measures cup diameter on a line parallel
to the disk line and offset anteriorly by 150 microns. The cup
offset is 150 microns by default and is adjustable. The optic
nerve head analysis results give the vertically integrated rim Fig. 9.2.1.37: Optic nerve head analysis
Fig. 9.2.1.36: RNFL thickness analysis

area volume, horizontally integrated rim width, disk area, cup resolution. It also gives better visualization of intraretinal
area, rim area, cup/disk area ratio, cup/disk horizontal ratio, layers such as the photoreceptor layers, ganglion cell layer,
and cup/disk vertical ratio. The depth values of the scans and plexiform and nuclear layers (Fig. 9.2.1.38).
are independent on the optical dimensions of the eye, and no
The advantages are:
reference plane is required.
• 3 µm axial resolution (>3 times finer resolution)
Schuman and coworkers133 evaluated the ability of OCT
• Transverse resolution better
to detect progressive RNFL loss in an experimental model
• Acquisition speed 25000 scans/sec (>50 times higher
of glaucoma using primate eyes. OCT demonstrated a linear
speed than OCT 3)
reduction in RNFL thickness over time in eyes with increased
• Minimal motion artifacts due to rapid image acquisition
IOP compared with control eyes in which there were no
by Fourier domain/spectral detection
detectable changes. Retinal nerve fiber layer thickness
• Creates a 3D image that shows the optic disk, macula
measurements in glaucomatous eyes are significantly less
and blood vessels
compared with normal eyes, and there is good correlation
• Does not need pupillary dilatation
between RNFL thickness measurements and visual
• Long working distance 22 mm from cornea to the ocular
function.134
lens
RNFL thickness measured on OCT serves as useful
adjuncts in accurately and objectively distinguishing normal Fluorescein angiography, ocular blood flow analysis via
from glaucomatous eyes. Even in the early stages of glaucoma, laser Doppler flowmetry, color vision measurements,
it helps to differentiate the various stages of glaucoma. contrast sensitivity testing, and electrophysiological tests (e.g.
Average and inferior RNFL thicknesses are among the most pattern electroretinograms) are used as research tools in
efficient parameters for distinguishing such a differentiation.135 the evaluation of POAG patients. Routine clinical use is not
The advantages are: advocated at this time.
1. Non-invasive
The author/editors have no financial interest in any product or procedure
2. Can be done in children
mentioned in this chapter.
3. High resolution
4. No reference plane required
5. Fast
6. Independent of refractive errors
The disadvantages are:

1. Image quality degraded by media opacity
2. Pupil diameter 3 mm or more
3. Operator skill dependent
4. Scan may not be possible in uncooperative patient
5. The computer may mis-identify inner and outer retinal
layer
6. Expensive equipment.
Ultrahigh resolution OCT: Ultrahigh-resolution OCT (UHR
OCT) images with axial resolutions of two to three microns
and has shown to improve the visualization of retinal and
corneal morphology and retinal pathology that has previously
been possible only with histopathology. It is a new OCT
imaging system using Ti:Al2O3 laser (femtosecond Ti:sapphire
laser) or superluminiscent broadwidth diode laser. High-speed
UHR OCT enables an increase in acquisition speed of 60
times relative to the StratusOCT and three times finer axial Fig. 9.2.1.38: Ultra high resolution OCT (RT Vue 100)
830 Glaucoma
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834 Glaucoma
9.2.2 Evaluation and Interpretation

of Visual Fields
Anuradha Chandra, Reena Sharma, Shalini Mohan
VISUAL FIELDS IN GLAUCOMA

Glaucoma is a progressive optic neuropathy that causes
morphologic changes of the optic disc and the retinal nerve
fiber layer, accompanied by associated effects on the visual
field. Glaucoma patients are diagnosed on the basis of
structural changes seen on the optic disk and functional
changes seen in the visual field. The functional measurements
can quantify the patient's visual status. Therefore, visual field
testing is a very important examination factor in the
management of glaucoma patients.
A visual field has been classically described by Traquair
as an island of vision surrounded by a sea of blindness.1,2
This three dimensional concept is reduced to quantitative
values by plotting lines (isopters) at various levels around the
island or by measuring the height of the stimulus (sensitivity)
at different points within the island of vision. Fig. 9.2.2.1: Goldmann visual fields
A normal patient can see 60o nasally, 110o temporally,
75 inferiorly and 60o superiorly. Therefore, a normal visual
o
field is horizontally oval, often with a shallow inferonasal The brightness can be increased if it has not been seen and
depression. The area of maximum visual sensitivity in the vice versa.
normal visual field at photopic conditions is at the point of
Kinetic: The stimulus of a particular shape, size and brightness
fixation corresponding to the foveola of the retina and appears
moves from the non-seeing area to the seeing area. The points
like a smooth rising peak surrounded with a high plateau.
are marked and joined to form an isopter. Examples are, the
The visual field then tapers down gradually until it again falls
Lister's perimeter, Bjerrum's screen, Goldmann perimeter,
abruptly in the peripheral limits.
etc.
The blind spot is the region of deep depression within
Goldmann perimetry is a common example of both kinetic
boundaries of the normal visual field corresponding to the
and static perimetry. The Humphrey Field Analyzer™
optic nerve head which lies temporal to fixation in the visual
(Humphrey, San Leandro, CA) is a common example of static
field. It has two parts; absolute and relative scotoma. The
perimetry.
absolute scotoma refers to the area of optic nerve head which
Perimeters can also be classified as manual or automated,
is devoid of photoreceptors and is seen as vertically oval.
depending on whether the stimulus is moved by hand as in
The relative scotoma surrounds the absolute scotoma and
the Goldmann perimeter, Bjerrum's screen or if the stimulus
corresponds to peripapillary retina which has reduced
location is changed by a computer (automated), as in the
sensitivity.
Humphrey visual field (HVF) analyzer.3,4
There are two basic types of visual field tests commonly
The classical perimeters include screening tests like Bjerrum's
used in the clinic. Depending on whether or not the stimulus
screen in which a large plane surface is used for detecting and
moves, the test can be classified as static or kinetic.1,3,4
plotting the central visual field (about 50º in diameter) by
Static: This includes Goldmann (Fig. 9.2.2.1) and automated moving the position of a stimulus (e.g. a white 1 mm pinhead).
perimetry. Here the stimulus of a particular threshold/ It consists of dull black cloth 1 meter square placed
brightness is presented at a particular point in the visual field. perpendicular to the line of sight 1 meter away from the
subject (2 meter for a 2 m2 gives more accuracy). In the the corrective lens (distance correction plus Goldmann add
center of the screen is a white spot that provides a fixation for age) is put into position and plotting of the central field is
point and a series of radial and circumferential lines are shown done. The blind spot is outlined with the smallest target that
or drawn to facilitate the localization of the stimulus. In fact, covers it. Then stationary targets are tested for scotoma. To
most commonly ordered visual fields only test the central avoid patient fatigue, the test should not exceed ten minutes.
portion of a patient's field of vision.5 The amount of field Fixation is checked through the observation tube during
tested depends on the test performed. Only a few tests, such movement of the pantograph handle. A gap of few seconds
as the Goldmann visual field (GVF), truly evaluate the whole is given at times to check the patient's response and
visual field. consistency.
Unlike defects on most automated visual fields (which
Goldmann Perimetry show up as dark areas), most defects on a GVF are changes
in the isopter. If the circle has an indented area, this represents
The Goldmann visual field (GVF) tests the entire visual field, an area of the visual field where the stimulus was not seen.
one eye at a time, by plotting points along circles known as Additionally, the distance between the isopters is important.
isopters. Each isopter should be color-coded to the size and Dense scotomas are depicted as shaded areas on the GVF.
intensity of the stimulus used.3,5,6 The size and intensity of Certain advantages of the GVF over automated tests
the stimulus can be adjusted. The stimulus size varies between like the Humphrey are that it tests peripheral field while
0 to V (Table 9.2.2.1), and the intensity varies between one Humphrey tests the central 30 degrees. It involves active
and four for each 5 dB (decibel) change and further differs interaction between the examiner and the patient making them
between a-e for smaller (1 dB) change (Table 9.2.2.2). For more alert during the test (Table 9.2.2.3). The disadvantage
example, a III 2e stimulus is larger and brighter than a I 2d is that the test is not easily reproducible and not sensitive in
stimulus, but not as large or as bright as a IV 3a stimulus. early glaucoma defects. The test does not have the advantage
The most common stimuli used are I4e for peripheral of computerised system of storage and comparison with
and I2e for central visual field. A GVF is performed by normative data (Table 9.2.2.4). However with severe vision
using the pantograph handle to move the stimuli from the loss (vision worse than 20/200), test-retest variability might
non-seeing area into a seeing area at about three to five be better in comparison to automated static testing. In addition,
degrees per second. The peripheral field is first determined it shows functional (non-organic defects on visual field testing)
without the correction. After the peripheral isopter is detected, better than automated testing.
Table 9.2.2.1: Goldmann stimulus size and area Table 9.2.2.3: Advantages of Goldmann visual testing
Name Diameter Area
(mm) (mm2 ) • Tests full extent of patient's visual field
• Better for mapping shape of defects
0 0.28 0.0625
• Can be carefully tailored to pathology
I 0.56 0.25
II 1.13 1 • Can be used in patients with poor vision
III 2.2 4 • Has a human interface, thus easier for the patients
IV 4.5 16 • Fixation of the patient is always under check, the test can
V 9.03 6.4 be stopped if the patient fails to concentrate.
Table 9.2.2.2: Types of Goldmann stimuli Table 9.2.2.4: Disadvantages of Goldmann visual testing
I (in asb) Brightness I (in asb) Brightness • Cumbersome and time consuming
13 1a 126 3a • Requires highly trained personnel
16 1b 158 3b • Does not provide the numeric data for comparing
20 1c 200 3c
25 1d 251 3d • Less sensitive for subtle visual field defects
32 1e 316 3e • Inter observer variation
40 2a 398 4a • Central field charting is not fully reliable
50 2b 501 4b
63 2c 631 4c • Inbuilt data record/saving system not available
79 2d 794 4c • Does not permit comparison of one examination to the other
100 2e 1000 4e as data cannot be stored.
836 Glaucoma
Indications: Goldmann Field The visual threshold7 is the physiologic ability to detect a
stimulus under defined testing conditions. The normal
1. The patient is not able to perform reliably on Humphrey
threshold is defined as the mean threshold in a normal
fields repeatedly.
population in a defined age group at a given location in the
2. A visual field defect appearing on both Humphrey and
visual field. It is against these values that the machine compares
Goldmann fields is likely to be a true visual field defect
the patient's sensitivity. Thresholds are reported in decibels,
rather than an artifact.
in a range of 0 to 50. The automated perimetry compares
3. Neurological disorders.
the patient's sensitivity to stored values that have been obtained
4. Visual acuity less than 6/60
from normal people; in other words, the normative data.8 The
normal thresholds are stored in the computer of the perimeter
Automated Visual Field
and it is against these normal thresholds that the perimeter
This is the most commonly used field test. There are mainly compares the patient's data.
two types of automated visual fields6 Interpretation of Humphrey's automated perimetry fields
1. Humphrey's (Carl Zeiss, Dublin, CA) is done in following order (Fig. 9.2.2.3):
2. Octopus (Haag Streit, Switzerland).
Humphrey's visual fields (Fig. 9.2.2.2) are more commonly Zone 1: This documents the patient's data.
used so it will be described in more details. There are certain The name of the patient, age, the test performed and threshold
terminologies with which the user needs to be familiar. used is documented. In this area, the type of target used, the
Decibels are a way of comparing the intensity of light to strategy (SITA or Full threshold), whether the fixation target
the maximum possible light intensity the machine can produce. was central or a large diamond (as is usually done when there
It does not have a value that can be measured somewhere is a central scotoma) are also documented. The birth date is
other than in the machine, like meters or pounds. Ten decibels very important as it determines the normative data with which
(10 dB) means that the light is 1/10th as bright as the brightest the field is compared. If not entered exactly, the patient's
light possible, 20 dB means that the light is 1/100th as bright threshold will be compared to the normals of the wrong age.
(it is based on log units). So, the higher the number of dB, the The refractive correction used should be appropriate,
dimmer the stimulus. otherwise a generalized depression is shown in the visual field
Fig. 9.2.2.2: Humphrey's visual fields printout with fixation losses Fig. 9.2.2.3: Zones in automated visual fields
printout. The pupil size should be at least 2.5 to 3 mm in interpretation: the darkest dots indicate that less than 0.5
diameter and must be similar in all fields. percent of the normal population would be expected to have
such a depression in those areas. The total deviation plot also
Zone 2: It shows the reliability indices and foveal threshold.1,8,9 highlights any scotoma that may be present, involving a large
Visual acuity must corroborate with the foveal threshold. It area of the visual field.
serves as an internal validation for the visual acuity; the two Generally the diagnosis of glaucoma depends on the
should correspond. If the visual acuity is good but the foveal identification of localized field loss. The total deviation plot
threshold is low, it may indicate be early damage to the fovea. in Zone 4 highlights any overall depression of visual field of
On the other hand if the foveal threshold is good and the the patient compared to age related normals. However, it
visual acuity is low, perhaps the patient needs refraction. does not reveal any hidden scotoma that may be present in
Reliability indices are false positive error, false negative this depressed field.
error and fixation losses. The machine will flag fixation losses
Zone 5: To produce this zone, the machine adjusts for overall
(20%), false-positive and false-negative errors (33%) above
depression of the visual field, due to cataract or some other
a certain percentage, indicating that the patient has low
reason. It adjusts for any overall sinking of the hill of vision.
reliability criteria. This does not necessarily imply that the
The Pattern Deviation Plot, draws attention to any localized
field will provide no useful information; it is just that such
scotomas that may have been hidden inside this depressed
fields were not included in the database. Hence, such fields visual field. The Pattern Deviation plot is also provided as a
must be interpreted with more caution. High false negative numerical plot as well as a probability plot.
errors is expected in advanced field defects.
• Fixation losses: The number of times a patient is looking Zone 6: There are four global indices. The Mean Deviation
at a wrong spot. It is tested by throwing the stimulus in (MD), the Pattern Standard Deviation (PSD), the Short Term
the blind spot which is normally not seen by the patient. Fluctuation (SF), and the Corrected Pattern Standard
If he can see it, that is counted in and converted to a Deviation (CPSD).1,6,8
percentage The Mean Deviation is derived from the total deviation
• False positive error (trigger happy patients): The number plot. Like the total deviation plot the mean deviation indicates
of times when the patient presses the button without seeing any overall depression (or elevation) of the patient's hill of
the light stimuli but by listening to the sound of the vision. A positive number indicates a better than normal field
machine (elevation of the hill of vision). A negative number indicates
a depression of the hill of the vision. This is likely to be
• False negative error: This is calculated as the number of
found in cases of media opacities such as cataract, corneal
times the patient does not respond to a brighter stimuli at
opacity, refractive error, or miosis. A large scotoma can also
a same spot where he was able to see a dimmer light, that
produce a negative mean deviation.
is, stimuli of lesser threshold.
The Pattern Standard Deviation is derived from the pattern
Zone 3: This is the gray scale that is meant for a visual deviation plot; and gives different information. Thus the
impression of the actual perimetry results that are used for Pattern Standard Deviation, like the Pattern Deviation plot,
interpretation and clinical decision making. It is useful in some highlights any scotomas that may be hidden in a depressed
instances where highlighted areas looked can be at in detail; it hill of vision.
is also useful when there are gross false-positive and false- The Short-term Fluctuation is the intra-test variation in
negative errors. But in general, a diagnosis is not to be made threshold. It is essentially the error in threshold determination.
based on the gray scale. Threshold values at ten predetermined points in the visual
field are obtained twice. The standard deviation of these
Zone 4: This is the Total Deviation plot. It is a point by point values is the short-term fluctuation. The short-term
difference of the patient's threshold from those expected in fluctuation is an indicator of reliability; but it could also be
age corrected normals. The shaded area in the total deviation an indicator of pathology. Diseased points have a greater
plot highlights an overall sinking of the patient's vision, as variability. If any of these predetermined fixed points were
compared to age-related normals. It is depicted as both a pathologic, the variability would be greater. In that case the
numerical plot and probability plot. The probability plot short-term fluctuation would reflect pathology. If all these
predicts the chances of such an abnormality occurring in the fixed points were tested in normal areas of the visual field, a
normal population. A scale is provided for ease of high short term fluctuation would indicate low reliability.
838 Glaucoma
The Corrected Pattern Standard Deviation (CPSD) draws Criteria for conformation of visual field defect suggestive of glaucoma
attention to any irregularities in the visual field (that is localized (Anderson's criteria)1,6,7
scotomas) irrespective of any overall depression due to media Criterion 1: There are three or more non-edge points that are
opacities as well as after adjusting for errors of threshold depressed to an extent that would be found in less than five
determination (as reflected by the short term fluctuation). percent of the population; one of those points should be
The double thresholding of ten points required for testing depressed to an extent found expected in one percent of the
for short-term fluctuation takes a lot of time. In the SITA population. These points should be clustered in the arcuate
program the short-term fluctuation and the CPSD are no area. In the pattern deviation plot, if it is a 30–2 program
longer available.1,7,9,10 The pattern standard deviation is (i.e. testing out to 30o), one has to ignore the outside edge
substituted as criteria in making the diagnosis. points. This is not needed for a 24–2 program.
Zone 7: This is a very important zone called the Glaucoma Criterion 2: The Corrected Pattern Standard Deviation (CPSD)
Hemifield Test. In the glaucoma hemifield test, five sectors (or the PSD) should be depressed to an extent found in less
in the upper field are compared to five mirror images in the than five percent of the population.
lower. If the values between any sector in the upper, and
lower zone differ to an extent found in less than one percent Criterion 3: The glaucoma hemifield test is outside normal
of the population, the glaucoma hemifield test is considered limits.1
"outside normal limits". If any one pair of sectors is depressed This entire criterion should be seen in two consecutive
to the extent that would be expected in less than 0.5 percent fields.
of the population, it is again considered "outside normal
limits". Progression in Visual Field Defect
If both these conditions do not apply, but the difference The single field is used to identify the defect but the most
between any one of the upper and lower mirror zones is common method to document visual field progression is
what might be expected in less than three percent of the longitudinal study of visual fields.11 In 1986, shortly after the
population, the glaucoma hemifield test is considered HFA was released, mean deviation was used to detect
"borderline". glaucoma disease progression.12,13 Decline in mean deviation
If the best part of the visual field is depressed to an was considered as increasing visual loss. Mean deviation was
extent expected in less than 0.5 percent of the population, plotted over time, and if the P value of the slope was less
the field test is considered to have an "abnormally low than five percent, it indicated that the visual field was
sensitivity". On the other hand, if the best part of the visual deteriorating at a statistically significant rate. Cataracts and
field is such as would be found less than 0.5 percent of the media opacities lead to fallacious results of progression of
population, it is considered to have an "abnormally high the disease.14
sensitivity". The Overview Program15 was a sequential series of fields
The glaucoma hemifield test is not designed to detect a of the same patient printed out on a single piece paper that
temporal wedge defect. Fortunately, such defects are rare. contained all the data that a single field analysis provides. Up
Finally, even if all the zones are normal, but the clinical to 16 fields could be printed on a single piece of paper. At
features are very suspicious, we would suggest that the actual that time, one may have considered decline in the pattern or
threshold values in the given patient be inspected for any corrected pattern standard deviation to indicate localized
pattern or scotoma. These values are shown in zone 8. It is progression, which was more likely to be due to glaucoma
to be remembered that a scotoma, as defined, is not compared than cataract.
to normals, but to the surround. By concentrating on the About three years later, the software called Glaucoma
actual threshold values, one may pick up a suggestion of a Change Probability15,16 became available. The plots took into
scotoma. If such defects are repeatable and correlate with consideration individual points over time rather than the entire
the clinical picture one may elect to treat. It is also of value field. This was an event-based analysis. Two baseline fields
to look at the thresholds in the upper arcuate area, compare were merged for comparison with subsequent fields. Black
it with the lower part in the arcuate area, and clinical triangles on the plots represented potential depressed points
correlation assessed. and were considered significant if confirmed on a follow-up
test. If two or more adjacent points within or adjacent to an The trend analysis graphic plots the visual field index on
existing scotoma were worsening at a P value less than five the Y axis against the patient's age on the X axis. It also projects
percent, a second or perhaps third visual field confirmed the the amount of additional field loss that would occur in five
progression. years if therapy is not changed and the patient's disease
In 2005, Glaucoma Progression Analysis (GPA)1 software continues to progress. This is a convenient, easily
for the HFA was introduced. GPA is similar to Glaucoma understandable way for the physician to convey to the patient
Change Probability, but it is better because it adjusts for the status of his or her glaucoma.
cataract, a common problem amongst glaucoma patients, in Short-wavelength automated perimetry (SWAP) is a visual
progressively worsening visual fields. It works with baseline function-specific field test that is processed preferentially by
full threshold fields, as well as baseline Swedish interactive short-wavelength-sensitive cones through their connections
thresholding Algorithms (SITA) fields. All follow-up fields, to the small bistratifed ganglion cells. These make up eight
however, must be SITA. It uses the criteria and statistical percent to ten percent of the retinal ganglion cells.18 SWAP
analysis from the Early Manifest Glaucoma Trial (EMGT) has been very useful for detecting glaucoma. However, an
to identify progression at individual points, which makes it an important clinical drawback of SWAP using the full-threshold
event-based analysis, and not a trend analysis. In the EMGT, (FT) algorithm has been the lengthy test time. SWAP applies
a patient was considered to have progressed if three or more a blue stimulus, Goldmann size V, on an intense yellow
test points in the same location showed deterioration at the background. The currently accepted clinical method, as
five percent level (P<0.05) on three consecutive field tests.17 incorporated in the Humphrey Field Analyzer (HFA; Zeiss-
GPA software compares current and previous perimetry Humphrey Systems, Dublin, CA), utilizes a Goldmann size V
results and uses a series of triangle symbols to plot the results narrow-band blue stimulus with a peak transmission of 440
of the comparison. When an individual point has deteriorated nm presented on a 100-cd/m2 yellow background. SWAP
from baseline to one follow-up test at P<0.05, an open white can detect glaucomatous visual field loss before conventional
triangle appears. If that point is confirmed on a second follow- white-on-white (WW) perimetry.
up test, a half-darkened triangle appears. If that point is Frequency Doubling Perimetry (FDP) is a relatively new
confirmed a third time, it is represented by a fully darkened psychophysical test that has good potential in screening for
triangle. When three or more points at the same location early glaucomatous visual damage.19,20 The technique consists
change in that manner on two consecutive tests, GPA reports of presentation of low spatial frequency sinusoidal grating
“possible progression”. When three or more points at the (<1 cyc/deg) undergoing high temporal frequency
same location change in that manner on three consecutive counterphase flicker at or above 15 Hz. This is perceived as
tests, GPA reports “likely progression”. the grating having double the spatial frequency. This
It is also possible to generate a single-page summary phenomenon was initially described as “frequency-doubling
printout. It displays the current field test results and an insert illusion”. The frequency doubling illusion is carried by the
box containing the current GPA, the "possible progression" magnocellular pathway, specifically the My-cell subset of
or "likely progression" message and the dates of baseline ganglion cells.
and previous follow-up tests. Quigley et al have shown that 20 to 35 percent of the
A single-page GPA printout is available which depicts a retinal ganglion cells could be damaged before a visual field
trend-based analysis. It includes the two baseline visual field defect develops on the standard white-on-white perimetry
tests, the current field test and the current GPA plot. It also (WWP).21 There is both histological and psychophysical
includes two additional pieces of information, a visual field evidence that the ganglion cells of the magnocellular pathway
index and its accompanying trend analysis graphic. are affected in early glaucoma. Two separate studies have
The visual field index is an improved metric of visual shown the ability of FDP to detect visual field defects before
field loss. It is a number between 0 and 100 percent with 100 the standard white-on-white field loss.
percent being a perfect visual field. Central points in the field The visual fields are important tools in diagnosis and
are weighted more heavily than those in the periphery. The monitoring progression of glaucoma. However, correlation
points closer to fixation are weighted more heavily because with optic disc changes is always warranted to analyze the
they are the points which warrant preservation. The index wide information available through visual fields and GPA.
calculation also reduces the contribution of cataract to the In a study on definition and classification of glaucoma in
measurement of visual field loss. prevalence studies, characteristics of glaucomatous field
840 Glaucoma
Table 9.2.2.5: Characteristics of glaucomatous field defects 8. Caprioli J. Automated perimetry in glaucoma. Am J Ophthalmol
1991;111(2):235-9.
1. Asymmetrical across the horizontal midline (in early/ 9. Heijl A, Asman P. Pitfalls of automated perimetry in glaucoma
moderate cases)
diagnosis. Curr Opin Ophthalmol 1995;6(2):46-51. Review.
2. Located in the mid-periphery (in early/moderate cases). 10. Thomas R, Paul P, Muliyil J. Use of pattern standard deviation
3. Clustered in neighboring test points. instead of corrected pattern standard deviation in Anderson's
4. Reproducible on at least two occasions. criteria. J Glaucoma 2000;9(6):480-2.
5. Not explained by any other disease. 11. Johnson C, Cioffi G, Liebmann J, Sample P, Zangwill L, Weinreb
6. Considered a valid representation of the subjects R. The relationship between structural and functional alterations
functional status (based on performance indices such as in glaucoma: a review. Semin Ophthalmol 2000;15:221-33.
false positive rate). 12. Naka M, Kanamori A, Tatsumi Y, Fujioka M, Nagai-Kusuhara A,
(Reproduced from The definition and classification of glaucoma Nakamura M, Negi A. Comparison of mean deviation with AGIS
in prevalence surveys, Foster PJ, Buhrmann R, Quigley HA, and CIGTS scores in association with structural parameters in
et al. Br J Ophthalmol 2002;86:238–42; Copyright notice year glaucomatous eyes. J Glaucoma 2009;18(5):379-84.
January 2011 with permission from BMJ Publishing Group Ltd.) 13. Xin D, Greenstein VC, Ritch R, Liebmann JM, De Moraes CG,
Hood DC. A comparison of functional and structural measures
for identifying progression of glaucoma. Invest Ophthalmol Vis
Sci 2010 Sep 16.
defects for the criteria of diagnosis is elucidated in Table 14. Rehman Siddiqui MA, Khairy HA, Azuara-Blanco A. Effect of
9.2.2.5. cataract extraction on SITA perimetry in patients with glaucoma.
J Glaucoma 2007;16(2):205-8.
The authors/editors have no financial interest in any product or procedure 15. Katz J, Gilbert D, Quigley HA, Sommer A. Estimating progression
mentioned in this chapter. of visual field loss in glaucoma. Ophthalmology 1997;104:1017-
25.
REFERENCES 16. Martinez-Bello C, Chauhan BC, Nicolela MT, McCormick TA,
Leblanc RP. Intraocular pressure and progression of glaucomatous
1. Anderson DR, Patella VM. Automated Static Perimetry, 2nd ed. visual field loss. Am J Ophthalmol 2000;129:302-8.
St. Louis: Mosby, 1999. 17. Heijl A, Bengtsson B, Chauhan BC, Lieberman MF, Cunliffe I,
2. Grzybowski A. Harry Moss Traquair (1875-1954), Scottish Hyman L, Leske MC. A comparison of visual field progression
ophthalmologist and perimetrist. Acta Ophthalmol 2009; criteria of 3 major glaucoma trials in early manifest glaucoma trial
87(4):455-9. patients. Ophthalmology 2008;115(9):1557-65.
3. Agarwal HC, Gulati V, Sihota R. Visual field assessment in 18. Johnson CA, Adams AJ, Casson EJ, Brandt JD. Blue-on-yellow
glaucoma: comparative evaluation of manual kinetic Goldmann perimetry can predict the development of glaucomatous field
perimetry and automated static perimetry. Indian J Ophthalmol. loss. Arch Ophthalmol 1993;111:645-50.
2000 Dec;48(4):301-6. 19. Maddess T, Goldberg I, Dobinson J, Wine S, James AC. Clinical
4. Khamar BM. Static perimetry in glaucoma (a comparison with trials of frequency doubled illusion as an indicator of glaucoma.
kinetic perimetry). Indian J Ophthalmol 1982;30(4):383-6. ARVO [Abstracts]. Invest Ophthalmol Vis Sci 1995;36s:335.
5. Morin JD. Changes in the visual fields in glaucoma: static and 20. Chandrasekhar G, Kunjam V, Rao VS, Nutheti R. Humphrey
kinetic perimetry in 2,000 patients. Trans Am Ophthalmol Soc visual field and frequency doubling perimetry in the diagnosis of
1979;77:622-42. early glaucoma. Indian J Ophthalmol 2003;51:35-8.
6. Cohen S, Kawasaki A. Introduction to formal visual field testing: 21. Quigley HA, Addicks EM, Green WR. Optic nerve damage in
Goldmann and Humphrey perimetry. J Ophthalmic Nurs Technol human glaucoma. III. Quantitative correlation of nerve fiber loss
1999;18(1):7-11. and visual field defect in glaucoma, ischemic neuropathy,
7. Stewart WC, Hunt HH. Threshold variation in automated papilloedema and toxic neuropathy. Arch Ophthalmol
perimetry. Surv Ophthalmol 1993;37(5):353-61. Review. 1982;100:135-46.
9.2.3 Optic Disk Imaging

in Glaucoma Suspects
Glaucoma is now recognized as an optic neuropathy which In the past decade, imaging modalities like the Heidelberg
shares a final common pathway of retinal ganglion cell (RGC) Retinal Tomogram (HRT) for the optic nerve head and the
death, retinal nerve fiber layer (RNFL) loss and characteristic Optical Coherence Tomography (OCT) for the RNFL
appearance of the optic nerve head (ONH).1 Since these are thickness measurements have made objective and
common end-points of a variety of glaucoma disorders, the reproducible assessment possible over a long period of time.
morphological appearance of the optic nerve head is usually At the present moment, imaging the optic disk is established
not very different. Clinical examination of the disk has been as a useful adjunct in the armamentarium of glaucoma
the basis of disk and nerve fiber layer evaluation but it is management.
marred by its subjectivity and non-reproducibility, in the
This chapter will diskuss imaging in glaucoma suspects
diagnosis and detection of glaucoma. Though visual field
and how it may help or at times adversely influence clinical
changes give concrete and reproducible evidence of
decision making.
glaucomatous changes, it becomes manifest only after
The broad categories of glaucoma suspects in whom optic
considerable damage has occurred to the retinal ganglion cells
disk imaging may be of use are:
(RGCs) and the nerve fibre layer (NFL). There are normally
a. Disk suspects: Those with suspicious optic disks but who
1.2 to 2.4 million nerve fibers and corresponding number of
are perimetrically normal.
ganglion cells in the retina. Kerrigan-Baumann and Quigley
HRT and OCT would be of immense help for baseline
et al2 documented that a loss of 35.7 percent of the RGCs
documentation and objective follow-up of these patients
was required for the manifestation of corrected pattern
(Fig. 9.2.3.1).
standard deviation (CPSD) <0.5 percent in the visual fields
b. Ocular Hypertension (OHT): Low-risk OHT whom one
and a loss of 5 dB in the sensitivity was associated with 25
would want to keep under observation without treatment
percent loss in the RGCs. Early glaucomatous damage
involves structural loss of the neuro-retinal rim or RNFL, or high risk OHT who need treatment.
which usually precedes functional deficit. This is attributed c. Pre-perimetric glaucoma: Visual fields are normal but
to redundancy of the retinal ganglion cells (RGCs), whereby structural defects on the optic disk or RNFL are present
surrounding areas perceive the presence of the visual field (Fig. 9.2.3.2).
target, and signal it as “seen” on visual field testing even There is always a dilemma about whether to treat patients
though glaucomatous damage has commenced. The stage of with normal visual fields even in the presence of structural
the glaucoma continuum where damage has started, but has defects, given the slow progression of disease and the potential
not manifest on standard automated perimetry (SAP) is called side-effects and quality of life issues with life-long medication.
pre-perimetric glaucoma. In such a scenario, judicious observation using these structural
A glaucoma suspect is a person with one or more risk imaging tools is of immense use.
factors for the development of glaucoma, including raised
intraocular pressure (IOP), or optic disk appearance suspicious ROLE OF IMAGING
for glaucoma but without visual field loss. A great overlap GLAUCOMA SUSPECTS
can exist between findings in people with early glaucoma and All of these instruments have been shown to match the
in those who are glaucoma suspects without the disease. sensitivity and specificity of stereo-disk photography in
Therefore there is a need for a modality to distinguish these predicting known cases of glaucoma.3-5 Several recent studies
subjects from normal individuals to detect the disease as early have analyzed the value of these techniques in glaucoma
as is possible, before the development of visual field loss as suspects. Bowd et al6 found no significant difference between
classically seen on SAP. stereo photography and confocal scanning laser
842 Glaucoma
Fig. 9.2.3.1: Large cup-disk ratio in a patient with large optic disks with normal visual fields and normal IOP. HRT classifies both optic disks as
glaucoma on the linear discriminate analysis, but notice the disc size as 3.36 and 3.59 mm2 respectively. The RNFL thickness measurements on
the OCT are within 95 percent of the inbuilt normative database and are therefore flagged in red
ophthalmoscopy (HRT) in predicting future changes in SAP. abnormalities. In one study using the OCT,8 114 glaucoma
They have recommended the use of HRT, however, due to suspects with normal standard automated perimetry (SAP)
the ease and rapidity of imaging and because photography and OCT, RNFL imaging at baseline were prospectively
required evaluation by trained experts. Kanamori and followed-up. After a 4.2 years average follow-up, 23 eyes
colleagues7 compared CSLO, SLP, and OCT in a population (20%) developed glaucomatous changes. After adjusting for
of ocular hypertensive patients, glaucoma suspects, and early age, IOP, CCT, and PSD in multivariate models, 10 µm thinner
glaucoma patients. They found that none of the instruments average, superior and inferior RNFL were found to be
reliably distinguished ocular hypertension from normal eyes predictive of glaucomatous change. Using the GDx,
while they were equally effective in identifying early glaucoma. Mohammadi et al9 studied 160 suspects of whom 16 eyes
In a study using the HRT,6 glaucoma-suspect eyes were developed glaucoma. Thinner baseline SLP-RNFL measure-
classified as converts or nonconverts based on the ments were independently predictive of visual field loss.
development of repeatable (either two or three consecutive) One pitfall of the newer imaging devices is that though
standard automated perimetry (SAP)-detected abnormalities they can discriminate suspicious optic disks from normals,
over the course of the study (mean follow-up, 4.5 years). they also have a tendency to misdiagnose normal optic disks
HRT classification techniques and stereophotograph as suspicious. In an Indian study using the OCT,10 the Area
assessment could detect optic disk topography abnormalities under receiver operating characteristic curves (AUC) for
in glaucoma-suspect eyes before the development of SAP discriminating between OHT and normal were 0.69 for the
Fig. 9.2.3.2: Eye with optic disc hemorrhage in left eye with normal visual fields. The spectral domain OCT in fact shows thickening of the RNFL
in the region of the disc hemorrhage which will have to be followed up once the hemorrhage absorbs. This is a patient who would require close
follow-up for normal tension glaucoma
inferior RNFL thickness measurements respectively. The The authors/editors have no financial interest in any
sensitivity was 60 and 80 percent specificity, which means product or procedure mentioned in this chapter.
that when 80 percent of normals are correctly diagnosed
normal, or 20 percent erroneously labeled ("produced") OHT, REFERENCES
40 percent of ocular hypertensives are, in fact, left out
undiagnosed. 1. Quigley, et al. Quantitative correlation of NFL and VF defects in
glaucoma. Arch Ophthalmol 1982;135-46.
CONCLUSION 2. Kerrigan-Baumrind LA, Quigley HA, Mary Peace, et al. Number
of ganglion cells in glaucoma eyes compared with threshold visual
There is a fair topographic relationship between structural field tests in the same person. IOVS 2000;41:741-8.
damage and functional loss. However, these diagnostic tools 3. Greaney MJ, Hoffman DC, Garway-Heath DF, et al. Comparison
cannot be used in isolation to formulate a diagnosis. Both of optic nerve imaging methods to distinguish normal eyes from
those with glaucoma. Invest Ophthalmol Vis Sci 2002;43:140-5.
structural and functional aspects should be evaluated in order 4. Wollstein G, Garway-Heath DF, Fontana L, Hitchings RA.
to obtain full characterization of glaucomatous judgement Identifying early glaucomatous changes: comparison between expert
for clinical diagnosis and treatment. These tools may have a clinical assessment of optic disk photographs and confocal scanning
greater role in objective follow-up over a period of time. ophthalmoscopy. Ophthalmology 2000;107:2272-7.
844 Glaucoma
5. Zangwill LM, Bowd C, Berry CC, et al. Discriminating between 8. Lalezary M, Medeiros F, Weinreib R, et al. Baseline optical
normal and glaucomatous eyes using the Heidelberg Retina coherence tomography predicts the development of
Tomograph, GDx Nerve Fiber Analyzer and Optical Coherence glucomatous change in glaucoma suspects. Am J Ophthalmology
Tomograph. Arch Ophthalmol 2001;119:985-93. 2006;142(4):576-82.
6. Bowd C, Zangwill LM, Medeiros FA, et al. Confocal scanning 9. Mohammadi K, Bowd C, Weinreib RN, Medeiros FA, et al.
laser ophthalmoscopy classifiers and stereophotograph evaluation Retinal nerve fiber layer thickness measurements with scanning
for prediction of visual field abnormalities in glaucoma-suspect laser polarimetry predict glaucomatous visual field loss. Am J
eyes. Invest Ophthalmol Vis Sci 2004;45:2255-62. Ophthalmol 2004;138:592-602.
7. Kanamori A, Nagai-Kusuhara A, Escano MF, et al. Comparison 10. Gyatsho J, Kaushik S, Gupta A, Pandav SS, Ram J. Retinal
of confocal scanning laser ophthalmoscopy, scanning laser nerve fiber layer thickness in normal, ocular hypertensive and
polarimetry and optical coherence tomography to discriminate glaucomatous Indian eyes: an Optical Coherence Tomography
ocular hypertension and glaucoma at an early stage. Graefes Arch Study. J Glaucoma 2008;17:122-7.
Clin Exp Ophthalmol 2006;244:58-68.
Chapter 9.3
GLAUCOMA: CLINICAL PROFILE
9.3.1 Clinical Profile of Primary Glaucoma

Glaucoma is now recognized to be an optic neuropathy where Since glaucoma is primarily an optic neuropathy, the
raised intraocular pressure (IOP) is the major risk factor. It is following section will give a detailed description of evaluation
not a single entity, but rather comprises a large group of of the optic nerve head.
diseases resulting in characteristic optic nerve damage with 1. Optic disk evaluation:
corresponding visual field defects. In order to recognize the The preferred method of evaluation is stereoscopic
precise entity, glaucoma can be classified into convenient assessment, which is the key to accurate diagnosis.
clinical groups. Stereoscopic key to accurate diagnosis: The most commonly
Adult glaucomas are broadly grouped into primary and used method is by slit-lamp biomicroscopy using a 90D
secondary glaucoma and open angle and angle closure or 78D lens. Monocular methods are commonly followed,
glaucoma. All entities can be grouped into these categories, but stereoscopic methods are preferable.
i.e. primary open angle glaucoma, primary angle closure
2. Documentation:
glaucoma, glaucoma suspect and secondary open angle or
Stereophotographs are the preferred method of disk
angle closure glaucoma. It is useful from both a diagnostic
documentation.
and management point of view, since the treatment of the
Disk drawing is useful in the absence of stereoscopic
various disease entities differ widely.
Each of these entities has a specific clinical profile, which, disk photographs. The following points must be noted
if recognized, makes the management and subsequent and reviewed at each visit:
investigations and treatment tailored appropriately to the • Demarcation of cup
disease process. The idea of clinical assessment is to determine • Exact position of vessels from disk margin
whether or not glaucoma is present, or likely to develop • Laminar pores
(assessment of risk factors and determination whether the • Disk hemorrhage
patient is a “glaucoma suspect”, which would include those • Peripapillary changes
individuals with optic disks with morphological features 3. Attributes to be looked for:
suggestive of glaucoma but normal visual fields, or an ocular Optic Disk Size
hypertensive, who would have raised intraocular pressures in The optic disk size is important to note. The mean area is
the presence of normal optic disk and visual fields). Once 2.1 to 2.8 mm2. It is estimated on slit-lamp biomicroscopy
glaucoma is confirmed, the next step would be to identify the and the obtained values usually have to be multiplied by a
underlying mechanism of damage to guide the choice of magnification factor which is unique to the lens being
management and identify suitable forms of treatment. used to examine the disk.
846 Glaucoma
• 90.0D – ×1.5 • Neuroretinal Rim (NRR)

• 78D – ×1.3 – Pink
• 60D – ×1 – Surrounds central depression (cup)
In case of monocular examination, the 5° aperture of – Normal NRR thickness varies topographically
direct ophthalmoscope, 1.7 mm2 is used. i. Inferior is thickest, followed by Superior, Nasal,
There is racial variation in the size of the optic disk, with and Temporal rims. (ISNT rule)
whites having smaller disks than blacks, and Asians coming • Cup
somewhere between. There is little variation in the disk size – Shape: slightly horizontally oval
within a refractive error of ±5.0D. – C/D ratio: mean is 0.3 to 0.4
It is good practice to remember to look for eight – Disparity of 0.2 over time or between two eyes should
intrapapillary and four peripapillary features. be viewed with suspicion.
• Intrapapillary features • Retinal Nerve Fiber Layer (RNFL)
– two aspects of optic disk – No defects are seen (which appear as dark areas
i. Size commonly superotemporal or inferotemoral to the
ii. Shape disk). It is best viewed by red-free light (Fig. 9.3.1.2).
– two aspects of neuroretinal rim (NRR) While looking for glaucomatous abnormalities, it is
i. Size important to look for alterations in size, configuration, and
ii. Shape color of the neuroretinal rim, peripapillary atrophic changes,
– three aspects of cup alterations in RNFL patterns or any disk hemorrhage (Fig.
i. Size 9.3.1.3). These appear as small flame shaped hemorrhages
ii. Shape on the optic nerve head which cross the disk margin and
iii. C/D Ratio spontaneously resolve.
– Position of central retinal vascular trunk Other important features to look for include circumlinear
• Peripapillary changes vessel baring (which means that the vessels outlining the cup
– Optic disk hemorrhage becomes bared as the cup enlarges), overpass cupping (cup
– RNFL assessment extends below the vessel leaving the vessel suspended),
– Arteriolar diameter bayoneting (when vessels crossing the rim disappear into the
– Parapapillary choroidal atrophy deep cup).
The normal optic disk (Fig. 9.3.1.1) can be described as 4. Evidence of visual field damage characterized by:
follows: a. Visual field damage consistent with retinal nerve fiber
• Shape layer damage (nasal step, arcuate field defect, or
– Slightly vertically oval paracentral depression in clusters of test sites)1
• Size b. Visual field loss in the upper hemifield that is different
– 1.5 to 1.8 mm vertically compared with the lower hemifield, i.e. across the
– Larger in myopic eyes horizontal midline (in early/moderate cases)
Fig. 9.3.1.1: Normal optic nerve head

Glaucoma: Clinical Profile 847
Fig. 9.3.1.2: RNFL defects seen on red-free light Fig. 9.3.1.3: Optic disk hemorrhage
Fig. 9.3.1.4: Gonioscopic appearance of an open angle
c. Reproducible 3. Evidence of optic nerve damage as characterized by:

d. Absence of other known explanations of the visual a. Diffuse thinning, focal narrowing, or notching of the
field defect optic disk rim, especially at the inferior or superior
Presented below is an overview of the following broad poles.
groups of primary glaucoma entities: b. Documented progression of cupping of the optic disk.
1. Primary open angle glaucoma and suspect. c. Diffuse or localized abnormalities of the peripapillary
2. Primary angle closure glaucoma and suspect. retinal nerve fiber layer, especially at the inferior or
superior poles.
CLINICAL PROFILES d. Disk rim or peripapillary retinal nerve fiber layer
hemorrhages.
Primary Open Angle Glaucoma e. Optic disk neural rim asymmetry of the two eyes
The broad clinical profile of primary open angle glaucoma consistent with loss of neural tissue.
4. Reproducible visual field defects corresponding to optic
(POAG) is as follows:2
disk damage.
1. Adult patient.
2. Open anterior chamber angles on gonioscopy (Fig. The IOP does not figure in the definition of POAG, even
9.3.1.4). though several population based studies have demonstrated
848 Glaucoma
that the prevalence3-10 and incidence of POAG,11-13 increases Primary Angle Closure (PAC)
as the IOP increases. In spite of this relationship between
elevated IOP and glaucomatous optic neuropathy, there are • Occludable angle with signs of angle closure such as iris
atrophy, whorls, PAS or raised IOP, but normal disk and
variations in the susceptibility of the optic nerve to IOP-
fields
related damage. Population based studies indicate that only
• Patients with PAC can present with either acute or chronic
one-tenth or less of patients with elevated IOP have
symptoms and signs or they may have both and present
glaucomatous field loss.4 Data from longitudinal studies suggest
with acute attacks superimposed on chronic angle closure.
that nearly ten percent of untreated ocular hypertensives In PAC the eye is at risk of developing glaucomatous
with IOP consistently 24 mm Hg or above develop glaucoma optic disk damage, particularly when associated with
in five years.14 Conversely, depending on the population elevated IOP
studied, from 3.6 to 61 percent of patients with glaucomatous • The fellow eye is at risk of angle closure also.30
disk and field changes were found to have IOP of 21 mm
Hg or lower.3,4,15 Primary Angle Closure Glaucoma (PACG)
Primary Open Angle Glaucoma Suspect • Occludable angle with signs of angle closure such as
iris atrophy, whorls, peripheral anterior synechiae (PAS)
The clinical findings that define a glaucoma suspect are:16-28
or raised IOP, and glaucomatous optic neuropathy with
1. Open anterior chamber angles by gonioscopy.
corresponding visual field changes comprise PACG.
2. Appearance of the optic disk or retinal nerve fiber layer
that is suspicious for glaucomatous damage. A brief discussion of the clinical entities described above follows:
3. A visual field suspicious for glaucomatous damage.
4. Consistently elevated intraocular pressure (IOP) associated Primary Open Angle Glaucoma
with normal appearance of the optic disk and retinal nerve
Primary open angle glaucoma (POAG) is defined as a chronic
fiber layer and with normal visual field test results (Ocular progressive optic neuropathy with characteristic morphological
Hypertension). changes in the optic nerve head and retinal nerve fiber layer,
in the absence of underlying ocular disease or congenital
Primary Angle Closure anomalies. Corresponding visual field losses are associated
Angle closure disease is now classified29 on the basis of the with these changes.1
amount of closure, the effect of that closure in the eye in The relative risk of POAG increases in proportion to the
terms of IOP and other iris signs, and the effect of that IOP intraocular pressure (IOP); however, there is no “cut-off ”
in producing optic nerve and visual field damage. The key is limit of IOP for the onset of the condition. Non-IOP
dependent factors such as vascular factors or disorders of
to recognize an occludable angle clinically. An occludable angle
optic disk perfusion are presumed to play a more important
is defined as that where the posterior pigmented trabecular
role when there is glaucomatous optic neuropathy with IOP
meshwork is visible in less than 90° of the circumference,
at lower levels. To reflect this, POAG is arbitrarily also divided
by gonioscopy.
into high pressure variety where it is conventionally called
Primary Angle Closure Suspect (PACS) POAG, and a low pressure variety, when it is conventionally
called normal tension glaucoma (NTG) though they may just
• Occludable angle with no signs of angle closure such as be part of a spectrum of optic neuropathies which are variably
iris atrophy, whorls, PAS or raised IOP, and normal optic sensitive to the IOP. Adding to the complexity is the issue of
disk and visual fields age. Though POAG is classically known to occur after 35
• Any eye that has a primary, abnormally narrow angular years1 or is of adult onset,2 an identical disease process may
width of the anterior chamber angle recess, wherein the be encountered in younger individuals. Those developing
peripheral iris is located close to, yet not touching the "POAG" type of disease in less than 35 years of age with no
posterior pigmented trabecular meshwork, is at risk of underlying cause or ocular abnormality are classified as having
angle closure. juvenile open angle glaucoma (JOAG).
Normal Tension Glaucoma and The Role of Vasospasm in NTG

Ocular Hypertension—Parts of
Optic nerve blood vessel diameter may be affected by
a Disease Spectrum
vasospasm and the association between vasospastic disorders
Primary open angle glaucoma is now recognized to be a and NTG may give some clues to the mechanisms of damage.
spectrum rather than a single disease entity ranging from Convincing associations have so far been drawn with
ocular hypertension at one end to normal tension glaucoma migrainous headache and Raynaud's phenomenon.23,24 Drance
(NTG) at the other. An ocular hypertensive would have et al25 found decreased finger capillary flow in NTG patients
intraocular pressures, which are higher than the statistical suggesting vasospasm as an underlying etiological factor.
"normal" range, usually taken as 21 mm Hg, but with normal Another study26 using color Doppler imaging found increased
optic disk appearance and normal visual fields. On the other resistance in the ophthalmic and central retinal artery in NTG
hand, normal tension glaucoma is defined as a condition with patients compared with controls. It has been postulated that
a clinical profile identical to primary open angle glaucoma this vasospasm may be reversible with calcium channel
with the important exception that the IOP never rises higher blockers, which leads to relaxation of the vessel walls. Netland
than 21 mm Hg at any time of the day. Usually, a diurnal et al27 retrospectively looked at NTG and HTG patients
variation of IOP is warranted in NTG to be sure that one who were on calcium channel blockers for medical reasons
has not missed out any IOP spikes which may occur during and found in the NTG group, that patients on these drugs
odd hours of the day. were less likely to progress.
Normal Tension Glaucoma Effect of Systemic Diseases
Although 21 mm Hg is considered the upper limit of statistically
There has been some investigations on the association of
normal IOP, at least one-sixth of patients with POAG have POAG with systemic diseases.
IOP levels below 21 mm Hg, which is considered statistically
normal in the 95th percentile range.2,9-11 Moreover, some whose Diabetes Mellitus (DM)
IOP levels are statistically abnormal (>21 mm Hg) have no
evidence of ON damage or loss of vision function, a condition There are inconsistent conclusions regarding the role of DM
known as ocular hypertension (OH). POAG in which the IOP in glaucoma. Some population based surveys indicated that
is typically below a certain level, typically 21 mm Hg, is known the risk is twice in diabetics, but others contradict this. The
as low tension or normal tension glaucoma (NTG). problem is that IOP is a common confounder between DM
The Collaborative Normal Tension Glaucoma Study clearly and glaucoma. Diabetics have slightly higher IOP and a higher
demonstrated that reducing the IOP by at least 30 percent, by prevalence of OHT and elevated IOP. In the Blue Mountains
whatever means, results in a slower rate of VF loss, a finding eye study,16 glaucoma prevalence and OHT were more
that was reconfirmed after follow-up periods of five and ten common in people with diabetes. Other prospective studies
years. Almost 60 percent of patients with NTG can maintain a of glaucoma management17,18 reported a greater likelihood
30 percent reduction in IOP with topical medication or ALT of progression in patients with diabetes. Interestingly, the
treatment or both. Nevertheless, even after lowering IOP by ocular hypertensive treatment study19,20 showed a protective
30 percent, the disease continued to progress in 12 percent of effect of DM, which could not be explained.
eyes with NTG. The study of normal tension glaucoma also
found that NTG is either slow or nonprogressive in nature. Systemic Blood Pressure (BP)
About 65 percent of untreated eyes showed no progression
of the disease over four years, and about one-half showed no Like DM, the effect of BP is also conflicting. There is
change over five to seven years. In those eyes that did have association between factors such as concurrent cardiovascular
progressive disease, the changes occurred slowly, and there disease and systemic hypertension.21 Some studies report
was a great variation in the rate of deterioration.22 higher BP while others report lower BP is related to POAG.
Some optic nerve head features believed to be more The prevalence of glaucoma appears to be lowest in the
common in NTG include localized rim notch early in the mid-range.
course of disease, splinter hemorrhage on disk margin, flat Rather than just considering systolic and diastolic BP, a
disk excavation, deep cupping, unusual, peripapillary choroidal more meaningful measurement in patients with glaucoma is
atrophy and narrowing of retinal arterioles. the diastolic perfusion pressure. This is calculated as the
850 Glaucoma
difference between diastolic arterial pressure (brachial sitting • Glaucoma suspect with moderate risk of visual loss
pressure) and IOP. It is considered significant if <55 mm Hg. – Glaucoma—like disk without detectable VF loss
Nocturnal arterial hypotension has been shown to be – Fellow eye of that with established primary
related to NTG. glaucomatous optic neuropathy
– OHT with suspicious disk
Migraine • Glaucoma suspect with low risk of visual loss
– OHT
The Collaborative Normal Tension Glaucoma Study
– Older age
(CNGTS)22 demonstrated that a history of migraine increased
– Occludable angles
the risk of progression of glaucoma by 2.6 times. Vasospasm
– Pigment Dispersion Syndrome (PDS); Pseudoexfoliation
was thought to play a central role in this phenomenon.
syndrome (PXFS)
– Asymmetric disk (>0.2 between 2 eyes)
Juvenile Open Angle Glaucoma
– Family history
This is considered an early onset variety of POAG. The typical – Glaucoma genes
patient profile would be as follows:1
• Onset 10 to 35 years of life1 Primary Angle Closure
• Family history may be present
Primary angle closure is appositional (Fig. 9.3.1.5) or synechia
• Peak IOP >21 mm Hg
(Fig. 9.3.1.6)l closure of the anterior-chamber angle caused
• Open angles on gonioscopy with multiple iris processes
by pupillary block, where the anterior lens surface is anterior
may be seen
to the plane of the iris insertion into the ciliary body.28 This
• Optic nerve head typically shows diffuse damage to the
causes resistance to aqueous humor flow to reach the pupil
optic rim, but any type of glaucomatous optic neuropathy and the resultant pressure gradient between the posterior and
described above is possible anterior chambers causes a forward bowing of the peripheral
• Visual field defects corresponding to optic disk damage
as listed above.
Glaucoma Suspect
A glaucoma suspect is an individual with clinical findings and
risk factors that indicate an increased likelihood of developing
POAG.2 This definition excludes known secondary causes
for potential open angle glaucoma, such as long-term steroid
use, pseudoexfoliation, pigment dispersion and traumatic angle
recession.
Raised IOP, older age, family history of glaucoma and
thinner central corneas have been implicated as important
risk factors in the development of glaucomatous optic nerve
Fig. 9.3.1.5: Appositional closure showing angle
damage, and glaucoma suspects with these additional features opening on indentation
warrant closer follow-up.
Owing to the higher prevalence of angle closure among
Asian populations, the Asia Pacific guidelines23 incorporate
features of angle closure disease into their definition. In these
guidelines, glaucoma suspects are classified into high, moderate
and low risk categories, as follows:
• Glaucoma suspect with high risk of visual loss
– Ocular Hypertension (OHT); IOP >30 mm Hg;
suspicious disk, normal fields
– Primary angle closure (PAC) with high IOP and
peripheral anterior synechiae (PAS) Fig. 9.3.1.6: Synechial angle
iris resulting in obstruction to all or part of the filtering conditions that are often difficult to distinguish from the PAC
portion of the trabecular meshwork (appositional angle entities resulting from pupillary block. It is important to
closure).29-31 This can lead to elevation of intraocular pressure recognize this condition because angle closure may persist
(IOP). Prolonged or repeated contact of the peripheral iris inspite of laser iridotomy, and there may be PAS progression
with the trabecular meshwork may lead to peripheral anterior after laser iridotomy. It may be responsible for angle closure
synechiae (PAS) and residual functional damage to the in myopes and younger patients.
trabecular meshwork. The angle closure may or may not be Plateau iris configuration: Unlike pupillary block, plateau iris
associated with elevated IOP or glaucomatous optic configuration (Fig. 9.3.1.7) results from a pre-existing
neuropathy, and may occur in either an acute or chronic anatomical situation. A large or anteriorly positioned ciliary
form. process holds up peripheral iris, and the increase in thickness
at the peripheral iris can completely occlude the iridocorneal
CLINICAL CHARACTERISTICS angle. It is characterized by a near-normal-depth central
Primary angle closure is generally bilateral, although patients anterior chamber, a flat iris profile, and crowding of the
often present with only one eye affected. Primary angle closure anterior-chamber angle by the iris base. The IOP may be
is now recognized as a continuous spectrum rather than a normal or elevated.
single disease entity. Plateau iris syndrome: This is defined as having a plateau iris
Despite this broad classification32 other terminology configuration with a closed anterior chamber angle and usually
pertaining to angle closure disease is still in use in clinical with elevated IOP, which persists despite the elimination of any
glaucoma management and must be clarified. pupillary block component by a patent iridotomy. Intraocular
Acute primary angle closure: If the entire circumference of the pressure elevation that is present before iridotomy may persist;
chamber angle is obstructed suddenly, the IOP rises rapidly the IOP typically increases after pupil dilation, which causes
to high levels.33 This may cause pressure-induced corneal greater occlusion of the angle by the peripheral iris.
edema (experienced as blurred vision and occasionally as Mixed glaucoma: This is not strictly a separate entity but a
multicolored halos around lights), vascular congestion, eye chance coexistence of open angle and angle closure glaucoma.35
pain, or headache. High IOP may be accompanied by nausea This diagnosis is made not uncommonly, especially when the
and vomiting. Acute attacks may be self limited and resolve differential diagnosis between open-angle and angle-closure
spontaneously or may occur repeatedly. Untreated, this entity glaucoma is uncertain. Clinically, the degree of IOP rise and
may cause permanent vision loss or blindness. consequent optic neuropathy is usually unexplained by the
Chronic primary angle closure: If only a portion of the angle degree of synechial closure present. The diagnosis of mixed
closes with PAS, either slowly over time with or without acute glaucoma is also complicated by the possibility that repeated
attacks, or rapidly after a resolved acute attack of angle episodes of angle closure may cause damage to the trabecular
closure, the IOP may be in the normal range or may be only
mildly elevated, and symptoms of acute PAC may be mild or
absent. Continued, slowly progressive closure of the angle
may ensue, eventually leading to sustained elevation of IOP
and glaucoma.
Creeping angle closure glaucoma: In some eyes with shallow anterior
chambers and narrow angles, an insidious and usually
symptomless angle-closure occurs until the unsuspecting
patient becomes aware of reduced vision.34 The root of the
iris slowly "creeps," or is pushed, into the depths of the narrow
angle until it gradually obstructs the outflow channels. Creeping
angle-closure glaucoma is therefore one cause of primary
chronic angle-closure glaucoma.
Plateau iris configuration and plateau iris syndrome: The definitions Fig. 9.3.1.7: Plateau iris configuration viewed on ultrasound
of these entities are included here because they are primary biomicroscopy as anterior rotation of ciliary processes
852 Glaucoma
meshwork, which is not gonioscopically visible. Such damage now increasing recognition that there may be likelihood of
would reduce the outflow facility and introduce an element glaucoma worsening among those with larger IOP swings
of apparent open-angle glaucoma. The appropriate treatment within defined time periods. The description short-term IOP
is peripheral iridectomy followed if necessary by the use of fluctuation reflects the IOP peak minus the IOP trough in a
the full range of antiglaucoma drugs and, occasionally, by a stated time period, generally understood to be 24 hours or
filtering procedure. less.37,38 When evaluating IOP fluctuation over a period of
time greater than 24 hours, the term long-term IOP
Relevance of Central Corneal Thickness fluctuation represents the IOP peak minus the IOP trough
(CCT) in IOP Measurement from visit to visit.35
In normal individuals, IOP fluctuates 2 to 6 mm Hg
The CCT is preferably measured by an ultrasonic pachymeter.
over a 24-hour time period.38,39 An IOP fluctuation of more
IOP is over estimated in thicker corneas and underestimated
in thinner ones. A thin central cornea (e.g. 490 µm) may explain than 10 mm Hg in a 24-hour time period suggests glaucoma.40
loss of visual field in an eye despite normal applanation To understand the extent of IOP change over a 24-hour
measurements of IOP, because the measurements do not time period, pressures need to be measured at various times
reflect a higher true IOP. Conversely, a thick central cornea during the day and night.38 Assessment of IOP fluctuation
(e.g. 610 μm) may explain high measured IOP associated becomes more significant given the fact that despite good
with a longstanding normal visual field and optic disk due to control, many patients continue to worsen.41 Mean IOPs of
a lower true IOP. those who progress to blindness do not differ from those
However, the relationship between CCT and IOP has who do not. Instead, what differs is the severity of glaucoma
not been precisely specified, and may or may not be linear. In at the time of diagnosis and the range of IOPs found during
1975, Ehlers31 reported a manometric study on 29 eyes follow-up (long-term IOP fluctuation).42
compared to Perkin's tonometry. Applanation tonometry Traditionally, IOP was believed to be highest in the
agreed with manometric readings only at a CCT of 520 morning, but recent research has indicated that the IOP may
microns. He noted the relation of central corneal thickness peak in the afternoon or evening or have no reproducible
to IOP in glaucomatous eyes to be as much as 7 mm Hg per pattern.43 It is now recognized that IOPs may tend to peak
100 microns. A more recent meta-analysis36 of 133 data sets during the night time sleep period—rather than during the
estimated the mean relationship to be 3.4 ± 0.9 mm Hg for morning hours as previously believed.39 Since many patients
every ten percent change in CCT. have both high IOPs and low systemic BPs at night, low
It is to be remembered that it is not the CCT alone perfusion pressures at night that might be deleterious to the
which would affect the IOP measurement. Corneal rigidity optic nerve Any treatment that can lower IOP maximally
plays an important role. In clinical situations, corneal edema, and not negatively influence systemic BP would have a
with excessive hydration of the stroma, would give rise to beneficial effect on perfusion pressure and might be more
falsely low IOP reading, even though the central corneal protective of the optic nerve.44
thickness would be increased. This is simply because it would
be easier to applanate the softer edematous cornea, and Investigations for Glaucoma
consequently the end point would be reached earlier than
usual. Similarly, a central corneal scar would result in a thinner Patients being investigated for glaucoma should have the
cornea in the region of the scar tissue, but the greater tissue following tests2 at baseline and follow-up visits which are
rigidity would give rise to falsely high IOP measurement. spaced according to the severity of the disease. All patients
should undergo a comprehensive ophthalmic examination
Diurnal Variation of IOP including slit-lamp biomicroscopy, tonometry, gonioscopy and
stereoscopic optic disk evaluation.
In routine clinical practice, single IOP measurements at the
The following tests should be included in roughly this
time of an office visit often provide the only information
order as a basic examination for glaucoma:
used to determine treatment decisions. Current literature
suggests that a random IOP measurement is a poor surrogate Pupil: The pupils should be examined for reactivity and an
for IOP levels throughout the day and across visits. There is afferent pupillary defect.45
Intraocular Pressure: Intraocular pressure should be measured 3. Dielemans I, Vingerling JR, Wolfs RC, et al. The prevalence of
in each eye, preferably using a Goldmann tonometer before primary open-angle glaucoma in a population-based study in The
Netherlands. The Rotterdam Study. Ophthalmology
gonioscopy or dilation of the pupil.46 Time of day should be
1994;101:1851-5.
recorded because of diurnal variation. In cases of suspicious 4. Sommer A, Tielsch JM, Katz J, et al. Relationship between
disks with normal office IOP recordings, a diurnal variation intraocular pressure and primary open angle glaucoma among white
test is useful. and black Americans. The Baltimore Eye Survey. Arch Ophthalmol
1991;109:1090-5.
Pachymetry: Measurement of central corneal thickness aids 5. Mitchell P, Smith W, Attebo K, Healey PR. Prevalence of open-
the interpretation of IOP measurement results and angle glaucoma in Australia. The Blue Mountains Eye Study.
stratification of patient risk as discussed above. Measurement Ophthalmology 1996;103:1661-9.
should preferably be done before gonioscopy. 6. Leske MC, Connell AM, Schachat AP, Hyman L. The Barbados
Eye Study. Prevalence of open angle glaucoma. Arch Ophthalmol
Gonioscopy: Every patient of glaucoma or suspected glaucoma 1994;112:821-9.
requires careful evaluation of the anterior-chamber angle to 7. Quigley HA, West SK, Rodriguez J, et al. The prevalence of
glaucoma in a population-based study of Hispanic subjects:
look for angle closure or secondary causes of IOP elevation
Proyecto VER. Arch Ophthalmol 2001;119:1819-26.
such as angle recession, pigment dispersion, peripheral 8. Leibowitz HM, Krueger DE, Maunder LR, et al. The Framingham
anterior synechiae, angle neovascularization, and trabecular Eye Study monograph: an ophthalmological and epidemiological
precipitates. study of cataract, glaucoma, diabetic retinopathy, macular
degeneration, and visual acuity in a general population of 2631
Optic nerve head and retinal nerve fiber layer: Careful examination adults, 1973-1975. Surv Ophthalmol 1980;24:335-610.
of the optic nerve head and retinal nerve fiber layer preferably 9. Klein BE, Klein R, Sponsel WE, et al. Prevalence of glaucoma.
by stereoscopic evaluation keeping in mind the features The Beaver Dam Eye Study. Ophthalmology 1992;99:1499-504.
10. Weih LM, Nanjan M, McCarty CA, Taylor HR. Prevalence and
detailed above is an imperative part of the examination. predictors of open-angle glaucoma: results from the visual
Glaucomatous changes detected by means of optic disk and impairment project. Ophthalmology 2001;108:1966-72.
retinal nerve fiber layer analysis may precede changes detected 11. Leske MC, Connell AM, Wu SY, et al. Incidence of open-angle
by standard automated perimetry. 47 It is important to glaucoma: the Barbados Eye Studies. The Barbados Eye Studies
Group. Arch Ophthalmol 2001;119:89-95.
document clinical features of the optic disk. Color 12. Mukesh BN, McCarty CA, Rait JL, Taylor HR. Five-year incidence
stereophotography or computer-based image analysis of the of open-angle glaucoma: the visual impairment project.
optic nerve head and retinal nerve fiber layer are the best Ophthalmology 2002;109:1047-51.
currently available methods of documenting optic disk 13. Le A, Mukesh BN, McCarty CA, Taylor HR. Risk factors associated
with the incidence of open-angle glaucoma: the visual impairment
morpholog y. In the absence of these technologies,
project. Invest Ophthalmol Vis Sci 2003;44:3783-9.
nonstereoscopic photograph or at least a detailed drawing of 14. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular
the optic nerve head should be recorded. Hypertension Treatment Study: a randomized trial determines
that topical ocular hypotensive medication delays or prevents the
Visual field evaluation: The preferred technique for evaluating onset of primary open-angle glaucoma. Arch Ophthalmol
the visual field is automated static threshold perimetry using 2002;120:701-13; discussion 829-30.
white-on-white standard automated perimetry such as the 15. Varma R, Ying-Lai M, Francis BA, et al. Prevalence of open-
Humphrey’s automated filed analyzer. A repeat, confirmatory angle glaucoma and ocular hypertension in Latinos: the Los Angeles
Latino Eye Study. Ophthalmology 2004;111:1439-48.
examination for field test results that are unreliable or show a
16. Mitchell P, Smith W, Chey T, Healey PR. Open-angle glaucoma
possible glaucomatous defect should be considered. It is and diabetes: the Blue Mountains eye study, Australia.
important to use a consistent examination strategy when visual Ophthalmology 1997;104:712-8.
field testing is repeated. 17. Leske MC, Heijl A, Hussein M, et al. Factors for glaucoma
progression and the effect of treatment: the Early Manifest
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18. The Advanced Glaucoma Intervention Study (AGIS): 12. Baseline
1. Terminology and Guidelines for Glaucoma. 3rd Edition. European risk factors for sustained loss of visual field and visual acuity in
Glaucoma Society. Eds, Savona; European Glaucoma Society, patients with advanced glaucoma. Am J Ophthalmol 2002;
2008;95. 134:499-512.
2. American Academy of Ophthalmology. Primary open angle 19. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular
glaucoma. Preferred Practice Pattern. San Francisco: American Hypertension Treatment Study: a randomized trial determines
Academy of Ophthalmology, 2007. that topical ocular hypotensive medication delays or prevents the
854 Glaucoma
onset of primary open-angle glaucoma. Arch Ophthalmol 2002; 34. Lowe RF. Primary creeping angle closure glaucoma. Br J
120:701-13; discussion 829-30. Ophthalmol 1964;48:544-9.
20. Gordon MO, Beiser JA, Brandt JD, et al. The Ocular Hypertension 35. Hyams SW, Keroub C, Pokotilo Mixed glaucoma. Br J Ophthalmol.
Treatment Study: baseline factors that predict the onset of primary 1977;61(2):105-6.
open-angle glaucoma. Arch Ophthalmol 2002;120:714-720; 36. Ehlers N, Bramsen T, Sperling S. Applanation tonometry and central
discussion 829-830. corneal thickness. Acta Ophthalmol (Copenh) 1975;53:34-43.
21. Tielsch JM, Katz J, Sommer A, et al. Family history and risk of 37. Doughty MJ, Zaman ML. Human corneal thickness and its impact
primary open angle glaucoma. The Baltimore Eye Survey. Arch on intraocular pressure measures: a review and meta-analysis
Ophthalmol 1994;112:69-73. approach. Surv Ophthalmol 44:367-408,2000.
22. Collaborative Normal-Tension Glaucoma Study Group. 38. Barkana Y, Anis S, Liebmann J, et al. Clinical utility of intraocular
Comparison of glaucomatous progression between untreated pressure monitoring outside of normal office hours in patients
patients with normal-tension glaucoma and patients with with glaucoma. Arch Ophthalmol 2006;124(6):793-7.
therapeutically reduced intraocular pressures. Am J Ophthalmol 39. Bengtsson B, Heijl A. Diurnal IOP fluctuation: not an independent
1998;126:487-97. risk factor for glaucomatous visual field loss in high-risk ocular
23. Corbett JJ, Phelps CD, Eslinger P, et al. The neurologic evaluation hypertension. Graefes Arch Clin Exp Ophthalmol 2005;243(6):
of patients with low-tension glaucoma. Invest Ophthalmol Vis
513-8.
Sci 1985;26:1101-4.
40. Asrani S, Zeimer R, Wilensky J, et al. Large diurnal fluctuations in
24. Phelps CD, Corbett JJ. Migraine and low-tension glaucoma. A
intraocular pressure are an Independent risk factor in patients
case-control study. Invest Ophthalmol Vis Sci 1985;26:1105-8.
with glaucoma. J Glaucoma. 2000;9(2):134-42.
25. Drance SM, Douglas GR, Wijsman K, et al. Response of blood
41. Drance SM. Diurnal variation of intraocular pressure in treated
flow to warm and cold in normal and low-tension glaucoma
glaucoma. Significance in patients with chronic simple glaucoma.
patients. Am J Ophthalmol 1988;105:35-9.
26. Butt Z, McKillop G, O'Brien C, et al. Measurement of ocular Arch Ophthalmol 1963;70:302-11.
blood flow velocity using colour Doppler imaging in low tension 42. Hattenhauer MG, Johnson DH, Ing HH, et al. The probability of
glaucoma. Eye 1995;9:29-33. blindness from open-angle glaucoma. Ophthalmology 1998;105:
27. Netland PA, Chaturvedi N, Dreyer EB. Calcium channel blockers 2099-104.
in the management of low-tension and open-angle glaucoma. Am 43. American Academy of Ophthalmology. Basic and Clinical Science
J Ophthalmol 1993;115:608-13. Course. San Francisco, CA, American Academy of Ophthalmology,
28. SEAGIG. Asia Pacific Glaucoma Guidelines. 2nd Edition. Sydney: 2006
SEAGIG, 2008;17-8. 44. Wax MB, Camras CB, Fiscella RG, Girkin C, Singh K, Weinreib RN.
29. Anderson DR, Jin JC, Wright MM. The physiologic characteristics Emerging Perspectives in Glaucoma: Optimizing 24-hour Control
of relative pupillary block. Am J Ophthalmol 1991;111:344-50. of Intraocular Pressure Am J Ophthalmol 2002;133:S1-10.
30. Tiedeman JS. A physical analysis of the factors that determine the 45. Kohn AN, Moss AP, Podos SM. Relative afferent pupillary defects
contour of the iris. Am J Ophthalmol 1991;111:338-43. in glaucoma without characteristic field loss. Arch Ophthalmol
31. Jin JC, Anderson DR. The effect of iridotomy on iris contour. Am 1979;97:294-6.
J Ophthalmol 1990;110:260-3. 46. Whitacre MM, Stein R. Sources of error with use of Goldmann-
32. Foster PJ, et al. The definition and classification of glaucoma in type tonometers. Surv Ophthalmol 1993;38:1-30.
prevalence surveys. Br J Ophthalmol 2002;86:238-42. 47. Sommer A, Katz J, Quigley HA, et al. Clinically detectable nerve
33. Lowe RF. Acute angle-closure glaucoma. The second eye: an fiber atrophy precedes the onset of glaucomatous field loss. Arch
analysis of 200 cases. Br J Ophthalmol 1962;46:641-50. Ophthalmol 1991;109:77-83.
9.3.2 Primary Angle Closure Glaucoma

Ramanjit Sihota
Primary angle closure glaucoma (PACG) results when an The term primary angle closure glaucoma includes a
anatomic configuration of the eye results in the iris becoming multiplicity of presentations, acute and chronic, leading to a
opposed/adherent to the trabecular meshwork, preventing transitory or permanent obstruction of the intracameral face
aqueous outflow and producing a rise in intraocular pressure. of the trabecular meshwork.
There is a significantly high incidence of primary angle • PAC—An eye with an occludable drainage angle and
closure glaucoma (PACG) in India, which forms almost half features indicating that trabecular obstruction by the
of all adult primary glaucomas seen in a hospital setting.1,2 peripheral iris has occurred, such as PAS, elevated IOP,
Population based surveys have also highlighted the higher iris whirling, 'glaucomflecken' lens opacities or excessive
prevalence of PACG in India3-9 (Table 9.3.2.1). pigment deposition on the trabecular surface. The optic
disc does not have glaucomatous damage.
DEFINITIONS • PACG—PAC together with evidence of glaucoma.
Clinical Classification by pathomechanisms causing iridocorneal apposition:

• Block at the level of the iris—Relative pupillary block
Traditional • Block at the ciliary body—Plateau iris
• Subacute or intermittent primary angle closure (PAC) is • Block by the lens.
intermittent, self limited, pressure elevations accompanied Each may have a component at the preceding levels.
by prodromal symptoms of headache, haloes, and blurred (Elaborated in detail in chapter 9.1)
vision, but with normal tension in the inter paroxysmal
period, in patients with an occludable angle Pathogenesis
• Acute PACG: Such eyes have pressure induced corneal There are anatomic features that predispose an eye to PACG,
edema (experienced as blurred vision and multicolored e.g.:11-17
halos around lights), vascular congestion and pain. This • AC depth—Shallow
may be accompanied by nausea and vomiting. Patients
• Axial length of the eye—Shorter
also have congestion of the eye, corneal edema, a vertically
• Lens—Increased thickness and anterior positioning
mid-dilated pupil, and very high IOPs.
• Iris—Thicker and more anteriorly inserted
• Chronic PACG: Patients with occludable angles have
• Cornea—Smaller diameter and radius of curvature.
peripheral anterior synechiae of more than 180 degrees
The inheritance of PAC appears to be polygenic, and
and a chronically elevated intraocular pressure. Repeated
with the frequency of occludable angles is 3.5 to 6 times
subacute attacks or an acute attack not treated early
higher in first degree relatives.
enough may result in the formation of peripheral anterior
Eyes with such features need a physiologic stimulus to
synechiae and a raised IOP. Some patients have no
develop angle closure.
symptoms, and have been termed “creeping PACG”, while
1. Relative pupillary block: Small anterior segments are more
others may be symptomatic.
crowded, and predisposed to a larger area of iris lens
Classification for Surveys contact.18,19 This hampers the easy movement of aqueous
from the posterior to the anterior chamber. The
(International Society of Geographical & Epidemiological sequestered aqueous then pushes the iris forward,
Ophthalmology, ISGEO):10 ballooning it anteriorly towards the peripheral cornea and
• Primary angle closure suspect (PACS)—An eye in which the trabecular surface. This is called a 'relative pupillary
appositional contact between the peripheral iris and
block' and can lead to peripheral iridocorneal apposition
posterior trabecular meshwork is considered possible.
or synechiae. Thickening and anterior displacement of
Table 9.3.2.1: Prevalence of primary angle closure
the lens associated with aging may further compromise
glaucoma around the world an already narrow angle, leading to an angle closure attack.
Race/Location Prevalence of angle closure 2. Uveal changes: Such as congestion during a Valsalva
glaucoma in older age population maneuver,20 or ciliary effusions are also being considered
(generally over age 40) in the pathogenesis of PACG.
White populations 0.1–0.6% Common lifestyle disturbances that allow the anatomic and
(Europe, Australia) physiologic factors to combine and cause PAC are:
Asian populations (Alaska, 0.3–2.7%
Japan, Mongolia, • Dim light
Singapore, India) • Accommodation
Hispanic population (US) 0.1% • Stress
Black populations (Africa) 0.5–0.6%
• Autonomic dysfunction–(sympathetic)
856 Glaucoma
Diagnosis sphincter atrophy, whorling of the iris radial pattern, sectoral

iris atrophy, pigment dispersal in the anterior chamber and
Symptoms suggestive of an attack of angle closure are, 'glaucomflecken' or anterior subcapsular lens opacities. On
unilateral headaches, transient blurring of vision, colored gonioscopy an occludable angle is a must for the diagnosis of
haloes around lights, ocular pain and redness of the eye, primary angle closure, i.e. with the patient looking straight
especially at twilight. In the early stages, these may be relieved ahead, the posterior trabecular meshwork should not be visible
by sleep or exposure to bright lights. due to the convexity of iris over at least 180 degrees (Fig.
Primary angle closure commonly occurs in smaller eyes, 9.3.2.2). It is essential to start gonioscopy with a 1 to 2 mm,
shorter axial length, shallow anterior chamber (AC) and smaller thin beam of light centered on the peripheral iris, to allow an
corneas. A shallow anterior chamber can be identified by accurate estimation of the angle recess. The light beam can
shining a flashlight from the temporal limbus, parallel to the then be lengthened and widened to view the depth of the
iris surface, when the iris convexity will not allow illumination angle. The angle recess in such eyes is generally less than 20
of the nasal limbus. Alternatively, a van Herick test21,22 using degrees, with clumps of pigment or peripheral anterior
a fine, bright slit placed at the extreme periphery of the cornea, synechiae visible after indentation or manipulative gonioscopy,
with the observation and illumination arms of the slit-lamp (Figs 9.3.2.3 and 9.3.2.4).
placed 60 degrees to each other, will allow a comparison of Provocative tests may be used in PACS eyes to determine
the corneal thickness with the depth of the peripheral AC. those likely to develop angle closure. The most physiological
An AC depth of less than ¼ of the cornea is most likely to test is the dark room prone test,24 in which a patient is placed
develop angle closure. prone in a dark room for 45 to 60 minutes, without sleeping.
Clinical signs of a prior angle closure attack include, a A rise in IOP of 8 mm Hg and gonioscopically confirmed
partial or total absence of the pupillary ruff23 (Fig. 9.3.2.1), angle closure is an indication for a laser iridotomy.
Fig. 9.3.2.2: occludable angle
Fig. 9.3.2.1: Pupillary ruff atrophy (black arrow) is an early sign of Fig. 9.3.2.3: After indentation, fine PAS and heavy pigmentation
angle closure, caused by minimal sphincter atrophy
PAS may not always mirror trabecular meshwork damage,

and 'target IOP' should be largely based on the patients' baseline
IOP, extent of visual field damage and age. Glaucomatous
optic neuropathy in these eyes appears to show more pallor
of POAG eyes, and the cupping appears to be shallower.
DIFFERENTIAL DIAGNOSIS
The diagnosis of acute primary angle closure glaucoma is
usually easy, however, the differential diagnosis includes uveitic
glaucoma, plateau iris syndrome, iridocorneal endothelial
syndrome, lens induced glaucoma, aphakic and pseudophakic
pupillary block, angle closure secondary to scleral buckling
surgery, to intraocular mass lesions, and neovascular glaucoma.
Fig. 9.3.2.4: Peripheral anterior synechiae in chronic PACG
Chronic PACG in Asian eyes is commonly asymptomatic,
and is often misdiagnosed as POAG.
SUBTYPES OF PRIMARY
MANAGEMENT
ANGLE CLOSURE
The different clinical stages of primary angle closure need
The subtypes of PAC are:25,26
individualized treatment, however the first step in all such
Subacute angle closure patients complain of intermittent blurred patients is to lower a raised IOP, appropriately. In acute PACG
vision accompanied by unilateral headache or colored haloes, this may require intravenous mannitol, or Diamox, oral
especially while doing near work in dim light. These episodes
acetazolamide and hyperosmotics, together with topical beta
may resolve on sleeping, or exposure to bright light, when
blockers or brimonidine. Pilocarpine is added to constrict the
miosis occurs. In some eyes, repeated angle closure may cause
pupil and draw the iris out of the angle. The baseline IOP in
peripheral anterior synechiae and trabecular meshwork damage
the other stages determines, the use of only topical therapy
leading to chronic PACG. Such eyes need lifelong evaluation
or additional systemic medication. In the presence of
even after laser iridotomy.
congestion, mild topical steroids may be used for a few days
Acute primary angle closure glaucoma typically presents
to control the inflammation.
with sudden unilateral headache, blurring of vision, colored
haloes around lights, and red eye. The abrupt rise in intraocular Once the IOP is within the normal range and the pupil is
pressure sometimes causes autonomic disturbances, e.g. constricted, a laser iridotomy is performed in both eyes.28-31
nausea, vomiting, bradycardia and sweating. There is The preferred laser in pigmented eyes is the Nd:YAG laser,
generalized conjunctival and ciliary congestion, with corneal using a power in the range of four to seven millijoule. The
edema, and the presence of aqueous flare. There is an laser is applied to a crypt, is present, between 11 and 1 o′clock,
irregular, mid-dilated non-reactive pupil, sector iris atrophy in the mid periphery of the iris, to produce an opening that is
of the iris, and pigment dispersion. Anterior subcapsular about 200 microns in size. The patency of the iridotomy is
discrete lens opacities called 'glaukomflecken' may be seen. identified by a gush of pigment while lasering, or by
The eye is generally stony hard on digital evaluation, with an retroillumination later. Prior to, and for three to five days
IOP often 50 mm Hg. Gonioscopically, the angle is closed, after the iridotomy, an additional antiglaucoma medication
but may not be visible due to corneal edema. Evaluation of will control post laser spikes in IOP that are seen in about six
the fundus after control of IOP, commonly shows a percent of individuals. Topical steroids should be prescribed
hyperemic optic nerve head. for five days. The patient should be reviewed after one to
Chronic primary angle closure glaucoma is asymptomatic two weeks to ensure the patency of the iridotomy, and on
in over 80 percent of individuals, and is commonly gonioscopy, the opening of the angle. At this time a diurnal
misdiagnosed as primary open angle glaucoma.27 Diagnosis phasing is advisable to look for the IOP status,32 which needs
depends on careful initial gonioscopy, which should be repeated to be adjusted to the requisite 'target IOP'.
periodically in all patients with glaucoma because progressive In eyes in which medical therapy does not break an acute
narrowing of the angle can occur over time. The extent of attack, corneal compression with a tonometer tip, a cotton-
858 Glaucoma
tip applicator, a muscle hook, or a four mirror goniolens may 3. Dandona L, Dandona R, Srinivas M, Mandal P, John RK, McCarty
help to break the attack by mechanically pushing aqueous CA, et al. Open-angle glaucoma in an urban population in southern
India: The Andhra Pradesh eye disease study. Ophthalmology
into the peripheral anterior chamber to open the angle. Other
2000;107:1702-9.
alternatives in resistant eyes include laser iridoplasty and 4. Dandona L, Dandona R, Mandal P, Srinivas M, John RK, McCarty
peaking of the pupil with the argon laser. It is estimated that CA, et al. Angle-closure glaucoma in an urban population in
50 to 75 percent of such acute PACG patients develop angle southern India: The Andhra Pradesh eye disease study.
closure in their fellow eye within five to ten years, even with Ophthalmology 2000;107:1710-6.
the use of chronic miotic therapy. 5. Jacob A, Thomas R, Koshi SP, Braganza A, Muliyil J. Prevalence
All PAC patients should be followed up life long after an of primary glaucoma in an urban south Indian population. Indian
J Ophthalmol 1998;46:81-6.
iridotomy, because of continuing age related changes in the
6. Ramakrishnan R, Nirmalan PK, Krishnadas R, Thulasiraj RD,
trabecular meshwork, as well as continued angle closure due
Tielsch JM, Katz J, et al. Glaucoma in a rural population of
to mechanisms other than relative pupillary block, such as a southern India: The Aravind comprehensive eye survey.
prominent last roll of iris or plateau iris syndrome. Ophthalmology 2003;110:1484-90.
Determination of 'target IOP' is similar to that in POAG 7. A population based survey of the prevalence and types of
eyes, and the choice of therapy,33-37 both medical and surgical glaucoma in rural West Bengal: the West Bengal Glaucoma Study.
is similar to POAG as well. All antiglaucoma medications have Br J Ophthalmol 2005;89(12):1559-64.
been shown to be similarly effective in PACG eyes as POAG. 8. Vijaya L, George R, Arvind H, Baskaran M, Paul PG, Ramesh SV,
In certain PACG eyes after iridotomy, long-term pilocarpine Raju P, Kumaramanickavel G, McCarty C. Prevalence of angle-
closure disease in a rural southern Indian population. Arch
therapy may help better IOP control, as it draws the iris out
Ophthalmol 2006;124:403-9.
of the angle recess in eyes with mechanisms of closure other 9. Vijaya L, George R, Arvind H, Baskaran M, Ve Ramesh S, Raju P,
than relative pupillary block. Kumaramanickavel G, McCarty C. Prevalence of primary angle-
If ‘target IOP’ is not achieved with maximal tolerated closure disease in an urban south Indian population and comparison
glaucoma therapy, a trabeculectomy is generally done, with with a rural population. The Chennai Glaucoma Study.
good long-term control of IOP. There is to date no evidence Ophthalmology 2008;115:655-60.
to support the use of cataract surgery to treat PACG, because 10. Foster PJ, Buhrmann R, Quigley HA, Johnson Gj. The definition
the raised IOP is due to trabecular changes that reduce aqueous and classification of glaucoma in prevalence surveys. Br J
outflow, not iridocorneal apposition. Ophthalmol 2002;86:238-42.
11. Sood NN, Jain RC, Agarwal HC. Ocular biometry in primary angle
closure glaucoma in Indians. Indian J Med Res 1988;88:190-1.
PROGNOSIS 12. Sihota R, Lakshmaiah NC, Agarwal HC, Pandey RM, Titiyal JS.
There is growing literature on what happens, in the long-term Ocular parameters in the subgroups of angle closure glaucoma.
to different stages of PAC.38-48 20 to 35 percent of PACS Clin Exp Ophthalmol 2000;28:253-8.
13. George R, Paul PG, Baskaran M, Ramesh SV, Raju P, Arvind H,
eyes progress to PAC over five to ten years. PAC eyes having
McCarty C, Vijaya L. Ocular biometry in occludable angles and
undergone an iridotomy, which do not have a raised IOP angle closure glaucoma: a population based survey. Br J Ophthalmol.
gradually tend to develop a raised IOP in about a third of 2003;87:399-402.
eyes over five years. A third of eyes having PAC with 14. Sihota R, Dada T, Gupta R, Lakshminarayan P, Pandey RM.
hypertension, tend to develop glaucomatous neuropathy over Ultrasound biomicroscopy in the subtypes of primary angle closure
five years. Chronic PACG eyes after an iridotomy seem to glaucoma. J Glaucoma 2005;14:387-91.
respond like POAG eyes on appropriate therapy. 15. Alsbirk PH. Primary angle closure glaucoma: oculometry
epidemiology and genetics in a high-risk population. Acta
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1. Sihota R, Agarwal HC. Profile of the subtypes of angle closure Johnson GJ, Foster PJ. Anterior chamber depth and the risk of
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Ophthalmol 1990;2:82-4. Baskaran M, Prasad KK; Latanoprost India Study Group. Efficacy
19. Mapstone R. Mechanics of pupil block. Br J Ophthalmol and safety of latanoprost for glaucoma treatment: a three-month
1968;52:19-25. multicentric study in India. Indian J Ophthalmol 2005;53:23-30.
20. Sihota R, Gupta V, Dada T, Deepak KK, Pandey RM. Narrowing 36. Gupta V, Srinivasan G, Sharma A, Kapoor KS, Sihota R.
of the anterior chamber angle during Valsalva maneuver: a possible Comparative evaluation of bimatoprost monotherapy in primary
mechanism for angle closure. Eur J Ophthalmol 2006;16:81-91. chronic angle closure and primary open angle glaucoma eyes: a
21. van Herick W, Schaffer RN, Schwartz A. Estimation of width of three-year study. J Ocul Pharmacol Ther 2007;23(4):351-8.
angle of anterior chamber. Incidence and significance of the 37. Agarwal HC, Gupta V, Sihota R. Effect of changing from
narrow angle. Am J Ophthalmol 1969:68:626-9. concomitant timolol pilocarpine to bimatoprost monotherapy on
22. Thomas R, George T, Braganza A, Muliyil J. The flashlight test and ocular blood flow and IOP in primary chronic angle closure
van Herick's test are poor predictors for occludable angles. Aust glaucoma. J Ocul Pharmacol Ther 2003;19(2):105-12.
N Z J Ophthalmol 1996;24(3):251-6. 38. Sihota R, Sood A, Gupta V, Gupta V, Dada T, Agarwal HC. A
23. Sihota R, Saxena R, Agarwal HC. Entropion uveae: early sphincter prospective long-term study of primary chronic angle closure
atrophy, signposting primary angle closure glaucoma? Eur J glaucoma. Acta Ophthalmol Scand. 2004;82(2):209-13.
Ophthalmol 2004;14(4):290-7. 39. Sihota R, Gupta V, Agarwal HC. Long-ter m evaluation of
24. Sihota R, Mohan S, Dada T, Gupta V, Pandey RM, Ghate D. An trabeculectomy in primary open angle glaucoma and chronic
evaluation of the darkroom prone provocative test in family primary angle closure glaucoma in an Asian population. Clin
members of primary angle closure glaucoma patients. Eye Experiment Ophthalmol. 2004;32(1):23-8.
2007;21(7):984-9. 40. Thomas R, George R, Parikh R, Muliyil J, Jacob A. Five year risk
25. Lowe RF. Clinical types of primary angle closure glaucoma. Aust of progression of primary angle closure suspects to primary angle
N Z J Ophthalmol 1988;16:245-50. closure: a population based study. Br J Ophthalmol 2003;87(4):
26. Leighton DA, Phillips Cl, Tsukahara S. Profile of presenting states 450-4.
of eyes in angle closure glaucoma. Br J Ophthalmol 1971; 55:577- 41. Ramani KK, Mani B, George RJ, Lingam V. Follow-up of primary
84. angle closure suspects after laser peripheral iridotomy using
27. Sihota R, Vishal Gupta, RM Pandey, D Kumar, Agarwal HC. ultrasound biomicroscopy and A-scan biometry for a period of 2
Comparison of symptomatic and asymptomatic chronic primary years. J Glaucoma 2009;18(7):521-7.
angle closure glaucoma, open-angle glaucoma, and controls. J 42. Pandav SS, Kaushik S, Jain R, Bansal R, Gupta A. Laser peripheral
Glaucoma 2000;9:208-13. iridotomy across the spectrum of primary angle closure. Can J
28. Slamovits T, Dutton J. Should patients with anatomically narrow Ophthalmol 2007Apr;42(2):233-7.
angles have prophylactic iridectomy ? Surv Ophthalmol 43. Thomas R, Parikh R, Muliyil J, Kumar RS. Five-year risk of
1996;41:31-63 progression of primary angle closure to primary angle closure
29. Stawowoski R, Bakunowicz-Lazarczyk A, Sobolewski P. glaucoma: a population-based study. Acta Ophthalmol Scand
Neodymium-YAG laser iridotomy in subacute and acute angle 2003;81(5):480-5.
closure glaucoma. Klin Oczna 1996;98:299-302. 44. Sihota R, Rao A, Gupta V, Srinivasan G, Sharma A. Progression in
30. Del Prioro LV, Robin AL, Pollack IP. Neodymium:YAG and argon primary angle closure eyes. J Glaucoma 2010;15.
laser iridotomy. Long-term follow-up in a prospective randomized 45. Friedman DS, Chew PT, Gazzard G, Ang LP, Lai YF, Quigley
clinical trial. Ophthalmology 1988;95:1207-11. HA, Seah SK, Aung T. Long-term outcomes in fellow eyes after
31. Kramer P, Ritch R. The treatment of acute angle closure glaucoma acute primary angle closure in the contralateral eye. Ophthalmology
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32. Sihota R, Saxena R, Gogoi M, Sood A, Gulati V, Pandey RM. A 46. Thomas R, Arun T, Muliyil J, George R. Outcome of laser
comparison of the circadian rhythm of intraocular pressure in peripheral iridotomy in chronic primary angle closure glaucoma.
primary chronic angle closure glaucoma, primary open angle Ophthalmic Surg Lasers 1999;30(7):547-53.
glaucoma and normal eyes. Indian J Ophthalmol 2005;53:243-7. 47. Alsagoff Z, Aung T, Ang LP, Chew PT. Long term clinical course
33. Agarwal HC, Gulati V, Sihota R. Study of Pulsatile Ocular Blood of primary angle-closure glaucoma in an Asian population.
Flow in Primary Chronic Angle Closure Glaucoma. Asian J Ophthalmology 2000;107:2300-4.
Ophthalmol 2002;4:6-10. 48. Rosman M, Aung T, Aung LP, Chew PT, Liebmann JM, Ritch R.
34. Sihota R, Saxena R, Agarwal HC, Gulati V. Crossover comparison Chronic angle-closure with glaucomatous damage: Long-term
of timolol and latanoprost in chronic primary angle-closure clinical course in a North American population and comparison
glaucoma. Arch Ophthalmol. 2004;122(2):185-9. with an Asian population. Ophthalmology 2002;109:2227-31.
860 Glaucoma
9.3.3 Congenital and Developmental

Glaucoma: Clinical Profile
Parul Ichhpujani, Suresh Kumar Gupta, Surinder Singh Pandav
The developmental glaucomas are a group of disorders TERMINOLOGY

characterized by improper development of the aqueous Primary congenital glaucoma: It is a specific term referring to
outflow system, usually manifesting in infancy and childhood. eyes that have an isolated maldevelopment of the trabecular
The childhood glaucomas are divided into three major meshwork without other developmental ocular anomalies or
categories: diseases that can raise intraocular pressure.
1. Primary congenital glaucoma, in which the developmental
anomaly is restricted to maldevelopment of the trabecular Infantile glaucoma: Primary infantile glaucoma is synonymous
meshwork; with primary congenital glaucoma.
2. Glaucoma associated with specific ocular or systemic Juvenile glaucoma: This is a non-specific term referring to any
congenital anomalies; and type of glaucoma occurring later in childhood (after 3 years
3. Glaucoma secondary to miscellaneous pediatric conditions of age) and through the second decades. Table 9.3.3.1 sub-
involving the eye, such as inflammation, trauma, or classifies some of the important causes of childhood
tumors. glaucoma.5
In this chapter, the first two categories would be discussed
in detail. Table 9.3.3.1: Pediatric glaucomas: Classification
HISTORY A. Primary glaucomas

i. Congenital/Infantile open-angle glaucoma
• Hippocrates, 400 years before Christ, and Celsus and ii. Juvenile open-angle glaucoma
iii. Primary glaucomas associated with systemic or ocular
Galen, 100 years after Christ, noted the phenomenon of abnormalities (like the autosomal dominant iridogoniodys-
buphthalmos but did not relate it to glaucoma genesis syndromes, chromosomal disorders, congenital
• Ambroise Paré wrote one of the first descriptions of infections like rubella, toxoplasmosis and herpes, metabolic
disorders like the mucopolysaccharidosis, phakomatosis like
buphthalmia in 1561
neurofibromatosis 1 and the Sturge-Weber's syndrome,
• Wolfrum1 demonstrated the true pathogeny of this disease aniridia, anterior segment dysgenesis syndrome and CHED).
• Taylor2 was the first to publish Carlo De Vincentis's B. Secondary glaucoma
surgical technique for the treatment of glaucoma i. Traumatic glaucoma which could be of acute onset
• In 1900, Scalinci presented 13 cases of congenital (because of hyphema or angle concussion) or late onset
(as that associated with angle recession)
glaucoma successfully operated using this technique. Otto
ii. Glaucoma secondary to intraocular neoplasm (like
Barkan3 revived it as an operation for congenital glaucoma retinoblastoma, leukemia and juvenile xanthogranuloma)
and called it goniotomy iii. Lens induced glaucoma (subsequent to spherophakia and
• One step forward was the introduction of trabeculotomy pupillary block and syndromes associated with subluxation
of the crystalline lens like the Marfan's syndrome)
by Burian, Harms, and Paufique, which improved the iv. Uveitic glaucoma
prognosis of congenital glaucomas greatly v. Aphakic glaucoma (after congenital cataract surgery)
• For the first time in 1987, R. Sampaolesi4 introduced vi. Steroid-induced glaucoma
vii. Glaucoma with increased episcleral pressure (as may
combined surgery (trabeculotomy and trabeculectomy) occur in arteriovenous fistulas, and the phakomatosis)
in a single surgical session for refractory congenital viii. Neovascular glaucoma (subsequent to retinoblastoma,
glaucomas Coat's disease and FEVR)
ix. Secondary angle-closure glaucoma (subsequent to aniridia,
• In 2005, he applied Koslov's technique of nonpenetrating
sclerocornea and cornea plana, PHPV, nanophthalmos,
deep sclerectomy to find the Schlemm’s canal, changing and microphthalmos).
Harms operation for the latter.
PRIMARY CONGENITAL angle structures, sclera, optic nerve, scleral canal, and lamina
(INFANTILE) GLAUCOMA cribrosa.12
An infant suspected to have congenital glaucoma is usually
The incidence of congenital glaucoma occurs in one out of
referred to an ophthalmologist because of clinically apparent
10,000 births, though there is tremendous geographical
corneal edema. In most cases, the commonly described triad
variability.6 In 80 percent of cases, it is bilateral. It affects
of epiphora, blepharospasm, and photophobia is seen (Fig.
males in 70 percent of cases. It is the most frequent cause of
9.3.3.1). The corneal edema ranges from being subtle,
early blindness of congenital origin and 50 percent of cases
especially in bilateral cases, to profound, with an enlarged
with blindness from glaucoma.
corneal diameter and globe, breaks in Desçemet's membrane
Heredity (Haab's striae), and sometimes even acute hydrops.
In children above two years of age, corneal enlargement
The varied incidence among different populations suggests a is not the predominant sign that glaucoma is present. In these
strong genetic component to the disease. Most cases (about children, decreased visual acuity, strabismus or progressive
90%) of primary infantile glaucoma appear to be sporadic, unilateral myopia prompts a referral and the correct diagnosis.
nonhereditary, and nonfamilial. However, in the remaining The enlargement of the globe with elevated IOP during the
10 percent there appears to be a strong familial component; first three years of life creates a myopic shift in the refractive
penetrance of the defect varies in the range of 40 to 100 percent. error, which may lead to amblyopia if significant
Francois and Duke Elder (1964) 7 have reported an anisometropia is present. The presence of Haab's striae often
autosomal recessive heredity pattern. Kluyskens8 was the first produces significant astigmatism, which also contributes to
to create genetic maps according to goniodysgenesis. The amblyopia, especially in unilateral or asymmetric cases.
exact cause and pathophysiology that underlies primary Suspicion for congenital glaucoma should be entertained if
infantile glaucoma remains a mystery. Several investigators the horizontal corneal diameter (in mm) is more than 12 mm
have localized primary infantile glaucoma related genes.9-11 between birth and the first six months of life (normal range:
Two loci GLC3A, linked to the 2p21 region, and GLC3B, 9.5–11.5 mm); more than 12.5 mm in a child between one to
linked to 1p36 region have been identified, and the presence two years of age (normal range: 10–12 mm) and more than
of at least a third locus in the human genome responsible for 13 mm in a child older than two years (normal range: ≤ 12
congenital glaucoma is suspected. The recent identification mm).13,14
of mutations in the gene for cytochrome P-4501B1 (CYP1B1)
linked to primary infantile glaucoma in large cohorts of Examination
affected families is a step towards better understanding of Depending on the age and level of cooperation of the patient,
the disorder. general anesthesia may be required to evaluate the child with
From a practical point of view, when their first child is glaucoma.
diagnosed with congenital glaucoma, parents want to know
the risk of having another child with the same disease. The
answer is that one out of four children is affected, though
this is not actually predictable and the chance of a second
child having the disease is small (1–3%).
Clinical Features
Congenital glaucoma is bilateral in 65 to 80 percent of cases,
although a significant IOP elevation may occur in only one
eye in 25 to 30 percent of the cases.12 The severity of
presenting signs and symptoms varies among infants with
primary infantile glaucoma, probably because of differences
in the magnitude and duration of the IOP elevation.
The neonatal globe is distensible and often greatly enlarges
with exposure to elevated IOP. Stretching of the infant eye is
not limited to the cornea and may involve the anterior chamber Fig. 9.3.3.1: A child with buphthalmos
862 Glaucoma
Office examination: A complete ocular examination, including slit- The hallmark of all forms of glaucoma, and the principal
lamp examination, applanation tonometry, pachymetry, cause of irreversible visual loss, is damage to the optic nerve.
gonioscopy, optic nerve evaluation, and retinoscopy, can be Evaluation of the optic nerve head is one of the most
performed in the office in children older than five years of age. important methods for diagnosing congenital glaucoma and
for assessing the response to therapy. It is now apparent that
Examination under anesthesia (EUA): General anesthesia is cupping may occur rapidly in infants, but that with surgical
required for a thorough examination of children under the treatment and normalization of IOP, this cupping is
age of five (Fig. 9.3.3.2). With a healthy child and an reversible.12 The morphology of glaucomatous optic atrophy
anesthesiologist experienced in dealing with infants, there is in childhood resembles that seen in adult eyes, with a
little risk. The sequential components of the EUA consists preferential loss of neural tissue in the vertical poles.15 A
of measuring the IOP, assessing the corneal thickness and child's eye does differ from that of the adult, however, in
diameters, gonioscopy, and ophthalmoscopy; additionally, axial that the scleral canal in children enlarges in response to elevated
length measurements, ultrasonic biomicroscopy, or cycloplegic IOP, especially in the horizontal meridian, causing further
retinoscopy may also be performed. All the essential enlargement of the cup in addition to that resulting from the
information regarding the presence and type of glaucoma, actual loss of neural tissue.15 The cupping appears to be
the extent of damage, associated findings, and the appropriate caused by incomplete development of connective tissue in
surgical options should be established in a prompt, methodical the lamina cribrosa, which allows compression or posterior
fashion. movement of the optic disc tissue in response to elevated
General anesthetics lower IOP to variable amounts and IOP, with an elastic return to normal when the pressure is
at variable times after administration, hence, intraocular lowered.16
pressure measurements should be taken as soon as the child After therapeutic normalization of IOP, cycloplegic
is quiet. refraction should be performed to correct significant
An effective measurement of the corneal diameter can differences in refractive errors between the two eyes.
be obtained using calipers to measure the horizontal diameter Table 9.3.3.2 presents some of the differential diagnosis
from the first appearance of the white scleral fibers at the that should be considered in a child suspected of having
limbus on one side to the same point on other side. Gonioscopy congenital glaucoma
can be performed with a smooth-domed Koeppe 14- to 16-
mm lens, with a Barkan light and hand-held binocular
Management
microscope. Contemporary four-mirror lenses, whose corneal
surface is less than 12 mm, can alternatively be used in A need for long-term surveillance and collaboration between
conjunction with an operating microscope. the physician and the family should be emphasized to the
Table 9.3.3.2: Congenital glaucoma:
Differential diagnosis
• Corneal edema or clouding
– Congenital hereditary endothelial dystrophy
– Mucopolysaccharidoses
– Cystinosis
– Sclerocornea
– Rubella keratitis
– Obstetric birth trauma ("forceps injury")
– Chemical injury
• Epiphora and/or red eye
– Nasolacrimal duct obstruction
– Conjunctivitis (viral, chlamydial, bacterial)
– Corneal epithelial defect, abrasion
• Photophobia
– Conjunctivitis
– Iritis
– Trauma (especially hyphema)
• Corneal enlargement
– Axial myopia
– Megalocornea (X-linked or sporadic)
– Microphthalmic fellow eye
Fig. 9.3.3.2: Evaluation under anesthesia
parents, as well as the need for frequent follow-up examinations It has been suggested that ultrasonography may be helpful
(often with general anesthesia), possible repeat surgeries, in documenting progression of infantile glaucoma by recording
chronic medication use, and amblyopia management for visual changes in the axial length of the globe.21 It has also been
rehabilitation. reported that the axial length may decrease up to 0.8 mm
after surgical reduction of the IOP.21
Medical Therapy
Congenital glaucoma is usually managed surgically, with DEVELOPMENTAL GLAUCOMAS WITH
medical therapy playing an adjunctive role. Preoperatively, ASSOCIATED ANOMALIES
medications may help clear the cornea to facilitate goniotomy Based on the observation that most of the ocular and facial
or to buy time till surgery is fixed, and postoperatively, if structures involved in these developmental disorders are of
surgery has incompletely controlled the glaucoma. Medical neural crest origin,22,23 the term neurocristopathies has been
therapy is also indicated in managing difficult cases in which appropriately coined for these disorders.24 Hoskins et al25
surgery poses life threatening risks.11 In general, the same advocated a shift away from eponyms and individual
basic principles of medical therapy apply to the treatment of syndromes names towards an emphasis on descriptive
congenital glaucoma as to adult glaucomas. One possible terminology. They suggested the terms trabeculodysgenesis,
exception is the use of miotics, which paradoxically may iridodysgenesis, and corneodysgenesis, or combinations
increase the IOP by collapse of the trabecular meshwork thereof, as a system of classifying the developmental defects.
because of the high insertion of uveal tissue into the posterior
meshwork. Axenfeld-Rieger Syndrome
Surgery These conditions have been designated in literature by three
eponyms:
The primary surgical techniques are designed to eliminate
• Axenfeld's anomaly (i.e. limited to peripheral anterior
the resistance to aqueous outflow created by the structural
segment defects)
abnormalities in the anterior chamber angle. This may be
• Rieger's anomaly (i.e. peripheral abnormalities with
achieved with incisional surgery, using an internal (goniotomy)
additional changes in the iris)
or external (trabeculotomy) approach. Some surgeons prefer
• Rieger syndrome (i.e. ocular anomalies plus systemic
to perform a combined angle and filtration surgery (i.e.
developmental defects).
trabeculotomy and trabeculectomy) as the initial procedure;
The similarity of anterior chamber angle abnormalities
others use this technique after initial angle surgery has failed;
in Axenfeld's anomaly and Rieger's anomaly and syndrome
and still others always perform filtration surgery only after
points towards the fact that these three arbitrary categories
angle surgery has failed.17-19
represent a spectrum of developmental disorders.26,27 Hence
the alternative term, Axenfeld-Rieger syndrome (A-R
Postoperative Care, Prognosis and Follow-Up syndrome), was proposed for all clinical variations within this
The follow-up care of patients with congenital glaucoma has spectrum of developmental disorders. This name retains
several important facets. In the early postoperative period, reference to the original eponyms and does not depend on
close observation is required regarding success of the any theory of normal development.
glaucoma procedure. In addition to IOP reduction, other
clinical indicators of successful glaucoma control include General Features
clearing of corneal edema, reversal of optic nerve cupping, All patients with the A-R syndrome, share the same general
and even reduction in myopia in some cases. features, bilateral, developmental disorder of the eyes; a frequent
Good vision may be achieved if the IOP is controlled family history of the disorder, with an autosomal dominant
before optic atrophy occurs. Occasionally, however, the acuity mode of inheritance; no sex predilection; frequent systemic
is poor despite adequate pressure control. In some cases, this developmental defects; and a high incidence of associated
is caused by optic nerve damage, corneal opacity from breaks glaucoma. The age at which the A-R syndrome is diagnosed
in Descemet's membrane or persistent stromal haze, or ranges from birth to adulthood, with most cases becoming
irregular astigmatism.20 recognized during infancy or childhood. The diagnosis may
864 Glaucoma
Fig. 9.3.3.3: Prominent, anteriorly displaced Schwalbe’s line
occasional patients with variation in the overall size. The

corneal endothelium is typically normal.
Anterior chamber angle: Gonioscopic examination reveals a
prominent Schwalbe's line, although there is considerable
variation among patients in the extent to which Schwalbe's
line is enlarged and anteriorly displaced. Tissue strands bridge
the anterior chamber angle from the peripheral iris to the
prominent ridge. These iridocorneal adhesions are typically
similar in color and texture to the adjacent iris. The strands
range in size from threadlike structures to broad bands
extending for a clock hour or more of the circumference.
Iris: Aside from the peripheral abnormalities, the iris may be
normal in some eyes with the A-R syndrome. In other cases,
defects of the iris range from mild stromal thinning to marked
atrophy with hole formation, corectopia, and ectropion uveae
(Fig. 9.3.3.4). In cases with corectopia, the pupil is usually
Fig. 9.3.3.4: Iris holes in a case of Axenfeld-Rieger syndrome displaced toward a prominent peripheral tissue strand, which
is often visible by slit-lamp biomicroscopy. The atrophy and
hole formation occurs in the quadrant away from the direction
result from discovery of an abnormal iris or other ocular of the corectopia. The progressive changes usually consist
anomaly, signs of congenital glaucoma, reduced vision in older of displacement or distortion of the pupil and occasional
patients, or systemic anomalies. thinning or hole formation of the iris. In some cases, these
progressive iris changes may be confused with those of ICE
Ocular Features
syndrome.
Ocular defects in the A-R syndrome are typically bilateral. Other reported abnormalities include strabismus, limbal
The structures most commonly involved are the peripheral dermoids, corneal pannus, cataracts, congenital ectropion
cornea, anterior chamber angle, and iris. uveae, congenital pupillary iris lens membrane, peripheral
spokelike transillumination defects of the iris, retinal
Cornea: The characteristic abnormality is a prominent,
detachment, macular degeneration, chorioretinal colobomas,
anteriorly displaced Schwalbe's line (Fig. 9.3.3.3). This appears
choroidal hypoplasia, and hypoplasia of the optic nerve heads.
on slit-lamp examination as a white line on the posterior
cornea near the limbus. The cornea is otherwise normal in Glaucoma: Slightly more than one half of the patients with
the typical case of the A-R syndrome, with the exception of the A-R syndrome develop glaucoma. The glaucoma may
manifest during infancy, although it more commonly appears • Ectopia Lentis et Pupillae: The corectopia in this
in childhood or young adulthood. The extent of the iris defects disorder may resemble that of the A-R syndrome, but
and iridocorneal strands does not correlate precisely with the the absence of anterior chamber angle defects is a
presence or severity of the glaucoma. differential feature
• Oculodentodigital dysplasia
Systemic Features • Aniridia
The systemic anomalies most commonly associated with the Management: Intraocular pressure elevation most often
A-R syndrome are developmental defects of the teeth and develops between childhood and early adulthood, but it may
facial bones. The dental abnormalities include a reduction in appear in infancy. With the exception of infantile cases,
crown size (i.e. microdontia), decreased but evenly spaced medical therapy should be initiated before surgical
number of teeth (i.e. hypodontia), and focal absence of teeth intervention is recommended. Trabeculectomy is the surgical
(i.e. oligodontia or anodontia).28,29 The teeth most commonly procedure of choice for most patients with glaucoma
missing are the anterior maxillary, primary, and permanent associated with the A-R syndrome. These patients must be
central incisors. Facial anomalies include maxillary hypoplasia followed throughout their lives to detect glaucoma. In infants
with flattening of the midface and a receding upper lip and and in cases refractory to medication and trabeculectomy,
prominent lower lip, especially in association with dental glaucoma implant surgery and cycloablation remain options
hypoplasia. Hypertelorism, telecanthus, a broad flat nose, for treatment.
micrognathia, and mandibular prognathism have also been
described. Other abnormalities reported in association with Aniridia
the A-R syndrome include redundant periumbilical skin and
hypospadias, oculocutaneous albinism, heart defects, middle General Features
ear deafness, mental deficiency, and a variety of neurologic, Congenital aniridia is a heritable disease of the eye
dermatologic, and skeletal disorders.30 characterized by an obvious iris defect (which varies from an
almost complete absence to relatively complete, albeit
Genetic Linkage abnormal, irides), decreased visual acuity with nystagmus,
Three chromosomal loci have been linked to A-R syndrome small corneas, small discs, foveal hypoplasia, and cataract.
and related phenotypes. These loci are on chromosomes 4q25, Glaucoma occurs in 50 to 75 percent of patients who have
6p25, and 13q14. The genes at chromosomes 4q25 and 6p25 aniridia.
have been identified as PITX2 and FOXC1 (formerly Aniridia may be either sporadic or familial. The gene for
designated FKHL7), respectively.31 aniridia has been localized to the short arm of chromosome
11; a deletion in this area results in a syndrome that comprises
Differential Diagnosis the ocular findings given above with, in addition, mental
retardation, genital anomalies, and a greatly increased risk of
• Iridocorneal endothelial syndrome: Clinical features that Wilms' tumor at a young age.32 Children of parents who have
distinguish the iridocorneal endothelial (ICE) syndrome aniridia are at a 50 percent risk of inheriting the syndrome.
from the A-R syndrome include corneal endothelial
abnormalities, unilaterality, absence of family history, and Clinical Features
onset in young adulthood. The membrane in the A-R
Although the majority of children who have aniridia go on to
syndrome represents a primordial remnant while that of
the ICE syndrome results from proliferation of the develop glaucoma, most do not do so until late in the first
abnormal corneal endothelium decade of life. This late onset glaucoma associated with aniridia
• Posterior polymorphous dystrophy: Differentiation can be made appears to be the result of a form of angle closure.33
on the basis of the typical corneal endothelial abnormality
• Peters' Anomaly: The spectrum of disorders that constitutes Management
Peters' anomaly involves the central portion of the cornea, In severe disease requiring surgery, trabeculectomy is the
iris, and lens procedure of choice, with recent reports suggesting that
• Iridogoniodysgenesis: Congenital hypoplasia of the iris is glaucoma drainage devices can also be helpful in refractory
present cases.32-35
866 Glaucoma
Peters' Anomaly Differential Diagnosis
General Features • Causes of central corneal opacities: Congenital glaucoma, birth

trauma, the mucopolysaccharidoses, and congenital
The condition is present at birth and is usually bilateral. Most hereditary endothelial dystrophy
cases are sporadic, although there are reported cases of • Posterior keratoconus
autosomal recessive inheritance. • Congenital corneal leukomas and staphylomas
Because of the varied genetic and nongenetic patterns
Management: Trabeculotomy or trabeculectomy may be
and the spectrum of ocular and systemic abnormalities, it is
reasonable in milder cases where there is adequate anterior
likely that Peters' anomaly is a morphologic finding rather
chamber depth. A drainage implant device or cyclodestructive
than a distinct entity.36 Peters' anomaly can be caused by
surgery is often needed in refractory or more severely affected
mutation in the PAX6 gene, the PITX2 gene, the CYP1B1
cases.
gene, or the FOXC1 gene. Penetrating keratoplasty is also frequently necessary,
although the results are typically poor, which is probably caused
Clinicopathologic Features in part by the associated glaucoma and its surgical treatment.
The hallmark of Peters' anomaly is a central defect in
Descemet's membrane and corneal endothelium with thinning Sturge-Weber Syndrome and Variants
and opacification of the corresponding area of corneal Glaucoma associated with encephalotrigeminal angiomatosis
stroma.36-38 Bowman's layer may also be absent centrally. (SWS) is one of the more frequently encountered forms of
Iris adhesions may extend to the borders of this corneal glaucoma of childhood.
defect.
The disorder has been subdivided into three groups, General Features
each of which may have more than one pathogenetic Classic SWS comprises the triad of port wine facial
mechanism.39 telangiectasis (nevus flammeus) in the distribution of the
• Peters' Anomaly Not Associated with keratolenticular contact or trigeminal nerve that respects the vertical midline, ipsilateral
cataract: The defect in Descemet's membrane may glaucoma, and intracranial angiomata.
represent primary failure of corneal endothelial
development.37 However, rare cases may result from Clinical Features
intrauterine inflammation, 38 which was originally
Cibis et al report that glaucoma occurs in about one-third of
postulated by von Hippel39 and gave rise to the term von
patients who have SWS.40 In patients affected by glaucoma,
Hippel's internal corneal ulcer
both the upper and lower lids usually are involved in the
• Peters' Anomaly Associated with keratolenticular contact or
facial telangiectasis.
cataract: Most histopathologic studies of this variation suggest
that the lens developed normally and was then secondarily Management
pushed forward against the cornea by one of several
mechanisms, causing the loss of Descemet's membrane.36,37 For cases presenting later in life, trabeculectomy,
It is also possible that some cases may result from incomplete cyclodestruction, and glaucoma drainage devices have been
separation of the lens vesicle from surface ectoderm advocated.41,42 The presence of choroidal hemangiomas in
• Peters' Anomaly Associated with Axenfeld-Rieger Syndrome. many of these patients increases the risk of choroidal
expansion or hemorrhage intraoperatively.
Glaucoma Congenital (primary infantile) glaucomas represent one
group of glaucomas in childhood. They are characterized by
Approximately one half of patients with Peters' anomaly a developmental abnormality of the anterior chamber angle
develop glaucoma, which is frequently present at birth. The without consistently associated systemic or other ocular
mechanism of glaucoma is uncertain, because the anterior anomalies. The conditions are believed to have a genetic basis,
chamber angle is usually grossly normal on clinical are often diagnosed during the first year of life, and are
examination. usually bilateral.
Several conditions are characterized by glaucoma due to displacement of the crystalline lens and increasing
developmental defects of the anterior chamber angle with iridolenticular contact.
additional ocular and systemic abnormalities. These disorders
are typically bilateral and are usually diagnosed at birth or in Management
early childhood. Most are thought to have a genetic basis.
Management of angle closure in these eyes may be challenging.
Axenfeld Rieger syndrome, is a spectrum of disorders in
Laser iridectomy should be performed to eliminate the
which the ocular anomalies include a prominent Schwalbe's
pupillary block component to the disease process. If the
line, tissue strands across the anterior chamber angle, and
anterior chamber angle remains appositionally closed after
varying degrees of iris distortion while the systemic defects
iridectomy, argon laser peripheral iridoplasty can be performed
involve the teeth and facial bones. Peters' anomaly also has
to mechanically open the angle.43 Miotics should be used
variable clinical manifestations, with alterations primarily of
with caution as these eyes may respond to miotics by a
the central cornea, iris, and lens. In aniridia, the hallmark is a
paradoxical shallowing of the anterior chamber due to
rudimentary stump of peripheral iris, although there may be
relaxation of the zonular apparatus with secondary anterior
additional ocular abnormalities of the cornea, lens, or fovea,
displacement of the crystalline lens. If uveal effusion is
as well as systemic disorders, including Wilms' tumor and
evident, cycloplegics may be beneficial by relaxing the ciliary
mental retardation. A large number of other syndromes with
muscle and tightening the zonular apparatus. In some cases
ocular and systemic abnormalities may occasionally have
vortex vein decompression may be required.45,46 If either
developmental glaucoma.
cycloplegics or miotics are used, subsequent gonioscopy
should be performed to minimize the likelihood of a
Nanophthalmos
pharmacologically induced attack of acute angle closure
Nanophthalmos is a form of pure microphthalmos resulting glaucoma. In some patients, additional systemic steroids may
from developmental arrest of the globe after closure of the be useful in the management of uveal effusion.
embryonic fissure. It is usually bilateral and may be inherited
in an autosomal dominant, autosomal recessive, or sporadic Juvenile Onset Open Angle Glaucoma
fashion.
Juvenile-onset open-angle glaucoma (JOAG) is an elevation
General Features of intraocular pressure after the 36th month of life, extending
to any time throughout childhood before 16 years of age.47,48
The typical clinical picture of nanophthalmos consists of JOAG differs from POAG mainly in the severity of disease
high hyperopia, short axial length, small corneal diameter and and age of onset.
angle-closure glaucoma. Due to progressive shallowing of
the anterior chamber and narrowing of the angle, these eyes
General Features
tend to develop angle closure glaucoma by the fourth to sixth
decade.43 Most cases of JOAG that have a strong family history of
disease are associated with defects in the myocilin gene
Mechanism of Glaucoma (MYOC).49 Myocilin associated glaucoma is inherited as an
autosomal dominant trait. That is, patients carrying a myocilin
The mechanism of angle closure may be multifactorial and
mutation that causes JOAG have a 50 percent chance of
includes crowding of the anterior chamber secondary to high
passing the gene (and high risk for glaucoma) to their children.
lens/eye volume ratio. This disparity then underlies
Some patients have the typical clinical features of JOAG but
progressive PAS formation from physical displacement of
do not have a family history of disease. The myocilin gene has
the iris against the trabecular meshwork or enhanced
a less important role in these sporadic cases of JOAG.
iridolenticular contact that leads to an increase in relative
pupillary block.44 The anterior chamber angle can also be
closed by physical displacement of the peripheral iris by Clinical Features
anteriorly rotated ciliary processes when nanophthalmos The clinical features of JOAG are the same as those of more
presents with annular ciliochoroidal effusion and ciliary body common forms of glaucoma (such as POAG). It is often
detachment. Uveal effusion can also induce relative papillary found associated with myopia. After the age of three, the
block by relaxing the zonular apparatus, allowing anterior sclera loses much of the elasticity and therefore, buphthalmia
868 Glaucoma
is not commonly seen. In contrast, the posterior sclera may 8. Kluyskens J. Le glaucome congénital. Bull Soc Belge Ophtalmol
still have some elasticity, permitting the posterior portion of 1950;94:3-248.
9. Sarfarazi M, Akarsu AN, Hossain A, et al. Assignment of a locus
the globe to expand secondary to the high IOP. This posterior
(GLC3A) for primary congenital glaucoma (buphthalmos) to 2p21
expansion may result in an increase in myopia.50 The corneal and evidence for genetic heterogeneity. Genomics 1995;30:171.
diameters of JOAG patients are usually normal and the 10. Sarfarazi M. Recent advances in molecular genetics of glaucomas.
patients are usually asymptomatic.47 Hum Mol Genet 1997;6:1667.
11. Akarsu AN, Turacli ME, Aktan SG, et al. A second locus (GLC3B)
Mechanism of Glaucoma for primary congenital glaucoma (Buphthalmos) maps to the 1p36
region. Hum Mol Genet 1996;5:1199.
A current theory is that JOAG is the result of the abnormal 12. DeLuise VP, Anderson DR. Primary infantile glaucoma (congenital
development of structures or the migration of the neural glaucoma). Surv Ophthalmol 1983;28:1.
13. Becker B, Shaffer RN. In: Diagnosis and therapy of the glaucomas.
crest cells.50 Tripathi & Tripathi6 reported that abnormal
St. Louis: CV Mosby, 1965.
migration or defective terminal induction of the neural crest 14. Kiskis AA, Markowitz SN, Morin JD. Corneal diameter and axial
cells played an important role in causing JOAG. Anomalous length in congenital glaucoma. Can J Ophthalmol 1985;20:96.
migration of neural crest cells may contribute to the abnormal 15. Anderson DR. Pathogenesis of glaucomatous cupping. A new
development of the anterior chamber angle, thus leading to hypothesis. In: Symposium on glaucoma. Transactions of the New
the obstruction of the aqueous outflow by one or more Orleans Academy of Ophthalmology. Mosby, St. Louis 1975;81-
94.
developmental defects at various levels of the trabecular
16. Robin AL, Quigley HA, Pollack IP, et al. An analysis of visual
meshwork and Schlemm's canal.46,49 acuity, visual fields, and disc cupping in childhood glaucoma. Am
J Ophthalmol 1979;88:847.
Management 17. Quigley HA. The pathogenesis of reversible cupping on congenital
For the management of JOAG, medical treatment may be glaucoma. Am J Ophthalmol 1977;84:358.
18. Elder MJ. Combined trabeculotomy trabeculectomy compared
initially effective but surgical treatment is generally required
with primary trabeculectomy for congenital glaucoma. Br J
to control the progress of glaucoma. Medical therapy is used Ophthalmol 1994;78:745.
preoperatively or sometimes postoperatively, if repeated 19. Mandal AK, Bhatia PG, Gothwal VK, et al. Safety and efficacy
surgical interventions fail.50-52 Goniotomy and trabeculotomy of simultaneous bilateral primary combined trabeculotomy-
are generally successful as they possibly reduce the aqueous trabeculectomy for developmental glaucoma. Indian J Ophthalmol
outflow resistance. If multiple incisional procedures fail, then 2002;50:13.
20. Mullaney PB, Selleck C, Al-Awad A, et al. Combined trabeculotomy
trabeculectomy can be tried. If all fails, then cyclodestructive
and trabeculectomy as an initial procedure in uncomplicated
procedures may be performed. congenital glaucoma. Arch Ophthalmol 1999;117:457.
21. Morin JD, Bryars JH. Causes of loss of vision in congenital
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51. body. Birth Defects 1975;11:19.
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30. Wesley RK, Baker JD, Golnick AL. Rieger's syndrome: (oligodontia 41. Cibis GW, Tripathi RC, Tripathi BJ. Glaucoma in Sturge-Weber
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and report of an isolated case. J Pediatr Ophthalmol Strabismus 42. Budenz DL, Sakamoto D, Eliezer R, et al. Two-staged Baerveldt
1978;15:67. glaucoma implant for childhood glaucoma associated with Sturge-
31. Steinsapir KD, Lehman E, Ernest JT, et al. Systemic Weber syndrome. Ophthalmology 2000;107:2105-10.
neurocristopathy associated with Rieger's syndrome. Am J 43. van Emelen C, Goethals M, Dralands L, Casteels I. Treatment of
Ophthalmol 1990;110:437. glaucoma in children with Sturge-Weber syndrome. J Pediatr
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genetics. Am J Ophthalmol 2000;130:107. 44. Singh OS, Simmons RJ, Brockhurst RJ, et al. Nanophthalmos: a
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34. Walton DS. Aniridic glaucoma: the results of gonio-surgery to 45. Kimbrough RL, Trempe CL, Brockhurst RJ, et al. Angle-closure
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84:59-70. 46. Brockhurst RJ. Vortex vein decompression for nanophthalmic
35. Arroyave CP, Scott IU, Gedde SJ, et al Use of glaucoma drainage uveal effusion. Arch Ophthalmol 1980;98:1987-90.
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Am J Ophthalmol 2003; 135:155-9. Alward WLM. Clinical features and linkage analysis of a family
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38. Stone DL, Kenyon KR, Green WR, et al. Congenital central and juvenile open-angle glaucoma. Arch Ophthalmol 2003;121:
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39. Polack FM, Graue EL. Scanning electron microscopy of 50. Sassani JW. Ophthalmic Fundamentals: Glaucoma. Thorofare,
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1979;88:169. 51. Tripathi BJ, Tripathi RC. Neural crest origin of human trabecular
40. von Hippel E. Uber hydrophthalmus congenitus nebst meshwork and its implications for the pathogenesis of glaucoma.
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9.3.4 Secondary Glaucoma: Clinical Aspects

Suresh Kumar Gupta, Parul Ichhpujani, Neeti Gupta, Surinder Singh Pandav
There are several systems by which the glaucomas may be • Glaucoma associated with trauma
classified. The most common are based on: • Steroid induced glaucoma
• Etiology: Based on the underlying disorder that leads to
an alteration in aqueous humor dynamics; and PIGMENT DISPERSION
• Mechanism: Based on the specific alteration in the anterior SYNDROME (PDS)
chamber angle that leads to a rise in intraocular pressure.
The term pigmentary glaucoma was first described in 1949
Some of the important conditions that are categorized as
by Sugar and Barboun. This is a rare condition which
being causes of secondary glaucoma are:
typically involves young myopic males.
• Pigment dispersion syndrome
• Exfoliation syndrome
Epidemiology
• Lens induced glaucoma
• Malignant glaucoma Pigmentary glaucoma roughly constitutes 1 to 1.5 percent of
• Glaucoma associated with retinal disorders all glaucomas.1,2 Young age, myopia, male gender and white
• Glaucoma associated with intraocular tumors race constitute important risk factors. Initially reported in the
• Glaucoma associated with inflammation white races, it has been reported throughout the world now.
870 Glaucoma
Clinical Features Heredity

Cornea No typical hereditary pattern is known in PDS. Most of the
Krukenberg's spindle is the hallmark of pigment dispersion patients are sporadic in nature. However, autosomal
syndrome. It is pigment accumulation on the corneal endothelium dominant6 and autosomal recessive7 patterns are reported.
in vertical shape. The spindle is usually wider inferiorly.3,4
Pigmentary Glaucoma
Iris Roughly 20 to 30 percent of the patients of PDS eventually
Pigment granules settle on the surface of iris. There is posterior develop rise in IOP.8,9 This condition is known as pigmentary
bowing of the mid peripheral iris. This leads to classic glaucoma (PG). Conversion from PDS to PG is slow and
peripheral, radial slit like transillumination defects in the iris. can take years. Pigmentary glaucoma is defined as intraocular
Transillumination defects can be seen using a fiber optic light pressure (IOP) greater than 21 mm Hg in the presence of
placed on the sclera in a darkened room. However, the best PDS, irrespective of the status of the optic nerve head and
way to see these defects is retroillumination with low visual fields. Some of the patients of PG can have slow
magnification at the slit-lamp. spontaneous resolution of glaucoma. Other patients can have
irreversible damage to the trabecular meshwork leading to
Lens/Zonules permanent rise in IOP.
There is collection of pigment in the form of interrupted
line son the posterior peripheral surface of the lens. Mechanism of Glaucoma
Gonioscopy with pupillary dilatation will demonstrate this The posterior bowing of the peripheral iris enhances the
interrupted line of pigment which is otherwise difficult to see friction between posterior surface of the iris and the anterior
on routine slit-lamp examination. surface of the zonular fibrils. This friction leads to release of
pigments whenever the iris rubs against the zonules and the
Angle peripheral lens. Obstruction and damage to the trabecular
Angle in PDS is always wide open and there is heavy dark meshwork is caused by pigment and macrophages laden with
brown to black pigmentation of the trabecular meshwork pigment. In the early stage of the disease, this damage to the
(Fig. 9.3.4.1).5 trabecular meshwork is reversible. However, this damage may
become irreversible and progressive and permanent glaucoma
may develop.
Pseudoexfoliation syndrome, uveitis, iris/ciliary body cyst
and iris/ciliary body melanoma have to be differentiated
from PDS.
Ancillary testing
Ultrasound biomicroscopy (UBM): UBM is very helpful in
confirming the peripheral posterior bowing of the iris and
showing iridozonular contact.10
Management
Fig. 9.3.4.1: Pigmentation in the angle in a case General principles include medical treatment, laser
of pigmentary glaucoma trabeculoplasty and incisional surgery.
Medical Therapy from zero in Eskimos to 21 percent in Icelanders.18-20 The

incidence of exfoliation among glaucoma patients varies from
Medical treatment in pigmentary glaucoma is similar to that
12 to 60 percent.21-23 The incidence of glaucoma in exfoliation
of primary open angle glaucoma (POAG). Beta blockers are
syndrome is around 22 to 49 percent.23,24
usually started and given twice a day. Pilocarpine11 can be
given if further reduction in IOP is required. Most of the
Bilaterality
patients having pigmentary glaucoma are young and myopic;
the tolerance of miotic therapy is poor. The gel preparation Since XFS is a systemic disease, unilateral or monocular terms
of pilocarpine used at bedtime is another alternative. Miotics are misleading. Patients presenting with XFS in one eye will
help patients with of PG by flattening the peripheral iris and invariably show exfoliation material in the other eye in
decreasing the pigment dispersion. conjunctival biopsy. The term unilateral or bilateral merely
represents clinically detectable exfoliation material at slit lamp.
Laser Treatment
Argon laser trabeculoplasty (ALT): The results of ALT in PG Clinical Features
are encouraging. Ritch et al12 reported 80 percent success
rate of ALT at the end of one year follow up. Less energy is Cornea
required in patients of PG as greater pigmentation of A small amount of pigment is often seen inferiorly on corneal
trabecular meshwork enhances energy absorption. A “just endothelium. Krukenberg spindle is an occasional finding.
visible” reaction in trabecular meshwork is required for
adequate treatment. Iris
Peripheral iridotomy (PI): Peripheral iridotomy may flatten The exfoliation material is deposited in the pupillary borders.
peripheral iris and help in decreasing further pigment release. Particulate pigment deposition on sphincter and peripheral
Peripheral iridoplasty: Argon laser peripheral iridoplasty (ALPI) iris is characteristic. Moth-eaten transillumination defects
may flatten peripheral concave iris and may be useful in occur at the sphincter, in contrast to mid-peripheral defects
patients of PG. seen in pigment dispersion syndrome. Absence of pupillary
ruff is commonly seen in XFS.
Surgical Treatment
Incisional surgery: Trabeculectomy is indicated in patients not Cataract
showing response to medical and laser therapy. The results An association between cataract and XFS exist. There is
of trabeculectomy in PG is comparable to the outcome of increased prevalence of cataract in XFS and vice versa.25
POAG patients. 13 Mitomycin C has to be used in low The exfoliation material gets deposited on the anterior lens
concentration for lesser time, so as to avoid hypotonic surface and zonules. The material gets rubbed off from the
maculopathy which is frequently seen in myopic patients midperiphery of the lens by continuous physiological
movement of the pupil. This gives rise to a central disk, a
EXFOLIATION SYNDROME peripheral band and a clear middle zone between the two.
Lindberg14 described the exfoliation syndrome (XFS) in 1917. Rarely, the central disk may be absent.
This condition is characterized by grayish white flecks on the The exfoliation material deposited on the iris, lens and
pupillary border. True exfoliation is seen in glass blowers. zonules predisposes the eye to complications during cataract
Other terms used for this condition are pseudoexfoliation surgery. The pupil dilates poorly in eyes with XFS. Various
syndrome, senile exfoliation syndrome, senile uveal exfoliation, intraoperative complications like capsular tear, zonular dialysis,
glaucoma senilis, complex pigmentary glaucoma and sticky lens cortex, vitreous loss have been reported. Intraocular
exfoliation of the pseudocapsule. The term exfoliation pressure elevation, cellular deposits on IOL and posterior
syndrome is considered to be most appropriate as true synechiae formation occurs more frequently in the
exfoliation syndrome is so rare. postoperative period.
Epidemiology Angle
Originally seen in Scandinavia, it has been reported from Trabecular meshwork shows increased pigmentation.
every area of the world.15-17 The reported prevalence varies Sometimes pigmentation of trabecular meshwork may be
872 Glaucoma
the earlier detected sign than the exfoliation material. Pigment

dispersion in XFS is uneven and sometimes appears as a
wavy line anterior to the Schwalbe's line (Sampaolesi's line).
Glaucomas
Glaucoma associated with XFS is known as glaucoma
capsulare.
Mechanism of glaucoma: The most common variety of glaucoma
associated with XFS is open angle glaucoma. Open angle
glaucoma is caused by blockage of trabecular meshwork by
exfoliation material and also pigments. The exfoliation material
also damages the trabecular cells. Angle closure glaucoma
has recently been recognized in XFS. Narrow angles are
reported to be 23 to 32 percent in XFS,26,27 although angle
closure glaucoma is uncommon. Pupillary block glaucoma Fig. 9.3.4.2: Pseudohypopyon in case of phacolytic glaucoma
can be caused by posterior synechiae, iris rigidity or anterior
lens movement resulting from zonular weakness. LENS INDUCED GLAUCOMA
Differential Diagnosis It has long been recognized clinically that several forms of
glaucoma may occur in association with the formation of
Pigment dispersion syndrome and capsular delamination (true cataracts and these forms are addressed in this section.
exfoliation) should be differentiated from XFS.
Phacolytic Glaucoma
Management
Lens induced glaucoma due to protein leakage from mature
Medical Treatment or hypermature cataract is termed as phacolytic glaucoma. It
was first described by Gifford in 1900.29
The medical treatment of XFS is similar to that of primary
open angle glaucoma. However, glaucoma in XFS is more Clinical Features
resistant and difficult to treat as compared to primary open
angle glaucoma. Beta blockers may be started twice a day as Clinically, phacolytic glaucoma usually occurs in elderly
the initial treatment. Epinephrine can be given as additive patients and presents in the acute form with sudden onset of
therapy. Miotics may be the best choice as initial agents, since pain, redness and watering in the eye. Patients typically have
apart from lowering IOP, it decreases the amount of sudden, high rise in IOP. The presentation is similar to that
exfoliation material released by the inhibiting pupillary of acute angle closure glaucoma. Slit-lamp examination often
movements. reveals diffuse corneal edema. Soluble lens proteins, and
aggregates of white material leaked from cataractous lens
Laser Treatment are seen in the anterior chamber (Fig. 9.3.4.2). There is heavy
flare in the anterior chamber that is often associated with
Argon laser trabeculoplasty is an effective modality for the hyper-refringent particle which are reported to be calcium
treatment of XFs. Patients are maintained on miotics after oxalate 30 or cholesterol crystles. 31 The lens is mature,
laser trabeculoplasty to prevent future release of pigment. hypermature or Morgagnian with wrinkling of the anterior
Laser iridotomy should be done for angle closure glaucoma lens capsule due to release of lens material. The angles are
associated with XFS. open on gonioscopy. However, angle recession is reported in
25 percent of eyes with phacolytic glaucoma.32
Surgical Treatment
Mechanism of Glaucoma
Trabeculotomy should be done in patients not showing
adequate control with medical therapy. Trabeculectomy shows There is release of lens proteins into the aqueous through
same results as for primary open angle glaucoma.28 microscopic defect in the lens capsule. It is presumed that
the macrophages engulf these proteins and block the trabecular Differential Diagnosis
meshwork which leads to increase in IOP.33 Another theory
Lens particle glaucoma should be differentiated from
says that high molecular weight soluble protein released from
phacoanaphylaxis, phacolytic glaucoma and uveitis associated
the lens directly block the trabecular meshwork.34
with primary open angle glaucoma.
Differential Diagnosis Management
Phacolytic glaucoma should be differentiated from Medical therapy: IOP can be reduced by combination of beta
phacomorphic glaucoma, acute angle closure glaucoma, blockers, carbonic anhydrase inhibitors and temporary
primary open angle glaucoma, and glaucoma associated with hyperosmotics. Topical cycloplegics and corticosteroids should
uveitis. be added to decrease inflammation, however, steroids should
be used only in moderate amount as it delays absorption of
Management lens material.36
Phacolytic glaucoma is an emergency and initial control of Surgical treatment: If pressures are not controlled medically,
IOP by medical therapy followed by cataract extraction is the surgical removal of lens material should be done.
the management of choice.
Medical therapy: The IOP can be lowered by hyperosmotic Phacoanaphylactic Glaucoma
agents, carbonic anhydrase inhibitors and topical beta blockers. Rupture of lens capsule can lead to intraocular inflammation
Topical corticosteroids can be used to decrease the in individuals who are hypersensitive to lens protein. This is
inflammatory component. also known as “endophthalmitis phacoanaphylactica”. It was
Surgical treatment: Extracapsular cataract extraction with first reported by Verhoeff and Lemoine in 1922.37
implantation of PCIOL shows good results. The anterior Clinical Features
chamber should be washed thoroughly to avoid postoperative
IOP rise. There is anterior uveitis which may be associated with
hypopyon. Keratic precipitates are present on the cornea.
Lens Particle Glaucoma Peripheral anterior and posterior synechia may be present.
Patient may develop pupillary block or chronic angle closure
It was once thought that primary toxicity of cataractous lens glaucoma. There is usually a preceding disruption of the lens
material caused an inflammatory reaction called phacotoxic capsule by cataract surgery or penetrating injury. The duration
uveitis and it leads to glaucoma. Subsequent studies did not of latent period and the severity of uveitis are not associated
support this concept that the liberated lens material is toxic.35 with the quantity of free lens material.
This term has been proposed for cases when lens particle
and debris are liberated in the anterior chamber after Mechanism of Glaucoma
disruption of lens capsule.36
Phacoanaphylaxis represents an immune complex disease that
Clinical Features develops when normal tolerance to lens protein is lost, rather
than a cell mediated rejection of foreign tissue.38 Glaucoma
It is typically associated with disruption of the lens capsule.
can also develop due to accumulation of inflammatory cells
Cortical lens material is seen in the anterior chamber with
which block the trabecular meshwork.
heavy flare and cellular reaction. Corneal edema may be
present if IOP is very high. Angles are open on gonioscopy Differential Diagnosis
and lens material may be seen in the angle.
Other forms of uveitis especially sympathetic ophthalmia,
phacolytic or lens particle glaucoma may mimic this condition.
The lens material obstructs the trabecular meshwork.33 Other Management
mechanisms may be associated with inflammation, due to Medical therapy: Typically the uveitis does not respond to topical,
surgery, trauma or retained lens material. subconjunctival or systemic steroids.39
874 Glaucoma
Surgical treatment: Surgical removal of residual lens material is procedures like trabeculectomy,41 cataract extraction,42 laser
required. The intraocular lens and the capsule can also be iridotomy,43 and YAG posterior capsulotomy.44 Rarely, it can
removed. Glaucoma can be controlled by topical beta blockers, occur spontaneously, without any previous history of
carbonic anhydrase inhibitors and hyperosmotics if IOP is intraocular surgery.
very high.
Clinical Features
Phacomorphic Glaucoma
The patients typically have shallow or flat anterior chamber,
Reduction in the anterior chamber angle due to swollen or and high IOP following an incisional surgery.
intumescent lens in advanced cataract which leads to increase
in the IOP is known as phacomorphic glaucoma. Differential Diagnosis
Clinical Features Choroidal Detachment
The lens appears pearly white with aqueous filled spaces or It commonly occurs after filtration procedure. The anterior
vacuoles inside the lens. The anterior chamber is shallow as chamber is shallow but IOP is low. Indirect ophthalmoscopy
compared to the other eye and the angles appear closed on shows elevated choroid in the periphery.
gonioscopy. Corneal edema, and conjunctival hyperemia are
noted if IOP is very high. Pupillary Block
Mechanism of Glaucoma Pupillary block can closely mimic malignant glaucoma. Patent
peripheral iridectomy rules out pupillary block. The anterior
Angle closure may be caused by pupillary block mechanism chamber is shallow in the periphery in pupillary block whereas
or by forward displacement of the lens iris diaphragm. in malignant glaucoma it is uniformly shallow. Ultrasound
biomicroscopy can be a useful diagnostic tool.45
Management
Medical therapy: The IOP can be controlled by hyperosmotic Suprachoroidal Hemorrhage
agents, carbonic anhydrase inhibitors and topical beta blockers. This entity is characterized by shallow or flat anterior chamber
Surgical treatment: Cataract extraction with intraocular lens and elevated intraocular pressure. On indirect ophthalmoscopy
implantation is the treatment of choice. examination, the choroidal elevation are dark reddish.
Ultrasonography will differentiate choroidal detachment from
MALIGNANT GLAUCOMA suprachoroidal detachment.
Malignant glaucoma is the term used for a condition having Management
high IOP and shallow to flat anterior chamber, typically after
an incisional surgery. Other terms used for this condition are Medical Therapy
“ciliary block” glaucoma or “aqueous misdirection syndrome”. The mydriatic-cycloplegic drops form the mainstay of medical
As it responds poorly to conventional treatment, it has been treatment. Initial treatment should be started with one percent
termed “malignant” glaucoma. atropine four times a day and ten percent phenylephrine four
times daily. Along with mydiatric-cycloplegic drops, 0.5 percent
Mechanism of Glaucoma timolol maleate twice daily, oral acetazolamide 500 mg twice,
Shaffer proposed that aqueous is misdirected posteriorly into oral glycerol 1.5 to 2 ml/kg/day is administered in two to
the vitreous cavity. What triggers this misdirection of aqueous three divided doses. The entire regimen is continued till
is not exactly known. Relative block to anterior movement IOP decreases and anterior chamber deepens. Gradually
of aqueous near the lens equator, ciliary processes and anterior hyperosmotic agents, oral acetazolamide, timolol maleate and
vitreous face may be the starting event. phenylephrine are discontinued.
Predisposing Conditions Laser Treatment

Classically malignant glaucoma follows an incisional surgery Nd:YAG laser hyaloidotomy: Laser can be used to disrupt
like peripheral iridectomy for angle closure glaucoma,40 other posterior capsule as well as anterior vitreous face. This
modality is mainly used for aphakic and pseudophakic 1. Genetic linkage: Patients with retinal detachments have larger
malignant glaucoma. There is immediate formation of anterior cup-to-disc diameter ratios and a higher prevalence of
chamber as the laser treatment establishes a communication corticosteroid responsiveness than would be expected in
between anterior and posterior chambers. the general population.48 Myopia is also associated with
glaucoma and retinal detachment. Patients with pigmentary
Argon laser treatment of ciliary processes: This may be tried in
glaucoma have an increased incidence of retinal
some cases where medical treatment fails. Two to four ciliary
detachment.49
processes should be lasered. The size of ciliary processes
2. Common underlying mechanism: Retinal detachment and
may shrink with laser treatment. Medical treatment has to be
glaucoma can be associated through a common underlying
continued simultaneously.
mechanism such as trauma, cataract surgery with vitreous
loss, proliferative retinopathy, or retinopathy of
Surgical Treatment
prematurity.
Pars plana vitrectomy should be done in cases where medical 3. Treatment for retinal detachment may cause glaucoma: Therapeutic
and laser therapy is unsuccessful. Vitreous cavity is entered agents and interventions such as corticosteroids, scleral
with a knife and suction cutter without infusion to remove buckling procedures, extensive retinal photocoagulation,
fluid and formed vitreous. This procedure is continued till and vitrectomy (with silicone oil (Fig. 9.3.4.3) or intraocular
the globe is soft. A large air bubble is injected to deepen the gas injection) are all capable of producing glaucoma.
anterior chamber. Atropine is instilled at the end of surgery 4. Treatment of glaucoma may cause retinal detachment: Strong
and continued for months in the postoperative period.46 miotic agents are capable of inducing retinal tears, vitreous
hemorrhage, and retinal detachment. There is suggestive
Fellow Eye evidence that standard cholinergic drugs can also cause
Nd:YAG laser iridotomy must be done in the fellow eye before retinal detachment.50
surgical intervention as patients who develop malignant
glaucoma in one eye are likely to develop it in the other Clinical Features
eye.47 Miotic therapy should be avoided in the fellow eye. Schwartz Syndrome
GLAUCOMA ASSOCIATED WITH In a minority of cases, retinal detachment causes a peculiar

RETINAL DISORDERS increase in IOP that is referred to as Schwartz syndrome.51 In
this syndrome, rhegmatogenous retinal detachment is
Several types of glaucoma are associated with diseases of associated with elevated IOP, diminished outflow facility, open
the retina. The most common of these is neovascular angles, and cell and flare in the aqueous humor. When the
glaucoma, which is usually associated with one of several retinal detachment is repaired, the IOP and outflow facility
retinal disorders, although some cases are associated with return to normal.51 It has been postulated that the glaucoma
other ocular or extraocular conditions. Retinal detachments
and a variety of less common disorders of the retina, vitreous,
or choroid may cause or occur in association with various
forms of glaucoma.
Neovascular Glaucoma
Most cases of rubeosis iridis are preceded by a hypoxic disease
of the retina. Diabetic retinopathy and occlusion of major
retinal vessels account for more than one half of these, with
the former possibly being slightly more common.
Retinal Detachment and Glaucoma

Retinal detachment and glaucoma are associated in a variety Fig. 9.3.4.3: Emulsified silicone oil globules
of ways, including the following: in the anterior chamber angle
876 Glaucoma
is related to angle recession, inflammation, pigment granules Surgical Management

released by the retinal pigment epithelium, and
glycosaminoglycans synthesized by the photoreceptors.52 With active rubeosis, however, standard filtering surgery has
a low chance of success, and a cyclo-destructive procedure
Neovascular Glaucoma may be preferable.
Table 9.3.4.1 presents factors that predispose to
The preglaucoma stage is characterized by normal IOP, unless neovascular glaucoma.
preexisting chronic open-angle glaucoma is present. Slit-lamp
biomicroscopy early in the disease reveals dilated tufts of
Table 9.3.4.1: Diseases in which
preexisting capillaries and fine, randomly oriented vessels on
rubeosis has been reported
the surface of the iris near the pupillary margin and is first
Retinal Ischemic Diseases
seen on the peripupillary iris. Gonioscopy may reveal a variable Diabetes
amount of angle neovascularization which is characterized Central retinal vein occlusion
Ocular ischemic syndrome/carotid occlusive disease
by single vascular trunks crossing the ciliary body band and Central retinal artery occlusion
scleral spur and arborizing on the trabecular meshwork. Retinal detachment
Leber's congenital amaurosis
Coats’ disease
Retinal Detachment Surgery and Glaucoma Eales disease
Sickle cell retinopathy
Elevated intraocular pressure in early postoperative period Retinal hemangioma
Persistent hyperplastic primary vitreous
of retinal detachment repair. Generally, angles are open but Norrie’s disease
an element of pupillary block can be associated with silicone Wyburn-Mason
Carotid-cavemous fistula
oil induced glaucoma, in eyes which have undergone vitreo Dural shunt
retinal surgery. Stickler’s syndrome
X-linked retinoschisis
Takayasu’s aortitis
Management Juxtafoveal telangiectasis
Surgically induced
Medical Therapy Carotid endarterectomy
Cataract extraction
Pars plana vitrectomy/lensectomy
When the IOP begins to rise, medical therapy is usually Silicone oil
required and is frequently sufficient to control the pressure Scleral buckle
Neodymium: yttrium-aluminium-gamet capsulotomy
during the open angle glaucoma stage of neovascular Laser coreoplasty
glaucoma. Prostaglandin analogs are rarely effective because Tumors
access to the uveoscleral route is generally compromised from Iris melanoma, hemangioma, metastatic lesion
angle closure, and there is a theoretical concern regarding Ciliary body: ring melanoma
Retina: retinoblastoma, large cell lymphoma
exacerbation of inflammation. Miotics are not helpful in the Choroid melanoma
acute situation and should usually be avoided because they Conjunctiva: squamous cell carcinoma
may increase the inflammation and discomfort. Topical Radiation

External beam
corticosteroids may be useful in minimizing the inflammation Charged particle: proton, helium
and pain. Plaques
Photoradiation
Laser Treatment
Inflammatory diseases
Uveitis: chronic iridocyclitis, Behcet’s disease
Vogt-Koyanagi-Harada syndrome
Ablation of the peripheral retina with laser photocoagulation Syphilitic retinitis
is the first line of therapy for most cases of neovascular Sympathetic ophthalmia
Endophthalmitis
glaucoma. With regard to central retinal vein occlusion, it is
Miscellaneous
apparently better to follow patients closely and intervene Vitreous wick syndrome
promptly with panretinal photocoagulation at the early signs Interferon alpha
of rubeosis. Even in the latter situation, panretinal (This table was published in Ophthalmology 2001; Vol 108, Au: Sivak-
photocoagulation may be useful in reducing anterior segment Callcott JA, et al. Evidence-based recommendations for the diagnosis and
treatment of neovascular glaucoma, p 1767–1778. Copyright Elsevier.
neovascularization before intraocular surgery. Copyright permission January 2011.)
GLAUCOMA ASSOCIATED WITH • With a ciliary body melanoma, a distorted pupil or vision
INTRAOCULAR TUMORS change from lenticular astigmatism may occur
• With choroid melanoma, the visual symptoms may be
Intraocular tumors are rare causes of glaucoma. In cases of
decreased vision or a change in the peripheral vision,
unexplained glaucoma, the possibility of an ocular tumor must
depending on the location of the tumor
be considered because of the dire consequences of a missed
• Melanocytoma of the optic disk is usually asymptomatic
diagnosis. The epidemiology, prognosis, and mechanism of
action depend on the specific tumor type. Diagnosis is assisted by gonioscopy, indirect ophthalmoscopy,
and ultrasonography. Clinical scenarios depend on tumor
Mechanism of Glaucoma location. Differentiation between benign and malignant
processes can be assisted by MRI and ultrasound evaluation.
Different mechanisms by which ocular tumors can cause For tissue diagnosis, fine-needle biopsy, aqueous aspiration,
glaucoma are: or excisional biopsy is needed. Diagnosis of iris nevus is aided
• Direct invasion by fluorescein angiography of iris, aqueous aspiration, or
• Pigment dispersion biopsy.
• Melanophagic Table 9.3.4.2 enumerates some of the causes of
• Hemolytic neovascular glaucoma.
• Uveitic
• Secondary angle closure Treatment
• Iris neovascularization
• Anterior displacement of lens-iris diaphragm Medical Management
• Choroidal detachment Glaucoma management itself begins with medical therapy,
• Suprachoroidal hemorrhage concurrent with treatment of the intraocular tumor through
surgery, radiation, chemotherapy, or a combination of these
Epidemiology
Table 9.3.4.2: Intraocular tumors causing elevated
Although individual rates vary, Shields et al showed a five intraocular pressure
percent incidence of increased intraocular pressure due to Iris
intraocular tumors in a series of 2597 patients with ocular • Nevus
tumors.53 This is in contrast to 50 percent incidence of • Melanocytoma
• Iris pigment epithelium adenoma
increased intraocular pressure in eyes enucleated for tumors.
• Malignant melanoma
Incidence of increased intraocular pressure is also dependent • Metastatic tumors
on location. Reports indicate a 17 percent incidence of Ciliary body
glaucoma in ciliary body melanoma, seven percent in iris • Medulloepithelioma
melanoma, and two percent in choroidal melanoma. Given • Melanocytoma
the relative infrequency of intraocular tumors, this condition • Metastatic
is a rare event. Choroid
Clinical Features • Metastatic
Optic nerve
Symptoms vary depending on the location of the ocular • Melanocytoma
tumor.54 • Metastatic
• Glaucoma symptoms are dependent on the speed at which Retina
the pressure rises. With acute glaucoma from angle closure, • Retinoblastoma
decreased vision, halos around lights, ocular pain, and Metastatic carcinoma
nausea may be present. With chronic glaucoma with Others
• Leukemia
progressive angle closure or open angles, no ocular • Lymphoma
symptoms may be present • Phakomatoses
• With iris melanoma, a hyperchromic heterochromia may • Multiple myelomas
• Juvenile xanthogranuloma
be present
878 Glaucoma
treatments.54 Anti-vascular endothelial growth factor (anti- Mechanism of Glaucoma

VEGF) therapy may be helpful in those cases where
Inflammation can produce glaucoma through a variety of
neovascularization plays a role in the pathogenesis of the
mechanisms, including:
glaucoma.55 In systemic lymphoma, leukemia, and metastatic
• Increased viscosity of aqueous humor and debris
malignancies, treatment often include systemic chemotherapy
• Swelling and dysfunction of the trabecular meshwork
and radiation, with current regimens favoring the use of
• Liberation of active substances such as prostaglandins
chemotherapy first.
• Scarring of the outflow channels
• Development of a cuticular endothelial membrane over
Surgical Treatment
the angle
• For smaller tumors, observation is warranted until growth • Neovascularization
is documented • Elevation of episcleral venous pressure
• Iridectomy or iridocyclectomy are options for removing • Forward displacement of the lens-iris diaphragm (uveal
smaller tumors effusion)
• For anterior tumors, argon laser trabeculopexy on the • Pupillary block
tumor-free areas is an option • Formation of peripheral anterior synechiae
• More posterior tumors may require local resection,
photocoagulation, or episcleral radiopaque therapy. Causes of Uveitic Glaucoma
Enucleation or exenteration is an option
• Glaucoma is associated with advanced stages of Many specific uveitic entities may lead to the development
retinoblastoma, and enucleation may need to be discussed. of glaucoma. Some of the more common syndromes are
Other therapeutic options include radiotherapy, listed below.
cryotherapy, and photocoagulation. Any intervention must
be tempered by the risk of extraocular spread Juvenile Rheumatoid Arthritis (JRA)
• Glaucoma is a common complication of chronic uveitis
GLAUCOMA ASSOCIATED WITH
in patients with JRA and most frequently is caused by
OCULAR INFLAMMATION
progressive closure of the angle by peripheral anterior
In 1813, Joseph Beer first reported the association of uveitis synechiae (PAS)
and glaucoma, describing it as arthritic iritis followed by • Since the uveitis is frequently treated with prolonged
glaucoma and blindness. In 1891, Priesley Smith proposed topical corticosteroids, steroid-induced glaucoma may
the first modern classification of uveitic glaucoma. Later, occur. The reported incidence of glaucoma varies from
specific types of uveitic glaucoma were described by Fuchs 14 to 22 percent.
in 1906 (Fuchs heterochromic uveitis) and Posner and
Schlossman in 1948 (glaucomatocyclitic crisis).56 Fuchs Heterochromic Iridocyclitis (FHI)
Elevated IOP can occur with any type of ocular
inflammatory disease but is more common in chronic forms • The glaucoma associated with FHI resembles primary
than in the acute forms. In most ocular inflammatory open-angle glaucoma (Fig. 9.3.4.4)
diseases, aqueous humor formation is reduced and IOP is • Gonioscopic evaluation may reveal multiple fine blood
low.56 If outflow facility is reduced as well, however, IOP vessels, arranged either radially or concentrically in the
can be elevated. Because of this dual involvement of aqueous trabecular meshwork
humor inflow and outflow, eyes with active inflammatory • Cataract is a constant feature of FHI, whereas glaucoma
disease often suffer wide swings of IOP, and glaucoma may has been reported to occur in 6 to 47 percent of cases
be missed if only occasional pressure measurements are • Low-grade inflammation does not need treatment with
made. anti-inflammatory or immunosuppressive agents.
Epidemiology Posner-Schlossman Syndrome

The prevalence of uveitis has been estimated at 38 to 730 This is characterized by a number of unusual features,
people per 100,000 worldwide. Approximately, 20 percent including unilateral involvement, recurrent attacks of often
of uveitis patients develop glaucoma. very mild cyclitis, marked elevation of IOP, open angle, and
Management
Medical Therapy
The treatment of glaucoma associated with ocular
inflammatory disease depends on the underlying conditions.
In most situations, inflammation is suppressed by a combi-
nation of topical, systemic, and periocular corticosteroids.
During this treatment, corticosteroid induced IOP elevations
may occur. Other medications employed to reduce
inflammation include cycloplegic agents, non-steroidal anti-
inflammatory drugs, and immuno-modulators such as
methotrexate, azathioprine, and chlorambucil. Elevated IOP
is generally managed by topical and systemic glaucoma
medications. Miotics are usually avoided because they increase
pain and congestion and may promote the development of
posterior synechiae. Prostaglandins are used with caution in
Fig. 9.3.4.4: Fuchs heterochromic iridocyclitis
uveitic patients because they might exacerbate inflammation.
Laser Treatment
occasional heterochromia.57,58 The condition typically affects Argon laser trabeculoplasty: This is not very helpful in eyes with
individuals aged 20 to 50 years and resolves spontaneously active inflammation. It may cause mild, acute anterior uveitis
regardless of treatment. in some patients and may also lead to peripheral anterior
synechiae.
Herpetic Uveitis
Surgical treatment: Surgery should be avoided in eyes with active
Herpes simplex: Disciform keratouveitis and necrotic stromal inflammation, but if a filtering procedure is required,
keratitis are associated more commonly with elevated IOP inflammation should be suppressed by topical and systemic
than epithelial keratitis. corticosteroids. Mitomycin-C59 or 5-fluorouracil (5-FU)60 are
The elevated IOP may be caused by trabeculitis, often useful in this situation, as are tube-shunt devices such
inflammatory obstruction of the trabecular meshwork, and as the Ahmed or Molteno valve. As a last resort, cycloablative
angle closure in severe keratouveitis. The management of techniques can be employed. Diode or Nd:YAG laser
elevated IOP is initially directed towards controlling the viral cyclophotocoagulation can be used to destroy the secretory
replication and inflammation. ciliary epithelium, leading to decreased aqueous production.
Unfortunately, cycloablative procedures often exacerbate the
Varicella zoster: IOP elevation and glaucoma are believed to
inflammation.
be caused by decreased outflow facility due to trabecular
obstruction from inflammatory debris, trabeculitis, and
GLAUCOMA ASSOCIATED
damage to the trabecular meshwork by recurrent inflam-
WITH TRAUMA
mation. Treatment with systemic acyclovir when the
cutaneous lesions are still active appears to reduce the risk Elevated IOP is frequently seen after trauma to the eyes.
of elevated IOP. Mostly it is seen in young patients. 61 Males are more
affected.62 Sports and domestic accidents account for almost
Clinical Features 2/3rd of these injuries. Elevated IOP can occur either early
(acute) or late (chronic) following blunt injury, penetrating
Symptoms with acute iridocyclitis may include blurred
injury, chemical burns, radiation therapy and electrical injuries.
vision, ocular pain, brow ache, and other ocular
disturbances. Signs of specific uveitic forms as described
Non-penetrating Trauma
above can be noted. Laboratory and imaging investigations
should be tailored to appropriate studies based on both It occurs mostly after injury with a blunt object which
the history and the physical findings. transiently displaces the cornea and anterior sclera posteriorly
880 Glaucoma
with compensatory expansion at the equator.63 There are circulating cells in the aqueous, total hyphema or an eight ball
seven anterior tissue rings described by Campbell63 which hyphema. The elevation of IOP associated with traumatic
may tear after blunt injury and should be looked for after hyphema has been correlated to the extent of the
blunt trauma. hemorrhage.64
• Sphincter pupillae (pupillary sphincter tear) Mechanism of glaucoma: The erythrocytes and the blood
• Iris root (Iridodialysis) products cause mechanical obstruction of the trabecular
• Anterior ciliary body (Angle recession) meshwork thus increasing the IOP. Pupillary block can also
• Ciliary body attached to the scleral spur (Cyclodialysis) occur due to the blood clot in cases with large hyphema.
• Trabecular meshwork (Trabecular dialysis)
• Lens zonules (Phacodonesis) Management: The goal of treatment is to prevent rebleed and
• Retinal attachments to the ora serrata (retinal dialysis and to control the IOP.
detachment) Hyphema resorption: Most patients can be treated on an
outpatient basis. Patient should be advised to restrict activity
Intraocular Hemorrhage and drugs with antiplatelet activity should be avoided. Systemic
Hyphema: It is most commonly seen after blunt or steroids are recommended but the role is controversial.
penetrating injury occurring in 81 percent of eyes reported Aminocaproic acid (a fibrinolytic agent) has been proven to
in one series.61 decrease rebleeding in some reports,65 but due to frequent
side effects and tendency to rebleed after stopping, it is rarely
Clinical features: It is characterized by red blood cells in the used nowadays.
anterior chamber (Fig. 9.3.4.5). It can present in the form of Treatment of elevated IOP: Elevated IOP can respond to topical
antiglaucoma drugs. If pressures are not controlled medically
and if there is chance of optic nerve damage or corneal
blood staining, the surgical drainage of hyphema is
recommended.
Ghost Cell Glaucoma: Following vitreous hemorrhage, the
degenerated erythrocytes (Ghost cell) migrate in the anterior
chamber through a disrupted anterior hyloid face and obstruct
the angle. It is characterized by khaki colored cells in the
aqueous and vitreous. The IOP can be normal to very high
depending on the number of ghost cells. There can be pain,
nausea, corneal edema and conjunctival congestion. Angle
appears open on gonioscopy and some times khaki colored
cells are seen especially inferiorly. Pseudo hypopyon66 may
be seen. Diagnosis can be confirmed by anterior chamber
paracentesis and cytological examination. Increase in IOP
can be controlled medically. Resistant cases may require
anterior chamber wash and/or pars plana vitrectomy to
remove the remaining reservoir of ghost cells.
Hemolytic Glaucoma: Rise in IOP occurs with days to weeks
after large intraocular hemorrhage. Reddish brown blood cells
are evident in the aqueous on slit-lamp examination. The
angles are open on gonioscopy and reddish brown pigment is
seen on the trabecular meshwork, especially inferiorly.67 There
is obstruction of the trabecular meshwork by macrophages
laden with pigments, erythrocytes and debris67 leading to
increase in IOP. Diagnosis can be confirmed by cytological
Fig. 9.3.4.5: Post traumatic hyphema examination which characteristically shows macrophages
successful. Nd:YAG laser trabeculopuncture has been

proposed as a surgical management but with mixed results.71,72
Filtering procedure is less frequently successful in patients
with angle recession, so wound healing modulation should be
considered even with initial procedures.73
Penetrating Trauma
Initially, IOP is low due to open wound or associated
iridocyclitis but after wound closure it may rise.
In the initial phase after injury, IOP may be elevated due to
inflammation, hyphema or angle closure due to swollen,
disrupted lens. In some cases, a cyclitic membrane may develop
Fig. 9.3.4.6: Angle recession as a result of inflammatory material. This membrane may
lead to closure of the angle or seclusion of the pupil.74
Prolonged intraocular retention of certain metallic foreign
containing golden brown pigment.67 Elevated pressure resolves body, may lead to delayed tissue alteration and thus delayed
spontaneously and responds to medical treatment. Resistant glaucoma.
cases may require anterior chamber wash or pars plana
vitrectomy. Management
Hemosiderotic Glaucoma: It occurs after long standing Proper treatment in the initial phase of injury may prevent
hemorrhage and is very rare. The hemoglobin is phagocytized development of glaucoma. This includes removal of portion
by the endothelial cells of the trabecular meshwork and the of incarcerated uveal tissue, aspiration of lens, if swollen or
iron liberated by the hemoglobin may cause siderosis of the disrupted, anterior vitrectomy, removal of foreign body and
trabecular meshwork,68 eventually leading to decreased meticulous closure of the wound. Corticosteroid therapy
aqueous outflow and increased IOP. avoids formation of cyclitic membrane and scarring in the
Angle Recession Glaucoma: Angle recession glaucoma anterior chamber and antibiotic prophylaxis is given to prevent
usually occurs years or even decades after blunt trauma. Some endophthalmitis.
studies have reported the development of delayed onset Anti glaucoma medication may be required to control
glaucoma in 6 to 20 percent of individuals with angle recession increased IOP, both during early and late phases. The drugs
of >180°angle.69 which reduce aqueous production are preferred. When medical
On gonioscopy, there is widening of the ciliary body band therapy is insufficient, filtering surgery should be recommended.
(characteristic of angle recession) and prominence of the
Chemical Burns
scleral spur (Fig. 9.3.4.6). There may be associated findings
like tear of the trabecular meshwork, iridodialysis or Acid and alkali burn of the eye may produce rapid, initial rise
cyclodialysis. of IOP. This is followed by return to normal or subnormal
pressure and then there is slower and sustained increase in
Mechanism of glaucoma: Scarring of ciliary body or trabecular
IOP. The mechanism of glaucoma is shrinkage of the cornea
meshwork tear leads to chronic obstruction in the aqueous
and sclera75 and increase in the uveal blood flow.76 In the
outflow.70 Another hypothesis is the formation of Descemet's
management, immediate ocular irrigation with copious fluids
like membrane which grows from cornea over the iridocorneal
and removal of any material retained in the cul-de-sac is
angle.70
recommended. Topical steroids are helpful to decrease
Management: High IOP can be controlled by beta blockers, inflammation. Antiglaucoma medication that decrease aqueous
alpha agonist and carbonic anhydrase inhibitors, although production is used. Miotics are usually avoided as they may
patients of angle recession do not respond well to standard aggravate anterior segment inflammation as well as contribute
antiglaucoma therapy. Laser trabeculoplasty is infrequently to formation of posterior synechiae.
882 Glaucoma
Thermal Burns History of steroid use, topical or systemic, is very

important for making the diagnosis of steroid induced
Transient rise in IOP is seen after accidental and therapeutic
glaucoma. Other clues for the diagnosis of steroid induced
electrical injuries such as electroshock or cardioversion.77,78
glaucoma can be posterior subcapsular cataract, ptosis,
The mechanism may be loss of iris pigment or venous dilation
and contracture of the extraocular muscles. Treatment is mydriasis and atrophy of eyelid skin. Intraocular pressure
seldom required because the increase in IOP is transient. elevation can occur weeks, months or years after the use of
corticosteroids. A number of factors like route of
administration, potency and frequency of application, and
Radiation Injury
steroid responsiveness determine the magnitude and time
Radiation therapy to structures near the eye may lead to taken for rise in IOP. The diagnosis is confirmed by the fact
increase in IOP. The possible mechanisms may be due to that IOP decreases when steroid is discontinued.
elevated episcleral venous pressure related to generalized
telangiectasia of the conjunctiva, neovascular glaucoma or Mechanism of Glaucoma
hemolytic changes associated with intraocular hemorrhage. Lysosomes in the trabecular meshwork regulate
In most of these cases, the visual prognosis is poor with both glycosaminoglycans (GAGs) metabolism. Corticosteroids
medical and surgical management. stabilize lysosomal membranes and this prevents
polymerization of GAGs. This accumulation of GAGs leads
STEROID INDUCED GLAUCOMA to decreased outflow. Steroid also prevents phagocytosis by
Steroid induced glaucoma typically develops due to topical trabecular endothelium and leads to accumulation of
use of corticosteroids. Occasionally, systemic administration trabecular debris.
of corticosteroids may lead to development of this glaucoma.
Prevention
Topical steroids in the form of creams, ointments on eyelids,
face or other sites can sometimes cause elevated IOP. Systemic, To avoid loss of vision from steroid-induced glaucoma,
periocular or inhaled steroids are responsible for rise in IOP physicians must know how to prevent or minimize the chances
occasionally. of its occurrence. This requires close attention to the patient's
history and to the selection and use of steroids.
Steroids Responders
Patient selection: Individuals with POAG or a family history of
79 80
Becker and Armaly demonstrated that a high percentage the disease are more likely to respond to chronic steroid
of patients with primary open angle glaucoma (POAG) showed therapy with a significant rise in IOP. High myopes,82
marked rise in IOP in response to topical corticosteroids diabetics, 83 and patients with connective tissue diseases
given for four to six weeks as compared to the general (especially rheumatoid arthritis)84 have a similar predisposition.
population. Becker divided steroid responders into three
Relative Pressure-inducing Effects of Topical Steroids: Although topical
groups: low, intermediate and high responders.
corticosteroids are more likely to cause an elevation of the
Low responders: Manifest with virtually no change in IOP. IOP than are systemic steroids, the topical route of
Intermediate responders: Display a moderate elevation of IOP administration is still generally preferred for ocular conditions.
(22–30 mm Hg). In general, the pressure inducing effect of a topical steroid is
proportional to its anti-inflammatory potency. Betamethasone,
High responders: Exhibit a marked elevation of IOP dexamethasone, and prednisolone are commonly used, potent
(>30 mm Hg). corticosteroids with a significant tendency to produce steroid-
induced glaucoma. However, the pressure inducing potency
Clinical Presentation is related to the dosage of the drug. A group of drugs closely
The clinical presentation in adults is similar to POAG. It is related to progesterone has been shown to have useful anti-
characterized by elevated IOP, optic disc changes, visual field inflammatory properties with significantly less pressure-
loss and open angles on gonioscopy. In children, steroid induced inducing effects. Fluorometholone (0.25%) is less likely to
glaucoma may present like congenital glaucoma with increase IOP in corticosteroid responders than 0.1 percent
edematous enlarged cornea, photophobia and tearing.81 dexamethasone.85
Management 13. Migliazzo CV, et al. Long term analysis of pigmentary dispersion
and pigmentary glaucoma, Ophthalmology 1986;93:1528.
Discontinuation of the Steroid 14. Lindberg JG. Kliniska undersokningar over depigmentering av
pupillarranden och genomlysbarket av iris vid fall av alderstarr
Discontinuation of the steroid is to be done and often, is all
samit i normala ogon hos gamla personer (Clinical studies of
that is required. The chronic form is said to normalize in one depigmentation of the pupillary margin and transillumination of
to four weeks, whereas the acute form typically resolves iris in cases of senile cataract and also in normal eyes in the aged),
within days of stopping the steroid.86 In rare cases, the doctoral thesis, Helsingfors 1917.
glaucoma may persist despite stopping all steroids. 15. Bartholomew RS. Pseudocapsular exfoliation in the Bantu of
south Africa, I . Early or pregranular clinical stage, Br J Ophthalmol
Medical Therapy 1971;55:693.
16. Tarkkanen A. Pseudoexfoliation of lens capsule, Acta Ophthalmol
The medical management of these cases is essentially the Suppl (Copenh) 1962;71:1.
same as for POAG. 17. Taylor HR. Pseudoexfoliation, an environmental disease? Trans
Ophthalmol Soc UK 1979;99:302.
18. Faulkner HW. Pseudoexfoliation of the lens among the Navajo
Surgical Treatment
Indians, Am J Ophthalmol 1971;72:206.
In all cases where depot steroid appears to be responsible for 19. Forsius H. Prevalence of pseudoexfoliation of lens in Finns,
the rise in IOP, the optimal treatment, if medical management Lapps, Icelanders, Eskimos and Russians, Trans Ophthalmol Soc
UK 1979;99:296.
fails, is to excise the depot steroid. Trabeculectomy or seton 20. Sveinsson D. The frequency of senile exfoliation in Iceland, Acta
implantation is indicated when the glaucoma is uncontrolled Ophthalmol (Copenh) 1974;52:596.
on maximum tolerable medication. 21. Gradle HS. Sugar HS, Glaucoma capsulare, Am J Ophthalmol
1947;30:12.
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syndrome and pigmentary glaucoma. A prospective study of aqueous. Am J Ophthalmol 1976;88:1026.
natural history, Arch Ophthalmol 1986;104:211. 31. Brooks AMV, Drewe RH, Grant GB, et al. Crystalline nature of
10. Potash SD, et al. Ultrasound biomicroscope in pigment dispersion the iridescent particles in hypermature cataracts. Br J Ophthalmol
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11. Campbell DG. Improvement of pigmentary glaucoma and healing 32. Smith ME, Zimmerman LE. Contusive angle recession in
of transillumination defects with miotic therapy, Invest phacolytic glaucoma, Arch Ophthalmol 1965;74:799.
Ophthalmol Vis Sci 23 (Suppl) 1983;173. 33. Epstein DL, Jedziniak JA, Grant WM. Obstruction of aqueous
12. Ritch R, et al. Argon laser trabeculoplasty in pigmentary glaucoma, outflow by lens particles and by heavy molecular weight soluble
Ophthalmology 1993;100:909. lens protein. Invest Ophthalmol Vis Sci 1978;17:272.
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molecular -weight soluble protein in aqueous humor in human Practice of Ophthalmology 1999.
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37. Verhoeff FH, Lemoine AN. Endophthalmitis phacoanaphylactica. 57. Hollwich F. Clinical aspects and therapy of the Posner-
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Ophthalmic Surg 1986;17:234. 60. Patitsas CJ. Glaucoma filtering surgery with postoperative 5-
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following cataract extraction and IOL implant, Ophthalmic Surg Ophthalmol 1969;8:290.
1982;13:713. 63. Campbell DG. Traumatic glaucoma. In Shingleton BJ, Hersh PS,
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46. Simmons RT, Maestro FA. Malignant glaucoma: In: Ritch R, glaucoma, Am J Ophthalmol 1976;81:441.
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47. Saunders PP, et al. Bilateral malignant glaucoma, Can J Ophthalmol 68. Vannas S. Hemosiderosis in eyes with secondary glaucoma after
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1982. the anterior chamber angle secondary to contusion, Am J
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51. Schwartz A. Chronic open-angle glaucoma secondary to glaucoma with traumatic angle recession, Grafes Arch Clin Exp
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experimental alkali burns and prostaglandin administration. Arch angle glaucoma. Am J Ophthalmol 1966;62:1039.
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77. Berger RO. Ocular complication of electroconvulsive therapy, Am J Ophthalmol 1971;71:1
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Invest Ophthalmol 1965;4:198. responders. Am J Ophthalmol 1986;102:159.
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Ophthalmol Vis Sci 1985;26:170.
Chapter 9.4
MANAGEMENT OF GLAUCOMA
9.4.1 Medical Management of Glaucoma

Geetha Srinivasan
Glaucoma is one of the leading causes of blindness worldwide. Role of Diurnal Variation or Phasing
The primary goal of treatment in glaucoma is to preserve
Assessment of IOP in a phased manner, at three hourly
the patient's visual function and quality of life.
intervals throughout the day (and night if feasible), is an
Despite various theories about the etiolog y and
ideal prerequisite in all glaucoma patients or suspects. This
pathomechanism, the cornerstone of therapy in glaucoma
not only helps establish the peak IOP, but also helps determine
still remains adequate control of intraocular pressure (IOP).
the amount of fluctuation in IOP. Fluctuation in IOP is said to
While there are numerous surgical procedures that facilitate
be more detrimental to the optic nerve head than a high
proper aqueous outflow and thus reduce IOP, the enlarging
pressure per se. Phasing helps in deciding the amount of IOP
armamentarium of anti-glaucoma drugs in recent times has
reduction desired in a particular patient and hence the drug
made medical therapy the first line of management.
of choice. It also tells the time point, if any, of peak IOP
The introduction of newer classes of IOP lowering drugs
thus enabling tailoring of medication accordingly.
in the past decade, has not only revived medical therapy in a
big way, but has also changed the medical approach to a case
Importance of Central Corneal Thickness
of glaucoma. Topical β blockers are no longer the only choice
for first line therapy, and the use of fixed dose combination It is well established that Goldmann applanation tonometry
therapy and more effective single dose therapies, has increased records falsely high IOP in thick corneas and falsely low
potential compliance and hence visual benefit to the patient. IOPs in thin corneas. This should be corrected for, while
Medical therapy should be tried in all patients of glaucoma estimating IOP in an individual. There are various correction
who tolerate therapy and are compliant with it. This, of course, factors including the original one by Ehlers. The evaluation
precludes patients with very high levels of IOP, which could of corrected IOP is especially important in patients with
cause, severe damage to optic nerve head function. normal tension glaucoma, ocular hypertension and those
showing evidence of progression.
APPROACH TO MEDICAL MANAGEMENT
Establishing Target IOP
Once the decision has been taken to treat a case of glaucoma
or a suspect, the physician has only one modifiable established Before considering individual groups of drugs to decrease
risk or causal factor, intraocular pressure. The mainstay of IOP, the concept of target IOP needs to be understood. The
glaucoma treatment is 24-hour IOP control. term target IOP is used quite often loosely. Although it is a
Management of Glaucoma 887
term used and accepted widely, it should be understood by Choice of Therapy

the treating physician that there is no clear consensus, either
While this is largely based on the requisite target IOP for an
on its definition or its calculation. This terminology was
individual patient, this may have to be modified keeping in
popularized through the American Academy of
mind the patient’s lifestyle and occupation, as well as the
Ophthalmology Preferred Practice Plan for open angle
patient’s affordability.
glaucoma, wherein they considered the calculations of two
IOP medications that minimally affect blood pressure
National Eye Institute sponsored trials (Advanced Glaucoma
are theoretically advantageous, in that they do not alter optic
Intervention and Collaborative Initial Glaucoma Treatment).
nerve head perfusion.
The limited definition of target IOP in these two groups of
As a general rule if a 20 percent IOP reduction is aimed
patients may not be adequate for clinical practice. It has to
for, a β blocker is chosen, if a 30 percent reduction is desired
be individualized to suit a particular patient.
a prostaglandin analog is preferred and if more than 30
Target Pressure percent reduction is needed either a prostaglandin analog
alone or a beta blocker in combination with either an α2
Target pressure is defined as “an IOP low enough to limit agonist or carbonic anhydrase inhibitor is preferred.
progression of visual field loss to a rate that will preserve the The ocular and systemic side effects and contraindications
patient's visual function and maintenance of their individual would of course have a bearing on the choice of therapy.
patterns of daily living.” It is apparent from this definition
that there can be no definite arbitrary target IOP for a First Line Therapy
particular baseline IOP. The influence of age, life expectancy,
severity of preexisting visual field defect as also risk factors Timolol maleate continues to be the first line of treatment in
like high myopia, central corneal thickness, family history, a case of glaucoma even today. However, because latanoprost
one eyed status and race (African heritage) and iris was found to be more efficacious than timolol maleate, it has
pigmentation cannot be overruled in determining the target replaced timolol maleate as the drug of choice for mono-
IOP, for a particular individual. So, as a broad guideline, if therapy in many countries. The only point disfavoring
there is early or no visual field damage the IOP should be prostaglandin (PG) analog is the cost of therapy.1
brought down to 75 to 80 percent of the baseline IOP, 70 to
75 percent in moderate perimetric damage and an IOP of ≤ Second Line Therapy
15 mm Hg in advanced damage. This of course should be in In the United States, second-line therapy is basically a personal
consideration with the other factors mentioned above. choice, with beta blockers being the most prescribed (46%),
As explained above, target IOP is not one fixed followed by prostaglandins (23%), dorzolamide/timolol fixed
standardized number for a particular baseline IOP. Further, combination (12%), dorzolamide (11%), and brimonidine
treated IOP may not necessarily be within the statistically (9%).
normal range though the decrease may be sufficient to prevent While Shin and associates2 showed in a multicenter,
further optic nerve damage. However as a broad guideline, prospective study that the latanoprost/timolol fixed
in current protocols it is recommended that the initial target combination was more efficacious than dorzolamide/timolol
IOP should be ≥20 percent lower than the baseline IOP. This fixed combination at certain specific time points, as well as
should be used as a guideline, keeping in mind that it must be the mean IOP reduction, Konstas et al3 did not find any
modified based on perimetric and/or optic nerve head difference in the efficacy of the two combinations.
changes and risk factors. In patients with other risk factors,
the aim should be a lower target IOP and, consequently, a
Unilateral Drug Trial
larger reduction of IOP. Another important fact to be
remembered is that target IOP may need adjustment during Once initiated, glaucoma therapy is usually lifelong. So, it is
the course of the disease. If the visual field deteriorates at a imperative to make sure that the drug instilled works. The
rate that is clinically significant, the target IOP has to be way to ensure this is to do a unilateral drug trial, by instilling
lowered. However, with reevaluation it is necessary to exclude the chosen drug in one eye, usually the worse eye and assessing
other factors, such as systemic hypotension, poor compliance its efficacy. If the chosen drug is effective in lowering IOP
or IOP spikes that may be responsible for the deterioration. satisfactorily, it can be continued. If it does not show an
888 Glaucoma
adequate response, it is preferable to switch to another class increased fluctuation and compliance should be assessed.
of drugs, rather than add another medication. In patients Steroid use and certain exercises which could increase IOP
who respond well, but need further lowering of IOP, a should be ruled out.
medication from another class may be added. Switch to a Last but not the least, significant diurnal dips or
fixed combination therapy may be done and results assessed. cardiovascular risk factors, which could explain the
deterioration, should be kept in mind.
Instructions Regarding
Instillation of Eye Drops Compliance
The treating physicians' task does not end with proper Notwithstanding proper prescription after assessment of
prescription of drugs. It is extremely important to demonstrate target IOP, poor compliance to therapy, either due to economic
to the patient how to instill the drop with nasolacrimal duct factors, lifestyle or lack of understanding of the disease can
occlusion. Nasolacrimal duct occlusion for five minutes after defeat the purpose of therapy. Monitoring by electronic
instillation of the medication, not only reduces the drug loss devices in the medication bottle showed that 41 percent of
through the duct significantly, thus making available a higher patients omitted at least ten percent of their prescribed
concentration in the anterior chamber; it also decreases or medication (pilocarpine) and 15 percent missed more than
prevents systemic side effects of the drug. one half of their drops. Another study demonstrated that
Some report that gentle eyelid closure for five minutes, also doctors overestimate their patients' adherence to the regimen
has a similar effect. by about 50 percent and patients' overstated their adherence
In case multiple drugs are prescribed, the patient should by about 100 percent. It is obvious that however effective
be instructed to wait for at least five to ten minutes between the medication, irregular usage is not going to fetch the desired
instillation of the drops. result. The way to ensure regular use of medication is to find
effective alternatives that do not demand frequent dosing
Follow-up and have fewer side effects. The last decade has seen the
It is usually adequate to have the first follow-up four to eight arrival of the prostaglandin analog and alpha, agonists that
weeks after initiation of therapy. Any patient with a very high have tried to address this issue.
IOP, in the late twenties or early thirties will need to be reviewed Assessing affordability for the medication prescribed is
earlier. At the first visit, the patient is asked if he is comfortable obviously of paramount importance for successful therapy.
with the medication and tolerance to the chosen therapy is Compliance can also be improved, by increasing awareness,
assessed. The range of IOP is checked. Ocular and systemic by educating the patient about the disease and its treatment.
side effects of the medication are ruled out. Many patients expect an improvement in their vision once
Diurnal variation is done with the new drug. If this is not they start instilling the eye drops. So, it is extremely important
feasible, due to practical constraints, the patient is assessed at to explain to them that the medication is to prevent loss of
different times at each follow-up. vision due to the disease process in future and does not
It is of utmost importance to assess compliance to therapy improve the current state of vision. Making the patient
including affordability. understand about the disease process should be done with
The number of follow-up visits is usually about four to the aim of removing baseless fears, as well as to make the
eight annually, depending on the severity of disease, as assessed patient comply with the therapy. A better understanding leads
by perimetry and imaging. to realistic expectations and a more satisfied patient, who
If the target IOP is not reached as seen at the first follow- complies with treatment.
up visit, or is no longer maintained as detected at subsequent Tailoring therapy to suit the professional and personal
follow-up visits, this calls for a change of therapy or additional demands of the patient, keeping in mind his lifestyle helps in
therapy. As a rule, switching medication is preferable to adding ensuring adherence to therapy. It must be remembered that
a new drug. A reverse uniocular trial is recommended by some, glaucoma is not about treating IOP. It is important to consider
wherein the effect of stopping the drug in one eye is studied. the social, economic and lifestyle changes to the patient
This can help detect if the raised IOP is due to failure of the because of the disease process. Therapy should keep in mind
drug or compliance. the overall welfare of the patient.
If there is confirmed progression on follow up, repeating A good doctor patient relationship goes a long way in
the diurnal variation is a good idea. Undetected IOP peaks, improving compliance.
Table 9.4.1.1: Available antiglaucoma medications and important side effects

Class Concentration Dose Mode of action Ocular side effects Systemic side effects
β adrenergic
blocking agents
Non-selective
Timolol maleate 0.25%, bid Decreased aqueous Burning, stinging, Bronchospasm, bradycardia,
/hemihydrate 0.5% production, by punctate keratitis corneal, arrhythmias, heart failure,
Carteolol 0.5% bid inhibition of cyclic anesthesia, decrease ankle edema, nocturnal
Levobunolol 0.5% od AMP. in tear break-up hypotension, depression,
Metipranolol 0.5% bid time, dry eye, fatigue, lethargy, memory
allergic conjunctivitis (3%). loss, disorientation, masking
Selective Granulomatous anterior of hypoglycemia, increased
Betaxolol 0.5% uveitis with Metipranolol. LDL and decrease in HDL.
Prostaglandin
analog
Latanoprost 0.005% od Increased Burning, stinging, foreign Flu like syndrome, myalgias,
Travoprost 0.004% od outflow by action body sensation, irreversible headache, dyspnea, asthma.
Bimatoprost 0.03% od on FP* receptors increase in iris pigmentation,
Unoprostone 0.15% od (Bimatoprost also periocular pigmentation,
increases trabecular reactivation of herpes,
ouflow). anterior uveitis.
Carbonic
anhydrase
inhibitors
Systemic
Acetazolamide 250 mg tab, 250–1000 mg 1. Decrease in Myopia, hypotony, Gastrointestinal side effects,
250 mg SR* in divided HCO3 ion in suprachoroidal paresthesias, decreased
capsule, doses posterior chamber, effusion. libido, depression,
500 mg vial 250–500 mg/day leading to decrease thrombocytopenia, aplastic
powder in aqueous humor anemia, urate stones,
Methazolamide 500 mg tab 50–100 mg production hirsutism.
bid/tid 2. Metabolic acidosis.
Dichlorphenamide 50 mg tab 50–100 mg bid/tid
Topical Allergic conjunctivitis, Thrombocytopenia, bitter
Dorzolamide 2% tid periorbital dermatitis, taste (25%)
Brinzolamide 1% bid stinging, superficial
punctate keratitis,
corneal edema, blurred
vision, dryness, tearing,
photophobia, hypotony,
suprachoroidal effusion.
Cholinergics
Pilocarpine 05%, 1–4%, qid Increase in Miosis, browache, Salivation, lacrimation,
6% soln; aqueous outflow anterior chamber emesis, diarrhea,
4% gel by ciliary muscle inflammation, bronchospasm, increased
Echothiophate 0.125% soln bid contraction in open retinal detachment. urination, hypotension/
iodide angles and pupillary hypertension.
constriction in closed
angles.
Adrenergic
agonists
Selective
Brimonidine 0.2% bid/tid Decrease in Allergic blepharo- Life threatening hypotension
aqueous conjunctivitis (10– apnea in children, fatigue,
production+ 50%). Acute drowsiness, headache,
increase in granulomatous hypotension.
uveoscleral anterior uveitis.
outflow.
contd...
890 Glaucoma
contd...
Apraclonidine 0.5%, 1% 1 drop one hour Also decreases Transient dry 1 case of near syncope
prior to laser episcleral venous nose/mouth and chest tightness
procedure and pressure. (30-50%). reported.
1 drop Higher incidence
immediately of ocular allergy,
after. conjunctival
blanching,
lid retraction,
mydriasis.
Nonselective
Epinephrine 0.5%,1%, bid Increase both Tearing, rebound Palpitation, tachycardia,
2% trabecular and conjunctival arrhythmias, extrasystoles,
uveoscleral congestion, hypertension.
outflow. adrenochrome
deposits, corneal
Dipivefrin 0.1% bid edema, cystoid
macular edema in
aphakes and
pseudophakes.
Hyperosmotics
Mannitol 10%, 20% 1–1.5 g/kgbw Reduce vitreous Gastrointestinal symptoms,
intravenous volume + diuresis with mannitol,
@3–5 ml/min acidemia, anaphylactic
Glycerol 50% oral 1–1.5 g/kgbw Via osmoreceptors reaction, chills, fever,
soln 1–2 g/kgbw in hypothalamus disorientation intracranial
Diisosorbide 50% oral insufficiency and urinary
soln retention, cardiovascular
overload.
* SR = Sustained Release; FP = Prostaglandin F receptors
Table 9.4.1.1 enumerates the drugs used in glaucoma 5. Carbonic Anhydrase Inhibitors
management. Systemic Acetazolamide, Methazolamide, Brinzolamide
The basic guideline to follow while prescribing anti-glaucoma Topical Dorzolamide, Brinzolamide
medication is to use the least number of medications that will 6. Hyperosmotic Agents
control the IOP adequately without any adverse effects. Parenteral Mannitol
Oral Glycerol, Isosorbide
Groups of Drugs Used in
Antiglaucoma Therapy
Beta Blockers
1. Beta Blockers
Selective Betaxolol History: β blockers were introduced in 1978 for the topical
Non-selective Timolol, Levobunalol, Metipranolol, Carteolol treatment of glaucoma. They still continue to be the
2. Prostaglandin PG Analogs mainstay of first line treatment in many parts of the world,
Latanoprost, Bimatoprost, Unoprostone, Travoprost though the option of other effective alternatives exist. There
3. Cholinergic Agonist/Miotics are presently five molecules of the compound, including
Pilocarpine, Echothiophate iodide both selective and non-selective β blockers. They are
4. Adrenergic Agonists considered the gold standard in the medical management
Non-selective Ephedrine, Dipivefrin of glaucoma and all new drugs are evaluated for their
Selective alpha agonists Brimonidine, Apraclonidine efficacy by comparison to timolol.
The β blockers Used in Glaucoma Therapy Are: found no correlation, between perfusion flow and reduction
of IOP.
Relative β blocking activity There are studies that suggest that betaxolol might have
(In comparison with Propanolol) an additional neuroprotective effect by decreasing the influx
Non-selective β blockers: of calcium into the retinal ganglion cells.
Timolol 5
Preparations: Several generic and trademark preparations
Carteolol 10
of β blockers are available. All of them are recommended at
Levobunolol 15
a dosing schedule of twice daily, except for Levobunalol and
Metipranolol
Timoptic XE (gel) which have been shown to be effective
(Withdrawn from clinical —
use in United Kingdom) when used once daily. Except for Timoptic XE, which contains
benzododecinium bromide as the preservative, all other β
Selective β blocker: blockers contain benzalkonium chloride. Timolol gel maintains
Betaxolol 1
the medication in contact with the eye for a longer period of
Non-selective β blockers have β blocking action both at time, but there is no significant difference with the solution
β1 and β2 adrenergic receptors. The only selective beta as regards its efficacy or adverse effects.
blocker is betaxolol, which exhibits a β receptor inhibition
only at the β1 receptors and hence has comparatively less Dosage and administration: The effect of the medication
effect on vascular and bronchial constriction. This may be starts after half an hour of instillation, with the peak effect
beneficial in some patients with obstructive pulmonary disease, in two hours and lasts for 12 to 24 hours. Though once daily
by not having any deleterious effect on expiratory flow administration may suffice, twice daily administration is
parameters. However, β1 selective drugs are slightly less commonly indicated.
effective when compared to the non-selective agents. While Dosing more than twice daily does not give further IOP
the latter exhibit an IOP reduction of 25 to 30 percent from lowering effect.
baseline, the former reduces IOP by a magnitude of 20 to The time needed for beta blockers to completely lose
25 percent from baseline. their activity is two to five weeks (wash out period).
Carteolol is a β blocker with intrinsic sympathomimetic While in most patients β blockers are effective for years,
activity (ISA). However, the clinical relevance of ISA in in some, the IOP lowering capacity decreases over the short
glaucoma therapy is not yet proven. term, called “short term escape”. In others, there is a decline
in the efficacy over long term, called “long term drift”.4 While
Mode of action: β blockers decrease aqueous production by
the former is due to up-regulation of B receptors, “long
binding to β adrenergic receptors and blocking sympathetic
term drift” has also been attributed to some alteration at the
transmission. They decrease aqueous humor production by
receptor site.
as much as 30 to 50 percent as has been substantiated by
tonographic and fluorometric studies. While their major action Combination therapy: β blockers show an additive effect
is to reduce aqueous humor synthesis at the nonpigmented with most other IOP-lowering agents, except with dipivefrin
ciliary epithelium, they also decrease capillary blood flow rate wherein the effect is minimal and adrenaline (epinephrine)
in the ciliary processes, thus reducing ultrafiltration. wherein a combination has no additional effect.
Additionally, they inhibit the β receptors mainly of the β2
subtype even in the pigmented epithelium of the ciliary Side effects: They are usually well tolerated locally, but have
processes, enabling the drug to act at this site directly. numerous systemic side effects, many of which can be
At the biochemical level, it is postulated that they act by dangerously harmful.
inhibiting the synthesis of cyclic AMP by the adenylate cyclase
enzyme. However, this effect is not seen at night, when the Ocular side effects: Stinging, photophobia, blurred vision, burning
resting sympathetic tone is low and aqueous humor synthesis and hyperemia have been reported. The latter two may be
is already reduced. isolated or occur with superficial punctate keratitis and corneal
Outflow facility does not appear to be reduced by timolol. anesthesia.
It has been suggested by some studies that β blockers also A study comparing betaxolol 0.5 percent and timolol 0.5
increase retinal perfusion by their effect on vascular tone percent demonstrated that some corneas develop long-lasting
and increased perfusion of the retinal vessels. Others have corneal anesthesia after use of the drops, which can predispose
892 Glaucoma
a patient to serious corneal complications, such as keratitis. Beta blocking agents have also been associated with
This is attributed to the membrane stabilizing activity of β nocturnal hypotension, which may be a risk factor in
blockers which tends to stabilize the nonmyelinic pain fibers progression of glaucomatous optic nerve damage.
of the cornea and thus decreases corneal sensitivity. This is One study reported that instillation of one drop of
more likely to occur in patients who are more than 70 years. non-selective β blocker is associated with decrease in pulse
Chronic therapy with timolol has been shown to affect rate of approximately five beats per minute, a reduction
the mucus layer of the tear film. Corneal epithelial erosions in cardiac contractility as well as oxygen consumption and
have been reported in two patients wearing gas permeable decrease in blood pressure.
contact lenses soon after starting topical timolol therapy. A 3. Central nervous system: Central nervous system effects
reduction of tear flow and shortening of tear break-up time occur in three to ten percent. Depression, fatigue, lethargy,
may be seen in patients who have low baseline tear flow. memory loss, disorientation, lack of concentration, bizarre
However, these are reversible on cessation of therapy. dreams and insomnia are some of the common side
Ocular discomfort due to the active compound, or buffer effects.
or preservative with about three percent developing allergic 4. Endocrine system: Hypoglycemia may be masked in
conjunctivitis has also been reported. insulin dependent diabetes mellitus, because the
Preservative free medication may help not only in reducing symptomatic response to hypoglycemia which is mediated
ocular toxicity, but also in preventing chronic conjunctival via β receptors can be delayed by β blockers.
inflammation and subsequent failure of filtration surgery. This group of drugs is contraindicated in hyperthyroidism.
Intraocular side-effects are almost nonexistent in the 5. Miscellaneous: Timolol can increase low-density
anterior segment of the eye. The most troublesome ocular lipoproteins and decrease high density lipoproteins (HDL),
reaction that has been reported with metipranolol is a but this effect has not been shown to be of any clinical
granulomatous anterior uveitis. This was thought to be due significance. One study reported that carteolol decreased
to the formulation used in the United Kingdom and the drug HDL by 3.3 percent as compared to timolol which
was withdrawn from clinical use. However, three cases have decreased it by eight percent. 5 Dermatologic and
also been reported in the United States. gastrointestinal problems, worsening of Raynaud's
Aphakic cystoid macular edema and periocular syndrome, myasthenia gravis, decreased libido and
pigmentation have been reported with betaxolol rarely. sometimes impotence can occur.
Pupillary size and accommodation are not affected by β blockers can be life-threatening in bronchial asthma,
these agents. history of obstructive pulmonary disease, sinus
A serious ocular side effect suspected to be due to timolol bradycardia, heart block, cardiac failure and diabetics
is ocular cicatrical pemphigoid (OCP). This is said to be due prone to hypoglycemic episodes. In the USA, around 50
to chronic inflammation from the irritation caused by the deaths have been attributed to β blocker eye drops, half
antiglaucoma medication or their preservatives and not due of them because of cardiac failure and 25 percent as a
to cell proliferation induced by the drug. However, in most result of an asthma attack.
cases developing OCP, patients also receive additional
antiglaucoma medication. Comparative efficacy: Timolol is as effective as apraclonidine
and brimonidine and more effective than pilocarpine,
Systemic side effects: The systemic adverse effects of β blockers epinephrine and dorzolamide. It is less effective when
are not only numerous, but can also be life- threatening. compared to prostaglandin analogs. When compared with the
1. Respiratory system: Bronchospasm and airways other β-blockers, timolol and levobunolol are equally effective,
obstruction are serious complications, which are whereas betaxolol hydrochloride is less effective than timolol.
comparatively less with the selective β blocker betaxolol.
However, even betaxolol is better avoided in patients Pregnancy and nursing mothers: It is used only if the
predisposed to bronchospasm. potential benefit justifies the potential risk to the fetus or the
2. Cardiovascular system: Usually, the cardiac side effects infant. Timolol has been shown to be secreted in breast milk
of β blockers occur within the first 24-hours of treatment. in a concentration one-eightieth of the cardiac effective dose.
Bradycardia, arrhythmia, heart failure, syncope, So it is considered relatively safe, although it is advisable to
bradycardia and ankle edema have been reported. keep a close watch on the infant of the treated mother.
Timolol 0.25 and 0.5 percent solutions should be cautiously Mode of action: Prostaglandins are autocoids (i.e. hormones
used in young glaucoma patients as well as in neonates because that are synthesized, released and active locally). They are
of the possibility of apnea. produced by the ciliary muscle and trabecular meshwork under
Drug interactions: Systemic beta blockers can exacerbate normal conditions. Derivatives of PGF2 α which are modified
the adverse effects of topical agents. Further, they block structurally to increase their ocular penetration and specifically
receptor sites and decrease the efficacy of topical agents. activate the FP-prostanoid receptor, are the most potent and
1. Oral or intravenous calcium antagonists: Co-administration of effective ocular hypotensive agents known. These prostaglan-
calcium antagonists and beta-adrenergic blocking agents din analogs decrease IOP by increasing uveoscleral outflow.
can cause atrioventricular disturbances, left ventricular This is done by a direct action on the FP receptor which
failure, and hypotension. leads to a remodeling of the extracellular matrix of the ciliary
2. Digitalis: The concomitant use of beta-adrenergic blocking muscle with consequent increase in permeability and lower
agents with digitalis may prolong conduction time. IOP. They also act to a smaller extent by relaxing the ciliary
3. Catecholamine-depleting drugs: Can cause hypotension and/ muscle, thus enlarging the spaces between the muscle fibers.
or marked bradycardia when given concomitantly. Unlike Latanoprost and travoprost, bimatoprost is a
4. Hormone replacement therapy: Headache can be aggravated synthetic molecule called a prostamide (since it has an amide
by concomitant administration of a beta blocker. Aspirin ethyl group at the C1 position) that is structurally and
and NSAIDs can decrease the effect of beta blockers. pharmacologically similar to PF-F2α. So, the site of action
Verapamil is of special concern because cases of complete of this molecule is postulated to be at prostamide receptor
heart block, atrio-ventricular nodal delay and sinus node sites.6 It is said to have better corneal and scleral penetrability
dysfunction have been reported when timolol was used in as well as higher ciliary body concentration. It is believed,
combination with this calcium channel blocker. that it also acts at the PG receptors present in cells of the
Diuretics increase the risk of systemic hypotension and trabecular outflow pathway also, thus decreasing IOP by acting
hypolipoproteinemia when given concomitantly. both on the unconventional and to a lesser extent the
conventional pathway.
Prostaglandin Analogs
Dosage, concentration and efficacy: Onset of action is in two
History: The prostaglandin analogs are the newest class of to four hours with the peak effect seen after 12 hours. Maximum
antiglaucoma medications. The prostaglandins (PG) belong IOP lowering is from three to five weeks after initiation of
to a pharmacologic family called eicosanoids, which are all therapy. The elimination half-life of this class of drugs is very
formed from the polyunsaturated fatty acid arachidonic acid. short, 2.3 minutes after topical administration for latanoprost
Prostaglandins are present in almost every body tissue and and 45 minutes after intravenous administration of bimatoprost.
fluid and act locally at those sites. The presence of ocular Despite this, all prostaglandin analogs except unoprostone are
prostaglandins was verified in the 1950s, but it was only in effective in a once daily dosing. More frequent dosing of these
1985 that the effects of prostaglandins on the human eye agents results in a decreased IOP lowering effect of the drugs.
were reported. Latanoprost, also called PhXA41 was the first The wash out period is four to six weeks.
drug in this class to be approved by the US Food and Drug Isopropyl unoprostone 0.15 percent is administered twice
Administration in 1996, though unoprostone has been in use daily.
in Japan since 1994. The potent IOP lowering action coupled All PG analogs have been demonstrated to be more
with minimal side effects, has made this class of drugs, an effective when administered at night. Though around the
alternative first line of therapy to beta blockers. clock efficacy of latanoprost has been demonstrated by some
studies, Scandinavian patients were found to have a
Drugs Conc. Synonym FDA Category significantly greater IOP reduction when the drug was instilled
approval
in the evening as compared to morning.
*Latanoprost 0.005% PhXA41 1996 Prostaglandin
Travoprost 0.004% AL-6221 2001 Prostaglandin Storage: The thermal and ultraviolet instability of latanoprost
Bimatoprost 0.03% AGN-192024 2001 Prostamide necessitates its refrigeration before it is opened. Once opened,
Unoprostone 0.15% UF-021 2000 Docosanoid
it can be stored at room temperature up to 25°C for up to
*Requires refrigeration (Details in Table 9.4.1.2) six weeks, but needs refrigeration for longer storage. The
894 Glaucoma
temperatures recommended for the other agents are 15 to must be mentioned to the patient especially when therapy is
25°C for bimatoprost and 2 to 25°C for travoprost and initiated uniocularly. Among the PG analogs, unoprostone is
unoprostone. less likely to change iris color.
Increased pigmentation of the periocular skin is also
Efficacy: The average drop in IOP after latanoprost usage
attributed to an increase in tyrosinase activity and alteration
in the six month trials ranged from 27 to 34 percent.7 One
of melanin chemistry.
Japanese study found that it maintains the visual field in
Thickening and lengthening of lashes, due to stimulation
approximately 70 percent of the eyes after treatment for
five years.8 Another two-year study from UK showed that of the growth phase of the hair cycle in the dermal papilla is
there was no drift in IOP at the end of the study period. especially reported in eyes with darkly pigmented hair.
Further, the 33 percent decrease in IOP by the drug was Dendritiform epitheliopathy, mild punctate corneal
statistically significant. epithelial erosions as well as anterior uveitis has been reported
One study suggested that travoprost may have a potentially in a few patients.
higher effect in decreasing IOP in African-Americans, though There are case reports of reactivation of herpes simplex
this has not been substantiated satisfactorily by others.9 keratitis in patients treated with latanoprost or bimatoprost.
Though a number of clinical studies have shown that PG In such patients, an alternative class of antiglaucoma drugs
analogs are superior to β blockers in IOP lowering efficacy, a may be a better option.
meta-analysis by the FDA concluded that there was no definite Cystoid macular edema can occur in aphakes,
proof that the peak efficacy of latanoprost differed pesudophakes and patients predisposed to macular edema.
significantly from the peak efficacy of timolol 0.5 percent. Systemic side effects: These are limited due to the low
The average IOP lowering efficacy of the various drugs
concentration and short half-life in the blood.
in this class are as follows:
Flu like syndrome, upper respiratory symptoms, myalgias
Bimatoprost 7 to 8 mm Hg (baseline 26 mm Hg) and headache are reported by a few.`
Latanoprost 6 to 8 mm Hg (baseline 24–25 mm Hg) Dyspnea, asthma, exacerbation of asthma have been
Travoprost 7 to 8 mm Hg (baseline 25–27 mm Hg) reported occasionally. However, one crossover study that
Unoprostone 3 to 4 mm Hg (baseline 24–25 mm Hg) compared the effects of latanoprost and placebo therapy on
It has been recommended by the FDA as adjunctive respiratory function in 24 patients with asthma, did not find
treatment for mild to moderate glaucoma. any change either in respiratory function or asthmatic
Side effects: PG analogs are relatively safe drugs, with no symptoms with latanoprost.
absolute contraindications to their use. Local side effects are Contraindications: There are no absolute contraindications.
more common than systemic side effects. Known allergy to the parent compound or preservative
Ocular: Conjunctival hyperemia is the most common side (benzalkonium chloride) precludes their use.
effect, but it is usually transient and mild. The frequency of They should be avoided in patients with, or predisposed
hyperemia (based on differing clinical end points) in the to, CME or uveitis and recent intraocular surgery.
product labeling are, 5 to 15 percent for 0.005 percent Patients should not administer these drugs while wearing
latanoprost, 15 to 45 percent for 0.03 percent bimatoprost, contact lenses, but contact lenses can be reinserted 15 minutes
35 to 50 percent for 0.004 percent travoprost, and 10 to 25 after administration of these drugs.
percent for 0.15 percent unoprostone. Pregnancy and lactation: To be used only if potential benefit
Burning and stinging, foreign body sensation, blurred vision justifies their use.
and itching are some common side effects.
Drug interactions: Not reported as yet.
Another common and disturbing side effect is change in
the color of the iris due to increased iris pigmentation. This Comparative efficacy: Addition of latanoprost that increases
is especially seen in blue/gray or brown irides. It is much uveoscleral outflow, to timolol, (an aqueous humor
more common, (up to 20–30%), in mixed green-brown color suppressant), decreases IOP by an additional 13 to 31 percent
and hazel irides as compared to solid colored irides. It is due depending on different racial populations in which it was
to an increase in the melanin content within the iris stromal studied. This shows that the complementary modes of action,
melanocytes as well as due to up-regulation of tyrosinase by these two drugs from different classes can be used to
activity in the melanocytes. It is an irreversible change and clinical advantage.
Latanoprost also appears to be effective as an adjunctive methazolamide is a minor modification of the molecule, with
agent with most approved antiglaucoma agents, except for better absorption and longer duration of action.
an uneven response when added to miotics. Efficacy: All three oral agents decrease aqueous humor
Miscellaneous: The main limiting factor that is preventing PG production by a maximum of 50 percent. The IOP reduction
analog group of drugs, from replacing the time tested beta of 50 mg methazolamide is slightly smaller than 250 mg oral
blockers as first line therapy in glaucoma management is their dose of acetazolamide. Since methazolamide is less bound to
cost. plasma protein as compared to acetazolamide (55% versus
95%), smaller doses of the former are able to reduce IOP
Carbonic Anhydrase Inhibitors satisfactorily.
The use of carbonic anhydrase inhibitors (CAI) in the Concentration and Dosage:
treatment of glaucoma started with oral acetazolamide in 1. Acetazolamide: 250 mg tablets, half life of four hours. The
1954. Since then other oral and topical drugs acting by the dose for the tablets is 250 to 1000 mg in divided doses.
same mechanism of action have been in use. The onset of action is within one hour, with a peak at
Systemic Acetazolamide four hours and duration up to 12 hours.
Methazolamide 2. Acetazolamide sustained–release capsules 250 mg. The dose is
Dichlorphenamide 250 to 500 mg daily. The duration of action is up to 24
Topical Dorzolamide FDA approval 1995 hours. Renal side effects are avoided with a dose of <2
Brizolamide FDA approval 1998 mg/kg/day.
3. Acetazolamide powder 500 mg vials for injection. The onset of
Mode of action: There are two main postulated mechanisms action is almost immediate, with a peak at 30 minutes
of action of CAIs. and duration of up to four hours.
1. Carbonic anhydrase enzyme catalyses the reversible 4. Methazolamide 50 mg tablets. Since it has a half life of
reaction CO2 + H2O = H2CO3. H2CO3 dissociates into about 15 hours, 50 to 100 mg twice daily is recommended.
H+ and HCO3– in the ciliary epithelium and the HCO3– The onset of action is within three hours, with a peak at
ion enters the posterior chamber, with a net flow of fluid six hours. It is excreted by the hepatic route predominantly,
into the posterior chamber. The main mechanism by which so it is safer in patients with renal disease.
CAIs reduce IOP is by a decrease in the bicarbonate ion 5. Dichlorphenamide (50 mg) tablets. 50 to 100 mg twice or
concentration in the posterior chamber that leads to a thrice a day. The onset of action is within an hour, with a
concomitant decrease in the sodium and fluid peak at three hours and duration of up to 12 hours.
concentration in the posterior chamber and a resultant Adverse Effects: Systemic CAIs have numerous side effects,
decrease in aqueous humor production. Ninety-nine which often necessitate stopping therapy. Compliance is poor
percent of carbonic anhydrase enzyme has to be inhibited and only about one-third of patients take their medication
for effective reduction of IOP. regularly.
2. Metabolic acidosis is also said to play a role in the reduction 1. Ocular side effects: Rarely, systemic therapy can lead to ocular
of IOP, especially with large doses. side effects like myopia, hypotony and suprachoroidal
3. Additionally, a reduction in uveal volume due to effusion due to the anterior rotation of the ciliary body.
vasoconstriction is seen at high doses and some studies 2. Systemic side effects:
have reported an improved ocular blood flow with the a. Gastrointestinal side effects: Anorexia, nausea,
topical CAI dorzolamide, though this has been refuted by diarrhea, flatulence, poor tolerance to carbonated
others. drinks.
b. Nervous system: Numbness and paresthesias,
Oral Carbonic Anhydrase Inhibitors
depression, decreased libido.
Introduction: Reduction of IOP by systemic administration c. Hematologic: Thrombocytopenia, idiosyncratic aplastic
of acetazolamide was first described by Becker and the oral anemia. Bone marrow suppression is a rare but
preparation was introduced in 1954 for the treatment of dreaded complication.
glaucoma. While there are three oral preparations for clinical d. Electrolyte disturbance: CAIs increase urate levels in
use, all members of the sulphonamide family, acetazolamide the serum. Metabolic acidosis can be life-threatening
still continues to remain the CAI of choice. Oral in diabetic patients who are susceptible to ketoacidosis,
896 Glaucoma
in hepatic insufficiency and in chronic obstructive Brinzolamide 1 percent: This drug is quite similar in its profile
pulmonary disease. Diuresis induced by the drug and dosing regimen to dorzolamide, but is said to cause less
causes loss of potassium which is usually mild unless burning and is better tolerated as compared to the latter. It is
the patient is on thiazide diuretics, digitalis or systemic less acidic with a more physiologic pH as compared to
steroids. However, dichlorphenamide can precipitate dorzolamide. Hence while the latter is delivered as a solution,
serious hypokalemia by itself and should be avoided brinzolamide is delivered as a suspension. It decreases IOP
during pregnancy. by about 20 percent, with the peak effect of 3.3 to 5.3 mm
CAIs can increase blood glucose levels. High blood Hg occurring two hours after dosing. At trough 12 hours
sugar levels are poorly tolerated with lowered levels after instillation, the IOP lowering is 2.8 to 4.9 mm Hg.
of potassium. Dorzolamide and brinzolamide are equal in their IOP
e. Renal system: CAIs can cause a decrease in excretion reducing capability and are additive to beta blocker timolol.
of renal citrate and form urate stones. There are some reports that suggest that topical CAIs
f. Miscellaneous: Hirsutism. may potentiate ocular blood flow. Laser Doppler flowmeter
g. In children: Growth suppression has been associated studies have shown an improvement in optic nerve head
with oral acetazolamide therapy, and infants may blood flow in animals after topical dorzolamide.11 Further,
experience severe metabolic acidosis. arteriovenous transit time as measured with a scanning laser
3. Contraindications: Allergy to sulphonamide group of drugs, ophthalmoscope was also found to be significantly better in
renal disease, chronic obstructive pulmonary disease and these studies, though there appeared to be no change in the
diabetic ketoacidosis. blood flow in retrobulbar vessels.
Topical carbonic anhydrase inhibitors: Maren and Side effects: Almost half the patients develop some side
colleagues first described the topical use of CAIs and effects with the topical medication. Since the pH of
dorzolamide was approved for use in the treatment of glaucoma dorzolamide is acidic (pH=5.6), ocular side effects are more
in the US in 1995. The main advantage of topical agents common as compared with brinzolamide.
(dorzolamide and brinzolamide) is that they cause fewer side Besides allergic conjunctivitis, periorbital dermatitis,
effects. They are being increasingly used, as second line therapy stinging on instillation (33%), superficial punctate keratitis
in the treatment of glaucoma. Both the topical agents are equally (10–15%) and allergic conjunctivitis which are quite common,
effective in reducing IOP (17%), though they are less effective less frequent side effects are myopia, corneal edema/
as compared to the oral agents (30%). Both agents are additive decompensation which can occur in susceptible individuals,
to timolol. Dorzolamide decreases IOP by an additional 13 to hypotony and suprachoroidal effusion. Blurred vision, dryness,
21 percent when added to timolol and eight percent when tearing, dryness and photophobia are also reported by some.
added to latanoprost. Thrombocytopenia has been reported with topical
dorzolamide.
Dorzolamide 2 percent: This topical agent, which was approved Bitter taste is a common complaint reported by almost
in 1995 by the FDA, acts by a similar mechanism as oral 25 percent patients after administration.
acetazolamide. However, the action at the pigmented and
nonpigmented epithelium of the ciliary process, specifically Comparative efficacy: The magnitude of IOP reduction is
on the carbonic anhydrase isoenzyme II is almost ten times almost the same as that obtained with β1 selective blockers.
more than the latter. This drug has a duration of action of As adjunctive therapy, dorzolamide is approximately
about eight hours and is recommended in a thrice daily dose equivalent to two percent pilocarpine in its IOP lowering
when given as monotherapy and twice a day when combined capacity.
with any other antiglaucoma agent. Studies have reported a Combination therapy: Aqueous flow was decreased by 18
decrease in IOP of 14.7 to 27 percent two hours after dosing percent for dorzolamide alone and 47 percent for timolol
and 12.9 to 17.5 percent after eight hours. The efficacy is alone, and the two used together were nearly completely
about 1 to 2 mm less than timolol solution. additive at 55 percent. As regards IOP reduction, dorzolamide
This drug is also available in 0.5 and 1 percent has been reported to cause an additional 13 to 21 percent
formulations in Japan. decrease in IOP when added to timolol and 8 to 15 percent
Patients placed on dorzolamide have been reported to when added to latanoprost. The fixed dose combination of 2
have improved contrast sensitivity after two to four weeks percent dorzolamide and 0.5 percent timolol is said to lower
of therapy, in one reported study.10 IOP to an equal extent as the individual drugs in combination.
Contraindications: The main contraindications to the use to get oxidized to allergy producing haptens, almost 20 times
of the topical agents besides allergy to sulpha drugs are renal lower when compared to apraclonidine. This may attribute
insufficiency, obstructive pulmonary disease and diabetic to the lesser incidence of allergy with this drug.
ketoacidosis. Efficacy: It has been reported to decrease peak IOP by a
Drug Interactions: The following are drugs that should be maximum of 20 to 30 percent.
used cautiously or avoided with CAIs due to the following It is as effective as apraclonidine in reducing postoperative
adverse effects: IOP spikes after anterior segment laser procedures.
1. Calcium channel blockers: Gastrointestinal effects are Dosage and concentration: In a 0.2 percent concentration,
worse; so also paresthesias. a thrice daily dosing has been recommended by the Food and
2. Diuretics: Chance of agranulocytosis is higher. Drug Administration, when given as monotherapy and twice
Hypokalemia is worsened and there can be a greater a day when given in combination with any other anti-glaucoma
toxicity from cardiac glycosides. medication.
3. Angiotensin converting enzyme inhibitors: Bone marrow The drug is additive to all other classes of antiglaucoma
suppression. drugs.
4. Beta blockers: Insomnia, dizziness, depression, nausea.
5. Aspirin: Metabolic acidosis can be aggravated as also Side Effects:
hypokalemia. Bone marrow suppression. 1. Ocular : The most annoying and common problems of
6. Cyclosporin toxicity: Acetazolamide increases blood patients on selective adrenergic agonists are allergic
cyclosporin levels and can thus cause toxicity of blepharoconjunctivitis, manifesting as conjunctival
cyclosporin. hyperemia with conjunctival follicles and dermatitis which
occur in 10 to 50 percent. The addition of purite
Adrenergic Agonists (Sympathomimetics) preservative to the parent compound is said to cause less
allergy.
Sympathomimetics include selective agents like apraclonidine Acute granulomatous anterior uveitis has also been
and brimonidine and nonselective agents' dipivefrin and reported.
epinephrine. While the former reduce IOP by decreasing 2. Systemic: Brimonidine is more lipophilic as compared to
aqueous production through their α2 agonist action, the latter apraclonidine. Hence it tends to cross the blood-brain
have the additional effect of increasing aqueous outflow. barrier relatively more, leading to a number of side effects
Nonselective agents are seldom used nowadays, because of that are especially noticed in the extremes of age. These
local side effects like irritation and conjunctival injection. They centrally mediated adverse effects like fatigue, drowsiness,
have been replaced almost completely by the selective agent headache and hypotension warrant its careful use especially
brimonidine. in children and old patients.
Non-selective Agents Epinephrine (Adrenaline) 0.5%, Contraindications: Besides allergy to the drug which is quite
1%, 2% frequent (15%), this drug has not been tested in children less
Dipivefrin 0.1% than two years and should be used with extreme caution
Selective Agents Apraclonidine 0.5%, 1% between two and seven years. Life-threatening hypotension
Brimonidine 0.2% and apnea have been reported in children treated with
Only the selective agents will be discussed in detail. brimonidine. There have been reports of somnolence,
hypotonia, hypothermia and bradycardia in infants and
Brimonidine: Brimonidine has a quinoxalline ring in its children after instillation of brimonidine.
molecule. It is 30 times more selective for the α2 receptor as It should also be used with caution in renal and hepatic
compared to apraclonidine, the other agent in this group. failure, vascular disease and hypotension.
Mode of action: Besides decreasing aqueous production, Drug interactions: NSAIDs and aspirin when given in
reduction of IOP is also achieved by an increase in uveoscleral conjunction with adrenergics can cause systemic hypertension,
outflow. Brimonidine does not affect aqueous humor outflow besides decreasing the ocular hypotensive effect of the
through the conventional pathway. Some studies have reported adrenergic drug.
an additional neuroprotective action, which has not been Alpha adrenergics may decrease the efficacy of ACE
clearly substantiated till date. It shows a reduced propensity inhibitors.
898 Glaucoma
Concomitant administration of calcium channel blockers Pregnancy: It should be used in pregnancy and lactation only if
and diuretics may increase the gastrointestinal side effects. the benefit outweighs the adverse effects.
Alpha adrenergic drugs stimulate hyperglycemia and Though chronic use of apraclonidine is not a preferred
decrease the effect of insulin. So, they should be used with practice, it is used in 0.5 percent concentration, three times a
caution in diabetics and patients on thyroid supplements. day, as an additive drug for patients receiving maximally
Concurrent use of brimonidine with monoamine oxidase tolerated medication. In Europe, the indication is limited to a
(MAO) inhibitors, beta blockers and CNS depressants should maximum period of one month because of the side effects.
be avoided. Non-selective adrenergic agonists: The two drugs in this
Apraclonidine: The role of apraclonidine in the management group are not used frequently in present day practice, since
of glaucoma is only for prevention of post-operative spikes they have been replaced by more effective drugs with fewer
of IOP after anterior segment laser procedures like side effects. Epinephrine was introduced as an anti-
trabeculoplasty, iridotomy and capsulotomy. It cannot be used glaucomatous agent in the 1920s. Dipivefrin, a prodrug of
for chronic treatment of glaucoma, because pharmacological epinephrine, with greater efficacy at a lower concentration
tolerance (tachyphylaxis) develops in 4 to 12 weeks. was introduced later. It was also found to have lesser side
effects.
Mode of action: It is a selective α2 adrenergic agonist like Both these drugs act directly on the alpha and beta
brimonidine. It is a para-amino derivative of clonidine, which adrenergic receptors and increase both conventional and
is a potent systemic antihypertensive agent. The decrease in uveoscleral outflow after three to four hours. Both epinephrine
aqueous production may be related to constriction of afferent and dipivefrin cause local side effects like tearing, irritation
vessels in the ciliary processes. The addition of the para- and headache, rebound conjunctival congestion, adrenochrome
amino group leads to reduced penetration across the blood- deposition, corneal edema and cystoid macular edema in
brain barrier and eliminates most of the centrally mediated aphakes and pseudophakes. They have been reported to cause
effects of the drug including systemic blood pressure lowering. palpitation, tachycardia, arrhythmias, extrasystoles and
Apraclonidine also decreases episcleral venous pressure, hypertension. Hence these agents are contraindicated in
unlike brimonidine. patients with cardiac disease, arrhythmias and essential
hypertension.
Dosage and concentration: 0.5 percent, 1 percent solution. They should not be used in narrow angle glaucoma because
one drop one hour before the procedure and 1 drop they can cause mydriasis and worsen the angle closure.
immediately after, is the recommended practice.
The action peaks at four to five hours and lasts 12 hours. Drug interactions: They are unsafe in patients on MAO
The drug has a washout period of one to three hours. inhibitors, glycosides and beta blockers. Tricyclic
antidepressants can potentiate the systemic side effects of
Efficacy: It is reported to decrease IOP by 19 to 26 percent. topical epinephrine.
It is additive to timolol.
Cholinergics/Miotics
Side Effects
Though cholinergics are the oldest of all antiglaucoma therapy,
1. Ocular: The incidence of ocular allergy is much higher
their use in present day practice is largely limited to selected
with apraclonidine than brimonidine (10–50%). indications. They are no longer the first line therapy in
Conjunctival blanching, lid retraction and mydriasis may glaucoma treatment.
be seen due to its effect on the alpha1 receptors. While pilocarpine is a directly acting acetylcholine receptor
2. Systemic: Transient dry nose or mouth is seen in 30 to 50 agonist, echothiophate iodide (phospholine iodide) is an
percent. Though serious systemic side effects are not indirectly acting cholinergic that potentiates the action of
frequent with this drug, it is appropriate to mention a acetylcholine by inhibiting the action of cholinesterase. In
reported case of near syncope and chest tightness ten comparison with physostigmine (eserine), which was available
minutes after a drop of apraclonidine 1 percent. for therapy before, echothiophate is a stronger inhibitor of
cholinesterase.
Drug interactions: Since it has an additive effect with CNS
depressants, this drug should be used with caution with tricyclic Pilocarpine: This drug was introduced in 1877 for the
antidepressants. treatment of glaucoma.
It was available as a gel, ocular insert and as drops. The hyaluronate, cyanoacrylate block copolymer, as well as other
IOP reduction with this agent is about 20 percent from baseline. soluble polymers have been explored, with the aim of
The ocusert and gel are no longer available. Its primary use optimizing delivery of the drug. Soft contact lenses soaked in
in present day therapy is prior to laser iridotomy to constrict pilocarpine and intraocular injection has also been tried.
the pupil and to break an attack of acute angle closure However, none of these have been approved for clinical
glaucoma. It is a second line choice for the chronic therapy use.
of both angle closure and open angle glaucoma. The ocular Combination therapy: Pilocarpine is a useful adjunctive drug,
adverse effects with this drug precludes long term therapy, which can be combined with any of the other classes of
especially with the available safer alternatives. antiglaucoma drugs to provide additional IOP lowering benefit.
It is also available in combination with timolol.
Mode of Action:
1. There are five distinct cholinergic muscarinic receptors, Side Effects
of which the M3 receptor is prominent in the ciliary Ocular
muscle and iris sphincter. 1. Miosis is a bothersome complaint, especially in the elderly
Stimulation of the muscarinic receptor causes an with cataract, where there is a decrease in the field of
increase in aqueous outflow, by ciliary muscle contraction vision. One study reported a decrease in the mean defect
in eyes with open angles and constriction of the pupil in in the visual field by 1.49 dB.
eyes with pupillary block glaucoma. Histological studies 2. Browache due to ciliary muscle spasm occurs especially
in human and primate eyes also show an increase in the in younger individuals. However, this complaint subsides
giant vacuoles, in the endothelium of the Schlemm's canal with continued use.
along with a pull on the scleral spur posteriorly and 3. Anterior chamber inflammation is common due to increase
widening of the trabecular space. in the permeability of the blood aqueous barrier. This
2. Besides an increase in outflow, this agent is also thought precludes its use in uveitis, postoperatively after any
to decrease inflow and this probably exceeds and outlasts intraocular surgery, in rubeosis and in patients with corneal
the improvement in outflow facility. In monkey eyes, it grafts.
has been shown to reduce the formation of aqueous 4. Allergic conjunctivitis and blepharitis due to hypersensitivity
humor.
to the active component is infrequently seen.
3. It also decreases uveoscleral outflow. This could account
5. Rhegmatogenous retinal detachment in predisposed
for the relative lack of efficacy in developmental glaucoma
individuals is a theoretical possibility. It is suspected mainly
wherein there is an abnormal insertion of the ciliary muscle
on circumstantial evidence. However, a thorough retinal
into the trabecular meshwork.
examination prior to prescribing this medication is not a
Dosage and concentration: Pilocarpine solutions are bad idea.
available as nitrate and hydrochloride salts, 0.5 percent, 1 Systemic
percent, 2 percent, 3 percent, 4 percent, 6 percent. The 1. It is not common to encounter systemic adverse reactions
maximum IOP lowering effect occurs within two hours and on chronic therapy. However, relatively larger doses used
lasts at least eight hours. prior to a laser iridotomy or to break an attack of angle
To ensure adequate dosage round the clock, the traditional closure are liable to cause the muscarinic effects of
dose is four times a day. salivation, lacrimation, emesis, increased urination,
Pilocarpine gel four percent was once available in a high diarrhea and bronchospasm.
viscosity acrylamide vehicle. The main advantage of the gel 2. There is one report of a second degree atrio-ventricular
was the constant level of the drug in the eye for almost 24
block getting converted to a 3rd degree block after
hours. Another advantage was that it induced less myopia
pilocarpine therapy.
and did not impair nocturnal visual acuity as much as the
3. It should be used with caution in patients with Alzheimer’s
drops. A large number of patients (69%) complained of mild
disease, who are more sensitive to this group of drugs
blurring with its use. A subtle diffuse corneal haze was
and manifest with progressive cognitive dysfunction.
observed in 20 to 28 percent of patients after prolonged use
4. Alteration in blood pressure, either increase or decrease,
of gel in one study, though this did not have any long term
depending on the degree of autonomic stimulation is
consequences.
present.
A number of alternate ways of drug delivery like a
membrane controlled delivery system, oily solutions, sodium The antidote for systemic pilocarpine toxicity is atropine.
900 Glaucoma
Relative Contraindications Hyperosmotics

1. It may impair the already critical aqueous outflow in
The main indication for the use of hyperosmotics is acute
developmental glaucoma and synechial closure of the
angle closure glaucoma with a very high IOP or other
angle.
conditions like neovascular glaucoma, inflammatory
2. It should also be avoided in patients with acute anterior
glaucoma, etc. which can manifest with dangerously high
uveitis, since it may exacerbate the ocular inflammation
intraocular pressures.
in these cases.
The use of hyperosmotics is generally for a short term,
3. In rubeosis iridis it can cause an increase of IOP.
to tide over the high pressure, till other laser or surgical therapy
4. It can cause bronchospasm and is better avoided in
patients with severe pulmonary disease. is initiated as the definitive treatment.
5. In eyes with a significantly reduced conventional outflow, Agents
it may cause a paradoxical rise in IOP by its action of 1. Glycerol
decreasing uveoscleral outflow. 2. Mannitol
3. Isosorbide dinitrate.
Drug interactions and combination therapy: Adrenaline
produces an additional IOP lowering when it is added to Mode of Action
pilocarpine. Addition of echothiophate iodide to pilocarpine 1. Though the ocular hypotensive effect is not fully
not only has no beneficial effect, it may in fact interfere with understood, the main mechanism by which hyperosmotics
the action of the latter. decrease IOP is said to be by shrinking the volume of
Adding a beta blocker to pilocarpine produces an additional the vitreous. This is because of the increase in the
reduction of 3 to 4 mm Hg. osmolality of the intravascular fluid compartment which
causes an osmotic gradient between it and the
Echothiophate iodide (Phospholine iodide): As described extravascular compartment and thus fluid leaves the latter
above, this drug causes miosis by improving aqueous outflow, to enter the former.
by inhibition of true cholinesterase in the iris sphincter. 2 Another postulated, but not fully accepted mechanism of
Dosage and duration of action: It is available as 0.125 action is that these agents cause osmoreceptors in the
percent solution. It has the advantage of a longer duration hypothalamus to decrease aqueous production. This is called
of action as compared to pilocarpine, with the peak effect at the central nervous system hypothalamic neural theory.
four to six hours. It is recommended for twice daily dosing. It Preparations
may be a useful drug in pseudophakic or aphakic eyes. Mannitol 10 percent, 20 percent; dose 1 to 1.5 g/kg body weight.
Intravenous route at 3 to 5 ml/minute.
Side Effects
IOP reduction occurs within 45 minutes, with a peak at
Ocular: Besides causing cataracts and ocular inflammation, one to two hours and duration of action up to six hours. If
iris cysts near the pupillary margin are common. Corneal crystals are seen in the 25 percent solution, the vial is warmed
epithelial toxicity is also quite common.
up to 60 to 80oC to dissolve the crystals and then warmed to
Systemic: Besides cholinergic effects as with pilocarpine, the body temperature before injection.
drug depletes both true and pseudo cholinesterase in the red Glycerol 50 percent oral solution 1 to 1.5 g/kg or 2 to 3 cc/kg of
blood cells and serum respectively. This also occurs in a 50 percent solution. It is better tolerated if mixed with
newborns, if the mother is on echothiophate in late pregnancy. orange juice and ice. Since it has poor ocular penetration, but
During anesthesia, use of succinylcholine (which needs is distributed throughout the extracellular space, it causes a
pseudocholinesterase for hydrolysis) can lead to prolonged substantial reduction of IOP in just ten minutes, with the
respiratory paralysis. Procaine and tetracaine, which are also peak at one hour and acts for four to five hours.
hydrolyzed in a similar manner, should be used cautiously
with echothiophate. Isosorbide dinitrate It is not available in the United States. It is
The antidote for echothiophate toxicity is pralidoxime not used commonly, but is better tolerated than glycerol and
chloride. does not produce hyperglycemia.
This drug is not readily available, is associated with serious Indications: This class of drugs is indicated only when oral
adverse effects and offers no advantage over pilocarpine. agents fail to lower the IOP satisfactorily.
They are generally indicated in acute rise of IOP and in Brinzolamide and travoprost: Addition of brinzolamide to
conditions like neovascular glaucoma, uveitic glaucoma, travoprost was found to decrease the peak by an additional
traumatic glaucoma and ciliary block glaucoma. 22.7±8.6 percent, with a mean additional decrease in diurnal
Side effects: The increase in the intravascular compartment IOP of 15.8±10 percent.
is the main cause of the adverse effects seen with this class Addition of brinzolamide to a combination of latanoprost
of agents. These can be serious and even fatal. with a beta blocker causes a further reduction in IOP of
1. This class of drugs can precipitate congestive cardiac 9.7±5.7 percent.
failure in a predisposed patient. Prostaglandin analog with beta blocker: Additional
2. In patients with renal failure, electrolyte imbalance caused decrease in IOP is reported to be 25.5 ± 12.4 to 26.0 ± 12
by hyperosmotics can lead to seizures and coma. percent at trough and from 23.5 to 27.7 percent at peak
3. Cerebral dehydration manifesting as headache and when prostaglandin analogs were added to a beta blocker.
disorientation.
4. Gastrointestinal side effects are also seen with the oral Fixed Dose Combination Therapy
agents. The nausea and vomiting induced by the oral
agents, leads to loss of the medication, and also creates Though attempts to develop fixed dose combinations date
problems during surgery. back several decades to the 1960s, when a pilocarpine/
5. Diuresis can be significant with intravenous drugs. epinephrine combination (now of historical interest) became
6. Anaphylactic reactions, backache, chills and fever, commercially available, it is only in recent years that it has
intracranial hemorrhage, pulmonary edema, and renal gained acceptance and approval by various regulatory bodies.
insufficiency are also known to occur. The use of fixed dose combination therapy is more widespread
in the European subcontinent. The main advantage of fixed
Contraindications: Oral glycerol is metabolized to glucose,
dose combinations is the decrease in the frequency of dosage
hence should not be used in diabetics. The osmotic diuresis
of the drug, with an improved compliance as a result. Since
and subsequent dehydration caused by this agent can be
dangerous in a diabetic. about 40 percent of glaucoma patients have been found to
All hyperosmotics should be avoided in renal failure, require more than one IOP lowering medication, this is a
cardiac failure and pulmonary edema. feasible alternative. Indeed, initial monotherapy fails to control
IOP within the first two years of treatment in upto 50 percent
Drug Combinations of glaucoma patients in the US, and a major clinical trial
recently demonstrated that 40 percent of Caucasian patients
The number of possible medical glaucoma medications is require more than one medication to achieve even the modest
innumerable. However, there are a few combinations that goal of a 20 percent reduction. Further, fixed dose
are logical and practical. The following gives a brief overview
combinations, translate to a reduction in the total number of
of the efficacy of the various common combinations used
drops and preservative instilled per day, cost savings,
in clinical practice. Combining medications from the first
improved tolerability and avoiding the washout effect resulting
choice classes leads to significant IOP reduction.
from rapid sequence instillation of multiple drops. It also
Topical CAI and betablocker: Addition of a topical CAI affords the physician flexibility in treatment.
to a beta blocker has been reported to cause a mean additional The fixed drug combinations available presently include
decrease in diurnal curve between 14.4±11.8 and 26.9±12.3 mainly betablockers with other classes of antiglaucoma agents:
percent. 1. Timolol maleate 0.5 percent and dorzolamide 2 percent
2. Timolol 0.5 percent and latanoprost 0.005 percent
Topical dorzolamide and brimonidine: The mean
3. Timolol 0.5 percent and travoprost 0.04 percent
additional decrease in diurnal curve IOP with the addition
4. Timolol 0.5 percent and bimatoprost 0.03 percent
of dorzolamide thrice daily to brimonidine twice daily was
5. Timolol 0.5 percent and pilocarpine 2 percent
found to be 22.3±7.9 percent.
6. Timolol 0.5 percent and brimonidine 0.02 percent
Topical dorzolamide with latanoprost: Dorzolamide added The fixed combination of betaxolol and pilocarpine was
to latanoprost showed an additional decrease in diurnal curve approved by the FDA in 1997, but was not made commercially
IOP of 11.6±7.7 and 14.2±7.9 percent in two studies. available.
902 Glaucoma
Timolol 0.5 percent and dorzolamide 2 percent: Available Limitations

in the US since 1998. While the fixed combination lowered
Fixed dose combinations may not provide the same efficacy
IOP more significantly than either component alone, it
at all time points, compared to the individual components
demonstrated equivalent or greater reduction of IOP to
used separately. They have not shown a clear cut superiority
separate concomitant therapy.
of the components in various trials. It should also be
Timolol 0.5 percent and latanoprost 0.005 percent: remembered that adding a third or fourth medication does
Numerous studies have demonstrated that adding a not significantly increase the percentage drop in IOP from
prostaglandin to a beta receptor antagonist results in additive baseline. A fixed dose combination providing an equivalent
efficacy. This combination was the first available fixed or better safety profile with the added advantage of ease of
combination of a prostaglandin analog with a beta blocker. dosing is an acceptable alternative to concomitant therapy
Two studies by Higginbotham et al12 and Pfeiffer et al13 on with the individual drugs. The single greatest advantage of
relatively large numbers, reported that the reduction of mean fixed combination therapy is convenience.
IOP was about 1 to 1.2 mm Hg more with fixed combination The drug interactions and contraindications of anti-
given once a day in the morning as compared to latanoprost glaucoma medications are elucidated in Table 9.4.1.2.
monotherapy. The difference in IOP reduction between the Table 9.4.1.3 demonstrates the efficiency of different
fixed and unfixed combinations was not significantly different. antiglaucoma drugs available in the market.
Timolol 0.5 percent and travoprost 0.004 percent: This
Glaucoma in Pregnancy
was first approved in Australia in 2005 and is now available
in other countries too. Once daily administration of the fixed Though available literature suggests that the risk of prescribing
combination in the morning produced statistically significant antiglaucoma medication to pregnant women is not significant,
IOP reductions at 7 to 8.2 mm Hg from baseline. there is no hard data to substantiate their safety in these
Timolol 0.5 percent and bimatoprost 0.03 percent: The fixed groups of patients. So the risk of prescribing these
combination of timolol 0.5 percent and bimatoprost 0.03 percent medications in these groups has to be weighed against the
was approved by the EU in 2006. The mean diurnal IOP of the benefit.
fixed combination versus concomitant therapy has been reported Most of the medications have not been studied for their
to be within 1.5 mm Hg (95% CI) at all time points tested. effects on pregnancy in humans. Based on animal studies,
brimonidine and dipivefrin have been presumed and declared
Timolol 0.5 percent and pilocarpine 2 percent: This safe in humans. Latanoprost did not cause any systemic side
combination provides an unstable mixture. Further, while effects threatening abortion or preterm delivery in a human
pilocarpine needs to be administered four times a day for study involving a very small number of patients. Timolol and
maximum effect, timolol provides adequate IOP lowering betaxolol have been found in breast milk of nursing mothers
with a once or twice daily dosing. This combination has not in a miniscule dose that was 1/80th of the cardiac effective
been approved for use in the US. It has been reported to be dose. However, it is recommended that a close watch of the
more effective when instilled in the late morning. It is more nursing infants be maintained. The fixed combination timolol
of historical interest now. 0.5 percent and dorzolamide 2 percent has been declared
highly unsafe during pregnancy and lactation, by the FDA.
Timolol 0.5 percent and brimonidine 0.02 percent: This
While numerous prospective and retrospective study trials
combination was approved in 2006 in the EU. The mean
have proven beyond doubt, that IOP is the major modifiable
IOP reduction with combination therapy has been reported
risk factor in glaucoma, other major outcome studies
between 4.4 and 5.7 mm Hg, with no significant difference
published in recent years like the Ocular Hypertension
between fixed dose and concomitant therapy.
Treatment Study, the Collaborative Initial Glaucoma
Treatment Study, the Collaborative Nor mal-Tension
Adverse Effects
Glaucoma Study, the Advanced Glaucoma Intervention Study
Fortunately, there is no difference in the side effects of the and the Early Manifest Glaucoma Trial have conclusively
fixed combination therapy as compared to the individual proven the benefit of IOP lowering in primary open angle
components. This is a definite advantage while prescribing glaucoma (POAG) and/or ocular hypertension (OHT). The
these medications.13 Early Manifest Glaucoma Trial (EMGT) showed that IOP
Table 9.4.1.2: Anti-glaucoma medications: drug interactions and contraindications

Class of anti- Drug interactions Contraindications
glaucoma drugs
Beta blockers Avoid with calcium channel Absolute—Chronic obstructive pulmonary disease, cardiac failure,
blockers, digitalis, catecholamine cardiac arrhythmias, heart blocks, bradycardia, depression,
depleting drugs. hyperthyroid state, impotence, depression, Raynaud syndrome,
myasthenia gravis.
Relative—Non-insulin dependent diabetes mellitus.
Prostaglandin analogs Not yet reported. No absolute contraindications.
Relative: Allergy, patient predisposed to cystoid macular edema,
uveitis, recent intraocular surgery.
Reinsert contact lenses 15 minutes after instillation of these drugs.
Carbonic anhydrase Avoid with calcium channel blockers. Absolute: Sulpha allergy, renal insufficiency, obstructive
inhibitors GI effects and paresthesias are pulmonary disease, diabetic ketoacidosis.
increased.
Diuretics: Agranulocytosis is a
potential risk.
ACE inhibitors: Bone marrow
suppression.
Beta blockers: Depression, insomnia,
dizziness.
Aspirin: Metabolic acidosis,
hypokalemia, bone marrow
suppression.
Cyclosporin toxicity.
Dilantin, aspirin and NSAIDs to be
avoided.
Adrenergic agonists Avoid with MAO inhibitors, beta Absolute: Allergy.
1. Brimonidine blockers and CNS depressants. Relative: Children and elderly (not tested in children < 2 years)
NSAIDs and aspirin can cause Stimulate hyperglycemia and decrease the effect of insulin. So
systemic hypertension and also use with caution in diabetics and patients on thyroid supplements.
decrease the IOP lowering efficacy.
Alpha adrenergics may decrease the
efficacy of ACE inhibitors.
Calcium channel blockers and
diuretics may increase the possibility
of gastrointestinal side effects.
Use with caution with tricyclic
antidepressants.
2. Apraclonidine
Epinephrine & Unsafe with MAO inhibitors, Absolute: Cardiac disease, arrhythmias, essential hypertension.
Dipivefrin glycosides, beta blockers.
Tricyclic antidepressants can
potentiate the systemic side effects
of topical epinephrine
Cholinergics Avoid glycosides and depolarizing Relative: Developmental glaucoma, synechial angle closure.
agents (indirect agents). Absolute: Rubeosis iridis, severe pulmonary disease, acute
anterior uveitis.
Hyperosmotics Absolute: Renal failure, cardiac failure, glycerol in diabetics.
reduction, by at least 25 percent reduced progression of Future Considerations in Medical Therapy

glaucoma to the tune of 45 percent in the treated group, as
compared to 62 percent in the untreated group. 14 The There is ongoing research to find agents that halt the
Collaborative Initial Glaucoma Treatment Study reported that irreversible process of apoptosis of the retinal ganglion cells.
lowering IOP by 35 percent decreased disease progression to These neuroprotective agents like N-methyl-D-aspartate
less than 15 percent.15 receptor antagonist memantine, nitric oxide synthase inhibitors,
904 Glaucoma
Table 9.4.1.3: Efficacy of different antiglaucoma drugs

3. Konstas AGP, Mikropoulos D, Dimopoulos AT, et al. Second-
line therapy with dorzolamide/timolol or latanoprost/timolol
Anti-glaucoma Reduction in IOP fixed combination versus adding dorzolamide/timolol fixed
drug/class baseline (%)* combination to latanoprost monotherapy. Br J Ophthalmol
2008;92:1498-502.
Selective beta blockers 20–25
4. Ritch R, Shields MB and Krupin T (eds) The Glaucomas. 2nd
Nonselective beta blocker 25–30 edn. St Louis, MO: Mosby, Inc, 1399-408.
Prostaglandin analog 27–34% (least with 5. Freedman SF, Freedman NJ, Shields MB, et al. Am J Ophthalmol
unoprostone) 1993;116(5):600-11.
Topical carbonic anhydrase 17 6. Woodward DF, Krauss AH, Chen J, et al. Pharmacological
inhibitors characterization of a novel antiglaucoma agent, Bimatoprost (AGN
Systemic carbonic anhydrase 30 192024). J Ocul Pharmacol Exp Ther 2003;305(2):772-85.
inhibitors 7. Alm A, Widengard I. Latanoprost: experience of 2-year treatment
Cholinergics 20 in Scandinavia. Acta Ophthalmol Scand 2000;78(1):716.
Brimonidine 20–30
8. Kashiwagi K, Tsumura T, Tsukahara S. Long-term effects of
latanoprost monotherapy on intraocular pressure in Japanese
Apraclonidine 19–26
glaucoma patients. J Glaucoma 2008;17(8):662-6.
*Average values derived from clinical study reports 9. Netland PA, Robertson SM, Sullivan EK, et al. Response to
travoprost in black and non-black patients with open angle
glaucoma or ocular hypertension. Adv Ther 2003;20(3):149-63.
10. Sponsel WE, Harrison J, Elliot WR, et al. Dorzox hydrochloride
peptides like vasoactive intestinal peptide, atrial natriuretic and visual function in normal eyes. Am J Ophthalmol
peptides, cannabinoids, ethacryanic acid, catecholaminergic 1997;123(6);759-66.
agents like haloperidol, calcium channel blockers and many 11. Siesky B, Harris A, Cantor LB, et al. A comparative study of the
effects of brinzolamide versus dorzolamide on retinal oxygen
others are being evaluated for their scope in reducing IOP saturation and ocular microcirculation in patients with open angle
by tackling the cause, rather than the effect. All these agents glaucoma. Br J Ophthalmol 2008;92(4):500-4.
are in various stages of investigation and not for clinical 12. Higginbotham EJ, Diestelhorst M, Pfeiffer N, et al. The efficacy
application presently. and safety of unfixed and fixed combinations of latanoprost and
other antiglaucoma medications. Surv Oph 20002;47 Suppl
The authors/editors have no financial interest in any 1:S133-40. Review.
product or procedure in this chapter. 13. Pfeiffer N. European Latanoprost Fixed Combination Study
Group. A comparison of the fixed combination of latanoprost
REFERENCES and timolol with its individual components. Graefes Arch Clin
Exp Ophthalmol 2002;240(11):893-9.
1. Schmier JK, Covert DW, Robin AL. Estimated first year costs of 14. Leske MC, Heijl, Hyman, et al. Early Manifest Glaucoma Trial:
prostaglandin analogs with or without adjunctive therapy for design and baseline data. Ophthalmology 1999;106(11):2144-53.
glaucoma management: a US perspective. Curr Med Res Opin. 15. Collaborative Normal Tension Glaucoma Study Group. Comparison
2007;23(11):2867-75. of glaucomatous progression between untreated patients with
2. Shin DH, Feldman RM, Shen WP, et al. Fixed combination normal-tension glaucoma and patients with therapeutically reduced
Latanoprost/Timolol Study Group. Ophthalmology 2004; intraocular pressures. Collaborative Normal Tension Glaucoma
111(2):276-82. Study Group. Am J Ophthalmol 1998;126(4):487-97.
9.4.2 Management of Primary

Congenital Glaucoma
Primary congenital glaucoma (PCG) is a potentially blinding glaucoma (PCG) is a specific, inherited developmental defect
disease of children, which if untreated, results in a lifetime in the trabecular meshwork and anterior chamber angle, which
of blindness. It occurs due to obstruction of the drainage of manifests in the neonatal or infantile period and is more severe
the aqueous humor caused by a primary developmental and difficult to manage than other types.
anomaly at the angle of the anterior chamber. The onset of It is generally agreed that the IOP elevation in congenital
disease is in the neonatal or infantile period, and is manifested glaucoma is a result of abnormal development of the anterior
by symptoms of raised IOP and corneal edema such as chamber angle that leads to inadequate drainage of the aqueous
excessive tearing, photophobia, and an enlargement of the humor. Most forms of congenital glaucoma are believed to
globe (buphthalmos). The consequences of persistently raised result from a developmental arrest of anterior chamber angle
intraocular pressure on the optic nerve are far more serious, tissue derived from neural crest cells leading to aqueous outflow
manifesting as axonal damage and eventual irreversible obstruction. The exact nature of the structural changes in the
blindness. angle that are associated with the disease has been debated.
Although primary congenital glaucoma is the most The early postulation of an imperforate mesodermal membrane
common glaucoma seen in infancy, it is still an uncommon covering the outflow channels has not been verified by electron
disease. The incidence varies from 1 in 1250 births in microscopy. Histopathological studies have observed that the
Slovakian Romanians1 to 1:10,000 in Scandinavian regions.2 iris insertion and anterior ciliary body overlaps the posterior
In India, the incidence has been reported to be 1:3300 live portion of the trabecular meshwork.14 It was concluded that
births,3 which, with an annual birth rate of 25 million, during anterior chamber development, the iris and ciliary body
translates to nearly 7,600 new cases per year. The variable failed to recede posteriorly. Tawara and Inomata15 studied
incidence in various ethnic groups point towards a genetic trabeculectomy specimens from eyes of patients with PCG
basis for the disease. and observed that the juxtacanalicular area was markedly
Most cases of primary congenital glaucoma occur thickened and consisted of many layers of spindle-shaped cells
sporadically, but in approximately ten percent of cases, an with surrounding extracellular matrix. In general, structural
autosomal recessive hereditary pattern is evident.4 The PCG studies agree that developmental defect affects all areas of the
gene has been mapped to three different genetic loci: GLC3A trabecular meshwork.
(2p21), GLC3B (1p36); and GLC3C (14Q24.3).5-7 The first These developmental anomalies of the anterior chamber
gene to be implicated in the pathogenesis of PCG was the angle prevent drainage of aqueous humor, thereby elevating
human cytochrome P450 gene (CYP1B1).5 The involvement intraocular pressure (IOP).
of CYP1B1 varies from 20 percent in Indonesians8 and Clinical features of PCG typically include tearing,
Japanese,9 to 50 percent among Brazilians,10 and nearly 100 photophobia, clouding of the cornea and buphthalmos
percent among Saudi Arabians11 and Slovakian Gypsies.12 In (enlargement of the globe) (Figs 9.4.2.1 to 9.4.2.3). Because
a study involving South Indian patients, 30.8 percent of 138 the ocular coat of the infantile eye is elastic, it stretches in
PCG cases were found to be positive for one of six mutations response to elevated pressure, resulting in an enlarged globe.
of the CYP1B1 gene.13 Ethnic differences and geographical The more serious consequence of elevated pressure is that it
variations may be associated with different mutation patterns. can rapidly lead to axonal loss and permanent visual
impairment in untreated children.
STRUCTURAL DEFECTS AND
CLINICAL FEATURES MANAGEMENT
The glaucomas are a heterogeneous group of insidious The management of congenital glaucoma starts with parental
diseases associated with elevated intraocular pressure (IOP) counseling which should include a discussion of what is
and optic nerve atrophy. Primary congenital (infantile) glaucoma; the need for surgery and possibilites of multiple
906 Glaucoma
Fig. 9.4.2.1: PCG presenting with watering and photophobia Fig. 9.4.2.3: PCG presenting with buphthalmos and hazy corneas
IOP in a hungry feeding baby while he is being fed. The

mean IOP in anesthetized newborns is 9 to 10.0 mm Hg.14
Other signs to alert the physician to underlying disease
are café au lait spots, in neurofibromatosis, as glaucoma occurs
in 50 percent of cases when the eyelid/eye is involved. It is
important to keep aniridia, and the rubella syndrome in mind
when evaluating possible glaucoma in young children.
Examination Under Anesthesia

The diagnosis of glaucoma depends upon several factors,
IOP is only one of them. Elevated IOP unless extreme, is
Fig. 9.4.2.2: PCG presenting with scarred corneas not sufficient to confirm glaucoma. It is important to look
for other signs such as corneal diameters, corneal haze,
surgeries, the need for life-long follow-up and the combination evidence of trabeculodysgenesis by gonioscopy, and increased
of problems to be tackled (IOP, amblyopia management, cup-disc ratio by ophthalmoscopy.
refractive correction, possible keratoplasty).
Intraocular Pressure (IOP)
Examination in Clinic/Office
It is important to measure the IOP as soon as possible after
Slit examination is usually difficult, but it helps to get as much induction to minimize the effects of anesthetic drugs. The
information as possible even with torchlight examination. It normal IOP in infants is slightly lower than in adults but 18
is important to observe the corneal size and clarity, degree mm Hg remains a useful upper limit. Most anesthetic agents
of tearing/photophobia, any discharge/swelling in the lacrimal reduce IOP. Under halothane, it is usually 16 mm Hg. Truly
sac area or a positive sac test. In case of total corneal opacity raised IOP often remains in the abnormal range. Asymmetric
in both eyes precluding any view of the fundus, B-scan IOP is more suggestive of an abnormality than bilateral
ultrasound is mandatory to rule out any causes of secondary borderline IOP measurements.
glaucoma such as that due to childhood tumors like
retinoblastoma. Corneal Diameter
The IOP in children may be fallaciously low due to low Usually the corneal diameter in infants is less than 12 mm
scleral rigidity, but nevertheless is an important parameter to Hg (Refer to chapter on congenital glaucomas).
monitor the disease. It is preferable to measure IOP using
Perkins applanation tonometer/tonopen, since the low scleral Corneal Haze and Haab's Striae
rigidity is likely to result in fallacious readings in infants if Haab’s striae are breaks in the Descemet’s membrane. As the
using a Schiotz tonometer. It may be possible to measure the cornea stretches, there is acute localized corneal edema and
deposition of new basement membrane into the hyaline ridges. Treatment of Congenital Glaucoma
These striae are oriented curvilinearly or horizontally. The
The treatment of PCG is surgical. Medical management has
incidence is about 25 percent at birth and 60 percent at six
a role as a temporizing measure until the child can be posted
months.
for general anesthesia. The goal of surgery is to normalize
and permanently control IOP without drugs if possible, clear
Gonioscopy
the cornea, prevent progression of disc cupping and increase
Direct gonioscope such as the Koeppe's lens is used to visualize in corneal diameters, preserve visual field and ocular integrity,
the angle. Usually there may be multiple hyaline processes and to stimulate development of binocular stereoscopic vision.
and/or high insertion of the iris. The surgical options include goniotomy, trabeculotomy,
combined trabeculotomy-trabeculectomy, trabeculectomy with
Optic Disk Evaluation antifibrotic agents and glaucoma drainage devices in
Dilated fundus examination should be a routine of EUA when recalcitrant cases.
media clarity permits adequate visualization. A cup-disc ratio Goniotomy
>0.3 is rare in normal infants. The infant glaucomatous cup
is more often round, steep walled, central and surrounded by The purpose of goniotomy (Fig. 9.4.2.5) is to clear the
uniformly pink neuroretinal rim. It is important to keep in obstruction to aqueous outflow from the eye, which in turn
mind that cupping in infants is often reversible, hence, proper lowers the intraocular pressure (IOP).
documentation at the time of initial EUA is of utmost Clear corneas are required for the procedure. Though
importance goniotomy is the classic surgical procedure described for
developmental glaucoma, it is less commonly performed in
Retinoscopy India, since it requires clear cornea and more than 80 percent
of Indian children present with severe corneal edema.
Buphthalmos usually results in myopia and proper periodic
retinoscopy with appropriate patching, if required must not Procedure: Once the patient is anesthetized, a forceps or
be forgotten while managing these children. sutures are used to stabilize the eye in the correct position.
Once the child is three to four years old, he/she can be The patient's head is rotated away from the surgeon so that
trained for measurement of IOP and appropriate slit-lamp the interior structures of the eye are more easily seen. Next,
evaluation (Fig. 9.4.2.4). with either a knife-needle or a goniotomy knife, the surgeon
Parental counseling is the next important step once a punctures the cornea while looking at the anterior chamber
diagnosis of glaucoma is confirmed in a child. angle through a microscope or a hand-held slit-lamp using
Fig. 9.4.2.4: A 4-year-old child with congenital glaucoma undergoing

sit-lamp examination including IOP recording by Goldmann applanantion
tonometry Fig. 9.4.2.5: Principle of goniotomy
908 Glaucoma
direct gonio lens. An assistant uses a syringe to introduce Trabeculotomy

fluid into the eye's anterior chamber through a viscoelastic
Trabeculotomy ab-externo was simultaneously and
tube as the surgeon goes on to perform the goniotomy.
independently described by Herman Burian and Redmond
A gonioscopy lens is placed on the eye. As the eye is
Smith in 1960, Two specially designed instruments called
rotated by an assistant, the surgeon sweeps the knife blade or
trabeculotomes are used. Trabeculotomy ab-externo results
needle through 90 to 120 degrees of arc in the eye, making
in the opening of the Schlemm’s canal into the anterior
incisions in the anterior trabecular meshwork, avoiding the
chamber and is especially used in cloudy corneas, which
posterior part of the trabecular meshwork in order to decrease
precludes goniotomy. There are two main procedures—the
the risk of damage to the iris and lens. Once the knife and
standard trabeculotomy and the 360° suture trabeculotomy.
tubing are removed, saline solution is introduced to maintain
the integrity of the eye and the incision is closed. a. Standard Trabeculotomy
The usual post-operative regimen includes antibiotics and Procedure:
corticosteroids to the eye to prevent infection and reduce A fornix-based conjunctival peritomy is followed by creation
inflammation. The head is then rotated away from the incision of a partial thickness scleral flap extending into the clear
site so that blood cannot accumulate. The second eye may be cornea. Gentle cautery is used for hemostasis. A sharp 15°
operated on at the same time. If the procedure needs to be stab blade is used to make a shallow 1.5 to 2.0 mm incision in
repeated, another area of the eye is treated. the bed of the scleral flap. The incision is slowly dissected
Follow-up: About ten percent of goniotomy patients under relatively high magnification to enter the Schlemm’s
experience a recurrence of the glaucoma in the same eye or canal (Fig. 9.4.2.6). An egress of aqueous or blood-tinged
it develops in the unaffected eye. As a result, the patient fluid marks entry into the Schlemm’s canal. A change in the
needs periodic eye examinations for the rest of his/her life. direction of scleral fibers to an orientation perpendicular to
If glaucoma does recur later in life, then either medical or the limbus is a clue to the location of Schlemm’s canal. Once
surgical treatment is instituted depending on the cause. it is reliably located, the arms of the trabeculotomes are
inserted one by one into each side to cannulate the Schlemm’s
Complications: Since goniotomy is performed under general canal and then turned anteriorly to enter the anterior chamber
anesthesia, there is the usual risk of GA to the child. The first with the left and then with the right probe. The partial
most common risk of general anesthesia in infants is thickness scleral flap is sutured with 10-0 nylon, and the
cardiorespiratory arrest. This complication is not common,
conjunctival flap sutured with 8-0 vicryl.
however, and occurs in fewer than two percent of patients
undergoing goniotomies. Hyphema is the most common b. 360° Suture Trabeculotomy
complication of goniotomy. In most cases, it resolves The initial steps are identical to a standard trabeculotomy.
spontaneously within a few days. Potential risks include Once the Schlemm’s canal is cannulated, a 6-0 polypropylene
iridodialysis or cyclodialysis, both of which can lead to suture fragment of 65 to 80 mm length with a rounded head
hypotony. Other complications of goniotomy are cataract
formation, uveitis, corneal scarring, subluxation or dislocation
of the lens, and retinal detachment. The intraocular pressure
may increase in spite of, or due to complications of the
procedure, and the goniotomy may have to be repeated. If
the goniotomy is not successful after two or three attempts, a
trabeculectomy with antimetabolites is required.
Prognosis: Goniotomy is most successful when the child is
between one month and three years of age; it is successful
in only 25 percent of cases in patients younger than one
month. It is also more successful when the corneal diameter
is less than 14 mm, is clear, and when the IOP is not
extremely high. Even if the IOP has been lowered, anti-
glaucoma medication or drops may still be needed after the
goniotomy. Fig. 9.4.2.6: Entry into the Schlemm’s canal with a trabeculotome
is taken. (The rounded head is made by cauterizing the sharp failure of conventional surgery. Aqueous shunt implantation
end of the suture). This suture is passed through the Schlemm’s may offer greater chance of successful glaucoma control in
canal after proper identification. The suture is passed right the first two years of life compared to trabeculectomy with
around the angle slowly until the entire Schlemm’s is cannulated. anti-metabolites. In a report of 52 eyes in pediatric patients
Gonioscopy is used to follow the suture around the eye. Once under the age of 18 implanted with an Ahmed Glaucoma
the suture is passed successfully 360° around the eye, and Valve. Chen et al17 reported success rates of 85 percent, 63
after both the proximal and distal ends are grasped by forceps, percent, 51 percent, and 41 percent at one, two, three and
the ends of the suture are pulled in opposite directions. This four years respectively.
movement results in breaking through the trabecular The authors/editors have no financial interest in any product or procedure
meshwork over the entire 360° of the eye, and the procedure mentioned in this chapter.
is completed.
REFERENCES
Prognosis: Reported success rates with trabeculotomies range 1. Gencik A, Gencikova A, Ferak V. Population genetical aspects of
between 70 to 90 percent with the highest successes noted primary congenital glaucoma. I. Incidence, prevalence, gene
when the infant presents before 12 months of age. frequency, and age of onset. Hum Genet 1982;61:193-7.
2. Francois J. Congenital glaucoma and its inheritance.
Trabeculotomy with Trabeculectomy Ophthalmologica 1972;181:61-73.
3. Dandona L, Williams JD, Williams BC, Rao GN. Population-
Trabeculotomy-trabeculectomy combined surgery has been based assessment of childhood blindness in southern India. Arch
found to result in more favorable outcomes and many surgeons Ophthalmol 1998;116:545-6.
prefer this approach. This procedure provides two major 4. Sarfarazi M, Stoilov I. Molecular genetics of primary congenital
pathways for outflow through the trabeculectomy opening glaucoma. Eye 2000;14:422-8.
and through the disruption of the Schlemm’s canal. Mandal 5. Sarfarazi M, Akarsu AN, Hossain A, Turacli ME, Aktan SG,
Barsoum-Homsy M, Chevrette L, Sayli BS. Assignment of a
et al in a study of 120 eyes reported a high success rate of
locus (GLC3A) for primary congenital glaucoma (Buphthalmos)
94.4 percent.16 to 2p21 and evidence for genetic heterogeneity. Genomics
After standard trabeculotomy, the anterior chamber is 1995;30:171-7.
entered and a trabeculectomy sclerostomy is made as for a 6. Akarsu AN, Turacli ME, Aktan SG, Barsoum-Homsy M, Chevrette
trabeculectomy. The rest of the procedure is the same as for L, Sayli BS, Sarfarazi M. A second locus (GLC3B) for primary
trabeculotomy thereafter. congenital glaucoma (Buphthalmos) maps to the 1p36 region.
Hum Mol Genet 1996;5:1199-203.
Trabeculectomy with Antimetabolites 7. Sarfarazi M, Stoilov I, Schenkman JB. Genetics and biochemistry
of primary congenital glaucoma. Ophthalmol Clin N Am
This is infrequently performed as a primary procedure in 2003;16:543-54.
primary congenital glaucoma, and is usually reserved for those 8. Sitorus R, Ardjo SM, Lorenz B, Preising M. CYP1B1 gene analysis
infants with other developmental anomalies such as Axenfeld- in primary congenital glaucoma in Indonesian and European
Reigers syndrome or repeat surgery required for recalcitrant patients. J Med Genet 2003;40:e9.
cases. Mitomycin C is the usual antimetabolite used in a 9. Kakiuchi-Matsumoto T, Isashiki Y, Ohba N, Kimura K, Sonoda
S, Unoki K. Cytochrome P450 1B1 gene mutations in Japanese
concentration of 0.2 percent for two minutes under the
patients with primary congenital glaucoma. Am J Ophthalmol
conjunctival flap. 2001;131:345-50.
Problems of Performing Trabeculectomy in Children: 10. Stoilov IR, Costa VP, Vasconcellos JP, Melo MB, Betinjane AJ,
Carani JC, Oltrogge EV, Sarfarazi M. Molecular genetics of primary
Trabeculectomy procedure in a small child is more challenging
congenital glaucoma in Brazil. Invest Ophthalmol Vis Sci 2002;
as compared to that in adults. Specific problems are difficulty 43:1820-7.
in making the scleral flap in a stretched and thinned out limbus, 11. Bejjani BA, Lewis RA, Tomey KF, Anderson KL, Dueker DK,
distorted angle anatomy, thick tenon's capsule prone to fibrosis Jabak M, Astle WF, Otterud B, Leppert M, Lupski JR. Mutations
and scarring with rapid wound healing, and low scleral rigidity. in CYP1B1, the gene for cytochrome P4501B1, are the
predominant cause of primary congenital glaucoma in Saudi Arabia.
Glaucoma Drainage Devices Am J Hum Genet 1998;62:325-33.
12. Plasilova M, Stoilov I, Sarfarazi M, Kadasi L, Ferakova E, Ferak
In cases of refractory cases not responding to surgery, a V. Identification of a single ancestral CYP1B1 mutation in Slovak
repeat surgery is needed. Shunts in the form of valved and Gypsies (Roms) affected with primary congenital glaucoma. J
non-valved implants have been reported to be successful after Med Genet 1999;36:290-4.
910 Glaucoma
13. Bejjani BA, Stockton DW, Lewis RA, Tomey KF, Dueker DK, 15. Tawara A, Inomata H. Developmental immaturity of the
Jabak M, Astle WF, Lupski JR. Multiple CYP1B1 mutations and trabecular meshwork in congenital glaucoma. Am J Ophthalmol
incomplete penetrance in an inbred population segregating primary 1981;92:508-25.
congenital glaucoma suggest frequent de novo events and a 16. Mandal AK, Bhatia PG, Bhaskar A, et al. Long-term surgical and visual
dominant modifier locus. Hum Mol Genet 2000; 9:367-74. outcomes in Indian children with developmental glaucoma operated
Erratum in: Hum Mol Genet 2000;9(7):1141. upon within 6 months of birth. Ophthalmology 2004;111:283-90.
14. Domoniguez A, Banos MS, Alvare MG, et al. Intraocular pressure 17. Chen TC, Bhatia LS, Walton DS. Ahmed valve surgery for refractory
measurements in infants under one year. Am J Ophthalmol pediatric glaucoma: a report of 52 eyes. J Pediatric Ophthalmol
1974;78:110. Strabismus 2005;42:274-83.
9.4.3 Trabeculectomy and Its Modifications

Kirti Singh, Shalini Gupta
Trabeculectomy, the most common glaucoma surgery • Aqueous flow into the cyclodialysis cleft created between
performed, allows drainage of aqueous humor from the the ciliary body and sclera if the tissue is dissected posterior
anterior chamber to the subconjunctival space from where it to the scleral spur.
is absorbed. This guarded filtration surgery has replaced free
filtering operations and retained some features of sclerostomy ANESTHESIA
(Elliot's trephining), peripheral iridectomy (Scheie's) and added
creation and suturing of the superficial scleral flap. It has Patients with advanced visual field compromise have to be
revolutionized glaucoma treatment and relegated the older given lesser volume of peribulbar injection since the
surgeries of thermal sclerostomy and posterior lip sclerectomy intraocular pressure spike induced by the local anesthetic
to oblivion.1-3 The first report of the success of the modified injection can cause further damage to the already
technique by Cairns appeared in 1968.4 Cairn's procedure compromised optic nerve head circulation. It is advisable to
involved removal of a portion of trabecular meshwork to avoid epinephrine in the injection, since it can cause
allow free access of aqueous into cut ends of the Schlemm's vasoconstriction of the small vessels supplying the already
canal. A partial-thickness scleral flap covered the sclerostomy compromised optic nerve head.6
and regulated aqueous outflow, thus the name guarded was In advanced glaucoma cases with a small window of
used. The previous technique of Sugar had involved tight residual visual field, the use of compressive ball like Super-
suturing of the flap which led to minimal subconjunctival Pinky or Honan is to be avoided, so that sustained mechanical
filtration and subsequent failure.5 pressure does not jeopardize the vulnerable optic nerve head
circulation.7 Instead, a controlled gentle digital massage with
MECHANISM OF TRABECULECTOMY the hand is advocated.
It aims at creating a bypass channel at the limbus which TECHNIQUE

circumvents the dysfunctional trabecular meshwork and allows
Site of Filtration Area
aqueous to drain into the subconjunctival space. The various
pathways adopted by the aqueous to drain in trabeculectomy The preferred filtration site is superior and slightly to the
are: nasal side, since it leaves adequate space on the temporal side
• Filtration through the sclerostomy around margins of the for a repeat surgery. Superior limbus has long been the
scleral flap into the subconjunctival filtering bleb conventional site since the bleb is snugly covered by the lid,
• Filtration through outlet channels in the scleral flap to the which both protects it and hides its unsightly appearance.
subconjunctival space The superior peripheral iridectomy (PI) is also covered by
• Aqueous flow into cut ends of Schlemm's canal into the upper lid and thus diplopia induced by an inadvertently
collector channels and subsequently episcleral veins large PI is avoided. An inferior trabeculectomy is not very
desirable since it has been observed that the incidence of the suture for superior rectus bridle can be 4-0 silk or even a
endophthalmitis increases with an inferiorly located bleb, simple autoclaved cotton thread.
especially if antimitotics have been used, by 7.8 percent per
patient per year which is six times the risk after a superior Conjunctival Incision
trabeculectomy.8,9 In cases of buphthalmos or advanced
Conjunctiva should be handled very gently. Rough handling
glaucoma, where the first surgery should ideally provide the
of conjunctiva entails buttonholing risk and causes subsequent
best rehabilitation, a true superior trabeculectomy is preferred
release of inflammatory mediators, which can lead to bleb
since it gives best exposure.
failure. The debate as to whether limbal or fornix based flap
After conjunctival dissection, if an emissary vein is spotted
is still on. Table 9.4.3.1 compares the differences between
in the proposed area, it is better to avoid the vessel, though it
limbal based and fornix based conjunctival flaps. A limbus
may not be possible in all cases (Fig. 9.4.3.1). This is because
based conjunctival incision is shown in Figure 9.4.3.3.
if these vessels are cut during scleral flap dissection, the ooze
Both limbal and fornix based conjunctival flap give
is troublesome and often requires cauterization. Excessive
equivalent IOP control. In eyes with prior ocular surgeries,
cauterization is to be avoided at all costs since it causes scleral
shrinkage.
Bridle Suture
The conventional superior rectus suture placed 10 to 15 mm
behind the limbus can give rise to a hematoma, which by
releasing growth factors facilitates healing of the wound (Fig.
9.4.3.2). Blood contains many growth factors, which promote
healing and thereby contribute to bleb failure.7 In a limbal
based conjunctival flap; the superior rectus traction suture
makes conjunctival suturing difficult. To avoid these
complications, clear corneal traction suture is advocated. The
pulling force of a corneal traction suture in rotating the eyeball
downward is superior to that of a superior rectus suture.
The surgeon needs to minimize the depth of penetration to
avoid corneal perforation and avoid taking too superficial a
bite to prevent cheese wiring the corneal tissue. The ideal
suture depth is till 3/4th of the corneal thickness. It is placed
1 mm from limbus and the bite width is 4 to 5 mm. The
suture material is either 6-0 silk or nylon. On the other hand, Fig. 9.4.3.2: Superior rectus suture bridles suture being applied
Fig. 9.4.3.1: Identification of an emissary vein is of significance. Fig. 9.4.3.3: Limbus based conjunctival flaps
912 Glaucoma
Table 9.4.3.1: Comparison between limbal versus fornix based conjunctival flap
Limbal based Fornix based
Location Incision is 8 mm behind the limbus Incision at limbus
Conjunctival incision length Relaxing incision more difficult to suture Can be shortened with an L shaped incision
Scleral and conjunctival handling More extensive, button-holing more common Less, button-holing incidence less
Hemorrhage More Less
Exposure of operating field Good Better
Scleral flap dissection Difficult Easier
Mitomycin application More cumbersome Easier
Releasable suture placement Technically more difficult Technically easier
Surgical time Longer Shorter
For combined surgery Cumbersome Easier
Wound leak risk Minimal Potential risk
Bleb morphology Overhanging bleb Posteriorly directed bleb
Bleb massage postoperatively Done with confidence Done with trepidation
Astigmatism induced Less More, especially with bleb
forming corneal sutures,
which reverts after suture
removal
In repeat surgery/pseudophakia More difficult to make Easier to make
the conjunctiva is often adherent to the underlying sclera at

limbal area thus making dissection difficult while lifting a
limbal based flap. In addition, studies have demonstrated a
more posteriorly located bleb with a fornix based approach.7
The reason for this is attributed to minimal conjunctival
manipulation with fornix based approach. Another cause is
the fibrotic band which often forms at the incision site during
healing in a limbal based conjunctival flap, which restricts
posterior flow of aqueous (Fig. 9.4.3.4). Labeled as a "ring
of steel" by Peng Khaw of Moorfield Hospital, UK it has
led many surgeons to switch to a fornix based flap.7
Tenonectomy
Some surgeons advocate tenonectomy as an aid in achieving
lower IOP,8-10 whereas others have concluded that it has no
beneficial effect.11-13 In fact, Scott et al opined that tenone-
ctomy was an etiological factor in the development of encysted Fig. 9.4.3.4: “Ring of steel” denoting the fibrosis taking place at the site
blebs.14 A comprehensive study from Turkey sought to prove of conjunctival suturing in a limbal based flap during the process of
healing
that leaving behind a thick Tenon capsule in young patients
undergoing Mitomycin-C (MMC) augmented trabeculectomy failure. Thus, meticulous subconjunctival and episcleral
would prevent bleb leaks. However, they found that over a hemostasis is not only essential for adequate exposure and
two year follow-up, avascular thin-walled bleb still formed in dissection, but also to ensure longevity of the bleb (Fig. 9.4.3.5).
84 percent eyes, shallow anterior chamber occurred in 31 Use of a Tadworth ball cautery is not recommended. Only
percent, hypotony in 16 percent, and endophthalmitis in 2 cautious wetfield cautery should be done. As already
percent. Thus, even a thick Tenon's capsule was no safeguard mentioned, emissary veins may be difficult to coagulate.
against MMC complications.12 Miller et al advocate partial Gentle cautery not aiming for a complete cessation is best in
tenonectomy as being equivalent to total tenonectomy.13 this situation. Once aqueous flow occurs, small ooze often
ceases on its own. Thus, aggressive cautery should never be
Hemostasis
performed. The keyword in glaucoma surgery is gentle
Blood releases healing factors, which cause conjunctival and handling of tissues to prevent excessive healing response which
scleral scarring, thereby precipitating and aggravating bleb would cause bleb failure.
Fig. 9.4.3.6: Scleral flap dissection
C (MMC) percolating through the scleral bed, and causing

toxicity to the ciliary body were proved to be ill founded,
Fig. 9.4.3.5: Gentle cauterization with the Wetfield thus intrascleral use of MMC has now become more
cautery is recommended common.16 Few studies state that intrascleral use of mitomycin
causes more ocular hypotony, choroidal detachment and
Scleral Flap Dissection
shallow anterior chamber.15-20 Thus, intrascleral application
A rectangular or a triangular flap is outlined in dimensions of although no longer a taboo, must be used judiciously.
4 to 4.5 × 4.5 to 5 mm (rectangular) or 4.5 to 5 × 3.5 mm
(triangular).14 The instrument used could be either a Bard Parker Technique of Application
handle, an eleven or fifteen number blade, a disposable cutting
Merocel sponges are cut into multiple pieces and MMC is
knife or a diamond knife. The tip of the triangle or one corner
squirted on the cut pieces of the Merocel sponges. Excess
of the rectangle is lifted with a non-toothed forceps. A lamellar
mitomycin is squeezed out with forceps. These soaked sponges
cleavage plane is then dissected with a crescent blade. It is best
are then placed under the conjunctiva in all directions. Contact
to aim at keeping the plane of dissection at 1/2 to 2/3rd
of MMC with cut edges of conjunctiva is to be avoided
depth of the sclera.
since that would prevent healing and cause wound leak.
The dissection is carried till one crosses the blue gray
Cutting of sponge into multiple pieces ensures coverage of
barrier where the white scleral fibers merge into the gray
large subconjunctival area. After the requisite time limit
zone. The white, opaque crisscrossing fibres of the sclera
ranging from two to four minutes, the sponges are removed
merge with a gray band of parallel fibers, which overlie the
and area washed with running Ringer lactate or saline. The
scleral spur. Anterior to this lies transparent corneal tissue.
cotton used to soak this fluid and the sponges are discarded,
The junction of the posterior border of the blue gray zone
the instruments used in MMC application are not used again
(trabecular band) and the sclera is the external landmark for
in the surgery, to avoid any MMC contamination of the
the scleral spur. The dissection is further carried on into 1
surgical field. It is advisable for the surgeon to change gloves
mm of clear cornea (Fig. 9.4.3.6). The Schlemm's canal is
at this stage, since any residual drug is toxic to tissues.
usually situated just anterior to the scleral spur, sometimes it
Mitomycin C is available in a vial in powder form in 2
is found behind it.14
mg or 10 mg (Biochem Laboratories, West Michigan, USA).
It is freshly reconstituted with distilled water or normal saline
Mitomycin C (MMC) Application
in a concentration of 0.2 to 0.5 mg/ml. After adding 10 ml
Mitomycin could be applied before, or after complete scleral of distilled water to the 2 mg bottle and shaking it, a potent
lamellar flap dissection.15,16 The previous fears of mitomycin drug assumes a light purple color. The concentration of MMC
914 Glaucoma
in such a preparation is 0.2 mg /ml. It can be used for multiple 5-Fluorouracil (5-FU): A pyrimidine analog, it acts by
surgeries done during the same day but should be discarded competitive inhibition of thymidylate synthase enzyme. This
at the end of the day. cell-cycle specific drug interferes with the S-phase of cell
replication. This specificity makes 5-FU more toxic to
Antimetabolites in Trabeculectomy
replicating cells than to non-proliferating cells. It is used as
Adjunctive antimetabolites are used to reduce postoperative multiple post-operative subconjunctival injections or as a single
subconjunctival fibrosis, which is especially important in cases intra-operative application. It is available in an ampoule of
with high risk of failure. Antimetabolites like mitomycin C 500 mg in 5 ml or 250 mg in 2.5 ml and is highly toxic to the
and 5-fluorouracil 5-(FU) inhibit fibroblast proliferation and cornea. The 5-FU injections are given daily by subconjunctival
subsequent scar tissue formation. route for a period of ten days, in the dose of 5 mg/day.
Indications for their use in glaucoma surgery Intra-operative dose of 50 mg/ml can be applied over the
1. Young patients less than 40 years of age.20 site with soaked Merocel sponges for a period of five minutes,
2. Secondary glaucoma (uveitic, neovascular, aphakic, post with equally efficacious results. A lower dose of 25 mg/ml
keratoplasty).20 has also been found to be effective.25,26
3. Failed trabeculectomy. Complications associated with the use of 5-FU include
4. High preoperative IOP more than 35 to 40 mm Hg at corneal and conjunctival epithelial toxicity, corneal ulcers,
presentation. However primary angle closure glaucoma conjunctival wound leaks, subconjunctival hemorrhage, and
(PACG) patients prior to peripheral iridotomy are an inadvertent intraocular spread of 5-FU. The increased
exception to this rule. If high pressures persist after a incidence of complications due to its intra-operative use has
patent iridotomy, only then should MMC be considered necessitated decrease in the use of intra-operative 5-FU.
for primary use in PACG eyes.
5. Initially, MMC was reserved for repeat surgery cases in Daunorubicin: Intraoperative daunorubicin has been found
buphthalmic eyes but recent trends show that more to be more effective and less toxic than 5-FU and MMC. It
surgeons are using it as a primary modality.21,22 is obtained from Streptomyces coerulorubidus and is also cytotoxic.
Mitomycin C: Mitomycin C is an antibiotic isolated from Intra-operatively, it is given on a 4x4 mm cellulose sponge in
Streptomyces caespitosus that acts independent of the cell cycle a dose of 0.2 mg/ml for three minutes. Ocular surface is
to crosslink DNA and inhibit cell synthesis. It is 100 times then rinsed thoroughly with 10 ml of Ringer lactate solution
more potent than 5-FU and is also toxic to the vascular before proceeding to the other steps of the trabeculectomy
endothelium.14-22 The duration for which MMC (0.2 mg/ procedure.27,28
ml) is applied varies from two to five minutes, however,
duration beyond three minutes increases the risk of hypotony Amniotic Membrane
and visual acuity loss. Comparison of different dosages of
MMC in the concentration of 0.1 mg/ml, 0.2 mg/ml and Mechanism of action: Amniotic membrane is used to prevent
0.4 mg/ml for durations of two and four minutes have been healing in the subconjunctival space and promote longevity
tried with variable success and complications.23,24 of blebs. Amniotic membrane promotes epithelialization of
Complications Associated with Mitomycin Use ocular surface, inhibits inflammation, angiogenesis and
• Cataract fibrosis.29,30 These effects are mediated by promoting epithelial
• Avascular blebs maturation and down-regulating fibrogenic TGF-β signaling
• Bleb leak and myofibroblast differentiation in subconjunctival tissue.
• Bleb dysesthesia: This is a condition caused by cystic, It has high hydraulic conductivity and poor immunogenicity,
overhanging or elevated blebs. These blebs lead to tear film and may also function as an anatomical barrier preventing
irregularities, blinking problems, dellen formation, dry eyes migration of fibroblasts and macrophages.
and foreign body sensation.
• Hypotony: Ocular hypotony, hypotonous maculopathy, Preparation of amniotic membrane: Amniotic membrane
choroidal detachment and shallow anterior chamber are is obtained under sterile conditions after elective cesarean
quite common after the use of mitomycin, more so with delivery from a seronegative donor. Human immunodeficiency
the intrascleral application. virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV),
• Risk of endophthalmitis. Creutzfeldt-Jacob disease (CJD) and syphilis must be
excluded.30 Under a lamellar flow hood, the placenta is first Surgical technique: Use of human amniotic membrane
washed free of blood clots with balanced physiologic saline implanted under the scleral flap/conjunctival flap has been
containing 50 µg/ml penicillin, 50 µg/ml streptomycin, 100 reported to be equally efficacious and much safer than the
µg/ml neomycin, and 2.5 µg/ml amphotericin B. The amniotic use of MMC. 29,30 In a comparison between amniotic
membrane is separated from the rest of the chorion by blunt membrane to MMC blebs, the latter gave rise to blebs which
dissection. The membrane is then flattened onto a were thin walled, leaky with increased incidence of persistent
nitrocellulose paper, with the epithelium/basement membrane hypotony and hypotonous maculopathy.31 An experimental
surface up. The membrane with the paper is cut into 4×4 cm study confirmed greater destruction of fibroblasts and
pieces and placed in a sterile vial containing Dulbecco's macrophages by MMC, versus amniotic membrane.32
modified Eagle’s medium and glycerol at a ratio of 1:1. The
vials are frozen at –80°C. The membrane is defrosted Side Port Creation/Paracentesis
immediately before use by warming the container to room After application of MMC, the anterior chamber is entered
temperature for ten minutes.30 The tissue is now available via a side-port incision (Fig. 9.4.3.7). This is made with V
commercially. lance as in phacoemulsification except that the direction of
entry should be oblique, downwards, parallel to iris and not
towards the center of the chamber as for phacoemulsification,
the rationale being that a central direction could damage the
crystalline lens inadvertently. If the pupil is dilated, as is the
case sometimes with retrobulbar block, intracameral
pilocarpine is injected just after creating the side port.
Sclerostomy
Anterior to the sclerolimbal junction (where the white sclera
merges into the blue translucent zone) is the clear cornea. A
beveled acute angle entry is made just where the translucent
zone merges into the clear cornea with the tip of the 3.2 mm
keratotome (Figs 9.4.3.8A and B). It is preferable to err on
the side of an anterior incision (nearer the cornea) than a
posterior one, since this would entail risk of ciliary body
damage. This can happen, especially in the stretched globe
of the buphthalmic eyes where the limbal stretching obscures
landmarks. After entering the chamber, a controlled withdrawal
is made, by slowly withdrawing the keratotome. The
sclerostomy block is cut with Vannas scissors, 11 number
Fig. 9.4.3.7: Side-port entry (Surgeon’s view) blade or Kelly Descemet's punch. While using the Kelly
Figs 9.4.3.8A and B: A beveled entry is made at an acute angle to the scleral bed. A Kelly Descemet's punch has been used to create a
sclerostomy. Note the scleral tissue of the sclerostomy held in the jaws of the punch
916 Glaucoma
Descemet's punch, a smaller sclerostomy of 1 to 1.5 by 2 to defect or further ganglion cell loss and resultant worsening
2.5 mm dimensions can be made. The other punches which of glaucomatous optic neuropathy. The vision loss in such
can be used are Luntz Dodick, Crozafon, De-Laage, Katena, situations is called as “snuff out” phenomenon.
Holth and Crestani. The flap may be triangular, rectangular or trapezoidal in
shape. In a triangular flap, the apex of the flap should be tied
Peripheral Iridectomy with a non-releasable suture, and the two sides secured with two
releasable sutures. If the base of the triangular/rectangular
This extremely important step is performed through the inner
scleral flap stops short of the limbus by 1 mm (safe surgery
sclerostomy with a Vannas scissors and a single toothed fine
forceps like Lim's or Pierce Hoskin's. The cut is performed technique) then three sutures (for triangular flap) and five sutures
keeping the scissors parallel to the limbus, so as to get a (for rectangular flap) are adequate. If however the sides of the
broad base (Fig. 9.4.3.9). Forceful pull on the iris is to be triangle/rectangle reach the limbus, then two additional sutures,
avoided as this may cause an iridodialyis and/or lens damage. one on each of the limbal edges of the side arms of the flap are
The rationale for performing an iridectomy is preventing iris required. These additional two sutures safeguard against hypotony,
incarceration into the sclerostomy and relieving the element once releasable sutures are removed. These limbal sutures are
of pupil block glaucoma. The iridectomy base should be wider not made releasable; instead the more distal ones are made
than the inner sclerostomy opening. releasable. The reasoning is, that once the proximal sutures are
released, aqueous flow would be directed parallel to the limbus
Scleral Flap Sutures thereby creating an overhanging bleb, whereas if the distal sutures
are released the aqueous flow would be directed posteriorly
Scleral flap sutures regulate aqueous outflow. The resistance toward the fornix and lead to a diffuse, posteriorly located bleb.
to bulk flow of aqueous is largely determined by the Suture tightness can and must be adjusted on the table by
apposition of the flap to the underlying sclera adjacent to the watching the egress of fluid from the scleral flap edges, by
sclerostomy, which in turn is determined by the suture position simultaneously titrating via the side port.
and tension. If the scleral flap is poorly constructed or too
loosely anchored, excessive trans-sclerostomy flow results in Releasable Sutures
hypotony. If on the other hand, the scleral flap is sutured too
tightly, damming up of aqueous causes high IOP, which places The use of releasable sutures allows the surgeon to tightly
the patient at risk from sudden loss of the remaining field in close the scleral flap, knowing that the flow can be increased
cases with a split macula and advanced glaucomatous field postoperatively. The externalized suture can be easily removed
in the postoperative period depending on factors like IOP,
bleb size, and anterior chamber depth. The other option of
removing scleral sutures is by laser suture lysis which is often
difficult to perform through the inflamed, hyperemic post
operative conjunctiva. Laser suturolyis is problematic with a
thick Tenon's tissue and also involves placing a focusing lens
on the operated site which is traumatic and painful to the
patient. Surgical placement of a releasable suture does away
with all these problems, not to mention avoidance of the
need of costly laser equipment. The various releasable
techniques described are Wilson's mattress-type suture with
an externalized knot on the cornea, Shin's removable knot
passed through the conjunctival bleb, Cohen and Osher's loop-
knot suture externalized through the cornea, Hsu and Yarng's
externalized hemibow tie in the center of filtering bleb,
Maberley's two-arm "U" suture that leaves no exposed suture
end until one arm of the suture is removed, and Johnstone's
tamponade suture.33-38
Releasable sutures have been documented to be as effective
Fig. 9.4.3.9: Peripheral iridectomy as laser suture lysis.39 The disadvantages include the need for
additional intraoperative manipulation and postoperative The knot can be cut later on the slit lamp, under topical
discomfort from the externalized suture, corneal epithelial anesthesia and the suture pulled out.
defects, increased risk of intraocular infection, and, if 2. Kolker's modification of Cohen and Osher technique
antimetabolites are used, the risk of an aqueous leak around of releasable sutures:35,36 (Figs 9.4.3.11A to E):
the suture site. • The needle of a 10-0 nylon suture is passed first into the
Various releasable sutures techniques have been described. intact sclera posterior to the scleral flap and then brought
Wilson described a mattress type scleral suture, which was out anteriorly through the superficial scleral flap.
externalized with the knot on the cornea. Postoperatively, the
suture could be cut or removed some of these techniques
are:
1. Richard Wilson's technique33 (Figs 9.4.3.10A to E):
The tightness of the sutures is adjusted to approximate the
edges of the scleral flap and aqueous flow is titrated by
injecting fluid from the side port and watching its egress from
the sides of the sutured scleral flap:
• The corneal end of the suture is then cut flush, to avoid
leaving a protruding suture end.
• Two such sutures are placed on the two sides of triangular
or apices of the rectangular scleral flap. Fig. 9.4.3.10C: Suture is then looped over the superficial scleral flap,
re-enters and traverses beneath superficial flap, into deep scleral flap
to exit on the corneal side, 0.5 mm away from limbal edge of the scleral
flap (Step 3). At this step it would lie over the suture limb in Step 3
Fig. 9.4.3.10A: A preplaced corneal grove is created at the base of

the scleral flap—1–1.5 mm from the limbus (optional) (step 1)
Fig. 9.4.3.10D: Emerges 1–1.5 mm in the clear

cornea adjacent to the step 1 suture (Step 4)
Fig. 9.4.3.10B: The first pass is taken from this groove/ clear cornea,
traverses diagonally beneath the superficial sclera flap, and out through
the scleral bed at the side of the superficial flap (Step 2) Fig. 9.4.3.10E: The two ends are tied (Step 5)
918 Glaucoma
Figs 9.4.3.11A to E: Kolker's modification of Cohen and Osher technique of releasable sutures. (A) The needle is passed into sclera and
through flap. Needle is then passed through based of sclera flap, beneath conjunctival insertion, and finally through peripheral cornea. (B)
Releasable suture is tied with quadruple-throw slip knot. (C) Rectangular sclera flap is closed with two releasable sutures. (D) Triangular
sclera flap is closed with one permanent suture at the apex and one releasable suture each side. (E) A second pass of the needle is made into
the peripheral cornea.
(Permission: This set of 5 figures (with legends) are taken from an article entitled, “Trabeculectomy with releasable sutures”. Kolker AE,
Kass MA, Rait JL (au), in the Trans Am Ophthalmol Soc 1993;91:131–41 and republished with permission of the American Ophthalmological
Society)
• This suture is then passed through the base of the scleral

flap, beneath the limbus, traversing through partial
thickness cornea and exiting 1 to 2 mm central to limbus
on to the epithelial surface of the cornea.
• A small superficial pass through the adjacent cornea is
then made—Kolker's modification.
• Four throws of the distal end of the suture are then
passed around the tying forceps before the suture end
lying on the surface of the scleral flap is grasped to make
a hemibow slipknot. (similar to the unmodified technique
as shown in Figure 9.4.3.11B).
• The tightness of the sutures is adjusted to approximate
the edges of the scleral flap and restrict aqueous flow.
The corneal end of the suture is then cut flush to avoid
leaving a protruding suture end. Fig. 9.4.3.12: Sutured conjunctiva after trabeculectomy. Note the
bleb which has already formed.
These sutures are released as and when required, under
topical anesthesia using the slit lamp. The exteriorized corneal
loop is pulled out with a suture holding forceps. The sutures to this needle and the anterior chamber is reformed through
are released one at a time, within 10 to 14 days of conventional the side port. The bleb is formed on the table, thereby ensuring
trabeculectomy. Suture removal usually produces an patency of the sclerostomy and adequate tightness of the
immediate increase in filtration with enlargement of the scleral sutures. In addition water tightness of the conjunctival
filtering bleb and a fall in IOP. Suture removal after two to closure is checked.
three weeks has little effect on bleb appearance or IOP.
However, in cases of trabeculectomy with antifibrotics, suture POSTOPERATIVE REGIMEN
removal maybe delayed until two to three weeks after surgery, Topical steroid antibiotic combinations are prescribed at two
as post suture removal hypotony is more likely prior to three to four hourly intervals to suppress wound healing for the
weeks. In case, the IOP remains controlled, the sutures need first two weeks. They are then tapered gradually and are
not be removed, until five to six weeks have elapsed. By this prescribed for a total of six to eight weeks. Prednisolone or
time healing has occurred, and removal of suture would not betamethasone combination with antibiotic is used. Topical
affect the IOP. cycloplegics namely homatropine drops or atropine ointments
are routinely used by some surgeons to reduce ciliary spasm,
Conjunctival Flap Closure
prevent synechiae, or deepen the anterior chamber.
In a limbus based flap, incision is closed with continuous 8-0
nylon, or 8-0 vicryl, the edges of which are interlocked (Fig. Postoperative Assessment
9.4.3.12). The superior rectus bridle suture is released at this
stage, to allow for proper coaptation of the wound edges. Assessment of Bleb Formation
Small closely spaced passes are taken in a running fashion. Formation of an appropriate bleb is one of the most
Interlocking of the suture is not necessary. The ends however important parameters through which the success of
are interlocked, tied on itself and not cut too short. The trabeculectomy is assessed (Fig. 9.4.3.13). The parameters
absorbable vicryl induces more inflammation but is the suture are:
of choice in children where conjunctival suture removal The quantification of a bleb has been attempted and
would necessitate giving another general anesthesia. standardized by various methods.40-43 A standard clinical method
by Migdal and Hitchings is elucidated. Other classifications like
Bleb Titration
the Indiana Bleb Appearance Grading Scale and the Moorfield's
At end of the surgery, titration is done from the side port Bleb Grading System have taken parameters like the height,
with a 24 or 26 gauge hydrodissection cannula. A 2 cc syringe extent, vascularity of the bleb along with assessment of Siedel's
filled with balanced salt solution or Ringer lactate is attached sign for bleb leaks41,42 and photographic evaluation43 of the
920 Glaucoma
Fig. 9.4.3.13: An ideal bleb with pale

and diffusely elevated conjunctiva Fig. 9.4.3.14: Algorithm for early post-operative complications of
trabeculectomy (AC = Anterior Chamber)
area, in an attempt to co-relate the same with the success of the

procedure. Both these grading systems have been effective for The most important parameters that have to be checked
such objective evaluation. after a trabeculectomy are IOP, visual acuity and bleb
Migdal and Hitching’s Grading40 morphology. Low IOP has to be correlated with anterior
chamber depth and macular anatomy, similarly bleb
Assessment of bleb formation morphology has to be evaluated in conjunction with IOP,
1. Absent visual field status, astigmatism and chamber depth.
2. Elevated engorged conjunctiva Table 9.4.3.2 elucidates some of the complications of
3. Pale elevated area within engorged conjunctiva trabeculectomy.
4. Residual conjunctival vessel engorgement around suture line
5. Pale and diffusely elevated conjunctiva Early Complications
6. Cystic conjunctival elevation.
(Reproduced from “The developing bleb: effect of topical Shallow Anterior Chamber
antioprostaglandins on the outcome of glaucoma fistulising surgery”. Table 9.4.3.2 elucidates some of the common causes and clinical
Migdal C, Hitchings R. Br J Ophthalmol 1983;67: 655–660; findings of post-operative shallow anterior chamber.
Copyright notice year January 2011 with permission from BMJ The severity of shallow anterior chamber can be graded
Publishing Group Ltd.) by the Spaeth grading system.47
The central anterior chamber depth can be described
SUCCESS PARAMETERS relative to the corneal thickness as in Von Herick’s classification.
OF TRABECULECTOMY Hypotony can induce ciliochoroidal detachment, decreased
Often success is defined only as postoperative IOP lower aqueous production, and gradual failure of the bleb, cataract,
corneal edema, or choroidal hemorrhage. Corneal edema and
than 21 mm Hg. Qualified success, implies that the target
folds in Descemet's membrane are typically present. In cases
IOP is achieved using one or more anti-glaucoma medication(s)
of bleb leak, a Seidel test is positive. Chronic hypotony, which
postoperatively.44-46
persists for at least three months, can be associated with
hypotony maculopathy and loss of visual acuity; in these cases
COMPLICATIONS OF TRABECULECTOMY
there are choroidal folds and retinal striae. Predisposing factors
Post-trabeculectomy complications can be divided into early for the development of hypotony, maculopathy are reportedly
and late and early, delineated by an algorithm (Fig. 9.4.3.14). young age, white race, and myopia.48,49
Table 9.4.3.2: Complications of trabeculectomy

1. Early complications
a. Shallow Anterior Chamber with low pressure can be due
to
• Leakage
• Overfiltration
• Choroidal Detachment
b. Shallow Anterior Chamber with high pressure can be
due to
• Pupillary block
• Malignant glaucoma
• Supra-choroidal hemorrhage
c. Hyphema is usually minimal and frequent. It clears within
few days with conservative management and is
inconsequential.
d. Blebitis/Endophthalmitis
2. Late complications
a. Encapsulated bleb/Tenon's cyst Fig. 9.4.3.15: Shallow anterior chamber with bleb
b. Failing/failed bleb leak confirmed by the Seidel test
c. Symptomatic bleb due to tear film abnormalities and
foreign body sensation
Management
d. Bleb rupture
e. Cystic bleb The need and urgency of the management of bleb leaks
f . Blebitis/ Endophthalmitis depend on several factors. Some cases, particularly in
3. Vision related complications monocular individuals, with leaking blebs that have had
a. Cataract is the most common complication
previous episodes of bleb-related infections, ocular hypotony,
b. Uveitis
c. Choroidal /Retinal detachment shallow-flat anterior chamber, loss of bleb elevation, or
d. Hypotony maculopathy reduced vision should be always treated. However, if there
e. Central snuff out. are no complications, such as in late leaks with formed blebs,
normal IOP, good central vision, and no history of bleb-
related infection, the leak may not require therapy.
Observation is, then, recommended to allow spontaneous
Bleb Leakage closure of the leak. Pharmacologic treatment with agents
Predisposing factors: Bleb leaks can occur early or months that decrease aqueous secretion (i.e. topical β blockers and/
to years after the filtration surgery. A buttonhole in the or carbonic anhydrase inhibitors) and discontinuation of
conjunctiva during surgery or a wound leak through the topical steroids, with or without patching, may help to
conjunctival incision can be responsible for an early leaking spontaneously close these defects by reducing flow of aqueous
bleb (Fig. 9.4.3.15). Spontaneous, late bleb leaks are more through the fistula. Prophylactic broad-spectrum antibiotic
frequent in avascular, thin blebs, when antimetabolites are coverage, alternating different antibiotics, is recommended
used in the filtering procedure, after full-thickness procedures. by some, although its efficacy has not been proved.50
Clinical Findings Some blebs leak intermittently. Many defects seal
Bleb leaks are detected with the Seidel test. After instilling temporarily only to reopen later. Some successful treatments
topical anesthetic drops, fluorescein strip is applied to the are temporizing procedures for closure of a leak. Long-term
suspected area of bleb leak and examined under cobalt blue follow-up of various therapies is needed to evaluate their
light. Fluorescein dye gets diluted by aqueous at the site of efficacy not only in resolving bleb leaks, but also in preventing
bleb leak, in case of a bleb leak. their recurrence. Surgical prevention of conjunctival
Leakage of the filtering bleb is associated with hypotony, buttonholing, intra-operative bleb titration and adequate
shallow-flat anterior chamber, or choroidal detachment, and suturing of the bleb (Fig. 9.4.3.16) are some of the maneuvers
it increases the chances for bleb infection and subsequent that present bleb leakage.
endophthalmitis. Early leakage can flatten the bleb and lead Treatments Used to Reverse Leaking Blebs
to subconjunctival-to-episcleral fibrosis, which could Therapeutic modalities to treat leaking blebs include the use
jeopardize a satisfactory long-term filtration. of pressure patching, bandage contact lenses (Fig. 9.4.3.17),
922 Glaucoma
Fig. 9.4.3.17: Standard-sized, soft bandage contact lenses have been

tried to seal leaks, but typically the lens diameter is not large enough to
Fig. 9.4.3.16: Suturing of the bleb with bleb forming sutures cover a filtering bleb. A long-acting collagen shield can also be used
the Simmons shell, symblepharon rings, cyanoacrylate glue,

fibrin tissue glue, autologous blood injection, cryopexy, argon
laser, thermal Nd:YAG laser, and surgical revision51-66 (Fig.
9.4.3.18).
Tissue glues: Fibrin/Cyanoacrylate tissue glue are applied under
topical anesthesia, on dry conjunctival leak area. Fibrin glue
is a mixture of fibrinogen and thrombin that induces clot
formation. It is non-irritating but requires bandage contact
lens or collagen shield to prevent dislodgement of the
adhesive. Corneal abrasions at the site of application are the
most frequent complication. Glues work best for early leaks
with healthy conjunctiva; in thin, avascular blebs with leaks
occurring in the very late postoperative period they should
not be tried.54-56
Surgical revision: When simpler methods have failed and
complications like persistent shallow chamber or risk of
infection is imminent then surgical intervention is indicated.
Fig. 9.4.3.18: Surgical revision in the case of a leaking bleb with
This includes direct suturing, conjunctival advancement advancement of the surrounding conjunctiva
with or without excision of the existing bleb, free
conjunctival graft, scleral patch graft, and amniotic membrane
graft.60-64,67,68 Frequently used techniques include free tissues. When local scarring adjacent to and surrounding the
conjunctival graft and advancement of adjacent conjunctiva. bleb precludes local revision, free conjunctival autograft can
Because of the friable nature of the conjunctiva in long- be used. In addition, scleral patch graft is indicated for scleral
established filtering blebs, it is often impossible to close the dehiscence.
defect directly with sutures. Therefore, conjunctival flaps or Symblepharon rings and the Simmons shell: In the early
grafts are required. The ischemic and thin-walled bleb tissue postoperative period, symblepharon ring and the Simmon's
is denuded of conjunctival epithelium and fresh conjunctiva shell effectively tamponade the bleb and maintain IOP.52,53,66
is mobilized to cover the previous filtration site by rotational The Simmons shell is a 22 mm dome-shaped shell of
or sliding conjunctival flaps. The conjunctiva is sutured over transparent polymethylmethacrylate which has a raised
the peripheral cornea, providing a watertight seal after platform on the concave inner surface to be placed over the
abrading the corneal margin to facilitate adherence between sclerostomy site. The curvature is designed to selectively indent
the perilimbal area when pressure dressing is applied. It is

however uncomfortable; precludes IOP monitoring; requires
close (daily) monitoring; decentration of the shell is common
unless the shell is sutured to the conjunctiva; and corneal
complications like epithelial defects are common. Its use is
limited in monocular patients.
Chemical irritants: Topical application of 0.25 to 1 percent
silver nitrate or 50 percent trichloroacetic acid to the bleb
surface has been used to manage focal bleb leaks with
hypotony and/or large blebs by inducing a chemical
conjunctival burn and consequent inflammation and
stimulation of healing.67
Cryotherapy: Cryo application effectively treats overfiltering
blebs and reverses hypotony57-68 by inducing inflammation.
The probe is applied initially to the lateral and superior borders
of the bleb. Prior to initiating the freeze, firm pressure needs
to be applied with the cryoprobe to bring the bleb surface Fig. 9.4.3.19: Shallow anterior chamber, with low IOP and an
tissues into apposition with the underlying sclera. Two to five extremely well formed bleb indicates bleb overfiltration
applications are placed with temperature range –50 to –80°C,
duration 10 to 30 seconds. Moderate inflammation and
pigment dispersion in the anterior chamber are frequent
complications, and topical cycloplegic and corticosteroid drops The IOP is low with an elevated bleb and shallow anterior
are prescribed postoperatively. More than one treatment chamber (Fig. 9.4.3.19).
session may be needed to achieve the desired goal. Inadvertent
eye movement during the freezing process can initiate a bleb Management
rupture. Thus the procedure should be performed under
peribulbar block for patients prone to movement. a. Observation: Hypotony caused by excessive filtration usually
resolves with routine postoperative medical management.
Argon laser/Nd:YAG thermal laser: Argon or continuous-wave
Therefore, the initial management of postoperative hypotony
Nd:YAG laser applies heat energy and induces sufficient
with a formed anterior chamber and elevated bleb is
inflammation to cause scarring and seal a bleb leak.58,69
conservative with strong cycloplegics and topical steroids.
Conjunctiva needs to be painted with methylene blue or Rose
Restrictions in activity (e.g. bending, weightlifting) and
Bengal dye to ensure that the laser energy is absorbed by the
avoidance of Valsalva-positive conditions (e.g. constipation,
superficial tissues only. Laser burns should not be delivered
vigorous coughing, sneezing, or nose blowing) are
to regions with very thin and transparent conjunctiva where
recommended. The use of pressure patching, large bandage
treatment itself can induce microleaks.
contact lenses, the Simmons shell, and symblepharon rings
Autologous blood injection: Injection of autologous blood into may be beneficial by tamponading the filtration site, which
the bleb is another useful modality.56 Inflammatory cells and allows gradual improvement in the anterior chamber depth.
serum proteins from the injected blood accelerate the However, a flat chamber with lens-corneal touch (grade III)
inflammatory and healing process, which decreases aqueous requires immediate intervention with prompt anterior chamber
filtration. Complications include hyphema, endophthalmitis, reformation; otherwise, rapid cataract development,
IOP increase, bleb failure, corneal blood staining, corneal irreversible corneal endothelial injury and extensive peripheral
graft rejection, and reactivation of previously quiescent ocular anterior synechiae form. The anterior chamber can be
toxoplasmosis.56 reformed with air, balanced salt solution, but a viscoadaptive
material like Healon GV is best.72-74
Overfiltration of Blebs
b. Bandage contact lenses: Large bandage contact lenses of 17 to
Persistent hypotony caused by excessive aqueous filtration is 20 mm diameter have been successively used in the early
more common after full-thickness procedures and after postoperative period, but the availability of lenses of these
antimitotics usage.70,71 dimensions is an issue.72-74
924 Glaucoma
Choroidal Detachment
Serous choroidal detachment involves transudation of serum
into the suprachoroidal space. The extent of detachment can
be limited to one or more sectors, with the lobe(s) limited by
the fibrous attachments corresponding to the vortex veins.
Annular detachments involve the circumference for 360°. A
large degree of fluid accumulation can cause contact between
lobes on the visual axis, with central retina-to-retina contact
(kissing choroidals). Visual acuity is significantly reduced
depending on the degree of interference with the visual axis.
Most serous detachments resolve spontaneously during first
few postoperative days or weeks. Medical management
includes administration of systemic and topical steroids with
atropine ointment. Surgical drainage is required in persistent
flat chamber over few weeks. 75 Persistence of choroidal
detachment results in perpetuation of a vicious cycle whereby
the hypotony persists due to percolation of fluids into the
choroidal space leading on to further choroidal detachment
and resultant hypotony. Persistent hypotony may result in
vision loss due to maculopathy.
Pupillary Block
Pupillary block can be caused by adhesions between the iris
and the lens, the intraocular lens or vitreous. The inability of
the aqueous humor to pass from the posterior chamber to
the anterior chamber results in the forward movement of
Fig. 9.4.3.20: Central shallowing of anterior chamber in a case of
the peripheral iris and closure of the drainage angle. It occurs
pupillary block glaucoma
as a central flat (shallow) anterior chamber with normal or
elevated pressure. The peripheral shallowing is less than the
Aqueous Misdirection and
central shallowing in typical pupillary block (Fig. 9.4.3.20).
Malignant Glaucoma
Distinguishing pupillary block from malignant glaucoma may
be difficult. Although a peripheral iridectomy is intended at Aqueous misdirection, also known as malignant glaucoma or
the time of filtration surgery, only the stroma of the iris is ciliary block glaucoma is characterized by a shallowing
removed and the posterior pigment epithelium is left intact (flattening) of the anterior chamber without pupillary block
in a few patients. In these patients, blockage may develop. In (i.e. in the presence of a patent iridectomy) or choroidal disease
other patients, the iris may become incarcerated in the wound (e.g. suprachoroidal hemorrhage) and an accompanying rise
or the iridectomy may be obstructed by inflammatory tissue, in IOP. It occurs in two to four percent of patients who have
intraocular tissue like Descemet's membrane, anterior hyaloid undergone surgery for angle-closure glaucoma, but can occur
surface, vitreous or even ciliary processes. Treatment with after any type of incisional surgery. In this condition, aqueous
topical cycloplegics may resolve pupillary block, but an humor is diverted posteriorly towards vitreous cavity,
Nd:YAG peripheral iridotomy should be performed. The increasing the vitreous volume which causes shallowing of
anterior chamber readily deepens after an iridotomy is the anterior chamber. The condition usually occurs in the
performed, although in the presence of localized early postoperative period after filtration surgery. A dilated
compartments of blockage, multiple iridotomies are necessary. fundus examination or B-scan ultrasound confirms the absence
Usually, this deepening is associated with the sudden escape of a choroidal effusion or hemorrhage. Decompression and
of aqueous humor through the iridectomy, confirming the shallowing of the anterior chamber in the intraoperative period
diagnosis of pupillary block. If the laser iridotomy cannot be predispose to the condition by inducing forward movement
completed, a surgical iridectomy should be performed. of the peripheral anterior hyaloid. The anterior hyaloid comes
in apposition with portions of secreting ciliary processes

causing aqueous to move directly into the vitreous cavity. In
hyperopic eyes with a crowded middle segment (angle closure
glaucoma cases), the peripheral anterior hyaloid in its normal
position is close to the posterior ciliary body.
A relative resistance to the anterior movement of the
aqueous present in the anterior vitreous/ hyaloid face occurs,
which is related to abnormal permeability of available hyaloid
surface area. Normally the anterior hyaloid and vitreous offer
insignificant resistance to forward fluid flow. Perhaps, a sudden
onset of pupillary block forces the aqueous humor into the
vitreous and expands the vitreous volume, with forward
displacement of the peripheral hyaloid into direct apposition
with the ciliary body.
Management: First line of treatment is medical which aims
to decrease the aqueous production, shrink the vitreous Fig. 9.4.3.21: Bleb related infection associated with severe anterior
chamber reaction. Note that the bleb is cystic and that uveal tissue
volume and thus push the iris lens diaphragm backward.
can be seen beneath the same. (Courtesy: Dr Parul Sharma)
Cycloplegic agents like atropine are given which pulls the lens
back and tightens the zonules. Hyperosmotics, topical beta
blockers and alpha agonists reduce aqueous production. The Frequency, Predisposing Factors,
medical regimen is curative in 50 percent of cases within and Pathogenesis
five days.76,77 If the condition persists beyond this time, surgical
Factors that can increase the risk of infection after filtering
intervention is indicated. Argon laser can be used through a
procedures are:80-82
peripheral iridectomy to diminish the volume of ciliary
• Use of 5-FU and mitomycin C during glaucoma surgery.
processes and, therefore, ciliolenticular block. Alternatively
• Inferior filtering procedures are more likely to lead to
Nd:YAG laser can break the anterior hyaloid to allow free
endophthalmitis as the bleb is more exposed , more likely
movement of fluid from the vitreous cavity to the anterior
to suffer from minor trauma. Epithelial drying,
chamber. Pars plana vitrectomy, with or without lensectomy,
accumulation of infectious agents in the tear lake also
disrupts the impermeable anterior vitreous face and reduces contribute to increased infection.
the vitreous volume. The goal is to create a direct • Trauma, use of contact lenses, and bleb leaks.
communication between the vitreous cavity and the anterior • An infectious conjunctivitis or blepharitis.
chamber. • Systemic diseases, such as diabetes mellitus, malnutrition,
or a compromised immune system.
Suprachoroidal Hemorrhage The commonly isolated bacteria in bleb-related
This presents after first few postoperative days with severe endophthalmitis mostly arise from the ocular flora, transient
pain and marked reduction in vision. Intraocular pressure is or permanent. These include Streptococcus species, Haemophilus
usually raised, anterior chamber is shallow or flat, and large influenzae, and Staphylococcus82 species. Regional differences are
choroidal detachments are present. Indications for surgical seen in the types of bacterial flora responsible for blebitis.
drainage are—associated retinal detachment, 360°
suprachoroidal hemorrhage, kissing choroidals, vitreous Clinical Findings
incarceration and vitreoretinal adhesions.78,79 Common subjective complaints include ocular pain, foreign-
body sensation, blurred vision and tearing. In cases of blebitis,
Bleb Related Ocular Infections
conjunctival and ciliary injection is localized around bleb edge.
They may occur both in early and late bleb related infections. Purulent discharge, chemosis, corneal edema, and anterior
Blebitis is a limited anterior form of endophthalmitis with a chamber reaction is present. The bleb has a milky-white
potential to rapidly spread posteriorly (Fig. 9.4.3.21). Once appearance with loss of clarity and a positive Seidel's test is
posterior segment is involved, the preferred term is bleb-related common. Untreated, the infection spreads, causing a full-
endophthalmitis. blown endophthalmitis.
926 Glaucoma
Bleb-related infections can be clinically classified into three

stages, with erythema in bleb area with milky-white appearance
of bleb and loss of clarity in the initial stages, anterior
chamber reaction with or without hypopyon subsequently
and full blown endophthalmitis subsequently.
Management of Blebitis and Endophthalmitis

Conjunctival exudate is subjected to microbiological
examination and culture. An anterior chamber tap is done if
there is a marked anterior chamber reaction before starting
with broad spectrum antibiotics. A vitreous tap with or without
vitrectomy may be performed in cases of full blown
endophthalmitis.
Treatment with fortified topical antibiotics is advisable.
Topical fortified cefazoline (50 mg/ml) has been used as a Fig. 9.4.3.22: Tenon's cyst. Note the extensive vascularization of
single agent, because it covers most of the organisms found the conjunctiva over the area of the bleb
in bleb-related endophthalmitis. However, topical fortified
vancomycin, 25 mg/ml, and amikacin, 50 mg/ml (or
tobramycin, 14 mg/ml), may be the preferred antibiotic thick connective tissue. It commonly appears within two to
combination to cover gram-positive and gram-negative four weeks after surgery. There is an increase in IOP after
microorganisms, respectively. The role of periocular and an initial period of pressure control following glaucoma
systemic antibiotics has not been evaluated. Systemic ofloxacin/ surgery. Their elevation can interfere with upper-lid movement
ciprofloxacin can be used because of their high penetration and tear film distribution, leading to corneal complications,
into the vitreous. If intravitreal antibiotics are required, either such as dellen and astigmatism.
through a pars plana injection or associated with a vitrectomy, Treatment:
systemic fluoroquinolones may be prescribed along with
Medical Management: Initial management includes antiglaucoma
fortified topical eye drops of the same antibiotics injected
medications in cases of elevated IOP, topical steroids, and
intravitreally. The role of pars plana vitrectomy and systemic
digital massage. Deciding between conservative management
antibiotics in the management of late endophthalmitis after
(medical) or a surgical approach (needling, bleb revision) is
glaucoma filtering surgery is not clear.
usually dependent on the severity of glaucomatous damage,
After resolution of the infection, the function of the
the level of IOP, and the response to conservative medical
filtration bleb may be impaired, requiring additional
management.
medication for adequate pressure control, especially in eyes
that had not received antifibrotic therapy.81,82 Surgical Procedures: Immediate IOP reduction can be provided
by cutting the fibrotic wall with a 27-gauge needle or a Ziegler
Late Complications of Trabeculectomy knife to restore aqueous runoff to a larger subconjunctival
area and excision of the encapsulated tissue. The use of 5-
Encapsulated Blebs FU after (dose 5 mg/0.1 ml) the surgical revision of bleb or
Frequency and Predisposing Factors: Encapsulated blebs bleb needling probably increases the chances of success.84
or Tenon's cysts develop few weeks after trabeculectomy The procedure is done under topical anesthesia and may need
(Fig. 9.4.3.22). Associated predisposing factors include male to be repeated.
gender, glove powder, topical steroids, prior treatment with
sympathomimetics, prior argon laser trabeculoplasty, and prior Symptomatic Blebs
conjunctival surgery.83,84 The causes are not clearly identified,
Predisposing Factors: Filtering blebs are usually
but inflammatory mediators are probably involved in their
asymptomatic or reasonably well tolerated. Most patients are
development.
aware of a conjunctival "blister"; however, others have various
Clinical Findings: These blebs are localized, high, and tense, degrees of discomfort. Common complications include
with vascular engorgement of the overlying conjunctiva and superficial punctate keratopathy, difficulty with blinking, tear
Fig. 9.4.3.23: Secondary dellen formation adjacent Fig. 9.4.3.24: Early failing bleb. Note the flat bleb with hyperemia and
to a cystic over-hanging bleb vascularization. Internal sclerostomy closure by iris tissue is the
etiology in this case
film abnormalities with secondary dellen formation (Fig. changes account for the majority of failures of external
9.4.3.23) or ocular surface irregularities, foreign-body filtering operations.
sensation, and induced astigmatism. The timing of IOP rise and the site of aqueous obstruction
Management: Frequent use of artificial tears and ocular should be considered in the evaluation of failing blebs. Bleb
failure can be clinically classified as early and late. The
lubricants is the recommended initial treatment for
symptomatic blebs and problems related to irregular tear etiopathogenesis, clinical findings and management of these
distribution. If the problems persist, surgical excision or two conditions are different:
conjunctival flap reinforcement is the primary treatment for “Early failing/failed blebs” are those occurring within the first
large blebs. Although the results of surgery are generally good, postoperative month. The IOP is high and the bleb is low
there is the possibility of bleb failure. More conservative and hyperemic (Fig. 9.4.3.24). It may be associated with internal
methods to shrink blebs include cryotherapy, Nd:YAG obstruction by blood or fibrinous clot, vitreous, iris,
laser thermotherapy, argon laser, diathermy, and cauteri- incompletely excised Descemet's membrane, scleral tissue,
zation. 57-59,68,69 Medial tarsorrhaphy can also alleviate or fibroblastic proliferation. Other causes of early failure
symptoms of a nasal bleb and it may even remodel and shift include subconjunctival and/or episcleral fibrosis, or a tight
the bleb superiorly over one to two months. At that time, the scleral flap.
tarsorraphy can be reversed. Prevention and Management
Large blebs that overhang the cornea lie on the cornea • Topical corticosteroids and antimetabolites: Topical
rather than dissecting into its tissue planes. They can, therefore, steroids are routinely used in the normal postoperative
be freed by blunt dissection, and the excess is excised with a course and are tapered after six to eight weeks. Steroids
cut parallel to the limbus.85 Usually there is surprisingly little decrease cellular tissue infiltration, fibrinous exudation
or no leak after this simple oversized bleb excision. from capillaries, inhibit fibroblastic activity86 which result
in decreased wound healing response and, therefore help
Failing and Failed Blebs to maintain an open fistula. Adjunctive antimetabolites
further reduce postoperative healing and subconjunctival
Clinical Findings: These blebs are associated with inadequate fibrosis which is especially relevant in cases with high risk
IOP control and impending or established obstruction of of failure.
aqueous outflow, respectively. In 1960s Maumenee divided • Digital ocular compression and focal compression: Digital
the cause of failure of filtering operations into intraocular, ocular compression can be applied to the inferior sclera
scleral, and extraocular factors, and recognized that extraocular or cornea through the inferior eyelid,87 or to the sclera
928 Glaucoma
posterior to the scleral flap through the superior eyelid. of these sutures increases the filtration in a graded manner
Focal compression is applied with a moistened cotton tip which may be helpful in resurrecting a failing bleb,
at the edge of the scleral flap.87 These procedures can be especially in the early postoperative period. However, such
useful to elevate the bleb and reduce the IOP in the early a release has to be performed with care. Improper release
postoperative period. This technique is not effective in not only results in "non-release" but can also cause bleeding
cases of internal obstruction of the sclerostomy. If digital (Fig. 9.4.3.25).
ocular compression seems effective, the patient can be • Laser internal revision: The Nd:YAG laser is useful in the
instructed to repeat this technique several times a day. early postoperative period when intraocular factors are
• Suture lysis: In the early postoperative period, argon laser responsible for the failing blebs, such as incarceration of
suture lysis can adjust the filtration flow in a controlled iris or vitreous, or early scarring of the filtration cleft at
fashion.88 It allows the surgeon to tightly close the scleral the flap-bed interface. The laser disrupts the tissue
flap intraoperatively and reduce probability of responsible for the obstruction, opening the sclerostomy.
postoperative hypotony and a flat anterior chamber. If a pigmented tissue like iris is responsible for the
Gonioscopy must be performed before the laser procedure obstruction, argon laser may also be successful. Very often
to confirm an open sclerostomy with no tissue or clot the obstruction, reforms after laser ablation.
occluding its entrance. Specially designed lenses, such as
“Late failing/failed blebs”: These are cases with a history of
Hoskins, Ritch, and Mandelkorn lenses, help identify and
good bleb function and adequate control of IOP
cut one or more trabeculectomy flap sutures selectively
postoperatively for at least 1 month. The common causes
through the overlying conjunctiva. Usually only one suture
are subconjunctival and episcleral fibrosis (Fig. 9.4.3.4). In
is cut at a time to avoid overfiltration and a flat anterior
these cases, the sclerectomy is patent on gonioscopy. The
chamber. A full-thickness hole of the conjunctival flap
danger signs are increased bleb vascularization, bleb
may rarely develop if excessive laser application is done.
inflammation, and/or bleb thickening. The normal healing
The procedure is performed within the first two weeks in
response is probably responsible for late bleb scarring. Several
trabeculectomy without antimetabolites. After this period,
factors have been identified as accelerating the subconjunctival
fibrosis of the scleral flap may negate any beneficial effect
fibrosis, such as black race, young age, postoperative
of this procedure. After mitomycin augmented
subconjunctival hemorrhage and inflammation. Internal
trabeculectomy suturolysis can be effective till four to
closure of the sclerostomy is less commonly responsible for
five weeks after surgery.
late bleb failure.
• Releasable sutures: The role and use of releasable sutures
has been described earlier in this chapter. Selective release Management
The management of late failing blebs depends primarily on
the site of aqueous resistance, which determines failure of
filtering blebs. In cases of subconjunctival and episcleral
fibrosis, an external approach is usually preferred; in cases
with obstruction of the sclerostomy, an internal revision can
be used. Finally, a repeat glaucoma surgery with another
filtration site can be considered.
• Internal revision: With the use of either the argon or Nd:YAG
laser, internal revision is now safer. The argon laser can
be effective for reopening the fistula occluded by an
internal membrane, if the tissues are pigmented,89 via an
internal approach. This technique may have more
favorable outcomes if the filtration bleb was well
established before the fistula became occluded and if
there is no significant subconjunctival scarring.
• External revision with laser: Treatment with the Nd:YAG
laser may be useful in some cases with episcleral or
Fig. 9.4.3.25: Bleeding while attempting to subconjunctival fibrosis, with or without simultaneous
release a "releasable" suture internal treatment.
• External revision by needling: In blebs that fail because of Cystic Bleb

episcleral and subconjunctival fibrosis, a 26/27 needle
This develops frequently after full-thickness filtration surgery
can be used to cut the edge of the scleral cap and restore
or trabeculectomy enhanced with antiproliferative agents (Fig.
aqueous runoff. 90 In encapsulated blebs, a needling
9.4.3.27). These blebs are more prone to develop
procedure can be used to puncture the fibrotic tissue.
endophthalmitis. Treatment includes conjunctival advancement
The intervention is performed under topical anesthesia.
with or without excision of the existing bleb, free conjunctival
Adjunctive injection of 5-FU or MMC is helpful.
graft, scleral patch graft, and amniotic membrane graft are
• Ab externo holmium—YAG laser sclerostomy: A laser
the affected area.60-64 Frequently used techniques include
sclerostomy is a potentially useful procedure for bleb
free conjunctival graft and advancement of adjacent
revision. The infrared wavelengths are highly absorbed
conjunctiva.
by water and quickly and easily perform sclerostomies.
The holmium or erbium laser offers the advantages of a
Bleb Infection
small conjunctival incision, access to areas difficult to
operate on by conventional filtering surgical procedures, This has been described in a previous part of this chapter. It
technical simplicity, and a shorter operative time. The is important to remember that bleb infection and
conjunctiva must be mobile in the proposed sclerostomy endophthalmitis may occur in the early and the late post-
site to allow proper probe placement without causing a operative period. Cystic blebs, bleb leaks and bleb rupture
conjunctival perforation.91 In cases of a late failing bleb, contribute to the genesis of these infections.
the probe should be directed to the area where the previous
sclerostomy and iridectomy were perfor med. Iris Vision Related Complications
incarceration in eyes without previous peripheral These are:
iridectomy is a frequent complication, which is less likely • Cataract
to occur in cases of late failing bleb with a peripheral • Uveitis
iridectomy. Additional 5-Fluorouracil injections are • Hypotony maculopathy
recommended after holmium laser sclerostomy revision. • Choroidal detachment
• Central snuff out
Overhanging Bleb
A large bleb extends down over the cornea due to the effect Cataract Formation
of lid movement (Fig. 9.4.3.26A). Patient may be Cataract formation and progression of pre-existing cataract
asymptomatic or complain of foreign body sensation, tearing often occurs after filtration procedures. Lens opacification is
and decreased vision due to significant astigmatism (Fig. one of the main causes of visual diminution after filtration
9.4.3.26B). Management includes use of artificial tears and surgery. Intraoperative lenticular trauma is possible and can be
adequate refractive correction. Surgical excision of the corneal recognized shortly after surgery. A postoperative flat anterior
portion of the bleb may be required in an advanced case. At chamber with lens-corneal touch rapidly precipitates cataract
all times, bleb integrity and function must be safeguarded. formation. Other probable risk factors include age, presence
Fig. 9.4.3.26A and B: A large overhanging bleb may cause significant astigmatism in addition to foreign body symptoms in the eye
930 Glaucoma
in IOP and severe postoperative hypotony are possible causes

for wipe out. This should be explained to ‘at risk’ patients
prior to surgery.
MODIFICATIONS OF TRABECULECTOMY
Certain modifications can be incorporated with the procedure
of trabeculectomy to enhance both the post-operative control
and visual rehabilitation. These are:
Combined Cataract Surgery

and Trabeculectomy
Cataract and glaucoma often coexist in the elderly patient
Fig. 9.4.3.27: Filtering cicatrix in the bleb area. These blebs are and either one may affect the treatment and prognosis of
prone to develop endophthalmitis
the other condition. Cataract can hinder the monitoring of
glaucoma whereas cataract surgery influences both intraocular
pressure and the functioning of a prior glaucoma filtering
of exfoliation, use of air to reform the anterior chamber,
surgery. Glaucoma surgery, on the other hand, increases the
profound hypotony, use of miotics and topical steroids, and
risk of cataract progression. Often the management of a co-
inflammation. The condition may necessitate early surgical
existent condition becomes a matter of controversy.
intervention for cataract extraction which has to be performed
via clear corneal temporal phacoemulsification. Surgical Options
The following surgical options are available for the patient
Uveitis
having coexistent cataract and glaucoma.
Anterior uveitis may be seen during early postoperative period. • Where the glaucoma is controlled on one topical
It is managed by topical steroids and cycloplegics. If severe, antiglaucoma drug, cataract extraction alone is performed.
it may impede vision. Infective uveitis and endophthalmitis This may do away with the need for single antiglaucoma
has been covered in a previous part of this chapter. medication in the immediate and intermediate follow-up
period. Over a long-term follow-up, glaucoma medications
Hypotony Maculopathy may need to be reintroduced.
Risk factors for the development of hypotony maculopathy • In advanced glaucoma where in a previously recorded
include young age, myopia, use of antimetabolites and 10-2 visual field testing (the current cataract status, may
preoperative use of carbonic anhydrase inhibitors. Fundus not allow a fresh 10-2 testing), the fields were so constricted
examination shows fine macular striae radiating from the that macular split was impending, then trabeculectomy
fovea, choroidal folds and tortuous retinal vessels. Visual acuity alone is done first. This strategy is particularly important
is markedly reduced and the loss may often be permanent. in eyes at high risk for filter failure, e.g. eyes with prior
intraocular surgery, neovascular glaucoma or young
Choroidal Detachment individuals. The cataractous lens is removed, by clear
corneal temporal phacoemulsification at a later date, which
Choroidal detachment has been discussed earlier in this
should be at least six months after the trabeculectomy.
chapter. Associated with hypotony maculopathy, it can
The rationale for this is that the target IOP required for
permanently affect vision. It may be associated with an
advanced glaucoma cases is in the low teens and a
exudative retinal detachment which would further exacerbate
combined procedure would rarely achieve that level of
the hypotony and result in significant visual loss.
pressure control even when augmented with
antimetabolites.92-94
Snuff-out Phenomenon
• Combined surgery is performed in the following case
Unexplained loss of the central visual field (wipe out) after scenarios, when in the presence of significant cataract,
glaucoma surgery is rare. Older patients with advanced visual there is:
field defects affecting the central field with split fixation are – Borderline controlled glaucoma despite maximum
at an increased risk. Early, undiagnosed postoperative spikes tolerable anti-glaucoma therapy
– Adequate IOP control but unacceptable drug side effects may be performed from the same site superiorly or may be
– Increased number of topical medications required to performed separately. Temporal phacoemulsification may be
control IOP (more than two). followed by superior trabeculectomy. A recent study by
– Poor socioeconomic status such that the patient cannot Shingleton et al compared the results of 1-site versus 2-site
go on with the cost of medical management of phacotrabeculectomy for over one year and found them to
glaucoma and the condition is such that glaucoma be similar with respect to IOP control and visual gain.98
surgery would be warranted at a later date. Comparable results have also been reported by other
– Poor access to medical care facilities/non-compliance workers.99,100 Over a longer follow up with MMC augmented
of the patients to medical therapy. phacotrabeculectomy, no difference was noted in the mean
– A one-eyed patient with significant cataract and IOP irrespective of number of sites used, although clinically
moderate glaucoma defect, with the other eye having apparent filtering blebs were more common in the 2-site
lost vision due to glaucoma. group.101,102 Despite this, some researchers have however,
The advantages of combined surgery are that: advocated a 2-site approach in which the phacoemulsification
– Two morbidities are handled in one sitting. component is performed through a temporal corneal
– It is more economical to the patient where cost is a approach followed by a trabeculectomy performed
factor. superiorly. 94 They contend that the 2-site phacotrabe-
– During the postoperative part of the cataract surgery, culectomy entails less conjunctival manipulation and leads to
the glaucoma patient is subjected to IOP spikes, which a slightly better control of IOP (around 1–3 mm Hg better).92
damage the vulnerable optic nerve head further. This
Manual Small Incision Cataract Surgery and Trabecu-
IOP spike has been documented to reach almost twice
lectomy: Manual non-phaco small incision cataract surgery
the pre-operative IOP levels. Combined surgery blunts
may also be combined with trabeculectomy. Thomas et al, on
this spike.
comparing manual SICs with trabeculectomy versus
– The need for frequent and long-term topical
phacotrabeculectomy, found the two techniques to be equally
corticosteroids post cataract extraction, may exacerbate efficacious.103
the glaucoma in steroid responders. Concomitant
glaucoma surgery would downplay this effect. Clear Lens Extraction in ACG: The crystalline lens has a
pivotal role in primary angle closure (PAC), both in the
Different Techniques of Combined Surgery pathogenesis of the pupil block and by exacerbating the effect
of non-pupil block mechanisms such as peripheral iris
Extra Capsular Cataract Extraction (ECCE) Trabecu-
crowding. Eyes with angle closure tend to have shallow anterior
lectomy: ECCE trabeculectomy is associated with excessive
chambers and thick, anteriorly positioned lenses when
conjunctival and scleral manipulations, thereby leading to
compared with normal eyes. Removing the lens creates more
scarring of the incision area and hence reducing the efficiency
space in the anterior chamber and widens the angle, which
as well as the longevity of the filtering bleb. The larger incision
may be enough to achieve intraocular pressure (IOP) control.
also causes more derangement of the blood aqueous barrier
The role of lens extraction as a treatment for angle closure
leading to increased inflammation, an increased incidence of
has been debated for many years.
wound leaks and subsequent shallow anterior chamber.
Removing the lens at an early stage deepens the anterior
chamber and opens the angle, thus hindering the formation
Phacotrabeculectomy
of peripheral anterior synechiae (PAS) and improving the
Phacotrabeculectomy minimizes the derangement in the prospects for good long term IOP control. In addition, many
balance of forces between the intravascular and interstitial of these patients eventually require surgery for visually
compartment by maintaining controlled chamber dynamics. significant cataract at some stage. However, this should be
This decreases chances of anterior chamber reaction, reserved for cases in which the acute attack is not responding
hyphema and hypotonous maculopathy.95 The smaller scleral to conventional medical and laser treatment. Some studies
and conjunctival incisions reduce stimuli to wound healing, suggest that cataract surgery may be as effective as filtering
inflammation and postoperative bleb scarring.95 This results surgery in controlling IOP in PACG cases. But it may be that
in better IOP control, reduced complications and improved the stage and chronicity of the angle closure process dictate
bleb longevity.96,97 The trabeculectomy and cataract surgery which surgery should be done to achieve optimum outcomes.
932 Glaucoma
In cases in which there is early optic disc cupping and mild tightly secured with six to seven 10/0 nylon sutures to ensure
visual field loss, lens extraction alone may be enough to achieve that an intrascleral chamber is created. Healon GV is left
adequate IOP control; whereas eyes with advanced beneath the superficial scleral flap.
glaucomatous optic neuropathy are more likely to have poor These procedures are indicated in patients with open angle
residual trabecular meshwork function as a result of PAS or glaucoma. It does not work for angle-closure glaucoma,
non-synechial damage. In such cases, phacotrabeculectomy because the barrier to outflow of aqueous humor is beyond
may be necessary to achieve the degree of IOP control the region removed in the procedure, making the intervention
required to prevent progression of glaucomatous optic ineffective. Collagen implants or MMC dramatically improve
neuropathy.104-106 the success and longevity of deep sclerectomy. Fibrosis at
the level of TDM despite implant usage is seen in more than
Complications half (51–63 percent) the patients.109-112 In this scenario a
Anterior chamber inflammatory reaction is usually more after technique known as goniopuncture needs to be performed.
phacotrabeculectomy than after plain trabeculectomy.107 It This is usually required 3 to 21 months after surgery. The
is hypothesized that the release of lenticular crystalline material hallmark of DS is minimal complications like less
and epithelial cells into aqueous humor, the effect of inflammation, less shallowing of the anterior chamber (AC)
ultrasound and/or the high volume of fluid passing through and the less cataract.112,113
the eye at the time of surgery up-regulates the production of
fibrogenic cytokines in the aqueous humor and breakdown Sinusotomy and Canaloplasty
of blood aqueous barrier lasts longer than in sole This surgery, first propounded by Krasnov in 1964, is
trabeculectomy. This lesser inflammation, accounts for the
performed in situations where trabeculectomy is not a practical
better IOP control seen after trabeculectomy alone as option, especially when there is extensive conjunctival scarring,
compared to phacotrabeculectomy. Fibrinous exudation is
thinning or adhesion. Canaloplasty was first attempted in the
the commonest complication observed followed by hyphema,
1960s with sinusotomy, a procedure in which one-third to one-
and choroidal detachment. The incidence of fibrinous reaction
half of Schlemm's canal was deroofed to restore the trabeculo-
after ECCE trabeculectomy has been documented to be as
canalicular outflow path.114 The limitations of operating
high as 27 to 54 percent.108 Late complications reported are
microscopes, at the time, made these procedures difficult to
posterior synechiae and posterior capsule opacification.
perform and yielded unpredictable results. In the 1990s, there
was a resurgence of interest in non-penetrating surgical
Nonpenetrating Glaucoma Surgeries
glaucoma procedures with deep sclerectomy and
Deep sclerectomy (DS) and viscocanalostomy (VC) lower viscocanalostomy. Later development of a 250-µm, flexible
intraocular pressure by reducing outflow resistance of which microcatheter by iScience allowed access to the entire length
trabecular meshwork contributes 75 percent and outer wall of Schlemm's canal and this led to the advent of canaloplasty.
of Schlemm's canal 25 percent. A deep scleral flap and In canaloplasty, identifying Schlemm's canal is crucial. In
external wall of Schlemm's canal (SC) is removed leaving order to gain access to it, a superficial partial-thickness, limbus-
behind corneal stroma, anterior trabeculum and Descemet's based scleral flap is initially made. Within the parameters of
membrane, thus creating a scleral lake. The aqueous humor this flap, a second, deeper partial-thickness scleral flap is
leaves the anterior chamber through the intact constructed. The dissection of the deep flap is then carried
trabeculodescemet's membrane (TDM) and reaches the scleral forward until the Schlemm's canal is unroofed. The
lake, from where it egresses into different pathways. In microcatheter, which has a lighted tip, is threaded into and
viscocanalostomy surgical steps are the same for deep around the circumference of the canal while the viscoelastic
sclerectomy till the Schlemm's canal is deroofed. Then by a is being injected. Once the lighted tip of the microcatheter
paracentesis the IOP is lowered, the two cut ends of has completed 360 degrees and exited, a 10-0 polypropylene
Schlemm's canal are cannulated with a special 165 μm canula suture is tied to this end. The microcatheter is then pulled
and high molecular weight sodium hyaluronate is slowly around in the reverse direction so that the suture traverses
injected into the canal. Upto one to two clock hours of the the entire length of Schlemm's canal. The suture loop is then
canal is atraumatically dilated. The slow injection is repeated secured with locking knots so that the canal and trabecular
six to seven times on each side.111 The outer scleral flap is meshwork tent inwards. This technique functions according
to the hypothesis that the permeability of the trabecular postoperative period compared with tube-shunt placement,
meshwork is improved with the tented opening of the but similar IOPs were observed after three months. Tube-
channels. The deep scleral flap is amputated, and the superficial shunt surgery was associated with greater use of adjunctive-
flap is secured with watertight sutures.115 Since the anterior medical therapy than trabeculectomy with MMC during the
chamber is not violated in canaloplasty, there is no bleb and first two years of the study. The incidence of postoperative
there is decrease in many complications seen with complications was higher after trabeculectomy with MMC
trabeculectomy (i.e. blebitis, endophthalmitis, late-onset bleb compared with tube-shunt surgery, but serious complications
leaks, hypotony, choroidal effusions, cataract formation, and associated with vision loss and/or reoperation developed with
bleb encapsulations). similar frequency after both surgical procedures. Cataract
Most common complications are hyphema, early elevated progression was common, but occurred with similar frequency
IOP, late elevated IOP, wound hemorrhage, Descemet’s with both procedures.
membrane detachment, suture extrusion through the The authors and editors have no financial interest in any product or procedure
trabecular meshwork and hypotony.116 mentioned in this chapter.
Glaucoma Drainage Devices

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114. Krasnov MM. Externalization of Schlemm's canal (sinusotomy)
surgery. Graefe's Arch Clin Exp Ophthalmol 1999;237:887-
in glaucoma. Brit J Ophthal 1968;52:157-61.
92.
115. Lewis RA, et al. Canaloplasty: Circumferential viscodilation and
102. Wyse T, Meyer M, Ruderman JM, et al. Combined trabeculectomy
tensioning of Schlemm’s canal using a flexible mircocatheter for
and phacoemulsification: a one site vs two site approach. Am J
the treatment of open-angle glaucoma in adults: Interim clinical
Ophthalmol 1998;125:334-9.
analysis. J Cataract Refract Surg 2007;33:1217-26.
103. Thomas R, Parikh R, Muliyil J. Comparison between
116. Lewis RA, et al. Canaloplasty: Circumferential viscodilation and
phacoemulsification and the Blumenthal technique of manual
tensioning of Schlemm’s canal using a flexible mircocatheter for
small-incision cataract surgery combined with trabeculectomy. J
Glaucoma 2003;12(4):333-9. the treatment of open-angle glaucoma in adults: Two- year interim
104. Lowe RF. Aetiology of the anatomical basis for primary angle- clinical study results. J Cataract Refract Surg 2009;35:814-24.
closure glaucoma. Br J Ophthalmol 1970;54:161-9. 117. Gedde SJ, Heuer DK, Parrish RK 2nd; Tube Versus Trabeculectomy
105. Gunning FP, Greve EL. Lens extraction for uncontrolled angle- Study Group.Review of results from the Tube Versus
closure glaucoma: long-term follow-up. J Cataract Refract Surg Trabeculectomy Study. Curr Opin Ophthalmol 2010;21(2):123-
1998;24:1347-56. 8.
9.4.4 Glaucoma Drainage Devices

Jaya Chandra Das, Neha Verma
Aqueous shunts are drainage devices that are used to control The treatment algorithm generally accepted in the
intraocular pressure (IOP) in the management of glaucoma. management of glaucoma begins with medical therapy and
Aqueous shunts, tube implants, tube shunts, and setons are laser surgery and proceeds to more invasive measures such
other terms for glaucoma drainage devices. Glaucoma as trabeculectomy and glaucoma drainage implant.
drainage devices have evolved over more than 100 years, The advent of the drainage implant provided a means to
and a range of materials has been used to accomplish artificial approach glaucoma refractory to traditional methods of
translimbal or transscleral drainage of aqueous humor.1 treatment. Currently, there seems to be a conditional shift in
this algorithm in that these implant devices are now being intraocular pressures. Molteno,7 in 1981, introduced the
regarded as first-line therapy options in various cases of double-plate implant and George Baerveldt, 8 in 1992,
glaucoma that are notoriously difficult to manage (i.e. introduced a non-valved silicone tube attached to a large
neovascular glaucoma).2 barium impregnated silicone plate.
Implants can be divided essentially into two groups, those
HISTORICAL PERSPECTIVE with valves and those without valves.
The nonvalved are the various types of Molteno implants,
The earliest attempts to drain fluid out of the anterior chamber the Baerveldt implant, and the Schocket encircling tube.
into the subconjunctival space at the limbus date back to Valved implants include the Krupin Disk, Ahmed valve,
1907 when Rollet implanted a horse-hair thread connecting White pump, Joseph tube, and the OptiMed glaucoma pressure
the anterior chamber to the subconjunctival space near the regulator.
limbus.3 All commonly used implants consist of a long tube
Numerous attempts have been made since then without through which aqueous drains from the anterior chamber to
much success, until 1969. These have included silk, gold, a posteriorly placed plate that acts as a bleb-spreading device.
platinum, tantalum, glass rod, and polythene tube implants. Most of the shunts in recent successful widespread clinical
All these operations failed because of excessive scar formation use (Ahmed [New World Medical, Inc., Rancho Cucamonga,
near the limbus, seton migration, conjunctival erosion, and CA], Baerveldt [Advanced Medical Optics, Inc., Santa Ana,
so forth.2 CA], Krupin [Eagle Vision, Inc., Memphis, TN], Molteno
Molteno, in 1969, introduced the concept of the large [Molteno Ophthalmic Ltd., Dunedin, New Zealand]) follow
surface area needed to disperse the aqueous.4 He inserted a the same biological principles. These devices include an explant
short acrylic tube attached to a thin acrylic plate and sutured plate that, when encapsuled, creates a potential space into
it to the sclera, adjacent to the limbus. Most of the operations which aqueous can drain via a connecting silicone-rubber
failed after the first three to six months because of plate tube. The explant plates are constructed from materials
exposure, tube erosion, and scar tissue formation. (polypropylene or silicone rubber) to which fibroblasts cannot
In 1973, Molteno introduced the concept of draining the adhere tightly. They have identical silicone-rubber tubes with
fluid away from the source to increase the success rate.5 All an outside diameter of approximately 600 µ and an inside
of the currently available glaucoma drainage devices are based diameter of approximately 300 µ that connect the explant
on this concept of the Molteno implant (Molteno Ophthalmic plate to the anterior chamber or vitreous cavity.
Limited, Dunedin, New Zealand), which has a long silicone The primary tube-plate junction in all four devices includes
tube attached to a large explant placed 9 to 10 mm posterior a rim through which the tube empties onto the explant plate
to the limbus. surface to ensure substantial physical separation of the
The Molteno and similar implants offer no resistance to posterior tube orifice from the eventual encapsulation of the
the outflow resulting in hypotony, flat anterior chambers, and device by fibrous tissue after aqueous flow begins.
choroidal effusions. Devices differ depending on explant surface areas, shape,
Since then, two major concepts have been introduced to plate thickness, the presence or absence of a valve, and details
modify glaucoma drainage devices.2 The first concept was of surgical installation.
that of a valve to offer resistance to the outflow and thus External portions of glaucoma drainage devices are made
reduce the incidence of postoperative hypotony. Theodore from materials that prevent fibroblast adherence. Different
Krupin, 6 in 1976, introduced the pressure-sensitive, materials may influence the amount of inflammation in
unidirectional valve that provides resistance to the flow of surrounding tissues. Polypropylene, used in the earlier models
aqueous and prevents early, post-operative hypotony. This of Ahmed and Molteno implants, appears to cause more
slit valve is designed to open at a pressure of 11 mm Hg and inflammation than silicone that is used in Baerveldt, Krupin
close at a pressure of 9 mm Hg. In 1993, Marteen Ahmed and newer models of Ahmed and Molteno implants.
introduced the Ahmed Glaucoma Valve2 (New World Medical, Alternative materials such as hydroxyapatite and expanded
Rancho Cucamonga, CA), a pressure sensitive, unidirectional polytetrafluoroethylene, which increase vascularization of the
valve that is designed to open when the IOP is 8 mm Hg. fibrous capsule around the plate, may offer a theoretical
The second major modification was the increase in the surface advantage by enhancing the efficacy, decreasing the capsule
area of the end-plate or the explant, resulting in lower size and increasing the functional lifetime of the implant.
938 Glaucoma
Experimental studies,1 including microperfusion flow The double-plate implant (Fig. 9.4.4.2) consists of two 13
experiments in monkeys and rabbits, have demonstrated that mm plates (surface area of 268 mm2). They are connected
the capsule around the explant provides the primary resistance to each other by a 10 mm silicone tube entering 90º away
to aqueous outflow through aqueous shunts. The standard from the primary, intracameral tube. The plates are sutured
tube contributes no measurable resistance to outflow, with to adjacent quadrants with the connecting tube placed either
physiologic perfusion flow rates of 2 to 4 µl/minute. Explant above or below the appropriate rectus muscle. The
size (mm2) has been shown clinically and experimentally to implantation of a double-plate involves more dissection and
correlate with the amount of drainage capacity and potential therefore is more demanding than the single-plate implant.
lowering of IOP. The two plates in effect double the amount of potential
Capsule thickness also correlates in experimental studies surface area through which aqueous can be absorbed. Molteno
(rabbits) with capsule hydraulic conductivity (flow in found that two plates provided better drainage than one, but
microliters per minute per millimeter of mercury per square four plates were not better than two.9 It has been observed
millimeter). that children initially controlled with double-plate implants
Aqueous moves through the capsule into surrounding may, over a period of years, require another double-plate
tissues by simple passive diffusion, demonstrated by using implantation for adequate control of IOP. Molteno noted
horseradish peroxidase and latex particles as markers of flow. that the single-plates have higher success rates in
pseudophakic/aphakic glaucoma, while double-plate implants
OPEN TUBE DRAINAGE DEVICES had better success rate in neovascular glaucoma.9
The top surface of the plate is divided into one smaller
Molteno Implant
and one larger chamber (Fig. 9.4.4.3) by the apposition of
The Molteno implant consists of a silicone tube (outer the overlying conjunctival and Tenon's layers. Aqueous flows
diameter 0.6 mm and inner diameter 0.3 mm) that opens (black arrow) into the smaller proximal chamber, until
onto the upper surface of a circular, acrylic plate 13 mm in sufficient pressure is achieved within the chamber to lift
diameter (Fig. 9.4.4.1). The conjunctival bleb that forms over (arrow) the overlying conjunctival layer to allow free drainage.
the implant cannot contract to a size smaller than the acrylic Other variations of the Molteno implant include a
plate.4,7 pediatric size plate (74 mm2) for use in eyes with short axial
The surface area of the single-plate model is 134 mm2. lengths, and the V-chamber plate. The V-chamber modification
The edge of the plate has a thickened rim 0.7 mm high that (Fig. 9.4.4.4) is designed to decrease postoperative hypotony
is perforated to permit suturing to the sclera thus preventing from over-filtration. The V-chamber implant contains a thin
plate migration. To increase the potential space available for V-shaped rim of polypropylene on the plate surface below
aqueous absorption, Molteno designed a double-plate model. the tube's entry, occupying one-eighth of the plate's area.
Fig. 9.4.4.1: The Molteno implant consists of a silicone tube (outer Fig. 9.4.4.2: The Molteno double-plate implant consists of two 13 mm
diameter 0.6 mm and inner diameter 0.3 mm) that opens onto the upper plates (surface area of 268 mm2). They are connected to each other
surface of a circular, acrylic plate 13 mm in diameter (Diagrammatic by a 10 mm silicone tube entering 90º away from the primary,
representation) intracameral tube (Diagrammatic representation)
Since this V-shaped ridge is the same height as the

circumferential rim of the plate, the weight of the overlying,
hydrated Tenon's tissue will in theory collapse and form a
temporary roof for the smaller V-chamber, thus limiting the
extent of the bleb and filtration. The clinical effectiveness of
this design has not yet been established.10
Baerveldt Implant
Fig. 9.4.4.3: The top surface of the Molteno plate is divided into a This implant is designed in such a way that it can be easily
smaller and a larger chamber by the apposition of the overlying implanted through a one quadrant conjunctival incision. A
conjunctival and Tenon's layers. Aqueous flows into the smaller
proximal chamber, until sufficient pressure is achieved within the
silicone tube is attached to a soft barium impregnated silicone
chamber to lift the overlying conjunctival layer to allow free drainage plate with a surface area of 250 mm2 (20×13 mm), 350
mm2 (32×14 mm) or 500 mm2 (36×17.5 mm). The 350
mm2 is currently a preferred size, in that it appears to be
safer and slightly more effective than the 500 mm2 implant.
The plate is positioned under the rectus muscle insertions,
typically in the superotemporal quadrant. The Baerveldt plate
(Fig. 9.4.4.5) has fenestrations that allow growth of fibrous
tissue through the plate serving to reduce the height of the
bleb and secure the implant in place.
A fibrous capsule forms after the first three to six
postoperative weeks into which fluid can drain and from
which the fluid can be absorbed by the surrounding tissues.
In terms of IOP control, the 350 mm2 implant was shown
to have similar rate of success but lower rate of complications
than the 500 mm2 model.11
Fig. 9.4.4.4: The V-chamber Molteno implant contains a thin V-shaped The Baerveldt 250 mm2 glaucoma implant provides good
rim of polypropylene on the plate surface below the tube's entry, intermediate-term success for the treatment of adult
occupying one-eighth of the plate's area.
refractory glaucoma.12
Schocket Tube Shunt

A silicone or silastic tube is extended from the anterior
chamber to a 360° encircling silicone band, as used in retinal
detachment repair, which functioned in developing the
reservoir for aqueous drainage.13,14
Modifications have included insertion of the tube into a
band extending for only 90° beneath two rectii muscles or
into the preexisting encircling band in eyes with glaucoma
after scleral buckling surgery.
FLOW RESTRICTED DRAINAGE DEVICES
Ahmed Glaucoma Valve

In this valved implant design (Fig. 9.4.4.6), a silicone tube is
connected to a silicone sheet valve, which is held in a
Fig. 9.4.4.5: The Baerveldt plate has fenestrations that allow growth
of fibrous tissue through the plate serving to reduce the height of the polypropylene or silicone body. There are adult (FP-7) and
bleb and secure the implant in place. (Diagrammatic representation) pediatric (FP-8) models available. The pars plana clip can be
940 Glaucoma
the IOP. As pressure reaches the pre-set threshold value, the

valve opens, thus decreasing eye pressure. In order for
Bernoulli's equation to be satisfied (fluid flowing into section
1 = fluid flowing out of section 2; where section 1 and 2 are
at the entry and exit of the elastomer membrane valve) the
fluid's velocity has to increase as it leaves the chamber through
the drainage tube. This increased velocity and non-obtrusive
flow account for the better evacuation and smaller valve
friction. The tension in the silicone membranes helps reduce
hypotony by closing after the pressure has decreased and
reached a normal level again.
Application of Bernoulli's equation (flow rate of a fluid
is inversely proportional to the pressure of the fluid) to the
parameters that exist within the physiologic IOP range shows
Fig. 9.4.4.6: Ahmed glaucoma valve that Bernoulli's effect is almost nonexistent in AGV.16
The Ahmed implant, has a hypertensive phase, which is a
transient phase of low capsule permeability seen four to eight
used in aphakic/pseudophakic, vitrectomized eyes through weeks postoperatively.16,17
pars plana into posterior chamber. There are tube extenders A concept of ‘No-Touch Zone’ on the AGV has been
(model TE) which may be necessary is some cases. Ahmed introduced which is the area of the implant covering the
glaucoma valve has also a model (F×4) with flexible non- chamber with the silicone leaflets. If the implant is grasped
valved plate be increase the surface area of drainage. The with the forceps along the center line, it may separate the valve
body of a most commonly used S2 model has a surface area cover from the implant. The external pressure on the valve
of 184 mm2 (16×13 mm) and is 1.9 mm thick. The valve chamber can explain a defect in closure of the valve with
mechanism consists of 2 thin silicone elastomer membranes, consequent early postoperative hypotony and fibrovascular
8 mm long and 7 mm wide, which allows one way regulation membrane ingrowth between the leaflets. This may lead to
of the flow with a goal of keeping the IOP between 8 and 10 failure of the valve due to adhesion of the valve membranes.18
mm Hg in the early postoperative period. A flexible silicone AGV (FP7, 0.9 mm thick) is available.
The inlet cross section of the chamber is wider than the After one year of follow-up, the silicone AGV is at least as
outlet, which offers a theoretical small pressure differential effective as the polypropylene19 AGV in IOP reduction but
between the anterior chamber and subconjunctival space, may be associated with a higher rate of nontube related
which is claimed to enable the valve to remain open even complications20 such as choroidal effusion, suprachoroidal
when only a small pressure difference exists.15 hemorrhage, hypotonic maculopathy. These differences are
The Venturi effect of the valve (Fig. 9.4.4.7) can be important for surgeons converting to use of the silicone AGV
explained by Bernoulli's equation of fluid dynamics. The aqueous in patients with glaucoma refractory to other forms of
humor flows slowly into the trapezoidal chamber and increases treatment.12,15,20
Fig. 9.4.4.7: Bernoulli's equation of fluid dynamics explaining the Venturi effect in an AGV
Attachments for an additional plate (Biplate models B1, SURGICAL TECHNIQUE

FX1), and insertion of a pars plana tube and tube extender
• Tractional suture is passed through superficial cornea near
are available. A small plate size of 96 mm2 (S3, FP8) is also
superior limbus for adequate surgical exposure.
available for children. Nonvalved models (B4, FX4) are also
• Fornix based conjunctival flap is made to expose the scleral
available. bed. Blunt dissection is done between the Tenon's capsule
The effect of intraoperative mitomycin-C (MMC) on and episclera.
polypropylene Ahmed glaucoma valve (AGV) survival two • Balanced salt saline (BSS) is irrigated through the tube of
years after implantation during the first two years of life was the implant before insertion into the AC to ensure that
studied. Rather than improving survival, intraoperative use the valve opens adequately.
of MMC was associated with shorter survival two years after External plate is tucked posteriorly into the sub-Tenon's
AGV implantation during the first two years of life. It was space and sutured to the sclera with 9-0 prolene sutures
speculated that MMC-induced tissue death can stimulate a through the anterior holes with the anterior border 8–10
reactive fibrosis around the AGV in very young eyes.21 mm posterior to the limbus.
Pressure in this zone will allow indentation of this area, • Larger sized implants can be tucked under adjacent rectus
damaging the plastic rivets attaching the valve cover to the muscles. 360° dissection is required for the Schocket
valve body. This allows formation of a gap between these implant.
structures and allows fibrovascular ingrowth.17 • The tube is cut, beveled up, to permit its extension 2 to 3
mm into the AC.
Krupin Implant • AC entry is made with a 23 gauge needle and the angle at
which the needle enters the AC is critical as the tube would
The original Krupin Denver valve was composed of an traverse the same track to be adequately positioned
internal Supramid tube cemented to an external silastic tube, between the cornea and the iris without touching the
designed to open at an IOP between 9 and 11 mm Hg. The cornea.
tube was short extending only a few mm subconjunctivally, • The tube is sutured to the underlying sclera with or without
and had no external plate. Fibrosis eventually closed the a patch graft.
subconjunctival portion of the valved tube leading to failure. • Conjunctiva is sutured over the implant.
Subsequently a long Krupin-Denver drainage tube with the • Subconjunctival antibiotic-steroid injection is given in
one way valve design was attached to a 180o Schocket type another quadrant.
scleral explant.21 • Routine postoperative management is followed.
This led to Krupin eye valve with a disk having a silastic
tube attached to an oval silastic disc.22-24 COMPLICATIONS
In the newer design of the Krupin implant, the valve lies
inside the rim of the plate at its insertion and is exposed The complications associated with GDD include:25-29
directly to the subconjunctival tissues.16
Intraoperative Complications
COMMON INDICATIONS a. Bleeding
FOR USED OF GDD – Occurs typically in neovascular glaucoma
– Large hyphemas must be evacuated as they can block
These are: the tube.
1. One or more filtering procedures that have failed b. Misdirection of the silicone tube into the posterior
2. Aphakic glaucoma chamber may occur in the presence of peripheral anterior
3. Pseudophakic glaucoma synechiae.
4. Uveitic glaucoma c. Loss of AC may occur if the port size is bigger than
5. Neovascular glaucoma tube.
6. Congenital glaucoma with iridocorneal dysgenesis This can be remedied by introduction of saline or
7. ICE syndrome viscoelastic through a previously placed paracentesis
8. Glaucoma following corneal transplantation. opening and choosing 23 or 24 gauge needle.
942 Glaucoma
Early Postoperative Complications too thick, it may elevate the limbal conjunctiva enough to
produce dellen formation.
a. Hypotony with or without associated choroidal effusions.
c. Plate migration may occur if the body is not fixed properly.
– Small effusions may be left to resolve spontaneously.
If the plate migrates towards the medial rectus muscle
– Large effusions resulting in kissing choroidals may
insertion, myositis may develop. It resolves after implant
have to be evacuated.
removal.
– Hypotony is best treated by prevention, either by the
d. Limitation of eye movements can occur spacially when
use of valved implants or by occlusion of the silicone
placed in upper nasal quadrant. The movement most
tube with a stent and/or a constricting ligature.
commonly affected is upgaze.
b. Increased IOP may occur due to occlusion of the silicone
Other patterns are exotropia, hypertropia and,
tube:
limitations of ocular rotations. Placement of the implants
– The opening of the tube may be obstructed by iris.
in the lower fornix restricts downgaze with associated
– This can be treated by YAG ablation of the iris tissue.
diplopia.
– Occlusion by vitreous in aphakes can be prevented
e. Endophthalmitis: Exposure seems to be the most
by thorough vitrectomy prior to tube insertion.
important risk factor for these infections. Surgical revision
c. Tube-corneal contact may occur. This can be prevented
with a patch graft is indicated in all these cases to prevent
by accurate tube placement intraoperatively away from
endophthalmitis.
the endothelium and parallel to the iris surface.
f. Other possible complications are:
Total tube corneal touch requires repositioning of the
• Epithelial downgrowth: It can cause implant failure,
tube and shortening the tube to project only 2 to 3 mm
corneal decompensation, and formation of a true
into anterior chamber.
Tenon's cyst.
d. Early postop endophthalmitis is a rare complication.
• Epithelial invasion into the fibrous capsule with
It can be treated by immediate removal of the implant
persistent aqueous leak.
and surgical management of the infection, with subsequent
• Sterile hypopyon.
placement of a new implant.
• Irregular pupil many years later due to adherence of
the iris root to the tube.
Late Complications
• Globe perforation while suturing the plate to the sclera
a. Encysted bleb can form. In its hypertensive phase, it results causing retinal detachment or vitreous hemorrhage.
in IOP elevation due to development of a thick capsule This is seen more commonly in high myopes with
around the plate four to six weeks postoperatively. thin sclera.
IOP can be controlled using hypotensive agents. • Retinal complications include retinal detachment,
Deflation of the bleb to allow compressed channels in suprachoroidal hemorrhage, vitreous hemorrhage,
the wall of the bleb to expand and reestablish drainage choroidal effusion.
may be necessary.
Encysted blebs contain a relatively large amount of NEWER SETONS
aqueous and as much as 1 cm3 of aqueous may be
withdrawn to deflate the bleb with no loss of anterior Glaukos iStent
chamber. Also as these blebs are relatively avascular, This is a light weight Titanium L-shaped device which is placed
needling them is less traumatic. inside Schlemm's canal (Figs 9.4.4.8 and 9.4.4.9).
A regimen consisting of diclofenac 75 mg daily, The heparin covered titanium is biocompatible, has
prednisolone 40 mg daily and topical corticosteroids may thrombolytic activity and prevents stenosis. A small, snorkel
be helpful if given not later than 14 days postoperatively shaped tube, about 0.5 mm in length sits in the peripheral
and continued for at least six weeks. AC, allowing aqueous to bypass the inner wall of Schlemm's
The hypertensive phase is common following canal and the juxtacanalicular trabecular meshwork.
implantation of the Ahmed valve which subsides in four The portion of the device that is placed inside the canal
to six weeks time. is 1 mm in length and is shaped like a half-pipe. It is designed
b. Erosion of the silicone tube through the sclera or scleral to fit within the lumen of the Schlemm’s canal, with the curved
patch and conjunctiva may occur. If the scleral graft is convex side lying against the inner wall of Schlemm's canal.
This avoids contact with the outer wall and the collector 5.2 mm long, 2 mm wide and 60 thick, containing multiple
channel orifices that enter the outer wall. The three barbed microchannels. Initially, half of these microchannels are open
ridges along this portion are designed to prevent loosening and the remainder closed by a thin film of gold which can be
and provide a secure placement of the stent in the canal. opened after implantation, using the titanium sapphire laser.
These can either be right handed or left handed. This reactivates the shunt's effect and additional drop in IOP
A temporal clear corneal incision is made, and the AC is can be obtained. This phototitration can be done at any time
filled with viscoelastic. An applicator grasps the device and postoperatively.
under gonioscopic guidance, traverses the AC to reach the The shunt is implanted through a 3 mm clear corneal
Schlemm's canal in the nasal quadrant. The pointed tip engages incision made at the limbus into the suprachoroidal space
the trabecular meshwork and the stent is inserted in place. using a preloaded insertion device. The channels in the shunt
form a bridge between the anterior chamber and
Gold Micro-Shunt suprachoroidal space.
The deep light glaucoma treatment system includes a titanium-
sapphire laser and a photo titratable gold micro shunt (Fig. Ex-PRESS Shunt
9.4.4.10). The laser emits microsecond infrared light pulses The Ex-PRESS mini-glaucoma shunt (Fig. 9.4.4.11) is a 400
that passes through the trabecular meshwork tissues, producing μm wide × 3 mm long, stainless steel device. It has a beveled,
significant opening of the trabecular meshwork, allowing sharpened rounded tip, a disclike flange (<1 mm2) at the
increased aqueous outflow.. The gold shunt is biocompatible proximal end and a spurlike projection that prevents its
and inert, made of 99.5 percent pure gold. It is a flat plate extrusion. The external flange and inner spur are angled to
conform to the anatomy of the sclera, and the distance
between them corresponds to the scleral thickness at the site
of implantation. The inner diameter of the silicone tube is
125 μm and the outer diameter is 250 μm, making the tube
narrow enough to fit the lumen of the Schlemm canal.30 The
implant is sterilized by gamma radiation and is a single-use
device that should be stored at a temperature between 15°C
and 30°C. The bleb formation starts immediately and
microcysts within the bleb can be seen within the first or
second post-operative day.
OptiMed Glaucoma Pressure Regulator

It is made of a silicone tube with a PMMA matrix plate. The
inner diameter of the tube is 0.38 mm and outer diameter is
Fig. 9.4.4.8: iStent is an L-shaped device and has a small, snorkel 0.76 mm. A 5 mm PMMA tube is inserted into the silicone
shaped tube, about 0.5 mm in length sits in the peripheral AC and the
base with dimensions of 1×2×3×4 mm. The base contains
1 mm long half-pipe shaped segment is placed inside the canal with
the curved convex side lying against the inner wall of Schlemm's 180 to 200 microtubules through which aqueous percolates
canal through to the subconjunctival space. Aqueous outflow
Fig. 9.4.4.9: Surgical procedure for implantation of the iStent

944 Glaucoma
mm from the limbus and yet allowing the plate to be placed at

10 mm from the limbus, reducing the likelihood of its extrusion.
The authors/editors have no financial interest in any product or procedure
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tube shunt to an encircling band in the treatment of neovascular
increases. The pressure gradient across the PMMA glaucoma and other refractory glaucomas: a long-term study.
microtubules is governed by Poiseuille's formula. Ophthalmology 1985;92:553.
15. Ishida K, Netland PA, Costa VP, Shiroma L, Khan B, Ahmed IIK.
Susanna Glaucoma Implant Comparison of polypropylene and silicone Ahmed glaucoma valves.
This has a reservoir body conforming to the shape of the 16. Lee VW. Glaucoma “valves”—truth versus myth. Ophthalmology
globe at its equator and a ridge in the end plate to protect the 1998:105:567.
inner opening of the silicone tube from blockage by fibrous 17. Hill RA, Pirouzian A, Liaw L. Pathophysiology of and prophylaxis
tissue growth. A fenestrating end plate promotes fibrous tissue against late Ahmed glaucoma valve occlusion. Am J Ophthalmol
2000;129:608.
anchoring, resulting in less micromotion that may cause more 18. Feldman RM, el Harazi SM, Villanueva G. Valve membrane
inflammation decreasing the permeability of the capsule. The adhesion as a cause of Ahmed glaucoma valve failure. J Glaucoma
foot plates measuring 4 mm in length allow easy fixation at 6 1997;6:10.
19. Coleman AL, Hill R, Wilson MR, et al. Initial clinical experience 25. Melamed S, Cahane M, Gutman I, Blumenthal M. Postoperative
with the Ahmed glaucoma valve implant. Am J Ophthalmol complications after Molteno implant surgery. Am J Ophthalmol
1995;120:23. 1991:111:319-22.
20. Law SK, Nguyen A, Coleman AL, Caprioli J. Comparison of 26. Ayyala RS, Harman LE, Michelini-Norris B, et al. Comparison of
safety and efficacy between Silicone and polypropylene Ahmed different biomaterials for glaucoma drainage devices. Arch
glaucoma valves in refractory glaucoma. Ophthalmology Ophthalmol 1999;117:233.
2005;112:1514-20. 27. Ayyala RS, Michelini-Norris B, Flores A, et al. Comparison of
21. Al-Mobarak F, Khan AO. Two-year survival of Ahmed valve different biomaterials for glaucoma drainage devices: part 2. Arch
implantation in the first 2 years of life with and without Ophthalmol 2000;118:1081.
intraoperative mitomycin-C. Ophthalmology 2009;116:1862-5. 28. Hong CH, Arosemena A, Zurakowski D, Ayyala RS. Glaucoma
22. Krupin T, Podos SM, Becker B, et al. Valve implants in filtering drainage devices: a systematic literature review and current
surgery. Am J Ophthalmol 1976;81:232. controversies. Surv ophthalmol 2005;50:48-60.
23. Krupin T, Kaufman P, Mandell A, et al. Filtering valve implant 29. Krupin T, Ritch R, Camras CB, et al. A long Krupin-Denver valve
surgery for eyes with neovascular glaucoma. Am J Ophthalmol implant attached to a 180 degrees scleral explant for glaucoma
1980;89:338. surgery. Ophthalmology 1988;95:1174.
24. The Krupin Eye Valve Filtering Surgery Study Group. Krupin eye 30. Dietlein TS, Jordan JF, Schild A, Konen W, Jünemann A, Lüke C,
valve with disk for filtration surgery. Ophthalmology 1994; Krieglstein GK. Combined cataract-glaucoma surgery using the
101:651. intracanalicular Eyepass glaucoma implant: first clinical results of a
prospective pilot study. J cataract Refraction surg 2008;34:247-
52.
9.4.5 Recent Surgical Advances in Glaucoma

The surgical management of glaucoma is offered to patients Most of these newer procedures have been discussed in
if drug and/or laser therapy has not been satisfactory or the previous chapters in this section. This chapter provides a
cannot be tolerated. The common indications include comprehensive overview.
uncontrolled intraocular pressure (IOP) despite maximum
medical therapy, failed laser therapy or poor laser candidate, POSSIBLE COMPLICATIONS
progressive glaucomatous cupping or visual field progression. OF TRABECULECTOMY
The most common conventional surgical technique for
glaucoma is trabeculectomy, which essentially involves making The main problem with conventional trabeculectomy is the
an incision in the eye and creating an exit path through which need for ocular entry which is responsible for possible early
the aqueous can egress and lower intraocular pressure (IOP). postoperative hypotony, and the attendant sequelae of
A peculiar problem with glaucoma surgery is that in an era hyphema, choroidal effusions, shallow anterior chambers, and
of “High Tech, see better the same day” concept made cataract. Avoiding these potential sight-threatening
popular by phacoemulsification, trabeculectomy offers stability complications has led to the concept of reducing intraocular
of vision and not improvement. It is a high risk surgery pressure by way of surgery while preserving the internal
compared to many other procedures, and the visual acuity trabecular meshwork.
can worsen by one or two lines. To add to the problems,
though the reported success rates of trabeculectomy are as Non-penetrating Glaucoma Surgery
high as 70 to 90 percent for a year, it is known to diminish
over a period of time,1 and many blebs eventually fail. Thus Recently, new techniques have been introduced 2-5 for
trabeculectomy is fraught with two major problems, risk of performing glaucoma surgery without opening the anterior
complications and the risk of failure. All recent advances in chamber, thus avoiding the complications which are commonly
the surgical management of glaucoma has been developed associated with penetrating glaucoma surgery. These methods
as a means to address these two major issues. involve exposure of the canal of Schlemm under a deep
946 Glaucoma
scleral flap without actually entering the anterior chamber stretched with sodium hyaluronate 1.4 percent (Healon
and sometimes insertion of a collagen sponge under the scleral GVTM).
flap. This has led to the development of non-penetrating Here, the superficial scleral flap is sutured down
glaucoma surgery (NPGS) to be a viable alternative to tightly, minimizing subconjunctival fluid outflow and bleb
conventional trabeculectomy in glaucoma management. formation.
The idea of non-penetrating surgery stems from the
recognition that the juxtacanalicular region and inner wall of Problems with NPGS
Schlemm’s canal are the major sites of resistance to aqueous Though it has been suggested that deep sclerostomy results
outflow. Rupture of the inner wall of Schlemm’s canal and in less hypotony, hyphema, cataract formation, 10 and
damage to juxtacanalicular tissue may be sufficient to relieve postoperative flare and cells,11 it is also true that widespread
abnormal resistance to aqueous outflow. The trabecular- acceptance of the procedure has been limited by the steep
Descemet's membrane can be left intact without violating learning curve associated with this type of surgery.12 One
the anterior chamber. This is thought to result in a more report found that inadvertent perforation of the trabecular
controlled drop in IOP. meshwork occurred in 30 percent of initial cases. 13
Non-penetrating surgery is broadly descriptive of two Perforation requires conversion to conventional
technical approaches, deep sclerectomy (DS) and visco- trabeculectomy which may result in suboptimal flap
canalostomy (VC). construction, leading to over-filtration. Following conversion,
the incidence of postoperative hypotony has been reported
Deep Sclerectomy: Deep sclerectomy, initially described by
to be 90 percent while hyphema was 68 percent.14
Krasnov6 creates a Descemet's window that allows aqueous
Late failures of the procedure require surgical revision
seepage from the anterior chamber. Subsequent fluid egress
which may be of two kinds. Internal revision employs the
is thought to proceed subconjunctivally, resulting in a filtration
transcameral approach, using a blunt cyclodialysis spatula or
bleb, as well as along deeper suprachoroidal routes. Further
coaxial diathermy probe to reopen the juxtacanalicular tissue.
placement of a collagen implant in the scleral bed has been
External revision employs needle revision along with
advocated to help maintain the scleral drainage reservoir.7,8
subconjunctival mitomycin C (MMC) or 5-Flourouracil
Viscocanalostomy: The second technique, viscocanalostomy,9 (5-FU).
also requires deep scleral dissection and creation of a filtering
window (Fig. 9.4.5.1). The aqueous outflow, however, relies Efficacy and Place of NPGS in
on the patency of aqueous exit channels, supposedly achieved Present Day Glaucoma Practice
through identifying and dilating. Schlemm's canal using high
Nonpenetrating glaucoma surgery is certainly safer than
density viscoelastic (Fig. 9.4.5.2). The Schlemm's canal is
trabeculectomy and thus may have a worthwhile role in early
deroofed and the ostia of Schlemm's canal probed and
open angle glaucoma. Its limitation in lowering IOP to the
mid- or late teens precludes its use for advanced glaucoma.15
The major controversy that arises is over the success rates
of NPGS compared to trabeculectomy. The steep learning
curve of this surgery and the need to consider goniopuncture
Fig. 9.4.5.1: Creation of trabeculo-descemet’s Fig. 9.4.5.2: Dilatation of Schlemms canal during viscocanalostomy
window in deep sclerectomy
as an adjuvant to the procedure are other issues which make lumen occlusion, corneal endothelial loss (even with proper
it a less viable option on a widespread scale. The use of tube positioning), tube migration, ptosis, and diplopia.
implants in nonpenetrating glaucoma surgery appears to result Given the potential complications and long-term failure
in better IOP control for longer periods, thus enhancing rate of subconjunctival glaucoma surgery, there is a recent
success rates. Variable definitions of success, different follow- renewed interest in surgery of the angle in an attempt to
up times, and variable study designs make direct comparisons increase aqueous drainage in a more physiological manner.
between reported results very difficult. This includes surgery in the Schlemms canal and goniosurgical
procedures such as laser ablation of the trabecular meshwork,
FAILURE OF STANDARD laser trabeculopuncture, goniocurretage, the Glaukos
TRABECULECTOMY trabecular micro-bypass iStent (Glaukos Corp., Laguna Hills,
Failure of the trabeculectomy bleb after an interval of CA, USA) and the Trabectome microelectrocautery device
apparent success is a fairly common problem. Filtration surgery (NeoMedixCorp., San Juan Capistrano, CA, USA). Non-
failure is most commonly due to fibrosis involving episcleral- penetrating surgery such as canaloplasty (iScience
tenon-conjunctival interface.16 It occurs mainly by proliferation Interventional Inc., Menlo Park, CA, USA) have also emerged
of subconjunctival fibroblasts and biosynthesis of collagen as external approaches to Schlemm's canal.
and other extracellular material.17,18 Fibroblast proliferation Aqueous humor also leaves the anterior chamber via the
can be decreased with introduction of antifibrotic agents such uveoscleral outflow pathway, consisting of the ciliary body,
as 5-FU and MMC resulting in increased success of filtering suprachoroidal space, and scleral vasculature. This has been
surgery in high risk patients.19 Anti-fibrotic agents inhibit DNA reported to comprise 20 to 54 percent of total aqueous humor
synthesis, and minimize recruitment, migration and egress in normal human eyes.27,28 Surgical approaches to
proliferation of fibroblasts. However, extended follow-up of augment suprachoroidal outflow have also been explored in
trabeculectomies even after using these antifibrotic agents the past with cyclodialysis, suprachoroidal implants and seton
shows that long-term failure in these high risk eyes is a major devices. More recently, an ab externo gold shunt (SOLX Inc.,
clinical problem.20,21 Waltham, MA), has been implanted in the suprachoroidal space.
An overview of some novel drainage devices and
Glaucoma Drainage Devices techniques of angle and Schlemms canal surgery is given
below. They are all in early stages of development, and appear
To obviate the problem of scarring and fibrosis in the bleb
very promising, but long-term IOP control with these
area, glaucoma shunt procedures have gained in popularity
procedures is not yet established. These procedures must be
over the years. This has been discussed in detail in the previous
chosen with caution in patients who have a narrow anterior
chapter.
chamber angle, as they may be more likely to form peripheral
Conventional Glaucoma Drainage Devices anterior synechiae postoperatively due to inflammation and
proximity of iris tissue to the angle. These are:
The first tube and plate glaucoma drainage devices were • Ex-PRESS mini-glaucoma shunt (Optonol Ltd, Kansas,
introduced by Molteno.22,23 This was later followed by other KS, USA)
designs, such as those by Krupin,24 Baerveldt25 and Ahmed.26 • Glaukos trabecular micro-bypass iStent (Glaukos Corp.,
Used frequently in patients with recalcitrant glaucoma, many Laguna Hills, CA, USA)
of whom have failed prior surgical treatments, these implants • Trabectome microelectrocautery device (NeoMedixCorp.,
consist of a tube placed into the anterior chamber through San Juan Capistrano, CA, USA)
which aqueous humor flows posteriorly into an encapsulated • Suprachoroidal outflow gold shunt device (SOLX Inc.,
filtration area typically 10 to 12 mm posterior to the limbus, Waltham, MA, USA)
into a reservoir sutured to the sclera. However, tube shunt • Nonpenetrating canaloplasty surgery.
surgery may be complicated by hypotony and overfiltration, These have been described in the pervious chapter.
sometimes leading to suprachoroidal hemorrhage. Therefore,
tube shunt devices commonly require flow restriction and
Ex-PRESS Mini-glaucoma Shunt
regulation, despite which, overfiltration and hypotony, bleb
encapsulation and may adversely affect the outcome. Other This is a stainless steel device designed to allow aqueous humor
potential complications include tube or plate exposure, tube filtration into the subconjunctival space.
948 Glaucoma
The shunt consists of a tip with one or several orifices

into the anterior chamber for draining aqueous in through
the 27-gauge shaft, which is designed to approximate the
thickness of human sclera. A spur present on the underside
of the shaft prevents extrusion of the device, while an external
plate prevents intrusion of the shunt into the anterior chamber
and occlusion of the external ostium. The external plate is
implanted under a trabeculectomy-style scleral flap.29-31
Biocompatibility has also been demonstrated in studies.32 When
implanted in ocular tissue, the device also appears to be safe
when undergoing magnetic resonance imaging (MRI).
Glaukos Trabecular Micro-bypass iStent

The trabecular micro-bypass stent named the iStent®, is
designed to be part in the anterior chamber and part in
Schlemm's canal, allowing direct access of aqueous humor Fig. 9.4.5.3: Electrocautery design to incise trabecular meshwork
via the stent into Schlemm's canal. The stent is placed via an
ab interno approach, through a corneal paracentesis-type
incision of approximately 1.5 mm in size. Alternatively, when known inert and noncorrosive metal, its biocompatibility as
performed in conjunction with cataract extraction, the cataract an implant is good.34 Gold as an intraocular foreign body in
incision may also conveniently be utilized. Much like other the anterior chamber has also been reported to have no
goniosurgical procedures, a gonioprism is required for adverse effects, even after many years.35
appropriate visualization of the angle.
Nonpenetrating Canaloplasty Surgery
Trabectome Microelectrocautery Device
Canaloplasty is a nonpenetrating ab externo procedure with
A new device, the Trabectome has been developed as a means the goal of reestablishing or augmenting aqueous outflow via
of incising trabecular meshwork via electrocautery. This novel the conventional pathway without dependence on a
new ab interno electrocautery device has been designed to subconjunctival bleb. This procedure involves 360° intubation
incise trabecular meshwork and the inner wall of Schlemm's of Schlemm's canal, along with suture-assisted distension of
canal for approximately 60° of arc, allowing aqueous access the canal. The patency of the canal is maintained by a device
to Schlemm's canal and the collector channels, bypassing the called the iScience (iScience Interventional Inc., Menlo Park,
juxtacanalicular meshwork resistance point. The surgical CA, USA) which is a 45 mm flexible polymer microcatheter
approach for the Trabectome is similar to that described for of 200 μm shaft diameter and a rounded atraumatic 250 μm
the Glaukos trabecular micro-bypass iStent (Fig. 9.4.5.3). tip to provide 360° catheterization of Schlemm's canal. There
The advantages of the trabecular micro-bypass stent and is aqueous egress via the conventional outflow pathway
the Trabectome are that a small incision is utilized, there is through Schlemm's canal and the collector channels.
avoidance of a filtering bleb, little postoperative management
is required, and there is preservation of conjunctival tissues. CONCLUSION
A follow-up study with the Trabectome showed IOP drop
New glaucoma surgical devices attempt to augment normal
from preoperative mean of 27.6 mm Hg to a mean IOP of
physiologic aqueous outflow pathways in order to provide
16.3 mm Hg after 30 months of follow-up in ten patients.33
effective IOP lowering with the avoidance of a bleb and its
related risks, perhaps providing safer and earlier surgical options
Suprachoroidal Outflow Gold Shunt Device
for patients. However, though devices continue to improve
The SOLX gold microshunt is an ab externo suprachoroidal the safety of glaucoma surgery and to lower risk profiles, further
drainage device that provides a conduit for aqueous humor studies must be done to show the long-term efficacy of IOP
to travel from the anterior chamber to the suprachoroidal lowering with these new procedures. Early data show great
space either through or around the device. Because gold is a promise for the future of advanced glaucoma surgery.
The authors/editors have no financial interest in any product or procedure 17. Costa VP, Spaeth GL, Eiferman RA, Orengo-Nania S. Wound
mentioned in this chapter. healing modulation in glaucoma filtration surgery. Ophthalmic
Surg 1993;24:152-70.
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trabeculectomy. Ophthalmology 1991;98:317-21.
1. ChenTC, Wilensky JT, Viana MA. Long-term follow-up of initially 19. Katz GJ, Higginbotham EJ, Lichter PR, et al. Mitomycin C versus
successful trabeculectomy. Ophthalmology 1997;104(7):1120-5. 5-FU in high risk glaucoma filtering surgery. Ophthalmology 1995;
2. Stegmann R, Pienaar A, Miller D. Viscocanalostomy for open- 102:1263-9.
angle glaucoma in black African patients. J Cataract Refract Surg 20. Kitazawa Y, Kawase K, Matsushita H, Minobe M. Trabeculectomy
1999;25:316-22. with Mitomycin C: a comparative study with 5FU. Arch
3. Mermoud A, Schnyder CC, Sickenberg M, et al. Comparison of Ophthalmol 1991;109:1693-8.
deep sclerectomy with collagen implant and trabeculectomy in 21. Skuta GL, Beeson CC, Higginbotham EL, et al. Intraoperative
open angle glaucoma. J Cataract Refract Surg 1999;25:323-31. MMC versus 5FU in high risk glaucoma filtration surgery.
4. Welsh MH, DeLange J, Wasserman P, et al. The “deroofing” of Ophthalmology 1992;99:438-44.
Schlemm's canal in patients with open-angle glaucoma through 22. Molteno ACB. New implant for drainage in glaucoma: animal
placement of a collagen drainage device. Ophthalmic Surg Lasers trial. Br J Ophthalmol 1969;53:161-8.
1998;29:216-26. 23. Molteno ACB. New implant for drainage in glaucoma: clinical
5. Carassa RG, Bettin P, Fiori M, et al. Viscocanalostomy: a pilot trial. Br J Ophthalmol 1969;53:606-15.
study. Eur J Ophthalmol 1998;8:57-61.
24. Krupin T, Podos SM, Becker B, Newkirk JB. Valve implants in
6. Krasnov MM. Sinusotomy: foundations, results, prospects. Trans
filtering surgery. Am J Ophthalmol 1976;81(2):232-5.
Am Ophthalmol Otolaryngol 1972;76:369-74.
25. Lloyd MA, Baerveldt G, Heuer DK, Minckler DS, Martone JF.
7. Auguste GY Chiou, Mermoud A, Underdahl JP, et al. An ultrasound
Initial clinical experience with the Baerveldt implant in
biomicroscopic study of eyes after deep sclerectomy with collagen
complicated glaucomas. Ophthalmology 1994;101(4):640-50.
implant. Ophthalmology 1998;105:746-50.
26. Coleman AL, Hill R, Wilson MR, Choplin N, Kotas-Neumann R,
8. Sanchez E, Schnyder CC, Sickenberg M, et al. Deep sclerectomy:
Tam M, Bacharach J, Panek WC. Initial clinical experience with
results with and without collagen implant. Int Ophthalmol 1996;
the Ahmed glaucoma valve implant. Am J Ophthalmol 1995;
20:157-62.
120(1):23-31.
9. Stegmann R, Pienaar A, Miller D. Viscocanalostomy for open-
27. Bill A, Phillips CI. Uveoscleral drainage of aqueous humor in
angleglaucoma in black African patients. J Cataract Refract Surg
1999;25:316-22. human eyes. Exp Eye Res 1971;12:275-81.
10. Mermoud A, Schnyder CC, Sickenberg M, et al. Comparison of 28. Toris CB, Yablonski ME, Wang YL, et al. Aqueous humor dynamics
deep sclerectomy with collagen implant and trabeculectomy in in the aging human eye. Am J Ophthalmol 1999;127:407-12.
open-angle glaucoma. J Cataract Refract Surg 1999;25:323-31. 29. Coupin A, Li Q, Riss I. Ex-PRESS miniature glaucoma implant
11. Chiou AG, Mermoud A, Jewelewicz DA. Post-operative inserted under a scleral flap in open-angle glaucoma surgery: a
inflammation following deep sclerectomy with collagen implant retrospective study. Fr J Glaucoma 2007;30(1):18-23.
versus standard trabeculectomy. Graefes Arch Clin Exp 30. Maris PJG, Ishida K, Netland PA. Comparison of trabeculectomy
Ophthalmol 1998;236:593-6. with Ex-PRESS miniature glaucoma device implanted under
12. Jay JL, Murray SB. Early trabeculectomy versus conventional scleral flap. J Glaucoma 2007;16:14-9.
management in primary open angle glaucoma. Br J Ophthalmol 31. Dahan E, Carmichael TR. Implantation of a miniature glaucoma
1988;72:881-9. device under a scleral flap. J Glaucoma 2005;14(2):98-102.
13. Karlen ME, Sanchez E, Schnyder CC, et al. Deep sclerectomy 32. Nyska A, Glovinsky Y, Belkin M, Epstein Y. Biocompatibility of
with collagen implant: medium term results. Br J Ophthalmol the Ex-PRESS miniature glaucoma drainage implant. J Glaucoma
1999;83:6-11. 2003;12(3):275-80.
14. Sanchez E, Schnyder CC, Mermoud A. [Comparative results of 33. Minckler D, Baerveldt G, Ramirez MA, Mosaed S, Wilson R,
deep sclerectomy transformed to trabeculectomy and classical Shaarawy T, Zack B, Laurie D, Francis B. Clinical results with the
trabeculectomy.] Klin Monatsbl Augenheilkd 1997;210:261-4. trabectome, a novel surgical device for treatment of open-angle
15. Wishart PK, Wishart MS, Porooshani H. Viscocanalostomy and glaucoma. Trans Am Ophthalmol Soc 2006;104:40-50.
deep sclerectomy for the surgical treatment of glaucoma: a long- 34. Eisler R. Mammalian sensitivity to elemental gold (Au). Biol Tr
term follow-up. Acta Ophthalmol Scand 2003:81:343-8. Elem Res 2004;100:1-17.
16. Skuta GL, Parrish R 2nd. Wound healing in glaucoma filtering 35. Sen SC, Ghosh A. Gold as an intraocular foreign body. Br J
surgery. Survey Ophthalmol 1987;32:149-70. Ophthalmol 1983;67:398-9.
Chapter 9.5
NEUROPROTECTION
Parul Ichhpujani
The diversity of optic neuropathies arises from the fact that retrograde transport of survival-provoking molecules
diverse mechanisms can affect the retinal ganglion cells (RGC) (neurotrophic factors).5
either at the cell body and dendrites, or at various levels 2. Excitotoxicity: Glutamate is the main excitatory
along the axon, from its unmyelinated portion in the retinal neurotransmitter in the central nervous system and is
nerve fiber layer to its myelinated parts in the lamina cribrosa present in neurons in very high concentrations. Glutamate
and the optic nerve. induced excitotoxicity occurs when extra-cellular glutamate
The optic neuropathies that are the primary focus of levels are increased, either due to increased release or
neuroprotective studies are glaucoma, ischemic optic decreased uptake from the synapse. High glutamate
neuropathy and inflammatory optic neuropathy. concentrations activate several types of cell receptors,
Glaucoma is the most common optic neuropathy in which including N-methyl-D-aspartate (NMDA) receptors that
the unmyelinated part of the axons is thought to be affected can allow entry of excessive amounts of calcium.
by forces related to the intraocular pressure, 1,2 and by Abnormally high Ca2+ concentration leads to inappropriate
perfusion instability due to vascular dysregulation. 3,4 activation of complex cascades of nucleases, proteases
Inflammatory optic neuropathies such as in multiple sclerosis, and lipases.6
neuromyelitis optica and optic nerve sarcoidosis also show 3. Inflammatory and autoimmune mechanisms: These are
similar axonal loss. involved not only in classically inflammatory diseases such
In the journey of mechanistic understanding of optic as neuromyelitis optica,7 but in the light of recent evidence
neuropathies, the concept that optic nerve fiber loss might appear to be involved in glaucoma.8 There is an early
be reduced by neuroprotection arose in the mid 1990s. upregulation of several complement components in
experimental glaucoma models and in human
Cellular Mechanisms glaucoma.9,10
The three main cellular mechanisms provoking RGC death Furthermore, serum autoantibodies to several retina
in optic nerve disorders are retrograde degeneration following or optic nerve proteins are increased in glaucoma.8 These
damage to the RGC axons, excitotoxicity, and inflammatory include autoantibodies against several heat shock proteins
mechanisms. All three of these mechanisms are postulated (HSPs), especially in glaucoma patients with normal
to contribute to glaucoma, and one or more are thought to pressures.
be involved in the other optic nerve disorders.
Bioenergetic based Neuroprotection
1. Retrograde degeneration: Retrograde degeneration occurs as
a result of compromised axonal flow in the RGC axons A new concept of bioenergetic based neuroprotection is being
due to mechanical causes and/or ischemia in the optic researched these days. This refers to the concept of protecting
nerve or proximal retina. Axonal flow is important for injured and threatened neurons by increasing their available
the health of neurons because they depend on the energy supply. This strategy is based on the notion that
Neuroprotection 951
depletion of adenosine triphosphate (ATP) is an important that inhibit glutamate (especially NMDA) receptors, caspases,
pathogenic component of central nervous system (CNS) nitric oxide synthases, or voltage-gated sodium and/or calcium
ischemic injury and certain neurodegenerative conditions. It channels, have been employed for neuroprotection in optic
has already had considerable success in experimental models nerve disorders. Though these drugs have been shown to
of several common debilitating neurological conditions, limit neuronal damage in animal models and/on disease, these
including stroke, motor neuron disease, Huntington's disease encouraging preclinical results almost invariably fail to translate
and Parkinson's disease.11-14 to the clinic.
In fact, only two neuroprotective drugs have been shown
Similarities Between Glaucoma and to improve outcomes in human clinical trials and been
Other Neurodegenerative Diseases approved for use by the United States Food and Drug
Many similarities between glaucoma and Alzheimer’s disease Administration (FDA), riluzole, for amyotrophic lateral
go far beyond the challenges encountered in their treatment: sclerosis,17,18 and memantine, for moderate to severe
(i) Retinal ganglion cells (RGCs) die by apoptosis in glaucoma Alzheimer disease.19 Even these have failed to have a dramatic
through activation of specific caspases, which are also impact on the course of these diseases.
activated in Alzheimer’s disease (ii) Caspase activation with No neuroprotectant drug has been approved for an optic
cleavage of amyloid precursor protein (APP) has been shown nerve disorder. A recent second phase 3 clinical trial examining
to up-regulate amyloid-beta production in Alzheimer’s disease the safety and efficacy of oral memantine for glaucoma
and in animal models of glaucoma; (iii) Age-related treatment has been reported. Although the study indicated a
mitochondrial dysfunction play a key role in the etiology of slower disease progression in patients receiving the higher
both neurodegenerative disorders; (iv) Elevated glutamate dose compared with the lower dose, there was no significant
and nitric oxide synthase up-regulation with reactive oxygen benefit compared to placebo-treated patients, so the first phase
species formation have been implicated in both glaucoma 3 trial was not confirmed.20
and Alzheimer's neurotoxicity and (v) Glutamate toxicity is At present, monitoring new drug efficacy in glaucoma
involved in both glaucoma and Alzheimer’s synaptic patients relies on the detection of visual field changes, which
dysfunction. All of these similarities have led glaucoma to be has accounted for a long period of follow-up (5 years)
dubbed the “ocular Alzheimer’s disease”.15 The obvious necessary for a clinical trial, such as the ongoing memantine
benefit to this likeness is the combining of forces in identifying clinical trial. Additionally, visual field testing is not a sensitive
new strategies to treat either disease. and accurate method to detect glaucomatous damage as it
has been estimated that up to 20 to 40 percent of RGCs are
NEUROPROTECTIVE AGENTS lost before visual field defects are detected. Moreover, given
that RGC loss plays a key role in glaucoma with RGC apoptosis
The rationale for treatment is that by acting as pharmacological
being recognized as an early event, it would be a fundamental
antagonists, neuroprotective agents can correct the imbalance
advance if RGC apoptosis could be monitored in evaluating
between cellular death and survival signals, thus preventing
therapeutic efficiency. There is currently no established clinical
RGC death and optic nerve damage. Also, self-repair via
end point for the assessment of neuroprotective strategies in
neuroprotection may lead to preventing the loss of RGC
function by targeting the various processes involved in causing glaucoma.
the death of RGCs.
Neurotrophins
Wheeler et al16 proposed four criterias to assess the likely
therapeutic utility of neuroprotective drugs with demonstrated Neurotrophins, especially nerve growth factor (NGF) and
utility in animal studies. The drug should have a specific brain-derived neurotrophic factor (BDNF), have been tested
receptor target in the retina/optic nerve; activation of the extensively in animal models of glaucoma, and have both
target must trigger pathways that enhance a neuron's resistance been found to reduce RGC death.21,22 Moreover, there is
to stress or must suppress toxic insults, the drug must reach recent evidence that NGF applied noninvasively in eye-drops
the retina/vitreous in phar macologically effective can give protection against glaucoma in a rodent model and
concentrations and the neuroprotective activity must be even in human patients.23
demonstrated in clinical trials. NGF and BDNF bind both to a specific high affinity
Hundreds of neuroprotective agents like neurotrophic receptor (trkA for NGF and trkB for BDNF) and to a low
factors, proimmune or anti-immune treatments and drugs affinity receptor, p75NTR that is common to all neurotrophins.
952 Glaucoma
Binding to either receptor leads to internalization, and when limitations in pharmacologic assessments that have been
this occurs at axon terminals, it is followed by retrograde identified in preclinical studies include lack of a complete
transport of the receptor-ligand complex. Pathways activated dose-response curve, insufficient data on central nervous
by trk family-neurotrophin complexes are survival-promoting, system penetration, inadequate assessment of therapeutic
but those activated by p75NTR-neurotrophin complexes can index, or a combination thereof.33,34
cause a variety of different effects.24 The authors/editors have no financial interest in any product or procedure
Antioxidants
Reactive oxygen species are involved in many kinds of REFERENCES
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occurring naturally during development. 25 Numerous protects the optic nerve? Surv Ophthalmol 2008; 53 (Suppl 1):S39-
intracellular pathways are involved, and recent attempts at 43.
protection have successfully employed antioxidants as diverse 2. Winkler M, Jester B, Nien-Shy C, et al. High resolution three-
dimensional reconstruction of the collagenous matrix of the
as methylene blue, thioredoxins, the free radical scavenger
human optic nerve head. Brain Res Bull 2010;81(2-3):339-48.
edaravone, nitric oxide synthase inhibitors and coenzyme 3. Pemp B, Georgopoulos M, Vass C, et al. Diurnal fluctuation of
Q10. 26-28 ocular blood flow parameters in patients with primary open-angle
glaucoma and healthy subjects. Br J Ophthalmol 2009;93:486-91.
Neuroprotection with Infrared Light 4. Leske MC. Ocular perfusion pressure and glaucoma: Clinical trial
and epidemiologic findings. Curr Opin Ophthalmol 2009;20:73-8.
Exposure to infrared or near-infrared light has been shown 5. Cooper NG, Laabich A, Fan W, Wang X. The relationship between
to have metabolism-enhancing, antioxidant and antiapoptotic neurotrophic factors and CaMKII in the death and survival of
properties, and recently transcranial delivery of near-infrared retinal ganglion cells. Prog Brain Res 2008;173:521-40.
light has been shown to give neuroprotection in an in vivo 6. Casson RJ. Possible role of excitotoxicity in the pathogenesis of
model of mitochondrial optic neuropathy.29 It was tested for glaucoma. Clin Experiment Ophthalmol 2006;34:54-63.
retinal neuroprotection on the grounds that it induces 7. Hinson SR, Roemer SF, Lucchinetti CF, et al. Aquaporin-4-binding
autoantibodies in patients with neuromyelitis optica impair
protective HSP72 in optic nerve head tissue, and it was found
glutamate transport by down-regulating EAAT2. J Exp Med 2008;
to protect RGCs in rats following optic nerve crush.30 205:2473-81.
Transpupillary laser irradiation of optic nerve head has also 8. Wax MB, Tezel G. Immunoregulation of retinal ganglion cell fate
shown some neuroprotective effect on retinal ganglion cells.31 in glaucoma. Exp Eye Res 2009;88:825-30.
9. Stasi K, Nagel D, Yang X, et al. Complement component 1Q
Other Modalities Being Explored (C1Q) upregulation in retina of murine, primate, and human
glaucomatous eyes. Invest Ophthalmol Vis Sci 2006; 47:1024-9.
Stem cell transplantation appears to ameliorate some 10. Kuehn MH, Kim CY, Ostojic J, et al. Retinal synthesis and
neurodegenerative conditions in the brain and spinal cord, in deposition of complement components induced by ocular
part by neurotrophic factor secretion. Intravitreal injection hypertension. Exp Eye Res 2006;83:620-8.
11. Beal MF. Bioenergetic approaches for neuroprotection in
of mesenchymal stem cells has been recently studied in a rat
Parkinson's disease. Ann Neurol 2003;53 (Suppl. 3):S39-
glaucoma model. Statistically significant increase in overall 47;discussion S47-8.
RGC axon survival and a significant decrease in the rate of 12. Browne SE, Beal MF. The energetics of Huntington's disease.
RGC axon loss normalized to cumulative intraocular pressure Neurochem Res 2004;29:531-46.
exposure were observed.32 13. Coskun PE, Beal MF, Wallace DC. Alzheimer's brains harbor
somatic mtDNA control-region mutations that suppress
mitochondrial transcription and replication. Proc Natl Acad Sci
Limitations of Clinical Research
USA 2004;101:10726-31.
In clinical studies of neuroprotection in ocular disease, it is 14. Dedeoglu A, Kubilus JK, Yang L, et al. Creatine therapy provides
difficult to know the true concentration of the drug at the neuroprotection after onset of clinical symptoms in Huntington's
disease transgenic mice. J Neurochem 2003;85:1359-67.
retina, optic disc, or optic nerve and to compare it with tissue
15. McKinnon SJ. Glaucoma: ocular Alzheimer's disease. Front Biosci
concentrations achieved in animals. Even if such tissue levels 2003;8:s1140-56.
are within the same order of magnitude, differences between 16. Wheeler LA, Gil DW, WoldeMussie E. Role of alpha-2 adrenergic
experimental animals and humans in postreceptor signaling receptors in neuroprotection and glaucoma. Surv Ophthalmol
may magnify the effects of concentration differences. Other 2001;45(Suppl)3:S290-6.
Neuroprotection 953
17. Bensimon G, Lacomblez L, Meininger V. A controlled trial of 25. Castagne´ V, Gautschi M, Lefevre K, et al. Relationships between
riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study neuronal death and the cellular redox status. Focus on the
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18. Lacomblez L, Bensimon G, Leigh PN, et al. A confirmatory dose- 26. Rojas JC, John JM, Lee J, Gonzalez-Lima F. Methylene blue
ranging study of riluzole in ALS. ALS/Riluzole Study Group-II. provides behavioral and metabolic neuroprotection against optic
Neurology 1996;47:S242-50. neuropathy. Neurotox Res 2009;15:260-73.
19. Reisberg B, Doody R, Stoffler A, Schmitt F, Ferris S, Mobius HJ. 27. Inokuchi Y, Imai S, Nakajima Y, et al. Edaravone, a free radical
Memantine in moderate-to-severe Alzheimer's disease. N Engl J scavenger, protects against retinal damage in vitro and in vivo. J
Med 2003;348:1333-41. Pharmacol Exp Ther 2009;329:687-98.
20. Yucel YH, Gupta N, Zhang Q, Mizisin AP, Kalichman MW, 28. Russo R, Cavaliere F, Rombola L, et al. Rational basis for the
Weinreb RN. Memantine protects neurons from shrinkage in the development of coenzyme Q10 as a neurotherapeutic agent for
retinal protection. Prog Brain Res 2008;173:575-82.
lateral geniculate nucleus in experimental glaucoma. Arch
29. Rojas JC, Lee J, John JM, Gonzalez-Lima F. Neuroprotective
Ophthalmol 2006;124:217-25.
effects of nearinfrared light in an in vivo model of mitochondrial
21. Weber AJ, Harman CD, Viswanathan S. Effects of optic nerve
optic neuropathy. J Neurosci 2008;28:13511-21.
injury, glaucoma, and neuroprotection on the survival, structure,
30. Kim SJ, Kim YJ, Park KH. Neuroprotective effect of transpupillary
and function of ganglion cells in the mammalian retina. J Physiol
thermotherapy in the optic nerve crush model of the rat. Eye
2008;586:4393-400. 2009;23:727-33.
22. Parrilla-Reverter G, Agudo M, Sobrado-Calvo P, et al. Effects of 31. Johnson TV, Bull ND, Hunt DP, et al. Neuroprotective effects of
different neurotrophic factors on the survival of retinal ganglion intravitreal mesenchymal stem cell transplantation in experimental
cells after a complete intraorbital nerve crush injury: a quantitative glaucoma. Invest Ophthalmol Vis Sci 2010;51(4):2051-9.
in vivo study. Exp Eye Res 2009;89:32-41. 32. Fernández E, Avilés-Trigueros M. Transpupillary thermotherapy:
23. Lambiase A, Aloe L, Centofanti M, et al. Experimental and clinical new observations on neuroprotection of retinal ganglion cells.
evidence of neuroprotection by nerve growth factor eye drops: Neurosci Lett 2010;476(1):1-2.
implications for glaucoma. Proc Natl Acad Sci USA 2009; 33. Wahlgren NG, Ahmed N. Neuroprotection in cerebral ischaemia:
106:13469-74. facts and fancies–the need for new approaches. Cerebrovasc Dis
24. Lebrun-Julien F, Morquette B, Douillette A, et al. Inhibition of 2004;17:153-66.
p75(NTR) in glia potentiates TrkA-mediated survival of injured 34. Tolias CM, Bullock MR. Critical appraisal of neuroprotection trials
retinal ganglion cells. Mol Cell Neurosci 2009;40:410-20. in head injury: what have we learned? NeuroRx 2004;1:71-9.
Chapter 10.1
LENS: BASIC ASPECTS
Aashima Aggarwal, Saurabh Sawhney
10.1.1 Embryology, Anatomy and Physiology
EMBRYOLOGY cells get filled with proteins, become transparent and are called
the primary lens fibers. Gradually their nuclei disappear and
Aristotle considered the lens to be an accumulation of phlegm
they form the embryonic nucleus.
that appeared as a postmortem artifact.1
The development of the eyeball commences during the
third week of gestation. An outgrowth from the
prosencephalon forms the optic vesicle (neuroectodermal).
At about 27 days of gestation, there is thickening of the
surface ectoderm overlying the optic vesicle. This thickening
forms the lens placode which invaginates in and separates
from the surface ectoderm to convert into the lens vesicle at
around 33 days of gestation (Fig. 10.1.1.1). The lens vesicle
consists of a single layer of cells surrounded by basal lamina.
The cells of the posterior wall of the lens vesicle elongate
rapidly, and grow towards the anterior wall thus obliterating
the lumen of the lens vesicle (Fig. 10.1.1.2). These elongated
Fig. 10.1.1.1: Formation of lens placode and lens vesicle Fig. 10.1.1.2: Development of the crystalline lens
958 Lens and its Anomalies
The secondary lens fibers are laid down by the active

equatorial cells of the anterior epithelium throughout life.
Between the 3rd and 8th month of gestation the secondary
lens fibers reach to both, the anterior and the posterior pole
and form the fetal nucleus which surrounds the embryonic
nucleus. These fibers of the fetal nucleus meet at suture lines
that appear as an erect Y anteriorly and an inverted Y
posteriorly.
Infantile nucleus is formed by the secondary lens fibers
laid down between the last month of gestation and puberty.
The fibers formed after puberty constitute the adult nucleus.
The most recent, superficial fibers form the cortex.
The lens capsule is a true basement membrane produced
by the lens epithelium on its external aspect.
The zonules develop from the neuroectoderm in the ciliary
area between the 3rd and 5th month of gestation.
The tunica vasculosa lentis is formed from the
mesenchyme surrounding the lens. It surrounds the lens and
supplies nourishment to it via the hyaloid artery. This blood
supply and the vascular capsule disappear before birth.
Fig. 10.1.1.3: Structure of the crystalline lens
ANATOMY OF THE LENS
The crystalline lens is a transparent, symmetrically biconvex to be added on the inside of the lens, thereby resulting in
structure, with a capacity to change shape. The posterior progressive increase in the bulk of the lens throughout life.
surface of the lens is attached to the vitreous by the Wiegert’s The lens capsule is highly elastic and is of variable thickness,
ligament. The anteroposterior diameter of the lens varies features that are believed to be pertinent to the lens’ function.
between 3.5 to 5 mm and the equatorial diameter is around 9 The thickness varies from about 5 micrometers to about 25
to 10 mm in adults. The refractive index of the lens is about micrometers.
1.39 on an average. It is slightly more for the nucleus than Epithelium: This is the cellular part of the lens, placed
for the cortex. anteriorly between the capsule and the fibers. The cells are
Position of the lens: The lens is placed between the iris and the simple cuboidal in the central area, becoming columnar
vitreous, in a small, slightly depressed space called the patellar towards the equator. No cells are present over the posterior
fossa. It is held in place by the zonules, which anchor it to the capsule. The metabolic activity of the crystalline lens is
ciliary body. Its normal position may be altered to some extent essentially confined to the epithelium. The physiological role
by the process of accommodation. Larger shifts are of the epithelium is to maintain the osmotic balance of the
pathological and may be developmental as in Marfan’s lens, which is vital to preserve its function.
syndrome or post-traumatic. Such subluxation may be Like any other epithelium, the cells divide and form new
compatible with vision, but at the cost of a large degree of cells, which eventually turn into lens fibers. This activity adds
refractive error, typically astigmatism. new lens fibers as long as the epithelium is present. The
equatorial cells are more active than the central ones. After
Structure: Structurally, the lens consists of a lens capsule, the extracapsular cataract extraction, lens epithelial cells continue
epithelium and the lens fibers (Fig. 10.1.1.3).
to proliferate, and may create a posterior capsular
opacification. The problem is particularly vexing in young
Lens Capsule
persons, who frequently require a secondary procedure to
The lens capsule is a smooth basement membrane primarily deal with it.
composed of type IV collagen and sulphated glycosamin- Altered lens epithelial function in response to physical or
oglycans. It is an inverted basement membrane in that it faces radiation injury, or following an attack of acute angle closure
the inside of a closed cavity. This causes any new lens fibers glaucoma may result in localized discrete opacities.
Lens: Basic Aspects 959
Anatomically and functionally, the zonular apparatus is

seen to have four broad subdivisions. The pars orbicularis is
the part lying over the pars plana, the zonular plexus between
the ciliary processes, the zonular fork and the zonular limbs.
The zonular fibers insert on the anterior, equatorial and
posterior parts of the lens capsule. The anterior insertions
are dense and bundled. These are thick, strong fibers. The
equatorial fibers are present in large numbers in young eyes,
but tend to become less numerous as age advances. Posterior
Fig. 10.1.1.4: Lens bow
fibers arise from either the ora serrata or the ciliary processes,
the latter being the most numerous of all zonular fibers. Their
insertions on the capsule are scattered and at various levels,
Interestingly, neoplastic changes in the lens epithelium are unlike the well organized anterior insertions.
not known to exist. As the zonular fibers insert on the lens capsule a narrow
Lens fibers: Lens fibers are formed by the elongating epithelial space is created around the equator which is called the canal
cells. They are responsible for forming the bulk of the lens. of Hanover.
As new fibers are laid down, older ones move inwards. The
PHYSIOLOGY OF THE LENS
shifting of the lens nuclei forms a visible line near the equator,
termed the lens bow (Fig. 10.1.1.4). The lens is composed of one-third protein and two-thirds
In accordance with their function, lens fibers are sparsely water, apart from minor constituents. This makes the lens,
endowed with organelles, even losing their nuclei as they age. the organ with the highest proportional protein content. In
As the fibers are arranged in concentric layers, their tips meet fact, considering the average water content of body tissues,
at well defined places where they form sutures. The ‘erect Y’ the lens is in a constant state of relative dehydration.
and ‘inverted Y’ shaped sutures of the embryonic lens are a A variety of lens proteins have been identified. They
constant feature, However, the later growth of these sutures comprise broadly of the insoluble albuminoids and soluble
is often haphazard and does not create any particular, crystallins. The latter are the structural proteins and are further
discernible patterns. subdivided into alpha, beta and gamma subtypes. As age
Lens fibers form compact areas, called nuclei, in a increases, the relative proportion of albuminoids increases.
chronological sequence. The innermost of these is the Lens proteins are antigenic in nature as they remain
embryonic nucleus, followed by the fetal nucleus, the infantile sequestered inside an avascular compartment during the
nucleus and finally the adult nucleus. The adult nucleus is development of the immune system. Thus, release of lens
constantly growing as new fibers are added. The peripheral protein into the anterior chamber, whether due to trauma or
part of the lens is composed of the most recently added in phacolytic glaucoma, is accompanied by an inflammatory
fibers and is termed the cortex. response.
Any injury to the lens may be reflected as opacity in the Other constituents of the crystalline lens are amino acids;
lens fibers. Since the opacity also gets buried deeper as time carbohydrates including glucose, fructose, glycogen, sorbitol
passes, its location serves as a rough guide to the time of and inositol; lipids; electrolytes such as potassium, calcium,
injury. For instance, opacity in the embryonal nucleus points sodium, anions; organic phosphates; glutathione and ascorbic
to an early gestational insult. acid.
Zonules: The zonules of Zinn (named after Johann Gottfried
Glucose Metabolism
Zinn), as they are properly named, are also called the
suspensory ligaments of the lens. They form the bridge Glucose is the primary fuel for the lens. Like all other
between the lens and the ciliary body. Zonular fibrils are metabolic requirements of the lens, glucose too is received
microfibrils composed of mucopolysaccharides and through the aqueous humor.
glycoproteins and are non-uniform in structure. The chemical Glucose metabolism provides energy to the lens, which is
nature of the zonular fibers permits enzymatic degradation, required for active transport of molecules. This includes water
a fact which allowed the use of alpha-chymotrypsin during transport that maintains dehydration and therefore
intracapsular cataract extraction.2,3 transparency. Additional energy requirement is for protein
synthesis which is an anabolic activity. Synthesis of reduced Accommodation, of course, declines with age, finally
glutathione (GSH), which is a cellular antioxidant, is also an resulting in presbyopia as the lens eventually loses all focussing
energy dependent phenomenon. Of the total energ y ability.
consumed by the lens, about 90 percent is used by active
transport mechanisms. Mechanisms of Accommodation
Anaerobic glycolysis is the primary metabolic pathway for Accommodation has been documented to occur by different
lenticular glucose. This is so because the bulk of the lens is mechanisms in different species. These include a change in
insulated from oxygen supply except in minor quantities. the shape of the lens, change in the position of the lens
The epithelium of the lens draws oxygen from the within the eye, and even a change in the length of the eye.
aqueous, but this is insufficient, so that only about three In humans, change in shape of the lens has been
percent of the lenticular glucose is metabolized via the Kreb’s definitively demonstrated. The exact mechanics of this,
cycle. However, since oxidative metabolism is so much more however, remain controversial.
efficient a process versus anaerobic glycolysis, the energy Helmholtz’s theory: This is the classical version of
generated comprises about 20 percent of the total lenticular accommodation. Helmholtz suggested that as the ciliary body
output. contracts, the zonules relax their grip on the lens, which then
The hexose monophosphate (HMP) shunt is a minor metabolic tends to acquire a more spherical shape.5 This results in
branch that essentially serves to provide intermediate accommodation. As age advances, the lens becomes more
metabolic products rather than energy. rigid and is unable to deform to a more spherical shape,
resulting in loss of accommodation or presbyopia.
The sorbitol pathway is yet another metabolic route that
lenticular sugars take. The exact significance and physiological Schachar’s theory: Schachar puts forth the view that ciliary
role is unclear as of now, but for a definitive implication in muscle contraction tenses the equatorial zonules, bringing
the so called sugar cataract. about shape changes that result in accommodation. He
suggests that the anterior and posterior zonules are merely
Lens Transparency supporting structures with no active role in accommodation.
As age advances, the diameter of the lens grows, and leaves
The lens transmits about 80 percent of the light it receives. less space for proper functioning of the ciliary muscles. Based
Factors responsible for maintaining transparency are thin on this theory, Schachar introduced scleral expansion bands
epithelium, regularly packed cells, orderly protein structure, that are surgically implanted to increase the perilenticular
relative dehydration and avascularity. The size of the protein space. These are thought to reverse presbyopic changes,
molecules has also been suggested as being less than the though scientific studies have been equivocal.6-8
threshold for interference with visible light.
The refractive function of the lens is due to its shape, Other theories: Apart from these well defined theories, there is
being a convex lens. Since it is located in a fluid medium, the still speculation to the role of the iris and the vitreous body
effective change in refractive index is not as much as for the exerting a positive pressure on the capsular bag. Coleman
anterior corneal surface. For this reason, the lens typically assumes that the lens and zonules form a diaphragm which is
contributes only about 18 to 20 diopters of power to the eye. held in a catenary shape due to the pressure difference between
The chief importance of the lens to the eye, and the individual, the aqueous and vitreous body of the lens, and the action of
lies in its ability to change its power, and therefore the point ciliary muscle is to alter this pressure gradient, thereby altering
of focus. The manner in which this is achieved is still somewhat the shape of the lens.9,10
mysterious, and may in fact differ across species. The capacity
to alter focus is termed accommodation. REFERENCES
With age a number of changes take place in the lens. The 1. Sir Stewart Duke-Elder, System of Ophthalmology: Volume XI:
refractive index of the central layers increases, increasing the Diseases of the lens and vitreous; Glaucoma and Hypotony, Mosby,
power of the lens and inducing myopia in some individuals – 1976.
2. Reich ME, Schmut O, Hofmann H. [The attack of different
index myopia. There is some evidence of UV protection to
proteases on isolated zonular fibers (author’s transl)] [Article in
the macula being afforded by a progressive yellowing of the German]. Albrecht Von Graefes Arch Klin Exp Ophthalmol
lens.4 1976;199(3):255-60.
3. François J, Verbraeken H. Complications in 1,000 consecutive 7. Schachar RA, Cudmore DP, Black TD. Experimental support for
intracapsular cataract extractions. Ophthalmologica 1980;180 Schachar’s hypothesis of accommodation. Ann Ophthalmol
(3):121-8. 1993;25(11):404-9.
4. Hood BD, Garner B, Truscott RJ. Human lens coloration and 8. Mathews S. Scleral expansion surgery does not restore
aging. Evidence for crystallin modification by the major ultraviolet accommodation in human presbyopia. Ophthalmology
filter, 3-hydroxy-kynurenine O-beta-D-glucoside. J Biol Chem 1999;106(5):873-7.
1999;274(46):32547-50. 9. Coleman DJ, Fish SK. Presbyopia, accommodation, and the mature
5. Jones CE, Atchison DA, Pope JM. Changes in lens dimensions and catenary. Ophthalmology 2001;108(9):1544-51.
refractive index with age and accommodation. Optom Vis Sci 10. Martin H, Guthoff R, Terwee T, Schmitz KP. Comparison of the
2007;84(10):990-5.
accommodation theories of Coleman and of Helmholtz by finite
6 Cross W. Theory behind surgical correction of presbyopia.
element simulations. Vision Res. 2005;45(22):2910-5.
Ophthalmol Clin North Am 2001;14(2):315-33, viii.
10.1.2 Etiopathogenesis of Cataract

There is a large and somewhat incongruous body of data Local pathological conditions in the eye may cause lens
pertaining to etiopathogenesis of cataract. Part of the problem opacities. These include:
lies in the varied forms of cataract, and the fact that whilst • Uveitis, whether it is anterior, posterior, or intermediate12
transparency of the lens is maintained by the interplay of • Glaucoma. In glaucoma patients, especially after filtering
various factors, its loss can be caused by a disturbance in any surgery has been done, there may be acceleration of
one of these factors. cataractous changes13
Senile cataract is the most common form of visually • Patients with high myopia and other degenerative conditions
significant cataract. It has been postulated that continual like retinitis pigmentosa are also predisposed to cataract
packing of lens fibers into the capsular bag by the ever active formation.14
lens epithelium leads to changes in the refractive index, a Another significant cause of cataract formation is trauma
phenomenon that initially causes index myopia, but may well to the eye. Traumatic cataracts following nonpenetrating injury
lead on to cataract. This would be a normal, age-linked change are typically rosette shaped initially, but often go on to complete
and implies the inevitability of senile cataract. This is clearly lens opacification.15
not the case, with many older patients presenting in the out- Pediatric cataracts are a whole complex subset of lenticular
patients department with clear media, as well as relatively pathology. The causes of cataract in a child are very varied,
early onset of cataract in some others. but usually fairly well defined. Some of these are as follows:
Other factors that have been implicated in senile cataract • Maternal infections, particularly infections attributed to
development are:
rubella, toxoplasmosis, cytomegalovirus, and herpes
• Exposure to sunlight, especially the ultraviolet
(TORCH infections).
component1,2
• Metabolic disturbances like galactosemia.
• Tobacco use 3
• Hereditary factors account for about a third of congenital
• Genetic predisposition4,5
cataracts.
At other times, there may be clear systemic comorbidity.
• Intrauterine insult of any nature.
Several diseases have been proven to be linked to the
• Maternal malnutrition.
development of cataract. These include:
• Diabetes mellitus6 • Maternal drug abuse.
• Myotonic dystrophy7,8 • Birth trauma has also been implicated in the etiology of
• Atopic dermatitis9,10 childhood cataract.
• Long-term intake of systemic steroids for pathologies On several occasions, the cataract is part of a larger
like asthma has been known to cause cataract, especially picture where the pediatrician diagnoses a specific syndrome.
of the posterior subcapsular form.11 (See chapter on Pediatric Lenticular Abnormalities).
CLASSIFICATION As time passes, degenerative changes begin to take place

in the mature cataract, changing it to a hypermature form. It
Cataracts can be classified by etiology, broadly into congenital
may become a sclerotic cataract, with calcific spots visible on
and acquired varieties. The acquired ones may further be
the capsular surface (Fig. 10.1.2.2), or it may begin to liquefy,
subclassified as being senile, traumatic, complicated, metabolic,
resulting in a partially absorbed cataract with a sunken nucleus,
or associated with systemic conditions. Other variants of
called a Morgagnian cataract. Leakage of lens proteins through
acquired cataract are drug-induced, radiation induced, or
the compromised capsule can cause an open angle glaucoma
subsequent to electric shock.16
called phacolytic glaucoma, which does not resolve till the
An alternative classification is based on the morphological offending agent, i.e. the hypermature cataract, is removed.
characteristics of the cataract. Broadly, based on the extent Even after this, medical or surgical therapy may be required
of the cataractogenesis, the cataracts may be immature, to control the intraocular pressure.
mature or hypermature. Immature cataracts are further An objective classification to categorize cataracts so they
subclassified depending upon the location of lens opacity. may be compared has been proposed. This is the lens opacities
Thus, immature cataracts may be anterior polar, anterior classification system (LOCS II and LOCS III).17,18 It requires
subcapsular, cortical, nuclear, posterior subcapsular, posterior examination of the cataractous lens through a dilated pupil
polar or a combination of any of these. on a slit-lamp. The parameters graded are nuclear color,
Cortical cataract may be further subdivided into cuneiform nuclear opalescence, cortical cataract, and the posterior
cataract, which occur in the peripheral part of the cortex, the subcapsular component. The system is a marked improvement
punctuate perinuclear cataract, and the cupuliform cataract over previous systems of cataract classification as it recognizes
that occupies the posterior cortex. the different components individually, and then scores them.
If no clear areas are left in the cataractous lens, it is A composite picture thereby emerges, and conveys a lot more
termed as a mature cataract. It typically presents as a white to the consumer of this information than hitherto arcane
reflex in the pupil with vision reduced to hand movements or descriptions that read nothing more than, say, advanced
perception of light. As a rule, projection of light is accurate. nuclear cataract. The major drawback of this system is the
On torch light evaluation, no iris shadow is discernible on the need to compare the clinical appearance to that of a ‘standard’
lenticular surface. photograph. Thus, some subjectivity still remains – whether
A mature, swollen, intumescent cataract can crowd the the given cataract resembles picture A or picture B more.
anterior chamber and cause a rise in intraocular tension by a Additionally, both the encoder and the reader need to possess
sheer morphological mechanism (Fig. 10.1.2.1). This type of the ‘standard’ photographs. A final shortcoming is the loss of
glaucoma is called phacomorphic glaucoma, and represents an nuances, like the extent to which a posterior subcapsular
ocular emergency. cataract encroaches upon the visual axis.
Fig. 10.1.2.1: : Intumescent cataract Fig. 10.1.2.2: Hypermature cataract with calcified capsule
APPROACH TO A PATIENT At times, the presence of a cataract might divert attention

WITH CATARACT from associated comorbidity. For example, a reduced visual
field and its associated problems might be incorrectly attributed
The cataract patient comes to the ophthalmologist with a to an immature cataract.
visual complaint, which may range from visual discomfort Review of ophthalmic therapy that the patient might be
and decreased contrast sensitivity in early cataract, to gross receiving should be done, particularly if the operating surgeon
visual disability in advanced cases, especially if the fellow eye is not the family ophthalmologist. Drugs like pilocarpine and
is affected. It is the duty of the ophthalmologist to assess the prostaglandin analogues need to be substituted well in advance
visual deficit and correlate it with visual requirements of the of planned surgery to avoid a high incidence of cystoid
patient. The process begins with meticulous recording of macular edema.19
history. Systemic comorbidity should be elicited for the following
reasons:
History Taking
• It may be necessary to modify the surgical plan in the
History should be elicited in such a manner that information presence of diseases such as diabetes or hypertension.
is obtained pertaining to three major areas, namely, ocular • These conditions may affect the eye in other ways, for
symptoms, systemic comorbidity, and factors that may instance by causing retinopathy, and thereby altering the
influence the treatment. visual prognosis that can be offered to the patient.
The ocular symptoms offered by the patient are: • In addition, treatment for comorbid pathology may need to
• Decreased vision or blurring is often the primary be modified. For example, anticoagulant therapy is stopped
complaint. about a week before cataract surgery is scheduled. 20
• Glare or intolerance of bright light is an early symptom, A special mention here is that of the intraoperative floppy
especially with posteriorly located cataracts. iris syndrome, or IFIS. 21 It is seen in patients receiving
• As the cataract progresses, there may be uniocular diplopia tamsulosin for benign prostatic hypertrophy (BPH). IFIS is
or polyopia. characterized by a poorly dilating pupil that progressively
• Progressive index myopia in the older patient may present shrinks as the surgery progresses, and the tendency for iris
with improved near vision, a phenomenon well known as tissue to prolapse out of the corneal incisions. It needs proper
the ‘second sight of the aged’. surgical planning if the situation is to be well managed,
• In some cases, there are rapid and frequent changes in including providing for special viscoelastic materials and
refraction. mechanical pupil dilators. The presence of BPH and the use
• Some patients report altered color and contrast perception, of tamsulosin should therefore be part of every cataract
especially if there is a difference in the lenticular questionnaire (See Section 10.11 for details).
transparency in the two eyes. A history of drug allergies is to be recorded prominently
• In children, symptoms may not be forthcoming but to avoid prescribing these drugs or their analogs in the pre or
behavioral disturbances on account of poor vision have postoperative period.
been noted. The child may be lagging behind in school, Another factor that may influence treatment is the
or may watch television up close. Parents might notice a assessment of visual need. Note is made of the daily routine
developing squint in cases of unilateral cataract, or even of the patient. For instance, a heavy vehicle driver with a lot
a white pupillary reflex. of night driving may need cataract surgery much earlier than
Symptoms need to be interpreted accurately. A complaint a retired person who likes to tend to his garden most of the
of poor near vision in a 42-year-old may be due to central day. In addition, special evaluation is required for patients
cataract rather than presbyopia, the problem being accentuated who are scheduled to be implanted with multifocal,
by the miosis of near reflex. Another example would be accommodative or toric IOLs, the details of which are covered
uniocular diplopia being mistaken for an ocular motility in another chapter of this section.
disturbance.
Apart from the symptoms related to cataract, careful Methods of Evaluation
attention should be paid to pick up clues to other occult The normal ophthalmic out-patients equipment is adequate
ocular pathologies that may adversely affect visual recovery, to evaluate cataract. Signs of cataract are:
such as a history of amblyopia prior to the development of • Diminished visual acuity.
cataract, glaucomatous damage, or macular degeneration etc. • Presence of iris shadow on the lens.
• Leucocoria, seen in advanced cataract. Macular Function Tests

• Transillumination shows dark areas in the red glow as
seen through distant direct ophthalmoscopy. Macular function tests are designed to predict the kind of
• Direct visualization of the cataract can be done on the results that one may expect from cataract surgery, assuming
that the surgery itself goes off as planned. They spare both
slit-lamp, preferably with the pupil dilated.
the surgeon and the patient the disappointment of an
• The pupillary reaction to direct and consensual light is an
unnecessary surgery.
important test in a mature cataract. An afferent pupillary
Color vision assessment is a fairly accurate macular
defect evidenced by a Marcus-Gunn pupil is bad news so
function test, since cones are concentrated at the macula.
far as visual recovery is concerned.
Two point discrimination test assesses the ability of the
Ancillary tests are performed to assess visual fields, which
eye to resolve two closely placed points of light as separate,
can be done by the confrontation method, comparing the
and is an indicator of good retinal function. However, it
patient’s field of vision to that of the examiner.
cannot be performed in the presence of significant media
Amsler grid mapping is useful to rule out a central scotoma
opacity, where diffusion of light may cause even widely
or metamorphopsia, and can be done unless the visual loss is
separated points to be perceived as a single, amorphous glow.
severe.
Maddox rod test asks the patient to visualize a light source
Apart from verifying the presence of cataract, other placed at a distance of about 33 cm, through a Maddox rod
factors that bear upon surgical treatment are also assessed at held close to the eye. Normal macular function can be
the same sitting. These include assessment of predicted by the perception of a linear bar of light. The test
• Corneal clarity and endothelial health. can be repeated with different orientations of the Maddox
• The capacity for mydriasis. rod. Discontinuity or distortion of the central portion of the
• Presence of subluxation or dislocation of the lens. perceived light-bar is consistent with macular dysfunction. It
• Evidence of trauma. may be useful even in advanced cataract.
• Estimation of the hardness of the cataract. Blue-Field Entoptoscopy or the flying corpuscle test asks
• Presence of any cortico-capsular adhesions. the patient to observe a bright blue light, whereupon he may
• Presence of posterior polar cataract. be able to describe ‘flying spots’. These are actually leukocytes
• Other ocular pathology, especially the presence of that flow in the macular retinal capillaries. The test is useful
uncontrolled glaucoma or retinal disease. Signs of active in moderately dense cataracts but fails in the presence of
and healed uveitis should be looked for, including cells, vitreous opacity.
flare, posterior synechiae and keratic precipitates. Other Laser interferometry seeks to predict postoperative visual
pathologies that have a direct prognostic bearing are recovery by projecting patterns through ‘clear windows’ in
nanophthalmos, ocular colobomata, retinal detachment, the cataract. 22,23 A helium neon laser produces a beam of
diabetic retinopathy and macular scarring or AMD. light that is optically divided, and then recombined to form
• Anterior vitreous can be examined on the slit-lamp, and interference patterns. Since they do not depend upon the
attention should be paid to the presence of cells therein, eye’s optical system for formation, ametropia is not a limiting
which indicate the possibility of intermediate uveitis. factor. For large refractive errors, a correcting lens should,
• Ocular adnexa, lids, eyelashes and ocular surface are also however, be used.
to be evaluated, including functional assessment for the These projections, if correctly oriented by the patient,
presence of lagophthalmos. indicate good macular function. Progressively finer patterns
• The lacrimal system should be evaluated separately to test the macular resolution. There is a tendency to overpredict
rule out a potential source of microorganisms. visual potential, especially in eyes with amblyopia. It cannot
B-scan evaluation of the posterior segment of the eye is be performed in the presence of a mature cataract, or in the
recommended in case of total cataracts. very young or very old, since patient cooperation is needed
Biometry to estimate the power of the intraocular implant for this test.
to be used is part of the preoperative assessment and is The potential acuity meter is fundamentally a similar test,
discussed in detail later. Wherever possible, pre-existing corneal but instead of interference fringes, a Snellen type letter visual
astigmatism (or the lack of it) should be noted so that induced acuity chart is projected on to the macula. It is easier to
astigmatism can be used to offset it. Biometry measurements perform than the laser interferometry. The instrument is
of both eyes should be done to improve accuracy of implant available as a slit-lamp attachment. It is of a greater predictive
power estimation. value than laser interferometry. For both these tests, there is
poorer correlation with the actual postoperative visual acuity in 12. Jancevski M, Foster CS. Cataracts and uveitis. Discov Med
the presence of macular disease.24 2010;9(44):51-4.
13. Edmunds B, Thompson JR, Salmon JF, Wormald RP. The National
Electrophysiological tests refer to the electroretinogram
Survey of Trabeculectomy. III. Early and late complications. Eye
(ERG), the electro-oculogram (EOG) and the visual evoked (Lond) 2002;16(3):297-303.
potential (VEP). The ERG typically warns against retinal 14. Hornbeak DM, Young TL. Myopia genetics: a review of current
disease and detachment, the EOG may help to pick up research and emerging trends. Curr Opin Ophthalmol
hereditary retinal pigment epithelium disorders, while the VEP 2009;20(5):356-62.
disturbances indicate anomalies in the visual pathway.25 15. Asano N, Schlötzer-Schrehardt U, Dörfler S, Naumann GO.
Ultrastructure of contusion cataract. Arch Ophthalmol
1995;113(2):210-5.
REFERENCES 16. Reddy SC. Electric cataract: A case report and review of the
1. Neale RE, Purdie JL, Hirst LW, Green AC. Sun exposure as a risk literature. Eur J Ophthalmol 1999;9(2):134-8.
factor for nuclear cataract. Epidemiology 2003;14(6):707-12. 17. Chylack LT Jr, Leske MC, McCarthy D, Khu P, Kashiwagi T,
2. Young RW. The family of sunlight-related eye diseases. Optom Sperduto R. Lens opacities classification system II (LOCS II)
Vis Sci 1994;71(2):125-44. Arch Ophthalmol 1989;107(7):991-7.
3. Raju P, George R, Ve Ramesh S, Arvind H, Baskaran M, Vijaya L. 18. Chylack LT Jr, Wolfe JK, Singer DM, Leske MC, Bullimore MA,
Influence of tobacco use on cataract development. Br J Bailey IL, Friend J, McCarthy D, Wu SY. The Lens Opacities
Ophthalmol 2006;90(11):1374-7. Classification System III. The Longitudinal Study of Cataract
4. Sacca SC, Bolognesi C, Battistella A, Bagnis A, Izzotti A. Gene- Study Group. Arch Ophthalmol 1993;111(6):831-6.
environment interactions in ocular diseases. Mutat Res 2009;667(1- 19. Henderson BA, Kim JY, Ament CS, Ferrufino-Ponce ZK,
2):98-117.
Grabowska A, Cremers SL. Clinical pseudophakic cystoid macular
5. Graw J. Genetics of crystallins: Cataract and beyond. Exp Eye
Res 2009;88(2):173-89. edema. Risk factors for development and duration after treatment.
6. Zghal-Mokni I, Nacef L, Letaief I, Mahjoub S, Bouguila H, J Cataract Refract Surg 2007;33(9):1550-8.
Blouza S, Jeddi A, Ayed S. Ocular manifestations of diabetes: 285 20. Benzimra JD, Johnston RL, Jaycock P, Galloway PH, Lambert G,
cases. Tunis Med 2008;86(11):1004-7. Chung AK, Eke T, Sparrow JM; EPR User Group. The Cataract
7. Ashizawa T, Hejtmancik JF, Liu J, Perryman MB, Epstein HF, National Dataset electronic multicentre audit of 55,567
Koch DD. Diagnostic value of ophthalmologic findings in operations: Antiplatelet and anticoagulant medications. Eye
myotonic dystrophy: Comparison with risks calculated by haplotype (Lond). 2009;23(1):10-6.
analysis of closely linked restriction fragment length 21. Chang DF, Campbell JR. Intraoperative floppy iris syndrome associated
polymorphisms. Am J Med Genet 1992;42(1):55-60. with tamsulosin. J Cataract Refract Surg. 2005;31(4): 664-73.
8. Reiter C, Gramer E. Anticipation in patients with iridescent 22. Green DG. Testing the vision of cataract patients by means of laser-
multicoloured posterior capsular lens opacities (“Christmas tree generated interference fringes. Science 1970;168(936):1240-2.
cataract”): The role in the diagnosis of myotonic dystrophy.
23. Faulkner W. Laser interferometric prediction of postoperative
Ophthalmology 2009;106(12):1116-20.
visual acuity in patients with cataracts. Am J Ophthalmol
9. Nakano E, Iwasaki T, Osanai T, Yamamoto K, Miyauchi M. Ocular
complications of atopic dermatitis. Nippon Ganka Gakkai Zasshi 1983;95(5):626-36.
1997;101(1):64-8. 24. Vianya-Estopà M, Douthwaite WA, Noble BA, Elliott DB.
10. Amemiya T, Matsuda H, Uehara M. Ocular findings in atopic Capabilities of potential vision test measurements: clinical
dermatitis with special reference to the clinical features of atopic evaluation in the presence of cataract or macular disease. J Cataract
cataract. Ophthalmologica 1980;180(3):129-32. Refract Surg 2006;32(7):1151-60
11. Wang JJ, Rochtchina E, Tan AG, Cumming RG, Leeder SR, Mitchell 25. Pérez-Salvador García E, Pérez Salvador JL. Variability of
P. Use of inhaled and oral corticosteroids and the long-term risk electrophysiological readings in mature cataracts. Arch Soc Esp
of cataract. Ophthalmology 2009;116(4):652-7. Oftalmol 2002;77(10):543-51.
10.1.3 Patient Preparation and Anesthesia
PREPARATION OF THE PATIENT Preoperative Workup

Although, cataract surgery has become routine for the cataract Once it has been determined that the patient needs to undergo
surgeon, it is not so for the patient. For more than half of cataract surgery, a thorough medical evaluation needs to be
the patients, it would probably be their first surgery in life. It done to rule out coexisting conditions like hypertension,
is important for the surgeon to understand this. diabetes, cardiovascular problems, respiratory dysfunction,
and drug allergies. These are often not volunteered by patients. systemic medication that the patient may be taking should be
This should be done even if one is planning to perform the continued as such, modified, or stopped altogether. Typically,
surgery under topical anesthesia, for a need to modify the oral antihypertensives, antiasthma drugs and antiglaucoma
anesthesia may arise midway through the surgery. The medication are continued as such. Oral hypoglycemic agents
internist’s help should be sought if there is any doubt regarding may be continued or supplemented by insulin, but that decision
the medical fitness of the patient. is taken by the internist. Oral anticoagulant therapy in the
form of clopidogrel or acetylsalicylic acid (low dose aspirin)
Patient Preparation is generally stopped a week before planned surgery, in
consultation with the physician.
The patient should be informed of the procedure that will
It is the surgeon’s responsibility that any change of systemic
be followed, including administrative items like admission,
change of clothes, etc. Well informed patients are less therapy is clearly conveyed to the patient.
apprehensive and appreciative of the care that the surgeon The preoperative instructions should be legibly written or
bestows on them. printed, and be unambiguous. There should be a contact
The eye that is scheduled for cataract surgery will not number for the patient to call if he does not understand any
always be the eye in which the patient perceives a greater of the instructions.
disability. There can be many reasons for this, and the
preoperative counseling should include a discussion of this Eyelashes
aspect, including specific mention of the eye to be operated. Trimming of the eyelashes is a practice that was popular in
At times, patients are under the impression that both eyes are the past, but with modern disposable draping systems that
to be operated simultaneously. This notion may or may not tuck the eyelashes away from the surgical field, it is no longer
be correct, as per the surgeon’s practice, but it definitely needs necessary.4 Any trichiatic lashes, however, must be removed
to be clarified to the patient. prior to surgery.
Preoperative Antibiotics
Povidone Iodine
A number of studies show that preoperative antibiotic eye
drops1-3 should be started on a t.i.d. basis three days prior to The surgical target area is painted with povidone iodine and
the surgery. These help to reduce the conjunctival flora and left to dry about five minutes prior to shifting the patient into
decrease the possibility of postoperative bacterial the operating room. The patient is instructed not to touch
endophthalmitis. In the case of a one eyed patient, or if the the painted part.
patient has suffered from endophthalmitis earlier when the
first eye was operated upon, a conjunctival swab should be Anesthesia
done before the antibiotic drops are started. The surgeon
may choose to add oral antibiotics, though rigorous scientific There are several options available for ensuring that the
proof for any beneficial effect that they may have is lacking. surgery is painless and comfortable for the patient. There are
specific risks and benefits associated with each.
Reporting Time
General Anesthesia
On the day of the surgery, the patient should be asked to
There are certain distinct advantages with general anesthesia.
report well ahead of the scheduled time, so that he has enough
It is the only method possible in children, mentally challenged
time to familiarize himself with the surroundings. He may be
and those who may be extremely apprehensive. The
asked to take a light meal in the morning, or be fasting, as per
anesthesiologist can control the depth of anesthesia and
the anesthesiologist’s instructions. Upon arrival, proper
consequent to that, the intraocular pressure, which is very
identification and tagging of the eye by means of devices
useful in open chamber surgeries. There is no risk of
such as a wrist band should be done.
inadvertent globe perforation. Of course, it obviously provides
the most comfortable and painless experience for the patient
Premedication
during the surgery.
The patient should be specifically instructed, in writing, about There is a significant risk of mortality, which, although
the premedication, which may include a mild sedative, and ever declining, must be considered. The patient has to be
mydriatic drops. It is also important to mention whether any admitted for a longer duration, and the cost of surgery is
higher. With the advent of topical anesthesia, general retrobulbar space. The needle is directed backwards and
anesthesia is slowly being restricted to a niche position, to be then slightly upwards as it passes behind the eyeball (Fig.
used only for special situations. 10.1.3.1). It provides very effective ocular akinesia by
blocking the ciliary nerves, the ciliary ganglion, and the
Local or Regional Anesthesia third and sixth cranial nerves as they enter the muscle
cone. It carries a major risk of globe perforation and
The influential politician told the attending physician, “I don’t want possible optic nerve damage, being essentially a blind
local anesthesia, give me only the imported stuff.” procedure. Another danger is that of retrobulbar
This is the most favored method, numerically, of hemorrhage, which can be managed conservatively but
conducting a cataract surgery. All techniques of cataract may necessitate postponement of the surgery.
extraction can be safely and comfortably performed using • Peribulbar block: It is a modification of the retrobulbar
regional anesthesia. The patient is awake during the procedure, block, wherein a shorter needle is so positioned (Fig.
and can be instructed and reassured from time to time, as 10.1.3.1) that it targets the peripheral space of the orbit.7
the surgery progresses. The agent of choice is lidocaine two No attempt is made to penetrate the muscle cone or to
percent, with adrenaline (1:100000). To this, one may add go behind the eyeball to deliver the anesthetic solution. It
bupivacaine, a longer acting anesthetic agent, and may be given as a single injection through the lower lid, at
hyaluronidase, an enzyme that permits the anesthetic solution the junction of the outer and middle thirds, or as a series
to infiltrate the periocular tissues rapidly. For all forms of of two injections, the second one being given through the
regional anesthesia, care must be taken to avoid intravascular upper lid, at the junction of the inner and middle thirds,
injection. beneath the superior orbital notch. A maximum of seven
• Facial block5: By blocking the terminal branches of the to eight ml of anesthetic solution (total) may be given.
facial nerve, the surgeon attempts to prevent the patient The injection is followed by gentle ocular massage to lower
from squeezing his eyelids during surgery, thereby not the intraocular pressure and to spread the solution. As a
allowing the intraocular pressure to rise steeply. There rule, sufficient anesthetic solution seeps into the lids to
are several techniques of facial block which are described obviate the need for any separate facial block.
as follows.
– Van Lint’s method—2.5 ml of the anesthetic solution Surface or Topical Anesthesia
is injected along the upper and lower lids, commencing
inwards from a point one cm lateral to the lateral This is the simplest form of anesthesia that can be used. It
canthus. It provides regional akinesia without affecting involves the use of lidocaine or proparacaine eye drops to
the other branches of the facial nerve. anesthetise the conjunctival and corneal surface. Additional
– O’Brien’s block—The proximal trunk of the facial
nerve is blocked adjacent to the condyloid process, in
front of the tragus of the ear. It is a painful technique.
Care is taken to avoid injecting the anesthetic solution
into the temporomandibular joint.
– Atkinson’s block—It targets the facial nerve along
the inferior margin of the zygomatic bone and across
the zygomatic arch.
– Nadbath block—It targets the facial nerve as it emerges
from the stylomastoid foramen, before it enters the
parotid gland. Respiratory distress is a potentially
serious complication associated with this technique.6
A separate facial block is now infrequently used as
the peribulbar block provides adequate lid akinesia.
• Retrobulbar block: Around two ml of anesthetic solution
is injected through the inferior eyelid, at the junction of
medial two-thirds and lateral one-third, targeting the Fig. 10.1.3.1: Peribulbar and retrobulbar blocks
intracameral lidocaine (1%, preservative free) should be used prospective randomized multicenter study. Jpn J Ophthalmol
once entry to the anterior chamber has been made, as it 2008;52(3):151-61.
2. Hammoudi DS, Abdolell M, Wong DT. Patterns of perioperative
really improves patient comfort.8,9
prophylaxis for cataract surgery in Canada. Can J Ophthalmol
Topical anesthesia is safe, simple and highly effective, but 2007;42(5):681-8.
one must have sufficient surgical skill to deal with the 3. Ang GS, Barras CW. Prophylaxis against infection in cataract
constantly moving eye, and to finish the surgery in a reasonable surgery: A survey of routine practice. Eur J Ophthalmol
amount of time, before the patient starts getting fidgety. 2006;16(3):394-400.
Topical anesthesia is used for phacoemulsification via the 4. Perry LD, Skaggs C. Preoperative topical antibiotics and lash
trimming in cataract surgery. Ophthalmic Surg 1977;8(5):44-8.
clear corneal incision.
5. F Schimek, M Fahle. Techniques of facial nerve block. Br J
Some surgeons augment surface anesthesia by injecting a Ophthalmol 1995;79(2):166-73.
small depot of lidocaine in the inferior fornix. This is a very 6. Koenig SB, Snyder RW, Kay J. Respiratory distress after a Nadbath
effective technique and should be used whenever needed. It block. Ophthalmology 1988;95(9):1285-7.
preserves all benefits of topical anesthesia while providing 7. Riad W. Peribulbar blockade with a short needle for phaco-
long lasting analgesia. emulsification surgery. Acta Anaesthesiol Scand. 2009;53(2):247-50.
8. Ezra DG, Nambiar A, Allan BD. Supplementary intracameral
Literature states that it is possible to do cataract surgery
lidocaine for phacoemulsification under topical anesthesia. A meta-
under no anesthesia, without even a single drop of analysis of randomized controlled trials. Ophthalmology
proparacaine. 10 However, it must be remembered that 2008;115(3):455-87.
anesthesia is a tool to improve patient comfort, and as 9. Crandall AS, Zabriskie NA, Patel BC, Burns TA, Mamalis N,
surgeons, patient comfort must rank very high on our list of Malmquist-Carter LA, Yee R. A comparison of patient comfort
priorities. during cataract surgery with topical anesthesia versus topical
anesthesia and intracameral lidocaine. Ophthalmology
1999;106(1):60-6.
REFERENCES 10. Pandey SK, Werner L, Apple DJ, Agarwal A, Agarwal A,
1. Inoue Y, Usui M, Ohashi Y, Shiota H, Yamazaki T. Preoperative Agarwal S. No-anesthesia clear corneal phacoemulsification versus
Disinfection Study Group. Preoperative disinfection of the topical and topical plus intracameral anesthesia. Randomized
conjunctival sac with antibiotics and iodine compounds: A clinical trial. J Cataract Refract Surg 2001;27(10):1643-50.
Chapter 10.2
INTRAOCULAR LENSES
Gauri Shah, Abhay R Vasavada
HISTORY lenses and closed loops caused pupillary distortion and

contributed to the uveitis-glaucoma-hyphema syndrome.
The development of modern Intraocular Lenses (IOL)
ACIOLs that were too short would spin, decenter, and injure
implantation began in 1949. Sir Harold Ridley, an English
the corneal endothelium. Complications associated with rigid
ophthalmologist, observed that PMMA fragments from
ACIOLs spurred the development of the flexible–loop
airplane cockpit windshields were well tolerated in the anterior
ACIOL. Additional advances included the development of
segment of the eyes of injured World War II pilots. Based on
open support arms with a four-point fixation. These
this observation, he placed a disk-shaped PMMA lens into
modifications have allowed ACIOLs to remain the preferred
the posterior chamber of a 45-year-old woman after he
performed extracapsular cataract extraction (ECCE). choice of surgeons while dealing with cases of compromised
Although, Ridley’s lens corrected aphakic vision, a high capsular bags or for secondary IOL insertion.
incidence of postoperative complications such as glaucoma, As a result of the conversion to modern ECCE, IOL
uveitis, and dislocation caused him to abandon his lens design. designs changed to allow placement in the posterior chamber
However, Ridley showed foresight in three important areas. with support from the lens capsule (Fig. 10.2.1).
First, he constructed his original PMMA lens using a biconvex
design. Second, he used extra-capsular surgery for the Classification of IOLs1
implantation of the lens. Third, he placed the lens in the
posterior chamber. Ridley set the stage for a period of • Generation One: Original Ridley posterior chamber,
advancement in cataract surgery that continues to this day. PMMA IOL manufactured by Rayner and Keeler, Ltd.
Extra-capsular cataract surgery in the 1950s was crude by • 1952-1962: Early anterior chamber IOLs.
modern standards and generally associated with retained lens • 1953-1973: Iris-supported IOLs. These include
cortex, which caused fibrosis and adhesions between the iris iridocapsular IOLs implanted after ECCE.
and the capsule. As intracapsular cataract surgery (ICCE) • 1963-1992: Transition towards modern anterior chamber
eliminated residual cortical material, it became the preferred IOLs.
procedure. Therefore in the early days of lens implantation, • 1977-1992: Transition and maturation of rigid PMMA
IOLs of that period featured optics with loops, struts or holes posterior chamber IOLs.
for sutures which were required to fix the IOL to the iris for • 1992-2000:
support. The anterior chamber was the alternative site for – Mature PMMA rigid IOLs.
supporting an IOL. The IOL was selected by estimating – Standard capsular IOLs designed specifically for in-
anterior chamber width. The IOL length was selected based the-bag implantation
on the horizontal corneal diameter. These IOLs were, however, – Anterior chamber IOLs
associated with many complications. The first anterior chamber • Kelman (flexibility)
intraocular lens (ACIOLs) were rigid and fitting the length of • Choyce (footplates)
the lens to the width of the chamber was difficult. Oversized • Clemente (no-hole three-point fixation)
• 1990s-present: can also cause recurrent UGH (uveitis, glaucoma, hyphema)

– Foldable small incision IOLs syndrome, in which case they have to be explanted which is
– Specialized IOLs, e.g. accommodative, phakic, toric, difficult.3
telescopic, and others.
POSTERIOR CHAMBER
ANTERIOR CHAMBER IOLs IOL IMPLANTATION
Angle-supported IOLs Ciliary Sulcus Fixation
The indications for anterior chamber IOLs are in conjunction The ciliary sulcus is that area of the posterior chamber
with intra-capsular cataract extraction, in cases of intra- bounded anteriorly by the peripheral iris, laterally by uveal tissue
operative rupture of posterior capsule, zonular dialysis or in apposition with the inner scleral wall, and posteriorly by
secondary lens implantation. For an anterior chamber IOL to the most anterior ciliary process. Intraocular lens haptics placed
be safe and effective, there should be minimal contact with in this region (sulcus fixation) therefore employ uveal fixation.
the drainage angle, stability within the anterior chamber with Indications for sulcus fixation of IOLs are rupture of the
a complete absence of micromovement in the angle, no iris posterior capsule yet retention of an adequate anterior capsule
chaffing, and no endothelial touch. To achieve this, the lens to support a posterior chamber IOL. A well-centered lens
should incorporate the Choyce principle of four-point fixation placed in the sulcus is preferable to an asymmetrically placed
with thin footplates. Moreover, the lens should be one-piece lens in the capsular bag, which may later decenter.3 Secondary
and either rigid or with open semi-flexible loops using the implantation is undertaken in cases of trauma or when primary
Kelman principle. There should be a perfect finish to the edges implantation has been postponed due to any reason. However
and adequate anterior vaulting. These IOLs are easy to insert, there are some reports of iris chaffing with unwanted sequelae
but it is difficult to insert them correctly so that the haptics of intermittent uveitis and late pigment dispersion glaucoma
rest at the scleral spur. Malpositions result in a range of associated with sulcus fixation. Other complications associated
complications starting from erosion of the ciliary body and with ciliary sulcus fixation are IOL decentration, pupil capture,
angle recession.2 posterior synechiae and erosion of the ciliary body.4
Iris-fixated IOLs In-the-bag Fixation

The position of the iris and the iris-claw lens is very predictable. It has been well established that capsular fixation of the
Therefore IOL power calculations are usually accurate. Iris posterior chamber lens is anatomically the most ideal site for
claw lenses are often used in children. However, some of these IOL fixation. To ensure implantation of the IOL in the bag, a
children may outgrow their calculated IOL power and become complete continuous curvilinear capsulorhexis is preferred.
high myopes. In such cases, it is possible to remove the iris The technique of in-the-bag IOL implantation is as follows:
claw lens automatically and replace it with one that has an prior to implantation the capsular bag is inflated with a
appropriate power. An example of an iris-fixated IOL is the viscosurgical device. In case of a rigid IOL (PMMA), the IOL
Lobster Claw lens which offers the advantage of being an is implanted in the capsular bag using a Kelman-McPherson
one-piece, one plane, loopless construction suitable for forceps and it is then dialed to ensure complete in-the-bag
modifications in certain conditions. Fixation is stable with no implantation. In case of a foldable IOL (Silicone/ Acrylic)
late decentration or dislocation. The lens may be easily removed the IOL is either injected in the bag or implanted using folding
or replaced. Fixation is not dependent on an intact iris as the forceps and later dialed into the desired position. The safety
lens can be used even when much of the iris tissue is missing. of capsular bag fixation has been demonstrated by observing
However, there are certain disadvantages associated with this the intraoperative behavior of the haptics using the Miyake
lens. Once in place, the iris-fixated IOL may decenter, deform posterior video simulation technique with human cadaver eyes.2
the pupil, or suffer from sunrise, sunset, and east-west In-the-bag IOL implantation offers the advantages of better
syndromes. The lens implantation technique requires skill and IOL centration, a more stable effective lens position, greater
learning time, a bimanual procedure is necessary, and high predictability in calculation and selection of IOL power,
demands are made on manufacturing quality to guarantee claw ensures sequestration of the IOL from the uveal tissue resulting
function, resilience and absence of iris chaffing. These IOLs in less complications, and less posterior capsule opacification.
Intraocular Lenses 971
Also, in-the-bag IOL implantation is an important pre-requisite Biocompatibility

for successful implantation of modern IOLs like
The biocompatibility of intraocular lens materials should be
accommodative IOLs, toric IOLs, and multifocal IOLs.5
assessed in terms of uveal biocompatibility as well as in terms
of capsular biocompatibility.
Scleral Fixation
Uveal biocompatibility is defined as the reaction of the
It is the preferred mode of IOL fixation during secondary uvea to the IOL. Monocytes and macrophages migrate through
IOL implantation in cases of complete loss of capsular the vessel walls into the aqueous humor and the IOL surface.
support or intra-operatively in cases of defective capsular Monocytes transform into small round cells and macrophages
support as in subluxations. However, scleral fixation of the into epithelioid and foreign body giant cells (FBGC) that are
IOL is a surgically demanding procedure and is associated responsible for the phagocytosis of debris, bacteria, etc. These
with complications like retinal detachment, choroidal cells reflect a natural immunological process in a foreign body
hemorrhage, lens dislocation, suture exposure and reaction. Small round cells, a sign of foreign body reaction,
endophthalmitis, glaucoma and persistent cystoid macular are usually present in the first few days and months after
edema.6 surgery, reflecting the reaction of the eye to surgical trauma
based on the blood-aqueous barrier damage and an
IOL MATERIALS immunological reaction to the IOL. Epithelioid cells and
FBGCs are formed by the differentiation and fusion of
The interactions that occur when an implant is placed in the macrophages. If the foreign body persists in situ, FBGCs and
body are influenced by many material properties like rigidity, epithelioid cells deposit on the IOL surface. The differences
biocompatibility, and bioactivity. The available IOL materials between the two types of cells are the size and number of
are PMMA (polymethylmethacrylate), first and second nuclei in the cells. Epithelioid and giant cells are usually found
generation silicone, hydrophilic acrylic and hydrophobic acrylic. in eyes with prolonged inflammatory reaction and are therefore
The characteristics of various IOL materials are: a good indicator of the uveal biocompatibility of IOL
materials. In a study comparing three IOLs, a PMMA IOL,
Rigid Versus Foldable IOL Materials silicone IOL, and AcrySof IOL, it was found that all three
IOLs were sufficiently biocompatible. However, AcrySof IOLs
One of the first IOL materials to be used was polymethyl- are associated with lower giant cell counts and there is the
methacrylate. It has a low refractive index of 1.49. It is a rigid possibility that they might produce better results in eyes with
IOL materials that cannot be implanted through a small pre-existing blood-aqueous barrier damage.7
incision. Capsular biocompatibility is determined by the relationship
Silicone material is hydrophobic, available in two refractive of the intraocular lens with the remaining lens epithelial cells
indices: 1.43 and 1.46. within the capsular bag, e.g. anterior capsule opacification,
Alcon AcrySof IOLs are made of two-phenylethylacrylate posterior capsule opacification, and lens epithelial cell growth
and two-phenylethylmethacrylate cross-linked with butanediol on the anterior surface of the IOL. Lens epithelial cells (LEC)
acrylate with a refractive index of 1.55. proliferate onto the IOL optic from the anterior capsular rim
Foldable materials like silicone, hydrophilic acrylic, and and play an important role in the pathogenesis of capsular
hydrophobic acrylic can be implanted through smaller opacification, which is regarded as a form of postoperative
incisions. Once implanted in the eye, however, the silicone inflammation. Lens epithelial cells express cytokines–
IOLs unfold quite abruptly in the bag, compared to the acrylic interleukin-1, interleukin-6 and transforming growth factor-
IOLs, which unfold more gradually and hence are less likely beta that are responsible for LEC proliferation and the
to cause injury to the surrounding intraocular structures. These synthesis of collagen fibers. These cytokines may act in an
characteristics of requiring smaller incisions for implantation autocrine and paracrine fashion influencing the postoperative
and therefore causing less post-operative astigmatism make proliferation of LECs in the capsular bag.
foldable IOL materials superior to rigid IOL materials. The Anterior capsule opacification occurs as a result of
only advantage of using rigid IOL material is the low cost myofibroblastic differentiation of the residual anterior lens
factor. epithelial cells. In a study evaluating four different IOL models,
Alcon AcrySof acrylic IOL showed the lowest presence of was similar to that in eyes with a three-piece acrylic IOL.10
fibrosis of the anterior capsule and no membrane growth was The longitudinal movement of the one-piece IOL was less
noted.7 than the movement of the three-piece IOL, resulting in less
Posterior capsule opacification is multifactorial in etiology. postoperative myopic shift. Studies have also compared the
Various factors like IOL material, IOL design, and optic edge rate of development of posterior capsule opacification in the
design can influence the development and progression of AcrySof three-piece IOL versus the single-piece design, but
posterior capsule opacification. no statistically significant difference has been reported.11
Bio-adhesive IOL Materials Plate-Haptic Versus Loop-Haptic IOLs

Bioactive materials are those which allow a single lens epithelial Loop-haptic IOLs are easier to implant as compared to plate-
cell to bond both with the IOL and the posterior capsule. haptic IOLs. On comparing the decentration rates between the
This would produce a sandwich pattern which includes the plate-haptic IOLs and loop-haptic IOLs, it was found that there
IOL, the cell monolayer, and the posterior capsule. This sealed was no statistically significant difference between the
sandwich structure might prevent further epithelial in-growth
and PCO. Theoretically, a bioactive material such as a
hydrophobic acrylic IOL would prevent posterior capsule
opacification better than PMMA and silicone IOLs, which
are biocompatible but also bio-inert. The degree of bioactivity
of different IOL materials can explain the differences in PCO
and Nd:Yag capsulotomy rates with different IOL materials.8
After cataract surgery with IOL implantation, proteins
from the plasma interact with the IOL and create a surface
that will then react with the LECs and the capsular bag. Various
in vitro studies demonstrated that IOLs of different materials
were associated with different quantities of protein adhesion
to their surfaces. Hydrophobic acrylic material binds more
firmly to fibronectin, a plasma protein that is also secreted by
LECs, as compared to PMMA, silicone, and hydrophilic acrylic
materials. Therefore, it has been established that hydrophobic
acrylic materials bind more firmly with the capsule. In another Fig. 10.2.1: Single Piece Acrylic IOL
study, it has been established that the AcrySof IOL material
binds three times more firmly to the capsule.9 Therefore, the
AcrySof IOL may prove to be more effective in preventing
the migration of lens epithelial cells to the posterior capsule.9
IOL DESIGNS
Single–piece Versus Multi-piece
IOL Design
In a study, the degrees of intraocular lens (IOL) decentration,
tilt, longitudinal movement, and refractive change after cataract
surgery were compared between eyes with a one-piece acrylic
IOL (Fig. 10.2.1) with soft acrylic loops and eyes with a three-
piece acrylic IOL (Fig. 10.2.2) with rigid polymethyl-
methacrylate loops. The degree of IOL decentration and tilt
in eyes with a one-piece acrylic IOL with soft acrylic loops Fig. 10.2.2: Three piece acrylic IOL
decentration rates of three-piece and plate-haptic IOLs. sharp bend created by the sharp posterior optic edges of the
However, the amount of decentration with the three-piece IOL IOL appear to induce contact inhibition of migrating lens
was significantly greater than that with the plate-haptic IOL.12 epithelial cells. Even though the course of formation of the
Further, when the plate-haptic IOLs were compared with capsular bend remains the same in all the IOLs, starting from
the loop-haptic IOLs to gauge their effect on the size of the the periphery of the capsular bag and prog ressing
capsulorrhexis opening, it was found that the decrease in the circumferentially towards the optic edges, the rate of formation
size of capsulorrhexis was more in plate haptic IOLs as of the capsular bend is different in different IOL designs.16
compared to loop haptic IOLs.13 This capsular bend creates a mechanical barrier preventing
the migration of lens epithelial cells to the posterior capsule.
Aspheric versus Spheric Therefore the sharp optic edge design was found to be more
IOL Optic Design effective in preventing the formation of posterior capsule
opacification compared to IOLs with round optic edges.17 The
In young eyes, the crystalline lens has a negative spherical
capsular bending effect of an IOL depends on the sharpness
aberration while the cornea has a roughly equal and positive
of the capsular bend and the quickness of the capsular bend
spherical aberration, usually resulting in excellent image quality.
formation.
However, with aging, the crystalline lens becomes progressively
more positive in spherical aberration while the cornea remains
Haptic Designs and Angulation
unchanged. Over time, the crystalline lens loses its ability to
compensate for corneal spherical aberration and the image There are various haptic designs available. Some examples are
quality deteriorates. Spherical aberration induces glare, haloes, C-loop, J-loop, L-loop, and haptics with AVH (anti-vaulting
and a decrease in contrast sensitivity especially in scotopic haptic) technology. The haptics with angulation tend to cause
conditions. more postoperative axial movement of the IOL compared
The parameters used to evaluate optical quality after with IOLs with zero haptic angulation and therefore before
intraocular lens implantation are visual acuity, contrast implantation of IOLs with haptic angulation, we need to pay
sensitivity, glare disability, night vision, higher-order attention to the A-constant of that IOL.18
aberrations, and subjective questionnaires. In a study
comparing spherical aberrations and contrast sensitivity in NEWER IOLs
patients implanted with spheric and aspheric IOLs, it was
found that aspheric IOLs can significantly decrease spherical Accommodating IOLs
aberration and improve visual performance without any Currently, two basic approaches can be identified for surgical
reduction in pseudo accommodation amplitude. The aspheric presbyopia correction, an increase in the depth of focus and a
IOLs had less wavefront aberrations and performed better restoration of accommodation in the eye after cataract
under photopic and mesopic conditions when contrast extraction and IOL implantation, i.e. a dynamic change in
sensitivity was compared to the spherical IOLs.14,15 These ocular refraction.19 The pre-requisites for an ideal intraocular
findings confirm that it is possible to improve the optical lens to restore accommodation are:
performance of IOLs by modifying their surfaces. Examples • The accommodation range of the IOL must be large and
of aspheric IOLs are Alcon AcrySofIQ (SN60WF, Alcon predictable to ensure comfortable reading.
Laboratories) which is a single-piece hydrophobic acrylic with • The refractive error of the patient should be accurately
symmetric biconvex optic, square–edge and asphericity corrected.
incorporated at the IOL’s posterior surface, Tecnis Z9000, • The IOL should be capable of compensating for corneal
Z9002, Z9003 (Advanced Medical Optics) which are silicone astigmatism.
and acrylic IOLs with asphericity incorporated on their anterior • Lastly the accommodating IOL should be operated by the
surface. Examples of sphericoptic IOLs are spherical biconvex human ciliary muscle.20
optic (Acrysof SN6OAT [Alcon Laboratories] or Sensar An example of an accommodative IOL is the Crystalens
AR40e [Advanced Medical Optics]. AT-45 (Bausch and Lomb) which is an FDA (US) approved
IOL to correct aphakia and presbyopia. It has a biconvex, 4.5
Round Optic Edge versus Sharp mm optic (now available in 5.0 mm) manufactured from a
Optic Edge IOL Optic Design third generation silicone material (biosil), with flexible, hinged
Optic edge design is known to influence the migration of plate haptics designed to allow movement or changes in the
lens epithelial cells on the posterior capsule. The discontinuous position and shape of lens haptic in response to the
accommodative effort. Unlike multifocal refractive or apodized Refractive Optics

diffractive IOL designs, there is no distribution of light energy
In refractive optics, the different zones of equal refractive
between multiple images or loss of available light into higher
power have a common focus. However, the light waves in this
diffraction orders. Recent studies using dynamic retinoscopy
common focus are out of phase. This results in partially
and monocular defocus have measured 2.42 D and 1.74 D of
destructive interference which negatively affects light intensity
accommodation with bilateral Crystalens implantations
in the focus and consequently leads to a considerable reduction
compared with 0.91D and 0.75 D, respectively with monofocal
in brightness and visual acuity. There is loss in contrast
IOLs.21 Accommodative IOLs offer the advantages of having
sensitivity up to 50 percent compared with monofocal lens.
no haloes and no glare. They also result in good intermediate
Due to the concentrical arrangement of the different refractive
vision. The disadvantages are the individual variability in the
zones, the visual acuity in either of the foci of a refractive
post-operative outcomes and near vision is poor with these
bifocal lens depends on the pupillary diameter.22 The example
IOLs.
of a refractive multifocal IOL is Advanced Medical Optics
Multifocal IOLs (AMO) Array multifocal IOL. It is characterized by five
refractive zones on the anterior surface of the optic: a central,
For many years, restoration of near vision in patients has been circular zone with the required power for distance correction
a major challenge. Traditionally, patients received monofocal and four annular zones of increasing diameter, giving an
intraocular lenses that gave them good distance vision but alternate sequence of near and distance power. An aspheric
spectacles were required for near and intermediate work. In transition between these zones provides intermediate vision.
the past decade, the use of bifocal and multifocal IOLs has The ReZoom (modelNXG1) is a zonal progressive IOL that
overcome the restrictions of monofocal IOLs by restoring incorporates a continuous range of foci. Compared to it’s
near vision without compromising distance vision. Multifocal predecessor Advanced Medical Optics (AMO) Array multifocal
IOLs providing multiple focal points are designed to allow IOL, the distance and near zones of the ReZoom IOL
for distance and near vision simultaneously. Clinically three decreases unwanted haloes under low light conditions. The
types of multifocal optics in IOLs are shown to be effective: add power of the IOL is 3.5D at the lens plane, resulting in
refractive, diffractive, and apodised-diffractive optics. 2.6D of add power at the spectacle plane.23
As with any IOL implantation, proper patient selection
and screening should be employed, taking into account factors Diffractive Optics
such as age, functional and occupational requirements, and
ocular pathology. Professional night drivers, patients with pre- Diffractive bifocal IOLs are based on the Huygens-Fresnel
existing ocular pathology, those with high degrees of principle. They have patterns of rings that produce two primary
preoperative astigmatism and those with unrealistic focal points independent of the pupillary aperture. The newer
expectations who want complete spectacle independence are generation, aspheric surface, diffractive, pupil-independent
not likely to be ideal candidates for multifocal IOL multifocal IOLs provide better near vision, equivalent
implantation. intermediate vision, less unwanted photic phenomena, and
Careful patient selection and accurate biometry can provide greater spectacle independence than both older and newer
excellent visual results with less photic phenomena, less generation zonal progressive refractive multifocal IOLs.
dependence on glasses, and higher patient satisfaction. Bilateral Refractive-diffractive optics can compensate for the
implantation of multifocal IOLs is strongly recommended to disadvantages of merely refractive optics.22
ensure optimal results. The incident light is distributed 65 percent to the distance
The best candidates for the implantation of multifocal focus and 35 percent to the near focus. This asymmetrical
IOLs are those with bilaterally symmetric cataracts, no light distribution considerably improves contrast sensitivity.
astigmatism, open-minded and flexible personality who The optics work independent of the pupillary size. An example
understand the need for postoperative visual adaptation and of a diffractive multifocal IOL is the Tecnis ZM 900 multifocal
the eventual presence of unwanted optic effects such as halos IOL. This is a three-piece foldable ultra-violet blocking
and glare, and the eventual need for laser treatment. polysiloxane (silicone) IOL which features a diffractive pattern
Principally two different types of optical concepts are on a modified, prolate 6 mm sharp-edged optic with C- haptics
applied. (AMO, Technis package insert). The diffraction pattern on
the posterior surface of the lens creates two major focal points satisfactory vision, the result can be considerably improved
that are 4.00 diopters (D) apart, which correspond through binocular implantation. Binocular implantation of
approximately to 3.00D on the spectacle plane. The light multifocal IOLs results in the best possible visual acuity.23
coming into the eyes is evenly distributed between the near
and distance focus allowing a full range of vision independent TORIC IOLs
of pupillary size. Another important feature of the Tecnis Pre-existing astigmatism can be corrected by incisional surgery,
IOL is the unique aspheric design based on wavefront laser, or toric intraocular lenses. While spectacles or contact
technology, which provides negative spherical aberration to lenses can correct astigmatism, they are patient dependent,
compensate for the average positive spherical aberration of associated with cosmetic and lifestyle issues, and are expensive.
the cornea. This results in improved visual function as reported Incisional technology lacks precision, is unpredictable, has a
for the monofocal model. This technical feature is particularly limited treatment range, and can regress. Lasers are associated
relevant under low luminance conditions because the amount with pain, infection, flap complications, glare, and halos. Toric
of spherical aberration increases as the size of the pupil IOLs are therefore the preferred treatment choice. There is
increases. The technique of insertion is similar to that used in no regression and the treatment can be reversed. However,
any other foldable design where after creating a circular 5.0 to toric IOLs do have limitations. For every degree of rotation
5.5 mm well-centered capsulorrhexis, routine phacoemulsi- of the toric IOL, 3.3 percent of the lens power is lost, so 30o
fication is performed. The IOL is loaded on the injector as of rotation could cause complete loss of cylindrical power.24
per the instructions given by the manufacturer. It is then Excessive rotation can induce additional astigmatism. Many
implanted in the capsular bag after filling the bag with models of toric IOLs are now available like the AcrySof toric
viscoelastics. Slow and controlled release of the IOL allows IOL, Rayner T-Flex IOL and the Staar toric IOL. The
correct placement of the lens in the capsular bag in all eyes. technique of implantation of the AcrySof toric IOL has been
described below.
The Apodised-Diffractive Optics
The refractive-diffractive structure of the optics incorporates Toric Intraocular Lens
both the refractive and diffractive principles. They are designed Implantation Technique
and manufactured with a soft transition (phase zones) between The Acrysof Toric IOL (Fig. 10.2.4) is based on the single-
the “main zones”. The advantage that these soft transitions piece design, with open-loop modified-L haptics, posterior
have over the conventional step structure is a significant toricity, and toric axis marks. Currently, the Acrysof Toric IOL
reduction in disturbing light phenomena such as scattered light
or halos. The positive spherical aberration of the human cornea
is corrected with an aberration correcting optic (negative
spherical aberration). This kind of optic influences the visual
acuity as well as depth of focus. An example of the refractive-
apodised diffractive optics multifocal IOL is the Alcon
AcrySof ReSTOR SN60D3 (Fig. 10.2.3). The apodised
diffractive region is within the central 3.6 mm optical zone of
the IOL. This area comprises 12 concentric steps of gradually
decreasing heights, creating bifocality from near to far. The
refractive region of the optic surrounds the apodised diffractive
region. This area directs light to a distant focal point for a
larger pupillary diameter and is dedicated to distance vision.
The overall diameter of the IOL is 13.0 mm, and the optic
diameter is 6.0 mm. The IOL power varies from +10.0 to
+30.0D and incorporates a +4.0D (add) near addition at the
lens plane which provides approximately 3.2D add power at
the spectacle plane. Although the monocularly measured Fig. 10.2.3: Refractive-apodised diffractive optics multifocal IOL:
uncorrected distance visual acuity provides the patient with the Alcon AcrySof ReSTOR SN60D3
proliferate and migrate towards the visual axis. These cells

form Elschnig pearls that can significantly decrease visual acuity
when located in the visual axis. They can also transform into
myofibroblasts, causing fibrotic changes, wrinkles and reduced
capsular elasticity, leading to IOL dislocation that can result
in glare, decreased contrast sensitivity, and increased higher
and lower aberrations. Till date improvements in surgical
techniques, IOL designs, and IOL biomaterials have
substantially reduced PCO. However, they have not eradicated
it completely especially in compromised eyes. Surgical removal
of the central part of the posterior capsule with a posterior
curvilinear continuous capsulorrhexis does not prevent LEC
migration. LECs can grow on the anterior membrane vitreous
without a posterior capsule. Posterior chamber IOLs which
are currently used are implanted in the capsular bag.
Fig. 10.2.4: The Acrysof Toric IOL Optical Principle and

Implantation Technique
is available in three powers. The first step in IOL A new IOL in which the anterior and posterior capsules are
implantation is the IOL power calculation. Preoperative inserted in a peripheral groove of the IOL optic is described.
measurements include manual or automated refraction This implantation technique has been called bag-in-the-lens.26
Keratometry and biometry. The Online Toric Calculator Alternatively, it could be called the twin-capsulorrhexis IOL.
(www.acrysoftoriccalculator.com) can be used for IOL The biconvex IOL (Morcher, Fig. 10.2.5) consists of a central
calculation of the Acrysof Toric model and the axis location optic and haptics comprising anterior and posterior peripheral
of the IOL in the capsular bag. The next step is to mark the flanges. The anterior flange is oval and is perpendicularly
reference points using the reference marker. This can be done oriented to the oval posterior flange. The suggested shape
using the slit lamp with the patient in the upright position and and orientation of both flanges are designed to prevent tilting
with a dry tear film. The marker should be placed at the limbus of the IOL once it is properly positioned in the eye. The IOL
in two locations 180o apart. Intraoperative axis marks are placed is placed in and supported by the anterior and posterior
on the eye using the preoperative reference marks for capsules. Before this, both the capsules are opened with
alignment. An astigmatism marker is used to mark the steep identical calibrated CCCs of 4.5 to 5.0 mm. The capsules are
axis of the cornea with which the IOL is to be aligned. For
gross alignment, the IOL should be rotated clockwise,
approximately 20 to 30 degree short of the desired position
while the IOL is unfolding in the capsular bag. Care should be
taken to prevent the IOL from rotating past the intended axes
during viscoelastic removal. For the final alignment, the IOL
should be rotated clockwise onto the intended axis of
alignment. To reduce residual astigmatism, the site of the
incision placement may be changed, for example, it can be
placed on a steeper meridian.25
BAG-IN-THE-LENS-IMPLANTATION
Smaller incisions provided by foldable intraocular lenses have
improved the outcome of cataract surgery. However, posterior
capsule opacification (PCO) remains a major complication.
Lens epithelial cells (LEC) remaining in the capsular bag Fig. 10.2.5: Morcher IOL – Bag in the lens implantation
placed in the IOL grooves, hence the term bag-in-the-lens macromer to eliminate this gradient. This process induces
technique. When both the capsules are well stretched around subtle changes in the profile of the IOL and thereby helps in
the optic, the LECs are captured in the remaining capsular the correction of spherical aberrations and astigmatism.28
bag and their proliferation is limited to this area. The IOL is a
foldable hydrophilic poly HEMA (acrylic) copolymer with Methods
approximately 24 percent water content. The IOL diameter
ranges from 6.5 mm to 8.5 mm and the optic is 5.00 mm. The The light adjustable IOL (Calhoun Vision LAL) is a foldable
total haptic thickness is 0.90 mm comprising two lips of 0.25 posterior chamber, UV-absorbing, three-piece photoreactive
mm each with a 0.40 mm groove between them. The foldable silicone lens with a blue polymethyl-methacrylate modified C-
IOL is inserted through a 3.2 to 3.4 mm temporal incision haptics, a 6.0 mm biconvex optic with a squared posterior
with forceps and placed on top of the anterior capsule. The edge and a overall length of 13.0 mm. The IOL is implanted
optic is gently pushed down until the posterior flange slips through 3.0 mm to 3.5 mm corneal incision with the help of
behind the posterior capsule at the 6 o’clock position. Both Nichamin-II foldable lens insertion forceps. The IOL is
capsules are gradually slid into the IOL’s groove with the available in the range of +10D to +30D. From +17.0D to
anterior chamber on top of the anterior capsule. The +24.0D, the LAL is manufactured in 0.5D increments and in
ophthalmic viscosurgical devices (OVD) in the anterior 1.0D increments from +10.0D to +16.0D and +25.0D to
chamber is removed. Acetyline chloride is used at the end of +30.0D. The LAL can undergo both spherical and cylindrical
the surgery to prevent iris capture. The anterior chamber power adjustments in the range of ± 0.25 to ± 2.0 D using a
incision is made water tight with 10-0 nylon sutures to avoid controlled application of UV–light (365 nm). The eyes are
anterior chamber collapse.19 Both capsules fit tightly around patched after the surgery. The patch is removed the next day
the peripheral groove surrounding the optic, blocking LEC and the patient are instructed to wear Calhoun Vision–supplied
migration. Thus LEC proliferation is confined to the remaining UV blocking photochromatic spectacles (7EYE, Pleasanton,
peripheral capsular bag.27 California, USA) at all times after surgery.
After a period of post-operative refractive stabilization,
LIGHT ADJUSTABLE IOLS typically 10 to 21 days, the patient returns for examination
and refraction by the surgeon to determine whether adjustment
As modern refractive cataract surgery is a continuously
in spherical and/or cylindrical correction is required. The light
evolving field of science, new developments are frequently
adjustable IOL is adjusted using a digital light device engineered
reported in all aspects of cataract extraction and IOL
by Carl Zeiss Meditec (Jena, Germany). The digital light device
implantation. But despite improvements in techniques of
uses a mercury lamp fitted with a narrow bandpass interference
biometry, instruments, IOL designs and materials, there remain
filter producing a beam at 365 nm (±4 nm full width half
some inherent limitations in predicting residual post-operative
maximum). The digital light device generates and projects a
refractive errors. Light adjustable IOLs (LAL) technology is a
spatial irradiance pattern onto the light adjustable IOL using
comparatively recent advancement, which allows post-
a digital mirror device. The digital mirror device is a pixilated,
operative re-adjustment of IOL power to meet the individual
micromechanical spatial light modulator formed monolithically
requirements of the patients.
on a silicone substrate. The digital mirror device chip enables
Principle: Light adjustable IOLs have been designed based customization of the irradiation profile to correct not only
on the principle of photochemistry and diffusion. The IOL spherical and astigmatic errors but also HOAs. The surgeon
comprises four basic components centers and focuses the treatment beam on the light adjustable
a. Silicone matrix polymer lens using an alignment reticule while the patient alignment is
b. Photoreactive macromer achieved using a fixation target, paracentral to the delivery
c. Photoinitiator and beam. All irradiation procedures are carried out with pupil
d. UV absorber fully dilated and the subject positioned in the chin and head
When light of appropriate wavelength falls on a LAL, it rests of the LDD. Following irradiation the adjusted lens power
polymerizes the silicone macromer in the exposed region which becomes stabilized within approximately 24 hours. At one or
is directly related to the amount of light used. This creates a two days after adjustment, the patient may return to the clinic
concentration gradient between polymerized and non- for clinical examination. If the desired refraction has been
polymerized macromer such that the non-polymerized achieved, the LAL is locked–in. If further refinement is
macromer moves towards the region of polymerized required, the LAL is adjusted again. The patient needs to wear
UV-protective glasses till the final lock-in procedure has been Silicone Oil Adherence to Silicone IOLs
carried out. Lenses not requiring further refractive adjustment
The interaction of silicone oil, used in vitreoretinal surgery,
are treated with a power neutral dose to consume silicone
with standard silicone intraocular lenses causes irreversible
macromer without producing a change in refraction. No re-
adherence of the silicone oil to the IOL optic leading to
adjustment in the IOL can be done once the IOL has been
complications such as visual disturbance for the patient and
locked-in.29,30
obstruction of the vitreoretinal surgeon’s view into the eye.
The more hydrophobic IOL materials with high dispersive
COMPLICATIONS OF INTRAOCULAR
energy and relatively higher contact angle have more silicone
LENS IMPLANTATION
oil adherence. In contrast hydrophilic IOL material with
Mechanical Damage to the IOL relatively low contact angles and low dispersive surface energy
demonstrate less silicone oil adherence.32
Single-piece hydrophilic IOLs with their high water content
are very soft and should be carefully handled intraoperatively, Calcium Deposits within the Optic
as the optics and haptics can be easily damaged during of the Hydrophilic Intraocular Lens
insertion. The three-piece silicone IOL must be handled
In a single-piece foldable hydrophilic IOL model SC60B-OUV
carefully when it is being inserted by an injector as the haptics
with 28 percent water content, late postoperative opacification
might break during insertion.
has been reported. The opacification was located in the
intermediate regions beneath the anterior and posterior
Posterior Capsule Rupture surfaces of the IOL. The area subjacent to the anterior and
Prior to insertion of the IOL in the bag by an injector, the posterior surfaces of the IOL and the central part of the IOL
surgeon should ensure that the bag is properly inflated with a remains clear. The deposits appear to be calcium and
viscoelastic like sodium hyaluronate which has good phosphates deposits. The mechanism of this deposition is
pseudoplasticity. If the bag is not completely filled with a not fully understood. Further biochemical studies are necessary
viscoelastic, the posterior capsule can rupture from the impact to reveal the complete biochemical profile of these
of the IOL when it is ejected from the injector. It is important alterations.33
that the bag is inflated with a viscoelastic and the anterior
chamber remains formed during IOL insertion. Posterior Capsule Opacification
Three Surgery-related Factors to Reduce PCO

Anterior Capsule Opacification
Hydrodissection enhanced cortical clean-up: With careful
The cuboidal cells lining the inner surface of the capsule are meticulous hydrodissection, the operation is much easier and
responsible for the anterior subcapsular opacification. faster, cortex and cell removal is more thorough, and formation
Cytokines released by the residual lens epithelial cells affect of an unwanted Soemmering’s ring is minimized.34
them in an autocrine manner, causing postoperative
In-the-bag fixation of the IOL: The primary function of in-
inflammation and proliferation. Factors such as size of
the-bag fixation is to enhance the IOL optic barrier effect
capsulorrhexis, IOL design and material and pre-existing
which is functional and maximal when the lens optic is fully
disorders like pseudoexfoliation syndrome, retinitis
in the bag in direct contact with the posterior capsule. In case
pigmentosa, diabetes and uveitis are known to influence
one or both haptics are not placed in the bag, a potential space
anterior capsule opacification.31 Anterior capsule opacification
is created allowing an avenue for cells to grow posteriorly
is more in the area of the capsule and IOL contact. It can
toward the visual axis.
result in IOL decentration and in extreme conditions capsular
phimosis and haptic bending. Nd:YAG capsulotomy is an Capsular cover on the IOL surface: A less obvious but
treatment of choice for anterior capsule phimosis. When the significant addition to precise in-the-bag fixation is creating a
anterior capsule contracts, it not only pulls the anterior capsule CCC diameter slightly smaller than that of the IOL optic. For
further onto the optic but also pulls the posterior capsule onto example, if the IOL optic is 6.0 mm, the capsulorrhexis
the anterior optic. Thus, careful slit-lamp examination is needed diameter should ideally be slightly smaller, perhaps 5.0 to 5.5
before Nd:YAG capsulotomy is performed for capsular mm. This places the cut anterior capsular edge on the anterior
phimosis.31 surface of the optic providing a tight fit (analogous to a shrink
wrap) which helps to sequester the optic in the capsular bag SUMMARY
from the surrounding aqueous humor.35
A foldable IOL can be safely implanted using an injector
through a small incision. It shows good bio-compatibility and
Three IOL Related Factors
bio-adhesivity, has an aspheric design with sharp optic edges
to Reduce PCO
and is associated with fewer long-term postoperative
In addition to the three above-mentioned surgery related complications like anterior capsule opacification and posterior
factors, three IOL-related factors36,37 which, play an important capsule opacification. Hence, it is the correct choice for
role in the eradication of PCO are described. implantation, currently.
Biocompatibility: It may be defined as the ability to inhibit The authors/editors have no financial interest in any product/procedure mentioned
stimulation of epithelial cellular proliferation. The lower the in this chapter.
cell proliferation, the lower the chances of secondary cataract REFERENCES
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Chapter 10.3
INTRAOCULAR LENS
POWER CALCULATION
10.3.1 Intraocular Lens (IOL) Implant Power

Calculation, Selection and Ocular Biometry
Vaishali A Vasavada, Abhay R Vasavada, Viraj A Vasavada
Over the last decade, Intraocular Lens (IOL) power calculations photoreceptors in the visual axis. Thus, a summation of A+B
have become a focal point of cataract surgery. In 1977, the is the axial length of the eye in the visual axis (C). Knowing ‘A’
state-of-the-art for estimating IOL power for emmetropia was and ‘C’ allows calculation of ‘B’ (B = C-A).
to simply add +19.0D to the pre-cataractous refraction. A
decade later, being within ±1.00D of the target refraction was BIOMETRY
still considered a reasonable standard. However, with Axial Length
improvements in surgical outcomes, surgeons are now aiming
for better and better refractive outcomes. A-Scan Ultrasound
The three major components of IOL power calculation Until recently, all axial length (AL) measurements were
are (1) Biometry (2) Formulae (3) Clinical variables. Biometry obtained using A-Scan Ultrasonography. The ultrasonic
can be further sub-divided into the following components: biometer measures the transit time of the ultrasound pulse
the axial length, the corneal power, and the IOL position and, using estimated ultrasound velocities through the various
(Effective Lens Position). Formulae can be classified based on media (cornea, aqueous, lens, and vitreous) calculates the
their generation, usage and personalization. Clinical variables distance. Any A-Scan instrument should have an oscilloscope
are related to specific patient eye conditions, patient needs screen which allows visualization of the true echo spikes. Also,
and refractive errors. it is very important that the instrument is regularly calibrated
and gives accurate measurements.
BASIC PRINCIPLE FOR IOL Two different A-Scan biometry techniques are currently
POWER CALCULATION being used:
a. Applanation A-Scan Biometry
In a pseudophakic eye, the optical system consists of two
b. Immersion A-Scan Biometry
refracting lenses (the cornea, and the IOL), which ultimately
project an image on the macula. ‘A’ is defined as the distance Applanation A-scan biometry: A-scan biometry by
from the anterior surface of the cornea to the principal plane applanation requires that the ultrasound probe be placed
of the IOL in the visual axis. ‘B’ is defined as the distance directly on the corneal surface. This is generally done by
from the principal plane of the IOL to the macular holding the ultrasound probe in the hand with the patient in
the sitting or supine position. Even in the most experienced

hands, some element of corneal compression is unavoidable;
this typically being 0.14 to 0.28 mm. Measurements taken by
applanation method will frequently show variability from one
to the next, as a result of inconsistent corneal compression,
and will be seen even under the most experienced guidance.
However, the advantage with this method is that it is easy and
quick to perform.
This can be avoided by changing to the immersion
technique.
Immersion A-scan biometry: The immersion technique of
Ossoinig is shown to be more accurate than the applanation
technique in several studies.1 Here, the ultrasound beam is
coupled to the eye through fluid. Because there is no corneal
compression, the displayed result more closely represents the Fig. 10.3.1.1: Immersion A-Scan being performed in the supine
true axial length. An average shortening of the axial length position with the shell inserted between the two eyelids
(AL) by 0.25 to 0.33 mm has been reported with the
applanation technique. 2,3
Technique: Examination can be performed with the patient
supine or semi-reclining in a chair (Fig. 10.3.1.1). After applying
topical anesthesia in the eye, a scleral shell (Prager, Ossoinig)
is placed between the lids and filled 3/4th with distilled water.
The ultrasound probe is placed into the solution and positioned
parallel to the axis of the eye to obtain AL measurement.
Errors in AL are the most significant in IOL power errors;
an error of 1 mm produces an inaccuracy of 2.5 to 3.0 diopters
in the IOL power (the error is 1.75D/mm in very long eyes
and 3.75D/mm in very short eyes).
Characteristics of a Good A-Scan

• Corneal echo is seen as a tall, single peak (Fig. 10.3.1.2)
• Aqueous chamber does not produce any echo
• Anterior and posterior capsule of the lens produce tall
echoes Fig. 10.3.1.2: The Immersion A-Scan display shows following
• Vitreous cavity produces few to no echoes spikes: C1- Anterior surface of cornea, C2- Posterior surface of
• Retina produces tall, echoes which rise sharply at a 90° cornea, L1- Anterior lens capsule, L2-Posterior lens capsule, R-
Retina. This needs to have a sharp 90° take off from the baseline.
angle
Echoes from the sclera are seen behind the retinal spike.
• Orbital fat produces medium to low echoes.
Pearl: AL of both eyes should be measured. Any asymmetry
Two currently available technologies, the Zeiss IOL Master,
of >0.5 mm should raise a suspicion, and repeat measurements
and the Haag Streit Lens Star are non-contact optical devices
should be performed.
that measure the distance from the corneal vertex to the retinal
pigment epithelium by partial coherence interferometry/
Ultrasound Velocities
optical low coherence reflectometry (Fig. 10.3.1.3). These
The ultrasound velocities4 for different parts of the eye, silicone devices are consistently accurate to within ± 0.02 mm or better.
oil, as well as different IOLs is shown in Table 10.3.1.1. Because these are optical devices, they can be confounded by
Intraocular Lens Power Calculation 983
Table 10.3.1.1: Ultrasound Velocities in different media

Ultrasound Velocity (m/sec)
Cornea and lens 1641 m/sec
Aqueous and vitreous 1532 m/sec
Silicone oil filled eye 1000 m/sec
PMMA IOL 2660 m/sec
Silicone IOL 980 m/sec
Acrylic IOL 2026 m/sec
Pearl: Always use the correct velocity when calculating AL.
Measuring an eye containing silicone oil with standard phakic
velocity (1555 m/sec) can lead to errors of up to 3 to 4 D).
* Optical Biometry (IOL Master/Lens Star)
Fig. 10.3.1.4A: A typical spike seen from the IOL Master
• Instrumentation being used

• Contact lens wear
• Presence of astigmatism
• Previous refractive surgery
• Corneal transplant eyes
It should be kept in mind that a 1D error in corneal power
estimation can lead to a 1D error in the IOL power calculated.
Pearl: Hard contact lens wear should be stopped for atleast
two weeks before measuring corneal power for IOL power
calculation.
Formulae for Calculating IOL Power

Fig. 10.3.1.3: Non-contact biometry being
performed with the IOL Master
Theoretical Formulae
corneal scarring, mature or posterior subcapsular cataracts, or Theoretical formulas are optical formulas based on the optical
vitreous hemorrhage. properties of the eye. They do a better job of predicting
These instruments perform four functions: measuring AL, postoperative outcomes for long and short eyes. There are
corneal power, anterior chamber depth, white to white three widely used theoretical formulas, each with their own
measurements and formula IOL power calculations (Figs. strengths and weaknesses: Holladay, Hoffer Q, and SRK/T.
10.3.1.4A and B).
Regression Formulae
Corneal Power Measurement
Regression formulas are based upon mathematical analysis of
Keratometry is based on the principle that the anterior surface a large sampling of post-operative results. The most familiar
of the cornea acts as a convex mirror, and the size of the regression formula is the SRK formula. The basic SRK formula
image formed varies with its curvature. Several instruments works well for eyes in the “average” measurement range; 22.5
are available for corneal power measurement, such as manual to 25.0 mm in axial length, with certain combinations of K
keratometer, autokeratometer, corneal topography, pentacam, readings. The formula does not work well for “long” (>25
IOL Master, and Lens Star. Important points to be considered mm) or “short” (<22.5 mm) power eyes. The advantage of a
when looking at the corneal power during IOL power regression formula is that the IOL is relatively simple to
calculation are: calculate.
Fig. 10.3.1.4B: Keratometry, axial length, white to white diameter and anterior chamber depth measurements in a composite printout
Further, depending on their evolution in time, the IOL Regression formula: In 1978, Lloyd and Gills, Retzlaff,6 and
power formulae have been grouped into four generations: later Sanders and Kraff,7 each developed a regression formula
based on the analysis of their previous IOL cases. An
First Generation amalgamation of their work led to the SRK I formula, which
is a regression formula. Three variables are accounted for in
Theoretical formulae: The first IOL power formula was
this formula:
published by Fydorov and Kolonko in 1967.5 Some of the
first generation formulae include Binkhorst formula, P = A – 2.5 L – 0.9 K
Colanbrander-Hoffer formula, Gill’s formula, Clayman’s where, P= IOL power, A= constant specific for each lens,
formula, Fydorov’s formula. L=AL in mm, K=average keratometry in diopters.
Second Generation Refraction formula: This formula is useful for an aphakic

eye, a pseudophakic eye (piggyback IOL) or a phakic refractive
Theoretical formula: In 1981, Binkhorst presented his
lens. It does not require AL, but requires corneal power,
modified formula which had better predictability than the first
preoperative refractive error, and desires postoperative
generation formula.
refraction, as well as the vertex distance of both.
Regression formula: The SRK-II formula uses the same
equation as the SRK-I. However, the A-constant was modified Personalization
based on the AL of the patient. The difference between SRK
The following parameters can be used to personalize the A
I and SRK II is given by the A1 constant. A1 is related to the
constant/ACD/Surgeon’s factor for each surgeon. This will
A-constant of the IOL
allow more predictable outcomes.
A1 = A + 3 for AL < 20 mm
• Axial length (preoperative)
A1 = A + 2 for AL < 21 mm
• Corneal power (preoperative)
A1 = A + 1 for AL < 22 mm
• IOL power
A1 = A for AL < 24.5 mm
• Stable postoperative refractive error.
Third Generation
Clinical Variables in IOL
In 1988, Holladay8 proposed a direct relationship between the Power Calculation
steepness of the cornea and the IOL position. Instead of
The targeted postoperative refraction should be based on
anterior chamber depth (ACD) input, the formula calculates
patient needs and ocular status. Patients who have been lifelong
the predicted distance from the cornea to the iris plane and
myopes are not happy being hyperopes postoperatively.
adds it to the distance from the iris plane to the IOL. This is
Similarly, patients who have a significant refractive error in
termed as the ‘surgeon factor’ and is specific for each IOL. This
the other eye need to have their IOL power adjusted to avoid
is called the Holladay-I formula.
anisometropia.
Also, in 1990, the SRK/T theoretic formula 9 was
introduced. The SRK/T formula was developed using the
IOL POWER CALCULATION
nonlinear terms of the theoretical formulas as its foundation
IN SPECIAL SITUATIONS
but empirical regression methodology for optimization.
Postoperative anterior chamber depth prediction, retinal Silicone Oil Filled Eyes
thickness, axial length correction, and corneal refractive index
were systematically and interactively optimized using an The velocity of ultrasound through silicone oil is different
iterative process on five data sets consisting of 1,677 posterior than that in the normal vitreous cavity (Table 10.3.1.1).
chamber lens cases. Hoffer10 also developed a formula, called Erroneous AL measurements is obtained if this velocity is
the Hoffer Q formula. This formula is believed to be best not changed in the A-Scan machine.
optimized for short eyes. If the machine does not have a provision to change the
The Haigis formula is another third generation formula. ultrasound velocity, the following formula can be used to
It is a hybrid of both theoretical and regression formulae, and correct for the axial length error.11 All eyes are measured at a
has three constants: a0, a1, and a2. This formula also requires velocity of 1532m/sec and to this value is added the corrected
preoperative ACD. It can be applied to all axial lengths; AL factor (CALF).
however, the limitation is that it requires personalization of CALF = TL × (1-1532/VL)
the three constants-a0, a1, a2 and that it requires preoperative Where TL is the axial thickness of the lens and VL is the
ACD as a parameter. sound velocity through that lens.
Another option is to measure the AL using optical methods
Fourth Generation
which will provide accurate measurements. There is a special
Holladay-II formula: Holladay used the preoperative ACD silicone mode available in these devices.
measurement, as well as corneal diameter, lens thickness, The second problem is that the refractive index of the oil
refractive error, and age to calculate an estimated scaling factor is much less than that of vitreous, and it acts as a negative lens
(ESF). This Holladay II formula is available as the Holladay in the eye. This effect depends on the shape of the back surface
IOL Consultant program. of the IOL. A biconvex IOL creates the worst problem and a
concave lens practically none. With a plano-convex lens, 2 to for IOL power calculation; accuracy with this method may
3 D must be added to the obtained IOL power in order to also not be 100 percent.
compensate for this effect. Silicone IOLs should be avoided
in these eyes. Piggyback IOLs
Piggyback IOLs maybe implanted as a primary procedure or
High Myopic Eyes
over a previously placed IOL. When piggyback IOLs are placed
In a myopic eye, obtaining the AL is often difficult. If the AL primarily, special calculations are needed to adjust for the lens
is very difficult to obtain, and the eye has an axial length shift of the posteriorly placed IOL.
>25 mm, a posterior staphyloma should be suspected. Secondary piggyback IOLs can be calculated with the
Performing an ultrasound B-Scan can be useful to identify refraction formula, based on the assumption that the primary
the macula and differentiate it from the staphyloma. Using IOL is more stable.
the IOL Master would be helpful in these eyes to avoid errors.
Of the IOL formulae, SRK/T is more accurate in Prior Keratorefractive Surgery
medium long (24.5–26 mm) to very long (>26 mm) eyes and
Keratorefractive surgery changes the profile of the cornea
Holladay I is accurate in medium long eyes (24.5–26 mm).
such that standard methods of measuring the corneal power
The Holladay II formula also gives good results in extremely
cause it to be underestimated. Keratometry and topography
long eyes.10
assume a normal relationship between the anterior and
posterior corneal curvatures, and measure the anterior corneal
Pediatric Eyes
radius. Incisional keratorefractive surgery for myopia flattens
The two challenges that present in pediatric eyes are to calculate both the anterior corneal radius and the posterior corneal
the IOL power, and, to select the appropriate IOL power. radius. Ablative keratorefractive surgery for myopia flattens
A proper examination under anesthesia should be performed the anterior corneal radius but leaves the posterior corneal
for very young children. AL measurement should be done using radius mostly unchanged.
the immersion ultrasound and hand held keratometry is used Standard keratometry measures an intermediate area and
for determination of corneal power. There is a steep AL growth extrapolates the central power based on some very broad
from birth until two years of age by about 6 mm, leading to assumptions. For this reason, keratometry, autokeratometry
myopization of the eye. On the other hand, the corneal power and simulated keratometry by topography typically over-
decreases from 54 to 44 dioptres. The ocular growth slows down estimate central corneal power, following keratorefractive
between two and five years of age, and almost no growth occurs surgery for myopia. Failure to keep this important fact in mind
after the age of 10 years. often results in an unexpected and unpleasant post-operative
Therefore, undercorrection of the IOL power should be hyperopic surprise.
done to prevent high myopic refractive errors when the child
grows. An initial hyperopia is aimed for, and the amount of Prior Radial Keratotomy
undercorrection depends on the child’s age; younger the child,
Unlike ablative forms of myopic keratorefractive surgery
higher the undercorrection.
(LASIK and PRK) in which the ratio between the posterior :
anterior corneal radii is decreased, for eyes that have previously
Corneal Transplantation
undergone radial keratotomy (RK), the ratio between the
There is presently no method that can be used to accurately posterior : anterior corneal radii is increased. This allows for a
carry out IOL power calculations in eyes that have had prior direct estimation of the central corneal power using elevation
corneal transplantation, or in cases where corneal data of the central 4.0 mm, if carried out in a certain way.
transplantation is combined with cataract removal and IOL For eyes with prior radial keratotomy, averaging the 1 mm,
implantation. This is because it is impossible to know the 2 mm, 3 mm and 4 mm annular power rings of the numerical
central power of the donor graft prior to surgery. Simply basing view of the Zeiss Atlas topographer typically gives a useful
pre-operative calculations on a “best guess” of post-operative estimate of central corneal power.
corneal power (such as 44.0 D) will quite often lead to an Patients with previous radial keratotomy will commonly
unpleasant post-operative refractive surprise. As a rough show variable amounts of transient hyperopia in the immediate
estimate, the keratometry values of the fellow eye may be taken post-operative period following cataract surgery. This is felt
to be due to stromal edema around the radial incisions, Intraoperative Retinoscopy method: Following removal of
producing a temporary enhancement of central corneal the cataract, an intraoperative aphakic retinoscopy is
flattening. performed. The IOL power is then calculated based on the
aphakic refraction.
Prior LASIK/PRK Pearl: Use of the Holladay II Consultant software alongwith
the Holladay II formula ensures optimal outcomes following
A major shortcoming of most third generation, two-variable
keratorefractive surgery.
formulas, such as SRK/T, is that they often assume that the
anterior and posterior segments of the eye are mostly
Microphthalmic Eyes
proportional and use only the axial length and keratometric
corneal power to estimate the postoperative location of the These eyes are anatomically different from normal eyes. K
IOL, known as the effective lens position (ELP). values are often high, and anterior chambers shallow. Further,
Unless a specific correction is made for this situation, the the ratio between the anterior and posterior segment may also
artifact of centrally flattened keratometry following be altered. Performing accurate axial length measurements is
keratorefractive surgery will have these formulas assume a very crucial in these eyes, as 1 mm error in AL can lead to
falsely shallow post-operative ELP. The end result is that about 3.75D of error in the IOL. The newer third and fourth
without a special correction, following LASIK these formulas generation formulae are best suited for short eyes. It has been
typically recommend less IOL power than is actually required. recommended that the Hoffer Q formula gives most accurate
Several methods are available, depending on whether pre- results in such eyes. However, studies have shown that even
refractive surgery data is available or not: the SRK/T formula and the Holladay II formula give accurate
results in short eyes.13
Clinical history method: Keratometry and refraction prior
to the keratorefractive procedure, as well as the stable CALCULATION OF IOL POWER FOR
postoperative refraction should be known. If the change in TORIC AND MULTIFOCAL IOLs
refraction from preoperative to postoperative is added to the Toric IOLs: Toric IOLs are beneficial in the correction of
presurgical corneal power, the effective corneal power of the regular corneal astigmatism. To obtain precise IOL calculations
eye is obtained. is a pre-requisite for these “premium” IOLs. Therefore, every
Estimated effective corneal power step of the process should be carefully performed and cross
K = Kpreoperative + Rpreoperative – Rpostoperative checked. A manual keratometry is performed in these eyes to
Feiz-Mannis method: IOL power is calculated based on the estimate both the magnitude and axis of astigmatism. The
pre-LASIK keratometry and axial length, and it is adjusted by IOL power is calculated using newer generation formulae such
change in spherical equivalent of refraction multiplied by 0.7. as the SRK/T or Holladay II.
For calculation of the toric model to be placed, there
Contact lens method: If a hard contact lens of plano power are special online calculators available online (www.acry-
(P) and base curve (B) equal to the effective power of the softoriccalculator.com).
cornea is placed on the eye, then the difference between
Surgically induced astigmatism : Another important step
refraction with contact lens R(cl) and without it R(nocl) should
in the calculation of toric IOLs is the knowledge of the
be zero.
surgically induced astigmatism (SIA). Each surgeon needs to
Estimated corneal power know his/her own SIA. This is calculated using mathematical
K = B + P + R(cl)-R(nocl) vector analysis. The pre and postoperative keratometry values
Maloney method: Central corneal power is determined with are recorded in atleast 30 eyes. It is important that the same
the Humphrey Atlas Topography System (Carl Zeiss Meditec incision size and location are used consistently in all eyes.
Inc., Dublin) and modified using the formula: The steep and flat K values and their axes, the SIA, and
Corneal power the spherical IOL power required are entered in this calculator.
= (Central topographic power × [376/337.5] - 4.9) An output is generated that gives the model of the toric IOL
required, and the axis at which the IOL should be aligned.
Arramberi “Double K” method: This method allows for Pearl: Achieving a spherical equivalent of within +/- 0.5D of
adjustment of central corneal power and can be used with the desired refraction is a must before implanting Toric and
SRK/T, Holladay I, or Hoffer Q formulae.12 Multifocal IOLs.
Multifocal IOLs: Here again, obtaining precise and reliable 5. Fydorov SN, Kolonko AI. Estimation of optical power of the
measurements are crucial. A target refraction of emmetropia intraocular lens, Vestnik Oftalmologic (Moscow) 1967;4:27.
or slight hyperopia should be aimed for. Newer theoretical 6. Retzlaff J: A new intraocular lens calculation formula, J Am Implant
formulae should be used for calculation of the IOL power. Soc 1980;6:148.
7. Sanders DR, Kraff MC. Improvement of intraocular lens power
AL measurements should be obtained using IOL Master or
calculation : regression formula, J Am Intraocul Implant Soce
Immersion Ultrasound. 1980;6:263.
There have been tremendous advancements in the 8. Holladay JT, Prager TC, Chandler TY, et al. A three-part system
technology for IOL power calculation. Attention to every detail for refining intraocular lens power calculations. J Cataract Refract
and performing a meticulous examination goes a long way in Surg 1988;14:17-24.
preventing IOL power errors. 9. Retzlaff J, Sanders DR, Kraff MC. Development of the SRK/T
intraocular lens implant power calculation formula. J Cataract
REFERENCES Refract Surg 1990;1:333-40.
10. Hoffer KJ. The Hoffer Q formula: a comparison of theoretic and
1. Ossoining KC. Standardized echography: basic principles, clinical
regression formulas. J Cataract Refract Surg 1994;19:700-12.
applications, and results. Int Ophthalmol Clin 1979;19:127.
2. Shammas HJF. A comparison of immersion and contact techniques 11. Holladay JT. Standardizing constants for ultrasonic biometry,
for axial length measurements. J Am Intraocul Implant Soc keratometry and intraocular lens power calculations. J Cataract
1984;10:444-7. Refract Surg 1997;23:1356-70.
3. Schelenz J, Kammann J. Comparison of contact and immersion 12. Aramberri J. Intraocular lens power calculation after corneal
for axial measurement and implant power calculation. J Cataract refractive surgery: Double K method. J Cataract Refract Surg
Refract Surg 1989;20:554-62. 2003;29(11):2063-8.
4. Mark HF, Bikales N, Overberger CG, et al. Encyclopedia of 13. Inatomi M, Ishii Koyde R, et al. Intraocular lens power calculation
Polymer Science and Engineering, 1989;1:147-9. Wiley & sons. for microphthalmos. J Cataract Refract Surg 1997;23:1208-12.
10.3.2 Post-refractive Surgery

IOL Power Calculations
M Vanathi, Manoj Gupta, Shibal Bhartiya, Saurabh Sawhney, Aashima Aggarwal
An unfortunate consequence of corneal refractive surgery is corneal asphericity and the relationship between anterior
difficulty in accurately calculating IOL power in eyes and posterior corneal curvatures.
undergoing cataract surgery.1-3 Although manual/automated • Incorrect estimation of effective lens position (ELP) by
keratometry and Placido disc based topography offer good the third or fourth generation formulas when the
accuracy in measuring central corneal power for calculation postoperative corneal power values are used4,5 (the Haigis
of IOL power when applied to healthy, unoperated corneas formula is an exception because it does not use the K-
with regular astigmatism, their use in measuring corneal power reading for ELP prediction).
following keratorefractive surgery can lead to significant Several methods have been proposed to improve the
postoperative refractive surprises. These IOL power errors accuracy of estimating corneal power following refractive
can be attributed primarily to: surgery. The approaches can be categorized according to the
• Inaccurate measurement of anterior corneal curvature as need for the knowledge of data acquired before the refractive
standard keratometry measures only four discrete procedure was performed.
paracentral points on the anterior corneal surface. Important records that must be kept for patients
• Inaccurate calculation of corneal power from anterior undergoing refractive surgery who are potential candidates
corneal measurement as this assumes a spherical central for future cataract surgery:
cornea with posterior corneal radius of curvature 1.2 mm • Pre LASIK spectacle correction
smaller than anterior surface. Keratorefractive surgery alters • Pre LASIK refraction measured at the corneal plane
Table 10.3.2.1: Methods of IOL power calculation

Pre-LASIK data required Pre-LASIK data not required
1. History derived method 1. Contact lens over refraction (CLOR)
2. Refraction derived method 2. Clinically derived method
3. Feiz-Mannis method 3. Maloney topographic method
4. Aramberri Double-K Method 4. Ianchulev Aphakic or Refraction Method
5. Topographical method based on adjusting the measured Eff RP 5. Corneal topography
6. R factor method 6. No history method (Shammas-PL formula)
• Post LASIK spectacle correction Rc Post [corneal plane refraction after refractive surgery]
• Post LASIK refraction measured at the corneal plane Kchd [keratometry by clinical history method]
• Amount of myopia corrected at the corneal plane Kpre [pre LASIK keratometry]
• Pre LASIK K readings CRc [refractive correction achieved at corneal plane]
• Post LASIK K readings It is to be noted that this formula only generates K values
• Axial length needed for IOL power calculations. These have to be used in
Various formulae, each with specific merits and demerits, conjunction with an IOL formula to predict the final IOL
use these parameters in various combinations to derive the power needed.
IOL power. These are shown in Table 10.3.2.1.
Refraction Derived Corrected
FORMULAS INCORPORATING Keratometric Value Method
PRE-LASIK DATA
This method was proposed by Koch et al5 and Holladay. Since it
History Derived Method considers the refractive power change of the cornea after refractive
surgery, the values obtained compensate for the underestimation
The change in power induced by the procedure is added to caused by manual keratometry. The disadvantage of refraction
the presurgical power in order to estimate the present power. derived keratometry (Kc.rd) is that it cannot be used in patients
Postoperative corneal power was obtained by subtracting the whose preoperative refractive data are unavailable.
refractive change (calculated at corneal power) induced by Kc.rd = Kpost (- 0.23 × CRc)
surgery from the pre-operative K readings. The refractive Kpost: Actual keratometry reading
change must be measured after stabilization of refraction CRc: Amount of myopia corrected at corneal plane
following surgery. No pre LASIK K values are required and the post LASIK K
The required parameters for this simple formula proposed values are reduced by 0.23D for each diopter of correction by
by Holladay and Hoffer are: LASIK at corneal plane.
• Pre LASIK keratometry spectacle refraction.
• Myopic correction achieved at corneal plane. Feiz- Mannis Method
The three basic steps to calculate IOL power are: Unlike the first two methods, this method generates the IOL
a. Determine pre and post LASIK refraction at corneal plane power required directly.
by using the formula: IOL power is calculated using pre-LASIK corneal power
Rc = Rs / (1- 0.012Rs) values and axial length measured prior to cataract surgery.6 To
b. Determine amount of correction obtained at cornea by this value is added the LASIK-induced change in refractive
refractive surgery error divided by 0.7. This formula does not require post
CRc = Rc Post - Rc Pre LASIK/PRK refraction data, which may be influenced by the
c. Determine keratometry factors mentioned earlier. A potential drawback is the higher
Kchd = Kpre - CRc risk of hyperopia due to IOL power underestimation in eyes
Rc [refraction at corneal plane] with higher preoperative myopia, besides low predictability.
Rs [refraction at spectacle plane] Feiz 6 also described the nomogram for IOL power if pre-
Rc Pre [corneal plane refraction before refractive surgery] LASIK keratometry is not available.
Aramberri Double-K Method base curve. It is better to do refraction with a trial frame rather
than with an autorefractor so that the vertex distance can be
The preoperative K reading (by keratometry) is used to
measured. The disadvantages is that it is time consuming,
calculate the effective lens position (ELP). The postoperative
inconvenient and cannot be used when lens opacity precludes
K reading (by clinical history method) is used for IOL power
refraction.
calculation. This reduces the erroneous ELP estimation that
Kccl = CL base curve + (CL over refraction - post LASIK
occurs if the post-refractive surgery keratometry is used in
refraction)
both portions of the IOL formula. This is true eve if the
post-refractive keratometry value is very accurate. The method
Clinically Derived Corrected
is not an estimation of actual corneal power, but a modification
Keratometric Value Method
of existing IOL formulae such as the SRK /T, and there is
significant improvement in IOL power prediction by using The advantage with this method is that pre-LASIK data is not
this method.4 required. This is also called adjusted K method.
Kccd = 1.14Kpost - 6.8.
Adjusted Effective Refractive Kccd = Clinically derived corrected keratometry
Power (Eff RP adj) Kpost = Actual keratometric reading
Since, the correction does not correlate with the amount
The effective refractive power (EffRP) is the refractive power
of treatment obtained by LASIK, higher the refractive
of the corneal surface within the central 3.0 mm pupil zone,
correction achieved by the excimer laser, greater is the
taking into account the Stiles-Crawford effect. The EffRP
likelihood of IOL power underestimation, as compared by
differs from simulated K-reading which gives the points along
the linear regression for the single-K clinically derived method
the 3.0 mm pupil perimeter. The EffRP adj is calculated by
(r = 0.7338).
multiplying the LASIK-induced refractive change (ΔMR) by
0.15D and subtracting this value from the measured EffRP,
Maloney Method
which is displayed in the Holladay Diagnostic Summary of
the Eye Sys Corneal Analysis System. The corneal power at the center of the axial topographic map
Eff RP adj = Eff RP - (0.15 × ΔMR). is modified according to this formula:
(ΔMR = Change in manifest refraction by LASIK) Central power = [central topographic power × (376/337.5)] –
4.9.
R Factor Method (Correction
Factor Method) Ianchulev Aphakic or Refraction Method
Rosa et al7 introduced a regression formula to calculate No axial length, K readings, or formulae are needed in this
correcting factor Y, related to axial length that varies between method. Instead it uses the aphakic refraction, determined
1.01 and 1.22 according to axial length. using a hand-held refractometer in the operation theater after
Y = 0.0276 × AL + 0.3635 the crystalline lens has been removed and prior to the IOL
Post operative radius as measured by Videokeratography placement.
(VKG) is multiplied by a correcting factor. Diopteric power is The IOL power (P) is calculated using the formula:
then obtained by 1.3375 - 1/corrected radius. P = 2.02 × Rx + (A-118.4)
According to the original study by Rosa et al, the correction [Rx-refraction, A - A constant]
factor seems to work best with SRK/T and Holladay 1 IOL
calculation formulae. Therapeutic Variable Refractive
Index (TRI)
PRE-LASIK DATA NOT REQUIRED
In this method described by Ferrara the change in the corneal
refractive index after excimer laser surgery is correlated to the
Contact Lens Over Refraction Method
axial length.8
It determines the difference between the postoperative TRI = 0.0006 × (AL × AL) + 0.0213 × AL + 1.1572
refraction with and without a plano hard contact lens of a Corneal power (P) = (TRI -1)/r
known base curvature and subtracts this difference from the r = corneal curvature in meters
Corneal Topography on refraction and K reading measurements made before

This method measures the corneal power within the central 3 refractive surgery.
mm of the cornea using a videokeratometer. Although
considered superior to standard keratometry values in CONCLUSION
abnormal corneal surfaces, the keratometric values so assessed Determination of corneal refractive power remains the most
may be significantly greater than the values obtained by a challenging aspect of IOL power calculation after refractive
keratometer thereby underestimating the calculated IOL surgery. Although, manual keratometry is simple and reliable
power. Using a net index of refraction (4/3) overestimates in eyes with unaltered corneas, it usually overestimates the
the power of cornea by 14 percent of the change induced by effective corneal power following refractive surgery which
the PRK or LASIK. results in oblate curvatures. Computerized videokeratography
measures more than 5000 points, more than 100 points of
Effective Lens Position which are within the central 3 mm, providing greater accuracy
Effective lens position (ELP) is related to anterior chamber than manual keratometry.
depth and has a relationship with corneal shape. Numerous Videokeratography is also not considered to be very
formulas, including SRK/T, Hoffer Q, and Holladay 1 and 2, accurate. The flattest K is known to have a large negative mean
use corneal power in their calculation of ELP, thereby deviation with a greater standard deviation than that for the
compounding the effect of changes in corneal shape after refractive history method.12 This achieves the most accurate
refractive surgery on IOL power calculation.9-11 K value in more eyes than any other method. When inaccurate,
Correction of ELP is required in IOL formulas in post this method usually underestimates the K value yielding myopic
refractive eyes. A 1 mm error in estimation of ELP affects refractive outcomes postoperatively which is more desirable
final refraction by 1.5D. than hyperopia.
The Aramberri Double K approach mentioned earlier Contact lens over-refraction method yields less accurate
separates IOL formula into two components using the pre-
but most consistent values overall while videokeratography
refractive surgery data to estimate the contribution of corneal
generates imprecise unreliable results.12
power to the overall refraction of the eye. However, if the
Each of these methods has practical limitations. The
pre-refractive surgery keratometric data is not available, the
refractive history method requires access to an accurate
Hoffer Q formula is considered better as it calculates a stronger
manifest refraction and keratometry prior to LASIK while
power for emmetropia in very flat corneas. Modern third
contact lens method loses accuracy when visual acuity drops
generation formula such as the Holladay, the Hoffer Q or
SRK/T should be used instead of SRK I/II.8-11 to 20/80 or worse.13 History derived method is the best
method if pre-refractive keratometry data are available.11 If
NEWER FORMULAS not, refraction method can be used when newer software
programs are not available.
Masket Regression Formula Double-K clinical history method provides the highest
IOL adjustment (from IOL master calculation) = d (prior laser accuracy in predicting postoperative emmetropia as shown by
treatment ) × (-0.326)+0.101 the fact that 96.9 percent of the eyes received the IOL power
The fallacy is that the formula assumes that cornea actually within ±0.5 D of the theoretical emmetropia and is not
has changed by the amount that was intended. To avoid this, influenced by the amount of refractive change induced by
the spherical change should be based on actual pre and post- LASIK. However, it requires pre-surgical K-readings and
operative refraction, if available. amount of attempted correction, being highly vulnerable to
bad data.
Corneal Bypass Method The Feiz-Mannis formula also provides IOL powers close
This method relies on pre-LASIK keratometry and post to emmetropia (87.7% of the eyes within ±0.5 D) and is an
LASIK axial length. The correct IOL power is obtained by alternative to Double-K clinical history method. Its advantage
plugging in the original K values, original target myopic is that it does not require post-LASIK/PRK refraction data.
refraction, current axial length and amount of cornea removed A potential drawback is the higher risk of IOL underestimation
by surgeon's myopic formula of choice. It, however, depends in eyes with higher preoperative myopia.
In general, differences between values obtained using zone from 2 to 12 mm, with 4 mm zone measured corneal
manual keratometer, refraction derived keratometry and power correlating best with the calculated power.
contact lens method increase as the refractive change after Feiz et al6 have proposed using either using pre-LASIK
surgery increases. If preoperative corneal power details are keratometry values and then modifying the resulting IOL
available, the smallest value and refraction derived keratometry power by the change in refractive status before and after
at the spectacle plane or the contact lens method should be LASIK or by calculating IOL power by using manual
used. If not, contact lens method can be used especially in keratometry and then using a standard normogram to adjust
cases with smaller change in spherical equivalent. for the change in refraction induced by LASIK.
Shammas 14 clinically derived method provides an Formulas used for post-RK and post-LASIK eyes with good
acceptable rate of theoretical emmetropia (40%). Unfortu- efficacy include Haigis, Binkorst, Holladay, Hoffer Q, and SRK/
nately, a considerable percentage of patients may be left T particularly after adjustments for ELP. The Holladay 2 formula
hyperopic because of IOL power underestimation (>0.5D in uses parameters of ACD, corneal diameter (WTW) and LT to
46.9% of cases and > 1D in 30.6% of cases), due to lack of
estimate the ELP. The Holladay IOL consultant includes a mode
correlation with the amount of attempted correction.
in which K values before refractive surgery if available or a
Packer et al15 evaluated the efficacy of corneal topography
default preoperative value of 43.86 D, maybe used for calculating
in patients of incisional and thermal refractive surgery using
ELP in postrefractive surgery eyes.
the effective refractive power and found 80 percent of patients
Awwad et al17 reported that regression formula based on
to be within 0.50D of emmetropia.
Rosa's factor method7 provided low mean corneal power, ACCP3 mm (average corneal power in central 3 mm) and
resulting in mean IOL power overestimation of 0.46 ±1.02D. DeltaSE (change in spherical equivalent) was very accurate in
Postoperative hyperopia was reported in 16.3 percent (IOL predicting refractive corneal power after myopic LASIK
power underestimation >0.5D), and myopia in >50 percent followed by formulas based on ACCP3 mm alone and SimK
of the patients. The main limitation of this method is that the and DeltaSE, all of which consolidate the validity of similar
correction factor varies with axial length of the eye, previously suggested methods, including EffRPadjusted .
compromising precision. The SRK-T DK, Hoffer Q DK, and Holladay 2 DK
Ferrara's method8 calculated the lowest corneal power with methods resulted in the highest accuracy.17,18 The accuracy
a difference in IOL power ranging between -1.48 and 4.77D. of none of these methods has been tested in a case control
Stakheev et al16 compared autokeratometry readings, simulated prospective series. It is therefore prudent to inform the patient
keratotopography readings, and topographically measured that none of these methods can predict the refractive outcome
average keratometric values with calculated refraction-derived and the possibility of a lens exchange, implantation of a
keratometric value. They concluded that to avoid piggyback lens, or some other surgical adjustment cannot be
underestimation, measured corneal power must be corrected. ruled out and the refractive results of IOL implantation using
More than one accessible method should be used, using the the same biometry data in eyes after LASIK can vary markedly.
lowest, most reliable data. The lowest corneal power should be used, aiming for a
Aramberri4 compared the refractive outcome predicted by myopic postoperative refraction, in order to avoid hyperopia.
the standard SRK/T formula to a "double-K" modified SRK/ The use of immersion ultrasonography and laser
T. The latter uses the pre-refractive surgery keratometric value interferometry is recommended to measure axial length. Qazi
to determine ELP and postrefractive surgery corneal power et al19 have recommended the use of Orbscan II, 5.0 mm
(determined by the clinical history method) to calculate IOL total axial power and 4.0 mm total optical power for more
power by vergence formula. Using the standard formula, the accurate prediction of corneal power particularly when
mean spherical error was 1.82 ±0.73D (range, 0.96 to 3.19D), preoperative data is not available.
while using the double-K method, it was reduced to 0.13 ±0.62D
(range -0.56 to 1.47D). REFERENCES
The second error with LASIK and PRK relates to the
change in the ratio of the back-to-front radius of the 1. Koch DD, Liu JF, Hyde LL, et al. Refractive complications of
cataract surgery after radial keratotomy. Am J Ophthalmol
curvatures, which is normally 82 percent. The Pentacam 1989;108:676-82.
directly measures the corneal power obviating the fallacious 2. Seitz B, Langenbucher A, Nguyen NX, et al. Underestimation of
readings due to non sampling of the central 2 mm of the intraocular lens power for cataract surgery after myopic
cornea by keratometry and topography. It has parameters in a photorefractive keratectomy. Ophthalmology 1999;106:693-702.
3. Gimbel HV, Sun R. Accuracy and predictability of intraocular lens 12. Randelman JB, Loupe DL, Song CD, et al. Intraocular lens power
power calculation after laser in situ keratomileusis. J Cataract Refract calculations after laser in situ keratomileusis. Cornea 2002; 21: 752-
Surg 2001;27:571-6. 5.
4. Aramberri J. IOL power calculation after corneal refractive surgery: 13. Zeh WG, Koch DD. Comparison of contact lens overrefraction and
The double-K method. J Cataract Refract Surg 2003; 29:2063-8. standard keratometry for measuring corneal curvature in eyes with
5. Koch DD, Wang L. Calculating IOL power in eyes that have lenticular opacity. J Cataract Refrac Surg. 1999;25:898-903.
undergone refractive surgery. J Cataract Refract Surg 2003; 29:2039- 14. H.John Shammas, Maya C Shamma S, Antonine Garabet, et al.
42. Correcting the corneal power measurements for intraocular power
6. Vahid Feiz, Mark J. Mannis, Francisco Garcia, et al. Intraocular calculations after myopic laser in situ keratomileusis. Am. J
lens power calculation after Laser in situ Keratomileusis for myopia Ophthalmol 2003;136:426-32.
and hypermetropia. Cornea 2001;20(8):792-7. 15. Mark Packer, Laurie K Brown, Richad S. Hoffman, et al. Intraocular
7. Nicola Rosa, Luigi Capasso, Michele Lanza, et al. Calculating IOL lens power calculation after incisional and thermal keratorefractive
power after refractive surgery. J Cataract Refract Surg 2005;31:1020- surgery. J Cataract Refract Surg 2004;30:1430-4.
24. 16. Stakheev A, Balashevich L. Corneal Power Determination After
8. Ferrara G, Cennamo G, Marotta G, Loffredo E. New formula to Previous Corneal Refractive Surgery for Intraocular Lens
calculate corneal power after refractive surgery. J Cataract Refract Calculation. Cornea 2003;22(3):214-20.
Surg 2004;20:465-71. 17. Awwad ST, Manasseh C, Bowman RW, Cavanagh HD, Verity S,
9. Wang L, Booth MA, Koch DD. Comparison of intraocular lens Mootha V, McCulley JP. Intraocular lens power calculation after
power calculation methods in eyes that have undergone Lasik. myopic laser in situ keratomileusis: Estimating the corneal refractive
Ophthalmology. 2004;111:1825-31. power. J Cataract Refract Surg 2008;34:1070-6.
10. Odenthal MTP, EgginkCA, Melles G, et al. Clinical and theoretical 18. Fam HB, Lim KL. A comparative analysis of intraocular lens power
results of intraocular power calculation for cataract after calculation methods after myopic excimer laser surgery. J Refract
photorefractive keratectomy for myopia. Arch Ophthalmol Surg. 2008;24:355-60.
2002;120:431-8. 19. Qazi MA, Cua IY, Roberts CJ, Pepose S. Determining corneal
11. Carlos Argento, Maria Cosentino, Daniel Baddoza. Intraocular lens power using Orbscan II videokeratography for intraocular lens
power calculation after refractive surgery. J Cataract Refract Surg calculation after excimer laser surgery for myopia. J Cataract Refrac
2003;29:1346-51. Surg 2007;33:21-30.
10.3.3 Analysis of Surgically

Induced Astigmatism
As cataract and refractive surgery establishes new standards (SIA). This change may be intended or incidental. Technically,
in postoperative visual improvement, the importance of not SIA = Postoperative astigmatism - Preoperative astigmatism.
having any residual astigmatism is clear. Not only should the
surgeon not add to the burden of astigmatism, but every effort Methods to Evaluate SIA
must be made to reduce that which is induced by surgery. For
In the past, a number of strategies have been adopted to
cataract surgeons, the use of premium IOLs like multifocals
estimate SIA. However, since astigmatism is a vector quantity,
or accommodating lenses depends upon having nearly zero
i.e., it possesses both magnitude and direction, the simplistic
astigmatism postoperatively. Towards this end, it is vital for
methods used earlier do not provide accurate results, and are
surgeons to understand how to calculate and manipulate
often misleading, in fact.
surgically induced astigmatism (SIA).
Accurate analysis of astigmatic changes requires that the
rules of vector transformation be followed. This can be done
SURGICALLY INDUCED ASTIGMATISM
by means of actual drawing of vectors, or by using
Astigmatic change introduced because of surgical treatment trigonometric functions to obtain the same results. This latter
of the cornea is referred to as surgically induced astigmatism approach is recommended as it is easier to extrapolate it to
aggregate analysis. Technically, it is possible to perform A similar transformation is carried out for the postoperative
aggregate analysis using traditional vector analysis, but observer vector, producing (Xpostop, Ypostop).
errors inherent in the process of physically drawing and The SIA coordinates are calculated by simply subtracting
measuring vectors makes it less accurate.1 the preop values from the postoperative values, independently
for 'x' and 'y'.
Modern Methodology for Evaluating SIA Thus,
The proper methods for evaluating vector changes have been XSIA = Xpostop - Xpreop (3a)
elucidated more than a century ago. The milestone in aggregate YSIA = Ypostop - Ypreop (3b)
data analysis was the paper in 1998, by Holladay et al, that laid The SIA Cartesian values now need to be converted back
down the methodology for calculating mean astigmatic into the vector form that can be understood clinically. The
vectors.2 magnitude of SIA (MSIA) and its axis (ASIA) are calculated
By convention, astigmatic analysis is performed using separately, as follows:
vectors in the plus-cylinder form. This is calculated by taking
the difference of the keratometric values in the two meridians 2 2
Magnitude of SIA (MSIA) = X Y (4a)
as the magnitude of astigmatism, and the axis of the steeper SIA SIA
meridian as the axis of astigmatism.
YSIA
Example 1 Angle of SIA (θ)= ½ θ arctan (4b)
X SIA
Consider the following values:
Kh = 44.50 D × 165° Note that the angle has been halved to revert back to the
Kv = 43.75 D × 75° orientational (refractive) scheme from the directional scheme.
The plus-cylinder format astigmatic vector would then be The angle of SIA thus obtained is not the final axis. It
0.75D × 165° needs further refinement as follows. The rules are valid for
This is the form in which calculations are performed and general conversion of (x, y) values to the vector form.
results presented. If XSIA > 0 and YSIA ≥ 0, then axis = θ (5a)
If XSIA > 0 and YSIA < 0, then axis = θ + 180° (5b)
Calculating SIA Using If XSIA < 0, then axis = θ + 90° (5c)
Trigonometric Functions If XSIA = 0 and YSIA > 0, then axis = 45° (5d)
If XSIA = 0 and YSIA < 0, then axis = 135° (5e)
The first problem encountered in using trigonometric
functions for astigmatic data analysis is the fact that whilst The last two caveats (5d and 5e) are specifically added to
astigmatic direction repeats after 180°, geometrical angles avoid the problem of dividing by zero.
repeat after 360°. In the field of directional statistics, the two In this manner, the SIA vector is obtained and represented
types of data are termed 'orientational' and 'directional' data as MSIA Diopters x ASIA degrees.
respectively. Let us see the process at work using hypothetical data.
This difficulty is tackled by doubling the angle of
Example 2
astigmatism prior to calculations, and halving it at the end of
the procedure, thereby adapting the 180° refractive scheme to Preoperative astigmatic vector = 1.5 D × 65°
the 360° geometrical one. Once this is done, the rest of the Postoperative astigmatic vector = 1.0 D × 35°
procedure follows standard trigonometric strategies. Then,
The preoperative astigmatic vector is transformed to a Xpreop = 1.5 θ cos 2 θ 65 = 1.5 θ cos130 = -0.964181
point on a Cartesian grid using the following equations: Ypreop = 1.5 θ sin 2 θ 65 = 1.5 θ sin130 = 1.149067
Xpreop = a θ cos 2p (2a) Xpostop = 1.0 θ cos 2 θ 35 = 1.0 θ cos70 = 0.342020
Ypreop = a θ sin 2p (2b) Ypostop = 1.0 θ sin 2 θ 35 = 1.0 θ sin70 = 0.939693
where 'a' is the magnitude of the astigmatic vector and 'p' is From the above values, it is fairly straightforward to calculate
the axis which is doubled to '2p' for the calculations. SIA(x,y) values.
The location of the point is now represented as (Xpreop, XSIA = Xpostop - Xpreop = 1.306201
Ypreop). YSIA = Ypostop - Ypreop = -0.20937
Applying Equations 4 and 5, Further descriptions of standard deviations for x,y values
Magnitude of Astigmatism, in each set have been quoted in literature.3,4
Automated computer software is available that can help
1.306201   0.20937 
2 2
MSIA= with the calculations. One such free software is the SIA
= 1.322875 Diopters Calculator Version 1.1, which can be downloaded from http:/
/www.insighteyeclinic.in
 0.20937 
Angle of SIA (θ)= ½ θ arctan   = -4.5533°
 1.306201  Interpretation of Data
Applying qualifiers as per equation 5
The centroid yields the mean astigmatic vector for a group of
Since × > 0 and y < 0, the final axis = θ + 180° = 175.4467° data points. It should be plotted on a double-angled plot
Therefore, SIA is 1.32 D × 175° (DAP), which is essentially a modification of the rose diagram.
The DAP is drawn in the form of concentric rings, each
A Word About Presenting Data representing an incremental step in the magnitude of
astigmatism.2,3 Thus, the innermost point is zero, the first ring
Notice that the use of mathematical functions allows
represents one diopter of astigmatism, the second ring
calculations up to as many decimal places as one wishes. The
represents two diopters, and so on and so forth. Typically,
final results must be rounded off to clinically relevant decimal
three to four rings would suffice for all depictions.
places for the evaluation to be meaningful. It is all too easy to
The axis on the DAP is marked at twice the standard
present diopteric values going to five or six decimal places,
notation for circles. Thus, the 0° and 180° marks coincide.
creating a false impression of great accuracy. The same holds
This is intended to allow visualization of clusters without
true for the direction data as well, where no decimal places
splitting the points around the 0° mark into a fallacious,
are recommended, just whole numbers.
bimodal-appearing pattern. The vectors are plotted as points
on the DAP, and the centroid can be plotted as a point of a
Aggregate Data Analysis different color or shape to highlight it.
The elegance of the Cartesian system is even more obvious When interpreting data on a DAP, one should look for
when analyzing aggregate data. The preoperative data is clustering of points. A good, tight cluster means that the data
converted to (x,y) format using equations (2a and 2b) above. is composed of similar vectors and has low variability, factors
For instance, if evaluating the outcome of twenty cases, one which make the set more useful clinically.
obtains a set of twenty preoperative 'x' values, twenty For example, the sample DAP (Fig. 10.3.3.1) represents
preoperative 'y' values, and similar sets of postoperative (x,y) the SIA vectors from a group of 20 cases.
values. From these, SIA (x,y) values can be generated (equations The vectors are clustered around the 90° mark, and the
3a and 3b). centroid occupies a position that instinctively appears to
Next, each of the x and y values are averaged to determine represent the mean. This is a tight data set, and can be used to
mean values. This is done by simply adding up all × values (in make accurate predictions.
our example, 20 values each for preoperative, postoperative In the subsequent DAP (Fig. 10.3.3.2), the points are spread
and SIA data), mindful of the sign, and then dividing by the out, creating no specific patterns. In such a case, the opposing
total number of cases (20, in our example). astigmatic vectors tend to neutralize each other, resulting in a
lower mean value. The centroid is therefore placed closer to
n
xi the center of the DAP, and is not truly representative of the
i
X (6) data. Therefore, the clinical utility of a data set with well-spread
n vectors showing poor clustering is rather limited.
Here, X is the mean value, Xi is the individual value, and CLINICAL APPLICATIONS
n is the total number of cases.
Now, the mean (x,y) values thus obtained are converted to SIA data is useful because the surgeon can predict with a fair
the vector form using the set of equations 4 and 5. degree of certainty the astigmatism that will result from a
The mean vector thus obtained is called the centroid. particular surgery.
Fig. 10.3.3.1: DAP demonstrating clustering of a set of data Fig. 10.3.1.2: DAP demonstrating spread out data
One such instance is the implantation of toric IOLs. The REFERENCES

website for Alcon has a calculator that lets the surgeon calculate 1. Sawhney S. Theoretical validity of vector analysis for aggregate
the toric IOL specifications, and one of the data that needs to astigmatic data. J Cataract Refract Surg 2002;28(3):385-6.
be input is the surgeons SIA. Obviously, if the surgeon has 2. Holladay JT, Dudeja DR, Koch DD. Evaluating and reporting
meticulously calculated mean SIA using his past surgical records, astigmatism for individual and aggregate data. J Cataract Refract
the output of the toric IOL calculator would be much more Surg 1998;24(1):57-65.
reliable than if mere guesswork is used to fill in the figure. 3. Holladay JT, Moran JR, Kezirian GM. Analysis of aggregate surgically
induced refractive change, prediction error, and intraocular
The surgeon may also choose to calculate SIA for groups
astigmatism. J Cataract Refract Surg 2001;27(1):61-79.
of patients. This way, better clustered groups can be analyzed, 4. Eydelman MB, Drum B, Holladay J, Hilmantel G, Kezirian G,
producing different mean SIA vectors for each group. This Durrie D, Stulting RD, Sanders D, Wong B. Standardized analyzes
information can be used to predict resultant astigmatism for a of correction of astigmatism by laser systems that reshape the
given case with much greater accuracy. cornea. J Refract Surg 2006;22(1):81-95.
Chapter 10.4
CATARACT SURGERY
10.4.1 Conventional Techniques

of Cataract Surgery
INTRACAPSULAR CATARACT help in exposing the anterior lens surface later in the
EXTRACTION surgery.
Intracapsular cataract extraction (ICCE) is largely obsolete • The lenticular cryoprobe is applied to the anterior lens
now, but deserves mention for three reasons. capsule and an iceball is allowed to form (Fig. 10.4.1.1). It
a. It may still be used in subluxated cataracts where the is important that the cryoprobe tip touches nothing other
zonules are compromised beyond salvage.1 than the lens capsule.
b. It deserves mention for the dominant position it held for • The cryoprobe tip temperature needs to be only 19°C,
a long time in the cataract surgeons’ armamentarium. but some instruments allow lower temperatures of upto
c. It was the first ever technique employed for cataract surgery,
in the form of couching, wherein the whole cataractous
lens was pushed back, intact, into the vitreous cavity, thus
removing it from the visual axis. The description comes
from Susruta Samhita, a 400 BC treatise by the Indian
surgeon Sushrut. The modern technique of ICCE, of
course, involves removal of the lens from the eye, not just
from the visual axis.
Steps of Surgery
• A conjunctival flap is created to expose the superior limbal
region, followed by light cauterization of bleeding vessels.
• A large curvilinear groove, extending five to six clock hours,
is made along the superior limbus using a no. 15 disposable
surgical knife. This should be at least 80 percent deep.
• The incision is created using the corneoscleral scissors
along the groove. A corneal suture is taken at this point to Fig. 10.4.1.1: Intracapsular cataract extraction
–4°C. This is unnecessary and may be detrimental in that • Secondary glaucoma

excessive freezing may break the posterior capsule and • Postoperative uveitis
cause greater inflammation postoperatively. • Aphakic or pseudophakic bullous keratopathy
• For mature and hypermature cataracts, a little extra time • Endophthalmitis.
for the ice-ball to permeate the entire thickness of the
lens may be required. EXTRACAPSULAR CATARACT
• An assistant’s help is taken to pull away the corneal lip EXTRACTION
whilst the surgeon extracts the cataractous lens as a whole. It is a group of techniques for cataract extraction that have
• An alternative technique employs a capsule holding forceps the common denominator of preserving the posterior capsule
to extract the cataract. This poses the risk of inadvertent of the lens. Historically, if one omits couching, extracapsular
tear in the anterior capsule and accidental extracapsular strategies were first tried but then discarded once intracapsular
extraction. techniques got more refined.
• The erysiphake is a special device that adheres to the There are certain distinct advantages to preserving the
anterior lens surface by means of a vacuum force. It can posterior capsule, which led to a return to prominence of the
be used in much the same manner as the cryoprobe, but extracapsular cataract extraction (ECCE) techniques.
has a weaker grip on the lens. The presence of an intact posterior capsule offers:
• One may also use a wire vectis, which is a ring shaped • Support for placing a posterior chamber IOL.
instrument, to prise the cataractous lens out. This has been • Retention of vitreous gel in its physiological space.
modified to include a lumen, the irrigating vectis, which • Lower incidence of cystoid macular edema, endophth-
helps to maintain the anterior chamber as the cataract exits. almitis and secondary glaucoma.
• The use of the forceps or the erysiphake can result in the
ECCE for the purpose of this chapter would refer to
lens being delivered in either of the following two manners.
surgery using a large non-valved incision. Other forms of
The classical description is ‘Tumble’, when the lens flips
ECCE include needling, manual small incision cataract surgery
over and the inferior pole is delivered first, or ‘Slide’, when
(SICS) and phacoemulsification.
the superior pole emerges first. With the cryoprobe, only
Needling, or breaking the capsule with a cystitome and
the ‘Slide’ technique is possible.
stirring up the contents of the capsular bag was also an
• Since, the whole lens is delivered intact with the capsule,
established form of cataract surgery, albeit one that is no longer
no irrigation and aspiration of cortical matter is required.
in use. It was a method that depended upon the body’s capacity
• An ACIOL, iris fixated or scleral supported IOL may then
to remove the flocculent lens matter in the young patient. There
be placed.
was the obvious disadvantage of inciting a lot of inflammation,
• A peripheral iridectomy is often performed. Any vitreous
and that the surgery resulted in aphakia, which is no longer a
in the wound or anterior segment should be meticulously
desirable end-point. Since it was used in the younger set of
removed to avoid the vitreous wick syndrome.
patients where no firm nucleus would be encountered, the
• The wound should be carefully closed using 10-0 nylon
incidence of posterior capsular opacification was very high.
monofilament. Interrupted sutures are preferred.
In paediatric surgery, as one will come across in a subsequent,
Alternatively, 8-0 nylon or steel sutures have also been used.
the standards of care are now very high indeed. Indications
for performing ECCE are:
Complications of ICCE
• Any surgical situation, for example, a dense cataract, where
• Intraoperative complications 2 like iridodialysis, the surgeon feels that ECCE would produce a better final
Descement’s detachment, inadvertent ECCE, nucleus or outcome than other techniques like phaco or SICS.
lens drop, hyphema, vitreous loss, expulsive hemorrhage • Whilst undergoing training as a surgical resident.
• Wound related complications like wound gape, iris • As a conversion from phaco if some complication arises,
prolapse, wound leak, fibrous ingrowth and epithelial for example, an impending nucleus drop.
downgrowth
• Vitreoretinal complications like cystoid macular edema, Steps of Surgery
postoperative retinal detachment, vitreous hemorrhage, • After regional block, the conjunctiva is irrigated with
and retention of lenticular fragments povidone iodine solution.
Cataract Surgery 999
• A superior rectus bridle suture is optional. It is grasp the anterior capsular tags or the posterior capsule or
recommended for beginning surgeons as it offers greater iris tissue.
control over the eyeball during surgery. It does, however, • Following removal of all cortical matter, the anterior
expose the patient to the possibility of perforation.3 There chamber is once again filled with viscoelastic solution and
is also some risk of postoperative ptosis if the bridle suture a posterior chamber intraocular lens is implanted.
has been used.4,5 • The placement of the IOL is either in the ciliary sulcus, or
• A fornix based, superiorly placed conjunctival flap is then in the capsular bag. A peripheral iridectomy is optional,
made, taking care to cut only as much tissue as required to but generally not done unless vitreous has been lost. If
provide access to the surgical site. The Tenon’s capsule the IOL is placed in the sulcus, pilocarpine is injected to
also needs to be included in the flap. constrict the pupil and thus stabilize the IOL.
• The exposed scleral bed is lightly cauterized; heavy cautery • The incision is closed using 10-0 nylon monofilament. The
is harmful as it impairs wound healing and may cause pattern of suturing may be interrupted sutures, (Fig.
collagen shrinkage and resultant astigmatism. 10.4.1.3) or continuous shoelace type. The surgeon should
• A deep curvilinear limbal groove is made, extending about apply uniform force across the entire section so that there
four to five clock hours.
• At the centre of this groove, a small part of the section is
opened with a blade or keratome to allow entry into the
anterior chamber. The incision is non-valved.
• Viscoelastic solution is injected to replace the aqueous
humor.
• An anterior capsulotomy is made to expose the lens
material. The capsulotomy can take various forms,
commonly the can-opener, the Christmas tree, or the
envelope style.
• The capsulotomy punctures should be made parallel to
the circumference of the lens nucleus and should be small
and numerous. The final opening should be large enough
so that the capsular bag is not pulled while expressing the
nucleus.
• The incision is enlarged using the corneoscleral scissors.
The initial limbal groove serves as the guide for this
Fig. 10.4.1.2: Nucleus delivery in extracapsular cataract extraction
enlargement. The section should be large enough to allow
the nucleus to come through unimpeded.
• The nucleus is separated from the surrounding cortex by
gentle irrigation, which may be assisted by manual rocking
of the nucleus.
• A vectis is then used to exert positive pressure at the 12
o’clock sclera just behind the incision. At the same time
counter-pressure is exerted against the cornea at 6 o’clock
position just inside the limbus (Fig. 10.4.1.2).
• The nucleus is slowly expressed by delivering the superior
pole first, which comes out of the eye as the posterior lip
of the incision is depressed. Additional help can be
obtained at this stage by gentle traction on the bridle suture.
Care should be taken that the manipulations are done
gently, to avoid rupturing the posterior capsule.
• Once the nucleus has been delivered, the remaining cortex Fig. 10.4.1.3: Interrupted sutures in
is aspirated using a Simcoe cannula, taking care not to extracapsular cataract extraction
is no undue astigmatism. The sutures should, of course, • Descemet’s membrane detachment can be extremely
be tight enough to prevent loss of anterior chamber fluid. difficult to identify, particularly when there is cortical matter
• At the end of surgery, all viscoelastic should be removed in the anterior chamber. The Descemet’s flap may also be
from the eye. This can be done before tying the last suture. confused with the anterior capsular flap. When uncertain,
Residual viscoelastic can cause marked rise in intraocular it is better to leave a capsular tag than to pull on the
tension and patient discomfort for days. Descemet’s membrane.
• Before patching the eye, the conjunctival flap is positioned The use of a good operating microscope goes a long way
back and a small subconjunctival depot of antibiotic steroid in preventing complications by affording good visualization
solution is injected. of intraocular contents and events. Even if a complication
does occur, it is usually picked up early and can thus be better
Complications managed.
Complications can occur during any of the above steps and SMALL INCISION
the surgeon should be well prepared to identify and deal with CATARACT SURGERY
them.
• The most common complication, encountered even by Small incision cataract surgery (SICS) is actually a group of
the most skilful of surgeons, is a posterior capsular tear related techniques with the following two common
(PCT). This may be accompanied by vitreous loss. denominators.
• As a result of a PCT, it may not be possible to place a a. Extracapsular cataract extraction
posterior chamber IOL without iris or scleral support. A b. Tunnelled, self sealing incision
thorough anterior vitrectomy is done to remove all vitreous Anesthesia Considerations
strands from the anterior chamber.
• Residual vitreous may cause pupillary distortion, IOL • It is generally accepted that regional block is necessary for
decentration or tilt, secondary glaucoma, retinal detach- making the scleral incision. This is especially true for the
ment, endothelial decompensation or cystoid macular beginning surgeon, although with experience it is possible
edema, besides increasing the risk of endophthalmitis. to perform the procedure under sub-conjunctival
• If the PCT is small, it may be possible to convert the infiltration anesthesia.
opening to a posterior capsulorrhexis. • Topical anesthesia is not a viable option because the patient
• Nucleus drop into the vitreous cavity may happen in case tends to roll up his eyes from time to time, which becomes
of an undetected PCT occurring early in the surgery. difficult to manage when one sits superiorly.
• The most serious complication is that of expulsive Steps of Surgery–the Site
hemorrhage, which may occur as soon as the anterior
chamber is entered. The usual cause is suprachoroidal • The eye is cleaned and draped, and the conjunctiva irrigated
hemorrhage, which increases the up-thrust and causes with povidone iodine solution.
intraocular contents to extrude through the main incision.6 • The superior rectus ‘bridle suture’ may be taken as per the
An early sign is shallowing of the anterior chamber to the surgeon’s requirements.
point of flatness with prolapse of iris. This is usually • The conjunctival flap is raised in much the same manner
followed by expulsion of the lens in toto, and vitreous loss. as when doing a conventional ECCE, but it is a smaller
If this sequence of events starts to take shape, the surgeon flap. The sclera is then lightly cauterized.
must immediately secure the wound, using 8-0 interrupted
sutures. This is accompanied by raising the head end of Steps of Surgery–the Incision
the operating table, posterior sclerotomies to drain the • There are several described locations for creating the
suprachoroidal blood, and administration of intravenous incision for performing SICS. These sites are corneal,
mannitol. This complication is more likely in glaucomatous limbal and sclera and for any given location, the incision
eyes and hypertensive patients. may be placed superiorly or temporally. These locations
• Other complications should also be watched for. While refer to the initial groove made on the surface of the eye.
passing the bridle suture, the needle may perforate the The inner aspect remains clear corneal, well clear of the
globe. This can be identified by sudden hypotony and the base of iris, in order to maintain the self-sealing, valvular
appearance of blood intraocularly. action.
• The initial groove in a SICS incision is very important. • The incision should have lateral extensions called
The more posterior it is placed, the lesser the induced side pockets, which help to guide the nucleus as it
astigmatism, but at a cost of progressively increasing emerges.
surgical difficulty. • The inner edge of this incision should extend to at least a
• The closest point of approach to the limbus is generally millimeter into clear cornea, to provide an effective ledge.
1.5 to 2 mm away, falling away on each side so that the This is essential for the valve effect to come into play which
final groove acquires the shape of a ‘frown’. This ‘frown’ permits sutureless wound closure. A spin-off advantage
shape is considered astigmatically neutral.7 The incision is that there is virtually no tendency for the iris to prolapse
can be straight also (Figs 10.4.1.4A and B). out, something one sees routinely in conventional ECCE.
• If the cataract is very large, the frown should be minimal • One or two side port incisions may be made at this point
and the incision closer to the limbus. These changes allow of time. Some surgeons prefer making the side-ports first,
easier expression of the nucleus. filling the anterior chamber with viscoelastic and thereafter
• The length of this groove is proportional to the anticipated
making the main tunnelled incision in a well pressurized
nuclear size.
eye (Fig. 10.4.1.6).
• A bevel up crescent knife is used to undermine the groove
• An additional inferior entry into the anterior chamber can
anteriorly, and the plane thus created is advanced into clear
be made to provide a steady source of balanced salt
cornea (Fig. 10.4.1.5).
Figs 10.4.1.4A and B: Frown incision (A) and straight incision (B) made for SICS
Fig. 10.4.1.5: Creation of the self-sealing Fig. 10.4.1.6: Side-port entry

tunnel with the crescent knife
solution. This is called an AC maintainer and it prevents probe, and if this nucleus is too large to slip through the
the anterior chamber from collapsing during surgery.8 CCC opening, one risks zonular damage as the capsular
• Once the entire tunnel has been properly defined, a sharp bag is pulled along. Thus, the CCC has to be a little larger
keratome is used to enter the anterior chamber. The in SICS than in phaco (Fig. 10.4.1.7).
anterior chamber is filled with viscoelastic. • In case of white cataracts, it is worthwhile using a dye to
enhance capsular visibility (Figs 10.4.1.8A and B).
Steps of Surgery–Capsulotomy
Steps of Surgery–Hydroprocedures
• The capsulotomy can be can-opener in form, or a
continuous curvilinear capsulorrhexis (CCC). • The main incision is now enlarged to the desired dimension
• There are many advantages in following the latter approach, using the 5.2 mm keratome.
as enumerated in the chapter on phacoemulsification. • Hydrodissection and hydrodelineation are done, and then
There is one potential pitfall, though, and it should be cortical wash is given. An exception here would be the
kept in mind. In SICS, the nucleus has to emerge from the presence of a posterior polar cataract, which has to be
bag without the benefit of piecemeal removal by the phaco dealt with in a specific manner described later. The aim of
these irrigating maneuvers is to free the nucleus of its
attachments and reduce its size by washing off adherent
cortex and epinucleus. After hydroprocedures, the nucleus
is rotated within the bag to confirm its separation from
the bag and cortex.
Steps of Surgery-Nucleus Management

The next step is to bring the nucleus out of the capsular bag
and into the anterior chamber. In case of a can-opener
capsulotomy, this is easily achieved by inserting a spatula under
the nucleus and tipping it forwards, or simply by directing a
flow of viscoelastic under the superior pole of the nucleus.
• Bringing a nucleus out through the CCC can be tricky,
especially if it is a large nucleus. If, in the surgeon’s
assessment, the CCC is too small to allow the nucleus to
Fig. 10.4.1.7: Large rhexis in SICS emerge easily, enlargement of the capsulorrhexis may be
Figs 10.4.1.8A and B: : Rhexis in a white cataract. Use of dye helps in delineating the capsule
considered. To do this, an angled cut is made along one support and direction. Care should be taken to protect
edge of the CCC with a Vannas scissors, and the flap thus the posterior capsule during this step.
created is raised using an Utrata’s forceps. The flap is then • The whole sequence of events can also be executed without
moved along in an arc, thus enlarging the CCC. using viscoelastics if an AC maintainer has been employed.
• Before prolapsing the nucleus, the anterior chamber is filled • The subsequent management of the nucleus is a matter
with viscoelastic. of some diverse opinions.9-12 It can be extracted as a whole
• The nucleus is then tilted to one side with a dialler, while a or in fragments.
spatula or a rounded repositer is pushed under the exposed • In viscoexpression, the anterior chamber is filled with
pole. viscoelastic and the nucleus maneuvered to a position near
• The spatula is then used to lift the superior pole of the the main incision. The posterior lip of the incision is
nucleus into the anterior chamber (AC). The nucleus is then depressed, allowing some viscoelastic to flow out. This
dialled while maintaining an upward force till it completely flow brings the nucleus with it.
comes out of the CCC (Figs 10.4.1.9A and B). • The nucleus may be brought out by placing a wire vectis
• If there is any difficulty while doing this, a second under it and then guiding it out. An irrigating vectis can
instrument in the other hand can be used to provide also be used (Fig. 10.4.1.10).
• The nucleus may also be pulled out using a fish-hook. This
technique requires a slightly larger incision size, but that
issue has been successfully addressed using the various
nuclear-fracture techniques.
• Nucleus fracture is achieved by dividing the nucleus into
two or more fragments using a variety of instruments or
wire snares. The individual pieces are washed out using
viscoexpression or the unidirectional thrust of an AC
maintainer. The obvious advantage offered is that of a
smaller incision size. There is, however, increased
endothelial trauma that results from the intraocular
manipulations to divide the nucleus.
• While viscoexpressing the nucleus, it is important to coat
both its surfaces with adequate viscoelastic to facilitate a
smooth exit with minimal endothelial damage.
Figs 10.4.1.9 A and B: Manipulation of the nucleus into the anterior Fig. 10.4.1.10: Extrusion of the nucleus through
chamber (A); diagrammatic representation of the same (B) the incision in SICS
• There may be an epinuclear sheet left after the nucleus has postoperative astigmatism. In such a situation, the IOL
been removed. This is usually easily removed by irrigation should be rotated through a full circle and another attempt
alone, along with depression of the posterior wound lip should be made to place the second haptic in the bag,
to allow the epinucleus to exit the anterior chamber. under adequate viscoelastic support. This consideration is
• The remaining cortex is cleaned up. This is done using a valid only in the presence of an intact capsular bag.
Simcoe cannula, but removing the subincisional cortex • If a can opener capsulotomy has been used, IOL placement
requires a J-shaped cannula. A much better and safer option is like in a conventional ECCE.
is to use automated bimanual irrigation and aspiration. It
not only helps to do a thorough job, including vacuum Steps of Surgery–Closure
polishing of the capsule, but also maintains the anterior • After the lens is well centered, viscoelastic solution is
chamber depth throughout the procedure. aspirated and incisions are hydrated to effect closure.
• The main incision may be left unsutured as it is self sealing,
Steps of Surgery–the IOL but sutures should be used if there is any doubt as to the
• A posterior chamber IOL is then inserted. integrity of the wound (Fig. 10.4.1.12).
• Since, the incision is larger than 5.5 mm in most cases, a • The conjunctival flap is repositioned to cover the external
rigid PMMA lens is well suited, though some surgeons wound. This not only reduces the odds of micro-organism
may want to implant a foldable IOL (Fig. 10.4.1.11). entry, but improves patient comfort in the long term by
• The anterior chamber and capsular bag are filled with covering the incision.
viscoelastic. • Subconjunctival steroid-antibiotic mixture is then injected
• The IOL is held so that the leading haptic enters the inferior and the eye patched.
fornix of the capsular bag. In the same movement, the SICS techniques offer a convenient, cost-effective
optic is also pushed past the CCC edge. alternative to phacoemulsification with the added advantage
• The hold on the IOL is now released, but since one haptic of being machine independent. SICS is probably a safer option
and the optic are already in the bag, the IOL stays in place. than phaco in situations like poor endothelial cell counts or
• If viscoelastic has been lost from the eye during this very dense cataracts. SICS can be used in almost any type of
maneuver, it should be replaced. cataract, and should certainly be preferred over conventional
• The trailing haptic is dialled into the bag. ECCE as a matter of routine.
• At times, the IOL just rotates and the trailing haptic does
Complications
not enter the bag. The IOL should not be left in this
position because uneven forces will cause decentration SICS shares many of the complications of ECCE, but some
sooner or later, and tilting of the IOL will add to the unique to SICS are:
Fig. 10.4.1.11: Insertion of a PMMA Fig. 10.4.1.12: A single suture prevents wound slippage and
IOL through the SICS incision significant postoperative astigmatism
• Tunnel related problems like thin superficial layer of the 4. Singh SK, Sekhar GC, Gupta S. Etiology of ptosis after cataract
corneoscleral tunnel, uneven depth of tunnel, surgery. J Cataract Refract Surg 1997;23(9):1409-13.
5. Bernardino CR, Rubin PA. Ptosis after cataract surgery. Semin
buttonholing, or cut through at the ends of the tunnel, Ophthalmol 2002;17(3-4):144-8.
and premature entry into the anterior chamber. 6. Ling R, Cole M, James C, Kamalarajah S, Foot B, Shaw S.
• The valve action may not be adequate if any segment of Suprachoroidal haemorrhage complicating cataract surgery in the
the inner lip is short. UK: epidemiology, clinical features, management, and outcomes.
• Descemet’s detachment from any of the incisions. Br J Ophthalmol 2004;88(4):478-80.
• Zonular dialysis or inadvertent ICCE while attempting to 7. Singer JA. Frown incision for minimizing induced astigmatism after
small incision cataract surgery with rigid optic intraocular lens
express the nucleus through an inadequate capsular implantation. J Cataract Refract Surg. 1991;17 Suppl:677-88.
opening. 8. Malik KP, Goel R. Nucleus management with Blumenthal
technique: Anterior chamber maintainer. Indian J Ophthalmol
REFERENCES 2009;57(1):23-5.
9. Ravindra MS. Nucleus management in manual small incision
1. Lee SB, Au Eong KG, Yong VS. Management of subluxated cataract surgery by phacosection. Indian J Ophthalmol
crystalline lenses with planned intracapsular cataract extraction 2009;57(1):41-3.
and anterior chamber intraocular lens implantation. Singapore 10. Srinivasan A. Nucleus management with irrigating vectis. Indian J
Med J 1999;40(5):352-5. Ophthalmol 2009;57(1):19-21.
2. François J, Verbraeken H. Complications in 1,000 consecutive 11. Hennig A. Nucleus management with Fishhook. Indian J
intracapsular cataract extractions. Ophthalmologica 1980;180(3): Ophthalmol 2009;57(1):35-7.
121-8. 12. Bhattacharya D. Nuclear management in manual small incision
3. Savir H. Scleral perforation during cataract surgery. Ann cataract surgery by snare technique. Indian J Ophthalmol
Ophthalmol 1983;15(3):247-8. 2009;57(1):27-9.
10.4.2 Phacoemulsification: Basics,

Techniques and Instrumentation
MACHINE FUNDAMENTALS • The second and third steps are incremental. In machines
offering dual linear control, there is additional parameter
The phaco machine is a complex bit of engineering that control on horizontal excursion
essentially controls the inflow and outflow of fluid from the • Linear control refers to the response of the footpedal in a
anterior chamber and provides ultrasonic energy to the tip. manner proportional to the amount of footpedal
These functions are controlled by a variety of modifiable depression. This allows the surgeon to fine tune the
factors and are ultimately governed by the surgeon’s will. The machine in real-time use. For instance, when the machine
surgeon controls these parameters intra-operatively by means has been set to provide a preset power of 80 percent, it
of a foot pedal (Fig. 10.4.2.1). will do so only if the footpedal is pressed down completely.
• In the standard phaco foot pedal, the vertical distance If the surgeon depresses the pedal only halfway, then the
travelled is divided into three zones power supplied will be 40 percent. Thus, a graph plotted
• The first step activates the irrigation mode and is an all or between power supplied and pedal depression would be a
none step straight line–linear graph
• The second step activates the aspiration system • In earlier machines, this linear control was not available,
• The third step activates phacoemulsification and the machine response was all-or-none. If the surgeon
Fig. 10.4.2.1: Schematic representation of foot pedal positions
depressed the pedal enough to enter the third position,

full preset phaco power would be made available. This
was termed the panel mode, and is still an option, though
one that is rarely used
• There are additional switches in the foot pedal that are Fig. 10.4.2.2: Phaco tip angulations
used to provide reflux of fluid, and facility to change from
one preset mode to another.
– First, is the physical movement of the tip that hits
There are two basic kinds of phaco machines, the peristaltic
the nuclear fragment and disintegrates part of it
and the venturi, differing in the manner in which they cause
(the jack hammer effect).
fluid outflow. The differences in the two systems are outlined
– A second mechanism is the generation of an implosion,
later in the chapter.
due to the vacuum created by the sudden backward
motion of the tip.
PHACODYNAMICS AND FLUIDICS
– A third postulated mechanism is the generation of
The flow of balanced salt solution inside the eye and how acoustic waves in the fluid medium surrounding the
closed chamber dynamics are active during phacoemulsification tip.
constitutes fluidics. The interaction of ultrasonic power and – Torsional shearing action of an angulated tip (like the
fluidics constitutes phacodynamics. Kelman tip) is seen in machines that specifically
offer torsional phaco, i.e. the tip has both
Power longitudinal and rotatory movement. This strategy
improves the efficiency of the process.3
• Power in a phaco machine is generated by the vibrating
Different types of phaco tips are available. These may vary
piezo-electric crystals. There may be two, four or six crystals
in angle from zero to sixty degrees, with greater angles being
in the hand piece. The individual crystals normally vibrate
associated with greater cutting ability but lesser grip (Fig.
at a frequency of 28,000 Hz to 60,000 Hz, which is the
10.4.2.2). Special microflow tips with reduced lumen and
domain of the ultrasonic.
external grooves for enhanced fluid cooling, and angled
• These provide a back and forth motion to the phaco tip,
Kelman tips are some of the other popular variants.
which in turn translates into cutting power. The excursion
of the phaco tip is termed its stroke length. This typically
Power Delivery
varies between 0.05 to 0.15 mm.
• For an individual machine, the frequency of vibration is a • Power is controlled by the surgeon by means of the foot
fixed entity, while the stroke length is variable. It is by pedal (Fig. 10.4.2.1).
varying this stroke length that variations in the power • In positions one and two, no phaco power is generated.
generated are achieved. • In position three, power may be generated proportional to
• There are four proposed mechanisms that explain the the amount of foot pedal depression (linear control), or full
cutting action.1,2 phaco power preset may be directly attained (panel control).
• The actual mode of delivery of power may be continuous or Aspiration System

pulsed.
Aspiration serves to remove the emulsified nucleus and cortical
• In the pulsed mode, the frequency of pulses is preset but the
matter from the anterior chamber. It also removes the heat
amount of power delivered per pulse depends upon the generated at the phacotip when it is vibrating. In addition,
amount of foot pedal depression. aspiration generates the holding power for the surgeon.
• The pulsed mode may itself be further fractionated, in There are two basic mechanisms by which aspiration is
that each pulse of power is actually composed of many achieved.
micropulses. a. The peristaltic pump (Fig. 10.4.2.3) works on the lines of the
• Pulsed power delivery offers the advantage of reducing gastrointestinal tract, by pinching away pockets of fluid in
chatter of the nuclear fragments at the phaco tip, thus a given direction. This is done by means of rollers, over
enhancing followability. Chatter is a specific description of which the aspiration tube is draped. Since very small
the tendency of the vibrating phaco tip to push away pockets of fluid are removed, only a minute amount of
material that comes in contact with it. vacuum is generated in the line. However, if further ingress
• Several other modifications are available in the process of of fluid is stopped, for example by occlusion of the
power delivery. These include a burst mode, where bursts of aspiration tip, then a large vacuum builds up step by step,
full power are delivered, at a frequency depending upon as each pocket of fluid is removed. The faster the rollers
the amount of foot pedal depression. move, the faster the vacuum builds up. In technical terms,
• These special modes reduce the overall energy delivered the higher the flow rate (liquid removed per unit time), the
to the eye, enhance followability and grip, and reduce the shorter the rise time (time required to reach the maximum
likelihood of corneal burns. preset vacuum). It should be noted that the peristaltic
system essentially pushes fluid one way, so there is
Irrigation System practically no vacuum unless the aspiration orifice is
occluded.
• Gravity is the primary determinant of the hydrostatic b. The venturi system uses the Bernoulli’s principle to create
pressure that drives the irrigation system. vacuum, which is then transmitted directly through the
• The pressure involved is proportional to the height of the aspiration tubing. Unlike a peristaltic pump, vacuum
irrigation bottle above the patient’s eye level. At resting creation precedes fluid removal. Thus, occlusion of the
state, a higher bottle height means more pressure in the phacotip is not a prerequisite to generate vacuum, a fact
closed system, which equates to a greater IOP and a deeper which affords much better ‘pull’ in a venturi system.
anterior chamber.
• As the aspiration system removes fluid from the closed Surge
system, an equal amount of fluid is replaced through the The aspiration tubing is deformable in nature, and this can
irrigation system. The higher the bottle, the more readily lead to some trouble.
this fluid is available. However, too high a bottle will cause • According to the laws of physics, vacuum is distributed
undue pressure to be exerted and result in zonular stress uniformly inside the lumen of the aspiration tubing. Thus,
and patient discomfort.
• On an average, a height of about three feet above the eye
level is sufficient.
• Increased availability of fluid to the anterior chamber can
be useful in preventing post-occlusion surge. This may be
achieved by using a positive pressure pump, which
essentially works in the same way as the raised bottle.
• Alternatively, additional flow can be generated by using a
TURP (trans-urethral resection of prostate) set or an
anterior chamber maintainer. The latter involves creation
of an additional corneal incision and provision of a
separate infusion line. Fig. 10.4.2.3: The peristaltic pump
there is a tendency for the tubing to collapse a little as Ocular Viscoelastic Devices
vacuum is generated. This tendency is called compliance.
Ocular viscoelastic devices (OVD) are viscous, gel like materials
• As occlusion breaks, there is an inflow of fluid and, at the
that are used temporarily during cataract surgery. They help
same time, the tubing also springs back to its original
by creating surgical space, protecting the non-target ophthalmic
volume.
tissues, providing mechanical mydriasis and by slowing down
• Thus fluid is suddenly taken up by the aspiration system,
events in phacoemulsification. They broadly behave in two
which may cause a temporary shallowing of the anterior
somewhat distinct manner.
chamber. This is called post-occlusion surge, and it can be very
dangerous. Cohesive viscoelastics, typified by sodium hyaluronate, are primarily
used to create space. They are composed of heavy-weight
It is interesting to note that there is a fundamental
(molecular weight more than one million Dalton) long chain
difference in how the peristaltic and venturi systems experience
molecules with high zero-shear viscosity that entwine and form
surge.
a mass that resists washing out. However, they can be easily
In a peristaltic system, loss of occlusion causes vacuum to
injected through a small bore cannula because pressure causes
drop to zero, permitting the aspiration tubing to regain its
alignment of the long chains parallel to each other. This
full, pre-occlusion volume. This draws in a greater amount of
property is called pseudoplasticity. They are very useful in creating
fluid and the surge experienced is bigger.
space and pressure even in the open eye, and therefore help in
In a venturi system, some vacuum remains in the tubing
consistently achieving a good capsulorrhexis even in adverse
even after the break of occlusion. The increase in volume of
conditions like an intumescent cataract. As these viscoelastics
the aspiration system is not as large as in a peristaltic system,
are cohesive in nature, it is easier to remove them totally from
and thus the consequent surge is also lesser.
the eye en masse following surgery. This can be important in
Higher end machines incorporate a variety of systems to
certain situations, for example when implanting toric IOLs,
detect occlusion and use technological solutions to prevent
where residual viscoelastic can cause rotation of the IOL
surge. These include customizable post occlusion settings that
postoperatively. Currently available viscous cohesive OVDs
effectively stop or slow down proceedings as occlusion is
include Healon (1% sodium hyaluronate, 4 million Daltons
achieved, resulting in an exceptionally safe surgical
AMO), Provisc (1% sodium hyaluronate, 2.4 million Daltons,
environment.4
Alcon), Amvisc Plus (1.6% sodium hyaluronate, 1.5 million
Daltons, Bausch and Lomb, B&L, Rochester, NY, USA),
Followability Amvisc (1.2% sodium hyaluronate, 2 million Daltons, B&L),
Removal of fluid from the anterior chamber sets up and many others. Healon GV is a super viscous cohesive OVD
unidirectional currents in the eye, simulating a source-sink (1.4% sodium hyaluronate, 5 million Daltons) with a zero-
system. This causes any loose material to flow towards the shear viscosity of 2 million milli-Pascal seconds (mPaS), about
aspiration port, creating an attracting force called followability. 10 times the zero-shear viscosity of regular viscous cohesive
The higher the flow rate, the better the followability. In practical OVDs, which results in it being able to perform all of the
terms, when the surgeon wants to attract loose material towards tasks above of a viscous-cohesive OVD better.
the tip, a higher setting for flow rate is used. The other group of viscoelastics is the dispersive group,
having lower molecular weight and have low zero-shear
Vacuum viscosity (less than 100,000 mPaS) and exemplified by hydroxy
propyl methyl cellulose. Since they are dispersive in nature,
Once the aspiration port is occluded, vacuum starts to rise. they can be washed away piecemeal by the irrigating fluid, but
The upper limit of attainable vacuum is preset by the surgeon, it is difficult to remove them entirely from the eye. The low
and the aspiration system continues to remove fluid till this internal cohesiveness causes the OVD mass to break up easily,
level is achieved. Vacuum in the system provides a hold over and small amounts of retained OVD causing IOP spikes in the
whatever occludes the port. In surgery, this means that early postoperative period is a common occurrence. The
whenever there is a need to grip the nuclear fragments, for defining characteristic of dispersive OVDs is an ability to coat
example while chopping, a higher vacuum is employed. surfaces, offering protection to ‘innocent bystanders’, particularly
the corneal endothelium. They create fractionated spaces, in Incision

that a part of the anterior chamber is filled with the OVD, while
a second space, filled with irrigating fluid, is available for The purpose of the phaco incision is to give access to the
carrying out the maneuvers of surgery. This property makes cataractous lens. At the same time, it should fulfill some
them very useful in prolonged cases and while handling important prerequisites.
complications. Dispersive OVDs that are currently available • Most importantly, it should not permit excessive leakage
internationally, include Viscoat (sodium hyaluronate 3%, of fluid so that fluidics can be used effectively.
600,000 Daltons and chondroitin sulfate 4%, 50,000 Daltons), • It must induce minimum astigmatism.
Ocucoat, (HPMC 2%, 80,000 Daltons, B&L) and Cellugel • It should be self sealing.
(Modified HPMC 2%, 300,000 Daltons, Alcon), among many Incisions have been described in various configurations
others. In India, one of the better products on offer is Appavisc that meet the above mentioned criteria. The choice of a
(Appasamy Associates). particular incision must be made by the surgeon considering
OVD classification has recently been modified to several factors, but perhaps most important is to take into
accommodate newer viscoadaptive OVDs. Healon5 (AMO), account surgeon comfort.
(2.3% sodium hyaluronate), is a viscoadaptive OVD with a Superior incisions are typically made at the limbus or sclera,
molecular weight of 4 million Daltons, DisCoVisc is a and generally under regional block.
combination of hyaluronic acid 1.6 percent and chondroitin
sulfate 4 percent, and is a higher viscosity dispersive OVD The advantages offered are:
(1.7 million Daltons). Viscoadaptive OVDs are different from – Easier to make for a person already used to making
the traditional dispersive and cohesive OVDs in that they are incisions for SICS.
extremely highly viscous and cohesive under low shear – Easier to abandon and convert to large section surgery
conditions; at low flow phacoemulsification, they do not should the need arise.
fracture and remain undisturbed while phacoemulsification – Lesser incidence of postoperative endophthalmitis.5
continues. By design, they also exhibit pseudodispersive – Lesser postoperative foreign body sensation.
characteristics under high shear conditions, because they begin
to fracture under stress, much as a solid would. They may The disadvantages of superior incisions are:
therefore be referred to as pseudodispersive. – Upper conjunctiva is disturbed, a situation which may be
For maintaining space and to protect tissues, the OVD undesirable if a later filtering surgery is required.
should possess high viscosity at low shear rates while low – More difficult to perform under topical anesthesia.
viscosity at high shear rates is required to permit passage – More difficult access to the cataract, especially when the
through a small bore cannula. For phacoemulsification and I/ eye is deep set.
A, some OVD should be retained throughout the procedure – Greater induced astigmatism than temporal incision.6
in the anterior chamber, protecting the endothelium; and for These points are reversed when one considers the clear
IOL implantation and movement of instruments, the OVD corneal temporal incision, which is a much favored one owing
should possess moderate viscosity at medium shear rate. As it to its greater convenience for the surgeon (Fig. 10.4.2.4).
is hard to meet all the above requirements by a single OVD, The incision, regardless of location, has to be bevelled.
and different newer OVDs (Healon5—viscoadaptive and The inner corneal lip extends a bit into the anterior chamber,
pseudodispersive, DisCoVisc—higher viscosity dispersive), forming a valve which is closed by intraocular pressure once
and OVD techniques (soft shell, ultimate soft shell) have been the phaco probe is out of the incision. This gives a truly self-
designed to try to achieve these objectives. Hence some sealing incision that starts working as soon as the surgery is
surgeons prefer using different OVDs during different phases over. The ideal configuration described for such a tunnelled
of phacoemulsification surgery. Recently several OVDs come incision is a square form, where the tunnel is as wide as it is
packaged in pairs. The choice of best OVD is based on long.7 In practice, however, a tunnel that is about 2.8 mm
personal surgical technique as well as individual case wide can be about 1.5 mm into the cornea and still be extremely
requirements. stable. For the valve to act properly, the inner lip of the incision
Fig. 10.4.2.5: Uniplanar incision

Fig. 10.4.2.4: Main clear corneal wound entry for performing
phacoemulsification
must be at a uniform distance from the limbus. Ragged or

wavy inner lip causes the wound to leak.
Entry Incision
Uniplanar incision: When making the tunnel, the surgeon enters

the anterior chamber at an angle, so that the outer point of
entry is near the limbus while the endothelial cut happens
about 1.5 to 2 mm into the anterior chamber. Here, the bevel
is purely according to the angle made by the blade with the Fig. 10.4.2.6: Biplanar incision
cornea (Fig. 10.4.2.5).
Biplanar incision: The surgeon first makes a vertical groove at
the limbus defining the outer limit of the incision. The blade
is then directed forwards and downwards into the corneal
substance till entry into the anterior chamber is achieved (Fig.
10.4.2.6). This permits a better valvular action but also induces
more astigmatism.
Triplanar incision: A triplanar incision is made in the same fashion
as above, but first the blade travels parallel to the corneal surface
and then dips down at the point where entry into the anterior
chamber is desired. This further enhances the valve action
(Fig. 10.4.2.7).
Fig. 10.4.2.7: Triplanar incision
Side Port Incision
It is necessary to have sharp blades and a tense eyeball to
In addition to the main incision, side ports are required. These
permit good incisions.
may be one or two in number, are placed about 80 degrees
away from the main incision, and are used to introduce
Capsulorrhexis
instruments like the chopper or the rhexis needle into the
anterior chamber. They are made in the manner of paracentesis A capsulorrhexis is a circular opening in the capsule. The
incisions, bevelled and pointing to the center of the eye. These anterior CCC (continuous curvilinear capsulorrhexis), as it also
should always be entirely corneal in location to permit good called, has several advantages over other openings such as the
sealing. can-opener or the envelope.
• Since, the margin of the opening is a continuum, it forms

a strong edge that resists backward extension.
• It allows insertion of IOL entirely in the capsular bag,
thereby enhancing stability and centration of the IOL.
• A well made CCC with an adequate overlap over the optic
edge promotes the formation of a shrinkwrap over the
IOL, accentuating the effects of the posterior square edge
in retarding posterior capsular opacification.
• It acts as a third ‘hand’ for the surgeon, holding back
nuclear fragments till the surgeon is ready to tackle them.
In-the-bag phaco thus performed is least traumatic for
the corneal endothelium.
• The absence of capsular tags permits a much more
thorough cortical clean-up. Fig. 10.4.2.8: Using a cystitome to create a capsulorhexis
• It provides a stable platform to rest the IOL even if there
is a posterior capsular break.
A capsulorrhexis can be created using either a bent 26-G
needle (Fig. 10.4.2.8), or a Utrata’s forceps. The basic idea is
to initiate a tear in the central part of the anterior capsule, and
then lift the capsular flap, which can be turned around the
central axis in a smooth, circular configuration. This creates a
central circular opening in the anterior capsule which provides
access to the underlying cataract. A good CCC is about 5 to
5.5 mm in diameter (Fig. 10.4.2.9).
Hydroprocedures
The use of balanced salt solution as a physical, cleaving force
constitutes hydroprocedures. These are hydrodissection and
hydrodelineation.
Hydrodissection is the passage of a fluid wave between
the capsule and the subcapsular cortical fibers (Fig 10.4.2.10). Fig. 10.4.2.9: Capsulorhexis
It creates a plane that separates these two structures and
permits easy removal of the lens matter. A good
hydrodissection wave is also helpful in lifting off posterior
subcapsular opacities and breaking cortico-capsular
adhesions.
Hydrodissection sends a wave of fluid that can be visibly
confirmed in cases of immature cataract. The trick is to send
forth a small bolus of fluid with a rapid injection rather than
a slow and continuous infusion. Hydrodissection should be
done in different segments to effect a proper separation (Figs
10.4.2.11 A and B).
In case of a posterior polar cataract, hydrodissection should
not be done as there is a great risk of capsular breakage and
subsequent loss of the cataract into the vitreous.
Hydrodelineation is the passage of a fluid wave similar to
hydrodissection, but here the aim is to separate the harder
endonucleus from the softer epinucleus (Fig. 10.4.2.10). As Fig. 10.4.2.10: Hydroprocedures
will be seen, this greatly aids in nucleus management and 80 to 90 percent depth. This is called trenching or sculpting
enhances the safety of the surgery (Figs 10.4.2.11A and B). (Fig. 10.4.2.12).
It is possible that fluid may get trapped inside the capsular • These are at right angles to each other, making a cross
bag during these maneuvers. This should be suspected if there sign as viewed from the microscope (Fig. 10.4.2.13).
is a sudden lift of the central lens matter and marked shallowing • The nucleus is then divided into four segments along these
of the anterior chamber. If further fluid is injected, raised grooves, and each segment is then emulsified independently
intracapsular pressure may force the contents of the capsular (Figs 10.4.2.14 A and B).
bag through the posterior capsule, a disaster. To prevent such • This is a particularly efficient technique for hard cataracts
a situation, gentle rocking motion of the nucleus should be and for the beginning surgeon.
done to release the injected fluid from time to time. A larger • The downside is increased phaco energy dissipated in the
capsulorrhexis is protective by providing a larger area for fluid eye during sculpting.
egress.
Stop and Chop
Nucleus Management Techniques
• In a stop and chop technique9 single deep trench is made
This is the crux of the surgery. The skill of breaking the nucleus and the nucleus bisected along it (Figs 10.4.2.15 and
into manageable fragments and removing them through the 10.4.2.16).
tiny lumen of the phacoprobe is nothing short of an art. All • The two hemi-nuclei are progressively chopped into smaller
action takes place in an area surrounded on all sides by the so- fragments and emulsified.
called ‘innocent bystanders’, where a momentary lapse can • Lesser phaco energy is used and more emphasis is placed
derail the whole sequence of events, at times irretrievably. on using fluidics to remove the cataract.
There are a multitude of approaches to managing the
nucleus, each with its own advantages and perils. Only the Direct Chop
more popular ones are discussed here.8,9,10
• In the direct chop technique10 no trench is made; the probe
Four Quadrant, or the Divide and Conquer 8 is buried in the center of the nucleus and fragments are
generated by chopping (Figs 10.4.2.17).
• In the divide and conquer technique,8 two deep grooves • Phaco energy required is the least when compared to other
or trenches are made in the nucleus, extending to about techniques.
Figs 10.4.2.11A and B: Injection of a wave of fluid through the immature cataract results in hydrodissection (A) Fluid aimed to separate
the harder endonucleus from the softer epinucleus, is termed hydrodelineation (B). Note the golden ring marking the reflecting interface
of the separated endonucleus, which would be emulsified
Fig. 10.4.2.12: The first step is sculpting to make the hard Fig. 10.4.2.13: Divide and conquer technique
endonucleus amenable to craking and subsequent emulsification
Figs 10.4.2.14A and B: Emulsification of the divided segments
Fig. 10.4.2.15: Stop and chop technique Fig. 10.4.2.16: The nucleus is bisected and cracked
Cortex Removal
Cortex removal is the subsequent task.
• Unimanual or bimanual automated irrigation aspiration is
used.
• The parameters on the phaco machine has to changed
from the phaco mode to the irrigation-aspiration mode
(IA) mode. These are separately calibrated for the phaco
probe and the IA tip because of different orifice sizes,
and settings for the phaco mode are not applicable for the
IA mode.
• Since the IA tip is smaller than the phaco tip, higher flow
settings can be used safely.
• The aspiration tip is positioned just below the rhexis margin
and in the middle of cortical fibers.
Fig. 10.4.2.17: Direct chop technique • Side to side movement of the instrument as the aspiration
is actuated prevents accidental capture of the capsular rim.
• Once the cortex has been firmly grasped, it is pulled to
• A good understanding of phacodynamics and proficiency the center, a movement that peels it from the equator and
in chopping are prerequisites to nucleotomy by direct chop. the posterior capsule.
• It is important to remember that the nucleus is also a • The free cortex is then aspirated. The process is repeated
resource that needs to be used properly during surgery. around the entire circumference.
Repeated attempts at burying without establishing a proper • When using bimanual IA, the irrigation tip should always
grip will lead to loss of this resource, and the surgeon may be well advanced into the anterior chamber. Inadvertent
be left stranded with a doughnut shaped nucleus-epinucleus removal of the irrigation tip can cause a sudden collapse
complex, which can be difficult to manage. of the anterior chamber, with possibly serious
consequences.
Epinucleus Removal • In case of residual cortical fibers sticking on the posterior
Epinucleus is the soft shell that surrounds the harder capsule, a low vacuum mode called the capsular vacuum
endonucleus. It can be roughly divided into anterior, equatorial mode may be employed.
and posterior parts. It requires the adroit use of fluidics to • Alternatively, it may be possible to just wash off the
remove it, understanding that a higher flow rate is more capsular fibers using the flow from the irrigation tip.
relevant than a higher vacuum. • Bimanual IA offers better control and access as compared
A round tip repositor is used for the manipulation of the to the unimanual method, but requires the use of two side
epinuclear plate. ports (Fig. 10.4.2.18 A and B).
• At the outset, the anterior part is grasped with the phaco • Some surgeons perform a modified form of bimanual IA
probe (bevel up), pulled towards the center and aspirated. using one side port and the main incision as the irrigation
• The remaining sheet is then rotated around so that a port but the chamber depth is always less stable.11
different, more accessible edge presents itself.
• Gradually most of the anterior and equatorial part is peeled Implantation Techniques for IOL
off. When only a small anterior edge remains, the plate Insertion (foldable and non-foldable)
needs to be flipped. Implantation of the IOL restores the optical system of the
• Care should be taken that not all such edges are removed eye and corrects the surgically induced aphakia.
without flipping, otherwise one is left with a ‘handleless
posterior plate’ that is not easy to remove. Implantation of Rigid IOLs
• Free use of the second instrument to manipulate the • The incision made for phacoemulsification needs to be
epinuclear plate is very important. As a rule, phaco energy enlarged to accommodate the optic diameter of the rigid
is not required during epinuclear plate removal, but short IOL. This is usually between 5.0 to 5.5 mm. The
bursts may be needed to clear the lumen of the phaco enlargement is done by a flat, bevelled blade called a 5.2
probe from time to time. keratome (Fig. 10.4.2.19).
Fig. 10.4.2.19: Enlargement of the section with a 5.2 keratome
• No attempt should be made to force the rigid IOL through

a narrow opening. Such an attempt will only enlarge the
incision in an irregular manner, besides having the potential
to detach the Descemet’s membrane. It may also deform
the haptics and scratch the optic.
• If viscoelastic has been lost during enlargement of the
incision, it should be replaced before inserting the IOL.
• The IOL is washed and then held firmly but gently using a
Kelman-McPherson forceps.
• The orientation of the haptics is now checked to ensure
that the IOL is not ‘flipped over’.
• The leading haptic is inserted first, sliding through the
incision and all the way up to the distal capsular bag fornix.
The optic follows and an attempt should be made to place
the optic inside the bag at this very point.
• The dialler is then used to rotate the trailing haptic into
the eye, using the optic-haptic junction as a holding point.
A ball dialler (dumb-bell dialler) or a Y-hook may also be
Figs 10.4.2.18A and B: Bimanual irrigation and aspiration used for the purpose. The smaller diameter PMMA IOLs
that are used after phacoemulsification do not have dialling
holes, unlike the 6.0 or 6.5 mm larger sized IOLs.
• The movement required to place the trailing haptic into
• The anterior chamber is well filled with viscoelastic. The the bag involves dialling the haptic optic junction, and
keratome is inserted so that the plane of the blade coincides pressing it slightly downwards so that the rhexis rim slides
with the plane of the incision, otherwise one edge of the over the haptic-optic junction easily. This, of course, is
blade will cut through the anterior part of the cornea. easier said than done for the beginning surgeon, who may
• The blade is advanced slowly, using the cutting sides to find that the trailing haptic has rotated over the bag or the
enlarge the incision. Firm pressure needs to be exerted iris. In such a situation, it is better to dial it all the way to
downwards on the heel of the blade to ensure a good, the original position and reattempt the insertion.
planar cut. As the blade is advanced, counter pressure is • The surgeon should remember that the bag and its
applied with the non-dominant hand. suspensory ligaments are a flimsy system that won’t tolerate
• At the end of the enlargement, the tunnel should be about rough handling. Excessive force may cause a posterior
5.5 mm by 2.0 to 2.5 mm. capsular tear or zonular dialysis.
Implantation of Foldable IOLs Wound Closure

• As a rule, insertion of foldable IOLs is done through the • Since the wound is self sealing by design, no closure is
phaco incision without enlarging it. The anterior chamber deemed necessary.
must be adequately filled with viscoelastic prior to inserting • Hydration of the corneal stroma around the wound to
the IOL. cause closure is a common practice but not universally
• There are two main types of delivery systems, the injector supported (Fig. 10.4.2.21).12,13
based or the forceps based. • In case of any doubt as to the integrity of the wound, a
• Injector based systems ensure delivery of the IOL straight single 10–0 nylon suture ought to suffice. Tissue adhesives
to the bag without the risk of picking up contaminants like cyanocrylate and fibrin glue have also been proposed
along the way. The lens may come preloaded, or with an for use in cataract wound closure.14,15
injector assembly. The latter involves placing the IOL in • More extensive suturing may be needed if the wound
the cartridge in a certain orientation, and then loading the construction is faulty or has been sacrificed during the
cartridge into the main injector. A trained assistant may course of the surgery, or if there has been a wound burn.
do this while the surgeon prepares the capsular bag for Wound closure in young children may warrant the routine
the implantation. use of sutures even if the incisions are well-constructed.
• Another method is to use special forceps to fold and implant • At this time, there is some evidence to support the use of
the IOL. The IOL is held by the ‘folder’, which folds it intracameral cefuroxime or moxifloxacin at the end of
along the optic as its arms are brought together. The folded surgery to reduce the odds of post-operative bacterial
IOL is then transferred to a slimmer forceps called the endophthalmitis.16,17
‘holder’, which is used for placing the IOL in the bag. This
system generally requires a larger incision size as compared Specific Complications of
to the injector system (Figs 10.4.2.20 A and B). Phacoemulsification
• Foldable lens handling should be well practised on dummy A detailed description of complications of cataract surgery
lenses before the actual surgery. For any new lens model, follows later in the section. An overview is presented
even experienced surgeons are advised to take a few • Leaky wound: This jeopardizes the performance of
practice runs. phacoemulsification as the chamber will not be stable.
IOLs made of silicone are very slippery when wet and • Oarlocking: If the wound is too tight, it restricts the
cannot be held by the forceps. A silicone IOL should not movements of the phaco tip inside the eye.
be rinsed prior to implantation if a forceps implantation • Conjunctival ballooning: This may occur if the irrigating fluid
is planned. finds its way below the conjunctiva. A small nick to drain
Figs 10.4.2.20A and B: Insertion of a foldable IOL with the help of a folding forceps (A) IOL in the bag (B)
LASER CATARACT SURGERY

The allure of using LASER for cataract surgery probably owes
itself to the fact that lasers have successfully been used in
other fields of ophthalmology. Indeed, laser cataract surgery
nearly became the buzzword around the turn of the century,
but multiple factors, including the cost and the inability to
tackle even moderately hard cataracts led to its falling by the
wayside.
Both Erbium and Nd:YAG lasers were employed by two
different manufacturers.21 The basic platform mimicked the
phacoemulsification process, but the energy supplied was
optical rather than ultrasonic.
The advantages that laser systems offered over ultrasonic
phacoemulsification were
Fig. 10.4.2.21: Hydration of the corneal stroma around the • Lesser overall energy used: This point is debatable to an extent
wound to permit wound closure
because only soft cataracts were treatable by laser, and use
the fluid as soon as the problem is detected is usually for denser cataracts was associated with greater incidence
adequate. of complications.22
• Progressive miosis: This may occur as the procedure gets • No possibility of thermal wound burns: This was a real, tangible
underway because of eddy currents inside the anterior advantage.
chamber. This is not a common occurrence but can be • Better endothelial protection: This is merely a consequence of
prevented to a large extent by ensuring preoperative the lesser overall energy required.
instillation of NSAID (nonsteroidal anti-inflammatory • Rounded lip: Since the energy dissipation was not dependent
on the physical movement of the phacoprobe, a rounded
drug) eyedrops.18,19,20
• Wound burn: If phaco power is used without adequate flow tip design that was considered safer for the posterior
capsule was used.
of fluid around the phaco tip, a corneal wound burn may
result. Typically, this is caused by an inexperienced surgeon The technique was essentially the same as phacoemulsi-
fication. The laser dissipates the cataract slowly, so the
keeping the foot pedal pressed fully, even after occlusion
has stopped fluid flow. Milking of anterior chamber procedure takes longer than a similar cataract dealt with using
ultrasound.
contents is a precursor as it indicates emulsification without
fluid removal. Better technology that makes ultrasonic phacoemulsi-
fication faster, easier and safer, even for hard cataracts, has
• Intraocular damage: The phacoprobe is a powerful tool. If
misdirected, it can easily damage the iris, capsule or corneal now made laser cataract surgery virtually obsolete.
Some recent interest has been generated by the use of
endothelium.
• Nuclear drop: If the posterior capsule breaks during the femtosecond laser for anterior capsulotomy and cataract
emulsification, but it is still very early to say whether it will
procedure, nuclear pieces may drop into the vitreous cavity.
This is a very serious complication and demands herald a shift from the ultrasonic gold standard.23 Other
interesting areas where femtosecond lasers are being evaluated
intervention by a vitreoretinal surgeon. Under no
circumstances should the surgeon chase the lost fragments. include creating the main incision for cataract surgery, and
creating limbal relaxing incisions for astigmatism control.
Phacoemulsification carries a difficult learning curve with
very little scope for error. Any minor setback in any of the
INSTRUMENTATION
steps progressively magnifies, especially in inexperienced hands.
IN CATARACT SURGERY
It is extremely important to have a back up plan when initially
performing phacoemulsification. One must transgress the The tools of the trade, as one may call them, are absolutely
boundaries of one’s comfort zone in order to learn and grow, vital. They must be well maintained so that they perform their
but it must be done in a slow and controlled fashion. functions perfectly, for any defect may lead on to complications
that are totally avoidable, for instance a malfunctioning

Vannah's scissors might crush the capsule rather than cutting
it, or may cut it in an undesirable manner.
Needless to say, the operating surgeon should also be
familiar with the instruments. Not just the method of
employment, but even the physical characteristics like weight
of the instrument are important. As the surgeon performs
more surgeries with a particular set of tools, a sense of comfort
begins to develop, and this leads to better calibration of the
amount of force used. The effect is similar to sportspersons
having a favorite tennis racquet or cricket bat, for instance.
This chapter illustrates some of the key instruments in
use in modern cataract surgery, as well as some tips on how to
maintain them (Figs 10.4.2.22 to 10.4.2.49).
Fig. 10.4.2.24: Superior rectus forceps
Fig. 10.4.2.22: Artery forceps Fig. 10.4.2.25: Heat cautery
Fig. 10.4.2.23: Wire speculum Fig. 10.4.2.26: Hydrodissection canula

Fig. 10.4.2.27: Wire vectis Fig. 10.4.2.30: Utrata's forceps
Fig. 10.4.2.28: Pierce-Hoskins forceps Fig. 10.4.2.31: Suture tying forceps
Fig. 10.4.2.29: Kelman-McPherson forceps Fig. 10.4.2.32: Vannas scissors

Fig. 10.4.2.33: Needle holder Fig. 10.4.2.36: Dialler
Fig. 10.4.2.34: Blunt chopper Fig. 10.4.2.37: Round-tipped repositor
Fig. 10.4.2.35: Blunt chopper-detail Fig. 10.4.2.38: Y-hook

Fig. 10.4.2.39: Ball dialler-detail Fig. 10.4.2.42: Test chamber
Fig. 10.4.2.40: Silicone sleeve Fig. 10.4.2.43: Bimanual IA-aspiration
Fig. 10.4.2.41: Phaco tip Fig. 10.4.2.44: Bimanual IA-irrigation

Fig. 10.4.2.45: Injector Fig. 10.4.2.48: Silicone IOL folder
Fig. 10.4.2.46: Acrylic IOL holder Fig. 10.4.2.49: Silicone IOL holder
Maintenance Tips
• The instruments should be used gently, and the staff
trained to do the same.
• The instruments should be cleared immediately after
surgery, using distilled water preferably. Normal saline
or Ringer's lactate is never to be used, as these are
corrosive to the instruments.
• An ultrasonic cleaner is a good idea to remove tiny debris
that cling on to the instruments.
• Instruments with a lumen to allow fluid passage, such
as canulae, should be rinsed with distilled water and then
blown dry.
• Instruments without a lumen, such as the chopper, may
Fig. 10.4.2.47: Acrylic IOL folder be left to dry.
• Instruments that have hinges need special care. Spring 6. Marek R, Kluœ A, Pawlik R. Comparison of surgically induced
scissors should be uncoupled at the back to allow astigmatism of temporal versus superior clear corneal incisions.
Klin Oczna 2006;108(10-12):392-6.
complete extension of the limbs. A small painting brush,
7. Masket S, Belani S. Proper wound construction to prevent short-
or even a used toothbrush, can be used to clean the area term ocular hypotony after clear corneal incision cataract surgery.
near the hinge. J Cataract Refract Surg 2007;33(3):383-6.
• Corrosive liquids like those present in dish cleaners are 8. Tsorbatzoglou A, Módis L, Kertész K, Németh G, Berta A.
to be avoided. Comparison of divide and conquer and phacochop techniques
• Use of soft paraffin wax helps to remove oil-based debris during fluid-based phacoemulsification. Eur J Ophthalmol
and also lubricates the instruments. 2007;17(3):315-9.
9. Can I, Takmaz T, Cakici F, Ozgül M. Comparison of Nagahara
• Sharp instruments need to be cleaned carefully. There is phaco-chop and stop-and-chop phacoemulsification nucleotomy
risk of injury, as well as the possibility of blunting the techniques. J Cataract Refract Surg 2004;30(3):663-8.
edge or tip. 10. Vajpayee RB, Kumar A, Dada T, Titiyal JS, Sharma N, Dada VK.
• Instruments that show signs of damage like rust should Phaco-chop versus stop-and-chop nucleotomy for phaco-
be replaced at the earliest. emulsification. J Cataract Refract Surg. 2000;26(11):1638-41.
• Autoclaving takes a toll on the instrument. For this 11. Lal H, Sethi A. Manual of Phaco Technique. Text and Atlas. CBS
Publishers and Distributors. 2002;160.
reason, repeated autoclaving of instruments that are not 12. Fine IH, Hoffman RS, Packer M. Profile of clear corneal cataract
needed for a particular surgery should not be done, just incisions demonstrated by ocular coherence tomography. J Cataract
because they are in the tray. This does not mean that Refract Surg 2007;33(1):94-7.
backup instruments should not be autoclaved. 13. Vasavada AR, Praveen MR, Pandita D, Gajjar DU, Vasavada VA,
• Flash autoclaving uses higher temperatures and Vasavada VA, Raj SM, Johar K. Effect of stromal hydration of
pressures, and may be more detrimental to instruments clear corneal incisions: Quantifying ingress of trypan blue into the
anterior chamber after phacoemulsification. J Cataract Refract Surg
than regular autoclaving.
2007;33(4):623-7.
• Instruments should not be packed very tightly. This 14. Kim T, Kharod BV. Tissue adhesives in corneal cataract incisions.
increases their contact with each other, thereby increasing Curr Opin Ophthalmol 2007;18(1):39-43.
the likelihood of damage. It also decreases the efficiency 15. Banitt M, Malta JB, Soong HK, Musch DC, Mian SI. Wound
of autoclaving. Instead of packing in a piece of cloth, integrity of clear corneal incisions closed with fibrin and N-butyl-
one should opt for a tray with a silicone mat. 2-cyanoacrylate adhesives. Curr Eye Res 2009;34(8):706-10.
16. Barry P, Seal DV, Gettinby G, Lees F, Peterson M, Revie CW;
Well kept instruments last a very long time. For instruments
ESCRS Endophthalmitis Study Group. ESCRS study of
that are delicate and prone to easy misalignment, titanium is a prophylaxis of postoperative endophthalmitis after cataract surgery:
better material than steel. Specifically, the Utrata's Preliminary report of principal results from a European multicenter
capsulorrhexis forceps and the Vannah's scissors are good study. J Cataract Refract Surg 2006;32(3):407-10.
buys in titanium, although if finances are not a concern, one 17. Kowalski RP, Romanowski EG, Mah FS, Yates KA, Gordon YJ.
could always have the whole set in Titanium. Intracameral Vigamox (moxifloxacin 0.5%) is non-toxic and
effective in preventing endophthalmitis in a rabbit model. Am J
The authors/editors have no financial interest in any product/procedure mentioned Ophthalmol 2005;140(3):497-504.
in this chapter. 18. Solomon KD, Turkalj JW, Whiteside SB, Stewart JA, Apple DJ.
Topical 0.5 percent ketorolac vs 0.03 percent flurbiprofen for
REFERENCES inhibition of miosis during cataract surgery. Arch Ophthalmol
1. Zacharias J. Role of cavitation in the phacoemulsification process. 1997;115(9):1119-22.
J Cataract Refract Surg 2008;34(5):846-52. 19. Roberts CW. Comparison of diclofenac sodium and flurbiprofen
2. Packer M, Fishkind WJ, Fine IH, Seibel BS, Hoffman RS. The for inhibition of surgically induced miosis. J Cataract Refract Surg.
physics of phaco: a review. J Cataract Refract Surg 2005;31(2):424- 1996;22 Suppl 1:780-7.
31. 20. Gimbel HV. The effect of treatment with topical nonsteroidal anti-
3. Rekas M, Montés-Micó R, Krix-Jachym K, Kluœ A, Stankiewicz inflammatory drugs with and without intraoperative epinephrine
A, Ferrer-Blasco T. Comparison of torsional and longitudinal on the maintenance of mydriasis during cataract surgery.
modes using phacoemulsification parameters. J Cataract Refract Ophthalmology 1989;96(5):585-8.
Surg 2009;35(10):1719-24. 21. Aasuri MK, Basti S. Laser-assisted cataract surgery and other
4. Yao K, Ye P, Tang X, Chen P, Shen-Tu X. Clinical evaluation using emerging technologies for cataract removal. Indian J Ophthalmol
Custom Control Software technology in coaxial phacoemulsi- 1999;47(4):215-22.
fication. Clin Experiment Ophthalmol 2006;34(9):861-5. 22. Vergés C, Llevat E. Laser cataract surgery: Technique and
5. Lundström M, Wejde G, Stenevi U, Thorburn W, Montan P. clinical results. J Cataract Refract Surg 2003;29(7):1339-45.
Endophthalmitis after cataract surgery: A nationwide prospective 23. Nagy Z, Takacs A, Filkorn T, Sarayba M. Initial clinical
study evaluating incidence in relation to incision type and location. evaluation of an intraocular femtosecond laser in cataract
Ophthalmology 2007;114(5):866-70. surgery. J Refract Surg 2009;25(12):1053-60.
10.4.3 Micro-coaxial, Bimanual and

Torsional Phacoemulsification
MR Praveen, Viraj A Vasavada, Abhay R Vasavada
Cataract surgical techniques have undergone a visible change MICRO-COAXIAL (MICROINCISIONAL)

in recent times with the widespread adoption of clear corneal PHACOEMULSIFICATION
incisions for phacoemulsification. These advances have
A recent development in coaxial micro phacoemulsification,
facilitated an appreciable decrease in the size of the incision
which facilitates IOL implantation through a 2.0 to 2.2 mm
from 3.0 to 1.2 mm through which the surgery is performed.1-
4 Currently, there are two methods of micro incision cataract incision (Figs 10.4.3.2 A to C). This technique, which is referred
to as microcoaxial phacoemulsification, offers all the
surgery which are popularly used, microcoaxial
advantages of standard coaxial surgery with the added benefit
phacoemulsification and bimanual phacoemulsification.
of using a small incision.7,8 Further, it is less invasive and safer
Standard coaxial phacoemulsification requires a 2.8 to 3.2
resulting in reduced postoperative intraocular inflammation,
mm wide incision with an internal entry of approximately 1.5
fewer incision related complications, lower surgical induced
mm inside the cornea so as to insert a phaco tip with a silicone
astigmatism, and fewer possibilities of wound leakage because
sleeve through a single main valvular incision for coaxial
of its smaller size. An advantage with this approach is that
aspiration and irrigation. This silicone sleeve acts to cool the
most of the popular IOLs (including aspheric, multifocal and
tip, seals and protects the incision from thermal injury when
toric IOLs) can be implanted through this incision.
performing phacoemulsification.
Both standard coaxial and microcoaxial phaco-
emulsification allow implantation of a full size IOL through
BIMANUAL PHACOEMULSIFICATION
their respective incisions without the need to enlarge it. Further,
Bimanual phacoemulsification is performed through minute reports demonstrated that micro coaxial phacoemulsification
incisions ranging from 0.8 to 1.5 mm.5,6 In this technique
irrigation and aspiration are separated from each other. Two
paracentesis incisions ranging from 0.7 to 1.5 mm are made.
A single-plane incision (0.8–1.2 mm) is employed with an
internal entry of approximately 1.0 mm inside the clear cornea
to accommodate a bare (sleeveless) phaco tip for aspiration.
Another separate incision of similar size with 1.0 mm inside
the cornea is made to allow the insertion of a 20/21 gauge
irrigating chopper (Fig. 10.4.3.1). However, a disadvantage
with such small incision sizes is the less amount of fluid
entering the eye, which may make the chamber unstable during
surgery. Forced infusion (pressurized infusion, e.g. air pump)
has been described to overcome this problem. Another
disadvantage is that there are not many IOLs available which
can be implanted through an incision of 1.5 mm. Therefore,
after emulsification, the incision has to be enlarged to 2.00
mm or more for IOL implantation. Recently, newer rollable
Fig. 10.4.3.1: Bimanual phacoemulsification. A 1.2 mm single-plane
IOLs have been introduced, which are compatible with incision accommodates a bare (sleeveless) phaco tip for aspiration.
bimanual phacoemulsification, but experience in these IOLs Another incision of 1.4 mm allows the insertion of a 20 gauge
is limited. irrigating chopper
Figs 10.4.3.2A to C: (A) Measurement of the width of the main incision using a specially designed gauge. The 2.2 mm gauge barely
enters the external incision, tunnel and the internal incision; (B) Fragment removal using the microcoaxial phacoemulsification technique;
(C) Increase in the incision width following IOL implantation is minimal (< 0.1 mm). The 2.3 mm gauge partially enters the external
incision and the tunnel. It cannot travel the internal incision
had a very favorable intraoperative performance profile, incisions, the surgeon should be aware of, and try to minimize,
allowing safe and efficient cataract removal and yielded post incision distortion as this could jeopardize the integrity of the
operative outcomes matching those achieved with standard incision.
coaxial phacoemulsification.9 The positive findings from the From a clinical perspective, microcoaxial phacoemulsi-
data of various clinical and experimental studies confirmed fication technique involves minimal learning curve. Further it
that the microcoaxial phacoemulsification technique affords also provides favorable fluidics, stable anterior chamber and
much better fluidics which translates into safer and more stable excellent post operative outcome. A major advantage is that
anterior chambers. the surgeon does not have to compromise on the quality of
The acceptance of the bimanual phacoemulsification the IOL. Established monofocal IOLs and emerging multifocal
technique has been slow because of suboptimal fluidics, and aspheric IOLs can be implanted without enlarging the
peroperative IOP fluctuations, compromised incision integrity, incision. The technique of IOL insertion varies slightly in that
and the necessity of enlarging or adding another incision for the cartridge snugly fits at the external entry. No attempt is
IOL. Recently, reports suggested that micro coaxial made to introduce the cartridge through the internal entry into
phacoemulsification was superior with respect to fluidics, heat the anterior chamber. A spatula inserted through the sideport
generation and incision competency when compared against helps stabilize the globe while the IOL is implanted in-the-
bimanual phacoemulsification. bag. This technique is called 'wound-assisted' insertion.
One of the most critical steps in contemporary cataract The ability to avoid drastic changes in surgical technique
surgery is the creation of a clear corneal wound. Even with and also implant a time tested IOL technology atraumatically
the adoption of small-incision cataract extraction techniques through an unenlarged microincision have been elusive goals,
(standard coaxial and microcoaxial phacoemulsification and until now. This new era of microcoaxial surgery enhances
bimanual phacoemulsification technique) wound integrity patient outcomes by minimizing surgically induced
could be a concern.10 These techniques use tighter wound astigmatism, theoretically provide a potent barrier against post
geometry, which may give rise to ''oar locking'' and thus lead operative infection, and encouraging faster postoperative visual
to difficulties in intraocular manipulations. At times, such recovery.
geometry adds stress to the incision, leading to wound A comparison of bimanual and microcoaxial techniques
distortion, corneal hydration, and thermal injury. It has been of phacoemulsification is presented in Table 10.4.3.1.
suggested that poorly constructed and distorted wounds may
increase the risk of postoperative endophthalmitis. Although, TORSIONAL ULTRASOUND-A NEW
smaller wounds self-seal more easily, this is possible only if TWIST TO PHACO
wound morphology and integrity are maintained. While it is Phacoemulsification uses an ultrasonically driven tip to
enticing to perform surgery through smaller and smaller fragment the lens nucleus and to emulsify these fragments.
Table 10.4.3.1: Benefits and drawbacks of conventional, microcoaxial and bimanual phacoemulsification
Conventional / Microcoaxial Bimanual
Benefits • Good Anterior Chamber Stability • Small Incision, induces less astigmatism
• Easy IOL Implantation • Ability for maneuvering irrigation separately
• Learning Curve-Easy • Subincisional cortex removal
Drawbacks • Astigmatism • Chamber instability
• Compromised fluidics
• Enlarging the incision for IOL implantation
• Limitations in IOL technology
• Steep learning curve
Incision Integrity • Secure • Integrity compromised
• Self Sealing Incision • "OAR LOCKING" present
• Minimal Wound Distortion • Leaky incision which may require suturing
• Stromal hydration
• Corneal burn
• Descemet's tear
The latest generations of phacoemulsification machines Torsional Ultrasound

provide a variety of options utilizing advanced power
The most recent innovation in ultrasound technology is the
modulation of ultrasound energy and improved fluidic control.
torsional ultrasound (OZil, Infiniti Vision System, Alcon
These advances in technology associated with improved
Laboratories, USA).
surgical techniques have enhanced surgical performance and
outcomes. • The OZil torsional technology incorporates a new
Longitudinal (or conventional) ultrasound, involves ‘to and handpiece capable of creating rotatory ultrasound
fro’ movements of the phacoemulsification tip (Fig. 10.4.3.3). movements of the phaco needle at 32 kilohertz (KHz).
Therefore, the energy is effective only half of the time.11 In The tip oscillates laterally at 5.5 degree (2.75º on each side).
addition, the ‘to and fro’ movements of the tip cause repulsion This translates to approximately 90 microns of stroke to
of the lens fragment at the tip. Aspirating can be problematic its cutting edge. However, its incision stroke is
because it has to overcome the repulsive forces. In essence, approximately half of it, i.e. 40 microns.
reducing repulsion and facilitating aspiration is the rationale These torsional movements create a side-to-side motion
behind innovations in ultrasound technology. at the tip, which allows emulsification on both excursions, with
reduced repulsion of fragments in contrast to longitudinal
phacoemulsification. Clinically this translates into more
effective aspiration of lens substance with torsional
phacoemulsification. More efficient use of power results in
less energy and heat dissipation and lesser complications.
Efficient Cutting Ability

Using the Kelman tip with the 45 degree bevel works best
with torsional phacoemulsification. When using a torsional
handpiece and angled phacoemulsification tip, the
phacoemulsification tip oscillates and creates a side-to-side
movement, which is more marked at the distal end of the
phacoemulsification tip. The continuous side-to-side
movement in each direction is more effective at emulsifying
Fig. 10.4.3.3: To and fro movement of conventional (i.e. improved cutting efficiency). This enhanced cutting ability
phacoemulsification and lack of repulsion are clinically very important.
Fluidic Harmony and iris prolapse. With torsional phacoemulsification it is

possible to achieve these without compromising on the
Energy and aspiration work in harmony with OZil because
efficiency of the procedure.
the lens substance is not pushed away; it stays at the tip. This
In eyes with compromised corneas, the torsional
implies that clinicians can use lower aspiration flow rates and
technology allows less fluid usage, low consumption of energy,
lower bottle height. The benefit of being able to use lower
and low surgical time. This minimizes the risk of endothelial
fluid parameters is that there is reduced chance of attracting
trauma.
the posterior capsule to the phacoemulsification probe. In
In summary, torsional phacoemulsification is an improved
addition less fluid turbulence within the anterior chamber
ultrasound phacoemulsification modality with increased
offers better endothelial protection. This harmony confers the
efficacy and safety that provides intra-operative facilitation of
dual advantages of increased efficiency and intra-operative
the procedure and good post-operative outcomes with regard
safety.
to endothelial cell loss and corneal condition when compared
to the traditional modulated longitudinal ultrasound.
Lens Substance Removal
The authors/editors have no financial interest in any product/procedure mentioned
The unique side-to-side ultrasonic movement of the tip leads
in this chapter.
to constant repositioning of the lens material at the tip. This
outstanding feature of torsional phacoemulsification appears
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2. Dholakia SA, Vasavada AR, Sing R. Prospective evaluation of
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Clinically this is translated into the lens substance remaining Refract Surg 2005;31:1327-33.
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material to be sheared with both directions of stroke. surgery with a 1.4 mm incision. J Cataract Refract Surg 2001;27:934-
As there is minimal or no repulsion of fragments with 40.
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to be sufficient to achieve effective removal. It reduces intra- Phacoemulsification through a 0.9 mm corneal incision. J Cataract
Refract Surg 2001; 27:1548.
operative turbulence. The low parameters, can also allow the 5. Braga-Mele R, Liu E. Feasibility of sleeveless bimanual
surgeon to safely perform phacoemulsification in the posterior phacoemulsification with the Millennium microsurgical system. J
plane away from the endothelium. Cataract Refract Surg 2003;29:2199-2203.
To a clinician, OZil is important because it controls the 6. Fine IH, Hoffman RS, Packer M. Optimizing refractive lens
intraoperative performance and ensures clear cornea on the exchange with bimanual microincision phacoemulsification. J
first postoperative day. Cataract Refract Surg 2004;30:550.
7. Alio J, Rodriguez-Prats JL, Galal A, Ramzy M. Outcomes of
microincision cataract surgery versus coaxial phacoemulsification.
Compromised Situations Ophthalmology 2005;12:1997-2003.
8. Menucci R, Ponchietti C, Virgilli G, et al. Corneal endothelial
With dense cataracts, performing phacoemulsification in the
damage after cataract surgery: Microincision versus standard
posterior plane is most critical. Dense nuclear fragments have technique. J Cataract Refract Surg 2006;32:1351-5.
been cited as a risk factor for corneal endothelial injury. 9. Vasavada VA, Vasavada VA, Raj SM, Vasavada AR. Intraoperative
Creating a central trench is important because it acts as a recess performance and postoperative outcomes of microcoaxial
where one can bring the fragments in the posterior plane before phacoemulsification. Observational study. J Cataract Refract Surg
removal. It is possible to achieve this rapidly, without stressing 2007;33:1019-24.
the sub-incisional zonules because of the excellent cutting 10. Johar SR, Vasavada AR, Praveen MR, Pandita D, et al.
Histomorphological and immunofluorescence evaluation of
ability. Due to more efficient use of ultrasound energy, the
bimanual and coaxial phacoemulsification incisions in rabbits. J
incidence of wound site thermal injury is significantly reduced Cataract Refract Surg. 2008;34(4):670-6.
in these dense cataracts. 11. Rekas M, Montes-Mico R, Krix-Jachym K, et al. Comparison of
In eyes with a small pupil and floppy iris, lower fluidic torsional and longitudinal modes using phacoemulsification
parameters are mandatory to prevent intra-operative miosis parameters. J Cataract Refract Surg. 2009;35(10):1719-24.
Chapter 10.5
PHACOEMULSIFICATION
IN SPECIAL SITUATIONS
Suhas S Haldipurkar, Vijay Shetty
10.5.1 Hard Cataract

The hardness or brunescence of the lens is a very crucial factor In spite of these multiple factors, it is possible to achieve
in determining the technical success of cataract surgery by successful outcomes consistently by doing a thorough
phacoemulsification. Phacoemulsification in hard cataracts preoperative assessment of the cataract, a careful planning
remains a challenge to even the most experienced surgeon. and execution of the steps involved and preparing in advance
Factors to be considered (Figs 10.5.1.1A and B) for any eventuality (as in having to implant a sulcus fixated
• Compromised visibility due to poor fundal glow. IOL or AC IOL).
• Changes in the capsule, making it fragile.
SURGICAL TECHNIQUE: GENERAL
• Large nucleus size reducing maneuverability within the
CONSIDERATIONS
capsular bag.
• Capsulo-cortical adhesions making nucleus rotation Anesthesia
difficult. The surgery may be performed under topical or peribulbar
• Scarce epinucleus which makes hydrodelineation almost anesthesia and the decision entirely depends on the surgeon’s
impossible. level of comfort with either technique.
Figs 10.5.1.1A and B: Hard cataracts

Phacoemulsification in Special Situations 1029
Capsulorrhexis
A complete and adequate sized capsulorrhexis is one of the
most crucial steps. If in doubt to the size of the rhexis, it is
better to err on the side of making a large one. Poor fundal
glow makes the capsulorrhexis difficult to perform. To add to
one’s difficulties, the capsule is fragile and tears easily in any
undesired direction. In difficult cases, an endoilluminator may
be used. It is probably advisable to use a rhexis forceps to
achieve better control on the thin capsule. The use of dyes to
improve visualization has completely revolutionized the step
of capsulorrhexis. This will be discussed in more detail later
in this chapter. Using a moderate molecular weight, dispersive
viscoelastic not only facilitates an easier rhexis but also increases
the depth of an otherwise shallow anterior chamber.
Hydrodissection and Nucleus Rotation Figs 10.5.1.2A to D: Four-quadrant technique of

phacoemulsification in a hard cataract
A gentle hydrodissection is performed to loosen capsulo-
cortical adhesions and aid nucleus rotation. A slight anterior
shift in the nucleus, unlike an obvious fluid wave seen in routine chopper and the vertical chop will require use of a sharp
cases, suggests an effective separation. Hydrodelineation is chopper.
not recommended. Forceful attempts to rotate the nucleus • Even after cracking a hard nucleus, a number of bridging
should be avoided. Bimanual rotation of the nucleus is helpful fibers may connect the individual fragments. These should
if there is resistance to rotation with a single instrument. be separated meticulously, otherwise they may interfere
with further chopping by dragging a larger nuclear piece
Phacoemulsification Procedure along with the fragment that is being emulsified.
Any of the three main strategies described earlier can be used • While emulsifying the individual fragments, it is important
for the nucleotomy, but a few points specific to the hard to bear in mind that these might have sharp edges that
can perforate the posterior capsule. A number of smaller
cataract are as follows.
nuclear fragments made by repeated chopping facilitates
• The nucleus occupies a larger proportion of the cataractous phacoemulsification. Care should be taken while aspirating
lens as compared to a softer cataract, and it may not be the last nuclear piece as the epinuclear cushion is either
possible to isolate it by hydrodelineation. Therefore, very thin or even absent and there is nothing to hold back
strategies that create space are preferred. These include the posterior capsule.
the trenching techniques, i.e. the four quadrant or the stop
and chop (Figs 10.5.1.2A to D). A number of variations Cortical Aspiration
on the theme have also been described.1-3
• While performing the initial sculpting, care should be taken There is minimal cortex in hard cataracts, so cortical aspiration
to minimize stress to the capsular bag and zonules. This is can be completed quickly. At the same time, the posterior capsule
done by using adequate power, so that the phaco tip cuts is thin and utmost care must be taken to avoid tearing it.
through the nuclear material rather than pushing at it. The
CONCLUSION
vacuum and flow rate settings are kept low. A bent phaco
tip such as the Kelman tip is particularly useful in sculpting There have been a number of studies offering innovative
the depths of the nucleus. nucleus management techniques for hard cataracts. The crater-
• If one is contemplating phaco-chop, planning should be and-chop technique, for instance, advocates the creation of a
either for horizontal or vertical chop or for a combination deep central crater before tackling the peripheral nucleus, thus
of both. A horizontal chop will require use of a blunt creating space for phacoemulsification and permitting in-the-
bag nucleus management.4 Eventually, the individual surgeon 2. Kamoi K, Mochizuki M. Phaco forward-chop technique for
must choose his or her own approach to the hard cataract. managing posterior nuclear plate of hard cataract. J Cataract Refract
Surg 2010;36(1):9-12.
The ultimate outcome of phacoemulsification in hard cataracts
3. Kim HK. Decrease and conquer: Phacoemulsification technique
is comparable to that in standard cataracts. for hard nucleus cataracts. J Cataract Refract Surg 2009;35
(10):1665-70.
REFERENCES 4. Vanathi M, Vajpayee RB, Tandon R, Titiyal JS, Gupta V. Crater-
1. Vasavada A, Singh R. Step-by-step chop in situ and separation of and-chop technique for phacoemulsification of hard cataracts. J
very dense cataracts. J Cataract Refract Surg 1998;24:156-9. Cataract Refract Surg 2001;27(5):659-61.
10.5.2 White Cataract

Of the numerous challenges that mature white cataracts by Horiguchi et al,2 and trypan blue dye 0.1 percent, as reported
present to the phaco surgeon, the most significant one is by Melles et al,3 each work effectively in this regard. They are
making a capsulorrhexis. Other factors which increase the both superior to fluorescein4 which, because it is a much
difficulty are absence of the red reflex, liberation of liquid smaller molecule, diffuses into the lens and the vitreous.
cortex following perforation of the anterior capsule which Dye should be used with caution while using with
further compromises visibility and the higher intralenticular hydrophilic acrylic IOL with water content more than 70
pressure in these lenses which is prone to cause peripheral percent as this can lead to permanent staining of IOLs.5 Trypan
radial extension of the capsular tear (Figs 10.5.2.1 and 10.5.2.2). blue is not used in pregnant woman on account of its
The zonular support may be compromised in a mature or teratogenic effects.6
hypermature cataract, and while this may not present with a Clinical studies on both these capsular dyes have been
clinically obvious subluxation of the lens, it is worthwhile published. In April 1998, Horiguchi et al reported the results
keeping this in mind while performing surgery. of their technique in a prospective, randomized study of 20
Various techniques have been proposed for improving patients with mature white lenses.2 Ten patients underwent
anterior capsule visualization. Although oblique illumination1 ICG capsule staining, and the other 10 served as a control.
with a fiber optic light pipe is effective, the most reliable method Specular microscopy and laser flare-cell photometry were
is the use of a dye to stain the anterior capsule (Figs 10.5.2.3A compared and showed no statistical difference between the
and B). Indocyanine green (ICG) dye 0.5 percent, as reported two groups.
Fig. 10.5.2.1: Mature cataract Fig. 10.5.2.2: Hypermature cataract with

fibrosed anterior capsule
very colored. However, once the tear is initiated, the white

cortex creates a “white reflex” against which the stained capsule
is easily delineated.
The use of capsular dye does not eliminate other problems
posed by mature white lenses. The egress of cortical “milk”
may still impair visibility of the anterior capsule. An irrigating
cystitome has the advantage of lavaging the milky material
away, and can be used in young patients to initiate the tear
Figs 10.5.2.3A and B: Trypan blue stained anterior capsule when this problem is anticipated. If there is liquified cortex,
the resulting intralenticular fluid pressure may also cause
peripheral radial extension of the capsular tear. One must
ICG results in pale green staining of the capsule, which
optimize control of the tear by proceeding slowly, frequently
disappears by the time the case is over. One slight disadvantage
regrasping and redirecting the flap, maintaining a deep
is that the dye is lyophilized and larger particles often remain
chamber, and erring towards a smaller diameter of the
suspended in the mixture. These may appear in the anterior
capsulorrhexis.
chamber, but seem to be eliminated during the ensuing
irrigation/aspiration steps of the cataract surgery. Other considerations are:
Trypan blue results in a much darker staining and provides • The release of ‘milk’ after opening the capsule not only
superior visualization compared to ICG. Unlike ICG, there is impairs visibility, but there is higher incidence of
no particulate suspension and it is much more convenient to postoperative inflammation in these eyes, possibly because
use because there is no mixing involved. Because it is supplied of the ‘milk’ proteins which scatter throughout the anterior
in a smaller amount, it is less expensive. Finally, trypan blue chamber and are not easily removed in entirety.
staining lasts longer and usually persists throughout the entire • The use of OVDs during capsulorrhexis in white cataracts
phaco step. Without a red reflex, phacoemulsification of the is crucial to the successful completion of the rhexis. Since
nucleus is challenging even with a completed capsulorrhexis there is high intralenticular pressure in mature cataracts,
because the capsule edge cannot be seen during sculpting or high viscosity cohesive viscoelastics are needed to equalize
chopping. For this reason, dye-aided visualization of the the pressure. Using the side port to make the rhexis can
anterior capsule can decrease the risk of inadvertently cutting help to keep the anterior chamber pressurized longer.
or tearing of the capsulorrhexis edge during these However, to do this, one must be adept at using the needle
phacoemulsification maneuvers. The more intense and cystitome through the side port, or a specially designed
persistent capsular staining provided by trypan blue dye is side-port capsulorrhexis forceps that passes through the
particularly advantageous in this regard. narrow opening may be used.
An identical technique is used for staining with either dye. • The presence of a mature cataract may hide a coexistent
Through a small paracentesis, the anterior chamber is filled posterior polar cataract. Hydrodissection should be limited
with an air bubble to avoid excessive dilution of the dye. Using and cautious.
a 30-gauge cannula, several drops of dye from a 2 cc syringe • A preoperative B-scan is absolutely essential before
are placed directly onto the anterior capsule surface, which is planning surgery. Additional signs of trouble in the
stained immediately. The air is then exchanged for BSS, which posterior segment include a poorly responding pupil or
is used to irrigate the dye out of the anterior chamber. Waiting an afferent defect. These must be meticulously sought and
10 to 15 seconds to remove the dye can intensify the staining. documented.
It is important to stain the capsule before viscoelastics have • A mature cataract associated with a shallow anterior
been introduced into the eye, since they impair staining. chamber is practically a phacomorphic glaucoma waiting
Following viscoelastic placement, the capsulotomy is to happen. In such cases, early surgery should be scheduled
performed in the usual manner. The use of a cohesive and mydriate evaluation should be reserved for the day of
viscoelastic is especially useful in this situation. No special surgery, dilating the pupil as close to the planned surgery
illumination is needed. At first the capsule may not appear time as possible.
REFERENCES 4. Fritz WL. Fluorescein blue, light-assisted capsulorrhexis for

mature or hypermature cataract. J Cataract Refract Surg 1998;
1. Bhattacharjee K, Bhattacharjee H, Goswami BJ, Sarma P.
Capsulorrhexis in intumescent cataract. J Cataract Refract Surg. 24(1):19-20.
1999;25(8):1045-7. 5. Ozbek Z, Saatci AO, Durak I, Gunenc U, Ergin MH, Cingil G.
2. Horiguchi M, Miyake K, Ohta I, Ito Y. Staining of the lens capsule Staining of intraocular lenses with various dyes: A study of digital
for circular continuous capsulorrhexis in eyes with white cataract. image analysis. Ophthalmologica 2004;218(4):243-7.
Arch Ophthalmol 1998;116(4):535-7. 6. Schmidt W, Sandor S, Checiu I, Stefãnescu S, Havlik I, Sere I,
3. Melles GR, de Waard PW, Pameyer JH, Houdijn Beekhuis W. Trypan Checiu M, Fazakas-Todea I, Eremia I. On the prenatal noxious
blue capsule staining to visualize the capsulorrhexis in cataract effects of trypan blue and of a related azo dye. Rom J Morphol
surgery. J Cataract Refract Surg 1999;25(1):7-9. Embryol 1991;37(1-2):31-9.
10.5.3 Small Pupil Phacoemulsification

A small pupil can be a big problem for the cataract surgeon. By is associated with floppy iris.1 It is discussed in detail later
definition, a small pupil is one which does not dilate adequately in this chapter.
in response to conventional mydriatics. The size of the pupil is
variable, but generally speaking, if it is less than 5 mm, then it PROBLEMS POSED BY THE SMALL PUPIL
poses a difficulty for the surgeon (Fig. 10.5.3.1)
The small pupil poses diagnostic problems at the outset. It is
difficult to assess the cataract, the presence of any subluxation,
CAUSES OF SMALL PUPIL
and whether or not a posterior polar cataract is present. In
These include: addition, fundus evaluation is compromised.
• Chronic iritis. During surgery, a small pupil does not pose any problems
• Prior glaucoma, pilocarpine therapy or trabeculectomy. if steps are taken to ensure mechanical mydriasis, as described
• Pseudoexfoliation syndrome. later. However, if the surgeon proceeds with a small pupil,
• Diabetes mellitus. then there are many potential pitfalls. The following points
• Post-traumatic synechiae. need to be considered.
• Idiopathic. • There is a tendency for iris prolapse. A tunnel that extends
• Tamsulosin use for benign prostatic hypertrophy. This is further into the cornea than usual helps prevent this.
a special situation where progressive intraoperative miosis • There is greater likelihood of catching the iris in the phaco
tip.
• The capsulorrhexis is either compromised for size, or the
surgeon has to make the rhexis underneath the iris, with
the attendant risk of losing control altogether. If the
cataract is mature, the trypan blue stain will only color the
exposed capsule, which can sometimes be a greater
hindrance than an entirely unstained capsule.
• Adequate hydrodissection and hydrodelineation should be
ensured, so that the nucleus is freely rotating before the
phacoemulsification commences.
• It is difficult to make a trench of adequate length in the
presence of a small pupil. It is better to go for direct chop,
or stop and chop procedure. It is preferable to use an angled
Kelman tip if the stop and chop technique is used. A short
deep trench is made. The Kelman tip is invaluable in
sculpting cataract especially when the small pupil hides
Fig. 10.5.3.1: Small pupil the hard cataract.
• Vertical chop is preferred over horizontal chop in small pupil inserted through side ports. The pupil is engaged 180 degree
surgery. Horizontal chop requires the placement of the apart, and the hooks are moved outwards towards the limbus,
chopper beyond the equator of the nucleus which is difficult thus stretching the pupil. The stretching is then repeated at
in a small pupil. Care has to be taken while chopping as one right angles to the original stretch. This procedure, however,
can inadvertently nick the hidden rhexis margin. All causes sphincteric tears and a slightly deformed pupil
manipulations of the nuclear fragments and the epinuclear postoperatively. A similar procedure is to cut the pupillary edge
plate should be done by the second instrument. using the Vannah’s scissors, thereby creating multiple small
• Bimanual irrigation aspiration is preferred over coaxial as sphincterotomies. The disadvantage of somewhat distorted
it gives better access and control. While aspirating the pupil postoperatively is offset by the advantage of better access
cortical matter, pull on the capsular bag is to be avoided. to the retina for any further interventions, e.g. panretinal
An accidental dialysis gets hidden by the iris and may be photocoagulation in a diabetic patient.
obvious only at an advanced stage.
• Prior to inserting the IOL, the anterior chamber and Iris Hooks
capsular bag must be filled with viscoelastic. It is difficult
Four iris hooks are inserted through four limbal paracentesis
to shift the IOL from the sulcus to the bag in the presence
incisions, placed at a gap of three clock-hours from each other
of a small pupil, so one should go slowly, carefully, and
(Fig. 10.5.3.2). These provide adequate exposure during
aim to place the IOL in the bag directly. The IOL is inserted
capsulorrhexis and phacoemulsification. At times tenting up
with the leading haptic touching down on the posterior
of the iris by iris hooks towards the cornea creates a hinderance
capsule, and then sliding it into the bag fornix. Next, the
to the insertion of instruments into the anterior chamber. This
trailing haptic is dipped posteriorly, sliding under the
occurs if the iris-hook incisions are corneal rather than limbal.
anterior capsulorrhexis margin with a Y-hook.
The decision to place iris hooks or to perform stretch
• Finally, at the end of the surgery, a Y-hook should be used
pupilloplasty or multiple sphincterotomies needs to be taken
to manually push back the iris in all regions to confirm the
before capsulorrhexis is done, otherwise one risks catching
IOL placement, and to make sure no nuclear fragments
the rhexis edge along with the iris.
are hiding behind the iris.
Malyugin Ring
MECHANICAL MYDRIASIS TO
TACKLE THE SMALL PUPIL The disposable Malyugin pupil expansion device is a foldable
square made of 5-0 polypropylene with a coiled scroll at each
The problems posed by the small pupil vanish if one uses any
of the four corners. A special holding platform contains the
of a variety of strategies to mechanically dilate the pupil.
unfolded square shaped Malyugin device. The injector tip fits
There are various devices designed to stretch the pupil
into the docking port of the holding platform and a sliding
during surgery.
• Use of viscoelastic (viscomydriasis)
• Stretch pupilloplasty (using instruments like Y-hooks,
Sinskey’s hook, etc.)
• Use of devices like the iris hooks, or the Malyugin ring (to
keep the pupil stretched during surgery)2,3
Viscomydriasis
High viscosity viscoelastic like Healon can dilate the pupil
mechanically and help the surgeon proceed with the surgery.
One needs to use low parameters during phacoemulsification
to slow down the aspiration of viscoelastic. The mydriasis is
obviously temporary and limited in nature.
Pupilloplasty
Stretch pupilloplasty using two Y-hooks is an easy and an
effective method of dilating the pupil.4 Two Y-hooks are Fig. 10.5.3.2: Placement of iris hooks
of sufficient OVD, is positioned over the anterior lens capsule

in the center of the pupil. There is no need for extra
paracentesis incisions. (Figs. 10.5.3.3A to D). Once the surgery
is over, the ring is easily removed through the same incision.
Other considerations are:
Touching the iris may be very uncomfortable for the patient
despite adequate intracameral lidocaine. The surgeon should
either use a peribulbar block, or keep the iris manipulation to
a minimum.
By the nature of its underlying etiology, as well as the need
for iris manipulation, a higher incidence of post operative
inflammation is anticipated in small pupil surgeries, particularly
the tendency for membrane formation. This is managed in
most of the cases by frequent use of topical steroids, NSAIDs
and cycloplegic eye drops. Occasionally, systemic steroids are
needed. Subconjunctival atropine after surgery can be very
helpful to keep the pupil at least semi-dilated, reducing the
inflammatory response.
REFERENCES
Figs 10.5.3.3A to D : Insertion of Malyugin Ring 1. Chang DF, Campbell JR. Intraoperative floppy iris syndrome
for pupil expansion associated with tamsulosin. J Cataract Refract Surg 2005;31(4):664-
73.
2. Malyugin B. Small pupil phaco surgery: a new technique. Ann
tab on the injector handle is used to manually extend a blunt Ophthalmol (Skokie) 2007;39(3):185-93.
3. Nichamin LD. Enlarging the pupil for cataract extraction using
hook from the distal tip. As the hook is retracted, it grasps the
flexible nylon iris retractors. J Cataract Refract Surg 1993;19(6):793-
proximal scroll and pulls the flexible device into the injector 6.
shaft The tip of the injector is then introduced through a 4. Fine IH. Pupilloplasty for small pupil phacoemulsification. J
phaco incision measuring at least 2.2 mm and, in the presence Cataract Refract Surg. 1994;20(2):192-6.
10.5.4 Phacoemulsification in Intraoperative

Floppy Iris Syndrome
Intraoperative floppy iris syndrome (IFIS) is a condition that • Marked propensity for the iris to prolapse to the phaco
most cataract surgeons have encountered. IFIS has a spectrum and side port incisions.
of severity ranging from a normal iris response to an atonic • Progressive pupillary constriction during surgery.
iris that dilates extremely poorly and billows and prolapses IFIS has been associated with the use of systemic alpha-
during surgery (Figs 10.5.4.1A and B). antagonists in general and Tamsulosin (used for benign
The IFIS has been defined according to a triad of signs2 prostatic hypertrophy) in particular.1,2 The alpha-1A receptor
• Floppy iris that billows in response to normal irrigation subtype seems a likely focus of action since this is the one
currents in the anterior chamber. that Flomax targets with high affinity and specificity. This
maneuver, and may or may not be successful in all cases of

IFIS.
Iris hooks and pupil expanders: These devices are effective means
of reliably enlarging the pupil and keeping it large. In addition,
they also stabilize the iris. Iris hooks can be difficult and time
consuming to insert and remove, and may also create an
irregularly shaped pupil that is often tented anteriorly toward
Figs 10.5.4.1A and B: (A) Iris knuckle prolapsing from the the cornea, especially in inexperienced hands. There is also
corneal wound; (B) Billowing of the iris intraoperatively the risk of endothelial damage. They also require the creation
of four paracentesis wounds, which added to two side-port
subtype appears to be the predominant subtype in iris dilator incisions and one main tunnel can be a bit overwhelming, but
muscle as well. It is postulated that iris billowing and propensity since these openings do not see much manipulation, they heal
to prolapse result from lack of tone in the dilator smooth quite nicely.
muscle. Alternatively, pupil expansion rings such as the Malyugin
Interestingly, discontinuation of tamsulosin therapy several device can be used to dilate the pupil. These do not require
months before the proposed intraocular intervention appears to additional corneal openings, but can be significantly more
have only a minor impact on the incidence of IFIS. Several patients expensive.
have IFIS even though they had stopped tamsulosin intake more Use of mechanical devices to enlarge the pupil is the most
than a year before the eye surgery, while others demonstrated a reliable and effective technique to manage small pupils in
somewhat better preoperative pupillary dilatation. This persistence general and IFIS in particular. Since the pupil has a tendency
of IFIS in the absence of ongoing tamsulosin is believed to be to shrink as surgery progresses, preoperative dilatation should
due to muscular atrophy and loss of tone.3 not be used as a benchmark in patients with known tamsulosin
use, or with a history of IFIS in the other eye. This is an
MANAGEMENT important point because it is more difficult and risky to place
Various techniques for handling IFIS have been proposed at pupil expansion devices after the CCC has been completed. It
different times. Some of the approaches tried include the is best to anticipate IFIS and use the pupil expansion aid right
following. at the outset.
Atropine: Atropine bid or tid for one to three days prior to REFERENCES
surgery may be helpful to achieve better dilation if it is noted 1. Chang DF, Campbell JR. Intraoperative floppy iris syndrome
that the pupil dilates poorly during the initial examination.4 associated with tamsulosin. J Cataract Refract Surg 2005;31(4):664-
73.
Epinephrine: Intracameral sulfite-free, preservative-free 2. Takmaz T, Can I. Clinical features, complications, and incidence
epinephrine may also help to further dilate the pupil.5 of intraoperative floppy iris syndrome in patients taking tamsulosin.
Viscoadaptive OVD: Healon 5 works very well to enlarge the Eur J Ophthalmol 2007;17(6):909-13.
3. Prata TS, Palmiero PM, Angelilli A, Sbeity Z, De Moraes CG,
pupil and stabilize the iris, but care must be used during
Liebmann JM, Ritch R. Iris morphologic changes related to
hydrodissection and phacoemulsification to prevent blowing alpha(1)-adrenergic receptor antagonists implications for
out the posterior capsule and creating a wound burn, intraoperative floppy iris syndrome. Ophthalmology 2009;
respectively. Surgeons must use low aspiration flow and 116(5):877-81.
vacuum settings (e.g. less than 22 mL/min and less than 200 4. Bendel RE, Phillips MB. Preoperative use of atropine to prevent
mm Hg respectively) to delay the viscoelastic's evacuation from intraoperative floppy-iris syndrome in patients taking tamsulosin.
the anterior chamber. Compared with expansion devices, usage J Cataract Refract Surg 2006;32(10):1603-5.
5. Liou SW, Yang CY. The effect of intracameral adrenaline infusion
of Healon 5 in this manner is more dependent upon surgical
on pupil size, pulse rate, and blood pressure during
technique and fluidic parameters, and is most effective when phacoemulsification. J Ocul Pharmacol Ther. 1998;14(4):357-61.
the preoperative pupillary diameter is reasonably large. 6. Arshinoff SA. Modified SST-USST for tamsulosin-associated
A layered viscoelastic shell has been described, which is intraoperative [corrected] floppy-iris syndrome. J Cataract Refract
meant to keep the pupil dilated in IFIS.6 This is a tricky Surg 2006;32(4):559-61.
10.5.5 Phacoemulsification
in the Diabetic Patient
PROBLEMS POSED BY THE operatively and the procedure is completed in the first week
DIABETIC CATARACT following cataract surgery. Pan-retinal photocoagulation is
advisable in patients with proliferative diabetic retinopathy
• Corneal epithelial and endothelial abnormalities.
(PDR) before cataract surgery.
• Rigid pupil with inadequate pupillary dilatation (Fig.
10.5.5.1). CONSIDERATIONS WHILE
• Compromised blood aqueous barrier. PERFORMING SURGERY
• Presence of diabetic retinopathy.
• Diabetic cataracts are usually harder and have more Preoperative Considerations
tenacious fiber structure than non-diabetic cataracts.
• Reduced immunity raises the odds of postoperative Good control of diabetes is essential prior to planned surgery.
bacterial endophthalmitis. Consultation with the diabetologist regarding any modification
• Comorbid conditions like glaucoma add extra factors to to the anti-diabetic therapy should be done well in advance.
Measurement of glycosylated hemoglobin gives an estimate
be considered.
of the glycemic control over the past three months, and is a
ROLE OF DIABETIC RETINOPATHY better indicator than blood sugar levels in isolation.
Modern cataract surgery seems to have less influence on the Capsulorrhexis

progression of diabetic retinopathy. Visual improvement is
Larger rhexis (5.5–6.0 mm) is planned, to allow easy
achieved in majority of patients with nonproliferative diabetic
visualization of the posterior segment postoperatively.
retinopathy (NPDR), but poorer visual outcome is observed
in patients developing macular edema.1 Focal laser should be
Phacoemulsification
done in clinically significant macular edema (CSME) before
cataract surgery (Fig. 10.5.5.2). If complete treatment is not Phacoemulsification is done using low parameters preferably
possible due to media opacity then partial laser is applied pre- under low illumination and filter to avoid phototoxic damage
Fig. 10.5.5.1: Inadequately dilated rigid pupil Fig. 10.5.5.2: Clinically significant macular edema
Special Points
The epithelium is more prone to disruption by surgical
instruments as compared to the epithelium in non-diabetic
patients, therefore extra care should be taken while introducing
instruments into the anterior chamber.3
ALTERNATE PROCEDURES
• In case of high risk PDR with vitreous hemorrhage and
cataracts, a pars plana lensectomy, vitrectomy, endolaser,
and an IOL implant should be considered.
• In cases of neovascular glaucoma with high IOP and
cataract, pan retinal photocoagulation and cryo-ablation
is recommended prior to cataract surgery. Also, glaucoma
shunt procedure at the time of the cataract surgery should
Fig. 10.5.5.3: Anterior capsular polishing decreases the chances
of PCO (Courtesy: Dr Saurabh Sawhney)
be considered. Recently, anti-vascular endothelial growth
factor (anti-VEGF) drugs like bevacizumab have been used
intracamerally in neovascular glaucoma before pan retinal
to the unhealthy macula. Any of the standard phaco- photocoagulation and filtering surgery with success.4
emulsification techniques can be used to remove the cataract. • If pupil dilation yields inadequate visualization, converting
Chopping technique may be preferred over nuclear fractis to an extraction technique should be considered.
technique to minimize phaco energy transmitted to corneal Conversion, may be considered particularly in cases of
endothelium. dense nuclear sclerosis and pseudoexfoliation in which
there is an increased risk of capsular disruption.
Cortical Aspiration All factors considered, phacoemulsification with a foldable
acrylic IOL remains the procedure of choice as it provides a
Thorough cortical clean-up should be performed after small wound, a large IOL and spares the superior conjunctiva
phacoemulsification. Careful polishing of posterior capsule for filtering procedures later, if required.
and undersurface of the anterior capsular rim also helps to
prevent posterior capsular opacity (PCO) (Fig. 10.5.5.3). REFERENCES
1. Krepler K, Biowski R, Schrey S, Jandrasits K, Wedrich A. Cataract
IOL Implantation surgery in patients with diabetic retinopathy: visual outcome,
A foldable acrylic or PMMA Intraocular Lens (IOL) with at progression of diabetic retinopathy, and incidence of diabetic macular
edema. Graefes Arch Clin Exp Ophthalmol 2002;240(9):735-8.
least a 6.0 mm optic or larger is preferable for diabetic eyes. 2. Senn P, Schmid MK, Schipper I, Hendrickson P. Interaction
Silicon IOLs are not a good choice if the patient is likely to between silicone oil and silicone intraocular lenses: an in vitro study.
undergo an air fluid exchange (due to condensation) or require Ophthalmic Surg Lasers 1997;28(9):776-9.
a vitreous substitute such as silicon oil (due to irreversible 3. Azar DT, Spurr-Michaud SJ, Tisdale AS, Gipson IK. Altered
silicon oil adhesion to the silicon IOL).2 In general, foldable epithelial-basement membrane interactions in diabetic corneas.
Arch Ophthalmol 1992;110(4):537-40.
IOLs are preferred, as they offer larger optic diameter, suitable 4. Duch S, Buchacra O, Milla E, Andreu D, Tellez J. Intracameral
for later fundus evaluation, in conjunction with smaller incision bevacizumab for neovascular glaucoma: A pilot study in 6 patients.
that heals quickly and is less liable to cause endophthalmitis. J of Glaucoma 2009; 18(2):140-43.
10.5.6 Phacoemulsification in
Posterior Polar Cataract
Posterior polar cataracts are relatively uncommon, yet they CLASSIFICATION OF POSTERIOR
pose a significant challenge to the cataract surgeon. The main POLAR CATARACTS
surgical concern is the presence of a posterior capsular plaque,
which is often associated with a delicate posterior capsule that Type 1: Opacity associated with posterior subcapsular cataract.
does not stand up very well to the usual stresses of cataract Type 2: Opacity with ringed appearance like an onion.
surgery. At times, there may be an actual deficiency of the Type 3: Opacity with dense white spots at the edge often
capsule in the region. The obvious risk is that of loss of nuclear associated with thin or absent posterior capsule.
fragments to the vitreous space.
Type 4: Combination of the above three types with nuclear
The incidence of posterior polar cataract is 5 in 1000.1
sclerosis.
Cataract surgery in these cases is frequently accompanied by
a high incidence of posterior capsule rupture (PCR). Osher (Reproduced from Phacoemulsification of posterior polar cataract, Lee
et al2 have reported an incidence of PCR of 26 percent while MV, Lee YC (Au), British Journal of Ophthalmology 2003, Volume
Vasavada et al3 has reported a 36 percent incidence of PCR 87 (11), page 1426-7, copyright notice January 2011 with permission
in posterior polar cataracts. Hayashi et al reported a 7.1 from BMJ Publishing Group Ltd.)
percent incidence of PCR.4
SURGICAL PROCEDURE IN
MORPHOLOGY POSTERIOR POLAR CATARACT
Posterior polar cataracts are associated with remnants of the
hyaloid system or the tunica vasculosa lentis. These cataracts Anesthesia
may also occur without any relation to hyaloid remnants and
Peribulbar block is the preferred method of anesthesia in these
appear as circular or rosette shaped opacities (Fig. 10.5.6.1).
patients.
They are hereditary and usually transmitted as a dominant
trait. The gene for this has been mapped to chromosome Capsulorrhexis
16q22.5
The morphology of posterior polar cataract as noticed The capsulorrhexis should be round, central and about 5.0
on slit lamp examination can be typified into one of the mm in diameter. These are precautions needed to ensure good
following four forms.1 posterior chamber IOL placement by capturing the optic and
leaving the haptics in the sulcus in the event of a PCR.
However, if the cataract is dense, a larger rhexis should be
aimed for. This allows easier emulsification without undue
stress on the weakened posterior capsule. Since the anterior
capsule may remain the only viable support for the lens, all
efforts must be made to secure a continuous curvilinear
capsulorrhexis.
Hydroprocedures
Hydrodissection is best avoided in such cataracts, as the fluid
wave generates pressure within the bag and may cause the
entire contents of the capsular bag to drop into the vitreous.
In case this unfortunate event does come to pass, pars plana
vitrectomy and nucleus removal by a trained vitreoretinal
Fig. 10.5.6.1: Posterior polar cataract surgeon is required.
Careful hydrodelineation can and should be attempted. dispersive viscoelastic should be injected over the defect to
Since the plaque is posteriorly located, hydrodelineation serves tamponade and push the vitreous face backwards. A dispersive
to separate the inner layers from the outer ones, effectively rather than a cohesive viscoelastic is preferable as it is more
isolating the plaque. In this way, the plaque can be handled at adapted to maintaining space and stabilizing the anterior
a much later stage of the surgery. vitreous face.1 If there is posterior capsular rent (PCR) with
One has to make sure that the hydrodelineation wave passes vitreous loss, a two port anterior vitrectomy is performed.
above the plaque. This is ensured by gently burrowing the Intraocular lens implantation in these cases would depend on
canula tip into the soft cortex before the injection is made. the extent of the PCR and the integrity of the remaining PC.
For harder cataracts where such burrowing is not feasible, In case of small central posterior capsule rent, the IOL is
inside out hydrodelineation avoids inadvertent hydro- placed in the bag. In case of a large posterior capsular defect,
dissection.6 A groove is made with the phaco probe and the IOL is placed in the sulcus.
hydrodissection is done starting deep inside the groove. Placement of a silicone IOL is generally avoided since these
Rotation of the nucleus should be avoided. unfold with some force, and the process may break the
posterior capsule. Since the capsule is weaker than usual,
Phacoemulsification polishing is avoided. It is better to opt for a YAG capsulotomy
later, if required.
Low vacuum, low aspiration and low inflow parameters ensure
It is important that the surgeon and the patient understand
a more stable anterior chamber. Cracking of the nucleus in
the technical difficulties associated and are aware of potential
the bag should be avoided as far as possible. The most effective
complications. With emphasis on gentleness, together with
strategy for dealing with the nucleus in the presence of
patience and a well practiced technique, the incidence of PCR
posterior polar cataract is to impale the nucleus with the
can be minimized in phacoemulsification for posterior polar
phacoprobe, lift it slightly and then proceed with a direct chop.
cataracts.1
This avoids stress on the posterior capsule.
Various techniques of nucleus and cortex management REFERENCES
have been described in literature. The Lambda technique
involves trenching in the shape of a Lambda or 'Y' to produce 1. Lee MV, Lee YC. Phacoemulsification of posterior polar cataracts-
a surgical challenge. Br J Ophthalmol 2003;87(11): 1426-7.
a three-pronged trench, which has been found to be useful to
2. Osher RH, Yu BC, Koch DD. Posterior polar cataracts: A
minimize stress on the capsular bag.1 Another approach is predisposition to intraoperative posterior capsular rupture. J
that of 'Layer by Layer' phacoemulsification, advocated for Cataract Refract Surg 1990;16(2):157-62.
posterior polar cataracts with established, pre-existing posterior 3. Vasavada A, Singh R. Phacoemulsification in eyes with posterior
capsular defect.7 polar cataract. J Cataract Refract Surg 1999;25(2):238-45.
4. Hayashi K, Hayashi H, Nakao F, Hayashi F. Outcomes of surgery
The cortical clean-up requires more diligence than in
for posterior polar cataract. J Cataract Refract Surg 2003;29(1):
routine case. It is important to be very cautious while peeling 45-9.
the cortex away from the periphery towards the center. Any 5. Finzi S, Li Y, Mitchell TN, Farr A, Maumenee IH, Sallum JM,
resistance should be respected and left to be dealt with later. Sundin O. Posterior polar cataract: genetic analysis of a large family.
The central part of the posterior capsule should not be Ophthalmic Genet. 2005;26(3):125-30.
touched, for even a slight contact may cause a tear. 6. Vasavada AR, Raj SM. Inside-out delineation. J Cataract Refract
Surg 2004;30(6):1167-9.
The status of the posterior capsule (PC) should dictate
7. Vajpayee RB, Sinha R, Singhvi A, Sharma N, Titiyal JS, Tandon R.
the action of the surgeon. Care should be taken to avoid 'Layer by layer' phacoemulsification in posterior polar cataract
chamber collapse or shallowing during change of instruments. with pre-existing posterior capsular rent. Eye (Lond) 2008;22(8):
If the PC is absent or torn but with no vitreous loss, a 1008-10.
10.5.7 Phacoemulsification
in the Subluxated Lens
Zonular weakness presents a serious challenge during cataract should be modified from the routine cataract consent and
surgery. Zonular compromise may be congenital, iatrogenic, should specifically include consent for placement of a capsular
post-traumatic, or associated with diseases like pseudo- tension ring (CTR) and suture fixated posterior chamber IOL.
exfoliation. Incidence of intraoperative complications like
vitreous loss, posterior capsular rupture, nucleus subluxation, CAPSULAR TENSION RING
and postoperative complications like decentration of the IOL
is higher in such cases. Introduction of the CTR has revolutionized the approach to
zonular dialysis. These PMMA rings can be inserted into the
PREOPERATIVE EVALUATION capsular bag at any point after capsulorrhexis, and the rest of
the surgery is done with an expanded and stabilized bag.2,3
A comprehensive preoperative evaluation helps the surgeon The CTR has limited utility in cases with extensive zonular
to anticipate the challenges to be dealt in the operating room. weakness and in pathology leading to progressive weakening
An assessment of the best corrected visual acuity for near of the zonules after the surgery.4 Modified CTR designed by
and distance should be determined. The surgeon should Dr Robert Cionni incorporates a unique fixation hook to
characterize and draw the zonular defect describing the provide scleral fixation.5
weakness in terms of clock-hours involved, location of the
defect, and presence or absence of vitreous in the anterior
Indications of CTR
segment (Figs 10.5.7.1A and B). Phacodonesis is better
appreciated in undilated pupil as dilatation stabilizes the ciliary • Cataract with zonular weakness.
body and iris and dampens the lens movement. Several subtle • Subluxated cataract.
signs point to a subluxation and should be specifically sought.1 • Progressive subluxation of the crystalline lens with
The presence or absence of additional ocular pathology must frequent change in refraction and anisometropia.
be taken into consideration and the patient counseled • Subluxated crystalline lens with excessive movement of
accordingly. Many patients with Marfan syndrome have the lens with intermittent phakic and aphakic visual axis.
significant systemic problems, which increase the risk of death • Clear lens with significant subluxation in a child where
or morbidity. The patient must be evaluated by the primary amblyopia cannot be treated with conventional means like
physician and cardiologist before surgery. Informed consent glasses, contact lenses and/or patching.
Figs 10.5.7.1A and B: Subluxation of the crystalline lens

The size of the CTR that is to used, follows certain in the earlier stages of surgery. Later on, when the bag is
guidelines, as indicated below. cleared of the lens material, the conventional or Cionni's
ring may be substituted (Fig. 10.5.7.2). Capsule hooks can
Design Specifications of be used to hold the rhexis rim, to support the capsular
Capsular Support Systems bag.
• Morcher capsular tension rings are available in three sizes.
– Size 14, which is 12.30 mm when open and compresses ANESTHESIA
to 10.0 mm. This size is recommended for eyes with Peribulbar block is preferred over topical anesthesia due to
axial length less than 24 mm the complicated nature of these cases. Massage of the globe
– Size 14A, which is 14.5 mm/12.0 mm, and is after the block is avoided, as it may further compromise zonular
recommended for use in myopic eyes with axial length integrity.
of greater than 28 mm
– Size 14C, which is 13.0 mm/11.0 mm, and used for PROCEDURE
eyes with axial length between 24 mm and 28 mm.
These rings may be inserted using a Kelman-McPherson The surgeon should make an attempt to place the main incision
forceps, or a disposable Geuder capsular tension ring away from the axis of zonular weakness. The surgeon should
injector which is commercially available. The EyeJet is the work with the smallest possible incision without compromising
preloaded version, and it is available separately for his ability to perform necessary maneuvers. A smaller incision
clockwise and anticlockwise emergence of the CTR. It is reduces fluid egress through the incision and therefore helps
important for the surgeon to be very gentle when inserting to limit the anterior chamber collapse.
these devices, or risk further zonular damage. The ring Capsulorrhexis should be initiated in an area away from
should never be placed in the presence of a torn rhexis or zonular weakness. A second blunt instrument like iris spatula
a posterior capsular deficit. may be used for counter traction if there is significant zonular
weakness. A forceps rhexis might be easier to perform and
• The Cionni rings have additional eyelets that allow scleral
control as compared to a needle rhexis. The capsulotomy
fixation of the whole ring, thereby attaching the capsular
should be large (5.5–6.0 mm).
bag to the sclera. The additional eyelet is placed slightly
The decision whether to insert CTR or Cionni's ring, or
above the plane of the ring, and is positioned just to the
to use disposable iris retractors to support the rhexis edge,
right or left of the deficient area of the CTR, a variation
can be taken depending upon the condition of the zonules as
that can be chosen by the surgeon. There is also a double
noted on the operating table. The supporting devices may be
eyelet Cionni ring that allows scleral fixation at two points.
placed at this point of time, or a little later in surgery, depending
• The Henderson ring is a design innovation that features
upon the extent of the zonular compromise.
eight equally spaced indentations spanning the
circumference of the ring creating a sinusoidal shape. This
prevents trapping of the lens material between the ring
and the equator of the lens. The ring may be rotated to
allow a 360° access.
• The Ahmed capsular tension segment (CTS) is a modified
design of the Cionni capsular tension rings, comprising
an arc of clear PMMA, with an eyelet for scleral fixation.
It usually covers about one quadrant. Since it is a smaller
device than the CTR, it may be placed with lesser trauma,
and earlier on during the course of the surgery. It is
available in two sizes, type 6D, which is 9.61 mm, and type
6E, which is 10.16 mm.
• Iris hooks that are used to mechanically dilate the pupil
may also be tucked under the rhexis rim to provide
temporary support to the capsular bag, especially valuable Fig. 10.5.7.2: Use of iris hooks and Cionni's ring
After hydrodissection and delineation, phacoemulsification tightened to achieve the centration of the bag. The PCIOL is
is performed with low bottle height, low aspiration flow rate then inserted into the bag. Anterior vitrectomy is performed
and low vacuum. The nucleus should be well separated from if required, and the conjunctival wound is closed.
the epinucleus and cortex in order to avoid undue zonular
strain. Care should be taken to minimize movement of the CONCLUSION
nucleus while sculpting, with the emphasis on cutting through
the nucleus, even if that involves a somewhat higher power Capsular tension ring (CTR) or Cionni's ring aids in-the-bag
setting. If a direct chop is used, the nucleus is lifted clear of placement of IOL in the most challenging situations, with
the posterior capsule and then chop. At no point of time good postoperative visual recovery. However, in extreme
should downward force be used, as this transmits to the cases, scleral fixated IOL, retro-fixated iris claw IOL or
posterior capsule, and from there to the zonules. ACIOL may be required.
Before introduction of the CTR, the surgeon should place The authors/editors have no financial interest in any procedure/product mentioned
viscoelastic just under the surface of residual capsular rim to in this chapter.
create a space for the CTR and to dissect the residual cortex
away from the peripheral capsule, making cortical entrapment REFERENCES
by the CTR less likely. Insertion of Cionni's ring begins by 1. Marques DM, Marques FF, Osher RH. Subtle signs of zonular
preplacing a double armed 9-0 prolene suture through the damage. J Cataract Refract Surg 2004;30(6):1295-9.
eyelet of the fixation hook. Cionni's ring can be introduced 2. Gimbel HV, Sun R. Clinical applications of capsular tension rings
with forceps and guided into the bag with a Y hook. The in cataract surgery. Ophthalmic Surg Lasers 2002;33(1):44-53.
needles are placed through the incision into the pupil, and 3. Tribus C, Alge CS, Haritoglou C, Lackerbauer C, Kampik A, Mueller
behind the iris. The needle and suture should remain anterior A, Priglinger SG. Indications and clinical outcome of capsular
to the capsule at all times. This needle is passed through the tension ring (CTR) implantation: A review of 9528 cataract
surgeries. Clin Ophthalmol 2007;1(1):65-9.
scleral wall at the site of maximum weakness. The needle
4. Gimbel HV, Condon GP, Kohnen T, Olson RJ, Halkiadakis I. Late
should exit the scleral wall approximately 1.5 mm posterior to in-the-bag intraocular lens dislocation: Incidence, prevention, and
the corneoscleral junction. This position the fixation management. J Cataract Refract Surg 2005;31(11):2193-204.
posteriorly enough to prevent post operative iris chaffing. The 5. Cionni RJ, Osher RH. Management of profound zonular dialysis
needle can either be passed several times through partial or weakness with a new endocapsular ring designed for scleral
thickness sclera or be tied under a flap. Suture loops are fixation. J Cataract Refract Surg 1998;24(10):1299-306.
10.5.8 Phacoemulsification in
Traumatic Cataract
Traumatic cataract may develop after various types of ocular iris, vitreous and retina. Blunt ocular trauma typically leads to
insults, including blunt or perforating trauma as well as ionizing, a stellate or rosette-shaped opacification that is axial in location
infrared or ultraviolet radiation.1 and involves the posterior capsule.1 In perforating trauma,
The human lens is known to be among the most direct compromise of the lens capsule by the penetrating object
radiosensitive structures of the body, with radiation dosages leads to cortical opacification at the site of injury. If the
as low as 2 Gy capable of inducing cataract. The exact capsular tear is large enough, the entire lens can rapidly opacify,
mechanism of induction of cataract is still elusive, though but a cataract caused by a small perforation may become sealed
recent evidence suggests that a linear, dose related relationship off and remain localized.3
may exist, with the threshold being as low as 0.5 Gy of
radiation.2 PREOPERATIVE ASSESSMENT
Besides cataract, ocular trauma can also induce lens A detailed preoperative examination is required to identify
subluxation or dislocation and cause injuries to the cornea, other pathology that may prevent optimal postoperative visual
recovery and help with the decision of which surgical approach Phacoemulsification should be initiated at the site of
to take. Open-globe injuries and retained intraocular foreign greatest zonular stability.8 Capsular staining with trypan blue
bodies must be ruled out before surgery.4,5 Abnormal findings in cases of poor visualization and generous hydrodissection
that predict poor postoperative visual outcome include corneal to avoid stress on the zonules during lens extraction are also
disease, iridodialysis, relative afferent pupillary defect, macular important steps.8 Low-flow, low-vacuum, supracapsular phaco
scarring, retinal detachment, and optic atrophy.6 B-scan is technique is preferred to minimize capsular and zonular stress.
necessary if the posterior pole cannot be visualized. The If zonular dehiscence and subsequent vitreous prolapse occur
physician should also examine patients for intraocular intra-operatively, a vitrectomy cutter should be used to remove
inflammation and increased IOP preoperatively and provide the vitreous.8 Subsequent surgical strategy depends on the
appropriate treatment. A careful assessment for zonular degree of zonular disruption, which is discussed later. The
disruption and associated lens subluxation or dislocation is posterior approach with vitrectomy and lensectomy is reserved
important in deciding which surgical approach to take. In for cases of posterior capsular rupture with vitreous prolapse
addition, the initial trauma, or subsequent procedures like pars or a posteriorly dislocated lens.8
plana foreign body removal, might cause posterior capsular The degree of zonular dehiscence dictates the management
break, which should be specifically looked for if possible, and approach for a subluxed or displaced lens. If the dehiscence
specifically planned for, if the lens opacity precludes a posterior is small with no vitreous prolapse, extra care should be taken
capsular visualization. not to stress the zonules; otherwise, routine surgery is
Maximal pharmacologic pupillary dilation may be necessary appropriate. Since, traumatic disruption of zonules is a process
to identify a subtle zonular dialysis. An anteriorly displaced that affects otherwise healthy zonules, it has been observed
lens may present with a shallow anterior chamber and requires that the remaining, intact zonules are more resistant than the
immediate removal due to the risk of pupillary block.7 A intact zonules in degenerative conditions like pseudo-
posteriorly subluxated lens may only be clinically evident during exfoliation. This means that traumatic zonular damage is more
an examination of the patient with a portable slit lamp while consistent with good surgical outcome than degenerative
he is in a supine position. 8 If available, ultrasound zonular dialysis.
biomicroscopy can be helpful for assessing capsular and For a larger zonular disruption, the surgeon should
consider the implantation of a capsular tension ring (CTR).
zonular integrity.
For zonular dialysis of up to 150°, the use of a conventional
ANESTHESIA CONSIDERATIONS CTR followed by standard phacoemulsification and PCIOL
insertion has been highly successful.9 The CTR is an open
The surgeon must choose appropriate anesthesia, bearing in ring made of a single piece of PMMA that is placed inside
mind both the patient's comfort and his own. One should the capsular bag (Fig. 10.5.8.1). The CTR reforms the
remember that traumatized iris is much more sensitive to pain posterior capsule, and produces a taut capsular equator that
than normal, and intracameral lidocaine might not suffice. If protects against aspiration of the capsular fornix, thereby
a peribulbar or retrobulbar block is used, massage is avoided preventing extension of the zonular dialysis during surgical
as it may further damage the zonules by physical pressure. manipulation. It also allows easier IOL placement, prevents
IOL decentration and reduces postoperative incidence of
SURGICAL CONSIDERATIONS posterior capsular opacification.9-12
Depending on the clinical situation, the surgical management The CTR may be implanted before or after
of a traumatic cataract is performed using either standard phacoemulsification. 8 Although early insertion provides
anterior limbal or posterior pars plana approach. An anterior support during phacoemulsification, the process of insertion
approach is best for traumatic cataract unless there is complete itself may create additional zonular trauma.13 The use of iris
lens dislocation or capsular rupture with significant lens or capsule retractors at the capsulorrhexis edge or the use of
material incarcerated in the vitreous. The surgeon should a capsular tension segment during phacoemulsification are
perform standard phacoemulsification cataract extraction other alternatives that do not induce significant capsular torque
using a large capsulorrhexis. Lack of zonular support makes during insertion. The CTR is a partial PMMA ring segment
capsulorrhexis difficult, and Utrata's forceps may be preferred containing an anteriorly offset eyelet through which an iris
over the cystitome for the purpose. retractor or suture may be placed.13
For more significant or progressive zonular dialysis, the The choice and positioning of the IOL depends on the
Cionni-modified CTR, has been demonstrated to be an useful degree and location of zonular disruption. In eyes with no
alternative to the conventional CTR (Fig. 10.5.8.1). It can be zonular disruption and an intact posterior capsule, a standard
sutured safely to the sclera without compromising the capsular capsular bag-fixated IOL may be used. With a small area of
bag, thus allowing the CTR and capsule to be held in place zonular incompetence, a capsular bag IOL may also be used,
even in the presence of significant zonular incompetence.14,15 but the haptics should be oriented toward the area of
Alternatively, one or two CTR devices may be used and may incompetence in order to expand and stabilize the capsular
also be placed in cases of an anterior capsular tear, incomplete bag fully. With more significant zonular disruption, IOL
capsulorrhexis, or posterior capsular rupture (Figs 10.5.8.2A implantation should be combined with CTR or capsular
and B). The use of aniridia implant devices such as iris tension segment (CTS) use.
diaphragm rings and iris sector shields is often appropriate in In cases of an unsalvageable capsular bag, other IOL
cases of a significant loss of iris tissue. These devices are not options include ciliary sulcus-fixated IOLs and trans-sclerally
FDA approved. sutured PCIOLs and ACIOLs. Although, the ACIOL has been
Pupilloplasty and/or repair of iridodialysis may also be advocated in special circumstances (elderly patient, good iris
required. There are two broad approaches to repairing support, no evidence of glaucoma, no vitreous in anterior
traumatized anterior uveal tissue, the sutured and the sutureless chamber), they should not be used in younger patients because
approaches.16 The former is more useful in iridodialyses with of the increased risk of corneal endothelial injury and
limited angular extent. The strategy is to create small sclera glaucoma from further angle injury.7 Using ciliary sulcus-fixated
openings level with the base of the iris. Vitreoretinal forceps IOLs in children following traumatic cataract removal resulted
are then used to incarcerate the iris into these channels, and in visual outcomes similar to those for capsular bag IOLs but
the conjunctiva is closed over the sclerostomies. One with more complications, in particular uveitis and pupillary
sclerostomy per clock hour is deemed adequate.17 A second capture.20 Scleral sutured PCIOLs were not compared directly
strategy for repairing iridodialysis utilizes a suture (McCannel) with capsular bag IOLs but produced good postoperative
passed from without inwards, through the sclera and the visual results.21
detached iris, then upwards through the cornea. The needle is The use of multifocal capsular bag IOLs following removal
then disinserted and externalized through the main incision. of traumatic cataract has also been explored. In comparison
This is tightened to approximate the base of the iris to the with the standard, monofocal, capsular bag IOLs, the
inner aspect of sclera.18 A modern modification is the use of multifocal lenses resulted in improved uncorrected near visual
the Siepser knot to tie the McCannel suture.19 acuity and stereopsis, as well as decreased spectacle
dependency.22 The rationale for using a multifocal IOL is the
fact that traumatic cataracts are more likely to occur in the
younger, pre-presbyopic age group, who would feel the loss
of accommodation more than the older patient. In the very
young, appropriate amblyopia therapy must be given.
Figs 10.5.8.2A and B: (A)Two capsular tension segment (CTS)

devices have been placed in the capsular bag for profound
generalized zonular compromise (B). Once sutures have been
threaded through the eyelets, a PCIOL can be placed within capsular
Fig. 10.5.8.1: The Cionni-modified capsular tension ring bag with optimal centration
POSTOPERATIVE MANAGEMENT 4. Kwitko MR, Kwitko GM. Management of traumatic cataract. Curr
CONCERNS Opin Ophthalmol 1990;1:25-7.
5. Irvine JA, Smith RE. Lens Injuries in trauma. In: Shingleton B,
• Post-trauma cataracts may be associated with a higher Hersh PS, Kenyon KR (Eds). Eye Trauma. St. Louis: CV Mosby
degree of inflammation and may need steroids topically 1991;126-35.
as well as systemically. The fact that the younger population 6. Greven CM, Collins AS, Slusher MM, Grey Weaver R. Visual results,
prognostic indicators, and posterior segment findings following
is usually involved also contributes to this. surgery for cataract/lens subluxation-dislocation secondary to
• Exposure of vitreous to the anterior chamber is likely, and ocular contusion injuries. Retina 2002;22:575-80.
this increases the risk of macular edema. Close follow-up 7. Zaidman GW. The surgical management of dislocated traumatic
and prophylactic non-steroidal anti-inflammatory eyedrops cataracts. Am J Ophthalmol 1985;22:342-6.
such as bromfenac may be indicated. The risk of rhegmato- 8. Mian SI, Azar DT, Colby K. Management of traumatic cataracts.
Int Ophthalmol Clin 2002;42:23-31.
genous retinal detachment is also high, both in perforating
9. Jacob S, Agarwal A, Agarwal A, et al. Efficacy of a capsular tension
injury where there may be direct trauma to the retina, or in ring for phacoemulsification in eyes with zonular dialysis. J Cataract
closed globe injuries that avulse the vitreous base. Refract Surg 2003;29:315-21.
• Possible intraocular contamination with pathogens might 10. Menapace R, Findl O, Georgopoulos M, et al. The capsular tension
occur at the time of initial perforating injury. This increases ring: designs, applications and techniques. J Cataract Refract Surg
the risk of postoperative endophthalmitis. 2000;26:898-912.
11. Gimbel HV, Sun R. Clinical applications of capsular tension rings
• IOL tilt may severely compromise vision by inducing high
in cataract surgery. Ophthalmic Surg Lasers 2002;33:44-53.
astigmatism as well as higher order aberrations. 12. D'Eliseo D, Pastena B, Longanesi L, et al. Prevention of posterior
• The risk of developing glaucoma is higher than in the capsule opacification using capsular tension ring for zonular defects
routine cataract surgery. This is attributed to angle recession in cataract surgery. Eur J Ophthalmol 2003;13:151-4.
following trauma, and the possibility of steroid-induced 13. Ahmed, IK, Kranemann CF, Crandall AS. Capsular tension segment:
glaucoma. next step in effective management of profound zonular dialysis.
Presented at: The ASCRS/ASOA Symposium on Cataract, IOL, and
• In children, special care has to be taken to avoid amblyopia.
Refractive Surgery Film Festival; April 13, 2003; San Francisco, CA.
14. Ahmed IK, Crandall AS. Ab externo scleral fixation of the Cionni
CONCLUSION modified capsular tension ring. J Cataract Refract Surg 2001;27:977-
81.
In summary, traumatic cataract is common after any form of
15. Moreno-Montanes J, Sainz C, Maldonado MJ. Intraoperative and
injury to the eye. Thorough preoperative ocular examination postoperative complications of Cionni endocapsular ring
is essential to properly assess the eye with a traumatic cataract. implantation. J Cataract Refract Surg 2003;29:492-7.
The surgical approach, potential use of capsular tension 16. Süreyya Gördüren . Operative Treatment Of Five Cases Of
devices, and choice of IOL are all dictated by the inherent Iridodialysis. Br J Ophthalmol 1948;32(7):429-35.
integrity of the zonules, lens capsule, and other associated 17. Richards JC, Kennedy CJ. Sutureless technique for repair of
traumatic iridodialysis. Ophthalmic Surg Lasers Imaging
anterior segment structures. Excluding other intrinsic causes
2006;37(6):508-10.
of visual dysfunction, an eye with a traumatic cataract is 18. McCannel MA. A retrievable suture idea for anterior uveal
amenable to treatment and has an excellent potential for problems. Ophthalmic Surg 1976;7(2):98-103.
significant postoperative visual improvement. 19. Chang DF. Siepser slipknot for McCannel iris-suture fixation of
subluxated intraocular lenses. J Cataract Refract Surg
REFERENCES 2004;30(6):1170-6.
20. Pandey SK, Ram J, Werner L, et al. Visual results and postoperative
1. Johns KJ, Feder RS, Bowes Hamill M, et al. Lens and Cataract. complications of capsular bag and ciliary sulcus fixation of
AAO Basic and Clinical Science Course Series. San Francisco: The posterior chamber intraocular lenses in children with traumatic
Foundation for the American Academy of Ophthalmology cataracts. J Cataract Refract Surg 1999;25:1576-84.
2001;50-54:213-6. 21. Chaudry NA, Belfort A, Flynn JW, et al. Combined lensectomy,
2. ASS Ainsbury EA, Bouffler SD, Dörr W, Graw J, Muirhead CR, vitrectomy and scleral fixation of intraocular lens implant after
Edwards AA, Cooper J. Radiation cataractogenesis: a review of closed-globe injury. Ophthalmic Surg Lasers 1999;20:375-81.
recent studies. Radiat Res 2009;172(1):1-9. 22. Jacobi PC, Dietlein TS, Lueke C, Jacobi FK. Multifocal intraocular
3. Shock JP, Adams D. Long-term visual acuity results after penetrating lens implantation in patients with traumatic cataract.
and perforating ocular injuries. Am J Ophthalmol 1985;100:714-8. Ophthalmology 2003;110:531-8.
Chapter 10.6
PHACOEMULSIFICATION
IN EYES WITH CO-EXISTING
OCULAR PATHOLOGY
There are a few other special situations where the surgeon episode increases the technical difficulty of carrying out the
needs do things a little differently. The more commonly surgery, whether by increasing posterior synechiae formation,
encountered conditions are co-existing uveitis, glaucoma and decreasing endothelial counts, or time-related increase in the
the post-vitrectomy eye. density of the cataract. Although the tools for managing these
'difficulties' exist, (see previous chapters on small pupil surgery),
UVEITIS it is better to strike pre-emptively.
Uveitis is linked both etiologically and prognostically to cataract Surgery
formation. Any form of uveitis can cause complicated cataract
over a period of time, especially posterior subcapsular cataract. During surgery, posterior synechiae may have to be released.
In addition, oral steroids used for the management of uveitis A small pupil may need to be enlarged by any of the various
may also lead to cataract in the long run. Prognostically, the strategies mentioned earlier (Fig. 10.6.1). This manipulation
incidence of macular edema is higher after phacoemulsification of the uveal tissue is usually painful to the patient, unless
in eyes with uveitis, although the use of oral corticosteroids adequate analgesia has been used. Peribulbar block may be a
and meticulous control of intraocular inflammation prior to better option than topical anesthesia in such cases. Surgical
surgery helps to reduce this.1,2 peripheral iridectomy may be planned as part of the procedure.
Preoperative Evaluation
While planning surgery in the uveitic patient, it is important
to assess the expected visual recovery. This may be compro-
mised due to co-existing retinal pathology like old cystoid
macular edema. Extent of pupillary dilatation, specular count
of endothelial cells and careful slit-lamp evaluation to rule
out active uveitis are other considerations.
The Decision to Operate

Cataracts associated with uveitis are usually diagnosed early,
since the patient is already under the ophthalmologist's care.
As a general rule, it is better to operate these cataracts early.
Once it is clear that the cataract is a significant contributor to
the declining vision, the only delay should be to make sure
that the eye is quiet. The reason for this approach is that uveitis Fig. 10.6.1: Cataractous eye with small pupil due to uveitis
is characterized by episodic exacerbations, and each such (Courtesy: Dr Zia Chaudhuri)
Phacoemulsification in Eyes with Co-existing Ocular Pathology 1047
IOL Implantation surgery, may cause the entire contents of the capsular bag to
sink into the vitreous cavity.
The decision to implant an IOL, and the material that is to be
There is a tendency for the depth of the anterior chamber
used, has been the subject of some debate,3,4 and IOL package
to fluctuate. 7 An AC maintainer may help reduce the
inserts to this date warn against use of these devices in an eye
fluctuation. Phacoemulsification should be performed in low
with a history of uveitis. However, modern phacoemul-
fluid turnover settings. Higher-end, low surge machines are
sification with IOL implantation provides satisfactory results
definitely superior to the basic models in the post-vitrectomy
in most cases.
eye.
Extra care should be taken to place the IOL in the bag.
The IOL implanted should ideally be foldable acrylic with
Hydrophobic acrylic IOLs have proven to generate less
a large (6.0 or 6.25 mm) optic size. Silicone IOLs are
inflammation than other IOL materials.5,6
contraindicated, because they preclude the later use of silicone
oil for retinal surgeries.8,9
Postoperative Care
If a PMMA lens is being used, the incision must be well
Postoperatively, increased anterior chamber reaction is to be secured by sutures, as it will come under stress if posterior
expected, and should be managed by high dose prolonged topical segment surgery is done later.
steroids. Mydriatics and NSAIDs are useful adjuncts. Oral steroids Intracameral antibiotics and lidocaine should be avoided
may be necessary in some cases, especially in the younger patients. as they can cause retinal toxicity, although there is some
evidence that lidocaine toxicity is only transient.10
POST-VITRECTOMY EYE In general, the incidence of posterior capsular plaques is
higher in the post-vitrectomy eye.11 If silicone oil has been
The fact that there has been some retinal pathology
used with the vitrectomy, its presence definitely predisposes
necessitating vitrectomy also limits the potential visual gain
to cataract formation, with literature quoting hundred percent
from the cataract surgery. However, cataract surgery may be
incidence in several studies.12,13
indicated not just for visual reasons; there may be further retinal
Capsular plaques may be tenacious and require laser
diagnostic or therapeutic procedures that cannot be done in
capsulotomy later; the Nd:YAG rate following cataract surgery
the absence of clear visualization of the retina. The
in these eyes can be as high as 44 percent.14
considerations that apply to the post-vitrectomy eye also apply
to the eye with a retinal detachment, whether visible clinically GLAUCOMA
or apparent on ultrasonic evaluation. The discussion is
important because many times it may be necessary to perform The presence of high intraocular pressure is a contraindication
cataract surgery before the retinal detachment can be treated, to cataract surgery. Before planning cataract surgery, the IOP
either at the same sitting or at a later date. should be well controlled. This may involve use of
antiglaucoma medication, surgery or laser treatment if there
Preoperative Evaluation is time at hand, or drastic measures like intravenous mannitol
in case rapid lowering of IOP is required.
Preoperatively, biometry is the chief concern. The axial length Even after adequate lowering of pressure, the
measurements may not be accurate, and it is better to use pre- glaucomatous eye is at a higher risk of expulsive hemorrhage
vitrectomy measurements if these are available, or use the than the normal eye.15 For this reason, phacoemulsification is
fellow eye parameters for calculating IOL power. Please refer the preferred mode of cataract extraction, as it permits good
to the chapter on biometry for further relevant details. anterior chamber stability. The other advantage of
The presence of retinal detachment causes faulty placement phacoemulsification is that the conjunctiva is not touched,
of A-scan spikes, resulting in underestimation of axial length thereby allowing greater freedom in the choice of subsequent
and consequent over-estimation of IOL power. glaucoma surgery.16
Since the angle of the anterior chamber may be
Surgery
compromised, the surgeon should always endeavour to place
The technical problem during surgery arises from lack of firm the IOL in the bag. Sulcus fixation, scleral fixation and anterior
vitreous support. There is also the possibility that the posterior chamber lenses are associated with a greater tendency for the
capsule might have been nicked during vitrectomy. In such a glaucoma to spiral out of control in the postoperative
case, the wave of hydrodissection, or pressure later on in the period.17,18
Glaucoma evaluation improves following cataract surgery Advanced Optic Nerve Damage
as investigations like perimetry and optic nerve-head evaluation
Despite impeccable surgery on the latest machines, eyes with
can be performed more accurately. Newer diagnostic modalities
advanced glaucomatous field defects stand the risk of losing
like optical coherence tomography, confocal laser scanning
the small island of vision following cataract surgery. There is
ophthalmoscopy and scanning laser polarimetry are also
no real way to predict or prevent such an event, but meticulous
significantly influenced by the presence of cataract.19
preoperative IOP control and good intraoperative anterior
chamber stability are protective.
Prexisting Open Angle Glaucoma
There is some evidence to suggest that the removal of the Combined Surgery
crystalline lens per se is associated with a reduction in the IOP It is possible to combine surgery for cataract and glaucoma.
postoperatively. The mechanism for such a change is still not Options include one-site phacotrabeculectomy or temporal
fully understood, but the effect is sustained and significant.20 phacoemulsification combined with conventional, superior
trabeculectomy, but there is no tangible difference in the final
Prexisting Angle-closure Glaucoma visual and refractive outcomes.23
The surgical procedure is technically more challenging as the The advantages of performing a combined surgery are:
anterior chamber is shallow. Though removal of the lens • Single surgical procedure is more convenient for the
deepens the anterior chamber, it is worthwhile to perform a patient.
surgical peripheral iridectomy along with the cataract • Immediate control of both the problems.
extraction. The disadvantages of a combined surgery are:
• When performing cataract and glaucoma surgery as part of
Post Trabeculectomy a single procedure, increased postoperative inflammation is
expected.
A functioning trabeculectomy should be taken care of. The • The possibility of the filtering surgery being compromised
main incision should not be placed around the trabeculectomy in either direction, i.e., overfiltration or underfiltration, is
site, nor should the bleb be sacrificed for cataract surgery. In also higher when cataract surgery is combined.
the post-trabeculectomy eye, the benefits of clear corneal • Greater risk of endophthalmitis.
temporal phacoemulsification are obvious, and immense. Finally, the decision to combine the two surgeries is an
There is a tendency for the pupil to be small and refractory individual surgeon's prerogative, with literature being divided
to mydriatics. Surgical techniques useful in small pupil surgery over the potential benefits and possible pitfalls.23
have been described earlier.
Lens Induced Glaucoma
Glaucoma Therapy
This is a special case of co-existing glaucoma and cataract, in
If the patient has been on long-term pilocarpine therapy, a that the cataract itself is the precipitating cause of the high
non-dilating pupil may be expected. The pupil may not dilate intraocular pressure. The mechanisms by which cataracts raise
to beyond one or two millimeter, even if pilocarpine has been the IOP are either by means of physically crowding the anterior
stopped well ahead of the planned surgery. chamber and causing angle closure, the phacomorphic
The use of prostaglandin analogues predisposes the eye glaucoma, or indirectly by immune reaction to the leaking lens
to cystoid macular edema.21 These drugs need to be stopped proteins, the phacolytic glaucoma. Both these situations arise
at least one week prior to the cataract surgery. One must be in the presence of a mature cataract, and control of IOP
careful to monitor the IOP in this window period. Usually, requires the removal of the cataractous lens.
additional anti-glaucoma therapy will be required to control Important points to remember when dealing with lens
the IOP whilst the prostaglandin analogues are not being used. induced glaucoma are:
However, in general, eyes with glaucoma have no greater • The eye is actively inflamed at presentation.
tendency towards cystoid macular edema (CME) than non- • One must take the time to control the IOP before surgery,
glaucomatous eyes.22 otherwise not only is the final outcome poorer, there is an
increased risk of intraoperative disasters like expulsive • Dye-assisted rhexis is always a good choice, even if the
hemorrhage. cataract is immature (Fig. 10.6.2).26
• It may take several drugs to control the IOP, including • Endoillumination can be effectively employed to get a
intravenous mannitol. Prostaglandin analogues, should not better view beyond the opacity.27
be used. • As the corneal opacity lies anterior to the cataract, the eye
• Control of IOP and relief of symptoms must not distract can be bimanually tilted to utilize parallax, and get a view
attention from the underlying cause. It is imperative to of structures that lie directly beneath the opacity.
remove the cataract as soon as possible. • The aim should be to get a large rhexis in place, as it
• If the cornea has cleared and the surgeon is comfortable facilitates phacoemulsification.
doing phacoemulsification, then that is the procedure of • A large diameter, square-edged IOL should be implanted
choice, through a temporal clear corneal incision with after meticulous capsular bag clean-up, to avoid posterior
preferably a foldable IOL. This leaves the conjunctiva capsular opacification. It may not be possible to focus the
untouched for later trabeculectomy, which may be required YAG beam accurately on to the posterior capsule later, in
if synechial angle closure has occurred. the presence of the corneal opacity.
• Age of the patient and duration of symptoms are • Gentleness is the key word, for the corneal opacity might
important prognostic indicators.24 However, the prognosis carry an underlying endothelial weakness that might later
remains guarded, no matter how short the duration of lead to bullous keratopathy.
• An interesting new approach uses the femtosecond-laser
the symptoms and how well the IOP is controlled.
to create a flap and corneal button for lamellar
• Important reasons for poor visual recovery are optic
keratoplasty.28 This is done at the beginning of the cataract
atrophy, uveitis and corneal edema.25
surgical procedure, and the button, which contains the
• There is a liability of more inflammation in the
opacity, is removed, allowing clear visual access for the
postoperative period than following standard cataract
cataract surgery. Another report has described the use of
extraction. Anti-inflammatory therapy should be strong
a microkeratome to create and lift a flap, repositioning it
and sustained.
after cataract surgery.29
CORNEAL OPACITY There have also been reports of combining deep lamellar
keratoplasty with cataract surgery, to tackle the problem of
Preoperative Considerations stromal corneal disease. The cornea is dissected to the point
For patients who have cataract and corneal opacity, the surgeon of having only the Descemet’s membrane intact, and
has a challenging task right from the beginning. phacoemulsification is then performed with low-flow settings.
The reasons are:
• It may be difficult to assess the relative contributions of
the two disease processes to the overall visual impairment,
and therefore it may be difficult to estimate the visual gain
that might be expected from surgery. In addition, the view
of the fundus may be compromised, and potentially
significant lesions like a macular scar might be missed.
• IOL power calculations depend upon accurate keratometry,
which may not be feasible. It is better to cross check
autokeratometry readings with manual keratometry. If the
mires are grossly distorted, a better approximation of the
true value can be obtained from the other eye. Sometimes,
using lubricant eyedrops can help.
Surgical Considerations
The corneal opacity offers varying degrees of obstruction to Fig. 10.6.2: Dye-assisted capsulorrhexis
the visualization of events happening in the anterior chamber. in the presence of corneal opacity
After the cataract has been removed and the IOL implanted,
a full thickness donor button (sans the Descemet’s membrane)
is sutured into place.30
ANIRIDIA
Aniridia is the absence of the iris which can be congenital or
sporadic. This usually occurs in both eyes if congenital. A
special subgroup of aniridia is post-traumatic, which is typically
unilateral. The incidence of cataract within the congenital
aniridia population ranges from 50 to 85 percent. The special
considerations of cataract surgery in the setting of aniridia
include:
• A number of associated co-morbid conditions that
influence the potential visual recovery, like sclerocornea
with nystagmus, microcornea, foveal hypoplasia, and
ectopia lentis may be present. Fig. 10.6.3: Patient with aniridia and ectopia lentis
• Most patients also have glaucoma which is difficult to (Courtesy: Dr Zia Chaudhuri)
control.
• The lack of control over incoming light intensity is a source
may be used when indicated. Morcher ring segments offer the
of visual disability in itself, but it also predisposes to photic
benefit of smaller incision size compared to Ophtec model
damage, including damage by UV rays. Cataract surgery
311, but that is relevant only if an IOL is not being implanted.
offers the opportunity to address this problem at the same
The Ophtec model 311 is a multifunctional device,
sitting. Reduction of aperture also helps improve contrast,
targeting both the aniridia and the aphakia at the same time. It
and reduces spherical and chromatic aberrations.
has a 4 mm pupil and is available in blue, green and brown
• The paucity of zonular support and the presence of
colors. Fixation holes for scleral fixation are provided on the
vitreous in the anterior chamber warrants the use of special
haptics.
techniques to remove the cataract (Fig. 10.6.3).
A special PMMA aniridia lens manufactured by IntraOcular
• Since, most of the cataracts occur before the age of 20
Care Pvt Ltd may also be used to simultaneously address the
years, all considerations of paediatric cataract surgery and
concerns of aphakia (postoperative) and aniridia. The device
postoperative care, including amblyopia therapy, are
consists of an inner 5.5 mm IOL optic that is clear and
relevant.
functions as the refracting surface, and an outer band of
pigmented PMMA that serves as the ‘pseudo-iris’. The haptics
Surgical Technique
are angulated PMMA, having holes to allow scleral fixation.
Routine phacoemulsification is often not possible,31 and the The use of glue to fixate this IOL has been described.
cataract may be removed by lensectomy combined with For patients where only cosmetic considerations are
vitrectomy. It is important to plan the aphakic correction. If relevant, corneal tattooing remains a viable option.
scleral fixated or glued IOLs are planned, then scleral pockets In general, implantation of posterior chamber implants in
need to be created before the main incision is made. aniridia patients has been relatively complication-free,
Intracapsular extraction is not feasible in many cases because producing satisfactory results.32
of the presence of vitreous. An additional confounding factor
The authors/editors have no financial interest in any procedure/product mentioned
is that the capsular thickness is lesser in these eyes, and there
in this chapter.
is a greater likelihood of breakage of the capsular bag when
attempting intracapsular removal. REFERENCES
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J Cataract Refract Surg 2002;28(12):2096-108. 21. Altintas O, Yüksel N, Karabas VL, Demirci G. Cystoid macular
7. Díaz Lacalle V, Orbegozo Gárate FJ, Martinez Alday N, López edema associated with latanoprost after uncomplicated cataract
Garrido JA, Aramberri Agesta J. Phacoemulsification cataract surgery. Eur J Ophthalmol 2005;15(1):158-61.
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8. Apple DJ, Federman JL, Krolicki TJ, Sims JC, Kent DG,
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1998;105(2):287-94. Endoillumination-assisted cataract surgery in a patient with corneal
12. Federman JL, Schubert HD. Complications associated with the opacity. J Cataract Refract Surg 2003;29(12):2277-80.
use of silicone oil in 150 eyes after retina-vitreous surgery. 28. Lee D, Kim JH, Oh SH, Choi SK, Kim JK. Femtosecond laser
Ophthalmology 1988;95(7):870-6. lamellar keratoplasty to aid visualization for cataract surgery. J
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14. Pardo-Muñoz A, Muriel-Herrero A, Abraira V, Muriel A, Muñoz- 30. Muraine MC, Collet A, Brasseur G. Deep lamellar keratoplasty
Negrete FJ, Murube J. Phacoemulsification in previously combined with cataract surgery. Arch Ophthalmol 2002;120(6):812-
vitrectomized patients: An analysis of the surgical results in 100 5.
eyes as well as the factors contributing to the cataract formation. 31. Biro Z, Racz P, Kovacs B. Phacoemulsification and foldable lens
Eur J Ophthalmol 2006;16(1):52-9. implantation in a patient with congenital aniridia and glaucoma.
15. Jiraskova N, Rozsival P, Pozlerova J, Ludvikova M, Burova M. Ann Ophthalmol 2001;33(2):169-71.
Expulsive hemorrhage after glaucoma filtering surgery. Biomed 32. Tanzer DJ, Smith RE. Black iris-diaphragm intraocular lens for
Pap Med Fac Univ Palacky Olomouc Czech Repub 2009; aniridia and aphakia. J Cataract & Refractive Surgery 1999;25(11):
153(3):221-4. 1548-51.
Chapter 10.7
PEDIATRIC LENTICULAR
ABNORMALITIES
Sajani K Shah, Abhay R Vasavada
Disorders of the pediatric lens include, in addition to cataract, CLASSIFICATION

abnormalities of shape, size, location and development
Pediatric cataract has been classified based on etiology,
(Table 10.7.1). Abnormalities of the pediatric lens may either
morphology, and anatomic location of lens opacities (Table
be isolated cases or may be associated with diseases of the
10.7.1). These cataracts may be isolated or part of a systemic
urinary tract, central nervous system, or skeletal system.
condition.
PEDIATRIC CATARACT
Table 10.7.1: Congenital lens abnormalities
Pediatric cataract is the most common cause of treatable Opacification
childhood blindness, accounting for 5 to 20 percent of A. Anatomical type Subtypes
blindness in children worldwide. 1-3 The physiology and
Anterior capsular cataract Anterior polar
anatomy of the growing eyes of children are very different Anterior capsular
from those of adults, and therefore, pediatric cataract also Anterior capsular plaque
appears and behaves very differently. Cortical cataract Anterior cortical
Posterior cortical
Membranous
EMBRYOLOGY AND GROWTH
Nuclear cataract Isolated nuclear
Primary lens fibers expel their intracellular contents, and form Lamellar
Sutural
an optically clear embryonic nucleus 0.35 mm in diameter
Punctate
during the 6th week of gestation. Equatorial, secondary lens Posterior capsular cataracts Posterior polar cataract
fibers migrate anteriorly and posteriorly to meet each other Posterior subcapsular
at the sutures (anterior upright Y and posterior inverted Y Posterior lenticonus
sutures). These sutures demarcate the embryonic and fetal Total cataract
nucleus. The secondary lens fibers continue to form the fetal Mixed cataract
nucleus up to the 8th month of gestation. Both fetal and Cataract with pre-existing
embryonic nuclei are present at birth. After birth, the posterior capsule defect
equatorial fibers grow and elongate to form the cortex. The Cataract with persistent
fetal vasculature
developing lens requires nutrition that is obtained through
B. Size Microspherophakia
the tunica vasculosa lentis. This gradually starts regressing C. Shape Spherophakia
after the 85th day of gestation and completely regresses by Coloboma Disciform
the 7th month. At term, only wispy remnants of the pupillary D. Location Suluxated
membrane are left, and a vestigial hyaloid artery (Mittendorf's Dislocated
dot) may often be attached to the axial posterior surface of E. Developmental Association Persistent fetal vasculature
(PFV or PHPV)
the lens.4,5
Pediatric Lenticular Abnormalities 1053
Other methods to classify are: place. They are usually stationary and not visually significant,
• Unilateral or bilateral but maybe associated with astigmatism,6,7 thereby leading to
• Congenital or acquired amblyopia, or may be found along with corneal guttata or
• Partial or complete aniridia. This kind of cataract could be associated with small
• Stable or progressive strands of the pupillary membrane between the polar opacity
• Inherited or sporadic. and the pupillary border. Association with corneal opacity and
other signs of keratitis could indicate an intra-uterine
Anatomical Classification inflammation or a healed corneal ulcer. Pyramidal cataract has
a greater impact on vision. Most cases do not warrant surgery.
Classification of lenticular opacities based on their anatomic
It is important to keep in mind that during surgery, anterior
location (Table 10.7.1) facilitates precise localization of the
capsulorrhexis is liable to tear out.
lens opacities. Using the location of the opacities, meaningful
information can be derived on the visual prognosis, timing Anterior capsular cataract: These opacities are plaques
and nature of the insult and progression. It can also aid in the which are generally confined to the anterior capsule, sometimes
identification of associated ocular and systemic anomalies. extending into the underlying cortex. They are axial, and maybe
Moreover it also helps the surgeon to plan appropriate unilateral or bilateral. When bilateral, they are usually
management strategies. symmetrical. They are generally visible even without a
microscope. This is why they are often diagnosed soon after
Anterior Cataract birth. They remain static, and if not situated axially are visually
insignificant. However, constant monitoring is required for
Anterior polar cataract: Anterior polar cataract presents as
any deterioration in vision. They are associated with persistent
a dot-like axial opacification on the anterior capsule (Fig.
tags of the pupillary membrane when situated in the pupillary
10.7.1). It may sometimes project into the anterior chamber
area. They are frequently hereditary, and the patient's offsprings
(pyramidal cataract). It is usually bilateral and symmetrical in
are at high risk of incurring this form of cataract. Acquired
both eyes. It represents anomalies of lens vesicle detachment
cataract can be associated with severe skin disease.
or an abnormal growth of the primary lens fibers before
closure of the lens vesicle. It is hereditary and transmitted as Anterior capsular plaque: These are axial opacities in the
an autosomal dominant trait. As the nucleus is clear, this capsular epithelium (Fig. 10.7.2). They are often associated
cataract develops relatively late in fetal life, not before the 4th with total white cataract but because of lack of contrast the
month of gestation. It has been suggested that the progressive diagnosis is often missed preoperatively. They occur either as
cortical opacification involved in certain types of anterior polar multiple plaques distributed throughout the anterior lens
cataract is due to epithelial cell dysfunction. The depth of epithelium or as a single large plaque which may be located
extension indicates the point at which the changes have taken centrally or eccentrically. They are commonly associated with
Fig. 10.7.1: Anterior polar cataract Fig. 10.7.2: Anterior capsular plaque
persistent pupillary membrane and/or microcornea. They children. The classically described ‘coronary cataract’ is a type
represent an abnormality in the regression of the pupillary of deep cortical cataract.8 It is bilateral and stationary. Usually
membrane. Management is similar to anterior polar cataract, sporadic, this is a developmental cataract that is diagnosed
requiring surgery only when they interfere with the around puberty and is not visually significant in most cases.
development of vision.
Membranous cataract: It is an advanced form of cortical
cataract where the entire lens substance is absorbed, leaving a
Cortical Cataract
thin grey-white capsular membrane which replaces the cortex.
Anterior and posterior cortical cataract: Isolated cortical It is frequently bilateral and visual prognosis is poor. It is often
cataract is less common in infants and young children, (Figs associated with aniridia and in congenital rubella as a
10.7.3 and 10.7.4). Posterior cortical cataract is more common consequence of intrauterine iridocyclitis that remains active
than anterior cortical cataract. Cortical cataract is usually after birth, leading to persistent fetal vasculature or
present as club shaped opacities in the periphery of the lens microphthalmos. It has been described in Lowe's syndrome.
cortex, which does not interfere with vision. Diabetes mellitus Most cases are sporadic and a familial or dominant
in children can infrequently cause cortical opacities in teenage transmission is rare. The surgical outcome is variable, and it is
very difficult to carry out in-the-bag IOL implantation in these
cases.
Nuclear Cataract
Isolated nuclear cataract: This has been classically described
as the ‘central pulverulent cataract’. The opacity involves the
embryonic nucleus and is caused by an insult occurring during
the first three months of development. It is always bilateral
and non-progressive. The white, discrete dots appear as a
granular disk in the center of the lens and sometimes the dot-
like opacities may extend into the overlying cortex. It is also
known as the ‘blue-dot cataract’. This form of cataract is
visually insignificant. It is usually diagnosed on routine slit-
lamp examination. Frequently it may present as a dense chalky-
white central cataract occupying the fetal nucleus and
sometimes the embryonic and infantile nucleus. Bilateral dense
Fig. 10.7.3: Anterior cortical cataract nuclear cataracts have been described with congenital rubella.
Rubella cataract: This cataract accounts for four to five
percent of all congenital cataracts in developing countries9
(Figs 10.7.5 and 10.7.6). The infection is contracted by the
mother during the first three months of pregnancy. This form
of cataract is bilateral, progressive and may be associated with
microphthalmos. It may present as dense nuclear cataract or
as total cataract soon after birth. Membranous cataract is also
commonly found in these eyes. A typical appearance is noted
with clusters of vacuolar opacities in the cortex. These discrete
clusters of opacities may represent pockets of viral replication.
Early surgical intervention is mandatory in these cases. This
cataract has demonstrated a strong autosomal dominant
inheritance.
Lamellar cataract: This form of cataract has been classically
described as "zonular" or "perinuclear" cataract (Figs 10.7.7
Fig. 10.7.4: Posterior cortical cataract and 10.7.8). It accounts for about 40 percent of congenital
Fig. 10.7.5: Typical rubella cataract (Case 1) Fig. 10.7.7: Lamellar cataract . The cataract does not involve the
entire nucleus
Fig. 10.7.6: Typical rubella cataract (Case 2) Fig. 10.7.8: Lamellar cataract. Slit view
cataract and is predominant in males. It occurs bilaterally, and into the clear overlying cortex), imply that the abnormality of
is symmetrical and stationary.10-12 It can either be congenital fiber formation persisted beyond that particular time.
(insult occurring prenatally) or developmental (insult occurring Lamellar opacities range from translucent, visually
postnatally). insignificant cataract to dense cataract, requiring early surgical
In the congenital form, the opacity is concentric, often intervention. Visual prognosis is better than in many other
occurring within the fetal nucleus and the embryonic nucleus morphological types.
is clear. The surrounding cortex also remains clear. The insult They are usually inherited as an autosomal dominant trait.
is caused after the first three months of embryonic In sporadic cases of the congenital form, parathyroid
development. More commonly the opacity lies outside the fetal deficiency resulting in hypocalcemia and avitaminosis-D in the
nucleus and represents an insult to the lens fibers later in mother during the last trimester of pregnancy or in the fetus
intrauterine life or after birth. These are evident at birth. could be a cause. In such cases, cataract is frequently associated
In the developmental form, lamellar opacities occur due with imperfect calcification of the enamel of the teeth.
to an insult inflicted in early infancy or even in adolescent life. The developmental form could be associated with infantile
The opacity, which is more than 5.75 mm, lies in the periphery tetany (carpopedal spasm, general convulsions and laryngismus
of the lens. Associated 'riders' (radial cataractous extensions stridulus) and rickets. Untreated galactosemia classically causes
Fig. 10.7.9: Oil droplet cataract in galactosemia Fig. 10.7.10: Sutural cataract with punctuate cortical opacities
an oil droplet (Fig. 10.7.9) or a lamellar cataract in infancy. A the lens. In the progressive form, radiating or punctate opacities
developmental (postnatal) lamellar cataract can develop in appear in the overlying posterior cortex after birth at ages
premature infants. ranging from 3 to 28 years. The nuclear layers remain clear.
This form of cataract is frequently bilateral. It is thought to
Sutural cataract: It is a Y shaped opacity affecting one or
represent a remnant of the vascular sheath of the lens, as a
both the sutures of the fetal nucleus (Fig. 10.7.10). The opacity
mild form of persistent primary hyperplastic vitreous. It has a
is either around the suture or involves the sutures, more
marked visual effect because of its proximity to the nodal
posterior than anterior. Opacification of both anterior and
point. Some posterior cataracts such as Mittendorff's dots (Fig.
posterior sutures is called stellate cataract. They are stationary,
10.7.11) and posterior lenticonus (lentiglobus) may have a good
bilateral and visually insignificant. Occasionally they may
visual prognosis. Posterior cataracts, especially if they are of
progress to form nuclear or central cataracts. This form of
congenital onset, may be associated with a poor visual
cataract is frequently associated with punctuate opacities
prognosis. There is a strong hereditary tendency that is almost
elsewhere in the lens. They are usually noted as an incidental
always dominant. During surgery, a breach in the posterior
finding. It is transmitted as a dominant trait. This could be
capsule should be anticipated.
present in obligate carriers of the Nance-Horan Syndrome
(supernumerary teeth, prominent teeth and ears and Posterior subcapsular cataract: This form of cataract is seen
developmental delay). as vacuolar or plaque-like opacities close to the posterior
Punctate cataract: The floriform and coralliform cataracts are capsule.13 Typically it is seen in older children following trauma,
types of nuclear cataract. In floriform cataract, clusters of uveitis secondary to rheumatoid arthritis (Fig. 10.7.12) or after
opacities are present around the fetal sutures. Sometimes they prolonged use of steroids for spring catarrh and radiation.
extend into the cortex which indicates their development after Plaque-like opacities may be seen in congenital cataract,
birth. They are transmitted as a dominant trait and could be myotonic dystrophies and Turner's syndrome. Being close to
associated with camptodactyly. Coralliform cataract has large the nodal point, they are visually significant but progress very
crystals accumulated in the center of the lens without reference slowly. During surgery, in cases of thick plaque, posterior
to the sutures. They radiate out without reaching the capsule. capsulorrhexis maybe required.
They are bilateral, axial, stationary and can impede vision. They Posterior lenticonus (Lentiglobus): It is a conoid protrusion
follow an autosomal dominant inheritance pattern. of the posterior lens substance. It maybe unilateral or bilateral,
and if bilateral, is asymmetric. There is variable opacification
Posterior Capsular Cataract
of the overlying cortex. Amblyopia is frequently present,
Posterior polar cataract: In the stationary form, classically, because of astigmatism, but vision may improve after
a dense, saucer-shaped opacity covers the posterior pole of postoperative occlusion. Pathogenesis is believed to be due to
Fig. 10.7.11: Mittendorf's dot with persistent fetal vasculature Fig. 10.7.13: Total cataract
management is mandatory for good visual prognosis. Though

uncommon, they may sometimes present as congenital
morgagnian cataracts.
Mixed Cataract
Instead of isolated opacities, often, more than one anatomic
types of cataract coexist in the same eye. Depending on the
type and severity of opacities, vision maybe affected.
Pre-Existing Posterior Capsule Defect

It has been reported that pre-existing posterior capsule defect
occurs in about 6.75 percent of Indian eyes.14 It is recognized
by the presence of well-demarcated, thick defect margins and
Fig. 10.7.12: Posterior subcapsular cataract
white dots on the posterior capsule and in the vitreous (Fig.
progressive thinning of the posterior capsule, which may 10.7.14). When the globe is moved with forceps, the dots in
eventually lead to a posterior capsule defect. Posterior the anterior vitreous move like a fish tail (fish-tail sign). These
lentiglobus is associated with Lowe's syndrome. It is inherited are frequently camouflaged by a mature cataract. They present
as an X-linked condition. bilaterally and are progressive. Unilateral posterior capsule
defects perhaps begin as a posterior lentiglobus. It is important
Total Cataract to recognize this entity, to avoid any surprises during surgery,
and to anticipate and plan a suitable safe surgical strategy.
It presents as a general opacity of all the lens fibers (Fig.
10.7.13). This occurs due to insult acting throughout the period
Etiological Classification of
of development or a severe insult late in fetal life. Some lenses
Congenital Cataract
are completely opaque when first diagnosed; in other cases
they develop from lamellar or nuclear cataracts. They are Numerous individual causes of cataract exist, and often,
frequently bilateral. In cases of early onset, they have a multiple factors act together, with plenty of scope for
profound effect on visual development and may often mask overlap between the groups. Some causes predispose to a
underlying posterior capsule defects or posterior segment specific morphological variety of cataract. Moreover, a given
pathologies. Total cataract is frequently reported with cause may produce more than one morphological form of
congenital rubella syndrome, Down's syndrome, acute cataract. The etiological classification of congenital cataract
metabolic or even sporadic cataracts. Aggressive surgical is elaborated in Table 10.7.2.
Contd...
Atopic dermatitis
Cockayne's syndrome
Marshall syndrome
With chromosomal disorders
Trisomy 13 (usually die within 1 year)
Trisomy 18 : Edward's syndrome
Trisomy 21 : Down's syndrome (often cataract formation
delayed until approximate age of 10 years)
Turner's syndrome
With metabolic disease
Galactosemia (autosomal recessive)
Galactokinase deficiency
Congenital hemolytic jaundice
Fabry's disease
Refsum's disease
Mannosidosis
With miscellaneous hereditary syndromes
Fig. 10.7.14: Classical pre-existing posterior capsule defect Norrie's disease
Hereditary spherocytosis
Myotonic dystrophy
Table 10.7.2: Etiological classification
of congenital cataracts Nonhereditary
Prenatal causes
Isolated Findings Rubella syndrome
Hereditary Toxoplasmosis
Autosomal dominant Varicella
Autosomal recessive Cytomegalovirus
X Linked Herpes simplex virus
Measles
Sporadic (one-third of all congenital cataracts)
Vaccinia
Part of Syndrome or Systemic Disease Intrauterine hypoxia or malnutrition
Hereditary Postnatal causes
With renal disease Retinopathy of prematurely
Lowe's oculocerbrorenal syndrome Hypoglycemia
Alport syndrome (autosomal dominant) Hypocalcaemia
With central nervous system disease Radiation
Marinesco Sjogren's syndrome (autonomic recessive) Trauma
Sjogren's syndrome (autonomic recessive) Chronic uveitis
Smith-Lemli-Opitz syndrome Diabetes mellitus
Laurence-Moon-Bardet-Biedel syndrome Wilson's disease
With skeletal disease Renal insufficiency
Conradi's syndrome (presence of cataract indicates Drug induced
worse prognosis) High voltage electric shock
Marfan's syndrome Associated with another ocular abnormality
Stippled epiphysis Persistence of fetal vasculature (PFV)
With abnormalities of the head and face Microphthalmos
Hallermann-Streiff syndrome Aniridia
Francois dyscephalic syndrome Retinitis pigmentosa
Pierre Robin syndrome Norrie's disease
Oxycephaly Colobomas
Crouzon's disease Lenticonus
Acrocephalosyndactyly (Apert's syndrome)
With polydactyly SPECIAL SITUATIONS
Rubinstein-Taybi syndrome
With skin disease Ectopia Lentis
Bloch-Sulzberger syndrome
Congenital ectodermal dysplasia of the anhidrotic type Ectopia lentis of the crystalline lens is a condition where the
Rothmund Thomson syndrome
Sucharfer's syndrome
crystalline lens is either partially or completely displaced from
Siemen's syndrome its original position (Fig. 10.7.15), due to the absence or
Incontinential pigmenti weakness of the zonules. In children this has been associated
Contd... with several clinical conditions (Table 10.7.3).15-17
visible and unbroken. On examination, there is iridodonesis,

phacodonesis, deep anterior chamber and small, non-dilating
pupils. Myopia and retinal detachment are common in the
second and third decades of life.
Regular retinal evaluation of patients with Marfan's
syndrome is mandatory, as there is an increased risk of retinal
detachment, which may occur years after surgery.
Homocystinuria
It is a rare, autosomal recessive condition. It is caused by an
abnormality in the enzyme cystathione ß-synthase, causing
accumulation of homocystine in the plasma and being excreted
in urine. Clinical features are variable, affecting the eye, skeletal
system, central nervous system and vascular system. Ocular
findings primarily consist of dislocated lenses (frequently
Fig. 10.7.15: Subluxated cataract in a child with loss of zonules
downward and nasally). Systemically, vascular complications
are common and secondary to thrombotic disease affecting
Table 10.7.3: Conditions associated with large or medium-sized arteries and veins all over the body.
subluxated lenses Patients are usually tall, with osteoporosis, scoliosis, and chest
Systemic Conditions deformities.
Marfan's Syndrome
Homocystinuria
Weil-Marchesani Syndrome Ectopia Lentis et Pupillae
Ehler-Danlos Syndrome
Hyperlysinemia Ectopia lentis et pupillae is a rare autosomal recessive
Sulfite-oxidase deficiency condition. It is manifested by bilateral displacement of the
Ocular Conditions pupil, usually inferotemporally, with lens dislocation in the
Aniridia
Iris coloboma
opposite direction. Patients have microspherophakia, miosis,
Trauma and poor pupillary dilatation with mydriatics.
Hereditary ectopia lentis
Complicated Cataracts
Marfan's Syndrome Complicated cataracts occur commonly as a result of uveitis,

often occurring in conjunction with arthritis (juvenile
It is an autosomal dominant inherited systemic disease, with rheumatoid arthritis, JRA) or as a result of posterior or
variable penetrance. It is the disease most commonly intermediate uveitis of any cause. Cataract may be the direct
associated with dislocated lenses. The syndrome consists of result of inflammation within the eye or can result from steroid
abnormalities of the cardiovascular, musculoskeletal and use to treat the condition. Cataracts caused by steroid ingestion
ocular systems. It is caused by mutations in the fibrillin gene are usually posterior subcapsular. Children with JRA associated
on chromosome. 15 Physical characteristics of affected cataracts also characteristically develop band keratopathy and
individuals include tall stature, arachnodactyly, loose, flexible posterior synechiae.18
joints, scoliosis and chest deformities. Cardiovascular
abnormalities are a source of significant mortality and maybe Secondary Cataracts
in the form of dilated aortic root, ascending aorta, dissecting
aortic aneurysm and floppy mitral valve. Ocular abnormalities Less frequently, a cataract may be seen secondary to an
occur in 80 percent patients, including ectopia lentis, myopia, intraocular tumor, a foreign body, or a chronic retinal
greater risk of retinal detachment. Typically, the lens is detachment. Cataracts have also been known to occur after
dislocated upward and temporally. The zonules are often laser treatment for threshold retinopathy of prematurity.
Persistent Fetal Vasculature blindness in most cases can be principally attributed to

unoperated cataract; dense amblyopia following delayed
Persistent fetal vasculature (PFV), previously known as
surgery, complications of surgery or associated ocular
persistent hyperplastic primary vitreous is a developmental
abnormalities may also be other causes of blindness.
ocular anomaly in which the embryonic hyaloid vasculature
Visually significant cataract in children calls for prompt
fails to regress normally (Fig. 10.7.11).19 The disease entity of
surgical intervention to clear the ocular media and provide a
PFV has a wide spectrum with varying degrees of persistent
focused retinal image. Indications for cataract surgery include
components of the fetal hyaloid system. This may present as
visually significant central cataracts, dense nuclear cataracts,
mild pupillary strands and a small central/paracentral posterior
cataracts obstructing the examiner’s view of the fundus and
capsular opacification (Mittendorf's dot) or as severe as
cataracts associated with strabismus.27 The timing of treatment
retrolenticular membrane, retinal dysplasia and retinal
is crucial to visual development and successful rehabilitation of
detachment.20 PFV is described as being anterior, posterior,
children, especially during early infancy. In case of a unilateral
or both depending on which ocular structures are involved.
dense cataract diagnosed at birth, the surgeon can wait until the
PFV is typically known as an idiopathic congenital
patient is four to six weeks of age. This decreases anesthesia
malformation that has no obvious cause and that is usually
related complications and facilitates the surgical procedure.
unilateral. The affected eye is often microphthalmic when
Waiting beyond this time, however, adversely affects the visual
compared with the unaffected eye. If the eye with PFV is not
outcome. In the case of bilateral cataract diagnosed at birth, a
shorter than the normal fellow eye, then glaucoma should be
good visual outcome can be achieved if the child is operated
suspected. The characteristic features of anterior PFV include
before ten weeks of age. It is important to keep the time interval
white vascularized retrolental tissue with or without a persistent
between the surgeries performed on the two eyes to a minimum.
hyaloid artery, centrally dragged ciliary processes, an anteriorly
shifted and/or swollen lens and varying degrees of lenticular Anesthesia: Pediatric cataract surgery is unique in that,
opacification.19-23 Over a period of time, the retrolenticular preoperatively, intraoperatively, and postoperatively, the child
membrane can progressively contract, leading to retinal requires multiple examinations under anesthesia. Before
detachment (RD).19,24,25 If left untreated, it can frequently lead administering anesthesia to the child, a thorough examination
to recurrent secondary glaucoma and eventual phthisis bulbi. should be performed. The surgeon should specifically ask for
Posterior PFV predominantly affects the posterior segment birth weight, prematurity, genetic diseases or congenital
of the eye and is associated with poor visual outcome. anomalies such as congenital heart defects.
Pediatric cataract surgery is a complex issue best left to
Traumatic Cataracts surgeons who are familiar with its long-term complications
They are a common cause of unilateral loss of vision in and prolonged follow-ups. Cataract surgery in children is the
children. Penetrating injuries are usually more common than first stepping stone in the long road to visual rehabilitation.
blunt injuries. Cataracts caused by blunt trauma classically form Treatment is often difficult and tedious requiring a dedicated
stellate-or rosette-shaped posterior axial opacities, which may team effort, the most important members of the team being
be stable or progressive, whereas, penetrating trauma with the parents. It is very important to counsel parents
disruption of the lens capsule forms cortical changes that may appropriately. Parents need to come for regular follow-up visits
remain focal if small or may progress rapidly to total and see that the child wears glasses or contact lenses and
opacification. complies with medication and occlusion therapy following
surgery. Maintaining a clear visual axis while correcting the
eye for a changing residual refractive error requires careful
MANAGEMENT OF PEDIATRIC
observation, sound judgment, and diligent follow-up.
CATARACTS
Pediatric cataract is the most common cause of treatable Preoperative Evaluation
childhood blindness, accounting for 5 to 20 percent of Preoperative examination includes age appropriate vision
blindness in children worldwide.1-3 The incidence has been testing and details of strabismus and nystagmus. Visual
reported as 2.5/10,000 by the age of one year, increasing to function in older children can be assessed with preferential
3.5/10,000 by age 15.26 It is estimated that over 2,00,000 looking charts such as Teller acuity card and Keeler acuity
children are blind from disorders of the lenses. Although cards, Lea gratings and symbols (Precision Vision, Lasalle,
USA), Sheridan Gardner tests, ‘E’ charts and Snellen’s pediatric cataract surgery has been proven to have an
alphabetical charts. In very young children, who cannot co- advantage, newer formulae like the SRK-T, Hoffer Q, or the
operate for vision tests, the ability to fixate or follow light or Holladay-II formula may be used.
objects should be assessed. The presence of squint or Implantation of a fixed-power IOL into an eye that is still
nystagmus should be noted. growing makes it difficult to choose the IOL power. The child's
Preoperative examination with fully dilated pupils, if growing eye is expected to develop a myopic shift in refraction.
necessary under anesthesia, is mandatory in both eyes. It IOL implantation at the calculated emmetropic power helps
includes examination under the operating microscope or slit to fight amblyopia during childhood, but there is the risk of
lamp biomicroscope to assess the cataract and tonometry to developing significant myopia at ocular maturity. On the other
rule out any association of glaucoma. The examination also hand, too much undercorrection of the IOL power will lead
includes measurement of corneal diameter, posterior segment to immediate postoperative hypermetropia with the possibility
evaluation, keratometry, biometry and gonioscopy. During the of amblyopia. An ideal IOL power should aim at prevention
examination, the surgeon must look for the type and severity of amblyopia in childhood with the least possible residual
of cataract including pre-existing posterior capsule defect. refractive error in adulthood.
Clinical examination of the child should include a complete Most surgeons tend to undercorrect the IOL power at the
examination of all systems, including respiratory, nervous, and time of surgery in anticipation of the postoperative myopic
cardiovascular systems. Supportive laboratory investigations shift. Several nomograms on IOL power selection have been
should include hemogram, blood sugar, titres for antibodies published in literature. However, these tables are only meant to
to TORCH agents, HIV, HBsAg and X-rays or echocardio- help as a starting point toward appropriate IOL power selection,
graphy, if required. Special tests to rule out metabolic diseases which is a multifactorial decision customized for each child based
should be ordered whenever necessary. on many variables (including age, laterality [one eye or both],
amblyopia status [dense or mild], compliance with glasses, and
Biometry: IOL Power Calculation family history of myopia). The axial length increases faster in
Calculation and selection of intraocular lens (IOL) power is the first few years of life. If the decision regarding IOL
one of the major challenges while managing pediatric cataract implantation needs to be changed, e.g. in cases of ciliary sulcus
surgeries. Obtaining reliable keratometry and axial length implantation, appropriate adjustment may need to be done. The
measurement are a prerequisite for accurate IOL power residual refractive error needs to be corrected with spectacles
calculation. Keratometry can be performed under anesthesia or contact lens that are adjusted throughout the growing period
with a handheld keratometer (Fig. 10.7.16). Ultrasound according to refractive development.
biometry is performed using the contact/immersion However, even after undercorrection, refractive surprises
technique for axial length measurement (Fig. 10.7.17). can occur. The long-term outcome will certainly remain an
Although, no single formula for IOL power calculation in open question for years to come.
Fig. 10.7.16: Handheld keratometry being performed Fig. 10.7.17: Immersion ultrasound biometry being performed
Bimanual irrigation and aspiration
The approach of the authors for undercorrection implanted, after injecting the OVD through the paracentesis
depending upon the age at the time of surgery is as follows: incision, a 3 mm single plane self-sealing valvular clear corneal
incision with a 2 mm internal entry should be made. The
Age Undercorrection (%)
incisions are sutured due to the low scleral rigidity and also
0-3 months 35% because children have a tendency to rub their eyes.
3-6 months 30%
6-12 months 25% Anterior capsule management: The anterior capsule in
1-2 years 20% children is very elastic, and therefore it may be difficult to
2-4 years 15%
4-6 years 10%
perfor m a controlled manual continuous cur vilinear
>6 years 5% capsulorrhexis (CCC). However, a manual CCC is the gold
standard in terms of maintaining the integrity of the capsular
As an example, in a seven months old child, if the edge. The shape, size and edge integrity of anterior
IOL power is calculated at +36.0D, it is undercorrected by 25 capsulotomy are very important for long-term centration of
percent. So IOL power to be implanted would be 36 - 9 = the IOL.28-30 Alternatives to manual CCC currently available
+ 27.0D. include vitrectorhexis, radiofrequency diathermy, Fugo plasma
blade,31 the two incision push pull technique, and the four
Surgical Technique incision technique.32,33
Pediatric cataract needs a special surgical strategy as these eyes Vitrectorhexis is easier to perform as compared to manual
have greater elasticity of the capsule, lower scleral rigidity, CCC, and is often the preferred approach. In contrast, a
higher incidence of inflammation and posterior capsule diathermy-cut capsulotomy, even when performed perfectly,
opacification (PCO), a thick vitreous gel, and it is a small, shows coagulated capsular debris along the edge. The Fugo
growing eye. The surgeon should strictly adhere to the blade is a unique cutting instrument that employs plasma for
principles of the closed chamber technique, such as valvular ablating tissue. It helps make a perfectly controlled anterior
incision, injection of ophthalmic viscosurgical devices (OVD) capsulotomy of any size, without the risk of radial tear. Fugo
before removing any instrument from the eye, and bimanual blade is recommended when fibrotic capsules are encountered
irrigation/aspiration. in white cataract in the absence of red reflex.
Two surgical approaches exist for lens removal in pediatric High viscosity OVDs 34 aid in performing, anterior
eyes: continuous curvilinear capsulorrhexis (ACCC), approximately
5.0 mm in diameter. Capsular staining with trypan blue35-38 or
Pars Plana Lensectomy indocyanine green is a useful adjunct in pediatric cataract
In children where aphakic spectacles or contact lenses are the surgery, especially in cases where there is poor glow. Localized
chosen means of visual rehabilitation, lensectomy may be capsular staining is performed with 0.0125 percent trypan blue.
performed through a pars plana incision with a vitreous cutting Capsulorrhexis is usually performed with Kraff-Uttrata
instrument or a manual aspirating device. Irrigation can be forceps. Care is taken to frequently grasp and regrasp the
provided by an integrated infusion sleeve or by a separate capsule to avoid peripheral extension of the CCC.
cannula for bimanual surgery. The disadvantage of this Cortical cleaving hydrodissection: After making the incision
approach is that since the capsular bag is not preserved, it and carrying out capsulorrhexis, multiquadrant hydrodissection
does not allow for in-the-bag IOL implantation either primarily is preferred, in all cases except in eyes with a white, mature
or later on in life. cataract or when a pre-existing posterior capsule defect is
suspected. It is documented that multiquadrant cortical-
Limbal Lensectomy cleaving hydrodissection in pediatric cataract surgery facilitates
This approach is often the chosen approach, especially when lens substance removal and also reduces removal time.39
either primary or secondary IOL implantation is planned. Lens removal: The lens material is usually aspirated
The incision: Pediatric cataract can be removed through a bimanually using separate irrigation and aspiration ports. Since
relatively small incision, as the lens has no hard nucleus. If no visual axis opacification (VAO) is one of the most frequent
IOL implantation is planned, two paracentesis incisions are complications in pediatric cataract surgery, meticulous removal
usually made at or near the limbus. When an IOL is being of the lens substance is crucial.
A bimanual approach minimizes anterior chamber Hence, anterior vitrectomy along with posterior capsulotomy
fluctuations and aids in thorough removal of the cortex, is advocated in infants and children younger than six to seven
especially in the subincisional area (Fig. 10.7.18). years of age.43 Most surgeons prefer manual anterior limbal
vitrectomy over pars plana vitrectomy. The adequacy of
Management of the Posterior anterior vitrectomy may be confirmed by injecting 0.1 to 0.2
Capsule in Children ml of preservative free triamcinolone (4 mg/0.1 ml) to aid
visualization of the vitreous.
The most frequent and significant problem following pediatric
However, considering the implications of vitrectomy,
cataract surgery is VAO, reaching up to almost 100 percent if
especially in children with a family history of myopia, diabetes
the posterior capsule is intact.40-42 The younger the child, the
mellitus, and possibility of cystoid macular edema, posterior
higher the incidence of VAO and the earlier the onset of VAO.
capsule management has been stratified according to the age
Maintenance of a clear visual axis remains a high priority when
of the child.44-46 Children under three years are subjected to
planning management of the posterior capsule in the
posterior continuous curvilinear capsulorrhexis (PCCC) and
amblyogenic age range. Posterior capsulotomy can be performed
anterior vitrectomy. Children between three to six years are
with various approaches including manual posterior continuous
subjected to PCCC but no vitrectomy. In children over six
curvilinear capsulorrhexis (PCCC), vitrectorhexis,
years, PCCC is not performed.
radiofrequency diathermy and Fugo plasma blade. Manual
PCCC is performed before IOL implantation, whereas, if a
Pre-Existing Posterior Capsule Defect
pars plana vitrectorhexis is performed, it is done after the IOL
is implanted. The size of the posterior capsulorrhexis should Congenital cataract in infants and children sometimes presents
be large enough to provide a clear central visual axis, but smaller with a pre-existing defect in the posterior capsule (PCD). Many
than the IOL optic, so as to allow stable in-the-bag IOL fixation. theories have been proposed to explain the development of
Manual PCCC offers the advantage of a controlled size and PCD. It is believed to begin as a posterior lentiglobus, which
strong edges but is more difficult to perform (Fig. 10.7.19). gradually progresses to a full blown posterior capsule defect.
PCCC alone may delay the onset of visual axis obscuration In classic cases of PCD, the defect is hidden behind a
but cannot eliminate it completely.43 The anterior vitreous face seemingly "routine" pediatric cataract when viewed through a
may act as a scaffold for the proliferating lens epithelial cells. normal sized, undilated pupil. The defect looks like a total
Moreover, since the inflammatory response in small children white cataract. Preoperative evaluation of such a cataract under
is severe, fibrous membranes may form on the intact anterior maximum dilation is mandatory to unveil the important
vitreous face (AVF), resulting in visual axis obscuration (VAO). diagnostic signs.14
Fig. 10.7.18: Bimanual irrigation and aspiration Fig. 10.7.19: Posterior capsulorrhexis
For bilateral cataract during this first year, aphakic glasses and/
or contact lens use may be a reasonable option. However, for
unilateral cataract, it is still controversial whether to offer
primary IOL implantation at the time of infantile cataract
surgery.
Both PMMA and hydrophobic acrylic foldable IOLs have
been widely used in pediatric eyes. However, several studies
have now shown that hydrophobic acrylic IOLs are preferable
as they offer better uveal biocompatibility and decreased
incidence of VAO,51-53 with hydrophobic acrylic IOLs causing
a delayed onset of PCO. A large randomized clinical trial-the
Infant Aphakia Treatment Study (IATS) is currently underway
to compare primary IOL implantation to contact lens
correction in children undergoing unilateral cataract surgery
in the first six months of life. In-the-bag fixation is the most
Fig. 10.7.20: “Fish tail” appearance of
preferred site of IOL implantation, although IOL may also
posterior capsule defects
be implanted in the ciliary sulcus in cases of inadequate
posterior capsular support.
Signs of pre-existing PCD are (Fig. 10.7.14):
• Demarcated thick defect margins. Optic Capture
• White dots on the posterior capsular and in the anterior
IOL optic capture through the posterior capsulotomy, with
vitrectomy.
the haptics placed in the capsular bag allows anterior vitrectomy
• Fish tail sign — a characteristic of PCD.
and minimize the risk of PCO. 54,55 However, anterior
When the globe is moved with forceps, the white granules
vitrectomy is necessary with optic capture even in children
in the anterior vitreous move with the degenerated vitreous
above five years,55 and it predisposes the eye to an increased
like a fish tail (Fig. 10.7.20).
inflammatory response.
It is important to recognize and suspect a pre-existing
posterior capsule defect. The surgical strategy includes avoiding Secondary IOL Implantation
hydrodissection in such cases, as it might lead to a blowout of
Eyes that are left aphakic are likely to require a secondary IOL
the posterior capsule.
implantation. Even if the surgeon is not planning to implant
an IOL primarily, it is important to leave behind sufficient
Intraocular Lens Implantation
anterior and posterior capsular support at the time of cataract
Options for optical correction following pediatric cataract surgery to facilitate in-the-bag or sulcus fixated IOL
surgery are primary intraocular lens (IOL) implantation, implantation so as to allow ciliary sulcus or in-the-bag
aphakic glasses and contact lenses. Primary IOL implantation placement of an IOL once the child and the eye grows.
has become the preferred approach in children above two
years.47-50 IOL implantation is still controversial in children COMMON COMPLICATIONS OF
under two years, especially those under one year, as the safety PEDIATRIC CATARACT SURGERY
of IOL implantation in these eyes is not proven. Patients with
Visual Axis Opacification
juvenile rheumatoid arthritis, microcornea, microphthalmos
and severe persistent fetal vasculature (PFV) may be considered Visual axis opacification (VAO) still remains the most frequent
as contraindications for IOL implantation. complication of pediatric cataract surgery. The most critical
IOL implantation in children has the benefit of providing factor influencing the occurrence of VAO is age at surgery.
at least partial optical correction which aids in visual While opacification is nearly universal in infantile eyes, the
development especially in eyes prone to amblyopia. Advances incidence decreases with increasing age. Primary management
in surgical techniques and instrumentation, combined with of the posterior capsule and anterior vitrectomy are effective
implantation of better quality IOLs has now resulted in fewer in preventing re-opacification of visual pathways.43 The type
IOL related complications in children. This encourages a larger and material of IOL also is a very important factor affecting
number of surgeons to use IOLs even in very young children. the incidence of VAO.
Management of PCO in Children Uveal Inflammation

This depends on the age of the child, his or her cooperation, Intense uveal inflammation or severe fibrinoid reaction is a
and on the density of the membrane. concern particularly in infants and young children. A traumatic
surgical technique and ciliary sulcus, or asymmetrical fixation
Nd:YAG laser capsulotomy: An Nd:YAG laser capsulotomy of the IOL are other contributing factors which may be
is preferred in children over five years as they can follow the responsible for producing an exaggerated inflammatory
instructions and co-operate during the procedure. This response.
procedure has been shown to effectively maintain a clear axis
in a significant proportion of children. However, a Other Complications
capsulotomy may have to be performed more than once in
certain situations. Retinal detachment (RD)58 and cystoid macular edema are
infrequent following aphakia in pediatric cataract surgery. The
Secondary surgical membranectomy with vitrectomy: In reasons for this low incidence of postoperative retinal
eyes in which the capsule is too thick and is not amenable to complications are not very well known.
Nd:YAG capsulotomy, or, when the child is too young to co- Corneal astigmatism is recognized as a problem arising
operate for a laser procedure, a secondary surgical from cataract surgery. Postoperative astigmatism is more
membranectomy/capsulotomy is done. The pars plana important in children than in adults because of its adverse
approach is preferred as it allows more direct and easier effect on vision development and the risk of amblyopia.
removal of the PCO.
NEWER APPROACHES
Glaucoma
Sealed Capsule Irrigation
Glaucoma is a recognized complication of pediatric cataract Several chemicals have been suggested in experimental settings
surgery. Despite improved surgical techniques, the incidence to remove or kill the residual lens epithelial cells (LECs).
of glaucoma following successful cataract removal remains However, these chemicals are also toxic to other ocular
high (ranging from 3 to 41%).56-58 A significant number of structures. Maloof and associates have designed a sealed
surgeons regard aphakia as a cause of glaucoma. However, capsule irrigation device (Perfect CapsuleTM) that can help to
the glaucoma occurring postoperatively may be better selectively irrigate the capsular bag. This may help pediatric
described as "glaucoma in aphakia" and "glaucoma in cataract surgeons to eliminate or delay VAO by using such
pseudophakia". The most common type of glaucoma that chemicals through this device.59
develops following congenital cataract surgery is open-angle
glaucoma. The risk factors include age at the time of surgery, Heparin in Irrigating Solution
pre-existing ocular abnormalities, type of cataract and the effect
of lens particles, lens proteins, inflammatory

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Postgraduate

Jaypee Brothers Medical Publishers (P) Ltd.

© 2012, Jaypee Brothers Medical Publishers

Inquiries for bulk sales may be solicited at: jaypee@jaypeebrothers.com

Publisher: Jitendar P Vij

The blessings of the Almighty

Balasubramanya Ramamurthy MD DNB Devendra V Venkatramani MBBS

Geetha Krishnan Iyer DO DNB FRCS Glasg J Nirmal M Pharm

Kalpana Narendran DO DNB Malvika Gupta DO DNB

Mridula Mehta MS Parul Ichhpujani MS

R Revathi DO MS Ramesh Murthy FRCS

Rajesh Ramanjulu MD Reshmi Bhaskar MS

Rupesh Agrawal MMed FRCS Glasg Sanjay Kai MD

S Senthilkumari M Pharm PhD Sathyarekha MS

Savitri Sharma MD FAMS Shraddha S Puranik MD

Shah Nawaz MBBS Soundarya Lakshmi Madhira MSc

Sujith Vengayil MD FRCS Glasg Sushmita Kaushik MS

Vaishali A Vasavada MS Vikas Menon DNB FLVPEI

SECTION 2: LIGHT, VISION, OPTICS AND REFRACTION

SECTION 3: CONTACT LENS

SECTION 4: LOW VISION

SECTION 5: APPLIED BASIC SCIENCES RELATED TO OPHTHALMOLOGY

SECTION 6: CORNEA AND EXTERNAL EYE DISEASES

6.3 Disorders of the Pediatric Cornea ....................................................................................................... 417-429

6.10.2 Lamellar Keratoplasty ............................................................................................................... 686-699

SECTION 7: REFRACTIVE SURGERY

9.3.3 Congenital and Developmental Glaucoma: Clinical Profile ................................................... 860-869

SECTION 10: LENS AND ITS ANOMALIES

10.5.4 Phacoemulsification in Intraoperative Floppy Iris Syndrome ............................................ 1034-1035

SECTION 11: UVEA

12.8 Systemic Diseases with Retinal Manifestations ............................................................................... 1212-1226

SECTION 13: ORBIT, EYELID AND LACRIMAL SYSTEM

13.9 Esthetic Eyelid Surgery .................................................................................................................... 1376-1381

SECTION 14: OCULAR ONCOLOGY

SECTION 15: SYSTEMIC OPHTHALMOLOGY

SECTION 16: NEURO-OPHTHALMOLOGY

16.1.3 Cranial Nerves Evaluation from an Ophthalmologist’s Perspective ................................. 1549-1557

16.10 Ocular Motility Disorders .................................................................................................................. 1712-1740

SECTION 17: NYSTAGMUS

SECTION 18: PEDIATRIC OPHTHALMOLOGY

SECTION 19: STRABISMUS

19.10 Myogenic Strabismus ....................................................................................................................... 2071-2077

SECTION 20: OCULAR TRAUMA

SECTION 21: LASERS IN OPHTHALMOLOGY

21.3 YAG Capsulotomy .............................................................................................................................. 2191-2196

SECTION 22: RELEVANT CONCERNS IN OPHTHALMIC PRACTICE

Appendices ..................................................................................................................................... 2303-2307

Index ..................................................................................................................................... 2309-2339

BACKGROUND retained till the 10th version of ICD. The recommended

Table 1.1: Categories of visual impairment and blindness

Table 1.2: Proposed revision of categories of visual impairment in ICD-10, 2008

Fig. 1.1: Commonly used definitions of blindness

Table 1.4: Global estimate of visual impairment by WHO subregion, 2002*

Global Trends in Blindness immunization, vitamin A supplementation, improved dietaries

Fig. 1.3: Global causes of blindness as a percentage of total blindness (2004)

Global Causes of Blindness

Earlier data from WHO did not include uncorrected

Table 1.5: Major causes of blindness in India

Table 1.6: Profile of blindness in India

LIGHT AND ITS PROPERTIES

Fig. 2.1.3: Figure of a wave demonstrating the concept of wave

Figs 2.1.4A and B: Demonstration of phase difference, constructive

Fig. 2.1.5: Ray diagram explaining the scattering of light

Scattering Fig. 2.1.6B: Perception of blue color of the sky at mid-day is