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Modern Ophthalmology, 3rd edition (Vol 2)
© 2005, LC Dutta, Nitin K Dutta
All rights reserved. No part of this publication should be reproduced, stored in a retrieval system,
or transmitted in any form or by any means: electronic, mechanical, photocopying, recording, or
otherwise, without the prior written permission of the editors and the publisher.

This book has been published in good faith that the material provided by contributors is original.
Every effort is made to ensure accuracy of material, but the publisher, printer and editors will
not be held responsible for any inadvertent error(s). In case of any dispute, all legal matters to
be settled under Delhi jurisdiction only.

First Edition: 1994

Second Edition: 2000
Reprint: 2003
Third Edition: 2005

ISBN 81-8061-470-0 (Set)

Typeset at JPBMP typesetting unit
Printed at Paras Offset Pvt Ltd., C-176, N.I.A., Phase-1, New Delhi
 Dedicated to
students who help us to
continue to learning and the patients
who constantly stimulate our search
for better methods of managing their eye ailments
 Contributors
Mary Abraham MS DOMS M Baskaran MD Dipak Bhuyan MS
Consultant Ophthalmologist, Chennai Consultant Assistant Professor
Shankara Nethralaya Regional Institute of Ophthalmology
Anil Kumar Agarwal
Chennai Guwahati
Fellow, Shri Sankaradeva Nethralaya,
Guwahati
Samar K Basak MD DNB VA Bidaye MS DO
BK Ahluwalia MS DOMS Disha Eye Hospitals and Research Medical Director
Professor of Ophthalmology Centre, Barrackpore Bidaye Hospital
Medical College, Rohtak West Bengal Baroda
David J Apple MD Surendra Basti MS Jyotirmay Biswas MS
Professor of Ophthalmology and Ex-Consultant Medical and Vision Research Foundation
Pathology LV Prasad Eye Institute Shankara Nethralaya, Chennai
Director Hyderabad
David J Apple Laboratories for Gagandeep S Brar
Ophthalmic Devices Research H Bhattacharjee MS Assistant Professor
John A Moran Eye Center Medical Director Department of Ophthalmology
University of Utah Shri Shankaradeva Nethralaya Post Graduate Institute of Medical
Salt Lake City, Utah, USA Guwahati Education and Research
Chandigarh
N Arivazhagan Kasturi Bhattacharjee MS
LV Prasad Eye Institute, Hyderabad Consultant Sanghamitra Burman
Hemamalini Arvind MS Shri Shankaradeva Nethralaya Oncology Oculoplasty Service
Glaucoma Service Guwahati LV Prasad Eye Insitute, Hyderabad
Shankara Nethralaya
Chennai Pankaj Bhattacharjee Girish Chandra MS FRCS FRC Ophth
Fellow Consultant Ophthalmologist
Supratik Bandopadhyay Shri Shankaradeva Nethralaya Harley Street
Senior Resident Guwahati London, UK
Department of Ophthalmology
Post Graduate Institute of Medical RP Bhatia MS Aman Chandra MBBS
Education and Research, Chandigarh Ex-Professor of Ophthalmology Senior House Officer
Institute of Medical Sciences London, UK
Souvik Banerjee MS DO PhD Varanasi
Assistant Professor Hari Charan FRCS FICS
A Bhatnagar MD
Department of Ophthalmology Director
Sir Gangaram Hospital
Ramakrishna Mission Seva Pratishthan KC Memorial Eye Hospital, Jaipur
New Delhi
Vivekananda Institute of Medical
Sciences, Kolkata Nitul S Bhatt MS DOMS
Neha Charan MS DNB
Consultant
Consultant
Ashish Kumar Bansal MS Vitreoretinal Centre, Mumbai
KC Memorial Eye Hospital, Jaipur
Consultant
Corneal Service Muna Bhende MS
LV Prasad Eye Institute Consultant Rohit Charan MS
Hyderabad Shankara Nethralaya Consultant
Chennai KC Memorial Eye Hospital, Jaipur
CK Barua MS
Director Pramod S Bhende Samrat Chatterjee MS
Regional Institute of Ophthalmology Consultant Consultant
Guwahati Medical College Shankara Nethralaya Cornea and Anterior Segment
Guwahati Chennai 139, MC Road, Guwahati
viii Modern Ophthalmology

Navneet Chauhan Nibaran Gangopadhyay MS SK Handique MD

Resident of Ophthalmology Consultant Senior Consultant Radiologist
AIIMS New Delhi Cornea and Anterior Segment Institute of Radiology
LV Prasad Eye Institute Guwahati Neurological Research
Sumit Choudhury MS DO Hyderabad Centre, Guwahati
Consultant
Eye Care and Research Centre Deepak Garg Madhavi G Hirode MS
Kolkata Consultant Consultant
Shankara Nethralaya, Chennai Vitreoretinal Surgeon
Tanuj Dada MD Gobind Clinic, Baroda
Assistant Professor Amala Elizabeth George DNB FRCS
Clinical Ophthalmology Consultant Santosh G Honavar MD
Dr Rajendra Prasad Centre for Sankara Nethralaya Consultant
Ophthalmic Sciences Chennai Ocular Oncology Service
All India Institute of Medical Sciences, LV Prasad Eye Institute, Hyderabad
New Delhi Viji K George MS
M and I Institute of Ophthalmology Anjli Hussain MS
Subhash Dadeya MD Ahmedabad Consultant
Senior Resident Vitreoretinal Service
Guru Nanak Eye Centre Stephen C Gieser MS LV Prasad Eye Institute, Hyderabad
New Delhi Christian Medical College
Schell Eye Hospital, Vellore Nazimul Hussain MS DNB
Hrishikesh Das Consultant
Resident Ruchi Goel LV Prasad Eye Institute
RP Centre for Ophthalmic Sciences Resident Hyderabad
AIIMS, New Delhi Safdarjung Hospital
New Delhi Tomohiro Iida MD
Subhra Das MS Professor and Chairman
Assistant Professor Lingam Gopal MS Department of Ophthalmology
Regional Institute of Ophthalmology Senior Consultant Fushikima Medical University
Guwahati Shankara Nethralaya Japan
Chennai
Tara Prasad Das MS Shyama Jain MD
Director AK Grover MS MNAMS Guru Nanak Eye Centre
Smti Kannuri Santhamma Chief Ophthalmic Surgeon New Delhi
Retina Vitreous Centre Sir Gangaram Hospital
LV Prasad Eye Institute New Delhi Subhadra Jalali MD
Hyderabad Consultant
Amit Gupta MS LV Prasad Eye Institute
Satyen Deka MS Resident Hyderabad
Consultant Department of Ophthalmology
Shri Shankaradeva Nethralaya Post Graduate Institute of Medical Barrie Jay MD FRCS FC Ophth
Guwahati Education and Research, Chandigarh Professor
Clinical Ophthalmology
B Dutta Institute of Ophthalmology
Consultant Amod Gupta MS University of London
Aditya Jyot Eye Hospital, Mumbai Professor and Head of Ophthalmology London, UK
Post Graduate Institute of Medical
LC Dutta DO (London) FRCS Education and Research, Chandigarh Marcelle Jay PhD
Director Senior Lecturer
Ex-Professor and Chief Organiser SK Gupta MD Institute of Ophthalmology
Regional Institute of Ophthalmology Senior Consultant University of London
Medical College, Guwahati LV Prasad Eye Institute, Hyderabad London, UK
Eye Foundation, Guwahati Vishali Gupta MS
Senior Resident, Ophthalmology Elizabeth Joseph MS
Nitin K Dutta DO Post Graduate Institute of Medical Consultant
Consultant Education and Research Little Flower Hospital
Eye Foundation, Guwahati Chandigarh Angamally
 Contributors ix
Kamlesh MD M Kumar Jnanankar Medhi MS
Professor Resident Trainee Consultant
Guru Nanak Eye Centre Guru Nanak Eye Centre Shri Shankaradeva Nethralaya
New Delhi New Delhi Guwahati

Chitra Kannabiran PhD K Lakshmanamurthy N Medhi MD

Scientist Consultant Senior Consultant Radiologist
Kallam Anji Reddy Molecular Genetics Arvind Eye Hospital, Madurai PRIMUS, Guwahati
Laboratory, LV Prasad Eye Institute
Hyderabad Sanjiv Lal MS AS Mehrotra MS FICS MAMS
Fellow Ex-Professor of Ophthalmology
Deva Prasad Kar MS Arvind Eye Hospital, Madurai SMS Medical College, Jaipur
Arvind Eye Hospital
Madurai Paolo Lanzetta MD Shantanu Mitra DOMS
Department of Ophthalmology, Eye Care and Research Centre
Sushismita Kaushik BS M Phil Ophth University of Udine, Udine, Italy Kolkata
Postgraduate Institute of Medical
Education and Research Bharti Lavingia MS Dinesh Mittal MD
Chandigarh Professor Formerly Senior Resident
M and I Institute of Ophthalmology RP Centre of Ophthalmic Sciences
Bakulesh Khamar MS Ahmedabad All India Institute of Medical Sciences
Assistant Professor of Ophthalmology New Delhi
NHL Municipal Medical College Lakshmi Mahesh MD
Ahmedabad Consultant, Shankara Nethralaya Soma Sheila I Murthy MD
Chennai Consultant
Mayuri Khamar MS Cornea and Anterior Segment
Assistant Professor of Ophthalmology Ajit B Majji MD Ocular Immunology and Uveitis Service
M and I Institute of Ophthalmology Consultant LV Prasad Eye Institute
Ahmedabad LV Prasad Eye Institute Hyderabad
Hyderabad
Sarfaraz Ali Khan MD Ramesh Murthy FRCS
Department of Vision Rehabilitation Sarmi Malik MD Oncology Oculoplasty Service
L V Pradad Eye Institute Resident LV Prasad Eye Institute
Hyderabad Sir Gangaram Hospital Hyderabad
New Delhi
AK Khurana MS MAMS Ranabir Mukherji MS DOMS PhD FC Ophth
Associate Professor of Ophthalmology KPS Malik MD Director
Postgraduate Institute of Medical Head Eye Care and Research Centre
Science, Rohtak Department of Ophthalmology Kolkata
Safdarjung Hospital
Kamal Kishore MS New Delhi PN Nagpal MS
RP Centre of Ophthalmic Sciences Director
All India Institute of Medical Sciences Nick Mamalis MD Retina Foundation
New Delhi Professor of Ophthalmology Ahmedabad
John A Moran Eye Center, University
S Krishnaiah MSc MPS of Utah, Salt Lake City, Utah, USA Milind Naik
Department of Ophthalmology Fellow
Postgraduate Institute of Medical Himanshu P Matalia MS Oculoplasty
Education and Research, Chandigarh Adjunct faculty LV Prasad Eye Institute, Hyderabad
Cornea and Anterior Segment Service
K Krishnakumar BS MPhil Opt Sudhakar and Sreekanth Ravi Stem Cell P Namperumalsamy MS
Lecturer, Sankara Nethralaya Biology Laboratory Director
Chennai LV Prasad Eye Institute Arvind Eye Hospital
Hyderabad Madurai
Amol D Kulkarni MD
Department of Ophthalmology Annie Mathai MS FRCS (Ed) Priya Narang
University of California LV Prasad Eye Institute M and I Institute of Ophthalmology
Irvine, California Hyderabad Ahmedabad
x Modern Ophthalmology

S Narang Suresh K Pandey MD Jagat Ram MS

M and I Institute of Ophthalmology Assistant Professor Professor Ophthalmology
Ahmedabad John A Moran Eye Center Post Graduate Institute of Medical
Department of Ophthalmology and Education and Research
SK Narang MS Visual Sciences, University of Utah Chandigarh
Director Salt Lake City, Utah, USA
M and I Institute of Ophthalmology Kavita Ramakrishnan MS
Ahmedabad Arvind Eye Hospital
Sobi Pandey MS Madurai
R Narayanan MD Consultant Ophthalmologist
Department of Ophthalmology Nav Dristi Eye Care Centre R Ramakrishnan MS FACS
University of California, Irvine, USA Kanpur Chief Medical Officer
Arvind Eye Hospital
S Natarajan DO Maurizio Battaglia Parodi MD SN High Road
Director Eye Clinic Tirunelvel
Aditya Jyot Eye Hospital, Mumbai University of Trieste, Trieste, Italy Tamil Nadu

G Natchiar MS Avinash Pathengay FRCS Sreeram Ramalingum MS

Deputy Director Consultant Consultant
Arvind Eye Hospital, Madurai LV Prasad Eye Institute Shankara Nethralaya, Madurai
Hyderabad
D Dwarak Nath MD KM Ranganath MS
Arvind Eye Hospital, Madurai Mahesh Pillai MD FRCS Consultant
Felow Ocular Immunology and Uveitis Udhi Eye Centre, Chennai
Arvind Neelakanthan MS Immunology Laboratory
Shankara Nethralaya, Chennai National Eye Institute B Sridhar Rao MS
Bethesda, Maryland, USA Ex-Consultant
Neena MD Shankara Nethralaya, Chennai
Senior Resident Mukesh Porwal MS
Ophthalmology Consultant GN Rao
RP Centre of Ophthalmic Sciences Retina Foundation Chairman
All India Institute of Medical Sciences Ahmedabad LV Prasad Eye Institute
New Delhi Hyderabad
Neelam Pusker MD
Randall J Olson MD Resident Anju Rastogi MS
Professor of Ophthalmology and RP Centre of Ophthalmic Sciences Associate Professor
Chairman All India Institute of Medical Sciences Guru Nanak Eye Centre, New Delhi
Department of Ophthalmology and New Delhi
Visual Sciences, John A Moran Eye KS Ratnakar MD FICS FIMSA
Center, University of Utah Suresh Puthalath MS Professor Pathology
Salt Lake City, Utah, USA Consultant Dean, Nizam’s Institute of Medical
Arvind Eye Hospital, Madurai Sciences, Hyderabad
Jyoti S Padalay MS
Ex-Professor Ophthalmology Biju Raju Dhanashree Ratra MS
JJ Hospital, Mumbai Ranjini Eye Care Consultant
Vyttila Cochin 682919 Shankara Nethralaya
Nikhil Pal MD Chennai
Resident Seemant Raizada MS
RP Center of Ophthalmic Sciences Research Fellow R Raveendran MS DO
All India Institute of Medical Sciences Medical and Vision Research Consultant Ophthalmologist
New Delhi Foundation Udhi Eye Centre, Chennai
Chennai
Anita Panda MS
Professor Ophthalmology LS Mohan Ram K Ravishankar FRCS DO DNB
RP Centre of Ophthalmic Sciences Retina-Vitreous Service Consultant
All India Institute of Medical Sciences LV Prasad Eye Institute Shankara Nethralaya
New Delhi Hyderabad Chennai
 Contributors xi
Mantosh Ray MD Pratik Sen Tarun Sharma MS
Senior Resident Consultant, Ophthalmologist Vitreoretinal Surgeon
RP Centre of Ophthalmic Sciences Shankaradeva Shankara Nethralaya
All India Institute of Medical Sciences Nethralaya, Chennai Chennai
New Delhi
Harinder Singh Sethi MD FRCS Vidushi Sharma MD FRCS (Edin)
Vijay Anand Reddy Senior Research Associate Senior Resident
Oncology Oculoplasty Service Dr Rajendra Prasad Centre for Dr Rajendra Prasad Center
LV Prasad Eye Institute Ophthalmic Sciences for Ophthalmic Sciences
Hyderabad All India Institute of Medical Sciences, All India Institute of Medical Sciences
New Delhi New Delhi
Madhukar Reddy MS
Consultant Ophthalmologist Vinay A Shah Yog Raj Sharma MS
Dristi Eye Centre University of Florida Professor
Hyderabad College of Medicine, Jacksonville RP Centre of Ophthalmic Scineces
Florida, USA All India Institute of Medical Sciences
N Rishita MSc PhD New Delhi
Community Ophthalmology Service Alpesh R Shah
LV Prasad Eye Institute Consultant Surendra Shetty MS
Hyderabad Ila Devi Cataract and Shankara Nethralaya, Chennai
IOL Research Center
JN Rohatgi MS DO FRCS FIAMS FC Ophth Raghudeep Eye Clinic Rajan Shonek MD
Ex-Professor of Ophthalmology Ahmedabad Fellow
Medical College, Patna Shankara Nethralaya
BR Shamanna Chennai
Shailendra Sabherwal MD MD Dip NBE (MCH) Dip NBE (SPM)
Fellow Consultant
LV Prasad Eye Institute, Hyderabad LV Prasad Eye Institute, Hyderabad Deepender V Singh
Resident
Mahipal S Sachdev MD Mahesh P Shanmugam MS RP Centre, AIIMS
Ex-Associate Professor Consultant, Shankara Nethralaya New Delhi
RP Centre, Centre for Sight Chennai
New Delhi Vinita Singh MS
B Shantha MS Professor of Ophthalmology
B Saharia MD Consultant KG Medical College
Senior Consultant Radiologist Shankara Nethralaya, Chennai Lucknow
Institute of Radiology
Guwahati Neurological Research Centre Dhananjay Sharma Archana Sood MS
Hyderabad Arvind Eye Hospital Senior Resident
Madurai RP Center for Ophthalmic Sciences
JS Saini MD MAMS AIIMS, New Delhi
Professor Ophthalmology Namrata Sharma MD
Post Graduate Institute of Medical Senior Resident Devindra Sood MBBS DO
Education and Research, Chandigarh RP Centre of Ophthalmic Sciences Consultant
All India Institute of Medical Sciences Glaucoma Imaging Centre
Virender S Sangwan MS New Delhi New Delhi
Head of Cornea and Anterior Segment
Service, Uvea and Immunology RK Sharma MS NN Sood DO FRCS FAIMS FC Ophth
Sudhakar and Sreekanth Ravi Stem Cell Consultant Ex-Professor
Biology Laboratory Retina Foundation RP Centre of Ophthalmic Sciences
LV Prasad Eye Institute Ahmedabad All India Institute of Medical Sciences
Hyderabad New Delhi
Savitri Sharma MD
Sandeep Saxena MS Devchand Nagin Das Jhaveri Manjula Sridhar MD
Associate Professor (Retina Vitreous) Microbiology Centre Consultant
Eye Department LV Prasad Eye Institute Shankara Nethralaya
KG Medical University, Lucknow Hyderabad Chennai
xii Modern Ophthalmology

M Srinivasan MS Sandeep Thakur MD Geeta G Vemuganti MD

Consultant, Arvind Eye Hospital Shankara Nethralaya, Chennai Ophthalmic Pathologist
Madurai LV Prasad Eye Institute, Hyderabad
Mathew A Thomas MD
L Vijaya MS DO
Kallukuri Sumasri BS Ophth Assistant
Head
LV Prasad Eye Institute Clinical Professor of Ophthalmology
Glaucoma Service
Hyderabad Washington University School of
Shankara Nethralaya, Chennai
Medicine
Subhuram MS MCh USA Usha H Vyas MS
Associate Professor of Neurology Professor
Medical College Ravi Thomas MS Ophthalmology
Thanjavur Director Nagari Hospital, Ahmedabad
LV Prasad Eye Institute
TS Surendran MS Hyderabad Ajeet Madhab Wagle MS
Medical Director Ex-Fellow
Medical Research Foundation Nitin Trivedi MS Shankara Nethralaya, Chennai
Shankara Nethralaya Assistant Professor
Chennai M and I Institute of Ophthalmology Liliana Werner MD PhD
Ahmedabad Assistant Professor
Sudha Sutaria MS David J Apple Laboratories for
Honorary Professor of Ophthalmic Devices Research
Ophthalmology (Retd) R Vadhani MS University of Utah, Salt Lake City
Mayo Hospital Retina Foundation Utah, USA
Nagpur Ahmedabad
M Edward Wilson Jr MD
Jaya Thakur MD Abhay R Vasavada MS DO FRCS Professor and Chairman
Consultant Ila Devi Cataract and IOL Research Storm Eye Institute
Tilganga Eye Center Center, Raghudeep Eye Clinic Medical University of South Carolina
Kathmandu, Nepal Ahmedabad Charleston, USA
 Preface to the Third Edition
A major change of this edition is the inclusion of around 50 new chapters relating to amongst others, the
latest technology of imaging systems in diagnosis of ophthalmic diseases like Ultrasound Biomicroscopy,
OCT, Computerized Tomography and Magnetic Resonance Imaging study of the retina and some neuro-
ophthalmological conditions. The chapters of the section on Retina —Vitreous has been completely reorganized
by Dr TP Das as Section Editor. I thank Dr Das for his efforts to make the section more attractive.
I congratulate the authors for their outstanding academic collaboration.
The first edition of Modern Ophthalmology was published in 1994 in one volume. More and more authors
joined for the second edition published in 2000 in two volumes and that edition had one reprint in 2003. I
thank Shri JP Vij, Chairman and Managing Director of M/s Jaypee Brothers Medical Publishers Pvt Ltd, for
bringing out the third edition in 3 volumes as an international publication. The publishers have shown utmost
promptness in publication of this edition. Mr Tarun Duneja, General Manager (Publishing) and his team
deserve special praise for their active support.
Dr Nitin K Dutta deserves special thanks for his immense involvement in bringing out this edition.

LC Dutta
 Preface to the First Edition
This multiauthored book contains contributions from different authors in their fields of prime interest.
Though all the dedicated researchers and clinicians in their diverse fields were approached, the editor was
unable to include the contributions from all of them.
Modern Ophthalmology is the first Indian text of its kind which has contributors spread over a number of
disciplines and specialties highlighting the recent trends on the subject. The chapters written on selected
topics have been contributed by ophthalmic clinicians, surgeons and research scientists most of whom have
dominated the national and international scene of ophthalmology, making significant contributions to the
advancement of knowledge. The text has been supplemented by other non-ophthalmic teachers and research
workers such as pathologists and geneticists who have been contributing to the world literature in their
respective specialties.
Almost each of the eleven sections of the book covers the topics over several chapters; the contributors
have attempted to give a broad view of the topic to the readers, keeping brevity and clarity of mind in a
comprehensive and lucid manner. The book strives to serve as a handy basic text to the postgraduate
students in ophthalmology. Also, the chapters have been structured so as to make the text a storehouse of
knowledge and an excellent resource book for the practicing ophthalmologists and clinicians enabling them
to sharpen their diagnostic, clinical and surgical skill in handling ophthalmic cases.
The book has been profusely illustrated with original black and white and color photographs, supplemented
by clearly drawn line diagrams wherever required. The text, which is replete with generous bibliographic
references, is also aimed to serve as a foundation/resource book for the research workers engaged in
different specialty areas of ophthalmology and other interdisciplinary subject areas.
The editor is indebted to the contributors who have willingly devoted a large amount of their valuable
time to share their most up-to-date knowledge and unique perspective by means of the written word. I am
specially grateful to my friends Dr BT Maskati and Dr PN Nagpal for helping me in the preparation of the
list of contributors. I wish to thank M/s Jaypee Brothers Medical Publishers (P) Ltd., for their valuable
technical assistance in publishing this book.

LC Dutta
 Contents
11. Viral Conjunctivitis 71
VOLUME 1 Bakulesh Khamar, Mayuri Khamar
Nitin Trivedi, Usha H Vyas
Section 1
12. Trachoma 76
DISORDERS OF THE EYELIDS Bakulesh Khamar, Mayuri Khamar
1. Anatomy of the Eyelids 1 Nitin Trivedi, Usha H Vyas
Bakulesh Khamar, Mayuri Khamar, 13. Bacterial and Special Conjunctival
Nitin Trivedi, Usha H Vyas Conditions 80
2. Congenital Eyelid Anomalies 4 Bakulesh Khamar, Mayuri Khamar,
Bakulesh Khamar, Mayuri Khamar, Nitin Trivedi, Usha H Vyas
Nitin Trivedi, Usha H Vyas 14. Laboratory Diagnosis of Extraocular
3. Anomalies of the Eyelid Margin and Cilia 7 Infective Organisms 85
Bakulesh Khamar, Mayuri Khamar, LC Dutta, Nitin K Dutta
Nitin Trivedi, Usha H Vyas 15. Allergic Conjunctivitis and
4. Blepharitis and Meibomian Allied Conditions 90
Gland Dysfunction 17 LC Dutta, Nitin K Dutta
Samrat Chatterjee, Nibaran Gangopadhyay 16. Dry Eyes 99
5. Inflammatory Diseases of the Eyelids 30 Bakulesh Khamar, Mayuri Khamar,
Bakulesh Khamar, Mayuri Khamar, Nitin Trivedi, Usha H Vyas
Nitin Trivedi, Usha H Vyas 17. Ocular Surface Squamous Neoplasia 110
6. Anomalies of the Eyelid Position 35 Samrat Chatterjee, Santosh G Honavar
Bakulesh Khamar, Mayuri Khamar, 18. Conjunctival Tumors 123
Nitin Trivedi, Usha H Vyas LC Dutta, Nitin K Dutta
7. Tumors of the Eyelids* 48 19. Degenerative Conditions of Conjunctiva 127
Bakulesh Khamar, Mayuri Khamar, Bakulesh Khamar, Mayuri Khamar,
Nitin Trivedi, Usha H Vyas Nitin Trivedi
8. Miscellaneous Conditions of the Eyelids 57
Bakulesh Khamar, Mayuri Khamar, Section 3
Nitin Trivedi, Usha H Vyas DISEASES OF CORNEA
Section 2 20. Applied and Functional Anatomy of
the Cornea 131
DISEASES OF CONJUNCTIVA Nitin K Dutta, LC Dutta
9. Anatomy of the Conjunctiva 61 21. Various Methods of Examination
Bakulesh Khamar, Mayuri Khamar, of the Cornea 137
Nitin Trivedi, Usha H Vyas S Basti, S Sabherwal, S Gupta
10. Clinical Manifestations of 22. Specular Microscopy 147
Conjunctival Diseases 66 M Srinivasan
Bakulesh Khamar, Mayuri Khamar, Nitin Trivedi, 23. Applications of Corneal Topography 154
Usha H Vyas Anita Panda, M Ray
xviii Modern Ophthalmology

24. Corneal Ulcer 161 42. Displacement of the Lens: Etiology

M Reddy, Savitri Sharma, GN Rao and Management 322
YR Sharma, Nikhil Pal, D Mittal, Deepender V Singh
25. Diagnostic Methods in Ocular
Microbiology 181 43. Etiopathogenesis of Senile Cataract:
Savitri Sharma Prospects of Medical Therapy 327
YR Sharma, Nikhil Pal, Kamal Kishore,
26. Keratomycosis 191 Deepender V Singh
Samar K Basak
44. Work-up for Cataract Surgery 332
27. Viral Keratitis 199 Sudha Sutaria
Anita Panda, Archana Sood, Navneet Chauhan
45. Evolution of Modern
28. Corneal Degenerations and Dystrophies 213 Intraocular Lens Surgery 335
CK Barua, LC Dutta Suresh K Pandey, Liliana Werner, David J Apple
29. Keratoconus 222 46. History of IOL 344
Bharti Lavingia, VK George Neha Charan, R Charan, H Charan

30. Peripheral Corneal Ulcers 226 47. Foldable IOLs 352

J Ram , SK Pandey Tanuj Dada, Harinder S Sethi
48. Anesthesia for Cataract Surgery 361
31. Ocular Chemical Burns 231
J Ram, SK Pandey
JS Saini, A Gupta
49. Extracapsular Cataract Extraction
32. Eye Banking 242 and IOL Implantation 367
JS Saini, SK Gupta Alpesh R Shah, Abhay R Vasavada
33. Penetrating Corneal Transplantation 252 50. Techniques of Nonphaco Small
AK Bansal, GN Rao Incision Cataract Surgery (SICS) 378
34. Current Status of Lamellar Keratoplasty 268 KPS Malik, Ruchi Goel
Anita Panda 51. Concept and Principles of Phacomachine 387
35. Evolution of Refractive Keratoplasty 276 Jagat Ram, Suresh K Pandey
LC Dutta, Nitin K Dutta
52. Removal of Subincisional Cortex in
36. Photorefractive Keratectomy Technique Small Incision Cataract Surgery 391
and Postoperative Regimen 279 Vilas A Bidaye
MS Sachdev, Namrata Sharma
53. Phacoemulsification in Difficult Situations 395
37. Laser-Assisted In Situ Keratomileusis K Ravishankar, Deepak Garg
(LASIK) 286
Dipak Bhuyan 54. Phacoemulsification for Surgeons
38. Limbal Transplantation of Stem Cells 298 in Transition 402
Anita Panda, Namrata Sharma Jagat Ram
39. Mooren’s and Ulcer 303 55. Complications of Phacoemulsification 409
M Srinivasan Mary Abraham
40. Scleritis and Episcleritis 307 56. Posterior Capsule Opacification:
JS Saini Pathogenesis, Management and Prevention 414
Jagat Ram, Gagandeep S Brar,
Section 4 Supratik Bandopadhyay
DISEASES OF THE LENS 57. Multifocal IOLs 421
Gagandeep S Brar, Jagat Ram
41. Anatomy-Histology of the
Human Crystalline Lens 315 58. Piggyback IOLs 430
Suresh K Pandey, Liliana Werner, Sushismita Kaushik, Jagat Ram,
David J Apple, Vidushi Sharma Supratik Bandopadhyay
 Contents xix
59. Secondary Intraocular Lens Implantation 434 77. Lasers Applications in Glaucoma 588
G Natchiar, Deva Prasad Kar S Ramalingum
60. Scleral-Fixated PCIOL 438 78. Phacotrabeculectomy 597
Dinesh Mittal, YR Sharma R Raveendran, KM Ranganath
61. Management of Postoperative 79. Antimetabolites in Glaucoma
Endophthalmitis 442 Filtration Surgery 603
S Natarajan, B Dutta, R Ramakrishnan, Kavitha Ramakrishnan
62. Ophthalmic Viscosurgical Devices 448 80. Management of Bleb-related Problems 608
Suresh K Pandey, Jaya Thakur, Liliana Werner, Hemamalini Arvind, L Vijaya
Nick Mamalis, Vidushi Sharma, David J Apple,
81. Artificial Drainage Devices in
Aman Chandra, Girish Chandra
Glaucoma Surgery 618
63. Complications of Intraocular R Thomas, SC Gieser
Lens Implantation 464
G Natchiar, Deva Prasad Kar
VOLUME 2
Section 5
Section 6
GLAUCOMA
64. Gross and Microanatomy of the Angle of DISEASES OF ORBIT
the Anterior Chamber 468 82. Applied Anatomy of the Orbit 625
S Choudhury AK Khurana
65. Gonioscopic Appearances of 83. Investigation of Orbital Space
Normal and Pathological Conditions 473 Occupying Lesions 631
S Choudhury AK Khurana, BK Ahluwalia
66. Primary Open Angle Glaucoma 479 84. Lymphoproliferative, Leukemic and
Devindra Sood, NN Sood
Histiocytic Lesions of the Orbit 646
67. Normal Tension Glaucoma 502 Ramesh Murthy, Sanghamitra Burman,
S Choudhury Santosh G Honavar, Geeta K Vemuganti,
68. Optic Nerve Head and Retinal Milind Naik, Vijay Anand Reddy
Nerve Fiber Layer Imaging 509
B Shantha, K Krishnakumar 85. Ultrasonography-guided Fine Needle
Aspiration Cytology in Orbital Lesions 653
69. Automated Perimetry 515
Anju Rastogi, S Jain, M Kumar
B Shantha
70. Primary Angle Closure Glaucoma 522 86. Phakomatosis 660
A Neelakanthan, S Rao P Namperumalsamy, K Lakshmanamurthy,
Madhavi Hirode
71. Secondary Glaucoma 536
NK Dutta, LC Dutta 87. Orbital Involvement in Diseases
72. Malignant Glaucoma 551 of the Paranasal Sinuses 671
SK Narang AK Khurana
73. Primary Pigmentary Dispersion Syndrome 88. Metastatic Tumors to the Orbit 676
and Pigmentary Glaucoma 555 Lakshmi Mahesh, Nitin K Dutta
LC Dutta, Nitin K Dutta 89. Orbital Blow-out Fractures 682
74. Pseudoexfoliation Syndrome 561 AK Khurana
Mayuri Khamar 90. Orbital Cellulitis 689
75. Pharmacognosy and Pharmacokinetics AK Khurana
of Ocular Hypotensive Agents 566
91. Painful Ophthalmoplegia 695
R Ramakrishnan, S Puthalath
Subhra Das, LC Dutta
76. Current Trends in Drug Therapy
of POAG 578 92. Thyroid Ophthalmopathy 699
LC Dutta, NK Dutta Subhra Das, LC Dutta
xx Modern Ophthalmology

93. Anatomy, Physiology and Diseases 110. Nystagmus Surgery: Current Concepts 864
of the Lacrimal System 708 Elizabeth Joseph
AK Grover, A Bhatnagar, Sarmi Malik 111. Evaluation of Strabismus 867
94. Radiographic Study of Lacrimal Passage 726 TS Surendran, Manjula Sridhar
AS Mehrotra 112. Sensory Adaptation in
95. Lacrimal Gland Tumors 729 Concomitant Squints 879
LC Dutta, KS Ratnakar JN Rohatgi
113. Introduction to Heterophoria 886
Section 7 SK Narang, S Narang, Priya Narang
114. Esodeviations 889
PEDIATRIC OPHTHALMOLOGY Sabi Pandey
INCLUDING STRABISMUS 115. Exodeviation 898
96. Neonatal Conjunctivitis 733 Kamlesh, S Dadeya
Samrat Chatterjee 116. A and V Syndrome 901
97. Amblyopia 744 JN Rohatgi
JN Rohatgi 117. Management of Double Elevator Palsy 906
98. Nutritional Blindness: Vitamin A Kamlesh, S Dadeya
Deficiency Disorders 751 118. Vertical Strabismus 908
Samar K Basak JN Rohatgi
99. Congenital Glaucoma 759 119. Special Forms of Strabismus 912
B Sridhar Rao LC Dutta, NK Dutta
100. Glaucomas Associated with 120. Nonsurgical Treatment of Squint 920
Developmental and Congenital Anomalies 765 Kamlesh, S Dadeya
S Choudhury, S Mitra 121. Surgical Treatment of Strabismus 924
101. Childhood Cataract and Other Vinita Singh
Abnormalities of the Crystalline Lens 774
Nitin K Dutta, LC Dutta Section 8
102. Management of Infantile-Pediatric Cataract 780 NEUROOPHTHALMOLOGY
Suresh K Pandey, M Edward Wilson,
Jagat Ram, Liliana Werner, David J Apple 122. Anatomy of Visual Sensory System 943
103. Lens Subluxation and its Management 808 G Natchiar, Subhuram
Kasturi Bhattacharjee,Harsha Bhattacharjee, 123. Neuroophthalmological Evaluation 948
Pankaj Bhattacharjee LC Dutta
104. Ophthalmic Manifestations of 124. Normal and Abnormal Pupils 958
Inborn Errors of Metabolism 818 G Natchiar, Subhuram
LC Dutta 125. Chiasmal Lesions: Chiasmal Syndromes 962
105. Pediatric Orbital Space Occupying Lesions 824 LC Dutta
LC Dutta, Nitin K Dutta
126. Visual Field Defects 969
106. Pediatric Posterior Uveitis 833 G Natchiar, Subhuram
V Gupta, A Gupta
127. Optic Neuritis: Optic Neuropathies
107. Retinopathy of Prematurity 838 Demyelinating Diseases 973
S Natarajan, B Dutta LC Dutta
108. Retinoblastoma 849 128. Ocular Motor Palsies 980
Ramesh Murthy, Santosh G Honavar, G Natchiar, Subhuram
Milind Naik, Vijay Anand Reddy
129. Supranuclear Disorders of the Eye
109. Infantile Nystagmus 860 Movements and Visual Integration 986
LC Dutta G Natchiar, Subhuram
 Contents xxi
130. Papilledema 992 145. Color Vision and Color Blindness 1144
LC Dutta YR Sharma, Nikhil Pal, Deependra V Singh
131. Idiopathic Intracranial Hypertension 146. Indocyanine Green Angiography in
(Pseudotumor Cerebri) 997 Neovascular Age-related Macular
LC Dutta, NK Dutta Degeneration 1151
Sandeep Saxena, Tomohiro Iida
132. Abnormalities of Optic Disk and
Optic Nerve 1001 147. Low Vision Devices 1160
G Natchiar, Subhuram Sarfaraz A Khan
133. Intracranial Space Occupying Lesions of 148. Amniotic Membrane Transplantation in
Ophthalmic Importance 1004 Ophthalmic Disorders 1169
LC Dutta Anita Panda, Hrishikesh Das
149. Limbal Stem Cells of Corneal Epithelium:
Section 9 Concepts, Disease and Management 1179
MISCELLANEOUS TOPICS Himanshu P Matalia, Virender S Sangwan

134. Applied Anatomy of the Eye and Adnexa 1011 150. Miscellaneous Aspects of Conjunctiva 1192
AS Mehrotra LC Dutta, Nitin K Dutta

135. Introduction to Computed Tomography 151. Neoplasms of Conjunctiva and Cornea 1201
and Magnetic Resonance Imaging in Anita Panda
Ophthalmic Practice 1020 152. Management of Corneal Epithelial Defects 1208
N Medhi, SK Handique Anita Panda, Neelam Pushker
136. Computed Tomography and Magnetic 153. Ocular Manifestations in Tropical Diseases 1215
Resonance Imaging of the Eye and Orbit 1028 R Mukherji
SK Handique, N Medhi, B Saharia
154. Eye in Connective Tissue Disorders 1220
137. Applications of Ultrasound Biomicroscopy 1062 Jyoti S Padalay
M Baskaran, M Bhende
155. Oxidative Stress and Antioxidants in
138. Laboratory Techniques in Ophthalmic
Ophthalmology 1227
Pathology 1071
Souvik Banerjee
Geeta K Vemuganti
156. Contact Lenses 1234
139. Viscoelastic Substances in Ophthalmology 1086
RP Bhatia, LC Dutta
Anita Panda
140. Principles of Biostatistics 1092
S Krishnaiah, N Rishita, BR Shamanna
VOLUME 3
141. Genetics in Ophthalmology 1100
Chitra Kannabiran Section 10
142. Molecular Genetics in Clinical DISEASES OF THE UVEAL TRACT
Ophthalmology* 1108
B Jay, M Jay 157. Anatomy of the Uveal Tract 1249
Jyotirmay Biswas
143. Infection Control Practices for
Ophthalmologists 1121 158. Uveitis: Classification, History-Taking,
Savitri Sharma Examination and Incidence 1254
Jyotirmay Biswas
144. Acquired Immunodeficiency Syndrome
and the Eye 1127 159. Clinical Approach to a Patient with Uveitis 1261
J Biswas, A George Virender S Sangwan
xxii Modern Ophthalmology

160. Anterior Uveitis: Diagnosis Section 11

and Management 1268
Virender S Sangwan RETINA-VITREOUS
Section Editor: TP Das
161. Intermediate Uveitis: Pars Planitis 1280
Jyotirmay Biswas 179. Anatomy of Retina and Vitreous 1435
162. Posterior Uveitis 1289 B Khamar
Annie Mathai, Virender S Sangwan 180. Retinal Viewing System: The Diagnostic,
Laser and Surgical Lenses 1442
163. Common Panuveitis Entities 1303 Vinay A Shah, R Narayanan, Amol Kulkarni
Soma Sheila Murthy, Virender S Sangwan 181. Electrophysiological Tests of the Eye 1455
164. Viral and Rickettsial Uveitis 1324 Subhadra Jalali, LS Mohan Ram
Jyotirmay Biswas 182. Clinical Application of Optical
165. Ocular Toxoplasmosis 1344 Coherence Tomography 1474
Vishali Gupta, Amod Gupta Anjli Hussain, Kallukuri Sumasri,
Tara Prasad Das
166. Ciliochoroidal Detachment 1352
Jyotirmay Biswas, S Raizada 183. Fluorescein Angiography 1480
Nazimul Hussain, Anjli Hussain,
167. Presumed Ocular Tuberculosis 1356 Kallukuri Sumasri, LS Mohan Ram
LC Dutta, Nitin K Dutta
184. Indocyanine Green Angiography (ICGA) 1489
168. Fuchs’ Heterochromic Uveitis 1362 Nazimul Hussain, LS Mohan Ram
Jyotirmay Biswas, S Raizada
185. Peripheral Retina, Pars Plana and
169. Serpiginous Choroiditis 1366 Vitreous Base 1496
Vishali Gupta, Amod Gupta Harsha Bhattacharjee, Satyen Deka, Jnanankar Medhi
170. Anterior Uveitis and Arthritis 1372 186. Retinal Telangiectasis 1511
Jyotirmay Biswas, A Wagle Vishali Gupta, Amod Gupta
171. Sympathetic Ophthalmia 1378 187. Age-related Macular Degeneration 1521
Vishali Gupta, A Gupta Raja Narayanan, Vinay A Shah,
Amol D Kulkarni, Paolo Lanzetta
172. Investigational Approach to Uveitis 1384 188. Endophthalmitis 1539
Jyotirmay Biswas Tara Prasad Das, Savitri Sharma, Subhadra Jalali
173. Management of Endogenous 189. Etiopathogenesis of Retinal Detachment 1552
Non-infectious Uveitis 1388 P Namperumalsamy, Madhavi G Hirode,
Virender S Sangwan D Dwarak Nath, S Lal
174. Uveal Malignant Melanoma 1397 190. Principles and Alternative Surgical
Jyotirmay Biswas Techniques for Retinal Detachment 1568
T Sharma
175. Intraocular Metastatic Tumors
191. Ocular Ischemic Syndrome and Retinal
LC Dutta, Nitin K Dutta
Arterial Obstruction 1577
176. Vascular Tumors of the Choroid and Retina 1414 Subhadra Jalali, TP Das
Mahesh P Shanmugam, Surendra Shetty, 192. Retinal Venous Occlusive Diseases 1584
Sandeep Thakur Subhadra Jalali, TP Das
177. Intraocular Biopsy Techniques 1422 193. Ocular Manifestations in 1599
Ajeet Madhab Wagle, Mahesh P Shanmugam Systemic Hypertension
TP Das, R Shonek, Subhadra Jalali
178. Controversies and Preferred Treatment of
Malignant Melanoma of the Choroid 1431 194. Diabetic Retinopathy 1605
Mahesh P Shanmugam Subhadra Jalali, TP Das
 Contents xxiii
195. Vitreous Hemorrhage 1624 208. Subretinal Surgery 1721
Harsha Bhattacharjee, Kasturi Bhattacharjee, S Saxena, MA Thomas
Anil Kumar Agarwal
209. Scleral Buckling: Concepts,
196. Proliferative Vitreoretinopathy 1633 Materials and Techniques 1730
Ajit Babu Majji PN Nagpal, RK Sharma, M Porwal
197. Retinitis Pigmentosa and Associated 1641 210. Pars Plana Surgery 1737
Retinal Degenerations P Namperumalsamy, Madhavi G Hirode, KL Murthy
Subhadra Jalali, LS Mohan Ram, Arivazhagan N
211. Vitreous Substitutes 1753
198. Familial Exudative Vitreoretinopathy 1650 PN Nagpal, RK Sharma, Rajshree Vadhani
Dhananjay Shukla
212. Laser Application in Retinal Disorders 1757
199. Degenerative Myopia 1656 Yog Raj Sharma, Deependra Vikram Singh
Maurizio Battaglia Parodi, Paolo Lanzetta
213. Retinoschisis 1767
200. CMV Retinitis 1668 YR Sharma, Deependra Vikram Singh
Avinash Pathengay
214. Central Serous Chorioretinopathy 1772
201. Eales’ Disease 1675
Avinash Pathengay
Subhadra Jalali, TP Das
202. Coats’ Disease 1681 215. Epiretinal Membrane 1779
Pratik Sen, Pramod S Bhende YR Sharma, Neena, D Mittal
203. Surgery for Macular Diseases 1689 216. Ocular Ischemic Syndrome 1783
Lingam Gopal Avinash Pathengay
204. Perfluorocarbon Liquids and 217. Management of Dislocated Nucleus 1788
Silicone Oil in Vitreoretinal Surgery 1701 Dhanashree Ratra
S Saxena, L Gopal
218. Laser Tissue Interactions 1793
205. Management of Giant Retinal Tears 1708 Biju Raju
Annie Mathai
219. Principles of Lasers in Retinal Diseases 1797
206. Principles and Techniques of Internal ` Biju Raju
Tamponade for Retinal Detachment 1714
NS Bhatt Appendix 1801
207. Retinotomy and Retinectomy 1719
PN Nagpal, RK Sharma, M Porwal Index 1805
 SECTION 6: DISEASES OF ORBIT

Chapter 82

Applied Anatomy of the Orbit

AK Khurana

BONY ORBIT
Size, Shape, and Relations
The two bony orbits are quadrangular truncated
pyramids situated between the anterior cranial fossa
above, and the maxillary sinuses below (Fig. 82.1). The
medial walls of the two orbits are parallel to each other.
They are in contact with the ethmoid and sphenoid
sinuses, which separate the orbits from the nasal
cavities. The lateral wall of each orbit lies at an angle
of 45° to the medial wall. The lateral wall of the two
orbits are at 90° to each other. The lateral wall separates Fig. 82.1: Schematic coronal section through the
orbits and nasal cavity
the orbit from the middle cranial fossa posteriorly and
the muscular temporal fossa anteriorly (Fig. 82.2).
The depth of the orbit is 42 mm along the medial and left lateral orbital margins is 100 mm. The
wall and 50 mm along the lateral wall. The base of the relationship between the height and width of the orbit
orbit is 40 mm in width and 35 mm in height. The is expressed by the orbital index. Orbital index =
interorbital width, i.e. the distance between the medial Height ÷ Width × 100. The index shows racial
margins of the right and left orbits is 25 mm. The variation. Races having an orbital index greater than
extraorbital width, i.e. the distance between the right 89 are termed as Megasenes (e.g. Orientals).

Fig. 82.2: Schematic transverse section through the orbits and nasal cavity. On left side, eye ball is shown in relation to medial
and lateral walls of the orbit. Anterior half of eye ball is not protected by bone on lateral surface. On right side is shown, inferior
orbital fissure and infraorbital groove, canal and foramen
626 Section 6: Diseases of Orbit
Mesosenes (e.g. Caucasians) have an orbital index
between 83 and 89. Africans with an index of less than
83 are termed as Microsenes. The volume of each orbit
is about 29 ml. The ratio between the volume of the
orbit and of the eye ball is 4.5:1.
Walls of the Orbit
The bony orbit has four walls, i.e. medial wall, lateral
wall, roof, and floor. These four walls are formed by
seven bones. The walls meet at the superior internal,
superior external, inferior internal, and inferior
external angles of the orbit.
Medial Wall
The medial wall of the orbit is quadrilateral in shape
and is formed by (from front to back) the frontal
process of the maxilla, the lacrimal bone, the orbital
plate of the ethmoid bone, and the body of the
sphenoid. The anterior part of the medial wall bears
the lacrimal groove, which is continuous inferiorly
with the nasolacrimal canal. The groove is bounded
anteriorly by the anterior lacrimal crest of the
maxillary bone, and posteriorly by the posterior
lacrimal crest of the lacrimal bone.
The medial orbital wall is the thinest wall of the
orbit. This accounts for ethmoiditis being the most
common cause of orbital cellulitis, especially in
children. The medial wall is frequently eroded by
chronic inflammatory lesions, cysts, and neoplasms
that originate in the adjacent air sinuses. It is easily
fractured during injuries as well as during orbitotomy
operations. During surgery along this wall
hemorrhage is most troublesome due to injury to
ethmoidal vessels. In addition, the medial-palpebral,
frontal and dorsal-nasal arteries pass forward near the
medial wall. The medial wall can be easily visualized
on the routine PA radiographs of the orbit.
Inferior Orbital Wall (Floor)
The floor of the orbit is triangular in shape. It is formed
by three bones, i.e. the orbital surface of the maxillary
bone medially, the orbital surface of the zygomatic
bone laterally, and the palatine bone posteriorly. The
posterior part of the floor of the orbit is separated from
the lateral wall by the inferior orbital fissure. This
fissure is continuous anteriorly with the infraorbital
groove which extends anteriorly as a canal. The canal
opens at the infraorbital foramen located just below
the infraorbital rim. The foramen transmits the
infraortibal nerve, the infraorbital artery, and the
infraorbital vein (which connects the inferior
ophthalmic vein to the facial vein) (Fig. 82.2).
The orbital floor being quite thin is commonly
involved in “blow-out fractures” and is easily invaded
by tumors of the maxillary antrum. The floor of the
orbit is best visualized with standard posteroanterior
radiographs. The orbital floor can be approached by
inferior orbitotomy (antral approach) easily. However,
the utility of this approach is limited as only a small
proportion of tumors are found in this area.
Lateral Wall
The lateral wall of the orbit, triangular in shape, is
formed anteriorly by the zygomatic bone and
posteriorly by the greater wing of the sphenoid bone.
On the posterior part of the lateral wall there is a small
bony projection (spina recti lateralis) which gives
origin to part of the lateral rectus muscle. More
anteriorly, the wall is marked by the zygomatic groove
and foramina (which are traversed by the zygomatic
nerve and vessels). On the anterior part of the wall
there is a projection, the lateral orbital tubercle of
Whitnal. It gives attachment to the check ligament of
the lateral rectus muscle, and to the suspensary
ligament of the eyeball.
The lateral wall of the orbit protects only the
posterior half of the eyeball. The anterior half of the
globe is not covered by bone on the lateral side
(Fig. 82.2). Hence, palpation of retrobulbar tumors is
easier from the lateral rather than from the nasal side
of the eyeball.
Because of its advantageous anatomical position a
lateral orbital surgical approach is popular. Further,
the lateral wall is almost devoid of foramina and so
its anterior portion can be broached without serious
hemorrhage (zygomaticotemporal vessels usually do
not pose a problem). However, the lateral rim of the
orbit, which is the forward extension of the lateral wall,
is the strongest portion of the orbit and needs to be
sawed open in lateral orbitotomy. The zygomaticos-
phenoid suture is an important landmark in creating
the flap in Kronlein’s operation and its all modifica-
tions. Once this bone flap has been turned, the surgeon
has direct access to the superolateral and inferolateral
retrobulbar quadrants of the orbit.
Since these quadrants are the common sites of
orbital tumors the surgical anatomy of this area is
important.
 Chapter 82: Applied Anatomy of the Orbit 627
Roof
Roof or vault of the orbit is triangular in shape and is
formed mainly by the orbital plate of the frontal bone.
Behind this, it is formed by the lesser wing of sphenoid.
The anterolateral part of the roof has a depression
called the fossa for the lacrimal gland. It is usually
quite smooth but may be pitted by the attachments of
the suspensory ligament of the lacrimal gland. The
fovea for the pulley of the superior oblique (trochlear
fossa) is a small depression situated close to the orbital
margin, at the junction of roof and the medial wall. Fig. 82.3: A schematic view of orbital cavity and orbital rim
The superior wall is rather thin throughout whole
extent, and the periorbita easily peels away from its
undersurface. On the cranial side, the dura can be
lifted almost easily. Because the roof is perforated
neither by major nerves nor by blood vessels, it can
be easily nibbled away in transfrontal orbitotomy.

Base of the Orbit

The anterior open end of the orbit is referred to as the
base. It is bounded by the orbital margins (Fig. 82.3).
The margins are formed by a ring of compact bone.
They receive contributions from the orbital arch of the
frontal bone (superiorly), the zygomatic bone and the
zygomatic process of frontal bone (laterally), the
zygomatic bone, maxilla, and nasal part of the frontal
bone (medially).
The supraorbital notch which transmits the nerve
and artery of the same name lies in superomedial part
of the orbital margin. The orbital periosteum is firmly
adherent to the orbital margin.
Apex of the Orbit
The orbital apex is the posterior end of the orbit. Here
the four orbital walls and angles converge. The apex
has two orifices, i.e. the optic canal and the superior
orbital fissure which are situated in the sphenoid bone
(where the body, greater wing, and lesser wing meet
each other) (Fig. 82.4).
The optic canal connects the orbit to the middle
cranial fossa. It transmits the optic nerve (surrounded
by meninges); and the ophthalmic artery. Normal
adult dimensions of the optic canal are attained by
the age of 4 to 5 years. Its standard average length is
6-11 mm (lateral wall is shortest and medial wall is
longest). At its orbital end, the canal is in the form of a
vertical oval (6 mm × 4.5 mm). At its center the canal
is circular (5 mm × 5 mm) and at its cranial end it
forms a horizontal oval (4.5 mm × 6 mm). Tumors such
Fig. 82.4: Structures passing through the optic canal and the
superior orbital fissure
as optic nerve glioma and meningioma may lead to
unilateral enlargement of the optic canal, which may
be detected on X-ray by various methods of radio
imaging.
The superior orbital fissure is a common-shaped
aperture in the orbital cavity. It is bounded by the
lesser and greater wings of the sphenoid. It is situated
lateral to the optic foramen at the orbital apex. The
fissure is divided into upper, middle, and lower parts
by the common tendinous ring (for origin of the recti).
The structures passing through the upper (and lateral)
part are the lacrimal and frontal nerves (branches of
ophthalmic division of Vth nerve), the trochlear nerve,
the superior ophthalmic vein, and the recurrent branch
of the ophthalmic artery. The middle part of the fissure
(within tendinous ring) transmits the superior and
inferior divisions of the oculomotor nerve, the
nasocilliary branch of the ophthalmic division of the
trigeminal nerve, and the abducent nerve. The lower
(and medial) part of the fissure transmits the inferior
ophthalmic vein (Fig. 82.4).
628 Section 6: Diseases of Orbit
PERIORBITA
The periosteum lining of the surface of the orbial bones
is called the periorbita. Generally, it is loosely adherent
to bone. However, it is firmly adherent at the orbital
margin, superior and inferior orbital fissures, the optic
canal, the lacrimal fossa, and the sutures. In the optic
canal, the dural sheath of the optic nerve is closely
adherent to periorbita. At the posterior lacrimal crest
the periorbita splits into two layers which reunite at
the anterior lacrimal crest. These two layers enclose
the lacrimal sac (in the form of lacrimal fascia).
ORBITAL FASCIA
The orbital fascia, is a thin connective tissue membrane
lining the various intraorbital structures. Recent
studies have shown that this is complex interwoven
connective tissue joining the various intraorbital
contents. Though the orbital fascia is one tissue, for
descriptive convenience it can be described under the
heads of fascia bulbi, muscular sheaths, intermuscular
septa, membranous expansions of the extraocular
muscles, and ligament of Lockwood (Figs 82.5
and 82.6).
Fascia Bulbi
Fascia bulbi, also called Tenon’s capsule, envelops the
globe from the margin of the cornea to the optic nerve.
Its inner surface is well defined and lies in close contact
with sclera to which it is connected by fine trabeculae.
Schwalbe described the fascia as having two opposing
layers lined by endothelium with a potential space in
between, thus forming an articular socket in which
the eyeball could move freely. However, it is now
considered that the globe and the capsule move
together in the surrounding fat. The outer surface of
the fascia bulbi lies in contact with orbital fat poste-
riorly and with subconjunctival tissue arteriorly with
which it merges near the limbus.
The lower part of the fascia bulbi is thickened to
form a sling of hammock on which the globe rests;
this is called the suspensory ligament of Lockwood.
Around the proximal end of optic nerve the fascia
is fused with the dural sheath of the optic nerve.
Schwalbe, however, considered it to be continuous as
a membrane surrounding the dural sheath to form a
supravaginal lymph space, a view which is now
considered doubtful. Fascia bulbi is pierced
posteriorly by the optic nerve, ciliary nerves and
vessels, just behind the equator by venae vorticosae,
and anteriorly by six extraocular muscles.
Fig. 82.5: Fascial expansions from extraocular muscle,
sheaths and aperatures at the base of orbit
Fascial Sheaths of Extraocular Muscles
There are two views about the origin of the extraocular
muscle sheaths. Some consider them to be a separate
membranous lining of muscles which blends
anteriorly with the Tenon’s capsule. However, most
workers consider them to be parts of the orbital fascia;
at the points where the fascia bulbi is pierced by an
extraocular muscle it sends a tubular reflection, which
clothes the muscles like a glove. These muscular
sheaths become continuous with the perimysium.
Fascial Expansions of Extraocular Muscles
The sheath of each extraocular muscle sends
expansions to the surrounding structures. Fascial
expansions of lateral and medial rectus muscles are
strong and attached to orbital tubercles on the
zygomatic bone and to the lacrimal bone, respectively.
These are also called lateral and medial check
ligaments. Expansion of superior rectus muscle is
attached to the levator palpebrae superioris. This
attachment ensures synergic action of the two muscles.
Thus, when the superior rectus muscle makes the eye
look up, the upper lid is also raised. In maximal levator
resection for ptosis, hypotropia can be induced if these
connections are not removed. An expansion from the
inferior rectus muscle is attached to the capsulo-
palpebral fascia, a tissue analogous to levator
aponeurosis in the lower lid. An expansion from the
superior oblique passes upto the trochlea; an
expansion from the inferior oblique passes to lateral
part of the roof of the orbit.
In addition to these well established expansions,
there are many more complex fascial attachments from
the sheath of each extraocular muscle. About five
different fascial expansions have been described for
the medial rectus muscle.
 Chapter 82: Applied Anatomy of the Orbit
Fig. 82.6: Schematic sections of the orbital cavity to
demonstrate surgical spaces of orbit. (i): Sagittal section. (ii)
Coronal sections at levels A, B and C. (1; Subperiosteal space.
2; Peripheral (anterior) space. 3; Central (posterior) space; 4;
Tenon’s space. 5. Apical space)
Further, from the anterior end of the expansion of
each extraocular muscle, a fibrous band passes to be
attached to the conjunctival cul-de-sac. These
connections account for the retraction of the
conjunctival sac when these muscles contract.
Intermuscular Septa/Membrane
The sheaths of the four rectus muscles are joined to
each other by a fascial membrane called the
intermuscular septum. The membrane divides the
orbital cavity and orbital fat into central and peripheral
parts.
SURGICAL SPACES IN THE ORBIT
The orbit is divisible into a number of spaces. These
are of importance as most orbital tumors tend to
remain within the space in which they are formed
(unless they are large or malignant or unless they
represent an infiltrative process such as
psuedotumors). Therefore, a knowledge of the main
compartments of the orbit and their boundaries helps
the surgeon in choosing the most direct approach to
the tumor. From the surgical point of view four spaces
can be described in the orbit (Fig. 82.6).
Subperiosteal Space
This is a potential space between bone and periorbita,
delimited anteriorly by the strong adhesions of
629
periorbita along the orbital rim. Tumors arising from
the bones separate periorbita from the bones. The
periorbita then becomes thicker and tougher, forming
an effective barrier against the spread of tumor toward
the eye, unless subjected to extreme pressure for a long
time. Meningiomas, dermoid cysts, epidermoid cysts,
mucoceles, subperiosteal abscess, myelomas,
osteomatous tumors, hematomas, and fibrous
dysplasia are commonly seen in this space. Plain X-
ray is most useful in diagnosing the tumors of this
space.
Peripheral Orbital Space (Anterior Space)
This space is bounded peripherally by periorbita,
internally by the extraocular muscle with their
intermuscular septa and anteriorly by the septum
orbitale (including tarsal plates and tarsal ligaments).
Posteriorly, it merges with the central space. Tumors
present in this space produce eccentric proptosis and
can usually be palpated. Common tumors found in
this space include malignant lymphoma, capillary
hemangioma of childhood, intrinsic neoplasm of the
lacrimal gland, and pseudotumor. Tumors residing
in this space are usually explored by anterior
orbitotomy and sometimes by lateral orbitotomy.
Contents of this space are: peripheral orbital fat;
superior oblique, inferior oblique, and levator
palpebrae superioris muscles; lacrimal, frontal anterior
ethmoidal, and posterior ethmoidal nerves; superior
and inferior ophthalmic veins; lacrimal gland and half
of the lacrimal sac.
Central Space
It is also called muscular cone or posterior or retro-
bulbar space. This space is bounded anteriorly by
Tenon’s capsule lining the back of the eye; and peri-
pherally by the extraocular muscles and their
intermuscular septa in the anterior part. In the
posterior part, where intermuscular septa are
imperceptible, this space becomes continuous with the
peripheral orbital space. Many of the circumscribed
orbital tumors such as cavernous hemangioma of
adults, the solitary neurofibroma, neurilemomas,
nodular orbital meningioma and optic nerve glioma
occur in this space and usually produce an axial
proptosis. Such tumors are often removed through a
lateral orbitotomy.
SubTenon’s Space
It is a potential space around the eyeball between the
sclera and Tenon’s capsule. Pus collected in this space
is drained by incision of Tenon’s capsule through the
conjunctiva.
630 Section 6: Diseases of Orbit
In the preceding paragraphs the surgical spaces
have been described using classical nomenclature.
However, some alternative terms are also used. As at
the apical part of the orbit, the peripheral (anterior)
and central (posterior) spaces merge with each other
to form a single space. Hence, it will be more
appropriate to divide the orbit into the following five
surgical spaces (Fig. 82.6).
1. The subperiosteal space.
2. The anterior (peripheral) space extending poste-
riorly upto the posterior limit of the intermuscular
membrane.
3. The posterior (central) space, also extending poste-
riorly up to the posterior limit of the intermuscular
membrane.
4. The apical space, bounded peripherally by
periorbita; anteriorly becoming continuous with
the anterior (peripheral) and posterior (central)
spaces, at the level of posterior limit of inter-
muscular membrane and ending posteriorly at the
apex of the orbit; and
5. The Tenon’s space.
ORBITAL FAT AND RETICULAR TISSUE
Normally, the orbital cavity is occupied by orbital fat,
which extends from the optic nerve to the orbital wall
and from the apex of the orbit to the septum orbitale.
The fat lobules lie in the interstices of a web of reticular
tissue called the ortibal reticulum. This tissue is the
supporting framework of the orbital fat, anchoring it
to the orbital fascia.
The orbital fat is divided into central and periphe-
ral parts by the intermuscular membrane. Posteriorily,
where there is no intermuscular membrane, the
peripheral and central fat pads are continuous with
each other. The peripheral orbital fat consists of four
lobules, namely superomedial, superolateral,
inferomedial, and inferolateral. If five surgical spaces
of orbit are considered then the orbital fat can be
divided into three parts, i.e. peripheral, central, and
apical.
Benign encapsulated tumors do not alter the
normal structure of reticular tissue and fat, except that
these structures are under great pressure and, when
the periorbita has been opened, they bulge out more
persistently into the operative field. However, in case
of malignant tumors, and infiltrative lesions like
pseudotumors and endocrine exophthalmos this basic
matrix may alter depending on the nature and
duration of the lesion.
The orbital fat and its reticular tissue are not as
inert as is commonly assumed. At times they may
become very reactive. Therefore, lesser the disturbance
of these structures during orbitotomy, the better the
functional and cosmetic results.
APERTURES AT THE BASE OF THE ORBIT
The base of the orbit is closed partially by the globe
and extraocular muscles with their fascial expansions.
These expansions and two oblique muscles bound
about five orifices between the orbital margin and
globe (Fig. 82.5). Through, these orifices fat may
herniate from the orbit to come into contact with the
septum orbitale. Further, these apertures form a
communication between the orbital cavity and deep
portions of eyelids. It is through them that blood and
pus pass out of the orbit from the space between
periorbita and peripheral fat. Their further spread in
the lids is stopped by septum orbitale. These apertures
are described below:
Superior Aperture
This is a comma-shaped orifice and lies between the
roof of the orbit and the upper surface of the levator
palpebrae superioris muscle. The head of the comma
lies near the trochlea, and the tail reaches the lacrimal
gland. Fat from the superomedial lobe may herniate
through this aperture to form a retroseptal roll, which
serves as an important landmark during levator
resection surgery for ptosis.
Superomedial Aperture
This vertically oval aperture lies between the reflected
tendon of the superior oblique muscle and the medial
check ligament. The infratrochlear nerve, the dorsal
nasal artery, and angular vein pass through this
aperture. Herniation of fat through this aperture is the
common cause of lobulated prominence around the
lids in old people.
Inferomedial Aperture
This is vertically oval in shape and lies between the
medial check ligament, origin of inferior oblique
muscle, and the lacrimal sac.
Inferior Aperture
This is triangular in shape and is bounded by the
inferior oblique muscle, arcuate expansion of inferior
oblique, and floor of the orbit.
Inferolateral Aperture
This is a small oval aperture situated between the
arcuate expansion of the inferior oblique muscle and
the lateral check ligament.
 Chapter 83

Investigation of Orbital Space

Occupying Lesions
AK Khurana, BK Ahluwalia

INTRODUCTION i. Infants are more likely to have congenital lesions

like craniostenosis, cephalocele, microophthalmia
Intraorbital space occupying lesions may be classified
with cyst, teratoma (Fig. 83.1), retinoblastoma
as the following:
(Fig. 83.2), capillary hemangioma, juvenile
a. Lesions from the contents of the orbit like orbital
xanthogranuloma, and metastatic
tissue, lacrimal gland, optic nerve, blood vessels,
neuroblastoma.
muscles, and nerves.
ii. Orbital lesions of childhood include dermoid cyst,
b. Invasive lesions from paraorbital regions, e.g.
lymphangioma, cavernous hemangioma, orbital
paranasal sinuses, cranial cavity, nasopharynx, etc.
varices, neurofibroma, rhabdomyosarcoma,
c. Orbital metastasis of malignancies from other
glioma of the optic nerve, intraorbital menin-
parts of the body and leukemia.
gioma (Fig. 83.3) orbital cellulitis, leukemic infil-
d. Extension of intraocular malignancy.
tration, granulocytic sarcoma, Burkitt’s lym-
e. Inflammation and lymphatic infiltration of the
phoma, eosinophillic granuloma, Hand-Schuller-
orbital tissue.
Christian disease, sinus histiocytosis, hydatid
Orbital lesions cause rise of pressure within the
bony orbital cavity and pushes the eyeball forward
(producing proptosis) because this is the only way
by which the pressure can be relieved. In order to
evaluate the cause of a case of proptosis following
clinicoinvestigative approaches may be useful.

CLINICAL EVALUATION
History
As in any other medical problem, the importance of
accurate and painstaking history need not be over-
emphasized. The nature of onset of proptosis and
chronology of symptoms and signs may serve as most
valuable diagnostic clues to the possible nature of a
lesion in the orbit. Meticulous history should provide
the following useful information:
Age of onset It is extremely important to know the
age of onset, because the etiology of orbital lesions Fig. 83.1: Congenital cystic teratoma of left
differs in infants, children, and adults. orbit in a 5-day old infant
632 Section 6: Diseases of Orbit

squamous cell carcinoma, basal cell carcinoma,

and sebaceous gland carcinoma), extension from
the paranasal sinuses, nasopharynx and cranial
cavity, metastatic carcinoma of the orbit, and
lesions of lacrimal gland.1
Nature of onset This also provides some important
clues for diagnosis, e.g.:
• Proptosis of sudden onset is seen in orbital emphy-
sema, retrobulbar hemorrhage, rupture and
infection of ethmoidal mucocele and acute orbital
infections.
• Proptosis with gradual onset indicates benign tumors
• Rapidly expanding orbital masses include rhabdo-

Fig. 83.2: An extensive growth of retinoblastoma

in a 3-year old child

Fig. 83.4: Secondary orbital meningioma

in a 26-year old female

Fig. 83.3: Intraorbital meningioma of right orbit in a 23-year

old person. The eyeball is proptosed and displaced upward

cyst, and fibrous dysplasia.

iii. Orbital lesions beginning in adulthood are secondary
orbital meningioma (Fig. 83.4), thyroid exo-
phthalmos (Fig. 83.5), pseudotumors, lympho-
proliferative disorders, fibrous histiocytoma,
hemangiopericytoma, cavernous hemangioma,
neurilemmoma, osteoma, mucocele, circulatory
disturbances (orbital varices, venous thrombosis,
cavernous sinus arteriovenous fistula), orbital
involvement secondary to neoplasms arising
from adjacent or nearby structures (such as
extensions from uveal malignant melanoma), Fig. 83.5: Bilateral exophthalmos with asymmetric
extension from tumors of the lids (such as retraction of eyelids
 Chapter 83: Investigation of Orbital Space Occupying Lesions 633
myosarcoma, neuroblastoma, Burkitt’s lymphoma, is observed in optic nerve tumors like optic
eosinophilic granuloma, capillary hemangioma, nerve glioma and optic nerve sheath menin-
lymphangioma and traumatic hematoma. gioma.
Duration Long standing and slowly progressive Lid edema is a common feature of orbital inflamma-
lesions are usually benign in nature and malignant tions and pseudotumors.
lesions are usually of short duration. History of thyroid disorder This may be of particular
importance in endocrinal proptosis.
Progression A continuous progression is noted in:
• Tumors and endocrine exophthalmos. Clinical Examination
• Intermittent postural proptosis (which disappears Inspection This is simple but most valuable in
and reappears) is observed in orbital varices and eliciting several signs. In many cases diagnosis may
in 20 percent cases of angiomas. become apparent by careful observation alone.
• Variable proptosis which persists but varies from Following observations should be done.
time to time is usually seen in pseudotumors and i. Whether proptosis is true or false Causes of
angiomas. pseudoproptosis are enlargement of the ipsi-
Pulsatile proptosis is a typical feature of arterio- lateral eye as in buphthalmos and high axial
venous aneurysms and cranioorbital communications. myopia, enophthalmos of the opposite eye,
retraction of the upper eyelid on the ipsilateral
Chronology of appearance of symptoms This may
side and shallow orbit (as in craniofacial dysos-
also be helpful in localization, e.g. visual loss followed
tosis or facial asymmetry).
by proptosis in a child indicates optic nerve glioma;
ii. Causes of unilateral proptosis
reverse chronology indicates meningioma of optic
— Congenital Dermoid cyst, orbital tera-
nerve in adults. toma and congenital cystic
History of associated symptoms Symptoms such as eyeball
pain, diplopia or swelling of lids may also give some — Traumatic Orbital hemorrhage, retain-
diagnostic clues. ed intra-orbital foreign
body, traumatic aneurysm
Pain The painful proptosis occurs commonly with and emphysema of the orbit.
orbital inflammatory disorders. It can also be seen is — Inflammatory Acute inflammations like
traumatic cases with orbital hematoma and later orbital cellulitis/abscess,
stages of malignancy. thrombophlebitis and caver-
nous sinus thrombosis
Diplopia It is a common symptom in orbital
(proptosis is initially
disorders related to paralysis of the extraocular unilateral but ultimately
muscles or mechanical restriction of ocular move- becomes bilateral)
ments. Lesion residing in the cavernous sinus or Chronic inflammation like
posterior orbit are responsible for paralytic abnor- pseudotumors tuberculoma,
malities of ocular movements. Anterior orbital lesions gumma and sarcoidosis
produce diplopia by means of a mechanical restriction — Vascular Angioneurotic edema, orbi-
caused by lesions that are immediately adjacent to tal varix and aneurysms
the extraocular muscles and diseases that involve the — Cysts of Hematic cyst, implantation
muscle tissue, such as myostis and Graves’ disease. the orbit cyst and parasitic cyst (hyda-
Visual loss Loss of visual acuity usually implies tid cyst and cysticercus cel-
involvement of optic nerve, either by compression, lulosae)
— Tumors Primary, secondary or meta-
infiltration, vascular compromise, or inflammation.
static
Relation of visual loss in a patient with proptosis with
the nature of lesion may be as below: Causes of bilateral proptosis
• Marked proptosis with no visual loss is seen in — Developmental Craniofacial dysostosis
cavernous hemangioma and neurilemmoma anomalies of e.g. oxycephaly (tower skull)
• Marked visual loss with mild to moderate proptosis skull
634 Section 6: Diseases of Orbit

— Osteopathies Osteitis deformans, rickets

and acromegaly
— Inflammatory Mikulicz’s syndrome and
late
condition stage of cavernous sinus
thrombosis
— Endocrine It may be thyrotoxic or
exophthalmos thyrotropic (most common
cause of bilateral proptosis
in adults, Fig. 83.5)
— Tumors Lymphoma, Lymphosarco-
ma, Secondaries from
neuroblastoma, Nephroblas-
toma, Ewing’s sarcoma and
Leukemic infiltration Fig 83.6: Mucocele of left ethmoid sinus.
— Systemic Histiocytosis, Systemic amy- Eyeball is displaced laterally
diseases loidosis, Xanthomatosis and
Wegener’s granulomatosis
iii. Direction of displacement medially, laterally,
superiorly or inferiorly can be a clue to the etio-
logy and site of the lesion. Axial Proptosis usually
indicates a mass inside the muscle cone, e.g. optic
nerve glioma (Fig. 83.7), hemangioma, menin-
gioma, Schwannoma and metastatic tumors
(from carcinoma of breast, lung and prostate).
Non-axial proptosis usually indicates a mass in the
peripheral space, e.g:
— Proptosis with lateral displacement of globe is
characteristic of ethmoidal sinus mucocele
(Fig. 83.6)
— Proptosis with downward and nasal displacement of
globe suggests a possible mass in the lacrimal Fig. 83.7: An unusual presentation as eccentric proptosis in a
fossa 10-year old child with left optic nerve glioma. Eyeball in displaced
— Proptosis with superior displacement of the globe anteriorly, upward, and laterally
is a feature of lesion near the orbital floor such
as growth in maxillary sinus (Fig. 83.8).
iv. Lid signs also provide some diagnostic clues. For
example, a swelling of lids associated with
ecchymosis of skin and chemosis of conjunctiva
may be seen in orbital cellulitis (Fig. 83.9). In the
presence of stare and lidlag, the possibility of
proptosis of neoplastic cause can be ruled out.
v. The rest of the body surface should be inspected
for related skin disturbances, such as heman-
gioma, melanoma, other metastatic lesions, or
the diagnostic cafe-au-lait spots associated with
neurofibromatosis.
Palpation Palpation of the following structures
should be done:
i. Retrodisplacement of the globe should be estimated Fig. 83.8: Proptosis in a 38-year old female with carcinoma
by applying equal digital pressure over the two of left maxillary antrum. Eyeball is pushed superiorly
 Chapter 83: Investigation of Orbital Space Occupying Lesions
Fig. 83.9: Orbital cellulitis in a 3-year old female child
eyes, simultaneously. This is best done with the
examiner’s thumb over the closed lids. Retro-
ocular resistance is encountered in the presence
of solid tumors. Compressibility is increased
where soft and vascular tumors are present. Any
pulsation of the globe may be confirmed by
palpation. Similarly, any thrill when present may
also be felt in highly vascular tumors.
ii. Palpation of the orbital rims should be done to
note any change in contour or dehiscence of any
orbital wall.
iii. In localizing anterior masses, palpation of the
orbit should be carried out between the globe
and the bony orbital rims in all the quadrants.
The findings should be compared with the other
side in unilateral cases to distinguish between
normal and abnormal findings. While palpating
a particular quadrant patients should be
instructed to look in the same direction. This
gives better access due to relaxation of the orbital
septum.
iv. Regional lymph nodes to be palpated are the
preauricular lymph nodes. These are the first site
of involvement in anterior extension of either
infectious or neoplastic processes. In addition,
other nearby nodes that might participate in
metastatic diseases from the orbits should also
be palpated. These include supraclavicular and
cervical nodes.
v. The paranasal (paraorbital) sinuses lend them-
selves very well to palpation or gentle
percussion, especially in the search for
inflammatory disturbances involving both
635
sinuses and orbits.
Auscultation Auscultation is primarily of value in
searching for abnormal vascular communications that
generate a bruit, such as carotidcavernous fistula,
arteriovenous aneurysm in orbit, etc. The orbit
should be auscultated by placing the stethoscope over
the closed lids in a quiet room.
Transillumination Though deep orbital lesions do
not lend themselves to transillumination, this
modality is often forgotten even in evaluation of
anterior orbital or lid lesions. Transillumination of
the lids may help to differentiate between solid and
cystic lesions and may also reveal certain radiolucent
foreign bodies. Transillumination is unavoidable in
unilateral proptosis of elderly persons. A flat sarcoma
of the choroid may present as exophthalmos due to
early perivascular extraocular extension.
Visual acuity Any loss of vision preceding exophthal-
mos suggests tumor of the optic nerve, e.g. glioma in
children. Orbital tumors may reduce central acuity
of vision by pressing on the back of eyeball producing
changes in refraction or Sallman’s macular folds.
Optic atrophy is responsible for loss of vision in late
cases.
Pupillary reactions Presence of Marcus Gunn pupil
is suggestive of optic nerve compression and is an
indication for plotting the visual fields in both eyes.
Funduscopy Venous engorgement, hemorrhage,
papilledema or optic atrophy may be observed on
funduscopy. These changes are caused by raised
intraorbital pressure. Choroidal folds and
opticociliary shunts may be seen in patients having
meningioma.3
Ocular motility Restriction of ocular movements
may be caused by restrictive myopathy as in thyroid
ophthalmopathy, splinting of the optic nerve as in
optic nerve sheath meningioma and neurological
deficit resulting from orbital apex lesions.
Forced duction test This test is done to differentiate
defective ocular movements due to neurological
lesions from those caused by mechanical limitations.
The test is positive when there is mechanical limitation
of ocular movements as in fibrotic contracture
(thyroid myopathy) and involvement of muscles in
malignant growths. It is negative if the muscle is
paretic due to neurological lesions.
Tonometry Orbital disease may cause raised intra-
ocular pressure. It is usually raised in cases of thyroid
636 Section 6: Diseases of Orbit

exophthalmos especially in upward gaze (positional

IOP changes).4
Exophthalmometry (Proptometry)Exophthalmometry
measures the protrusion of the apex of cornea from
the outer orbital margin (with the eyes looking
straight ahead). In absolute exophthalmometry,
results are compared to known normal values which
vary between 10 to 21 mm. It is not of much clinical
significance. In relative exophthalmometry, results
of the two eyes are compared and a difference of
more than 2 mm is considered significant. This
method is essential to establish the presence of
proptosis. Since, the estimation of unilateral proptosis
is usually relative to the “supposed to be” normal Fig. 83.10: Leudde’s exophthalmometer
other eye, one must not overlook the possibility of
natural asymmetry, unequal bilateral proptosis or
contralateral enophthalmos. Comparative exophthal-
mometry is a follow up study of proptosis to compare
the progress of the disease on subsequent visits.
Postural exophthalmometry changes are diagnostic
in Graves’ ophthalmopathy.5
Many exophthalmometers are available in the
market.
— Leudde’s exophthalmometer (Fig. 83.10). It is the
simplest form. This is made up of a thick trans-
parent plastic material with a groove which fits
into the outer bony margin of the orbit. A scale is
engraved on both sides and the observing eye is Fig. 83.11: Simultaneous bilateral exophthalmometry with
aligned with them to read off the level of the apex Hertel’s exophthalmometer
of the cornea.
— Hertel’s exophthalmometer (Fig. 83.11) It is the most
commonly used instrument. Its advantage is that
it measures the prominence of the two eyes (from
the lateral orbit rim), simultaneously.
— Mutch exophthalmometer It measures each eye
separately with the cheek or brow as reference
point. It is useful in cases of orbital fractures, etc.
Systemic Examination
i. General systemic examination should be conducted
to rule out proptosis (especially when bilateral)
associated with systemic diseases such as amy-
loidosis, histiocytosis or Wegner’s granulo-
matosis.
ii. Since endocrine dysfunction is the most common
cause of bilateral proptosis, thyroid evaluation
is important.
iii. It is also essential to search for primary neoplasm
elsewhere in the body whenever metastatic deposits are
Fig. 83.12: Bilateral proptosis due to metastatic Ewing’s
suspected in the orbit (Fig. 83.12). The metastatic
sarcoma in a 12-year old emaciated child with markings for
neoplasms of the orbit are predominantly carci- radiotherapy of primary Ewing’s sarcoma of the right iliac crest
 Chapter 83: Investigation of Orbital Space Occupying Lesions
nomas from the breast, lung, stomach, thyroid,
kidney, prostate or adrenals.6 The second most
common metastatic tumor of the orbit is neuro-
blastoma. Other metastatic tumors are malignant
melanoma, hemangiopericytoma, and Ewing’s
sarcoma.2
iv. Otolaryngological examination is necessary when
the paranasal sinus (Fig. 83.7) or a nasopharyn-
geal mass appears to be a possible etiological
factor in producing proptosis
LABORATORY INVESTIGATIONS
Thyroid function tests Extimation of protein bound
iodine (PBI), radioactive iodine uptake (RAIU), serum
TSH, T3,T4 levels, effective thyroxine ratio (ETR), and
thyroid scanning may be necessary when thyroid
ophthalmopathy is suspected.
Hematological studies TLC and DLC help in diagnosis
of inflammatory lesions or blood dyscrasias, e.g.
leukemias. Relative eosinophilia may indicate hydatid
cysts. Casoni’s test Casoni’s test is done to exclude
hydatid disease, but is of value in 50 percent of cases
only.
Urine analysis Urine analysis for Bence Jones protein
may reveal multiple myeloma.
SPECIAL INVESTIGATIONS
Even after a thorough and meticulous clinical
examination, the diagnosis of orbital diseases is not
clear many a times. Therefore, special investigations
are often required in a case of proptosis, which in
addition to helping in diagnosis are also useful in
planning the management of orbital lesions. Special
investigations for orbital lesions include:
• X-rays examination,
• Computerized tomography (CT) scanning,
• Orbital ultrasonography,
• Magnetic resonance imaging (MRI) and
• The invasive investigations such as contrast
orbitography, orbital venography and carotid
angiography which are sparingly used nowadays.
PLAIN X-RAY EXAMINATION
This helps to diagnose most extraorbital causes of
proptosis. Even now, in evaluation of an orbital lesion,
a plain skiagram is the most frequently used initial
X-ray examination of the orbit. The following
exposures are frequently required:
i. The Caldwell view is valuable and frequently
637
employed view for detection of orbital lesions.
The skiagram is taken with the patient’s nose
and forehead touching the film. The beam is
angled at about 25° so that the petrous pyramids
do not obscure orbital details. This view
demonstrates the superior orbital fissure, the
greater and lesser wings of the sphenoid bone,
the floor of the sella turcica, ethmoid and frontal
sinuses, and the innominate or oblique orbital
line.
ii. The Water view provides excellent details of the
maxillary sinuses, zygomatic arches, and orbits
(particularly the orbital rim and roof). This view
is obtained with the patient’s chin touching the
film and nose raised off the film by 2-3 cm.
iii. A lateral view generally shows the anterior
clinoid processes, the sella turcica, and the
sphenoid sinus clearly.
iv. The Rhese view is a special projection used to
visualize the optic foramina. Views of both optic
foramina, preferably on a single film should be
obtained for comparison of symmetry and size.
v. Some other projections may be helpful but are
not usually a part of routine orbital series.
These radiological views provide finite diag-
nostic information in approximately 50 percent of
orbital cases. The positive yield from such studies is
greatly increased by the following dictum: “The
roentgenologist should see the patient and the
ophthalmologist must see the film.”
Commonly observed X-ray signs of orbital
Fig. 83.13: Enlargement of left orbit in a
case of congenital teratoma
638 Section 6: Diseases of Orbit

diseases are outlined below:

Size of the orbit Enlargement of the orbit (Fig. 83.13)
is not an uncommon finding in orbital space occu-
pying lesions. In infants and children orbital enlarge-
ment occurs within 1 to 3 months while in adults it is
a sign of a long standing benign tumors (1-3 years
duration).
i. Symmetrical enlargement of the orbit is observed
in mass lesions of the muscle cone (intraconal
lesions) like optic nerve glioma, hemangioma,
and neurofibroma. Occasionally it may also be
seen in pseudotumor and retinoblastoma that
extends into the muscle cone.
ii. Asymmetrical orbital enlargement is a sign of
extraconal tumors like rhabdomyosarcoma, lacri-
mal gland tumor, dermoid cyst, hemangioma, Fig. 83.14: Calcification in a phthisical eye
etc.
early carotid angiography. Other causes of widening
Change in bone density Increased density is
of superior orbital fissure include intracavenous
observed in sphenoidal ridge meningioma, chronic
periosteitis, fibrous dysplasia, Paget’s disease, and aneurysm, intracranial extension of orbital tumors,
osteoblastic metastasis. extraseller extension of pituitary tumors, and
i. Localized decreased density/indentation of the meningiomas.
orbital wall is observed in benign tumors such Changes in optic canal: Normal adult dimensions
as dermoid and mixed cell lacrimal gland tumor. of optic canal are reached by the age of 4 to 5 years
ii. Diffuse bony destruction may signify malignant and its standard size is 4 to 6 mm. Measurements for
tumors like lacrimal gland carcinoma and spread 7 mm or more are always pathological. However, it
of tumors from paranasal sinuses. is to be stressed that one should always compare the
Change in orbital shape This is usually due to fossa two before giving final verdict on the size of the optic
formation, as a result of local expansion of the orbital foramina. In normal subjects the diameter of the two
wall. It occurs in orbital dermoids and encapsulated canals should not differ by more than one mm.
lacrimal gland tumors. i. A uniform regular concentric enlargement of the
optic canal is seen typically in cases of optic nerve
Dehiscence of orbital bones This may be observed
glioma (Fig. 83.15).
in lesions like mucocele of paranasal sinuses,
aneurysm, neurofibroma, lacrimal gland tumors, and
fractures.
Intraorbital calcification This may occur in many
lesions such as retinoblastoma (fine stippled calcifi-
cation), optic nerve sheath meningioma, lacrimal
gland carcinoma, orbital varix (Phlebolith), mucocele,
parasitic cyst (hydatid cyst), aneurysm, hematoma,
and phthisical eyes (Fig. 83.14). Calcified intracranial
lesions that may rarely have associated orbital or
intraocular lesions are toxoplasmosis, tuberous
sclerosis. Sturge-Weber syndrome, and von-Hipple
Lindau disease. Actual ossification due to metaplasia
of ocular tissue is rarely seen.
Enlargement of superior orbital fissure This is a
classical diagnostic sign of infraclinoid carotid Fig. 83.15: Enlargement of right optic foramen (R)
aneurysms (75% of cases), and therefore, calls for an
 Chapter 83: Investigation of Orbital Space Occupying Lesions 639
ii. A uniform irregular enlargement may be obser-
ved in meningioma of the optic nerve sheath,
retinoblastoma, and orbital neurofibromas.
iii. Erosion of its inferolateral margin is a sign of
infraclinoid lesions such as aneurysms and
meningiomas.
iv. Erosion of its upper margin is a sign of raised
intracranial pressure.
v. Total destruction of the margins indicates some
malignant neoplasm arising from one of the
paranasal sinuses.
vi. Occasionally, narrowing and hyperostosis
around the optic foramina may be observed in
meningioma en plaque.
Fig. 83.16: Thickened extraocular muscles in a
Computerized Tomography Scanning (CT Scan) case of Graves’ ophthalmopathy
CT scanning is a recent and valuable, noninvasive
method employed in the diagnosis of orbital and
related lesions. It uses thin X-ray beams to obtain
tissue density values. These values are processed by
a computer to provide detailed cross-sectional images.
The advent of CT scanning has transformed the
investigation of orbital disorders. A combination of
axial (CAT) and coronal cuts (CCT) enables a space,
occupying lesion within the orbit to be visualized in
three dimensions. CT scan with contrast medium may
further enhance the radiographic shadow of some
orbital tumors. CT scanning is, therefore, extremely
useful for determining the location and size of a space
occupying orbital lesion. Its main disadvantage is its
inability to distinguish between pathological soft
tissue masses which are radiologically isodense.
Advantage of CT scan is that it is capable of
visualizing various structures like globe, extraocular Fig. 83.17: Sphenoidal ridge meningioma invading left orbit
muscles (Fig. 83.16), and the optic nerves (from and temporal region; coronal section
retroocular space to optic canal). This technique is
also useful in examining areas adjacent to the orbit,
that is, orbital walls and intracranial structures, if
there is a suspicion of diseases such as meningioma
(Figs 83.17, 83.18, and 83.19), optic nerve glioma (Fig.
83.20) or metastasis (Fig. 83.21).

Ultrasonography
It is a nonradiational, noninvasive, well tolerated,
completely safe technique, and is of particular value
as an initial scanning procedure. A-scan produces a
unidimensional image and echoes are plotted as
spikes; B-scan produces a two-dimensional dotted
picture of orbital structures; thus the latter gives an
anatomical display which is much easier for the Fig. 83.18: Sphenoidal ridge meningioma invading left orbit
nonexpert to interpret. C-scan is useful for visualizing and temporal region; axial section
soft tissue of the orbit in the coronal plane. In the
diagnosis of orbital lesions, ultrasonography is
640 Section 6: Diseases of Orbit
Fig. 83.19: Extensive bone destruction in a case of
sphenoidal ridge meningioma
Fig. 83.20: Very large optic nerve glioma. Note
marked proptosis of right eye
Fig. 83.21: Bilateral metastatic Ewing’s sarcoma
superior to CT scanning in actual tissue diagnosis. It
can usually differentiate vascular lesions from
metastatic or inflammatory pseudotumor. It is,
however, less useful than CT scanning in the
evaluation of lesions against bony structures at the
apex of the orbit.
The ultrasonographic patterns of pathological
lesions depend mainly on the displacement of the
orbital fat. Differential diagnosis is usually based on
the patterns of sound reflectivity at the surfaces of
the mass and the transmission characteristics of the
sound wave as it passes through the lesions. From
these, the surface of the mass can be classified as
smooth or irregular and, the character of the mass
can be subclassified as solid, cystic, vascular or
infiltrative. Commonly observed ultrasonic patterns
are discussed below:
Normal Echo Pattern
When the scan passes through the plane of the optic
nerve, the normal echo pattern appears as a W-shaped
acoustically opaque area (Fig. 83.22A). Anteriorly, it
is separated from the globe by a concavity; and
posteriorly it is bounded by an empty notch formed
by the optic nerve. The retrobulbar fat pattern is
bounded nasally and temporally by the rectus
muscles.
Echo Pattern in Mass Lesions
Ultrasonographically, mass lesions of the orbit can
be differentiated into the following main groups:
a. Cystic swellings of the orbit such as mucocele and
dermoid cysts are characterized by sharply
defined round borders with good sound
transmission and no internal reflection, as they
are homogenous and fluid filled (Fig. 83.22B).
b. Solid tumors of the orbit also have round well
outlined borders, but a poor sound transmission
and variable encapsulated neurolemmoma, optic
nerve glioma, (Fig. 83.22C) and primary orbital
meningioma.
c. Spongy lesions of the orbit like hemangioma are
diagnosed from irregular shape, good sound
transmission, and strong internal echoes from
connective tissue septa. Compression of the orbit
with the examining probe often demonstrates a
spongy consistency (Fig. 83.22D).
d. Infiltrating orbital lesions like pseudotumors,
 Chapter 83: Investigation of Orbital Space Occupying Lesions
Fig. 83.22A: Ultrasonic pattern (B-scan) of orbital lesions
(diagrammatic). Normal orbit at optic nerve plane. Note W-
shaped acoustically opaque area
Fig. 83.22B: Ultrasonic pattern (B-scan) of orbital lesions
(diagrammatic). Cystic orbital mass having round borders, good
transmission and no internal echoes
Fig. 83.22C: Ultrasonic pattern (B-scan) of orbital lesions
(diagrammatic). Solid orbital tumor (optic nerve glioma)
641
Fig. 83.22D: Ultrasonic pattern (B-scan) of orbital lesions
(diagrammatic). Spongy tumor exhibiting irregular shape, good
transmission, and strong internal echoes
Fig. 83.22E: Ultrasonic pattern (B-scan) of orbital lesions
(diagrammatic). Infiltrating lesion, having irregular shape, poor
transmission, and minimal internal echoes
lymphangioma, malignant lymphoma and metas-
tatic carcinoma exhibit irregular variable shape,
poor sound transmission, and minimal internal
echoes due to homogenous infiltrating tissue
(Fig. 83.22E).
Ultrasonography in Graves’ Ophthalmopathy
This is very helpful in diagnosing early cases without
manifesting clinical signs of proptosis and in picking
up bilateral changes in apparently unilateral cases.
The characteristic feature is thickening of extraocular
muscles. Usually, the medial rectus is the first muscle
to enlarge. Normal thickness of extraocular muscle
in Indians is 4 mm. In addition to enlargement of
extraocular muscles, erosion of the temporal wall of
642 Section 6: Diseases of Orbit

the orbit, accentuation of retrobulbar fat, and

perineural inflammation of the optic nerve on B-scan,
have also been demonstrated in early Graves’
ophthalmopathy.6

Ultrasonic Features of Orbital Foreign Bodies

Localization of orbital foreign bodies by B-scan is
difficult, as often these are lost in the highly reflective
fatty tissue at high sensitivity settings. The demons-
tration of a trail of reduplication echoes behind the
foreign body is often the first clue of its presence.
Reduction of sensitivity is helpful in differentiating
stronger foreign body echoes from those of orbital
tissue.
Echo pattern in acute inflammation of the Fig. 83.22F: Ultrasonic pattern (B-scan) of orbital lesions
orbit With acute inflammation of the ocular wall or (diagrammatic). Fluid accumulation within Tenon’s capsule and
anterior orbit, edema fluid often collects beneath perioptic nerve swelling in a case of acute orbital inflammation
Tenon’s capsule. On ultrasonography, this
accumulation of fluid can be easily detected as an hydrogen nuclei when tissues are exposed to a short
echo-free space just outside the strong scleral electromagnetic pulse. Sensitive receivers pick up the
reflection (Fig. 83.22F). Differential diagnosis of electromagnetic echoes produced. MRI promises to
orbital lesions based on orbital ultrasonography is distinguish between lesions based not only on
summarized in Figure 83.23. location and tissue structure, but also on their
metabolic profile. It is very sensitive for detecting
Magnetic Resonance Imaging (MRI) differences between normal and abnormal tissues and
This technique represents a major advance in imaging has excellent image resolution. The technique
methods. It depends on the rearrangement of produces tomographic images which are superficially

Fig. 83.23: Ultrasonographic differential diagnosis of orbital lesions

 Chapter 83: Investigation of Orbital Space Occupying Lesions
very similar to CT scan but rely on entirely different
physical principles for their production. Unlike
conventional radiography and CT scanning, MRI does
not subject the patient to any ill-effects of ionizing
irradiations. So, it is safer for the patient. Further,
there is no need for contrast injections.
MRI is superior to tomography in evaluating
intracanalicular, chiasmal, and postchiasmal extension
of tumors. It has the added advantage of not being
hampered by bone and also proves to be more
sensitive in delineating subtle differences in fat
content and hydration of neural tissues. Further,
phosphorus MRI may provide increased accuracy and
specificity for tissue characterization. MRI is certainly
an excellent tool for investigation of orbital space
occupying lesions.7
Contraindications of MRI include pregnancy,
epileptic fits, cardiac pace-makers (metallic implants),
and surgical clips.
Contrast Orbitography
Orbitopneumography This old procedure, using
retrobulbar injection of air (negative contrast orbito-
graphy) is of historical interest only. This invasive
technique frequently results in chemical inflammation,
allergic reactions, air embolism and even exoph-
thalmos.
Injection of radioopaque dye in retrobulbar space
This is another abandoned method of contrast orbito-
graphy. The dye may cause toxic-optic neuropathy.
Orbital venography Presently, orbital venography
is required in a minority of patients, principally in
those who are clinically suspected to have orbital
varix. In these cases venography is indispensable not
only to confirm the diagnosis but also, more impor-
tantly, to outline the size and extent of the anomaly
to facilitate proper surgical planning. Another
indication for venography is in the diagnosis of
inflammatory processes of orbital veins, e.g. Tolosa-
Hunt syndrome, wherein obstruction may be shown
in the venous system due to pressure of granulation
tissue.
For orbital venography, 10 to 12 ml of suitable
contrast medium is injected preferably into the frontal
vein on the side of proptosis. Flow of dye into the
orbits is facilitated by a tourniquet tied around the
forehead, and by digital pressure over the fascial
veins. Anteroposterior view (of orbital venogram)
provides more information than lateral view. The
venous pattern of the uninvolved orbit may be used
643
as a control for interpretation.
Carotid angiography The introduction of compu-
terized tomography has made carotid angiography
a less frequent investigative procedure for evaluation
of cause of proptosis. Arteriography is done in
selected cases:
i. Patients suspected to have an arteriovenous shunt
or other intracranial vascular anomaly.
ii. Patients with a vascular tumor in the orbit where
it is important to identify the feeding vessel prior
to surgery.
iii. To identify the location and extent of ophthalmic
artery aneurysms.
iv. To identify the pathologic circulation associated
with various arteriovenous communications
along the ophthalmic artery-cavernous sinus
complex (that can produce unilateral proptosis).
v. Angiography should be performed in all the cases
of pulsating exophthalmos alone and in cases
which are associated with bruit or thrill.
Radioisotope studies Now a days, radioisotope
studies are sparingly employed in investigations of
proptosis. Radioisotope arteriography was found
useful in proptosis of vascular lesions.
HISTOPATHOLOGIC STUDIES
The exact diagnosis of many orbital lesions cannot
be made without the help of histopathological studies
which can be accomplished by fine needle aspiration
biopsy, incisional biopsy, excisional biopsy, core
biopsy or endoscopic biopsy.
Fine Needle Aspiration Biopsy (FNAB)
It is a type of nonexfoliative cytodiagnostic technique
and is described in detail in Chapter 85 (Ed).
Incisional Biopsy
Undoubtedly, for accurate tissue diagnosis a proper
biopsy specimen, at least 5 to 10 mm in length is
required and, preferably, it should include material
from the periphery as well as interior of the lesion.
However, such incisional biopsies, often have a
deleterious effect on the course of the tumor, or on
symptoms of patients. This embarrassing circum-
stance may be further compounded if the results of
the incisional biopsy are inconclusive. Therefore, the
scope of incisional biopsy in the overall scheme of
diagnostic search of orbital tumors is still not clearly
defined.
644 Section 6: Diseases of Orbit
Incisional biopsy along with frozen tissue study
may be undertaken in infiltrative orbital lesions which
remain undiagnosed. Recently, endoscopic orbital
biopsy carried out under general anesthesia is being
considered. In this technique sufficient biopsy
material is aspirated out endoscopically and is
interpreted by a trained cytologist.
Excisional Biopsy
It should always be preferred to incisional biopsy in
orbital masses which are well encapsulated or circum-
scribed. Further, whatever be the enthusiasm of the
ophthalmologist for incisional biopsy, it should be
tempered by the understanding that the removal of
an orbital tumor, not biopsy, is the main objective. It
is the orbital mass which brings the patient to the
clinician, and the feature for which he seeks relief.
For excisional biopsy, the following three proce-
dures are available:
i. Anterior orbitotomy for a mass in the anterior
part of the orbit is readily reached either by
transcutaneous or transconjunctival approach
(Reese).
ii. Lateral orbitotomy for a mass in the posterior
part (retrobulbar) or at the apex of the orbit
(Kronlein).
iii. Transcranial approach is employed when the
tumor extends into the cranial cavity
(Naffzeiger).
CORE BIPOSY
Core biopsy is a new diagnostic technique. The three
part instrument consists of a trephine, an obturator
and a tissue fixator. Using local anesthesia, a 2mm
skin incision is made in the eyelid area nearest the
tumor as ascertained by palpation and CT scan. The
obturator is then passed through the trephine into
the soft tissue tumor. The obturator is then removed
and the tissue fixator is passed into the trephine. with
a clockwise rotating motion, the tissue fixator is bored
into the tumor. Once it is fully engaged, the tissue
fixator and the trephine are withdrawn and the
cylinder of tissue is removed from the coil of the
tissue fixator. The solid tissue obtained by this
technique facilitates microscopic diagnosis and has
distinct advantage over the cellular specimen obtained
by means of a fine needle biopsy.
ENDOSCOPIC BIOPSY
Endoscopic biopsy involves the use of a fiberoptic
endoscope to visualize orbital lesion directly and a
specially designed instrument to take a biopsy of the
lesion. Orbital CT or MRI is used to guide placement
of the endoscope for the biopsy. Endoscopic biopsy
has an advantage over the fine needle biopsy and
core biopsy in that the surgeon can visualize the
surface of the lesion directly and select a biopsy site
that does not contain large blood vessels and is distant
from vital areas. A distinct disadvantage of the
technique is that the orbital fat obscures good
visualization.
IMMUNOHISTOCHEMISTRY
• Immunohistochemistry techniques can be applied
to orbital tumors and related lesions to aid
differential diagnosis. These highly sensitive tests
have contributed greatly to the understanding and
classification of orbital tumors. Basically, immuno-
histochemistry involves the use of antibodies that
are specific for certain antigens. The completed
antigen antibody reaction is identified by an
enzyme linked to the antibody, that generates
a color reaction when introduced to a certain
chemical.
• The glial fibrillary acidic protein (GFAP) has been
shown to be highly specific for glial cells, thus
aiding in the recognition of glial tumors.
• Factor VIII related antigen is synthesized by
vascular endothelial cells and can be identified in
tumors of vascular origin such as capillary
hemangioma, cavernous hemangioma and angio-
sarcoma.
• S-100 protein is believed to be a helpful marker
for cells of neural crest origin and can therefore,
helps to identify tumors of nerve origin and
melanomas.
• Use of antibodies against surface antigens of B
and T lymphocytes has also been applied recently
to the differentiation of orbital tumors.
• Myoglobin is the oxygen binding heme protein
found in cardiac and skeletal muscles but not in
smooth muscles.
SUMMARY
• A thorough evaluation of a case of proptosis is
extremely important before starting any treatment
procedures. A systematic approach with a know-
ledge of various etiopathogenic mechanisms can
help the ophthalmologist to arrive at a relatively
short list of differential diagnosis (Fig. 83.24).
 Chapter 83: Investigation of Orbital Space Occupying Lesions 645

Fig. 83.24: Scheme to short list the differential diagnosis of a case of proptosis

Sophisticated orbital imaging techniques now
permit to come to a conclusion rapidly and to
precisely plan the approach for prompt and
accurate management of a case of proptosis.
REFERENCES
1. Peyman GA, Sanders DR, Goldberg MF. Principles and Practice
of Ophthalmology. WB Saunders Company, Philadelphia/
London/Toronto, 1980.
2. Khurana AK, Ahluwalia BK, Gupta S et al. Bilateral proptosis
due to metastatic Ewing’s sarcoma of the orbit: FNAB and
histopathology of a case. Indian J Ophthalmol 1992;40:15.
3. Hollenhorst RW Jr, Hollenhorst RW Sr, and MacCarty CS. Visual
prognosis of optic nerve sheath meningiomas producing shunt
vessels on the optic disc: The Hoyt-Spencer syndrome. Trans
Am Ophthalmol Soc 1977;75:141.
4. Gamblin GT, Harper GD, Galentine P et al. Prevalence of increa-
sed IOP in Graves’ disease: Evidence of frequent subclinical
ophthalmopathy. New Eng J Med 1983;308:420.
5. Haurer J. Clinical observations in exophthalmos. Br J
Ophthalmol 1957;40:533.
6. Col DJ, Jack RL, Franzen LA, et al. High resolution, B-scan
ultrasonography of the orbit—Part V: Eye changes of Graves’
disease. Arch Ophthalmol 1992;88:465.
7. Boparai MS. Mangetic resonance imaging and proptosis. Proc
48th All India Ophthalmol Soc Conf 1990;257.
 Chapter 84
Lymphoproliferative, Leukemic
and Histiocytic Lesions
of the Orbit
Ramesh Murthy, Sanghamitra Burman, Santosh G Honavar,
Geeta K Vemuganti, Milind Naik, Vijay Anand Reddy
INTRODUCTION
Lymphoid tumors and leukemias constitute the largest
sub-group among orbital tumors. Lymphoid tumor
can occur in the orbit with or without associated
systemic disease. Recent advances in diagnostic
techniques have led to a better understanding of
orbital lymphoproliferative lesions.
The most important differential diagnosis of orbital
lymphoproliferative lesions is the group of infla-
mmatory pseudotumor. In contrast to inflammatory
pseudotumor, lymphoid tumor are predominantly
composed of small lymphocytes. The inflammatory
pseudotumors are also usually responsive to anti-
inflammatory agents or to specific treatment directed
towards the causative agents. It is important to
establish the diagnosis by a biopsy. The preferred
technique is to do an incisional biopsy with careful
handling of the tissue and subjecting the sample to
immunophenotyping and molecular studies. Fine
needle aspiration biopsy (FNAB) is usually not done,
as the tissue yield is not usually sufficient to confirm
the diagnosis.
CLASSIFICATION
Due to the advent of newer immunodiagnostic
techniques and understanding that these tumors arise
from the immune system, newer classifications have
been proposed. Various systems of classification for
Non-Hodgkins lymphomas have been in vogue.
Rappaport in 1966 proposed a classification based on
the histologic differentiation of the lesions and this
classification is still being used. About a decade later,
the Lukes Collins and Kiel classification came into
vogue. 1 In 1982 the Working Formulation was
proposed for understanding the different classi-
fications of Non Hodgkin’s lymphomas.2 In recent
times this has been replaced by the Revised European
American Lymphoma (REAL) classification system
proposed by the International lymphoma study group
(ILSG). 3 A World Health Organization (WHO)
classification based on the REAL system has also been
proposed recently.4 The REAL classification system
has replaced the Rappaport and Lukes Collins systems
for the classification of orbital lymphomas (Table 84.1).
Rootman et al, have classified the lesions into 4
types based on the clinical presentation. 5 Type 1
lesions have an insidious onset and are painless orbital
masses. This is the largest group and consists of mainly
low-grade lymphoproliferative lesions. Type 2 lesions
include the fulminant lesions, which have a more rapid
onset and are aggressive. In addition this group of
patients are also prone to secondary infectious
disorders. Type 3 lesions secondarily involve the orbit
from the bone, the paranasal sinuses or the skin. Type
 Chapter 84: Lymphoproliferative, Leukemic and Histiocytic Lesions of the Orbit
Table 84.1: REAL classification
• Clinically indolent (low–risk)
— Chronic lymphocytic leukemia (CLL) or small
lymphocytic lymphoma
— Lymphoplasmacytic lymphoma
— Follicular lymphoma, grades I-II
— Marginal-zone lymphoma, extranodal, nodal and
splenic
— Plasmacytoma/myeloma
— Mycosis fungoides/Sezary syndrome
• Clinically aggressive (Intermediate risk)
— Follicular lymphoma, grade III
— Diffuse large B-cell lymphoma
— DLBC lymphoma
— Mantle cell lymphoma
— B-cell prolymphocytic leukemia
— Peripheral T- cell lymphomas (PTCL) and anaplastic
large cell lymphoma
• Clinically very aggressive (High-risk)
— Lymphoblastic lymphoma
— Burkitt’s lymphoma
— Adult T-cell leukemia/ lymphoma
4 patients present with neuroophthalmic compli-
cations due to the lymphoproliferative lesions.
For the purpose of simplicity and easy under-
standing, we will classify the lesions as suggested by
Rootman et al.5
1. Lymphocytic tumor
a. Reactive lymphoid hyperplasia
b. Non Hodgkin’s lymphomas
i. Small B cell lymphomas
ii. Diffuse large B cell lymphomas
iii. Burkitt’s lymphoma
iv. T cell lymphomas
2. Leukemic lesions
a. Leukemia
b. Granulocytic sarcoma
3. Plasma cell tumors
a. Solitary plasma cell tumors
b. Multiple myeloma
4. Hodgkin’s lymphoma
5. Histiocytoses
a. Langerhans’ cell histiocytosis
b. Malignant histiocytosis
6. Miscellaneous lesion
Lymphocytic Lesions
These lesions usually have a gradual onset in the 6th
or 7th decade of life with proptosis or diplopia. Visual
acuity and ocular motility are usually only slightly
impaired. The lesions are usually located in the
647
anterior orbit and may involve the conjunctiva,
appearing as a pink fleshy mass (‘Salmon patch’
appearance). They mould the globe and are commonly
found at an extraconal location. They usually have an
oblong or pancake shape. On palpation they have a
rubbery consistency. Bilateral lesions are found in one
third of the cases and usually indicate a more
aggressive course. 6 These tumors also have a
predilection for lacrimal gland involvement.7
Reactive Lymphoid Hyperplasia
These lesions are characterized by a polymorphous
collection of lymphocytes and plasma cells. They show
the presence of polyclonality, lymphoid follicles,
vascular hyalinization, hemosiderin deposition and
endothelial proliferation. Immunohistochemical
methods show the polyclonal nature of the lesion with
the presence of T and B-lymphocytes.8
Clinically these lesions have a more indolent course
and appear as firm, rubbery lesions. They are usually
painless and are usually in the anterior part of the
orbit. The possibility of malignant transformation is
rare and there is a 15 to 25% chance of eventual
systemic involvement. 9 These lesions are probably
MALT (mucosa-associated lymphoid tissue) lympho-
mas and are not likely to progress. 10
These lesions respond to steroids. Some of them
need radiotherapy in the doses of 1500 to 2000 cGy.
Those not responsive to steroid and radiotherapy need
immunosuppression or cytotoxic therapy is usually
indicated.11 If future research shows that these tumors
are actually MALT lymphomas, then it might be
possible to spare the patients from radiation.12
Small B cell lymphomas
Most of the lymphoid lesions in the orbit belong to
this group. The WHO classification of small cell
lymphomas is given in Table 84.2.
Small lymphocytic lymphomas consist of normal
appearing lymphocytes and are characterized by the
presence of growth centers. The lymphoplasmacytoid
lymphoma shows the presence of plasma cells and
Table 84.2: WHO classification of small cell lymphomas
• B-cell chronic lymphocytic leukemia/ small lymphocytic
lymphoma
• Lymphoplasmacytic lymphoma
• Mantle cell lymphoma
• Follicular center lymphoma, follicular, grades I-II
• Diffuse follicular center lymphoma
• Extranodal marginal zone B cell lymphoma of MALT type
648 Section 6: Diseases of Orbit

frequently Russell (intracytoplasmic inclusions of systemic involvement occurs in most of the cases. They
immunoglobulins) and Dutcher bodies (periodic acid also tend to involve the central nervous system and
Schiff positive intranuclear inclusions of immuno- sometimes affect the vitreous and the retina. They
globulins). The mantle cell lymphomas are more consist of large atypical lymphocytes and are
aggressive and show the presence of mitotic figures. sometimes poorly differentiated. Management is by
The follicle centre lymphomas consist of small-cleaved systemic chemotherapy combined with radiotherapy
cell lymphocytes. The MALT lymphomas have for the orbital disease. The prognosis is usually poor
reactive lymphoid follicles and involve mucosal and owing to involvement of the central nervous system.14
epithelial surfaces throughout the body. These lesions
are usually of a more benign nature. Burkitt’s Lymphoma
These tumors show an insidious onset usually in
Denis Burkitt first described this in 1958.15 This tumor
the sixth or seventh decade of life. They are usually
is endemic in Central Africa and has a predilection
located in the anterior orbit and may be associated
for the jaws and the abdomen.15 In addition there is a
with subconjunctival lesions. They present with mild
possible infectious etiology with involvement of the
proptosis with the globe usually displaced infero-
Epstein-Barr virus16 and chromosomal abnormalities
medially. Bilaterality is present in about 25% of the
involving translocation of the c-myc gene. It is also
cases. Systemic involvement is likely to occur in nearly
common in the presence of HIV infection.
60% of the patients over 10 years. CT scan reveals the
The African form of the disease usually presents
presence of well-defined, homogeneous lesions
with rapidly progressive proptosis and upward globe
usually in an extraconal location characteristically
displacement owing to the origin of the tumor from
isodense to muscle. They mould to the globe or the
the maxillary bone. It frequently occurs in the first
adjacent structures. Though usually lobulated, they
decade of life. The non-African form usually occurs
may sometimes assume a more nodular and infil-
in the first 3 decades of life and abdominal involve-
trative character. Lacrimal gland involvement is
ment is more common than facial tumors.
common. MRI is not very useful in the diagnosis of
The clinical presentation of an abdominal tumor
these lesions. On T1 weighted images these lesions
with proptosis especially upward globe displacement
are hypodense to the orbital fat. On T2 images the
in an African child is suggestive of this lymphoma.
tumor is hyperintense to both fat and muscle. These
CT scan usually demonstrates the maxillary lesion
lesions show gadolinium enhancement on T1 weigh-
with secondary involvement of the orbit.
ted images.
Histopathology reveals the presence of uniformly
It is important to confirm the diagnosis by an
packed lymphocytes containing fat filled cytoplasmic
orbital biopsy and stage the disease and look for any
vacuoles. Interspersed between these lymphocytes are
evidence of systemic involvement before starting
phagocytic histiocytes, which impart a ‘starry sky’
treatment. Lesions localized to the orbit are best
appearance.14
treated by radiotherapy at a dose of 2500 to 3000 cGy.13
Management involves a biopsy to confirm the
If there is evidence of systemic lymphoma, it is best to
diagnosis. Debulking can be attempted. This tumor
administer chemotherapy and institute orbital
shows a dramatic response to chemotherapy espe-
radiotherapy for the orbital lesion. The prognosis after
cially to cyclophosphamide, methotrexate and
treatment is excellent.
vincristine. Adjuvant radiotherapy can also be
Diffuse Large B Cell Lymphomas employed especially in cases refractory to chemo-
therapy.
These are the second most common form of Non- The prognosis has greatly improved after the
Hodgkin’s lymphomas after the small cell variety in advent of chemotherapy. Favorable prognostic factors
the orbit. It was previously believed to originate from are localised disease and younger age.
the tissue histiocytes and was called as ‘reticulum cell
sarcoma’ and ‘histiocytic lymphoma’.14 They are rare; T Cell Lymphomas
in the Mayo clinic series they comprised about 1.3%
of the orbital lesions. Clinically these lesions are These can be classified as
usually unilateral and present with eyelid swelling 1. Precursor T-cell lymphomas
and proptosis. These are aggressive tumors and 2. Peripheral T-cell lymphomas
 Chapter 84: Lymphoproliferative, Leukemic and Histiocytic Lesions of the Orbit
3. Cutaneous T-cell lymphomas
a. Mycosis fungoides
b. Sezary syndrome
The precursor T-cell group includes the subtype,
lymphoblastic lymphoma that commonly involves the
anterior mediastinum, central nervous system and the
peripheral blood and rarely involves the orbit. The
T/NK (T-cell/Natural Killer) lymphomas of the
peripheral T-cell lymphoma group rarely involve the
orbit and orbital involvement is usually secondary to
spread from midfacial lesions.
The cutaneous T-cell lymphomas (CTCLs) includes
two overlapping entities, Sezary syndrome and
mycosis fungoides.17 Sezary syndrome presents with
erythematous skin nodules, lymphadenopathy,
abnormal lymphocytes in the blood and organo-
megaly. Mycosis fungoides is characterized by
predominant skin involvement.
Diagnosis is by the identification of anaplastic large
T lymphocytes which have irregular nuclear outlines
and irregular indentations in their nuclear membrane
called as Sezary cells.17 A complete blood count should
also be performed to identify these abnormal cells.
Skin lesions show these lymphocytes within the upper
dermis and the epidermis and characteristic micro-
abscesses (Pautrier’s micro abscesses).
Clinically these tumors present mostly in males in
the 4th decade of life. Orbital involvement occurs due
to spread of the cutaneous disease and can affect the
lids and conjunctiva as well. The T/NK lymphomas
can secondarily involve the orbit and can cause cranial
nerve palsies.
Management of these tumors is mainly by radio-
therapy with occasional use of psoralen ultraviolet
(PUVA) light therapy. Chemotherapy is given for
widespread disease. The T/NK lymphomas are
treated by irradiation.
Leukemic Lesions
Leukemia
Leukemia is a common childhood cancer and
commonly involves the bone marrow. The eye and
the adnexal tissue is rarely involved especially in the
acute lymphoblastic form. It is usually unilateral and
presents with a rapid onset of proptosis due to either
soft tissue involvement or hemorrhage. Hemorrhages
in the retina and leukemic infiltration of the uvea, optic
nerve and meninges may be present. Orbital involve-
ment indicates a grave prognosis. Systemic and
649
intrathecal chemotherapy with local irradiation may
prolong survival.
Granulocytic sarcoma
Also called as chloroma, this usually is an extra-
medullary form of acute myeloblastic leukemia or of
chronic granulocytic leukemia entering blast crisis.18
It usually affects boys in the first decade of life. The
orbit may be the initial site of presentation but usually
progresses to systemic leukemia. It presents with a
rapid onset and progression of unilateral proptosis.18
The mass typically involves the lateral walls of the
orbit. Only 10% of the cases are bilateral. CT reveals
the presence of a large irregular mass sometimes
eroding the bone or extending into the temporal fossa.
Diagnosis is by a biopsy as this mimics infla-
mmatory lesions owing to the rapidity of progression.
Giemsa stained smears reveal the presence of
cytoplasmic granules and Auer rods indicating the
myeloid origin of the cells. The name chloroma is
derived from the presence of myeloperoxidase in the
tissue, which imparts a green color to the tissue.
Immunohistochemical techniques with the use of the
Leder stain in formalin fixed tissue for chloroacetate
esterase can facilitate the diagnosis.
The prognosis is poor and treatment consists of
local irradiation and intensive chemotherapy.
PLASMA CELL TUMORS
The plasma cell tumors are rare in and around the
orbit. In conditions like Waldenstrom’s macro-
globulinemia there can be excess production of IgM
paraproteins. Neuro-ophthalmic disorders and ocular
lesions like retinal hemorrhages, microaneurysms and
thrombosis can occur in multiple myeloma. Orbital
involvement by these tumors is rare.
Histology reveals the presence of plasma cells,
which are oval cells with an eccentric nucleus
containing chromatin arranged in the form of a
cartwheel and a paranuclear halo. Intracytoplasmic
inclusions (Russell bodies) and intranuclear inclusions
(Dutcher bodies) consisting of immunoglobulin
deposits are also present.
Solitary Plasma Cell Tumors
These could be polyclonal or monoclonal. Polyclonal
lesions consist of a mixed population of plasma cells
and lymphocytes with reactive changes. Diagnosis is
by identifying kappa and lambda light chains by
650 Section 6: Diseases of Orbit
immunostaining. These lesions are commoner in the
conjunctiva than the orbit. Treatment is by surgical
excision followed by radiotherapy. The solitary
extramedullary plasmacytomas are rare monoclonal
infiltrates in soft tissue or bone. Orbital involvement
is extremely uncommon and is usually secondary to
paranasal sinus involvement. Radiotherapy is the
mainstay of management, with surgery and chemo-
therapy being used in recurrent or unresponsive
disease.
Multiple Myeloma
This condition commonly presents with bone pains,
fractures, anemia and recurrent infections. It rarely
involves the orbital tissues. It usually presents in the
7th decade of life and predominantly affects males. In
most cases of ocular involvement, it presents initially
as proptosis.19 Retinal vascular changes like cotton
wool spots, retinal hemorrhages, microaneurysms and
pars plana cysts can occur in patients with multiple
myeloma. Central nervous system involvement can
cause papilledema and cranial nerve palsies. Diagnosis
is by immunostaining and detection of monoclonal
light chains. Multiple osteolytic lesions, hyper-
calcemia, uremia, hyperglobulinemia and Bence Jones
proteinuria are suggestive of this condition. Histology
reveals the presence of large atypical plasma cells with
giant cells and multinucleated cells. Treatment is with
systemic chemotherapy and local radiation.
HODGKIN’S LYMPHOMA
This tumor commonly affects the lymph nodes and
extranodal involvement is rare. The WHO classi-
fication of Hodgkin’s lymphoma is given in Table 84.3.
In Hodgkin’s lymphoma orbital involvement follows
systemic involvement and usually occurs in the
advances stages of the disease. It affects middle-aged
adults with progressive proptosis.
The diagnostic feature is the presence of Reed
Sternberg cells, which are large, irregular, binucleate
Table 84.3: Classification (World Health Organization) of
Hodgkin’s lymphoma
• Nodular lymphocyte-predominant Hodgkin’s lymphoma
• Classical Hodgkin’s lymphoma
— Nodular sclerosis Hodgkin’s lymphoma
— Lymphocyte-rich classical Hodgkin’s lymphoma
— Mixed cellularity Hodgkin’s lymphoma
— Lymphocyte depletion Hodgkin’s lymphoma
or multinucleate histiocytes with a foamy cytoplasm,
in a matrix of lymphocytes, eosinophils, plasma cells
and neutrophils.
The occurrence of an orbital mass in a patient with
a previous diagnosis of Hodgkin’s lymphoma should
be viewed with suspicion.
The prognosis depends on the cytology and the
staging of the lesion. The staging is commonly done
by the Rye classification (Table 84.4).
Management includes a biopsy to confirm the
diagnosis followed by orbital irradiation and systemic
chemotherapy. The prognosis is guarded as orbital
involvement usually indicates advanced disease.
HISTIOCYTOSES
Langerhans’ Cell Histiocytoses
This entity was previously called as histiocytosis X
and includes three disorders Hand-Schuller-Christian
disease, Letterer Siwe disease and Eosinophilic
granuloma.
This is a disease of young boys and ocular
involvement occurs in about 10% of the cases. Most
of the children present with bony involvement while
one third of the patients present with disseminated
disease.
There is an accumulation of dendritic histiocytes
especially Langerhans’ cells of the epidermis. These
large mononuclear cells have an indented nucleus
with a central striated line. On electron microscopy,
the cells show the presence of characteristic ‘racquet
shaped’ cytoplasmic granules called Birbeck granules.
Table 84.4: Staging of Hodgkin’s lymphoma
(Rye classification)
• Stage I: Disease limited to one anatomic region (stageI1)
or to two contiguous anatomic regions on the same side
of the diaphragm (stage I2)
• Stage II: Disease in more than two anatomic regions or in
two non-contiguous regions on the same side of the
diaphragm
• Stage III: Disease on both sides of the diaphragm but not
exceeding beyond the involvement of lymph nodes,
spleen or Waldeyer’s ring
• Stage IV: Involvement of the bone marrow, lung
parenchyma, pleura, liver, bone, skin, kidneys, gastro-
intestinal tract or any tissue or organ in addition to lymph
nodes, spleen or Waldeyer’s ring
*All stages are subclassified as A or B to indicate the absence or
presence of systemic symptoms (fever, night sweats, weight loss
> 10% of baseline).
 Chapter 84: Lymphoproliferative, Leukemic and Histiocytic Lesions of the Orbit
Eosinophilic Granuloma
This is the most common variant and commonly
presents with a painful swelling in the superolateral
orbit with overlying skin erythema.20 The frontal and
zygomatic bones are most frequently involved.
Hand-Schuller-Christian Disease
The classical triad seen in this condition included
bilateral proptosis, diabetes insipidus and multiple
bony lesions of the skull but the complete picture is
rarely seen.
Letterer-Siwe Disease
This entity shows the presence of hepatospleno-
megaly, lymphadenopathy and osseous defects with
occasional diffuse infiltration of the uveal tract.21
CT scan in cases of eosinophilic granuloma reveals
the presence of an osteolytic lesion in the orbital bones
superotemporally with irregular margins and
hyperostosis.
Management of eosinophilic granuloma is by
removal of the lesion by curettage followed by adjunc-
tive radiotherapy. Intralesional methylprednisolone
has been used for quicker resolution. Chemotherapy
has also been tried in severe forms of the disease.
Eosinophilic granuloma has an excellent prognosis.
Prognosis is poor in cases of Letterer-Siwe disease.
Malignant Histiocytosis
This is a rare condition characterized by an abrupt
onset of fever, anemia, leukopenia and hepato-
splenomegaly. Histology reveals diffuse infiltration
by pleomorphic histiocytes showing erythrophago-
cytosis. Prognosis is poor, but some cases have shown
remission with chemotherapy.
MISCELLANEOUS LESIONS
Sinus histiocytosis with massive lymphadenopathy
This entity is also called as Rosai Dorfmann syndrome.
This is a benign pseudolymphomatous entity characte-
rized by infiltration of the lymph nodes and extranodal
soft tissues by sheets of histiocytes. This usually occurs
in the first decade of life and presents with cervical
lymphadenopathy.22 Orbital involvement occurs in
about 11% of the cases. This usually presents with
proptosis, eyelid swelling and associated cervical
lymphadenopathy. There is a painless, rubbery mass
palpable in the superior orbit. Serum protein
651
abnormalities are sometimes present in this condition.
Histology reveals the presence of lymphocytes and
histiocytes, which have phagocytosed erythrocytes,
lymphocytes and plasma cells, a phenomenon called
as ‘emperipolesis’. This condition is often self-limiting.
In localized disease surgical excision and low dose
radiotherapy may be helpful. Systemic involvement
is usually treated by a combination of radiotherapy,
chemotherapy and corticosteroids.
Xanthogranulomas
These are histiocytic tumors in which the histiocytes
contain lipid deposits. They are grouped into three
categories—juvenile xanthogranulomas, Erdheim-
Chester disease and necrobiotic xanthogranuloma. An
immunologic basis has been suggested for the
etiopathogenesis. It has been suggested that serum
immunoglobulins are complexed with lipids and are
deposited in the skin eliciting a giant cell foreign body
reaction.
Histopathologically they are characterized by a
granulomatous inflammation with histiocytes,
lymphocytes and plasma cells. The distinctive feature
is the presence of Touton Giant cells in which nuclei
are arranged in a circular fashion around a central area
of eosinophilic cytoplasm. Necrobiotic xanthogranulo-
mas are characterized by the presence of areas of
collagen destruction.
Juvenile xanthogranuloma usually presents in
children with cutaneous eruptions and usually affects
the anterior uveal tract; orbital involvement is rare.
In cases of orbital involvement the presentation is
usually during the first few weeks after birth with
proptosis, without the typical skin lesions. These
lesions are best managed by surgical excision followed
by radiotherapy and steroids.
Erdheim Chester disease is the association of adult
onset xanthogranulomas with systemic disease
especially with diffuse sclerosis of the diaphysis and
metaphysis of long bones and sometimes with
hepatosplenomegaly, hepatic adenomas and infil-
tration of the lungs, kidneys and heart. 23 This
condition is usually responsive to corticosteroids.
Necrobiotic xanthogranuloma is characterised by
association with paraproteinemias and other entities
like IgG monoclonal gammopathy, plasmacytosis,
cryoglobulinemia, complement deficiency and
leucopenia.24 Multiple myeloma and non-Hodgkin’s
lymphoma have been associated with this condition.
652 Section 6: Diseases of Orbit
The treatment modalities tried include steroids,
chemotherapy and management of the associated
diseases.
REFERENCES
1. Lukes RJ, Collins RD. New approaches to the classification
of lymphomata. Br J Cancer 1975;31(suppl 2):1.
2. Non-Hodgkin’s Lymphoma Pathologic Classification Project:
National Cancer Institute-sponsored study of classifications
of non-Hodgkin’s lymphomas: Summary and description of
a working formulation for clinical usage. Cancer; 1982;
49:2112.
3. Harris NL, Jaffe ES, Stein H et al. A revised European-
American classification of lymphoid neoplasms: a proposal
from the International lymphoma Study Group. Blood;
1994;84:1361.
4. Harris NL, Jaffe ES, Diebold J, et al. World Health
Organization classification of neoplastic diseases of the
hematopoeitic and lymphoid tissues: report of the Clinical
Advisory Committee Meeting-Airlie House, Virginia,
November 1997. J Clin Oncol 1999;17:3835.
5. Rootman J, White VA, Connors JM, Gascoyne RD. Lympho-
proliferative, leukemic and Histiocytic lesions of the orbit. In
Rootman J, ed. Diseases of the orbit. JB Lippincott Company:
Philadelphia, 2001.
6. Jakobiec FA, McLean I, Font R. Clinicopathologic charac-
teristics of orbital lymphoid hyperplasia. Ophthalmology
1979;86: 948.
7. Shields JA, Bakewell B, Augsburger JJ et al. Classification and
incidence of space occupying lesions of the orbit: A survey
of 645 biopsies. Arch ophthalmol 1984;102:1606.
8. Knowles DM, Jakobiec FA, Halper JP. Immunologic
characterisation of ocular adnexal lymphoid neoplasms. Am
J Ophthalmol 1979;87:603.
9. Knowles DM, Jakobiec FA. Orbital lymphoid neoplasms. A
clinicopatholgic study of 60 cases. Cancer 1980;46:576.
10. Lauer SA. Ocular adnexal lymphoid tumors. Curr Opin in
Ophthalmol 2000;11:361-66.
11. Schick U, Lermen O, Unsold R, Hassler W. Treatment of
primary orbital lymphomas. Eur J Haematol 2004 ;72:186.
12. Hardman-Lea S, Kerr-Muir M, Wotherspoon AC, et al.
Mucosa-associated lymphoid tissue lymphoma of the
conjunctiva. Arch Ophthalmol 1994;112:1207-12.
13. Hasegawa M, Kojima M, Shioya M et al. Treatment results of
radiotherapy for malignant lymphoma of the orbit and
histopathologic review according to the WHO classification.
Int J Radiat Oncol Biol Phys 2003;57:172.
14. Henderson JW, Farrow GM. Orbital tumors (2nd Ed). New
York, Brian C Decker (Thieme Stratton) 1980;344.
15. Burkitt D. A sarcoma involving the jaws in African children.
Br J Surg 1958;46:218-223.
16. Henle W, Henle G. Evidence for an oncogenic potential of
the Epstein-Barr virus. Cancer Res 1973;33:1419.
17. Meekins B, Proia AL, Klintworth GK. Cutaneous T cell
lymphoma presenting as a rapidly enlarging ocular adnexal
tumor. Ophthalmology 1985;92:1288-1293.
18. Zimmerman LE, Font RL. Ophthalmologic manifestations of
granulocytic sarcoma. Am J Ophthalmol 1975;80:975-990.
19. Hamburger HA. Orbital involvement in multiple myeloma
a new angiographic presentation. J Clin Neuro Ophthalmol
1984;25:4.
20. Baghdassarian SA, Shammas HF. Eosinophilic granuloma of
orbit. Ann Ophthalmol 1977;9:1247.
21. Mittelman D, Apple DJ, Goldberg MF. Ocular involvement
in Letterer Siwe disease. Am J Ophthalmol 1973;75:261-265.
22. Rosai J, Dorfman RF. Sinus histiocytosis with massive
lymphadenopathy. A pseudolymphomatosis benign dis-
order. A newly recognised benign clinicopathologic entity.
Arch Pathol 1969;87:63-70.
23. Egan AJM, Boardman LA, Tazelaar HD et al. Erdheim-Chester
disease: clinical, radiologic and histopathologic findings in
five patients with interstitial lung disease. Am J Surg Pathol
1999;23:17-26.
24. Kossard S, Winkelman RK. Necrobiotic xanthogranuloma
with paraproteinemia. J Am Acad Dermatol 1980;3:257-270.
 Chapter 85
Ultrasonography-guided Fine
Needle Aspiration Cytology
in Orbital Lesions
Anju Rastogi, S Jain, M Kumar
INTRODUCTION
The orbit has a complex of neurosensory, vascular,
motor and secretory tissue types confined to a 30 cm3
area surrounded by bone, nasal sinuses, and intra-
cranial structures. Consequently, a large number of
pathologic processes can involve the orbit, the diag-
nosis of which is a challenge to the clinicians.
Systematic work-up of a orbital lesion includes
careful clinical examination followed by noninvasive
investigations like standard X-rays, ultrasonography,
CT scan, and MRI. The extent and size of the lesion
can be accurately demarcated with these procedures,
but the morphology and pathological nature, essential
to evaluate and manage the disorder may remain
nonelusive. In this chapter the role of diagnostic
surgical biopsies and fine needle aspiration biopsy
(FNAB) has been described. Surgical biopsy unlike
FNAB is painful, time consuming, and an aggressive
procedure with its attendant complications.
Fine needle aspiration biopsy (FNAB) is a tech-
nique which involves the use of a fine bore needle to
aspirate a solid or a cystic mass and to subject it to
cytodiagnosis. The cytology of the aspirate has been
found to correlate with the postoperative histology in
many studies. 1-4 Now it is believed that proper
identification of most of the lesions is possible with
fine needle aspirate. FNAB provides clinicians with a
reliable, rapid, and low cost method of diagnosis of
lesions. It is an outpatient procedure and can be carried
out without anesthesia. In addition to its clinical
applications, FNAB provides tissue for use in the
development of new processing methods which
include tissue culture, immunoglobulin analysis, and
electron microscopy.5-7
HISTORICAL BACKGROUND
Kun was the first person to report the use of aspiration
biopsy in 1847.8 However, the technique got recog-
nition only in the 1930s as a means of diagnosis of
human tumors.9-11 Franzen et al further refined and
popularized the technique.12 Now FNAB has become
an extremely valuable diagnostic aid used for almost
all organs of the body including bone marrow, spleen,
liver, breast, thyroid, lymph nodes, salivary glands,
kidney, gonads, prostate, orbit, and lately the eyeball.13
Schyberg of Sweden was the first person who in 1975
applied the technique of FNAB to diagnose orbital
lesions.14
TECHNIQUE
FNAB requires simple equipment, viz. 21-25 gauge
needles varying in length from 3.0 to 3.75 cm; 10 and
20 ml disposable syringes; a syringe holder (pistol);
glass slides; and fixatives such as 95 percent ethyl
alcohol or methanol.
Anterior Orbital and Palpable Lesions
In these cases a transcutaneous biopsy is performed.
The skin is cleaned with an antiseptic and the
654 Section 6: Diseases of Orbit
suspected area is fixed with the thumb and forefinger
of one hand. The needle, attached to a syringe
mounted on a syringe holder, is inserted through the
skin into the lesion. No anesthesia is required. When
the needle has entered into the lesion, the plunger of
the syringe is retracted creating a vacuum in the
system. In order to aspirate sufficient material, the
needle is moved back and forth, and sideways into
different areas of the lesion, always maintaining the
vacuum. At the end of aspiration, the pistol is released,
the pressure is allowed to equalize with the atmos-
phere, and the needle is withdrawn from the lesion
(Fig. 85.1). FNAB may also be performed by the
conjunctival approach. This requires topical anesthesia
and an antibiotic drop to be instilled in the conjunctival
sac before the procedure.
Posterior Orbital and Nonpalpable Lesions
The lesions which cannot be palpated require
localization for accurate placement of the tip of the
aspirating needle within the mass. This may be done
with the help of ultrasound, CT scan or MRI.15-16
Fig. 85.1: Schematic representation of FNAB technique.
(A) The needle, attached to its syringe and holder, is introduced
into the lesion. (B) The plunger is retracted to create a negative
pressure in the system. The needle is moved back and forth
and sideways to aspirate sufficient material. (C) The plunger is
released and the needle withdrawn
Ultrasound-guided FNAB for Posterior
Orbital and Non-palpable Lesions
Ultarsound is more economical, and requires rela-
tively less set-up and time than CT scan or MRI. It
may be done as an office procedure. Ultrasound
displays a real time B-scan image that allows the
clinician to observe the tip of the aspirating needle as
it advances and enters the tumor, at which time the
aspiration is performed. When FNAB is done with the
help of B-scan guidance it has the following distinct
advantages:
a. It gives an accurate diagnosis and helps clinicians
avoid exploratory surgery in nonpalpable lesions.
This allows an appropriate clinical evaluation and
an early treatment.
b. B-scan guidance helps obtain a tissue diagnosis in
malignant deep seated lesions where early
radiation therapy can prove to be life saving.
c. This technique has proven to be a boon in
debilitated persons where clinical diagnosis can be
rapidly and accurately confirmed by FNAB
without resorting to surgery.
However, ultrasonically-guided FNAB is better for
lesions located in the anterior and mid orbitals. Less
than excellent ultrasound imagery of deeper orbital
areas, makes CT guided FNAB more useful in biopsy
of deeply situated orbital masses.
Guidelines
Certain specific points are to be kept in mind while
doing FNAB: (a) The lesion must be approached
through the shortest possible distance. (b) In general,
the orbit should be entered from the side of the globe
and not directly above or below it, to avoid globe
perforation. (c) Optic nerve tumors are to be appro-
ached as for giving retrobulbar anesthesia. (d) A
needle longer than 3.75 cm is not to be used to avoid
the chances of intracranial injury.17 (e) For lesions
located posteriorly, the needle is directed without its
attachments initially. (f) After confirmation that the
tip of the needle is in the lesion by ultrasound or CT
scan the syringe is attached to the needle and
aspiration is performed.
After aspiration of material from the lesion, air is
forced out through the needle whose tip is in light
contact with a glass slide. The expressed aspirate is
macroscopically inspected. It generally consists of a
droplet of fluid with or without blood and/or
semisolid material. The semisolid aspirate is spread
 Chapter 85: Ultrasonography-guided Fine Needle Aspiration Cytology in Orbital Lesions 655
along the slide with the use of flat pressure by another
glass slide. Fixation of the smear is done either by dry
method using air, or by wet method using 95 percent
ethyl alcohol. The common staining methods include
Papenheim (May-Grunwald-Giemsa) and Wright
stain for air dried smear; and Papanicolaou and
hematoxylin-eosin stain for wet fixed smear. The
availability of both the types of smears increases the
diagnostic accuracy. The air dried smears have more
differentiated staining of the cytoplasm and extra-
cellular substances such as mucus or colloid. The wet
fixed smear gives better presentation of nuclear detail.
Air dried smears can be stained rapidly with May-
Grunwald solution for 30 seconds followed by
Giemsa’s stain for 1 minute.18 For wet smears fixed Fig. 85.2: Plasmacytoma. FNAB from 70-year old female with
with 95 percent methanol, Harris hematoxylin stain acute axial proptosis and bone pain. Smear shows large round
for 2 minutes followed by rinsing in tap water is a to oval plasma cells with eccentric nuclei. Occasional binucleate
rapid method. cells seen (Giemsa x 400)

CYTOLOGICAL INTERPRETATION
the equator of the globe.19 Ultrasound-guided
A combination of relative loss of cell cohesion by
FNAB in these cases gives good results and helps
repeatedly moving the needle within the mass and
avoid a more invasive surgical biopsy as in
strong suction allows aspiration of cells by the FNAB
tuberculosis, lymphoma, and histiocytosis
technique. The interpretation of these cellular types
(Fig. 85.3).
is being more demanded than the normal histological
Jackobiec et al21 advise biopsies to diagnose all lacri-
sections. It needs a highly skilled cytopathologist to
mal gland swellings (Fig. 85.4). Any mass localized in
correctly diagnose a pathology, from one drop of
the lacrimal fossa must undergo histological confir-
aspirated material. Nevertheless, a number of authors
mation before surgery except when pleomorphic
have confirmed the accuracy and reliability of FNAB
from orbit. The cytohistological correction performed
in many instances justifies the faith placed in the
technique.1-4

INDICATIONS
FNAB has been found to be a valuable diagnostic
adjunct in a variety of orbital disorders. The main
clinical situations in which FNAB from the orbit is
indicated are outlined below:
1. FNAB is specially useful in the diagnosis of inope-
rable metastatic neoplasms of the orbit.15,19-20 In
these situations, more often than not, the neoplasm
cannot be removed and the use of FNAB to confirm
the diagnosis aids clinicians in planning
appropriate palliative therapy as in rhabdo-
Fig. 85.3: Histiocytosis X. FNAB from 4-year old male with axial
myosarcoma and plasmacytoma (Fig. 85.2). This
proptosis and hepatosplenomegaly. He was diagnosed clinically
saves the patient from the discomfort of surgical as tuberculosis. Smear shows many proliferating histiocytes
biopsy. with prominent nuclear indentation and lobulation. Occasional
2. FNAB is useful in lesions not easily accessible to eosinophils and large osteoclastic giant cells are seen (Giemsa
biopsy, especially those which are situated behind x 400)
656 Section 6: Diseases of Orbit

Fig. 85.5: Pleomorphic adenoma. FNAB from 55-year old

Fig. 85.4: Adenocarcinoma of lacrimal gland. FNAB from 47-
year old female with acute painful swelling of the lacrimal gland,
diagnosed clinically as dacryoadenitis. Smear shows
moderately pleomorphic epithelial cells having scanty cytoplasm
and hyperchromatic nuclei. A papillaroid pattern is seen
(Giemsa x 250)
female with a large mass involving upper lid and lacrimal fossa
with bony destruction. Clinical suspicion pointed towards
adenocarcinoma of the lacrimal gland. Smear shows numerous
clusters of monomorphic epithelial and spindle cells and
abundant metachromatically stained stromal mateiral in the
background (Giemsa x 250)

adenoma is suspected. This tumor is well encap-

sulated, and capsule violation through biopsy is likely
to lead to a more aggressive behavior of the neoplasm.
But, Midena et al22 plead that due to the small caliber
of the FNAB needle used, tumor dissemination should
not be a problem (Fig. 85.5). Indeed, tumor dissemi-
nation has not been reported to be a complication of
FNAB from the orbit.
The diagnosis of pseudotumors is one of the excep-
tions. FNAB is useful in evaluating some patients with Fig. 85.6: Pseudotumor (inflammatory orbital disease). Many
presumed orbital pseudotumors (Fig. 85.6). In diffuse degenerating polymorphs, histiocytes, and plasma cells are
disease FNAB has limited role because the diagnosis seen (Giemsa x 400)
requires histological architecture for identification.
Patients with a predominantly fibrotic disease usually
provide a negative aspirate due to diminished
cellularity. In patients who have a well-defined mass,
FNAB gives a high yield of positive results. Char and
Miller 23 achieved a success rate of 90 percent in
establishing the diagnosis of pseudotumor. However,
they used routine flow cytometry and Southern blot
analysis to further characterize the lesion.
Benign and malignant lymphoid proliferations
have shown variable results on FNAB. In difficult
cases the differentiation of these two conditions may
induce an error rate as high as 40 percent.24-25 But, it is
thought that the use of immunoperoxidase and other Fig. 85.7: Non Hodgkin lymphoma (low grade small lymphocytic
methods23 on aspiration biopsy smear, to further type). FNAB from 50-year old male with progressive painless
characterize the lymphocytic proliferation may make axial proptosis. He was suspected to have pseudotumor. Smear
shows good cellularity comprising of monomorphic population
FNAB almost as accurate as standard histology for of small lymphoid cells. Some of the cells are immature (Giemsa
the diagnosis of lymphoid neoplasms (Fig. 85.7). x 400)
 Chapter 85: Ultrasonography-guided Fine Needle Aspiration Cytology in Orbital Lesions
Nonspecific and unusual inflammatory masses
that have not responded to medical therapy can be
analyzed by FNAB to either establish or confirm the
diagnosis,26 e.g. tuberculosis, fungal infections, etc.
(Fig. 85.8).
Tumor recurrence in cases of orbital retinoblastoma
(Fig. 85.9) and uveal melanoma have been followed
up with FNAB.27 Any suspected regrowth is subjected
to FNAB to identify the cellular type.
Fig. 85.8: Cryptococcosis. FNAB from 65-year old female with
painless swelling on right temporal forehead and lacrimal fossa
and proptosis. Smear shows numerous aggregates of spherical
encapsulated yeasts with budding. Typical car tyre appearance
seen (Mucicarmine x 400)
Fig. 85.9: Round cell tumor (Retinoblastoma). FNAB from 4-
year old male with fungating orbital mass and preauricular lymph
nodes. This is a recurrence following enucleation of the eyeball
6 months back for retinoblastoma. Smear shows predominantly
scattered and few clusters of small round cells. Focal rosettoid
pattern is seen (Giemsa x 250)
657
In cases of optic nerve tumors where observation
is contemplated or the planned surgical procedure is
radical. FNAB is indicated. In these cases generally
the eye is blind and a morphologic confirmation helps
clinicians in making the diagnosis.2,19,28
COMPLICATIONS
The only complication reported earlier was subcon-
junctival hemorrhage.19 Liu29 reviewed the compli-
cations associated with FNAB of the orbit in 152
patients. These included orbital hemorrhage,9 motility
disturbance, 2 ptosis, 2 etc.—all of these resolved
without sequelae. One case had prominent scar
following FNAB. The cause of this complication was
not clear and it was hypothesized that probably the
patient was a keloid former or had a coincidental
eyelid injury. The more serious complications reported
were orbital hemorrhage with no perceptions of light,1
globe perforation with vitreous hemorrhage,2 motility
disturbance with permanent defect,1 blindness,3 and
death.3 The reasons for deaths were direct intracranial
injury, meningitis, and brain abscess in the 3 cases,
respectively. However, the experience of other
ophthalmologists undertaking the FNAB procedure
routinely has not been so devastating. Kennerdell,17
reported the occurrence of orbital hemorrhage and
globe perforation as the only serious complications of
the procedure, if done in the prescribed way. Most of
the serious complications occur when FNAB is per-
formed by an ophthalmic surgeon not trained in the
technique. Consequently, it is emphasized that only
an experienced orbitologist should undertake the
FNAB procedure following the prescribed standard
technique.
Local Dissemination of Tumor Cells
As the cells are aspirated from the lesion with the help
of a strong suction force, there has been a fear of tumor
dissemination through the needle tract in FNABs from
any part of the body. However, the reported occu-
rrence of actual tumor dissemination through the
needle tract has been too low in comparison to the
number of FNAB performed. Engzell et al30 suggest
that in clinical situations, the number of malignant
cells along the needle path is small, and these cells are
destroyed by the body’s defense mechanisms before
giving rise to local growth. Those cases in which
aspiration biopsy proves a malignancy, undergo
treatment in the form of excision or irradiation. This
destroys the small number of malignant cells that may
have reached the needle tract.
658 Section 6: Diseases of Orbit
LIMITATIONS
FNAB, though useful and indicated in a large number
of cases, does have some limitations.
FNAB provides few cells for examination by the
cytopathologist. One of the most frequent short-
comings of the procedure has been scanty material
obtained on aspiration. This necessitates repeated
aspiration, and if still unsuccessful, surgical biopsy is
made. Fortunately, the need for surgical biopsy rarely
arises.
The availability of a well-qualified cytopathologist
trained in orbital lesions is an absolute necessity for
successful FNABs. The diagnosis of specific disease
entities from examination of few cells and absence of
histological architecture is more difficult than
standard histology techniques. Therefore, the
experience of cytopathologist finally determines the
accuracy and success rate of FNABs.
Localization of the orbital tumors is an important
aspect. The use of ultrasound, CT scan, and MRI have
opened up new frontiers for accurate placement of the
needle tip within the lesion, and thus have succeeded
in decreasing the rate of false-negative FNABs.
Orbital tumors wherein the predominant content
is fibrous tissue do not provide enough material on
aspiration. The strong cohesion in these lesions and
diminished cellularity lead to false-negative results.
The identification of sarcomatous growth has been
difficult with the use of FNAB.31
Well encapsulated tumors like hemangioma and
pleomorphic adenoma require complete surgical
excision. These lesions should not be unnecessarily
subjected to FNAB as capsule violation may lead to a
more aggressive behavior of the tumor.19,21 FNAB is
contraindicated in cystic lesions like orbital cysti-
cercosis because capsule violation may lead to a
violent inflammatory reaction.
CONCLUSION
FNAB has proved its value and is here to stay. When
coupled with lymphocytic markers and antigen-
antibody tests, its accuracy closely approaches
standard histopathology, in the hands of an expe-
rienced cytopathologist. The ease of performing the
technique and the low to almost absent complication
rate, make FNAB more acceptable to the patient and
the surgeon. Like all procedures it too has its
limitations and controversies. Even well encapsulated
lesions are now being subjected to FNAB. In posterior
orbital lesions, FNAB should ideally be done only
when the eye is blind. Fibrous lesions may not give a
good diagnostic yield. However, time has shown that
FNAB provides a rapid and accurate tissue diagnosis
which makes it a valuable tool.
REFERENCES
1. Kennerdell JS, Maroon JC, Dekker A, et al. Microsurgery and
fine needle aspiration biopsy of orbital tumors. Trans PA
Acad Ophthalmol Otolaryngol 1979;32:147-50.
2. Meyer E, Malberger E, Gdal-On M, et al. Fine needle
aspiration of orbital lesions. Ann Ophthalmol 1983;15:635-
38.
3. Tarkkanen A, Koivuniemi A, Liesmaa M, et al. Fine needle
aspiration biopsy in the diagnosis of orbital tumors. Graefes
Arch Clin Exp Ophthalmol 1982;219:165-70.
4. Arora R, Rewari R, Betharia SM: Fine needle aspiration
cytology of orbital and adnexal masses. Acta Cytol
1992;36:483-91.
5. Berkman WA, Chowdhury L, Brown NL, Padleckas R. Value
of electron microscopy in cytologic diagnosis of fine needle
biopsy. Am J Roentgenol 1983;140:1253-58.
6. Domagala W, Koss LG. Configuration of surfaces of human
cancer cells obtained by fine needle aspiration biopsy: A
comparative light microscopy and scanning electron
microscopy study. Acta Cytol 1980;24:427-34.
7. Nadji M. The potential value of immunoperoxidase technique
in diagnostic cytology. Acta Cytol 1980;24:442-47.
8. Webb AJ. Through a glass darkly: The development of needle
aspiration biopsy. Bristol Med Chir J 1974;89:59-68.
9. Coley BL, Sharp GS, Ellis E. Diagnosis of bone tumors by
aspiration. Am J Surg 1931;13:215.
10. Ferguson RS: Prostatic neoplasms: Their diagnosis by needle
puncture and aspiration. Am J Surg 1930;9:507-11.
11. Martin HE, Ellis EB. Aspiration biopsy. Surg Gynecol Obstet
1934;59:578-89.
12. Fox CH. Innovation in medical diagnosis. The Scandinavian
curiosity. Lancet 1979;1:1378-88.
13. Zajicek J. The aspiration biopsy smear. In: Koss LG. Diagnostic
cytology and its histologic bases. JB Lippincott Company (3rd
ed) 1979;2(29):1001-1104.
14. Schyberg E. Fine needle aspiration biopsy of orbital tumors.
Acta Ophthalmol 1975;125(Suppl):11.
15. Spoor TC, Kennerdell JS, Dekker A et al. Orbital fine needle
aspiration biopsy with B-scan guidance. Am J Ophthalmol
1980;89:274-77.
16. Dubois PJ, Kennerdell JS, Rosenbaum AE, et al. Computed
tomographic localization of fine needle aspiration biopsy of
orbital tumors. Radiology 1979;131:149-52.
17. Kennerdell JS, Discussion in Liu D. Complications of fine
needle aspiration biopsy of the orbit. Ophthalmology
1985;92:1768-71.
18. Boccato P. Rapid staining techniques employed in fine needle
aspirations. Acta Cytol 1983;27:82-83.
 Chapter 85: Ultrasonography-guided Fine Needle Aspiration Cytology in Orbital Lesions
19. Kennerdell J, Dekker A, Johnson B, et al. Fine needle
aspiration biopsy. Its use in orbital tumors. Arch Ophthalmol
1979;97:1315-17.
20. Kopelman JE, Shorr N. A case of prostatic carcinoma
metastatic to the orbit diagnosed by fine needle aspiration
and immunoperoxidase staining for prostatic specific antigen.
Ophthalmic Surg 1987;18:599-603.
21. Jakobiec FA, Haller Yeo J, Trokel SL et al. Combined clinical
and computed tomographic diagnosis of primary lacrimal
fossa lesions. Am J Ophthalmol 1982;94:785-807.
22. Midena E, Segato T, Piermarocchi S, et al. Fine needle
aspiration biopsy in ophthalmology. Surv Ophthalmol
1985;29:410-22.
23. Char DH, Miller T. Orbital pseudotumor. Fine needle
aspiration biopsy and response to therapy. Ophthalmology
1993;100:1702-10.
24. Morgan G, Harry J. Lymphocytic tumors of indeterminate
nature: A 5-year follow up of 98 conjunctival and orbital
lesions. Br J Ophthalmol 1978;62:381-83.
659
25. Jakobiec FA, McLean I, Font RL. Clinicopathologic character-
istics of orbital lymphoid hyperplasia. Ophthalmology
1979;86:948-66.
26. Kew YT, Cuesta RA. Nodular fascitis of the orbit diagnosed
by fine needle aspiration cytology. A case report. Acta Cytol
1993;37:957-60.
27. Westman-Naeser S, Naeser P. Tumors of the orbit diagnosed
by fine needle biopsy. Acta Ophthalmol 1978;56:969-76.
28. Pennelli N, Montaguti A, Carteri A, et al. Juvenile pilocytic
astrocytoma of the optic nerve diagnosed by fine needle
aspiration biopsy. Acta Cytol 1988;32:395-98.
29. Liu D. Complications of fine needle aspiration biopsy of the
orbit. Ophthalmology 1985;92:1768-71.
30. Engzell U, Esposti PL, Rubio C, et al. Investigation on tumor
spread in connection with aspiration biopsy. Acta Radiol
(Stockh) 1971;10:385-98.
31. Naeser P, Mostrom U. Liposarcoma of the orbit: A clinico-
pathological case report. BJ Ophthalmol 1982;66:190-93.
 Chapter 86
Phakomatosis
P Namperumalsamy, K Lakshmanamurthy, Madhahvi Hirode
Phakomatosis (Greek: Phakos, a lentil) is a group of
hereditary disorders characterized by the presence of
hamartias and hamartomas involving different organ
system derived from all the three embryonic layers.
The term was introduced by van der Hoeve and
colleagues in 1917 and 1923 to unify the diverse
manifestations of tuberous sclerosis and neuro-
fibromatosis, both of which involve multiple organs
and could be present either in the newborn child or
might arise later in life. Because of the inborn nature
of the tumors they were called phacomata from the
Greek phakos, meaning “mother spot”. Inherent in the
original concept was that some growths might become
malignant. Hamartomas are thus congenital tumors
composed of an abnormal mixture of tissue elements
or an abnormal proportion of a single element usually
found in the organ or the area from where they arise.
The four classic syndromes included among the
phakomatoses are tuberous sclerosis (Bourneville’s),
neurofibromatosis (von Recklinghausen’s), angio-
matosis retina (von Hippel-Lindau), and encephalo-
facial angiomatosis (Sturge-Weber). The Sturge-Weber
syndrome is not as clearly hereditary as the three
classical phacomatoses; the vascular tumors in Sturge-
Weber are generally present at birth, rather than
arising de novo in later life, and malignant trans-
formation is rare.1 Hamartomas are to be contrasted
with choristomas, which are tumors, such as dermoids.
CLASSICAL FEATURES OF PHAKOMATOSES
a. Hamartias Hamartias are nontumorous growths on
the skin or mucous membranes that arise from cells
normally found in the tissue at the involved site,
e.g. congenital vascular malformations of ataxia
telangiectasia.
b. Hamartomas Hamartomas are localized tumors
arising from cells normally found at the site of
growth, e.g. glial tumors of tuberous sclerosis:
(tumorous malformations of hamartias are hamar-
tomas).
c. True neoplasms These originate from undifferentia-
ted embryonic cells or differentiated mature cells.
d. Other associated congenital abnormalities.
Summing up, disorders included in this group are:
1. Tuberous sclerosis (Bourneville’s disease)
2. Neurofibromatosis (von Recklinghausen’s
disease)
3. Angiomatosis retinae (von Hippel-Lindau
disease)
4. Encephalotrigeminal angiomatosis (Sturge-
Weber disease)
5. Klippel Treanaunay-Weber syndrome (in its
pure form)
6. Diffuse congenital hemangiomatosis
7. Basal cell nevus syndrome
8. Racemose angioma of the retina (Wyburn-
Mason syndrome)
9. Oculodermal melanocytosis (Nevus of Ota)
10. Ataxia telangiectasia (Louis-Bar syndrome).
Even though phakomatoses are not systematically
classified, they may be differentiated embryologically
depending on the germ layer affected. For instance,
neurofibromatosis and tuberous sclerosis are neuro-
ectodermal dysplasias whereas encephalotrigeminal
angiomatosis and angiomatosis retinae are meso-
dermal disorders.
TUBEROUS SCLEROSIS
(BOURNEVILLE DISEASE)
Tuberous sclerosis is a neuroectodermal disease
characterized by hamartomatous tumors of the brain,
 Chapter 86: Phakomatosis
skin, viscera, and the eye. Although von Reckling-
hausen described the cerebral and visceral manifesta-
tions first is 1882, Bourneville introduced the term
tuberous sclerosis in 1880. The disorder continues to
bear his name, even though he regarded the cutaneous
anomalies as incidental findings. Vogt (1908) proposed
epilepsy, mental retardation, and adenoma sebaceum
as a diagnostic traid.2 Epiloia, a term formed by the
contraction of the words epilepsy and anoia (mindless-
ness), is occasionally used to designate this disorder.3
It is generally regarded to be transmitted as an
autosomal dominant pattern and the defective gene
was found on chromosome 9. However, most cases
(80-85%) appear sporadic with no evidence of an
affected antecedent family member.3 There is no
sexual or racial predilection.
Course About 30 percent of patients die by the fifth
year of life. The average age at death is between 20-24
years as a result of cachexia, pulmonary or cardiac
disease or status epilepticus. The diagnosis is usually
made during the first 10 to 20 years of life.
Clinical Features
Cutaneous Involvement
The skin lesions include the following:
a. Adenoma sebaceum These are usually apparent
between the age of 2-5 years and seldom appear
after the age of 10 year. Adenoma sebaceum is
considered a pathognomonic lesion of tuberous
sclerosis and are seen in at least 90 percent of all
patients with Bourneville’s disease. In approxi-
mately 30 percent of all individuals this may be
the only cutaneous manifestation. The typical
lesions consist of multiple small reddish-brown
nodules distributed over the nose and cheeks in a
butterfly configuration which tend to enlarge until
puberty. Telangiectatic vessels are common
especially on the nose. The term adenoma seba-
ceum is a misnomer, since histologically these
lesions represent angiofibromas and the lesion
does not actually involve the sebaceous glands.
b. Ash leaf spots of depigmentation These are hypo-
pigmented macular or patch lesions, pathologically
achromic nevi, which are evident under ultraviolet
illumination (Wood’s lamp), and may be present
at birth.
c. Periungual and subungual fibromas These often
appear after puberty. They are seen in about 40
661
percent of all patients and begin as small nodules
at the margin of or beneath the nails of the fingers
and toes and enlarge and cause pain.
d. Vitelliginous patches, shagreen patches and cafe-
au-lait spots.
Central Nervous System
Not only the cerebrum but also the cerebellum,
medullary, and spinal chord are involved in tuberous
sclerosis. The majority of these hamartomas are of two
types, i.e. cortical foci (tubers) and subependymal
nodules along the ventricular system. These hamar-
tomas are composed of typical astrocytes. Patients
may have associated mental retardation and convul-
sive disorders. Cranial hyper-ostosis and cerebral
calcification occur in at least half of the cases and their
presence provides a useful X-ray aid in diagnosis.
Visceral Involvement
Hamartomas may involve any organ. Cardiac lesions
include rhabdomyoma, rhabdoleiomyoma, and
rhabdomyolipoma. Unfortunately, these may appear
early in life and are responsible for fatal arrhythmias
in 50 percent of the affected children during the first
years of life and 90 percent before puberty.
About three-fourths of patients have renal hamar-
tomas. These may cause genitourinary symptoms or
renal failure. About two-thirds of the patients have
cystic lesions of the pulmonary parenchyma that show
a honeycomb appearance on radiologic examination.
These may cause spontaneous pneumothorax and
right-sided heart failure.
Ocular Involvement
The characteristic ocular lesion is a retinal hamartoma.
More than 50 percent of the patients have bilateral
lesions. Morphologically the retinal hamartomas are
divided into the following three types:3
1. Relatively flat, soft looking and semitransparent
lesions,
2. Elevated, nodular, and solid-appearing masses,
3. Combination of the two.
Type I retinal hamartomas may be single or
multiple and are usually seen at the posterior pole.
These tend to be oval or round and have gelatinous
indistinct boundaries of light grey or faint yellow
color. They are slightly elevated and cause a small
decrease in the visibility of the underlying retinal
vessels.
662 Section 6: Diseases of Orbit
Type II hamartomas are elevated usually 1/2 to 4
disc diameters, achromic and multinodular, often
occurring near or along the disc margin and also in
the retinal midperiphery. Their appearance has been
compared to that of tapioca, white mulberries, or
salmon eggs. When located near the optic nerve head,
these lesions may resemble and be confused with
hyaline bodies or drusen of optic disc. It is currently
believed that Type I lesions eventually evolve into
Type II lesions.
Type III hamartomas have morphologic features
of both Types I and II. The base or border of the tumor
is relatively flat, soft and translucent, while centrally
the tumor is elevated, nodular or calcific. The fundi
of patients with tuberous sclerosis can exhibit
midperipheral depigmented lesions with a surroun-
ding rim of pigment proliferation, somewhat resem-
bling pavingstone degeneration or a lacunated patch
of congenital hypertrophy or retinal pigment
epithelium.
The retinal hamartomas usually do not produce
any significant loss of vision unless they are located
in the papillomacular bundle, which is uncommon.
These lesions do not cause secondary intraocular
inflammation or glaucoma. They rarely cause vitreous
hemorrhage.
Histology The retinal tumors are composed of a felt-
like network of atypical astrocytes and small blood
vessels located in the superficial layers of retina or
optic nerve head, where they envelop the major retinal
vessels. The large, nodular hard lesions may show
cystic degeneration with hyaline and calcific deposits.
Differential Diagnosis of Astrocytic Hamartomas4
A. Retinal astrocytic hamartoma
1. Retinoblastoma
2. Myelinated nerve fibers
3. Coats’ disease
4. Other cause of retinal telengiectasia
5. Retinal capillary angioma
6. Toxocara canis, toxoplasmosis
7. Other causes of choroiditis/scleritis
8. Other causes of exudative retinal detachment
with underlying mass lesion.
B. Optic disc astrocytic hamartoma
1. Optic disc drusen
2. Retinitis pigmentosa associated with optic disc
excrescences (hyaline bodies)
3. Optic disc glioma (variant of optic nerve
glioma)
4. Other primary optic disc tumor
5. Other causes of unilateral optic disc swelling
or papillitis.
NEUROFIBROMATOSIS
(VON RECKLINGHAUSEN’S DISEASE)
Neurofibromatosis is primarily a neuroectodermal
dysplasia characterized by tumor like formations
derived from proliferation of peripheral nerve
elements (Fig. 86.1). It was first identified as a distinct
entity by von Recklinghausen in 1882, after whom this
disease is named. The disease is inherited by means
of an autosomal dominant gene with almost complete
penetrance but variable expressivity. It is estimated
to occur in one of every 3000 live births.3
Two forms of neurofibromatosis have been
described, i.e. the classic von Recklinghausen disease
as Neurofibromatosis 1 (NF1) and bilateral acoustic
neurofibromatosis as Neurofibromatosis 2 (NF2). The
gene for NF1 has been localized in chromosome 17
and for NF2 in chromosome 22. Neurofibromatosis is
diagnosed when two of the following criteria are
present in a patient provided no other disease accounts
for the findings:
1. At least five cafe-au-lait maculas over 5 mm in
greatest diameter, and if prepubertal, six cafe-au-
lait maculas over 15 mm in greatest diameter.
2. Two or more neurofibromas of any type, or one
plexiform neurofibroma.
3. Multiple axillary or inguinal freckles.
4. Sphenoid wing dysplasia or congenital bowing or
thinning of long bone cortex, with or without
pseudoarthrosis.
Fig. 86.1: Neurofibromatosis
 Chapter 86: Phakomatosis
5. Bilateral optic nerve gliomas.
6. Two or more iris Lisch nodules on slit lamp exami-
nation.
7. A parent, sibling or offspring with von Reckling-
hausen disease by above criteria.
Neurofibromatosis 1 may be present at birth or
may appear early in infancy, although in many
patients the initial clinical manifestations develop later
in childhood or in adult life.
Ocular Involvement
The eye and adnexa manifest an unusual assortment
of features of this disorder and scarcely any structure
or tissue within or around the eye.
Cornea It may exhibit the so-called Lignes grises,
representing hyperplastic intrastromal nerves.5
Conjunctiva Neurofibromatosis of conjunctiva may
appear as one or more small, localized, elevated
tumors 1-3 mm in diameter. They are firm, nontender,
fixed in position and covered by normal epithelium.
In diffuse orbital neurofibromatosis, numerous
enlarged tortuous nerves may appear under the
conjunctiva.
Uveal Tract
The iris may be sparsely or diffusely peppered with
small “Lisch spots” which are lightly pigmented,
almost gelatinous lesions resembling nevi. Histo-
pathologically, they are composed of a focal collection
of small spindle cells containing various amount of
pigment. The choroid and ciliary body may show
localized lesions or diffuse thickening due to
hyperplasia of neurons, Schwann cells, melanocytes
and ovoid bodies. These ovoid bodies are typical
histological findings in choroidal neurofibromatosis.
Retinal and Optic Nerve Lesions
The retinal hamartomas, which are rare, are identical
to those seen in tuberous sclerosis. Congenital
medullation of nerve fiber layer is a more frequent
finding. Approximately 15-20 percent of gliomas
arising in the optic nerve are associated with
neurofibromatosis. These slowly expanding lesions
occur in young children and cause unilateral loss of
vision, proptosis, and optic atrophy. Enlargement of
the optic foramen and deformity of prechiasmal bony
structures are the X-ray findings.
663
Eyelid and Orbital Lesions
Neurofibromatosis of the eyelid and orbit is an easily
recognized manifestation of von Recklinghausen’s
disease. The eyelid may show plexiform neuroma,
fibroma molluscum, schwannoma, and cafe-au-lait
spots. The hypertrophied nerves of plexiform neuroma
feel like a bag of worms and knotted cords. Involve-
ment by plexiform neuroma may be so extensive so
as to cause elephantiasis of lids and face (elephantiasis
neuromatosa) and may extend into the region of the
temporal fossa, where it may be associated with a bony
defect in the temporal fossa. Bony defects of orbital
roof may allow herniation of intracranial tissue into
the orbit to produce a pulsating exophthalmos.
However, there is no associated bruit of arterialization
of capillaries of the conjunctiva as seen in exophthal-
mos associated with caroticocavernous sinus fistula.
Glaucoma
It appears that glaucoma associated with neuro-
fibromatosis characteristically occurs with palpable or
visible neurofibromasis of the ipsilateal upper eyelid
or hemiatrophy of the face.
The possible mechanism suggested for glaucoma
are:
1. Infiltration of angle structures and obstruction
of aqueous outflow by the neurofibroma.
2. Closure of angle due to forward displacement
of anterior uvea as a result of infiltration by
neoplastic tissue.
3. Secondary fibrovascular proliferation and
closure of filtration mechanisms by synechiae.
Systemic Manifestations6
The cutaneous manifestations include cafe-au-lait
patches, fibroma molluscum, and plexiform neuro-
fibromas.
a. Cafe-au-lait spots are tan in color and macular in
configuration with smooth edges. They vary in size
from a pinpoint to large sheet like plaque. They
usually occur on the trunk but can be seen on the
face and extremities (Fig. 86.2). Histologically, these
lesions show hyperpigmentation of the basal cell
layer of epidermis that is attributable to an
increased number of Dopa-positive melanocytes.
b. The fibroma molluscum is a soft, elevated ped-
unculated nodule that occurs widely all over the
body. Histologically, they represent neurofibromas
or schwannomas of the cutaneous nerves.
664 Section 6: Diseases of Orbit
Fig. 86.2: Dilated and tortuous vessels with angioma
at the periphery
c. The term plexiform neurofibroma is applied to
cutaneous involvement of multiple superficial
nerves, most commonly appearing in the upper
eyelid, adjacent to the temple or side of the face.
Neurofibromas of central nervous system are
usually multiple and may produce a spectrum of
sensory and motor signs depending upon involvement
of brain, meninges, spinal cord, cranial or peripheral
or sympathetic nerves. Acoustic nerve is most
commonly involved. Extradural tumors from root
sheaths of spinal canal or intraneural neurofibromas
can produce neuromuscular symptoms and cord
compression.
Any viscera in the gastrointestinal system may be
involved. It is reported to occur in the tongue, pharynx,
esophagus, stomach, small bowel, colon, rectum, and
gallbladder. Associated endocrine abnormalities
include changes in height, hyperparathyroidism,
myxedema, Addison’s disease, tetany, diabetes or
retarded sexual development. The abnormalities of
sexual maturation are usually related to involvement
of the target organs but also may reflect central lesions
in the hypothalamopituitary axis. Disturbances in the
development and growth of both long and flat bones
include defects of bones, intraosseous cysts, abnor-
malities of vertebrae, scoliosis and pathological
fractures.
Pathology
It is not clear whether neurofibromas develop from
the neuroectodermal sheath cells of Schwann or
mesodermal connective tissue elements of the nerve
sheath or both. Neurofibromas appear benign
histologically. Although malignancy is uncommon in
other hamartomatous syndromes, there is a significant
risk or sarcomatous transformation in neurofibro-
matosis. The most common malignancy is neuro-
fibrosarcoma.
Treatment
Treatment of this disease needs a multidisciplinary
approach in tackling various lesions. The role of the
ophthalmologist is to treat glaucoma and other eye
related problems and prompt referral to the concerned
specialist. Glaucoma is managed along similar lines
as other congenital glaucomas but mostly surgically.
ANGIOMATOSIS RETINAE
(VON HIPPEL-LINDAU DISEASE)
A retinal hemangioma was illustrated for the first time
by Panas and Remy in 1879. Progression of retinal
angiomas was described by von Hippel (1904) and
later Lindau (1926) described cerebellar angiomas.7
The combination of these two is referred to as von
Hippel-Lindau disease.
The inheritance pattern is autosomal dominant
with incomplete penetrance and delayed expression.
While the disease usually presents in the second and
third decade of life, retinal angiomas have been
discovered in premature infants, fetuses, and in
persons as late as in the sixth decade.8 A correlation
has been found between increasing age at presen-
tation, systemic evidence of the disease, and size and
appearance of the angioma.9 Bilateral involvement is
seen in 30 to 50 percent of cases.
Clinical Picture
This may be variable and often difficult to recognize.
The presenting symptoms are most frequently
attributable to the effects of retinal or cerebellar
tumors.
The ocular changes occur in the following stages:
1. The early stage of angioma formation with
development of feeder and draining vessels.
2. The stage of exudation, hemorrhage, and retinal
detachment.
3. The final stage of destruction of the eye with
secondary glaucoma and phthisis bulbi.
The ocular disease may be present for a consider-
able period before subjective symptoms appear
because of peripheral location of most of these tumors.
 Chapter 86: Phakomatosis
Ocular symptoms include blurring or loss of vision
due to exudative detachments, macular exudates or
ocular pain due to advanced disease and development
of secondary glaucoma.
The earliest fundus sign is a fullness of retinal veins
in one segment which becomes dilated and tortuous.
The dilated vessels are found to feed angiomatous
formation which are usually found far in the periphery
especially on the temporal side (Fig. 86.2). Some of
these may be quite small, light or dark red or yellowish
gray areas with an even surface, circular or oval in
shape. In about 33 percent of cases the lesions may be
multifocal. As the tumor grows the angioma becomes
larger and the afferent and efferent vessels become
thick, tortuous and dilated. Later it becomes difficult
to differentiate between artery and vein. The usual
direction of growth is toward the vitreous but
occasionally the tumor invades the choroid and may
become so aggressive as to invade the lens and cornea
or to perforate the globe.
Less classically retinal angiomas may occur as
small red or pale gray nodules with or without feeder
vessels and even without fluorescence on fluorescein
angiography. In addition to vascular anomalies and
retinal angiomas, there is characteristically a massive
outpouring of lipid into and beneath the retina. The
angiomatous tumor itself is capable of forming lipid,
but exudation of serum and lipid also occur in areas
remote from the primary lesion, particularly in the
macular area. A macular star figure or circinate figure
may be the presenting sign (Fig. 86.3). Even though
exact pathogenesis of macular involvement is not
known, the suggested theories are:8
Fig. 86.3: Dilated vessels with macular star
665
a. Leaking vessels of the angiomatous malformation
pour protein rich fluid into the surrounding retina,
which traverse the retinal extravascular pathways
to reach the macula; some of it is resorbed, but the
lipid and protein remain as exudates.
b. There is progressively increasing shunting of blood
from normal areas of the retina to the angioma,
thereby leading to hypoxia in the capillary bed
ultimately involving the macula, which causes
breakdown of integrity of macular vessels.
Systemic Features
The disease can affect the central nervous system and
the patient may initially present with symptomatology
referrable to an intracranial tumor—mainly headache,
nausea, vomiting, and cerebellar disturbances.
Cerebellar hemangioblastoma is the most common
involvement of the central nervous system. The
disease can involve other locations in the central
nervous system, especially the spinal cord where
usually they are asymptomatic. Visceral tumefactions
and cysts can involve the pancreas, kidneys, adrenal
glands, epididymis, ovaries, spleen, liver, and urinary
bladder. Hypernephroma and pheochromocytoma
have been reported to cause significant morbidity and
mortality in a large number of patients with von
Hippel-Lindau disease. Because of substantial visceral
involvement and associated morbidity and mortality,
a complete medical work-up is indicated for patients
with angiomatosis retinae.
Pathology
The retinal tumor and those tumors involving the
central nervous system and viscera are histologically
hemangioblastomas. The retinal tumor, which usually
involves the entire thickness of the retina is composed
of proliferative endothelial cells lining blood filled
laminae. The cells exhibit a slight embryonic (blast
like) appearance in contradistinction to a simple
hemangioma which is composed of more mature
endothelial cells. Large number of round, lipid laden
foam cells are seen. There is also abundant glial
proliferation and fibrosis throughout the tumor.
Fundus Fluorescein Angiography (FFA)
FFA is useful for detecting minute angiomas that
would otherwise be missed by ophthalmoscopy and
for the study of in vivo hemodynamics and transu-
dation from the retinal angiomas. The early phase of
666 Section 6: Diseases of Orbit

angiography delineates the feeding and draining

vessels. The angiogram also reveals a rapid arterio-
venous shunt through portions of the tumor. The late
phase of the angiogram shows diffuse leakage of dye
from the tumor, demonstrating the transudative
nature of these lesions (Fig. 86.4). The angiogram also
helps to distinguish the retinal microvascular changes
that usually accompany these tumors, such as
microaneurysms and areas of capillary nonperfusion.
It also helps in assessing the result of treatment of these
lesions. Complete destruction of retinal angioma
should be ascertained by the absence of perfusion and
leakage from successfully treated angiomas. Some-
times false-negative results may be obtained with
angiography because visible tumor may be found Fig. 86.4: Late stage of fluorescein angiography showing dilated
histologically even when angiography shows absence afferent and afferent vessels with minimum leakage of dye
of perfusion. Thus, repeated careful stereoscopic or
regular fundus color photography should be done
both of the treated eye and the fellow eye routinely at
six months interval to detect any change in the retinal
vessel configuration (Fig. 86.5).

Treatment
Angiomas should be treated as soon as possible. After
the advent of laser application in retinal disease,
procedures like trans-scleral irradiation, electro-
cautery or diathermy are obsolete now. Either xenon
or argon laser can be used at 500 or 1000 μ spot size at
0.5 second setting (Fig. 86.6). Photocoagulation is done
in one or more sitting. Small to medium sized
angiomas are treated successfully by conventional
Fig. 86.5: Clumps of exudate in patch of
photocoagulation or cryotherapy. If the tumor is large, hemorrhage adjacent to a dilated vessel
feeder vessels are treated with argon laser to create a
spasm and thereby reduce the amount of blood
flowing through the tumor during the actual photo-
coagulation of the tumor. The patient is cautioned that
vision may become much more blurred during the
following two to three weeks and is advised to avoid
activities that would simulate a Valsalva maneuver,
and if further photocoagulation is required, it should
be done four to six weeks later.
Photocoagulation becomes technically difficult and
inadequate in treating very peripherally located angio-
mas, those occurring in eyes with rather opaque media
and thick angiomas with surrounding exudative
retinal detachment. In these conditions cryotherapy
becomes a more convenient method of therapy. With
this therapy the iceball is made to engulf the tumor Fig. 86.6: Xenon arc photocoagulation mark
and triple freeze rather than a single freeze thaw cycle seen around the angioma
 Chapter 86: Phakomatosis
should be employed in treating the angiomas. The
feeding and draining vessels should not be treated.
These treatments should be repeated at six weekly
intervals until the tumor appears to have satisfactorily
regressed.8
Successful treatment should be assessed by fluore-
scein angiography which shows absence of perfusion
of successfully treated angiomas. Careful clinical
follow-up is mandatory to detect recurrences as well
as to detect the evolution of new angiomas. Eye wall
resection is necessary for very large tumors for which
conventional therapy is considered ineffective.8 Apart
from treating the individual with angiomas, all family
members and blood relatives should undergo a
complete ocular and systemic examination.9 Conti-
nued follow-up to find and adequately treat the
earliest manifestation of the disease will be necessary.
ENCEPHALOFACIAL ANGIOMATOSIS
(STURGE-WEBER SYNDROME)
Schirmer first reported a case with facial angioma; later
Sturge described an association of facial angioma, ipsi-
lateral congenital glaucoma and hemiparetic epilepsy.
Although port-wine stains may occur anywhere on
the body, Sturge observed that patients with unilateral
facial port-wine stains (nevus flammeus) regularly had
seizures and hemiparesis of the contralateral side and
speculated correctly that this was the result of an
intracranial hemangioma. Weber described the
characteristic linear calcification seen on skull X-rays.
The disease occurs in all races with no sex
predilection. Unlike other hamartomatous disease,
there is no evidence of genetic predisposition or
inheritance, nor is there an increased frequency of
consanguinity among parents. Chromosomal abnor-
malities have been reported in some patients.
Clinical Features
The clinical manifestations include convulsive
disorder (89%), facial angioma (86%), abnormal X-ray
findings (63%), mental retardation (54%), ocular
abnormalities (37%), and hemiplegias (31%) (Fig. 86.7).
Ocular Involvement
a. Glaucoma It occurs in about one-third of the
patients with Sturge-Weber syndrome. Anderson’s
rule says that when nevus flammeus involves the
upper lid, there is ipsilateral intraocular involve-
ment.1 Bilateral cases are rare and may occur when
667
Fig. 86.7: Facial lesions in Sturge-Weber syndrome
vascular malformation is widespread. In two-
thirds of the patients who develop glaucoma, the
clinical features resemble those of congenital
buphthalmos. However, late onset glaucoma,
occurring in adolescence or young adult life may
resemble primary open angle glaucoma. The
following etiologic explanations for the glaucoma
have been advocated:
i. Mechanical theory Developmental anomalies of
the anterior chamber angle may cause an
increased resistance to aqueous outflow.
ii. Vascular theory Glaucoma due to presence of
vascular malformations that might increase
production, decrease outflow or actually
change components of aqueous fluid or inter-
fere with extrascleral drainage.
Elschnig suggested that, because of the frequent
occurrence of choroidal angiomas, an increased
permeability of uveal vessels may be responsible
for hypersecretion of aqueous (Plethoric glau-
coma).
b. Choroidal hemangioma Choroidal hemangioma are
reported in approximately 40 percent patients with
Sturge-Weber syndrome. They may occasionally
occur as solitary tumors situated at the posterior
pole temporal to the optic nerve. Ophthalmoscopi-
cally, they appear as salmon orange, elevated
masses with indistinct margins (Fig. 86.8). They
have been mistaken for amelanotic malignant
melanoma or metastatic carcinomata. The diffuse
thickening of the choroid caused by the heman-
668 Section 6: Diseases of Orbit
gioma produces a deep red color in the posterior
fundus, the “tomato-ketchup” fundus, which is
almost obvious when compared to the uninvolved
eye.
The fluorescein angiographic features are
characteristic and consist of a rapidly appearing,
diffusely speckled choroidal flush beginning in the
early transit phase. B scan ultrasonography charac-
teristically shows a solid echogenic reflectivity
(Fig. 86.9).
Histologically, the angioma is composed of
widely dilated endothelial lined spaces. The
hemangioma grows very slowly but can cause
secondary serous retinal detachment and cystoid
Fig. 86.8: Ultrasonography showing elevated
solid echogenic mass with high internal reflectivity
Fig. 86.9: Fundus picture of Sturge-Weber syndrome showing
salmon orange elevated mass with indistinct margins
retinal degeneration. The exudative detachment
may lead to secondary glaucoma and blindness.
c. Ipsilateral hyperchromia of iris.
d. Spontaneous dislocation of lens.
e. Conjunctival and episcleral vascular lesions.
f. Megalocornea in the absence of glaucoma.
Cutaneous Involvement
The facial angiomatosis, is present at birth. It consists
of one or several red patches of irregular outline,
usually unilateral, that are distributed over the upper
one-third of the face, mostly the supraocular region.
However, it does not strictly conform to the distri-
bution of the trigeminal nerve, often falling short of
or crossing over the midline or even extending into
the upper cervical region. Occasionally, telangiectasia
of the ipsilateral conjunctival and episcleral vessels
occur. Ipsilateral hemiatrophy of the face is often
present: the globe on the affected side may be enlarged
even without glaucoma.
Visceral Involvement
Localized or diffuse angiomas are seen in kidneys,
spleen, ovaries, intestines, adrenals, thyroid gland,
and lungs.
Central Nervous System Involvement
Usually leptomeningeal angiomas are present on the
same side as the facial lesion. The subarachnoid space
contains closely spaced, thin walled, endothelial lined
capillaries and small venous channels, sparing the
dura mater. It usually affects the occipitoparietal area,
but may extend over the entire hemisphere and
occasionally to the opposite side. The leptomeninges
as well as the underlying cerebral cortex usually show
calcification of small blood vessels and extravascular
calcific deposits in the outer cortex. In time, this
deposit results in distinctive, gyriform double
contoured patterns described by radiologists as a
“train-track” sign.
Patients with this disorder exhibit various degrees
of mental retardation, epilepsy, and hemiplegia or
Jacksonian epileptiform attacks.
Treatment
Management is a multidisciplinary approach.
Epilepsy is treated by anticonvulsant therapy. Deep
X-ray therapy for angiomas of the face may be tried
 Chapter 86: Phakomatosis 669
but are rarely found to be beneficial. Glaucoma cases venous anastomosis associated with arteriovenous
are managed with drugs lowering aqueous production malformations in the homolateral mid-brain region.
if there is no buphthalmos. If medical therapy fails or Other synonyms for retinal malformations are
congenital glaucoma is present, trabeculectomy is racemose hemangioma and cirsoid aneurysm. They
preferred. occur sporadically, no inheritance pattern has been
found. Most of the patients present with decreased
KLIPPEL-TRENAUNAY-WEBER SYNDROME vision much earlier than they do with neurological
symptoms.11
This syndrome is characterized by a triad of cutaneous
hemangiomas extending over the limb, varicosities in
Ocular Features
the affected limb and hypertrophy of bone and soft
tissue. It is inherited on an irregular dominant pattern. Retinal involvement is the most important mani-
Ocular findings include enophthalmos, conjunctival festation of this disease. Other features include
telangiectasia, heterochromia iridis, iris coloboma, proptosis which is usually reducible, and visual field
oculosympathetic palsy, retinal varicosities, and defects due to involvement of the central nervous
choroidal angiomas. system by vascular malformations.
Retinal involvement is almost always unilateral
DIFFUSE CONGENITAL HEMANGIOMATOSIS and mostly homolateral with vascular malformation
of the midbrain. The extent and severity of retinal
It is a rare disease in which multiple small cutaneous
vascular malformation can vary widely, ranging from
hemangiomas are associated with visceral heman-
a localized area of small arteriovenous communi-
giomas.10 Death usually occurs within first few months
cations limited to one quadrant of the eye to large
of life. Ocular findings include hemangiomas of iris,
racemose vascular malformations involving the entire
conjunctiva and lid, abnormal chorioretinal vascula-
fundus. They extend from the optic nerve toward the
ture, microphthalmos, and glaucoma. Central nervous
retinal periphery, mostly on the temporal side
system hemangiomas may lead to cortical blindness
(Fig. 86.10). Because of the shunting of oxygenated
and third and sixth nerve palsies.
blood to the area of malformation, veins assume a
similar color to arteries, making it difficult to identify
BASAL CELL NEVUS SYNDROME
them separately; they do not exhibit spontaneous
It is a genetically determined disorder in which there pulsations. Fluorescein angiography demonstrates
are multiple skin tumors, histologically indistinguish- nearly simultaneous filling of the venous and arterial
able from basal cell carcinoma. In addition there may
be defects in other tissues such as cysts of the jaw,
bifid ribs, and abnormalities of vertebra. Renal defects
in tubular resorption of phosphate has also been
reported. It is transmitted by a highly penetrant
autosomal dominant gene. The skin tumors may be
present at birth, but are usually seen at adolesence.
Most lesions are benign but may become invasive.
They are found mostly in the eyelids, nose, cheeks,
and trunk.
Ocular findings reported are congenital cataract,
strabismus, coloboma of the choroid and optic disc,
and corneal leucomata.

WYBURN-MASON SYNDROME
It is a rare oculocephalic syndrome in which arterio-
venous malformations of the retina and brain were
found. Wyburn-Mason has done detailed analysis of Fig. 86.10: Dilated tortuous vessels arising from disc with no
cases in which there were abnormal retinal arterio- distinct difference between arteries and veins
670 Section 6: Diseases of Orbit
trees in the involved area. These retinal malformations
are remarkably stationary. Rare complications like
lipid exudation, exudative retinal detachment,
vitreous hemorrhage or neovascular glaucoma are
noted. There are several reports correlating the extent
and the size of the retinal arteriovenous communi-
cation to central nervous system involvement, which
aid in selecting the appropriate investigation to
undertake. A small retinal vascular malformation in
a normal patient does not require invasive procedures
and large lesions warrant detailed investigations to
rule out neurological involvement.
Neurological signs depend upon the topographic
location of the vascular malformation. Pyramidal
tracts are commonly involved. Other lesions include
cranial nerve palsies.
Cutaneous malformations noted are nevus flam-
meus, subcutaneous arteriovenous malformations in
the area of distribution of the trigeminal nerve and
marked dilatation of the blood vessels on the
homolateral side of the face.
Treatment
Ocular lesions rarely need any treatment. These
patients should be promptly referred to neurologists
for investigations.
OCULODERMAL MELANOCYTOSIS
This is also called as nevus of Ota. It is characterized
by deep dermal pigmentation in the distribution of
the first and second divisions of the trigeminal nerve.
It is usually unilateral and nonfamilial. Other ocular
findings include hyperpigmentation of the globe
structures involving the sclera, conjunctiva, cornea,
iris, and fundus. There is an increased incidence of
uveal and orbital melanomas. Glaucoma is reported,
the mechanism of which is not clear.
ATAXIA-TELANGIECTASIA
(LOUIS-BAR SYNDROME)
It is a recessive inherited multisystem disease with
special mechanisms of malignancy.1
1. Ocular lesions. Bulbar conjunctival telangiectasis
is an essential component of the disorder. It is not
present at birth, but is usually noted between 4 and
7 years of age. Abnormalities of eye movements
are consequent to the CNS abnormalities.
2. Cutaneous manifestations have been reported but
are not pathognomonic of the disorder.
3. Systemic manifestations.
a. CNS: Progressive ataxia in childhood is a
striking feature.
b. Immune deficiency: Thymic hypoplasia is
associated with a profound defect in cell-
mediated immunity (T cells) and a selective
humoral deficiency of IgG21, IgG4, IgA, and
IgE. This immune deficiency appears to be
caused frequent pulmonary infections.
REFERENCES
1. William P, Boger III, Robert A Petersen. Pediatric Ophthal-
mology: In Manual of Ocular Diagnosis and Therapy (4th
edn): Little Brown and Company, 1996;286.
2. Cruen AF. Tuberous sclerosis and the eye. In Ryan SJ (Ed).
Retina, St. Louis: CV Mosby Company 1989;1: 571-79.
3. Asdourian GK, Lewis RA. The Phakomatoses. In Peyman GA,
Sanders DR, Goldberg MK (Eds). Principles and Practice of
Ophthalmology. Philadelphia: WB Saunders Company
1980;1186-1204.
4. Don H, Nicholson. Capillary hemangioma of the retina and
von Hippel-Lindau disease. In Ryan SJ (Ed): Retinal. St. Louis:
The CV Mosby Company 1989;1:563-70.
5. Retinoblastomas, leucokoria and phakomatose. In Apple DT
and Rabb MF (Eds). Ocular Pathology, St. Louis: The CV
Mosby Company 1985;290-95.
6. Rubenstein AE. Neurofibromatosis: A review of the clinical
problem. In Rubenstein AE, Bunge RP, Housman DE (Eds).
Neurofibromatosis: Ann NY Acad Science 1986;480:1.
7. Weiss JS, and Ritch R. Glaucoma in the phakomatosis. In Ritch
R, Shields B, Kurpin T (Eds). Glaucomas. St. Louis: The CV
Mosby Company 1989;905-29.
8. Peyman GA, Rao KV, Rednasm, Lippa LM and Flood T.
Treatment of large von Hippel tumor by eye wall resection.
Ophthalmology 1985;90:840.
9. Salazar FG, Lamiell JM. Early identification of retinal
angiomas in a large kindred with von Hippel-Lindau disease.
Am J Ophthalmol 1980;90:540.
10. Weiss MJ, Ernst JT. Diffuse congenital hemangiomatosis with
infantile glaucoma. Am J Ophthalmol 1976;81:216.
11. Femy AP, Comb J. Other phakomatoses. In Ryan SJ (Ed):
Retinal. St. Louis: The CV Mosby Company 1989;1:581-90.
 Chapter 87

Orbital Involvement in Diseases

of the Paranasal Sinuses
AK Khurana

Anatomically, the orbital cavity is bounded on three

sides by the paranasal sinuses (also called paraorbital
sinuses) (Figs 87.1 and 87.2). This intimate topo-
graphical relationship of the orbit to the paranasal
sinuses indicates that the former may be involved in
majority of expanding or bone eroding lesions
originating in the sinuses and in the nasopharynx.
From this point of view the paranasal sinuses can be
divided into two groups; i.e. anterior, in relation to
the anterior half of the orbit and the eyeball; and
posterior, in relation to the orbital apex and the optic
nerve (Fig. 87.2). The anterior group includes the
frontal sinus related to the orbital roof, the anterior
ethmoidal sinus related with its medial wall and the
maxillary antrum related with its floor. In the posterior
group these are the posterior ethmoidal and the Fig. 87.1: Coronal section through the orbits and nasal cavity
sphenoid sinuses which are in relation to the medial
aspect of the orbital apex, and the palatine air cells f. Miscellaneous associated features:
which are related to its floor. The intimacy of the i. Orbital neuralgia
topographic association is increased by the papery ii. Lid swelling
thinness and fragility of the many partitioning bones iii. Optic neuritis
and also by the small intercommunicating canals iv. Periosteitis and osteomyelitis of orbital
traversed by vessels and nerves. bones.

ORBITAL MANIFESTATIONS OF Orbital Cellulitis and Abscess

PARANASAL SINUS DISEASES
Orbital manifestations of paranasal sinus diseases
include the following clinical entities:
a. Orbital cellulitis and abscess
b. Proptosis
c. Enophthalmos
d. A mass in the orbital cavity
e. Superior orbital fissure syndrome
Orbital cellulitis and abscess formation is a common
complication of acute infection of the paranasal
sinuses; particularly when ethmoidal cells are affected
especially in children. The most common causative
organisms of this type of cellulitis are Streptococcus
pneumoniae, Staphylococcus aureus, Streptococcus
pyogenes and in children below the age of five years
Hemophilus influenzae.
672 Section 6: Diseases of Orbit
Mode of Spread of Infection
Direct spread, through bony wall owing to topo-
graphic intimacy, papery thinness of bones, dehis-
cences of the walls, and through fracture lines after
surgical or accidential trauma.
Vascular spread, in the form of septic venous
thrombosis both advancing and retrograde; thrombo-
phlebitis of minute veins between sinus mucosa and
the orbit; and retrograde spread from the cavernous
sinus.
Lymphatic spread, along perivascular lymphatics
through vascular foramina.
Clinical Features
Direct and lymphatic spread of infection usually
results in a subperiosteal inflammation and abscess
formation; while spread via phlebitic veins results in
a rapidly progressing cellulitis of the periocular fat
and the soft tissues. Both conditions are characterized
by considerable lid swelling, chemosis, and proptosis
(see Fig. 83.9). Pain is variable but may be severe.
Frequently, there is mild to severe restriction of eye
movements. In uncomplicated cases vision remains
good and pupillary reflexes are normal. The most
important blinding complications are central retinal
artery occlusion and optic neuritis. Unless treated
promptly, the potentially lethal systemic compli-
cations like meningitis, brain abscess, and cavernous
sinus thrombosis may develop.
In most of the cases, associated paranasal sinus
involvement is easily demonstrated on plain X-ray. A
specific radiological sign of acute sinus infection is
presence of a fluid level. Ultrasound may be helpful
in detecting the development of an orbital abscess.
Treatment
Treatment of orbital cellulitis consists of intensive
antibiotic therapy. Indications of surgical intervention
include decreasing vision due to pressure on the optic
nerve by the inflammatory products. Drainage is
accomplished by making a 2-3 cm curved incision in
the most dependant part of the localized abscess
commonly in the lower medical quadrant. Alter-
natively, drainage is performed through external
ethmoidectomy. In most cases it is necessary to drain
the orbit as well as the infected sinus.
Proptosis
Proptosis is a common manifestation of paranasal
sinus disease involving the orbit. Lloyd1 reported that
in approximately 20 percent of the patients presenting
with proptosis the cause is found in paranasal sinuses
or nasopharynx. Orbital invasion by malignant tumors
of the paranasal and nasal sinuses occurs in 50 percent
of patients.2
Direction of displacement of the globe is different
in lesions of different paranasal sinuses. Maxillary
sinus disease cause superior displacement of the globe
(see Fig. 83.7). Lesions of the ethmoidal sinus extend
in the direction of least resistance which is the lamina
papyracea, thus causing lateral displacement of orbital
contents (see Fig. 83.6). Frontal sinus expansion causes
downward and outward displacement of orbital
contents. The sphenoidal sinus lesions may extend into
the retrobulbar space, and the proptosis produced
often interferes with the nerves and vessels of the
eyeball.
Mechanism of Proptosis
The different mechanisms by which disease of
paranasal sinuses can produce proptosis are given
below:
1. Sinus distention producing displacement of the
orbital contents (Fig. 87.2A).
2. Compression of the orbital veins causes stasis of
edema fluid (Fig. 87.2B).
3. Destruction of bony wall of sinus helps the patho-
logical process to invade the orbit (Fig. 87.2C).
4. Spread of the disease in the orbit through the
vessels and foramina causes orbital involvement
(Fig. 87.2D).
Lesions of Paranasal Sinuses Causing Proptosis
Inflammations
i Acute inflammation, of the paranasal sinuses
produces proptosis by causing orbital cellulitis
or orbital abscess formation as described earlier.
ii. Chronic inflammation of paranasal sinuses,
nonspecific as well as specific, may sometimes be
associated with granulomatous changes or
pseudotumor formation.
Mucoceles Mucoceles of the paranasal sinuses
consist of dilated mucous containing sacs lined by
sinus epithelium. A mucocele develops when the
drainage of normal sinus secretions is obstructed, from
scarring, infection, trauma, tumor formation (such as
osteoma) or cystic degeneration of mucosa. When
infected, a mucocele becomes a mucopyocele.
 Chapter 87: Orbital Involvement in Diseases of the Paranasal Sinuses
Figs 87.2A to C: Schematic drawing of four mecha-
nisms by which proptosis can be caused by diseases
of paranasal sinuses. (A) Sinus distention. (B) Stasis of
edema fluid in orbit. (C) Orbital invasion after destruction
of bony wall
673
Fig. 87.2D: Spread of paranasal sinus disease in orbit through
connecting foramina or blood vessels (vascular spread)
Orbital invasion usually occurs either from frontal
or ethmoidal mucoceles (see Fig. 83.6) and only very
rarely from those arising from the maxillary sinus.
Expansion of the sinus is palpable in most patients
and often the clinical diagnosis is more obvious than
radiological. X-ray signs consist of enlargement of the
sinus with characteristic smoothening of the scalloped
margin of the normal sinus wall. In most patients the
sinus is more opaque than normal due to fluid
accumulation within its cavity. Treatment of muco-
celes involves radical operations on the sinus involved.
Pneumatosinus dilatans This term refers to an
abnormal expansion of part of the paranasal sinuses
containing only air and lined by normal sinus
epithelium. The lesion is predominantly encountered
in males. The dilated part of the sinus may invade
orbit producing proptosis.
Other cystic swelling Cystic swellings like dental
cyst, dentigerous cyst of paranasal sinus may also
produce proptosis.
Traumatic lesions of paranasal sinuses Traumatic
lesions of paranasal sinuses may cause proptosis by
spread of infection through fracture line. Fractures of
ethmoid labyrinth or of lamina papyracea may cause
some degree of proptosis following nose blowing. The
associated subcutaneous emphysema of the lids is
diagnostic.
Tumors Orbital involvement is common in benign
as well as malignant tumors of the paranasal sinuses.
Malignant tumors of the paranasal sinuses, in general,
carry a very poor prognosis unless diagnosed early.
674 Section 6: Diseases of Orbit
Ocular clinical features range from occasional slight
epiphora in case of tumor of maxillary sinus to gross
proptosis and ophthalmoplegia. Important rhino-
logical clinical features include facial pain, mucosal
congestion, epistaxis, and nasal discharge. By far the
most common malignant tumor to invade the orbit is
squamous cell carcinoma of the maxillary antrum.
Abrel 3 has reported 184 cases of proptosis of
rhinologic origin. Out of these 113 cases were due to
tumors (30% benign and 70% malignant).
Treatment
Treatment of such cases is primarily in the domain of
rhinologists. However, a team approach with the
ophthalmologist will be helpful in the successful
management of such cases and avoiding ocular
complications at surgery or thereafter.
Foster4 aptly stated, “there is neither cash nor credit
in the orbital tumors and that the surgical treatment
is deep, dark, and bloody and not a gentleman’s
operation from view of the ophthalmologists”. This
holds true equally for the rhinologists as well.
However, it is emphasized, that the awareness about
the possibility of the proptosis being due to tumor of
paranasal sinus is important in order to avoid delay
in diagnosis and early treatment.
Outline of Treatment
a. Benign tumors of paranasal sinuses usually need
complete surgical removal.
b. Malignant tumors can be treated by radiotherapy,
chemotherapy, surgical excision or combinations
of these methods, depending upon the stage and
extent of tumor.
i. Radical surgical excision, if diagnosed early,
provides the only chance for cure for malignant
tumors. Unfortunately, most of the patients pre-
sent in advanced stage, and need radiation
therapy in addition to surgical excision. There
is controversy over, whether, radiotherapy
should be employed preoperatively or post-
operatively. Each regime has got its own
advantages and disadvantages.
ii. Radiotherapy or chemotherapy or both the
measures can be attempted in patients who
refuse surgery, are too ill to tolerate a surgical
procedure or whose tumors are unresectable.
Radiotherapy can be of the following types: (a) con-
ventional; (b) teleradiation Co;60 or (c) intracavity
irradiation.
Chemotherapy may be administered: (a) intra-
arterial; (b) intravenous; (c) oral; or (d) local irrigation.
Surgical Approaches
1. Tumor involving maxillary antrum can be treated
by partial, total or extended maxillectomy depen-
ding upon the extent of the tumor.
2. Lateral rhinotomy (Moure’s approach) is preferred
for tumor involving maxillary antrum and lateral
wall of the nasal cavity.
3. Wilson’s transpalatal approach is engaged for
tumors involving nasopharynx.
4. Ethmoidectomy for tumors involving ethmoidal
sinus can be performed through intranasal,
extranasal or transantral approach.
5. Sphenoidal sinus tumors can be excised through
intranasal, transnasal, transpalatal, transseptal or
extended external ethmoidectomy approach.
6. Frontal sinus may be approached by Lynch-
Howrath’s external-frontal exploration.
7. Combined rhino-neurosurgical approach is best,
because of the following advantages:
i. Enblock removal of tumor mass is possible.
ii. Avoids tumor spill over during excision.
iii. Only approach to excise tumors of paranasal
sinuses with intracranial extension.
iv. Morbidity is minimal.
v. Operative mortality is low.
vi. Rehabilitation with prosthesis is possible.
Enophthalmos
Enophthalmos, i.e. recession of the eyeball into the
orbit is an important and frequently subtle clinical
sign which is easily overlooked. In fact, about 50
percent of patients with enophthalmos are initially
misdiagnosed as having ipsilateral ptosis or contra-
lateral proptosis. Enophthalmos of paranasal sinus
origin may be seen under the following circumstances:
• Contractures of orbital tissues following orbital
cellulitis secondary to acute sinusitis;
• Sinus operations;
• Injuries of sinus walls with prolapse of orbital
contents especially blow-out fracture of the medial
wall and floor of the orbit.
• Enophthalmos resulting from mucoceles of the
maxillary antrum has also been reported. Here the
mucocele expands, destroying the roof of the
antrum by pressure and thus resulting in evacua-
tion of the mucocele producing enophthalmos.
 Chapter 87: Orbital Involvement in Diseases of the Paranasal Sinuses
A Mass in the Orbit
Sometimes, a palpable mass in the orbit without
proptosis may be the first sign of sinus disease. A mass
in the region of the infraorbital rim may represent
extension of osteoma, mucocele or carcinoma of
maxillary sinus. A mass medial to the inner canthus
may indicate disease of an ethmoidal sinus. Similarly,
a mass behind the supraorbital rim usually indicates
extension of frontal sinus lesions.
Superior Orbital Fissure Syndrome
Superior orbital fissure syndrome may occur as a rare
complication of sphenoidal sinus disease (infla-
mmatory of neoplastic) involving the orbit. The clinical
features consist of deep orbital and unilateral frontal
headache associated with progressive palsy of 6th, 3rd
and 4th cranial nerves, usually in that order. The
treatment consists of exploration of the sphenoidal
sinus by transethmoidal approach.
Miscellaneous Associated Features
Orbital Neuralgia
Persistent pain in and around the orbit may be the
presenting symptom in many patients of the early
stages of orbital involvement of paranasal sinus
disease like sinusitis, benign tumors, and malignant
tumors.
Lid Swelling
Inflammatory edema of the eyelids may occur with
acute maxillary ethmoid or frontal sinusitis. This
675
edema is soft with no point of tenderness or locali-
zation, such as that found in acute infections of the
glands of lids. In general, upper lid is more swollen
with frontal sinusitis, both lids are equally swollen
with ethmoiditis and lower lid is more swollen with
maxillary sinusitis.
Optic Neuritis
Approximately 15 percent of cases retrobulbar neuritis
is caused by sinus disease. This is due to the fact that
the optic nerve is in close relationship to the sphenoid,
ethmoid and maxillary sinuses, depending upon their
pneumatization. The inflammatory process may
spread directly through the sinus wall or by phlebitis.
Periosteitis and Osteomyelitis
Periosteitis and osteomyelitis of the orbital bones may
occur as a complication of sinusitis, especially after
surgery on the infected sinuses.
REFERENCES
1. Lloyd GAS. The radiological investigations of proptosis. Br J
of Radiology 1970;44:373.
2. Shaw HJC. The clinical importance of orbital signs in cancer
of the paranasal sinuses. Proc of the Royal Soc Medicine
1964;57:742.
3. Abrol BM. Proptosis of Rhinologic origin. Proc All India
Ophthalmol Soc 1970;30:67.
4. Foster JC. Trans Ophthalmol Soc, UK 1948;68:369.
 Chapter 88
Metastatic Tumors to the Orbit
Lakshmi Mahesh, Nitin K Dutta
Metastatic tumour is described as primary extra-
ophthalmic neoplasm that spreads hematogenously
to the eye and the orbit. Metastatic tumors of the orbit
represent an important group of orbital space
occupying lesions. It is a malignant neoplasm which
spreads to different parts of the body including the
eye, more commonly to the uveal tract than to the
orbit. Uveal metastasis is 8 to 9 times more common
than orbital metastasis. It may also involve the iris
and ciliary body, optic nerve and sometimes the
vitreous. Ocular metastasis is usually developed in
one eye, commonly the left eye; but bilateral cases are
not rare. Occasionally, the orbital tumor may be the
initial manifestation of an undetected malignancy in
the body.1,2 30 to 61 percent of patients with orbital
metastasis develop ocular symptoms prior to the
diagnosis of primary tumor site. Metastatic tumor to
the eye is a poor prognostic sign for long term survival.
PRIMARY TUMOR SITES
As the types of malignant tumors are basically
different in children and adults, the primary sites of
the malignancies also may be different in children and
adults.
Childhood malignancies are most likely to arise
from embryonal cells. Sarcoma, neuroblastoma,
Ewing’s tumor (of bone). Wilms’ tumor (of kidney)
are more likely to metastasize to the orbit.5-7
In adults most metastatic tumors are carcinoma
which arise from the epithelial structures of the breast,
prostate, lung, gastrointestinal tract, kidney, thyroid,
and urinary bladder in order of frequency. Depending
upon the origin of cell type, nonepithelial metastatic
tumors found in the orbit include neuroblastoma,
sarcoma, and melanoma of the choroid of the other
eye as well as melanoma of skin and conjunctiva.
Adenocarcinoma is believed to be the most common
epithelial tumor and it originates, in order of fre-
quency, in breast, lung, prostate, thyroid, kidney, and
adrenal gland. Uncommon primary tumors are lipo-
sarcoma, tumors from testicle, liver, pancreas, parotid
gland, male breast, ovary and choroid (Table 88.1).
Common orbital metastatic tumors3
• Breast 42%
• Lung 11%
• Prostrate 8%
• Melanoma 5%
• Unknown 11%
BEHAVIOR OF DIFFERENT METASTATIC TUMORS
Prostate carcinoma contributes to 17 percent of orbital
metastatic tumors. Most bony metastatic prostate
carcinoma causes destruction of bone. Orbital
metastasis develops in or on the surface of the orbital
bones. When the metastasis is on the surface of the
bone, there is osteoblastic reaction; bone destruction
does not occur.4,8
Breast carcinoma constitutes more than half of the
orbital metastatic carcinoma and most of them present
with proptosis. In some cases, schirrous carcinoma of
the breast causes enophthalmos. Orbital metastatic
breast carcinoma is more likely to be bilateral.
Commonly metastatic orbital tumors are unilateral but
may be bilateral also. When unilateral, left orbit is
commonly affected; it may be due to the fact that the
left common carotid artery arises directly from the
arch of the aorta and hence embolic phenomena of
tumor cells are more likely to occur in the left side of
head and neck region.
Carcinoid tumor is a rare tumor arising from the
embryonic precursors in the germinative mesoderm
represented by the chromaffin cells of the gastro-
 Chapter 88: Metastatic Tumors to the Orbit 677
intestinal tract including the bile duct, pancreatic duct, also be present in gastrointestinal, lung, and prostate
and also the bronchial tract. It is named as carcinoid tumors. Another mechanism of enophthalmos is
because its histological picture is like that of cancer destruction of the bony wall of the orbit resulting in
but it tends to grow slowly and hence is considered biologic orbital decompression with consequent
thought to be of low malignant character. Choroidal enophthalmos.14,15
and orbital metastases of carcinoid tumors have been Metastasis of squamous cell carcinoma causes
reported.9,10 The tumors may be hard in consistency proptosis of acute onset with conjunctival congestion
and of lobulated configuration. The hard tumor may and “frozen globe” causing exposure keratitis and
even indent the globe. corneal ulcer leading to perforation of the globe.
Renal cell metastatic carcinoma is soft in consis-
tency due to its rich vascularity.11 The metastatic Factors Facilitating Metastasis16
orbital mass causes proptosis or displacement of the Following three hypotheses are postulated to explain
globe. Sometimes it becomes pulsatile.12 Renal cell the organ specificity of metastasis:
carcinoma manifesting as an orbital mass with bony a. Mechanical,
destruction may be the initial manifestation of primary b. Seed and soil, and
tumor. c. Specific tumor cell adherence.
The mechanical theory describes organ specific
Presentation (Fig. 88.1) metastasis to variation of blood flow and capillary
Majority of metastatic orbital tumors present with sieving due to vascular architecture phenomena which
known history of malignant tumor elsewhere in the may explain left sided dominance of orbital metastasis.
body. However, in a significant proportion of cases; The seed and soil theory and the specific tumor
the orbital tumor may be the presenting sign of cell adherence theory are similar in that they
systemic cancer (occult primary).13 In cases where the hypothesize tumor cell-host tissue interaction of the
primary tumor site is not significant, history of microenvironment and of the cell surface antigens,
previous cancer should be diligently pursued in respectively.
patients with signs of evident orbital metastasis. Initial
location of the metastatic tumor to the orbit is most Diagnostic Modalities (Table 88.1)
common in superolateral quadrant of the orbit. The Physical Examination
incidence of location in four quadrants of the orbit is
This includes thorough ocular and orbital evaluation.
as follows:
Breast and prostate should be methodically examined
Lateral 39 percent
Superior 32 percent
Medial 20 percent
Inferior 12 percent
Presenting symptoms may be variable. Proptosis
and diplopia are the most common symptoms.
However, defective vision can also be a symptom due
to pressure on the optic nerve. The condition is initially
painless. Onset of pain indicates bony involvement.
There may be mechanical motility disturbances of the
globe and blepharoptosis; however paresis of the
extraocular muscles due to involvement of the nerves
in the tumor mass is not uncommon. Pulsatile
exophthalmos is an unusual but interesting sign of
some metastatic tumors11—this occurs in metastatic
renal cell carcinoma and also due to the destruction
of orbital bone leading to transmission of cerebral
pulsation. Enophthalmos is a constant feature of
orbital metastatic diffuse schirrous breast carcinoma
due to contraction of fibroblastic tissue leading to Fig. 88.1: Displacement of the globe forward and
posterior traction and tethering of the globe; it may downward resulting from a metastatic carcinoma to the orbit
678 Section 6: Diseases of Orbit

Table 88.1: Characteristics, diagnosis, and therapy of various orbital metastases

Tumors Characteristics Diagnosis Therapy
Breast Enophthalmos in schirrous carcinoma. Bone, muscle involved Hormone therapy
Infiltrative method of presentation. May be diffuse infiltrate
Long latency-may metastasize after FNAB usually successful Radiotherapy
primary cancer diagnosed. Hormone receptor
Lung Short latency, after “silent” primary. Radiotherapy
X-ray chest may be normal. Rapid
progression of symptoms. Patient
often systemically ill. Chemotherapy (Oat-cell).
Poor survival.
Prostate Older patient, may have pain, CT scan-hyperostotic bony Hormone therapy
longer survival. involvement. Needle biopsy Radiotherapy: Orchidectomy.
Melanoma Long latency, short survival CT scan involves muscle Radiotherapy, chemotherapy
after metastasis develops.
Gastro- Short latency, may have Radiotherapy
intestinal tract infiltrative syndrome
Thyroid Primary tumor may have been CT scan bone involvement Radiotherapy
“read” benign, long latency, may be osteocytic Radioactive iodine.
long survival, may have pulsation.
Carcinoid Long latency, long survival, CT scan-typically well defined Radiotherapy
may have carcinoid syndrome, mass. Urinary 5-HIAA may be Surgical excision if isolated
potentially isolated metastasis. elevated, specially with liver
involvement
Renal Varied presentation—may be Radiotherapy
latent or fulminant, may have pulsation.
Seminoma Young males, non-metastatic proptosis Radiotherapy
Pancreas Fulminant course. Radiotherapy

to exclude primary tumors. During abdominal exami-
nation, possibility of carcinoma of the gastrointestinal
tract, renal malignancy including Wilms’ tumor and
neuroblastoma should be kept in mind. Following
modalities of investigation are also necessary before
planning the management of the condition:
1. Laboratory examination Both specific and non-
specific laboratory tests are needed in the work-
up of patients with metastatic tumors.17
a. Estimation of carcinoembryonic antigen (CEA).
This may be elevated and the degree of
elevation may relate to the tumor load. How-
ever, a negative test does not rule out metastatic
disease.
b. Serum acid phosphatase for prostate cancer.
c. Human chorionic gonadotrophin for seminoma
testes.
d. 5-Hydroxy-indol-acetic acid (5-HIAA) in urine
for carcinoid tumor.
2. Ultrasonography Metastatic tumors are usually
infiltrative although they can be very well circum-
scribed. The lesions can invade the orbital walls
and cause extensive bony destruction. They are
typically hard and nonvascular and they produce
weak sound attenuation. In irregularly shaped
infiltrative metastatic tumor USG shows medium
to high reflectivity and irregular internal structure.
Carcinomas that grow within a confined space like
beneath Tenon’s capsule or the periosteum are
more regularly shaped and show low to medium
reflectivity.18
3. Computerized tomography (CT scan) CT scan is the
practical standard modality for the diagnosis of
orbital disease. It not only allows localization of
the tumor within the orbit but also can provide
important clues regarding tissue characteristics. A
mass lesion, diffuse involvement, primarily bone
involvement with hyperostotic or hypostotic
appearance or muscle enlargement may be the
 Chapter 88: Metastatic Tumors to the Orbit
various types of findings in CT scan. The most
common presentation is a mass followed by bony
involvement (Figs 87.2 and 87.3). Usually breast
carcinoma shows as a mass or muscle involvement.
Prostate carcinoma causes bone involvement and
melanoma commonly shows muscle involvement.
4. Magnetic resonance imaging (MRI) MRI of metasta-
tic tumors show an irregular orbital mass with
a hypointense signal in respect to the orbital fat on
T-weighed images.19 Metastatic carcinoid tumors
Fig. 88.2: Bony erosion of the superior orbital wall
caused by metastatic orbital cancer
Fig. 88.3: Sclerotic change of the involved lateral orbital
wall by metastatic orbital tumor
679
and metastatic skin melanoma to the orbit
demonstrate well circumscribed appearance.
Carcinoma of prostate metastatic to the orbit shows
osteoblastic changes. The replacement of the fatty
bone marrow by the tumor and hyperostotic bone
appears as hypointense area indicating the
extension of the secondary tumor. MRI can
differentiate melanin from the rest of the compo-
sition of metastatic lesions but pigment in RPE can
give some false-positive results in favor of
choroidal melanomar. However, out of the above
three imaging procedures, CT scan is the most
accurate.20,21
5. Biopsy After localizing the tumor by the above
methods, fine needle aspiration biopsy (FNAB) or
incisional surgical biopsy should be done for tissue
diagnosis. Metastatic orbital tumor is one of the
best indications for FNAB. Hormone receptors and
surface antigen studies can be performed directly
on the specimen if adequate specimen is obtained,
specially in cases of prostate carcinoma.15
As the majority of metastatic tumors are poorly
differentiated or “round cell” tumors, special histo-
chemical, immunohistochemical, and electron
microscopic techniques are employed for further
differentiation.22 In case of hormonally responsive
tumors, steroid receptor studies on biopsy tissue
are important from therapeutic point of view.
Metastatic Cancer of Unknown Origin
Despite the existing modalities for investigation, in
about 10 to 30 percent of metastatic tumors the
primary cancer is not established. These tumors are
typically “silent” metastatizing early in their course.
Cancers of lung, stomach, colon, pancreas, thyroid,
and ovary are the common causes of such cryptic
metastases.
Treatment
It is to be noted that treatment of orbital metastatic
tumors is usually palliative.21 The principal modalities
are radiotherapy,23 hormone therapy,24 chemotherapy,
and surgery. Although the patients have a short
expected life span and even in cases where no direct
treatment is available, patients with symptoms like
pain and decreased vision can often get dramatic relief
with radiotherapy or chemotherapy. The importance
to provide continued function and comfort is of
paramount importance.
680 Section 6: Diseases of Orbit
Radiotherapy
Usually a total of 3000 to 4000 rads (30 to 40 Gy) is
given in divided dosed over a period of one to two
weeks. Improvement in signs and symptoms includ-
ing visual recovery is not uncommon. Complications
of radiotherapy like cataract and dry eye are few.
Nevertheless, radiotherapy is the mainstay of
treatment of orbital metastatic tumor.
Hormonal Therapy
Hormonal therapy is useful in metastatic prostate and
breast carcinoma. 25,26 The presence of hormone
receptors on the surface of these tumors can be
detected and measured in the laboratory with
adequate specimen of fresh tissue. If these tumors are
fairly well differentiated they may show a modulation
of growth in response to hormonal treatment. Diethyl
stilbesterol (DES) with or without orchidectomy has
been the mainstay of hormonal therapy since the 1950s
for prostate cancer. Specific luteinizing-hormone-
releasing hormone (LHRH) agonists have been
introduced to avoid the feminizing side effect of the
above two modalities of treatment.27 This method of
treatment is contraindicated in compressive spinal
cord and compressive orbital apex lesions due to the
initial testesterone surge and tumor growth in the
initial weeks. In one study28 it was found that 55-60
percent of metastatic breast tumors are positive for
estrogen receptors (ER) and are responsive to
endocrine therapy.28 The presence of progesterone
receptors (PgR) adds even greater predictive value.
Chemotherapy
Small cell carcinoma of the lung and neuroblastoma
are particularly chemosensitive. It plays an important
adjunctive role in palliative therapy of orbital
metastasis.
Surgery
In general, surgical treatment has got no role in
metastatic orbital tumors. However, in certain
metastatic carcinoid tumors, which are slowly
growing tumors, excision of the metastasis along with
the primary can provide long-term relief of symptoms
and improve survival rate.9,10 Surgery is also helpful
in containing solitary renal cell metastatic carcinoma.29
In cases where pain and gross proptosis are present
and other modalities are unsuccessful in relieving
symptoms, surgical debulking can be considered
despite the poor prognosis.
REFERENCES
1. Wobin MJ. Metastatic renal cell carcinoma manifesting as an
orbital mass. Am J Ophthalmol 1993;115:542.
2. Handerson JW. Metastatic carcinoma. Orbital tumors.
Philadelphia: Saunders, 1980.
3. Shields JA, Backwell B, Augusburger JJ et al. Classification
and incidence of space occupying lesions of the orbit: A
survey of 645 biopsies. Arch Ophthalmol 1984;102:1606.
4. Ferry AP, Font RL. A carcinoma metastatic to the eye and
orbit: A clinicopathological study of 227 cases. Arch
Ophthalmol 1974;92:276.
5. Goldberg RA, Rootman J, Cline RA. Tumors metastatic to
the orbit: A changing picture. Surv Ophthalmol 1990;35:1.
6. Shields CL, Shields JA. Metastatic tumors to the orbit. Intl
Ophthalmol Clinc 1933;33(3):189.
7. Albert DM, Rubenstein RA, Scheie HG. Tumors metastasis
to the eyes: Incidence in 213 adult patients with generalized
malignancy. Am J Ophthalmol 1967;63:723.
8. Font RL, Ferry AP. Carcinoma metastatic to the eye and orbit
III: A clinico pathologic study of 28 cases metastatic to the
orbit. Cancer 1976;38:1326.
9. Rush JA, Walley RR, Campbell RJ. Orbital carcinoid tumor
metastasis from colon. Am J Ophthalmol 1980;89:636.
10. Fan JT, Buettner H, Bartley GB et al. Clinical features and
treatment of seven patients with carcinoid tumor metastatic
to the eye and orbit. Am J Ophthalmol 1993;119:211.
11. Howard GM, Jakobeic FA, Troker SL et al. Pulsating
metastatic tumor in the orbit. Am J Ophthalmol 1978;85:767.
12. Wolin MS. Metastatic renal cell carcinoma manifested as an
orbital mass. Am J Ophthalmol 1993;115:542.
13. Henderson JW, Farrow GM. Metastatic carcinoma in
Henderson JW. Orbital tumors. New York, Brian C. Decker
1980;451-71.
14. Reifler DM. Orbital metastasis with enophthalmos: A review
of literature. Heny Ford Hosp Med J 1985;73:171.
15. Cline RA, Rootman J, Enophthalmos. A clinical review.
Ophthalmology 1984;91:229.
16. Fidler IJ, Hart IR. Principles of cancer biology. Cancer
metastasis. In DeVitu VT, Heilman SA (Eds). Cancer:
Principles and practice of oncology. Philadelphia: Lippincot
1985;113:124.
17. Reifler DM, Kini SR, Liu D et al. Orbital metastasis for
prostatic carcinoma: Identification by immunology. Arch
Ophthalmol 1984;102:292.
18. Byrne SF, Green RL. Ultrasonography of the Eye and Orbit.
Mosby year book. 291-95.
19. Peyster RG, Shapiro MD, Haik BG. Orbital metastasis: Role
of magnetic resonance imaging and computed tomography.
Radiology Clin N Am 1987;28:647.
20. Shields CL, Shields JA, Eagle RC et al. Orbital metastasis from
a carcinoid tumor. Computed tomography, magnetic
resonance imaging, and electron microscopic findings. Arch
Ophthalmol 1987;105:968.
21. Shields CL, Shields, JA. Metastatic tumors to the orbit. Intl
Ophthalmol Clinc 1993;33(3):189-202.
 Chapter 88: Metastatic Tumors to the Orbit
22. Jakobeic FA, Font RL. Orbital metastasis. In Spencer WH (Ed):
Ophthalmic Pathology. Philadelphia:Saunders1986;3:2750-65.
23. Glassburn JR, Lionsky M, Bradley LW. Radiation therapy for
metastatic disease involving the orbit. Am J Clin Oncol
1984;7:145.
24. McGuire WL. Current status of estrogen receptors in human
breast carcinoma. Cancer 1975;36:638.
25. Blodi HS, Nerad JA. Orbital metastasis from prostatic
carcinoma. Arch Ophthalmol 1988;106:1403.
681
26. Rootman J, Ragaz J, Cline R et al. Orbital metastasis. In:
Rootman J. Disease of the orbit. Philadelphia: JP Lippincot
1988;405-07.
27. Huben RP, Murphy GP. Prostate cancer: An update. Ca A.
Cancer J Clinicians 1986;36:274.
28. McGurie WL. Current status of estrogen receptors in human
breast cancer. Cancer 1975;36:638.
29. Tolla BM, Whitmore WF. Solitary metastasis from renal cell
carcinoma. J Urol 1975;115:836.
 Chapter 89
Orbital Blow-out Fractures
AK Khurana
In this era of high speed traffic, incidence of maxillofa-
cial injuries is increasing. Maxillofacial injuries may
be divided into three types:
a. Upper part injuries above supraorbital margin;
b. Middle part injuries between supraorbital margin
and upper teeth; and
c. Lower third injuries below the upper teeth.
The lower third does not concern the eye surgeons.
The pattern of fractures of the middle third of the face
varies with the direction and force of blow. Various
authors have investigated the mechanism of facio-
maxillary fractures. In 1901, LeFort1 described three
anatomical lines of least resistance in the facial skeleton
and his name has been given to the fractures which
follow these lines. Two of these (Lefort types II and
III fractures) involve the orbit. LeFort’s theory was
discussed by Rowe and Killey,2 who postulated the
presence of the following of four major vertically
oriented components in the middle third of the facial
skeleton: (a) the nasoethmoid, (b) nasomaxillary, (c)
dentoalveolar, and (d) zygomatic. These are related
to the transmission of masticatory forces to the base
of the skull. These buttresses are relatively resistant
to vertically directed trauma and are more susceptible
to horizontally directed blows. These influence the
displacement of fragments. Their knowledge helps in
understanding of maxillary fractures. However,
Reichenbach3 states that in practice extensive facial
fractures are unpredictable and in only 20 percent fall
into any pattern.
For the purpose of description orbital fractures can
be grouped as under:
1. Fractures of orbital rim
a. Superior orbital rim (including orbital roof and
frontal sinus)
b. Lateral orbital rim
c. Inferior orbital rim (with or without fracture of
floor)
d. Medial orbital rim
2. Fractures of orbital walls
a. Orbital floor
b. Medial orbital wall
c. Lateral orbital wall
d. Orbital roof.
3. Bilateral fractures of the orbital walls—craniofacial
dysjunction fracture.
4. Optic canal fracture.
Depending upon the features of the fractured bone
segments, the orbital fractures can be divided as:
i. Sprain fractures in which the orbital wall is dis-
located together with a big fragment of the
zygomatic bone or maxilla.
ii. Fragmentary fractures wherein the solid orbital
rim is broken by bending and tossing.
iii. Isolated comminuted fractures—they have
been described by Lang (1895) 4 and Fuchs’
(1891)5 before the turn of the century and again
in 1957 by Converse and Smith6 who named
them “blow-out fractures”. They occur when
the orbital walls are pressed indirectly. Blow-
out fractures mainly involve orbital floor and
medial wall.
INCIDENCE OF BLOW-OUT FRACTURES
Schultz7 reported that out of 1042 cases of maxillofacial
injuries 60 percent had fractures in and around the
orbit. In another series8 of 610 skull fractures 78 percent
patients presented with ocular signs and symptoms.
In yet another series of 178 orbital fractures 72 percent
patients had multiple fractures and in 20 percent of
cases both orbits were involved.9 Some authors state
that blow-out fractures are the most common orbital
 Chapter 89: Orbital Blow-out Fractures
fractures10 and “pure blow-out fractures” represent
40 percent of orbitomalar fractures.11
MECHANISM OF BLOW-OUT FRACTURE
Basically there are two theories regarding mechanism
of blow-out fractures of the orbit:
i. The classical mechanism was first defined by
Smith and Regan in 195712 (Figs 89.1A and B). The
“blow-out fracture” generally results from
trauma to the orbit by a relatively large, often
rounded object, such as tennis ball, cricket ball,
human fist or some part of an automobile. These
are swift, blunt, nonpenetrating injuries. The force
of trauma is transmitted to the globe and soft
tissues of orbit; some of this is cushioned by the
orbital rim. Thus, the force of the blow causes a
separately or jointly.
683
backward displacement of the eye and an increase
in intraorbital pressure with a resultant fracture
of the weakest point of the orbital wall. Usually
this point is the orbital floor, but this may also be
the medial wall of the orbit in the region of the
lamina papyracea. Approximately, 75 percent of
blow-out fractures of the orbital floor involve its
posteromedial aspect. In fact, the blow-out
fractures of the floor act as a decompression
mechanism. Herniation of the soft tissues occurs
into the maxillary antrum; the inferior rectus or
the inferior oblique or both the muscles may be
caught in this herniation resulting in impaired
ocular mobility.
ii. The second theory is that the force of the blow on
the orbital rim (which is not fractured) is
transmitted as a buckling force along the orbital
floor. This may produce a linear or frank
fracture.13 In this situation the orbital fascia may
be trapped in the linear fracture or ruptured
tissues may herniate through a defect as the result
of a secondary rise in orbital hydraulic pressure
due to edema and hematoma.
It is probable that both mechanisms may work

CLASSIFICATIONS OF BLOW-OUT
FRACTURE OF ORBITAL FLOOR

Depending upon the Fractured Bones

1. Pure blow-out fracture This term is used to describe

Fig. 89.1A: Showing mechanism of ‘blow-out fracture’ by a a specific type of orbital fracture which is not
blow from hurling ball and human fist associated with involvement of the orbital rim.
2. Impure blow-out fracture This is associated with
other fractures about the middle third of the facial
skeleton.

Depending upon the Extent of Fracture

1. Egg-shell blow-out fracture This is the fracture with

hammock like sagging of the floor into the
maxillary antrum.
2. Trap-door blow-out fracture In this a trap-door
piece of bone hangs on a periosteal hinge into the
maxillary sinus.
3. Linear blow-out fracture It is just capable of
pinching the undersurface of the orbital contents.
4. Blow-out fracture with a large opening into maxillary
Fig. 89.1B: Showing mechanism of ‘blow-out fracture’ sinus This is associated with herniation of orbital
by a blow from human fist contents into the maxillary antrum.
684 Section 6: Diseases of Orbit

Depending upon the Location of Fracture b. Injury to motor nerves supplying the inferior
rectus and inferior oblique muscles.
1. Diffuse (generalized) blow-out fracture in which a
c. Direct injury and laceration of the muscles by
major portion of the floor is collapsed into the
bone fragments.
maxillary sinus.
d. Hemorrhage into the muscle on disruption of
2. Localized (limited) blow-out fracture may be: (i)
its attachment.
medial blow-out fracture which often occurs in
The presence of muscle restriction can be confirmed
impure type, associated with a naso-orbital
by a positive “Forced Duction Test” and “Differential
fracture, and a fracture of the medial orbital wall;
Intraocular Pressure Test”. To perform the “forced
(ii) central blow-out fracture is commonly of the
duction test” the conjunctival sac is anesthetized with
pure blow-out type; and (iii) lateral blow-out
a drop of local anesthetic solution and traction is
fracture of the floor is usually of the impure type
applied by grasping at the insertion of the inferior
associated with fracture of zygoma.
rectus muscle with forceps about 7 mm from the
limbus (Fig. 89.3). In positive forced duction test globe
CLINICAL FEATURES
cannot be rotated upward because of incarceration of
The clinical features of a blow-out fracture of the inferior rectus muscle in blow-out fracture.
orbital floor vary according to the severity of trauma
and the time interval between the injury and the
presentation of the patient.
Initially, there is periorbital edema and blood
extravasation in and around the orbit (such as subcon-
junctival ecchymosis). This may mask certain signs
and symptoms seen later.
• Emphysema of the eyelid may occur more frequently
with fracture of medial wall than that of the floor;
it may be made worse by blowing of nose.
• Paresthesia and anesthesia of the skin over the area
of distribution of the infraorbital nerve, viz lower
lid, cheek, side of nose, upper lip, and upper teeth
are common signs.
• Ipsilateral epistaxis as a result of bleeding from
maxillary sinus into nose is an early sign. A variable
degree of proptosis may also be present initially Figs 89.2A to C: Three mechanisms producing enophthalmos
because of associated orbital emphysema, edema, of ‘blow-out fracture’ of orbital floor. (A) Escape of orbital fat
and hemorrhage. into maxillary antrum. (B) Backward traction of globe by
entraped muscle. (C) Enlargement of orbital cavity
After about 10 days, due to resolution of the causes
of proptosis, the eyeball appears to be displaced back-
ward and downward. Three factors are responsible
for producing this enophthalmos: (i) escape of orbital
fat into maxillary sinus; (ii) backward traction on glove
by entrapped inferior rectus muscle; and (iii) enlarge-
ment of orbital cavity from displacement of fragments
(Fig. 89.2).
• Diplopia is another symptom. It typically occurs
in both up and down gaze (double diplopia).
Possible causes of diplopia are the following:
a. Entrapment of the inferior rectus, inferior
oblique, suspensory ligament of Lockwood,
periorbita and, fascial expansions in the lips of
the fractured bone. Fig. 89.3: Forced duction test
 Chapter 89: Orbital Blow-out Fractures 685
The following permutations and combinations of ii. Fracture of the inferior orbital rim;
diplopia and enophthalmos may be observed in blow- iii. Partial to complete opacification of the under-
out fractures: lying maxillary sinus due to hemorrhage;
iv. Orbit emphysema may be seen especially when
Diplopia with enophthalmos This condition results
an associated ethmoid fracture is present; and
from incarceration of orbital contents in the area of
v. Fracture of medial orbital wall, indicated by
the fracture.
extension of orbital soft tissue shadow into the
Diplopia without enophthalmos This condition may plane of ethmoid cells.
occur with fixation of orbital contents in a linear Not all blow-out fractures are seen roentgeno-
fracture. There is no escape of orbital fat, no graphically. The “trapped door” variety has minimal
enlargement of the orbit, and hence no enophthalmos. bony displacement and no floor deficiency.
Enophthalmos without diplopia This occurs when
Computerized Tomography Scanning
the inferior orbital contents are not entrapped in the
fracture. The periorbita is torn and an opening has It is of greater value for detailed visualization of soft
occurred allowing escape of orbital fat only. Alte- tissue. Coronal sections are particularly useful in
ratively, the orbital cavity may be sufficiently enlarged evaluating the extent of the fracture, as well as
to result in enophthalmos. determining the nature of antral soft tissue densities.
No diplopia and no enophthalmos This condition
MANAGEMENT
occurs when the fracture neither causes fixation of
orbital contents nor disturbs the anatomy of periorbital Time for Treatment
or orbital cavity.
At one time it was considered necessary that repair of
Associated severe ocular damage is rare because
blow-out fractures should be made within 48 hours
blow-out fracture is itself a protective measure for the
of trauma to achieve a satisfactory result. However, it
globe. Nevertheless, the eye should be carefully
is now established that the optimal time for surgery,
examined to exclude the possibility of intraocular
when indicated, is within 10-14 days of injury.15
damage (reported in 14% of cases in one study).14 This
During this period, local edema and periorbital
includes hyphema, traumatic iridodialysis, contusion
hematoma settles sufficiently to allow adequate
cataract, lens subluxation, angle recession, vitreous
examination of ocular position and movements, and
hemorrhage, retinal dialysis, giant retinal tear,
fibrosis within the orbit does not occur to a significant
commotio retinae, and preretinal hemorrhage.
extent. Thus, careful clinical and radiological
ROENTGEN EXAMINATION
Plain X-rays
The most useful projection for detection of orbital floor
fracture is nose-chin (Water’s) view. Other views like
Caldwell, frontooccipital projection, oblique view, and
anteroposterior projection may also be required. Poly-
directional tomography is diagnostic in 95 percent of
cases. The common Roentgen findings are:
i. Fragmentation and irregularity of orbital floor;
ii. Depression of bony fragments;
iii. A “hanging drop” opacity of the superior
maxillary antrum from orbital contents herniating
through the floor (Fig. 89.4).
In addition, the following Roentgen findings may
be seen:
i. Increased orbit density with thickening of the
soft tissue shadow over the inferior orbital rim Fig. 89.4: Plain X-ray of orbit (AP view) showing herniated
due to edema; orbital contents (arrow) with blow-out fracture of left orbital floor
686 Section 6: Diseases of Orbit

assessment in the first two weeks permits a reasoned
decision to be made whether to operate or not on any
particular patient. However, a late primary treatment
(beyond 21 days) after malunion of fracture, fibrosis
of the injured orbital structures, with established
diplopia and enophthalmos, is more difficult. Many
cases with discernible traces of orbital injury are left
alone.15
Aims of Treatment
To prevent permanent vertical diplopia and cosme-
tically unacceptable enophthalmos.
are raised from the tarsus, the septum orbitale becomes
visible and the dissection is continued downward until
the rim of the orbit is reached. Next, periosteum is
incised a few millimeters below the actual rim, and is
elevated to expose the orbital floor. During this
maneuver care should be taken to avoid injury to
infraorbital nerve. The entrapped orbital contents are
released from the area of blow-out fracture. Verifi-
cation that the globe has been freed from the fracture
site is obtained by “traction test”.

Indications of Surgical Intervention

Given the results of X-ray and clinical tests, the
indications of surgical intervention are:
i. diplopia not resolving significantly within reason-
ably early period following the injury, in the early
days after trauma;
ii. a fracture with a large herniation of tissues into
the antrum;
iii. incarceration of tissues in the fracture with
resulting globe retraction and increased appla-
nation tension on attempted upward gaze; and
iv. enophthalmos greater than 3 mm.
Any of the above factors either alone or combined,
could indicate that early surgery is necessary.

Surgical Technique
Surgical approaches Surgically the orbital floor may
be approached through the eyelid or through the
canine fossa and the maxillary sinus. Eyelid approach
is usually preferred as it permits easy disengagement
of entrapped orbital tissue. Approach to the orbital
floor through the canine fossa and the maxillary sinus
is indicated for removal of bone fragments in the
maxillary sinus and has merit in cases of severely
comminuted fracture of the maxilla and other bones
of the midfacial area.
Incision sites for eyelid approach to the orbital
floor Four major incision sites, used for orbital floor
repair through eyelid approach, are: (i) below lash
margin; (ii) lower lidline; (iii) inferior orbital rim; and
(iv) conjunctival cul-de-sac. Presently, the most
commonly preferred incision site is 3 mm below the
lash margin, as it leaves a very inconspicuous scar and
allows easy exposure.
Exposure of the orbital floor (Fig. 89.5) The incision
is made through the skin and orbicularis until the
tarsus is reached. At this point the muscle and skin
Fig. 89.5: Schematic sagittal section showing surgical technique
of exposure of orbital floor. (1) Septum orbitale. (2) Periosteum
of floor of orbit. (3) Orbicularis
Restoration of the continuity of the orbital floor
Restoration of the continuity of the orbital floor may
be made with or without implants. Repair without
implants may be possible when fractures are (i) linear;
(ii) small; or (iii) trap door. Otherwise, a bone graft or
alloplastic implant may be used to fill the gap.
Recently, most orbital surgeons have reported good
results with the subperiosteal use of 1 mm thick Teflon
sheets. However, smooth materials such as Teflon tend
to slide forward and protrude under the skin of the
eyelid. Therefore, the implant should be anchored to
the orbital rim with the help of stable steel wire.
Another method to prevent implant extrusion is to
prepare a tongue of the implant and introduce it under
the anterior edge of the bony defect in the orbital floor
(Fig. 89.6).
 Chapter 89: Orbital Blow-out Fractures
Fig. 89.6: Technique to prevent forward displacement
of a Teflon implant
MANAGEMENT OF BLOW-OUT FRACTURES:
AN ALTERNATIVE VIEW
Putterman and associates16 are not in favor of early
surgery for pure blow-out fractures because it is: (i)
impossible to determine accurately during the first few
weeks after trauma which patient definitely needs
surgery; (ii) the surgical treatment has multiple
complications including blindness; (iii) most patients
become asymptomatic and have a cosmetically accept-
able appearance without surgery; and (iv) visually
handicapping diplopia and cosmetically unacceptable
enophthalmos can be managed months later.
In view of the above, it is recommended that all
patients with pure blow-out fractures of the orbital
floor be followed for 4 to 6 months without surgery.16
Later, Putterman17 modified this approach slightly by
recommending that all such patients be followed up
without surgery until diplopia and enophthalmos
have stabilized.
If visually handicapping diplopia persists follow-
ing stabilization after trauma, it can usually be relieved
successfully by release of entrapped orbital tissues
within one month after trauma, or by extraocular
muscle surgery if stabilization occurs after one month.
Cosmetically unacceptable enophthalmos can be
treated after it stabilizes, with (i) an orbital floor
implant, if there is downward sinking of the eye; (ii) a
Muller muscle-conjunctival resection ptosis proce-
dure, if there is a narrow palpebral fissure that
687
18
responds to the phenylephrine test, or (iii) excision
of skin and orbital fat and elevation of the crease on
the contralateral upper lid, if a deep supratarsal sulcus
exists.19
MEDIAL BLOW-OUT FRACTURES
A medial blow-out fracture refers to fracture of lamina
papyracea with an intact orbital rim. Medial wall
blow-out fracture may occur alone or in association
with the blow-out fracture of the orbital floor.
Clinical Features
The medial blow-out fracture is characterized by
edema and ecchymosis of the eyelids, orbital or lid
emphysema, horizontal diplopia retraction of the
globe on attempted abduction, and enophthalmos. A
positive forced duction test of medial rectus muscle
helps to distinguish entrapment from restricted
movements due to nerve damage, muscle edema and
hematoma.
Imaging Studies
Plain radiographs using Water’s and Caldwell views
will show clouding of the ethmoidal air sinus. A break
in the vertical radiopaque lamina papyracea and
orbital emphysema may not be detectable.
CT Scan
Axial and coronal computerized tomography allows
detailed examination including medial rectus
entrapment.
• CT scan accurately localizes the bone fragments of
the fractured lamina papyracea even if the orbital
sinus adjacent to the fracture is opacified. A
variable degree of medial displacement of the thin
lamina papyracea may be present and often there
may be increased density of the ethmoidal sinuses
due to edema and blood accumulation. CT scan
also detects entrapment of the medial rectus muscle
recognized by displacement of the muscle into the
fracture site.
• A CT scan reliably demonstrates whether acute
proptosis in a patient is secondary to orbital hemor-
rhage or orbital emphysema.
• Echography also could aid in distinguishing these
two distinct entities. B-scan ultrasound has proven
to be reliable in diagnosing medial wall fractures
because a good correlation was found between
ultrasound and CT scan. However, edema, hemorr-
hage and swelling may influence the accuracy of
the scan.
688 Section 6: Diseases of Orbit
MANAGEMENT
Medical Therapy
Most isolated medial wall fractures this is no treatment
except ice compress, warning patients to avoid
blowing their nose, decongestants and systemic
antibiotics. The antibiotics are recommended to reduce
the risk of sinusitis and orbital cellulitis: Cephalexin
at a dosage of 250 mgm every 6 hours is a prophylactic
regimen.
Systemic corticosteroids have been advocated to
speed up the resorption of the edema, as well as the
hemorrhage, thus allowing the surgeon to more
accurately assess any muscle entrapment and orbital
damage. Prednisolone (60-80 mg/day) is initiated
within 48 hours of the injury and is continued for five
days. Steroids are also indicated if severe visual loss
develops. In this case the dosage is higher: 250 mg of
methyl prednisolone administered intravenously
every 6 hours.
Surgical Therapy
Indications
The indications for surgical treatment include:
persistent diplopia, enophthalmos and limitation of
abduction of the eye on the affected side.
Goals
The goals of surgical treatment for medial wall
fractures are restoration of good ocular motility,
including binocular single vision in all fields of gaze
and significant improvement of enophthalmos. The
primary goal is the complete reduction of the
entrapped medial rectus muscle along with any other
herniated orbital soft tissues. This may be followed
by covering the bony defect with an implant to prevent
prolapse of tissue with possible reincarnation of tissue
or late enophthalmos.
Surgical approaches
The fractured wall may be repaired through a medial
approach. The two most common approaches are
Lynch incision and the transcaruncular approach. The
Lynch incision which involves incising skin directly
over the superomedial orbital rim provides excellent
exposure but can result in severe scarring or webbing.
The transcaruncular approach avoids leaving a visible
scar. In isolated medial wall fractures, this approach
provides adequate exposure to the medial wall and
to the area of tissue incarceration. Once the incision is
made, blunt dissection to the periosteum is performed
and the periosteum is incised. Care is taken to avoid
damage to the trochlea superiorly. The lacrimal sac is
identified and carefully separated from the fossa. The
anterior ethmoidal vessels are identified and co-
agulated. The fracture site is identified and a posterior
elevator is used to gently remove the incarcerated
tissues from the fracture.
The bony defect can be closed with 1 mm silicone
elastomer sheet (silastic) or cortical bone from an intact
antral wall. Prior to closure, forced duction test should
be performed to confirm complete release of the
entrapped orbital contents or muscles. Finally, the
incision site is closed with absorbable sutures.
REFERENCES
1. LeFort RC. Etude experimental e surles fractures de la
machoire superieure. Rev Chir 1901;23:208.
2. Rowe NL and Killey HC. Fractures of Facial Skeleton. E and
S Livingston Ltd: Edinburgh, 1955.
3. Reichenbach E. Die bruche der mittelgesicht-Knochen. Arch
Ohr Nos Kahlkopfheild 1954;165:9.
4. Lang W. Methodical Examinations of the Eye. Longmans,
Green, London, 1895.
5. Fuchs E. Lehrbuch der Augenheilkunde; 2 Auflage. Deuticke,
Leipzig, 1891.
6. Converse JM and Smith B. Enophthalmos and diplopia in
fractures of the orbital floor. Br J Plast Surg 1957;9:265-74.
7. Schultz RC. Intraorbital and glabellar fractures. Plast Reconsti
Surg 1970;45:227.
8. Blakeslec GA. Eye manifestation in fracture of skull. Arch
Ophthalmol 1929;2:566.
9. Pettinati S. Lindagine radiologica neck fracture dell’ orbita,
Rass Ital. Ottal 1955;24:294.
10. Zizmor J and Noyek AM. In TH Newton and DG Potts (Eds):
Orbital Trauma (radiology of skull and brain). Bode 2, CL
Morby: St. Lovis, 1971;1.
11. Pfeiffer RL. Traumatic enophthalmos. Arch Ophthalmol
1943;30:718.
12. Converse JM, Smith B, Obear MF and Wood Smith D. Orbital
blow out fractures: A ten-year study plast. Reconstr Surg
1967;39:20.
13. Fujno T and Makino K. Entrapment mechanism and ocular
injury in orbital blow-out fracture. Plastic and Reconstructive
Surgery 1980;65:571.
14. Milanskas AT and Femger FG. Serious ocular complications
associated with blow-out fractures of the orbit. Am J
Ophthalmol 1966;62:670.
15. Dulley B and Feels P. Long-term follow-up of orbital blow-
out fractures with and without surgery. Med Probl
Ophthalmol 1975;14:467.
16. Putterman AM, Stevens T and Urist MJ. Nonsurgical manage-
ment of blow-out fractures of orbital floor. Am J Ophthalmol
1974;77:232.
17. Putterman AM. Late management of blow-out fractures of
the orbital floor. Trans Am Acad Ophthalmol Otolaryngol
1977;83:650.
18. Putterman AM and Urist MJ. Muller muscleconjunctiva
resection. Technique for treatment of blepharoptosis. Arch
Ophthalmol 1975;93:619.
19. Putterman AM and Urist MJ. Reconstruction of the upper
eyelid crease and fold. Arch Ophthalmol 1976;94:1941.
 Chapter 90
Orbital Cellulitis
AK Khurana
INTRODUCTION
Orbital infections have been classified into five
groups:
Group I—Preseptal cellulitis;
Group II—Orbital cellulitis;
Group III—Subperiosteal abscess;
Group IV—Orbital abscess; and
Group V—Cavernous sinus thrombosis.
This classification system does not necessarily
imply an order of disease progression; however, it
helps to explain the physical signs and symptoms of
the various infections and helps to organize a
treatment plan.
Orbital cellulitis is referred to infection of the soft
tissues of the orbit (without abscess formation)
posterior to the orbital septum, differentiating it from
preseptal cellulitis, which is infection of the soft
tissues of the eyelids and periocular region anterior
to the orbital septum.1,2
It is one of the few ophthalmic emergencies which
can have severe systemic implications besides causing
loss of vision, if appropriate management is not
instituted in the right time.
ETIOPATHOGENESIS
Predisposing Factors
Age Orbital cellulitis is more common in children,
and more severe in diabetics and immunocompro-
mized patients.3, 4 In Schramm’s series of 303 cases of
orbital cellulitis, 68% of the patients were younger
than 9 years of age and only 17% were older than
age 15 years.5
Laterality There seems to be an unexplained
preponderance of left sided orbital infections as
compared with right sided infections.6
Season Orbital cellulitis is reported to be more
common, in winter because of increased prevalence
of sinusitis when the weather is cold.
Race No racial predilection exists for orbital
cellulitis.
Sex No frequency difference exists between the
sexes.
Routes of Infection
Extension of the Infection from the
Periorbital and Intraocular Structures
Paranasal sinuses Orbital involvement occurs in
0.5 to 3 pcercent of the patients with acute sinusitis.7
In adults, pansinusitis is often associated with orbital
cellulitis and spread is believed to occur through the
ethmoidal or frontal sinus.
The main factor predisposing the orbit to spread
of sinus infection is the free vascular communication
between the orbit and the sinuses.8 The orbital veins
are valveless, and the flow occurs in either direction,9
through the anterior and posterior ethmoidal
foramina. Also, the medial orbital wall has got
numerous defects (Zuckerkandl dehiscences).10
This combination of thin bone, foramina for
neurovascular passage, and naturally occurring
defects in the bone allows easy communication of
infectious material between the ethmoidal air cells
and the subperiorbital space in the medial aspect of
the orbit.
Orbital fracture can also spread existing chronic
sinus infection into the orbit.2 Mucoceles, slowly
690 Section 6: Diseases of Orbit
enlarging mucus filled cysts within the sinuses that
enlarge by pressure erosion of adjacent orbital and
intracranial structures, can become infected and result
in mucopyoceles that cause cellulitis.11
Other periorbital structures like face, globe and
lacrimal sac can also be the source of spread of
infection to the orbit.
• Approximately 15 percent of the cases of orbital
cellulitis occur from sources in the cervical
region.12,13
• Dental surgical procedures or an infected dental
cyst may also rarely cause orbital cellulitis through
spread of infectious phlebitis across the pterygo-
palatine venous plexus.16
Endophthalmitis from a variety of endogenous or
exogenous causes may extend extraocularly to
involve the orbit.
Direct Inoculation of the Orbit
From trauma or surgery Surgery of eyelid, dacryo-
cystorhinostomy, strabismus and retinal surgery
result in orbital cellulitis.15 Orbital inflammation may
develop within 48 to 72 hours after injury.
Foreign bodies such as wood, glass or orbital floor
implants, can cause orbital cellulitis refractory to the
treatment with antibiotics that requires removal of
the nidus of infection.
Embolic Source
Orbital cellulitis can also occur secondarily from
embolic spread in subacute bacterial endocarditis.
Pathophysiology
Regardless of the anatomic site of origin, edema
develops as the orbital infection spreads within the
connective tissues. Septic thrombophlebitis may ensue
and increase both edema and orbital pressure as
blood flow is impeded. Microflora indigenous to the
sinuses18 and upper respiratory tract proliferate and
invade the edematous mucosa, resulting in suppura-
tion. The infection may consolidate to form an abscess.
It may spread through the vascular emissaries into
the cavernous sinus or intracranially, causing
cavernous sinus thrombosis, meningitis, carotid
occlusion and subdural, epidural or brain abscess.
Pathological features of orbital cellulitis are similar
to suppurative inflammations of any part of the body.
Following factors play additional role in causation
of the pathology:
i. Due to absence of lymphatic system, the
protective agents are limited to local
phagocytic elements provided by the orbital
reticular tissue,
ii. Due to tight compartments, the intraorbital
pressure is raised which augments the virulence
of the infection causing early and extensive
necrotic sloughing of the tissues and
iii. As in most cases infection spreads as thrombo-
phlebitis from the surrounding structures, a
rapid spread with extensive necrosis is the rule.
Microbiology
Bacteria
It is often difficult to determine the causative orga-
nism, therefore all cultures must be interpreted
cautiously. Information can be gained from blood
cultures, conjunctival culture, nasopharyngeal culture,
cultures of aspirate of the leading edge of spreading
cellulitis, and cultures of sinus aspirates.
Furthermore, patients who were previously
treated with antibiotics may have negative cultures,
despite demonstrably purulent sinus infection.14
In children with orbital cellulitis preponderant
organisms isolated by sinus aspiration are Staphylo-
coccus aureus, Streptococcus species and anaerobic species.17
In adults, S. aureus, E. coli, Streptococcus pneumoniae,
and mixed flora including anaerobes are the most
common organisms responsible for orbital cellulitis.
Other organisms, which have also been reported
to cause the orbital cellulitis, are Enterococcus, Echin-
ococcus granulosus, Pseudomonas aeruginosa, Klebsiella
species, E. coli, Treponema pallidum,19 Eikenella Corro-
dens,20 Mycobacterium tuberculosis21 and M. avium. H
influenzae is most commonly seen in children younger
than age 4 and is rare after that age.
Conjunctival and nasopharyngeal cultures contain
mixed flora, do not correlate accurately with blood
culture results and are believed to be misleading in
orbital cellulitis.22 Despite this, cultures must be
obtained since they may indicate a predominant
organism or a refractory organism that may explain
persistent or deteriorating clinical picture.
Fungi
Fungi can also enter the orbit especially in diabetics
and immunocompromized patients. Clinically signifi-
 Chapter 90: Orbital Cellulitis
cant causative fungi are Phycomycetes (Mucor) and
Ascomycetes (Aspergillus species). Mucormycosis is
widespread in distribution, while aspergillosis is
more commonly seen in warm humid climates. Mucor
is typically found in diabetics.
Parasites
Parasitic diseases common in endemic areas include
the infections with Echinococcus granulosus, Taenia
solium, Trichinella spiralis, and Toxoplasma gondii.
CLINICAL FEATURES
Symptoms
Orbital cellulitis may present with pain, globe
displacement, diplopia or vision loss. Other associated
symptoms may be fever, headache, malaise, nausea,
vomiting and prostration.
In children, fever occurs in 62 percent of the
patients while in adults, it may be absent in 66 percent
cases.23
Significant past medical history may include:
• History of headache, rhinitis, sinusitis, polyposis,
nasal discharge, anosmia or recent upper respi-
ratory tract infection.
• History of prior orbital fracture or of orbital
fracture surgery with implantation of alloplastic
materials.
• History of prior ophthalmic surgeries, e.g. DCR,
history of strabismus surgery or scleral buckling
procedures.
• History of prior surgery of eyelids or facial
skeleton with insertion of wires, rigid internal
fixation, alloplastic plates or non-dissolving suture
material.24
• History of recent dental work, specifically dental
extractions.25
• Past medical history significant for HIV, diabetes,
steroid use, renal disease and travel is important.
Signs
• Lid edema Lid edema in orbital cellulitis is secon-
dary to a decrease in venous outflow (through
infected orbit); therefore, edema may be occasio-
nally cool, doughy and nontender. However,
when orbital cellulitis follows preseptal cellulitis,
the edema caused by an infection of subcutaneous
tissue is present. The edema is brawny, tender
691
and taut.
• Chemosis of conjunctiva is usually marked, which
may protrude and become desiccated or necrotic.
• Proptosis is usually axial and rapidly progressive.
• Restriction of eye movements varying from mild to
severe is usually present.
• Intraocular pressure may be raised.
• Visual impairment may occur rapidly.
COMPLICATIONS
Complications are quite common if orbital cellulitis
is not treated promptly and include:
• Optic neuropathy, when occurs, is characterized by
pupillary findings of a relative afferent pathway
defect (RAPD) and optic nerve head findings such
as optic disk edema.
• Central retinal vein occlusion (CRVO) or even Central
retinal artery occlusion (CRAO) may occur with the
increase in orbital pressure.
• Exposure keratitis and corneal ulceration may result
due to marked chemosis and proptosis not
allowing the lids to close.
• Intraocular spread of infection is characterized by
hypotony, choroidal folds and anterior segment
inflammation with hypopyon.
• Subperiosteal or orbital abscess formation may occur
in 7 to 9 percent cases.
• Orbital apex syndrome, characterized by signs of
3rd, 4th and 6th nerve involvement and anesthesia
in the region supplied by the ophthalmic division
of trigeminal nerve, occurs when infection spreads
to the orbital apex.
• Cavernous sinus thrombosis (1%) may occur when
the infection spreads posteriorly through the
superior orbital fissure. Cavernous sinus thrombo-
sis manifests with bilateral symptoms, bilateral
orbital apex syndrome, ophthalmoplegia, pro-
ptosis and corneal anesthesia.
• Brain abscess or meningitis (2%) can result from any
stage of orbital infection.
• Septicemia or pyemia and even death can occur
sometimes.
DIFFERENTIAL DIAGNOSIS
Orbital cellulitis sometimes may need to be
differentiated from thyroid eye disease, idiopathic
inflammatory orbital pseudotumor, orbital myositis,26
orbital abscess,27 ruptured dermoid cyst, necrotic
692 Section 6: Diseases of Orbit
intraocular melanoma, orbital trauma, orbital foreign
body, orbital vasculitis, Wegener’s granulomatosis,
carotid- cavernous fistula, rhabdomyosarcoma,
mucormycosis, sarcoidosis and allergic reactions.
Retinoblastoma28 sometimes presents with orbital
cellulitis type of picture, which requires early
diagnosis and treatment.
LABORATORY AND IMAGING STUDIES
Laboratory Studies
a. Complete hemogram with TLC, DLC. Leukocytosis
more than 15000 with a shift to the left is
commonly seen29
b. Blood culture is obtained prior to the administration
of any antibiotics, although they are unlikely to
reveal the causative organisms. Purulent material
is also collected from the nose with a cotton or
calcium alginate swab, smeared for gram stain,
and cultured on both aerobic and anaerobic media.
Cultures of the leading edge of the cellulitis are
performed if there is an obvious sign of an entry
wound responsible for the cellulitis. Needle
aspiration of the orbit is contraindicated.
c. ESR may be elevated in orbital cellulitis.
d. Antistreptolysin O (ASO titer) may be elevated, if
the infection is from α-hemolytic streptococcus.
Imaging Studies
Ultrasound
Ultrasound in orbital cellulitis is useful in ruling out
orbital myositis, in determining the location of orbital
foreign bodies or abscesses, and in follow-up of
patients with drained orbital abscesses to rule out
reaccumulation.
Ultrasound is not helpful in distinguishing
inflammatory transudate from infectious exudates or
hemorrhage.
CT Scan
High resolution CT scan, including axial and coronal
views, is essential. If orbital cellulitis has resulted
from the adjacent intercurrent sinus infection, then
the extent of sinus disease can be estimated on CT
scan. Sinuses may show features of osteomyelitis with
blurring of the osseous margins of the sinuses, air
fluid levels or inflammatory tissue within the
normally aerated sinus.29
In orbital cellulitis, an extraconal or intraconal
mass may be present. With intraconal involvement;
proptosis is seen with obliteration of the normal soft
tissue shadows. “Patchy enhancement” of the intra-
conal fat in orbital cellulitis has been described.30
The rectus muscles, particularly the medial rectus,
and the optic nerve may be thickened.
Magnetic Resonance Imaging (MRI)
On MRI with gadolinium contrast enhancement,
orbital cellulitis may show a smearing or a linear
streaking of the normal fat shadows on T2-weighted
images. MRI is superior to CT in the diagnosis of
cavernous sinus thrombosis. Both CT and MRI can
help in the planning of surgery and in the evaluation
of efficacy of treatment.
Other Tests
a. Fiberoptic nasopharyngeal endoscopy: It is done if any
suspicion of mucormycosis exists.
b. Rapid Plasma Reagin (RPR) is particularly required
in cases of insidious onset or those with a history
of syphilis.
MANAGEMENT
1. Antibiotics: Prompt administration of appropriate
antibiotics is the key to successful treatment of
orbital cellulitis. After appropriate work up, all
periorbital and orbital infections should be treated
with broad spectrum antimicrobial agents in the
hospital setting. Antibiotics may be altered after
culture results. Intravenous administration is the
preferred route.
The appropriate antibiotic choice should be
made in consultation with the internist or pediatri-
cian, whose help will also be invaluable in determi-
ning the presence or absence of other systemic
findings, in guiding fluid and electrolyte therapy
and in the management of any other concomitant
medial problems.
The patients should be treated with parenteral
antibiotics until they show clear evidence of
clinical improvement as manifested by a decrease
in orbital congestive signs such as proptosis, gaze
limitation, and edema.
Intravenous therapy should continue for a
minimum of 3 days. Oral antibiotic therapy may
then be instituted for a total course of 10 days to
3 weeks, depending on the severity of infection.
 Chapter 90: Orbital Cellulitis 693
Table 90.1: Antibiotics for treatment of bacterial orbital cellulitis
Age Drugs Used Efficacy of the drug used
In children younger — Ticarcilline-Clavulanic acid 200-300 mg/kg/day Effective against
than age of 4 years in four divided doses — H. influence
— Cefotaxime 80-120 mg/kg/day in four — S. aureus and
divided dose Streptococcus
— Cefuroxime 75-150 mg/kg/day in three
divided doses
In patients allergic to — Clindamycin 24-40 mg/kg every 6 hrs
penicillin — Chloramphenicol 50-100 mg/kg every 6 hrs
In adults — Cefuroxime 750 mg-1.5 mg every 8 hours Effective against most of
— Ceftriaxone 1-2 g/day gram positive of gram
positive and gram negative
organisms except pseudomonas,
methicillin resistant staphylococcus,
many strains of group D Streptococci.
To the above add metronidazole 15 mg/kg over
1 hour fooled by 7.5 mg/kg over 1 hr. every 6 hrs.
After loading doses

Associated bacteremia, however, should be
treated with 7 to 10 days of intravenous therapy.
Treatment regimens vary, depending on
whether the infection is from a cutaneous or
metastatic source; on the age of the patients;
patient’s culture results and immune status.
Once the congestive and orbital inflammatory
signs diminish, oral antibiotics can be substituted.
In patients with cutaneous cellulitis, Dicloxacillin,
25-40 mg/kg/day in four divided doses can be
substituted for Nafcillin. Alternatively, Cefaclor
40 mg/kg/day in divided doses every 8 hours
and Amoxicillin + clavulanate potassium 40 mg/
kg/day in divided doses every 8 hours can be
substituted (Table 90.1).
During intensive antibiotic therapy, a careful
follow-up is needed in all patients. This includes
twice daily examination with attention to visual
acuity, confrontation visual fields, exophthalmo-
metry, motility and pupillary examinations.
2. Anti-inflammatory drugs and analgesics are helpful
in controlling pain and fever.
3. Nasal decongestants are used to drain the sinuses.
4. Other measures useful in management are:
• Some authors suggest the use of cool com-
presses to reduce swelling while the others
suggest the use of warm compresses to
facilitate vascular dilatation and hence delivery
of antibiotics.
• Head end elevation may hasten the resolution
of periorbital edema.
• Patients with severe proptosis and exposure
may require lubrication of the ocular surface
as well as the use of plastic wrap or exposure
bubbles to manage nocturnal exposure due to
lagophthalmos.
Surgical Intervention
Indications
Indications for surgery in orbital cellulitis include:
• Suspicion of orbital abscess or foreign body,
• Progression of visual loss,
• Extraocular motility deficit,
• Worsening proptosis despite appropriate medical
therapy after 24-48 hour period,
• Size of the orbital abscess does not reduce on CT
scan within 48-72 hours after antibiotic therapy.
Timing
Timing for surgical intervention is critical. In cases
of orbital cellulitis without abscess formation, in
which visual acuity is 20/60 or lesser declines with
appropriate medical management, orbital exploration
should be emergent. In cases in which the acuity is
better than 20/60, the patient should be followed
seriously, expectantly and frequently while more
conservative management is initiated.
Procedures
Surgical procedures include:
694 Section 6: Diseases of Orbit
• A free incision should be made into the abscess
when it points under the skin or conjunctiva.
• Subperiosteal abscess is drained by 2-3 cm curved
incision in the upper medial aspect.
• In most cases it is necessary to drain both the
orbits as well as the infected paranasal sinuses.
• If brain abscesses develop and do not respond to
the antibiotic therapy, craniotomy is indicated.
MORTALITY/MORBIDITY
Prior to the development of antibiotics, patients with
orbital cellulitis had mortality rate of 17 percent; and
20 percent of the survivors were blind in the affected
eye. However, with prompt diagnosis and use of anti-
biotics, this rate has been reduced significantly.
MEDICAL/LEGAL PIT FALLS
Orbital cellulitis should be suspected in any patient
with adnexal, facial or dental infection when orbital
pain, proptosis, limitation of ocular motility, lid
edema, or orbital congestion develops. Failure to
consider the diagnosis is the most common medico-
legal problem. Immediate CT scan should be
obtained and the patient should be placed on broad-
spectrum intravenous antibiotic therapy as deemed
appropriate.
REFERENCES
1. Bergin DJ, Wright JE. Orbital cellulitis. Br J Ophthalmol
1986;70:174.
2. Schramm VL Jr, Curtin HD, Kennerdell JS. Evaluation of orbital
cellulitis and results of treatment. Laryngoscope 1982;92:732-
38.
3. Watters EC, Wallar H, Hiles DA, et al. Acute orbital cellulitis.
Arch Ophthalmol 1976;94:785.
4. Gellady AM, Shulman ST, Ayoub EM. Periorbital cellulitis in
children. Pediatrics 1978;61:272.
5. Chandler JR, Langenbrunner DJ, Stevens ER. The pathogenesis
of orbital complications in acute sinusitis. Laryngoscope
1970;80:1414.
6. Schramm VL Jr, Myers EN, Kennerdell JS. Orbital compli-
cations of acute sinusitis: Evaluation, management and
outcome. Trans Am Acad Otolaryngol. 1978;86:221.
7. Gans H, Sekula J, Wlodyka J. Treatment of acute orbital
complications. Arch Ophthalmol 1974;100:329.
8. Molarte AB, Isenberg SJ. Periorbital cellulitis I infancy. J
Paediatr Ophthalmol Strabismus 1989;26:232.
9. Batson OV. Relationship of the eye to the paranasal sinuses.
Arch Ophthalmol 1936;16:322.
10. Jackson K, Baker SR. Clinical implications of orbital cellulitis.
Laryngoscope 1986;96:568.
11. Rubinstein JB, Handler SD. Orbital and periorbital cellulitis in
children. Head Neck Surg 1982;5:15.
12. Krohel GB, Kraus HR, Winnick J. Orbital abscesses: Presentation,
diagnosis, therapy and sequelae. Ophthalmology 1982;89:492.
13. Shapiro ED, Wald ER, Broznski BA. Periorbital cellulitis and
paranasal sinusitis: A Reappraisal. Paediatr Infect Dis J
1982;1:91.
14. Williamson-Nobel FA. Diseases of the orbit and its contents
secondary to the pathological conditions of the nose and the
paranasal sinuses. Ann R Coll Surg 1954;15:46.
15. Wilson ME, Paul TO. Orbital cellulitis following strabismus
surgery. Ophthalmic Surg 1987;18:92.
16. Janakrajah N, Sukumaran K. Orbital cellulitis of dental origin:
Case report and review of literature. Br J Oral Maxillofac Surg
1985;23:140.
17. Weiss A, Friendly D, Eglin K et al. Bacterial periorbital and
orbital cellulitis in childhood. Ophthalmology 1983;90:195.
18. Quick CA, Payne E. Complicated acute sinusitis. Laryngo-
scope 1972;1248.
19. Bergin DJ, Wright JE. Orbital cellulitis. Br J Ophthalmol
1986;70:174.
20. Hemady R, Zimmerman A, Katzen BW, et al. Orbital cellulitis
caused by Eikenella corrodens. Am J Ophthalmol
1992;114:584.
21. Smith TF, O’Day D, Wright PF. Clinical implications of
preseptal cellulitis in childhood. Pediatrics 1978;62:1006.
22. Gamble RE. Acute inflammations of the orbit in children. Arch
Ophthalmol 1933;10:483.
23. Steinkuller PG, Jones DB. Microbial preseptal and orbital
cellulitis. In Tasman W (Ed): Clinical Ophthalmology.
Philadelphia: Lippincott, Williams and Wilkins 1999;1-8:17-
29.
24. Jordan DR, St Onge P, Anderson RL et al: Complications
associated with alloplastic implants used in orbital fracture
repair. Ophthalmology 1992;99:1600.
25. Bullock JD, Fleishman JA. The spread of odontogenic infections
to the orbit: Diagnosis and management. J Oral Maxillofac
Surg 1985;43:749.
26. Bach MC, Knowland M, Schuyler WBJ. Acute orbital myositis
mimicking orbital cellulitis. Ann Intern Med 1988;109:243.
27. Hornblass A, Herschorn BJ. Orbital abscess, Survey
Ophthalmol 1984;29:169.
28. Shields JA, Shields CL, Suvarnamani C et al. Retinoblastoma
manifesting as orbital cellulitis. Am J Ophthalmol 1991;
112:442.
29. Jones DB, Steinkuller PG: Strategies for the initial management
of acute preseptal and orbital cellulitis Trans Am Ophthalmol
Soc 1988;86:94;discussion108.
30. Goldberg F, BerneAS, Oski FA. Differentiation of orbital
cellulitis from preseptal cellulitis by computed tomography.
Pediatrics 1978;62:1000.
 Chapter 91
Painful Ophthalmoplegia
Subhra Das, LC Dutta
Some neuro-ophthalmic disorders presenting with
ophthalmoplegia and cephalic pain are grouped as
painful ophthalmoplegia. They frequently cause
vexing problem to the ophthalmologist and not infre-
quently a neurologist’s help is sought in establishing
the correct diagnosis and help in its management. This
group includes the following conditions:
Nasopharyngeal tumor,
Tolosa-Hunt syndrome
Gradenigo’s syndrome
Giant cell arteritis
Raeder’s paratrigeminal syndrome
Ophthalmoplegic migraine
Parasellar syndrome (Pituitary apoplexy)
Aneurysm of posterior communicating artery of
circle of Willis.
NASOPHARYNGEAL TUMORS
Tumors originating from the roof of the nasopharynx
infiltrate the parapharyngeal space through various
foramina and fissures to invade the base of the skull,
middle cranial fossa, accessory nasal sinuses, superior
and inferior orbital fissure, cervical lymph nodes, and
cervical sympathetic chain.1,2
These tumors are common in the age group of 40
to 60 years but not uncommon in children also. The
nasopharyngeal tumors are mostly malignant. Some
tumors like nasopharyngeal fibroma may produce
symptoms even before malignant changes occur.
Histopathologically, the nasopharyngeal tumors may
be fibroma, squamous cell carcinoma, reticullum cell
sarcoma, and lymphoepithelioma. These tumors
rarely present with nasopharyngeal symptoms.
Twenty-five percent of the nasopharyngeal tumors
present with only ophthalmic manifestation and 35
percent of the cases are found to have neuro-
ophthalmic findings. The usual route of spread of the
tumor from the nasopharynx to the orbit is through
the superior orbital fissure after it has entered the
middle cranial fossa through the basal foramina.
Clinical Features
Diplopia is the earliest and most common presenting
feature. 3rd, 4th, 6th, and ophthalmic division of 5th
cranial nerves are commonly involved. Facial pain
with horizontal diplopia is an important diagnostic
feature. 50 percent of the patients develop ENT
symptoms like loss of hearing, sense of ear plugging
or fullness, as the tumor mass involves the eustachian
tube and nasal sinuses.3 9th, 10th and 11th cranial
nerves may be involved in different combination in
varying degree in different stage of the pathology.
Horner’s syndrome may develop due to damage
of the oculosympathetic pathway. In most cases (10
to 30%) visual loss occurs late in course of the disease
as one or both optic nerves are affected either in the
cranial cavity or in the orbit. Papilledema is rare but
optic atrophy is common. Another cause of visual loss
is due to neurotrophic keratitis due to paralysis of the
ophthalmic division of the trigeminal nerve. Proptosis
may develop in 6 percent of the cases due to extension
of the tumor into the orbit.
CT scan, MRI, and sometimes biopsy of enlarged
lymph nodes help to confirm the diagnosis.
TOLOSA-HUNT SYNDROME
Tolosa-Hunt syndrome is a variant of acute infla-
mmatory pseudotumor affecting the cavernous sinus
or superior orbital fissue. This is characterized by
severe unilateral periorbital pain or hemicrania,
696 Section 6: Diseases of Orbit
oculomotor nerve paralysis, pupillomotor dysfunc-
tion, and sensory loss in the area of supply by 1st and
2nd divisions of trigeminal nerve. These nerves are
affected in the cavernous sinus or on their way upto
the orbital apex. Vision may be affected due to involve-
ment of optic nerve at the orbital apex.4
Pathology of this condition is orbital periosteitis
with granulomatous vasculitis in the cavernous sinus
and angiographically demonstrated carotid peri-
arteritis. Histopathological study shows lymphocytes,
epitheloid cells and giant cells.
Clinical course of the condition is characterized by
(a) remission and relapse, (b) high ESR, and (c) prompt
response to steroid. These criteria help to differentiate
Tolosa-Hunt syndrome from cavernous sinus throm-
bosis, aneurysm and invasive tumors from the
paranasal sinuses.
GRADENIGO’S SYNDROME
This condition is characterized by sixth nerve paralysis
associated with severe trigeminal pain due to
suppurative process of otitis media. This syndrome
was first described by an Italian otologist Gradenigo
in 1904.
It is due to involvement of the apex of the petrous
part of the temporal bone secondary to chronic masto-
iditis or middle ear infection. At this site the sixth
cranial nerve and inferior petrosal sinus run within a
common dural sheath known as Dorello’s canal which
opens into the cavernous sinus. Edema resulting from
the meningeal inflammation compresses the nerve and
causes paresis within 4 to 6 weeks of onset of the otitis
media. Pain is due to contiguous inflammation of the
Gasserian ganglion. CT scan is very helpful for
diagnosis of this condition.5
GIANT CELL ARTERITIS
Giant cell arteritis, also called temporal arteritis or
cranial arteritis is due to autoimmune connective
tissue disorder affecting the internal elastic lamina and
tunica media of middle sized predominantly
extracranial arteries of the carotid system and
sometimes the aorta and its primary branches. It is
common in elderly people of 70 years or above.
Females are more commonly affected than males in
the ratio of 2:1.
Clinical Features
a. Nonophthalmic symptoms These include headache,
jaw claudication often precipitated by chewing or
talking, polymyalgia, fever, anorexia, unwanted
weight loss, malaise, neck pain, and severe scalp
tenderness. Headache often followed by intense
pain on the temporal region with swollen and
tender temporal artery which is a characteristic
presentation.6
b. Ophthalmic symptoms These include prodromal
transient attacks of amaurosis followed by sudden
loss of vision in one eye. The second eye is affected
within few days or weeks if left untreated.
Diplopia may develop in 10 percent of the cases
due to infarction of the extraocular muscles. Visual
field defects vary from complete loss of vision to
central, altitudinal or arcuate type of field defects.
Ophthalmoscopic examination in the initial stage
may not reveal any abnormality; however, in late
stage pale swollen optic disk with peripapillary
splinter hemorrhage and soft exudates may
present. There may be also optic atrophy with neo-
vascularization of the optic disk in late and
recurrent cases.7,8
Pathology
Histopathological examination of the affected
temporal artery shows granulomatous inflammation
with epitheloid cells, lymphocytes, and giant cells.
Fragmentation or disruption of the internal elastic
lamina leads to reduction in size of the lumen of the
arteries due to edema of the intima.
Diagnosis
Diagnosis is usually made on the basis of high ESR
(40-130 mm) and more definitely by temporal artery
biopsy. High concentration of C-reactive protein is
present in temporal arteritis (4.35 mg/dL).
Treatment
Giant cell arteritis is an ophthalmic emergency; early
diagnosis and treatment is essential to prevent further
vascular occlusion. It exquisitely responds to steroid
therapy and may restore the vision almost completely
but there is every likelihood of recurrence. The dose
of steroid is to be titrated with repeated estimation of
ESR level.
RAEDER’S PARATRIGEMINAL SYNDROME
This syndrome is common in middle aged men having
severe unilateral facial pain similar to that of tic
 Chapter 91: Painful Ophthalmoplegia
dolourex, along the 1st and 2nd division of trigeminal
nerve associated with ocular sympathetic paralysis
(postganglionic Horner’s syndrome). 9,10 Nasal
stuffiness and conjunctival congestion may also be
present. Most of the patients give history of throbbing
headache of variable intensity lasting for many years
and resolving spontaneously. The mechanism of
Raeder’s syndrome is believed to be similiar to cluster
headache although it may not have its cyclical pattern.
Two basic types of Raeder’s syndrome are:
a. Raeder’s type I—consists of multiple cranial nerves
involvement (3rd, 4th, 5th, 6th) in addition to
headache and Horner’s syndrome.
b. Raeder’s type II—includes only hemicrania and
ipsilateral ocular sympathetic paresis.
Involvement of cranial nerves with neurological
deficits suggests that etiology of Raeder’s syndrome
is a result of middle cranial fossa lesion like pituitary
adenoma, chondroma, meningioma, and aneurysm of
internal carotid system. A complete neuroradiological
investigation is necessary to exclude such lesions.
OPHTHALMOPLEGIC MIGRAINE
Ophthalmoplegic migraine is a rare form of migraine
complicated by third and sixth cranial nerve palsy. It
is found predominantly in children and young adults.
It is sometimes called Mobius disease or trigeminal
ophthalmoplegic syndrome.
The ophthalmoplegia usually starts at the height
of the attack of headache or after its cessation.
Sometimes with the onset of ophthalmoplegia the
headache disappears. Initially, transient ophthalmo-
plegia lasts for 1 to 4 weeks, but after repeated attacks
permanent oculomotor nerve paralysis results.
Presumably intense vascular spasm affects the optic
nerve and retinal vessels. Retinal hemorrhage,
attenuation of retinal arterioles, disk edema and
peripapillary hemorrhages are common association of
retinal and optic nerve ischemia.11 Congruous type of
contralateral homonymous hemianopia may also
develop due to occlusion of the calcarine branch of
posterior cerebral artery supplying the visuosensory
cortex.
The diagnostic criteria of ophthalmoplegic
migraine are the following:
a. Onset at the first decade of life.
b. History of multiple typical episodes.
c. Ipsilateral ophthalmoplegia.
d. Negative sign in CT scan and angiography.
697
A complete neuroradiological investigation may
be necessary to rule out an aneurysm, a rare cause of
third nerve palsy in children, before diagnosis is
confirmed.
PARASELLAR SYNDROME
(PITUITARY APOPLEXY)
Many lesions adjoining the sella turcica involve the
sensory and motor nerves in the cavernous sinus.
Pituitary apoplexy occurs as a result of infarction or
hemorrhage into a pituitary adenoma which has
outgrown its blood supply.12 It may be precipitated
by radiation therapy, trauma, and pregnancy. It is
characterized by acute onset of headache, unilateral
or bilateral ophthalmoplegia, bilateral amaurosis,
drowsiness or coma, and subarachnoid hemorrhage.
The CSF shows blood xanthochromia, pleocytosis, or
elevated protein, and sometimes CSF may be normal.
Headache is usually of sudden onset and may be
generalized or only retrobulbar. Unilateral or bilateral
ophthalmoplegia is due to involvement of 3rd, 4th,
and 6th cranial nerves in the cavernous sinus. The
classical triad of pituitary apoplexy is headache,
diplopia, and sub-arachnoid hemorrhage. Diagnosis
is confirmed by CT scan and MRI. Pituitary apoplexy
should be differentiated from chiasmal apoplexy; in
the latter condition the visual loss results from
hemorrhage from an intrachiasmal vascular malfor-
mation of blood vessel or into an optic glioma.
Chiasmal apoplexy is recurrent; surgical evacuation
of the hemorrhage or complete removal of the tumor
may be necessary.
Pituitary apoplexy is a life-threatening condition
and needs prompt treatment. High dose of corti-
costeroid with careful monitoring and stabilization of
electrolyte balance is needed. In cases where severe
visual loss, mental impairment or progressive
deterioration occurs, surgical removal of hematoma
or tumor is indicated through transcranial or
transsphenoidal route.
Carotid Cavernous Aneurysm
Aneurysm of the carotid artery inside the cavernous
sinus presents predominantly with orbital pain and
diplopia. This condition also causes cavernous sinus
syndrome which consists of ophthalmoplegia, Hor-
ner’s syndrome, upper facial hyposthesia and periorbi-
tal pain. These syndromes are caused by compression
of the various contents of the cavernous sinus, viz.
698 Section 6: Diseases of Orbit
third, fourth and sixth nerves, ocular sympathetic
system and the ophthalmic branch of the fifth cranial
nerve. The first nerve to be involved is the sixth cranial
nerve because of its close relation to the artery in the
inferior part of the cavernous sinus. Pain along the
distribution of the first division of the fifth nerve is
the most common manifestation of early trigeminal
nerve involvement and complete anesthesia of the
supplied by the nerve results. After chronic compres-
sion neurotrophic keratopathy is an associated
manifestation of fifth nerve compression. Visual
blurring could be due to paralysis of accommodation
resulting from 3rd nerve involvement and visual
pathway compression. Proptosis is a late complica-
tion, this is mainly due to compression of the venous
channels interfering with drainage of the venous blood
to the sinus from the orbital content leading to
engorgement of the orbital veins; which may also
cause secondary glaucoma due to raised episcleral
venous pressure.
Imaging procedures: Only MRI is useful to confirm
diagnosis of cavernous sinus syndrome due to carotid
artery aneurysm in the cavernous sinus.
ANEURYSM OF POSTERIOR COMMUNICATING
ARTERY OF CIRCLE OF WILLIS
Aneurysms are common near the origin of the
posterior communicating artery and at the termination
of the internal carotid artery. Due to sudden increase
in size of aneurysm or hemorrhage there is compre-
ssion of the oculomotor nerve which lies adjacent to
posterior communicating artery.13 The diagnostic
clues include the following:
a. Common in elderly females between the age of 50
and 70 years with a history of hypertension.
b. In 90 percent of the cases pain precedes ophthal-
moplegia due to paralysis of third nerve.
c. Pain may be localized in the area supplied by first
division of trigeminal nerve.
d. Associated pupillary dilatation is due to affection
of pupilloconstrictor fibers of the 3rd cranial nerve.
Diagnosis may be confirmed by carotid angio-
graphy, but it should not be done within one month
of development of symptoms. CT scan is usually
helpful in diagnosis of aneurysm. The symptoms of
severe unilateral frontal headache along with diplopia
suddenly followed by ipsilateral visual loss should
be considered to be due to leaking aneurysm of circle
of Willis, unless proved otherwise.
REFERENCES
1. American Academy of Ophthalmology, Section 5, Neuro-
ophthalmology 1982-83;132-35.
2. Neil R, Miller R (Eds). Walsh and Hoyt’s Clinical Neuro-
ophthalmology (4th edn). Williams and Wilkins: Baltimore,
1988;4:1670.
3. Godfreson E, Lederman N. Diagnostic and prognostic signs
and symptoms in malignant nasopharyngeal tumors. Am J
Ophthalmol 1965;59:1063.
4. Smith J, Taxad D. Painful ophthalmoplegia. The Tolosa-Hunt
syndrome. Am J Ophthalmol 1966;61:1466.
5. Raynolds D Maurice. Principles of Neurology (5th edn).
Mcgraw Hill Information Services Company, Mcgraw-Hill
Book Company, Singapore.
6. Keltner JL. Giant Cell Arteritis: Signs and symptoms. Ophthal-
mology 1982;89:1101.
7. Miller NR. Walsh and Hoyt’s Clinical Neuroophthalmology
(4th ed). Williams and Wilkins: Baltimore, 1998;2601-27.
8. Liu GT, Glasser JS et al. Visual morbidity in giant cell arteritis.
Ophthalmology 1994;101:1779-85.
9. Boniuk M, Schezinger NS. Raeder’s paratrigeminal syndrome.
Am J Ophthalmol 1962;54:1074.
10. Grimson BS, Thompson HS. Raeder’s syndrome: A clinical
review. Surv Ophthalmol 198;24:199.
11. McDonald WI, Sander MD. Migraine complicated by ischemic
pupillopathy. Lancet 1980;2:521.
12. Miller NR. Walsh and Hoyt’s Clinical Neuroophthalmology
(4th ed). Williams and Wilkins: Baltimore, 1988;1452.
13. Helper RS, Cantu RC. Aneurysm and third nerve palsies. Arch
Ophthalmol 1967;77:604.
 Chapter 92
Thyroid Ophthalmopathy
Subhra Das, LC Dutta
Involvement of the eye in thyroid disorder has
evoked immense interest among the ophthalmologist
since Robert Graves in 1835, first noticed the
association of exophthalmos in patients suffering from
hyperthyroidism. The ophthalmopathy may be
present in hyperthyroid, hypothyroid or even in
euthyroid states. As many as 13 terms have been used
to describe the characteristic ophthalmic
manifestations that may accompany Graves’ disease,
hypothyroidism or Hashimoto’s thyroiditis (Table
92.1). Sometimes thyroid ocular findings including
proptosis or exophthalmos, eyelid retraction, lid lag,
restrictive ocular myopathy or optic neuropathy can
occur without any objective evidence of thyroid
dysfunction. This condition is known as euthyroid
Graves’ disease. However, this may be attributed to
inadequate sensitivity and specificity of available
laboratory tests.
BASIC PHYSIOLOGY OF THYROID HORMONE
The normal weight of the thyroid gland is 20 to
25 gm. It is composed of multiple lobules, each
Table 92.1: Descriptive terms of thyroid ophthalmopathy
Euthyroid ophthalmopathy
Thyrotoxic exophthalmos
Endocrine exophthalmos
Malignant exophthalmos
Progressive exophthalmos
Exophthalmic ophthalmoplegia
Hyperophthalmopathic form of Graves’ disease
Edematous exophthalmos of endocrine origin
Infiltrative ophthalmopathy
Exophthalmic goiter
Thyrotropic exophthalmos.
supplied by an end artery .Each lobule is a
congregation of about 40 follicles each measuring
about 300 millimicron. The follicles are lined with
single layer of cubical epithelium. The resting follicles
contain colloid in which thyroglobulin is stored. The
thyroid hormones triiodothyronine (T 3 ) and
thyroxine (T 4 ) are formed and bound to
thyroglobulin within the colloid. The synthesis of
hormones in thyroid gland occurs in the following
stages:
• Trapping of inorganic iodine from blood.
• Oxidation of iodide to iodine and binding of
iodine with tyrosine to form iodotyrosine.
• Coupling of monoiodotyrosine and diiodotyrosine
to triiodothyronine
• (T3), and thyroxine (T4).
When hormones are required the complex is
absorbed into the cell and thyroglobulin is broken
down. T3 and T4 are released into the blood stream
where they are bound to serum proteins.
The process of synthesis and liberation of the
hormones is under the control of thyroid stimulating
hormone (TSH) from the anterior pituitary gland
which in turn is regulated by thyrotropin releasing
hormone (TRH) from the hypothalamus.
TRH, a tripeptide of hypothalamus origin,
stimulates the secretion and synthesis of TSH, by
binding to thyrotroph cells in the anteromedical
portion of adenophysis. This action is inhibited by
free T3 and T4 hormones which reduce the number
of available TRH receptors on the pituitary
thyrotrophs and diminish the TSH secretion. TSH, a
glycoprotein acts on the thyroid gland where it
stimulates thyroid iodine metabolism leading to
synthesis and secretion of thyroid hormones. This
700 Section 6: Diseases of Orbit

action of TSH results from binding to TSH receptors

on the membrane of follicular cells and subsequent
activation of plasma membrane.
Adenylate cyclase . In hyperthyroidism high levels
of serum T3 and T4 suppress the TSH secretion and
in hypothyroidism it stimulates TSH secretion1,2 (Figs
92.1 to 92.3).

GRAVES’ DISEASE (THYROID

ASSOCIATED OPHTHALMOPATHY)
The term Graves‘ disease is used to describe the
syndrome consisting of goiter, hyperthyroidism, and
often associated with eye signs. The systemic effects
of hyerthyroidism are weight loss, tremor, hyper-
tension, tachycardia, and raised BMR. Ophthal-
mopathy is present clinically in 50% of the Graves’
disease and in 5% of case it may be without clinical
or laboratory findings of hyperthyroidism. Fig. 92.1: Schematic diagram of hypothalamic
-anterior pituitary thyroid pathways
Nevertheless, clinically detectable ophthalmic
manifestations can occur in hypothyroid or
euthyroid condition. Therefore, the ophthalmic
manifestations are grouped together as Thyroid
Associated Ophthalmopathy (TAO) or Thyroid Eye
Disease (TED) rather than Graves’ eye disease.
Graves‘ disease has been defined as the presence of
one of the following three sets of characteristics:
• A history of a thyroid disorder; presence of at
least two of the following: exophthalmos, lid
retraction, muscle involvement, and positive CT
scan findings.
• The presence of exophthalmos, lid retraction, and
extraocular muscle involvement, at least two of
which must be bilateral.
Fig. 92.2: Control of T2, T3 metabolism
• Positive CT scan and at least two of the following
on at least one side: exophthalmos, lid retraction, protein, 23 kd and 66 kd fibroblast proteins, extra-
and extraocular muscle involvement.3-5 cellular matrix proteins). The nature of the primary
The exact mechanism of thyroid ophthalmopathy antigen (s) that is recognized by immunocompetent
is not known. However, there is a general acceptance cells and autoantibodies has not been definitely
that it is an autoimmune disorder. The orbital antigen identified. Candidate antigens include Thyroid
responsible for immune response has not yet been stimulating (TSH) receptor protein may be expressed
clearly identified. on orbital fibroblast and extraocular muscle antigen
It is not definite whether altered immunogenic of 64 kd.8-10
homeostatic mechanism resulting in aberrant T cell
activity toward orbital connective tissues and Epidemiology
extraocular muscles or in between both thyroid and Age and sex incidence It is mostly diagnosed at 3 rd
orbital tissue.6, 7 or 4th decade of life with female preponderance-M:F
It is uncertain whether T-cells are involved in cell 1:7.11
mediated or humoral response. Both cellular and Hereditary: A strong hereditary influence is
humoral immunity has being detected against various observed in Graves disease.12 It is relatively more
orbital antigens (e.g. 55 kd and 67 kd eye muscle common among patients with positive family history
 Chapter 92: Thyroid Ophthalmopathy 701
Lid Signs
Lid Retraction (Dalrymple Sign)

Table 92.2: Classification of ocular signs16

Class Grade Ocular symptoms and signs
N 0 no signs or symptoms
O 1 only signs, no symptoms (upper lid
retraction and stare, with or without lid
lag or proptosis)
proptosis associated with class 1 only
(difference of 3 mm or more between
eyes or progression of 3 mm or more)
Fig. 92.3: Extreme degree of bilateral lid retraction
O absent (20 mm or less)
a minimal (23 mm)
of autoimmune disorder like pernicious anemia,
b moderate (27 mm)
myasthenia gravis, rheumotoid disease, Hasimotos c marked (28 mm)
disease, etc. S 2 soft tissue involvement
HLA antigen and thyroid disease There is altered O absent
a minimal (edema of lids and conjunctiva,
incidence of HLA B 8, Bw 35, Cw 3 and HLA-DR 3 fullness of lid, conjunctival congestion,
Graves disease. orbital fat extrusion, palpable lacrimal
Tobacco smoking It increases the risk for ophthal- gland)
b moderate (above plus lagophthalmos)
mopathy.13
c marked
P 3 proptosis associated with class 2 through
Ocular Manifestations in Thyroid class 6-(difference of 3 mm between eyes
Ophthalmopathy or progression
of 3 mm or more)
Thyroid ophthalmopathy is diagnosed on the basis
O absent
of characteristic ocular finding supported by orbital a minimal (23 mm)
imaging like CT scan or echography and often a b moderate (27 mm)
history of thyroid hormone dysfunction. The thyroid c marked (28 mm)
hormone imbalance is not an absolute finding. The E 4 Extraocular muscles involvement (with
patients may have clinical evidence of hyper- diplopia)
thyroidism or euthyroidism and frequently gives a O absent
history of past treatment for hyperthyroidism. a minimal (limitation of motion at extreme
gaze)
Graves’ disease usually has its natural course of six b moderate (restriction of motion without
months to several years. Presenting symptoms are fixation of globe)
photophobia, tearing, gritty foreign body sensation, c marked (fixation of position of a globe or
ocular pain, lid edema, diplopia, blurred vision and globes)
field defects. On physical examination Graves’ C 5 Corneal involvement (primarily due to
ophthalmopathy may exhibit any one of the following lagophthalmos)
findings; eyelid retraction, eyelid lag, proptosis, o absent
a minimal (stippling of cornea)
restrictive extraocular myopathy, optic nerve
b moderate (ulceration)
compression, soft tissue swelling and thyroid c marked (necrosis and perforation)
dermatopathy (acropathy) affecting the peripheral S 6 sight loss (due to optic nerve involve-
parts of the limbs. ment)
In 1969 Werner14 formulated the classification for o absent
thyroid eye disorder for American Thyroid Asso- a minimal (v/a 6/6-6/18 disk pallor/
ciation with acronym of NOSPECS and it was further edema/or visual field defect)
b moderate (v/a 6/12-6/60, disk pallor/
modified in 1977 as shown in Table 92.2.
edema, or visual field defect)
c marked (v/a-less than 6-60).
702 Section 6: Diseases of Orbit
On looking straight forwards the normal position of
the upper eyelid is 1 to 2 mm below the superior
corneal margin. In lid retraction the upper lid margin
is at or above the superior corneoscleral limbus in
primary position without frontalis muscle contraction.
It is present in 37 to 92% of thyroid ophthalmopathy.15
Lid retraction may be unilateral. When associated
with lid lag (von Graefe’s sign) it is highly suggestive
of thyroid ophthalmopathy.16 Lid retraction may be
due to the following factors:
• In hyperthyroidism high concentration of serum
thyroid hormones increases the sensitivity of
smooth muscle of upper lid to normally circulating
adrenaline.
• Inferior rectus may be also responsible for eyelid
retraction. The superior rectus—levator muscle
complex overacts on attempted upgaze to counte-
ract the fibrotic inferior rectus muscle.
• Exophthalmos may itself can cause lid retraction
due to anterior displacement of the globe resulting
from increased orbital volume.
• Mechanical stretching of the levator palpebrae
superioris tendon due to swelling of this muscle
as well as the superior rectus muscle.17 However,
the degree of involvement of each of the factors
are difficult to assess in all cases of lid retraction.
• Retraction of lower lid also may occur but this
varies directly with the degree of proptosis.
• Pseudo- retraction of upper eyelid may occur due
to aponeurogenic ptosis of the contralateral eyelid
and in patients with diplopia caused by hypotropia
as the patient’s attempts to elevate the eye, the
lid retracts but the globe fails to elevate fully.18
Lid Edema or Fullness
Lid edema or fullness is a constant sign of thyroid
ophthalmopathy. This may be due to raised intra-
orbital pressure causing venous stasis or extrusion
of orbital fat behind the orbital septum. Conjunctival
chemosis may be of mild to severe form depending
upon the degree of raised intraorbital pressure . There
may be congestion of conjunctival vessels overlying
the insertion of rectus muscle commonly seen over
the lateral rectus.19
Superior Limbic Keratoconjunctivitis
Superior limbic keratoconjunctivitis may be present
in significant number of dysthyroid patients. Its exact
etiology is not known and it usually passes off after
about few months.20
Thyroid Myopathy
Progressive enlargement of extraocular muscle is a
constant feature in thyroid ophthalmopathy. Muscle
size may increase upto 6 to 8 times of its normal. The
pathological changes occurring in these are thought
to be due to autoimmune reaction. In thyroid
myopathy there is characteristic involvement of the
non-tendinous part of the muscles. There is infiltration
of lymphocytes, plasma cells and few mast cells with
deposition of mucopolysaccharides. The fibroblasts
present in the extraocular muscles and in orbital
connective tissue are stimulated to produce
mucopolysaccharides specifically hyaluronic acid.21
Initially only the endomysium is involved but in due
course of time the perimysium and epimysium are
also inflamed. 21 Histological examination of the
muscles in late stage of the disease shows loss of
striation of muscle fiber leading to fibrosis causing
tethering to the globe literally called Forzen Globe or
Restrictive Myopathy. The inferior rectus muscle is
most frequently involvement (60-70%) followed by
medial rectus (25%) less frequently superior rectus
and lateral rectus. 22 Rarely oblique muscles are
involved leading to cylodeviation or inflammatory
Brown’s syndrome. 23 The specific involvement of
extraocular muscles in thyroid ophthalmopathy may
be due to
a. its presence of unique sensory mechanoreceptors
b. densely innervated and greater variation of fibers
c. its rich vascular supply
Patients with thyroid myopathy often present with
unilateral or bilateral apparent elevator palsies and
vertical diplopia. Electromyography (EMG) of
extraocular muscles or Tensilon tests does not reveal
any abnormality.27, 28 CT scan and ultrasonography
show more generalized involvement of the
extraocular muscles than that can be clinically
appreciated.
IOP in Thyroid myopathy Intraocular pressure in
attempted upgaze becomes high even though it is
normal in primary position. If this difference is more
than 4 mmg of Hg, then it is confirmatory of thyroid
ophthalmopathy. This is due to restrictive myopathy
or orbital congestion.29 The IOP in primary position
also can be high in long standing case and maybe
associated with optic disk cupping.30
Exophthalmos
About 25% case of Graves’ disease and 90% of
ophthalmic Graves’ disease present with exophthal-
 Chapter 92: Thyroid Ophthalmopathy 703
mos. Clinically exophthalmos is often unilateral
though pathological infiltration is bilateral. Thirty
percent of exophthalmos in general is due to thyroid
ophthalmopathy. Proptosis in thyroid ophthalmo-
pathy maybe due to combined effect of enlargement
of the extraocular muscles or increased volume of
orbital fat. The role of the latter is unclear as some
reports demonstrated that there is no significant
change in volume or density of retrobulbar fat in
thyroid eye disease (Fig. 92.4). If the difference in
exophthalmometry reading between the two eyes is
more than 6 mm then space occupying lesion should
be suspected. The thyroid ophthalmopathy is
described as a self limiting disease but not
infrequently the infiltrative process ceases only after Fig. 92.4: Full blown case of bilateral thyroid
disorganization of the eyeball due to ulceration of ophthalmopathy
cornea resulting from severe degree of exophthal-
mos (Fig. 92.5). Increased orbital pressure results in
venous compression which thereby produce a vicious
cycle of further edema and raised intraorbital
pressure.
Vision threatening complication of Graves’ disease
results from the exophthalmos which may causes:
• Exposure keratitis leading to corneal perforation
and its complications.
• Optic neuropathy which develops in 5% of thyroid
ophthalmopathy.
The optic neuropathy is mainly due to increased
intraorbital content or by apical compression of the
nerve by the enlarged extraocular muscles.
The optic nerve damage is more likely to occur in
patients with shallow orbit or strong orbital septum
Fig. 92.5: Perforation of both the globes in last stage of thyroid
where the chances for self decompression by anterior ophthalmopathy. The proliferative process of the orbital fibrofatty
displacement of the globe is less. 31 Visual loss, tissue has ceased after globe perforation
afferent pupillary defect, Marcus Gunn pupil, field
defects, disk edema or atrophy are the features of function.
optic nerve damage.
THYROID FUNCTION TESTS
LABORATORY INVESTIGATIONS AND
Thyroid function tests which are commonly done are:
ORBITAL IMAGING
a. Estimation of serum T3 and T4 Normal level of (i)
In patients having characteristic eye signs and Total serumT3-0.12 μg/dl (ii) Total serum T4.12μ/
evidence of hyperthyroidism diagnosis of thyroid dl (iii) Free serum T3-0.28 ng/dl, and free serum
ophthalmopathy is easy. But it is difficult and T4 0.1ng/dl. Estimation of free T3 and T4 are more
problematic to establish the diagnosis when a case of representative of hormone level available to the
thyroid ophthalmopathy presents with unilateral individual body cells and is thought to give exact
proptosis or without any sign of systemic manifes- information of any abnormality of thyroid
tation of hyperthyroidism. function. In hyperthyroidism serum T 3 and T 4
It is imperative that patients with suspected
levels are raised but in some cases only T 3
thyroid ophthalmopathy should have baseline
elevation occurs known as T3 toxicosis.
laboratory tests and periodic evaluation of thyroid
704 Section 6: Diseases of Orbit
b. Estimation of serum TSH level (normal .4-5 mu/l)
This is the most useful test for screening of thyroid
patients and it also helps in follow up of patients
receiving thyroid hormone therapy.
Antithyroid antibodies This is helpful in euthyroid
patients whose clinical finding overlaps with other
disease and there are no available clinical
confirmatory tests. TSH-receptor antibodies are
present in 90% of Graves’ disease.32
Antimicrosomal antibodies are present in Hashi-
moto’s (90%) and Graves’ disease (80%). Recently
TSH binding inhibitor immunoglobulin antibody (TB
II) and thyroid stimulating antibody (TSAb) are
found as sensitive marker of Thyroid associated
ophthalmopathy.33, 34
Orbital Imaging
Computed Tomography
CT scan has become the modality of choice in
diagnosis of thyroid ophthalmopathy. CT scan shows
definite enlargement of nontendinous part of
extraocular muscle in 85% of patients with thyroid
ophthalmopathy. 35, 36 Clinically in patients with
unilateral thyroid ophthalmopathy CT scan often
shows bilateral orbital involvement.
The CT scan can detect:
a. Compression of optic nerve by the enlarged
extraocular muscles at the orbital apex,
b. Enlargement of inferior rectus muscle which can
simulate an orbital growth,
c. Normal orbital fat volume and also
d. Helps in defining the paranasal sinuses before
orbital decompression surgery.37
Magnetic Resonance Imaging (MRI)
MRI is very useful in Graves’ disease patients without
clinical thyroid disorder as it can detect the enlarge-
ment of extraocular muscles. MRI in thyroid ophthal-
mopathy can detect the compression of optic nerve
more distinctly than CT scan.38
Ultrasonography
The role of ultrasonography has become less popular
in diagnosis of thyroid ophthalmopathy due to
increasing popularity of superior imaging of CT scan
and MRI. A scan and B scan can be used to visualize
the enlargement of the extraocular muscles and the
ocular structures of interest but it has limitation to
detect lesions of the posterior orbit and the adjacent
structures.39-42
Treatment
The thyroid ophthalmopathy is usually a self-limiting
disease which may last for 1 year to many years.
Therefore, primary aim of the treatment is to arrest
the progression of the disease and once it is stabilized
treatment can be directed to the specific conditions.
Majority of the patients with Graves’ disease seek
treatment for the cosmetic appearance due to lid lag
or lid retraction, exophthalmos or immobile globe.
Treatment for Eye Lid Retraction
Cosmetic disfiguring of eyelid retraction in thyroid
ophthalmopathy may resolve spontaneously. Tempo-
rary relief may be obtained by Guanethidine eye
drops (2 or 5 %).42 Surgical correction for lid retraction
is only indicated when (a) the disease is stabilized
for 1 year (b) to prevent exposure keratitis and (c)
after orbital decompression. The various surgical
procedures are (a) recession of levator complex ( b)
surgery of lower lid retractors (c) use of spacers like
scleral grafts, autologous fascia or cartilage (d)
tarsorhaphy.43,44
Treatment for Thyroid Myopathy
Restrictive myopathy causing diplopia is a common
complication of thyroid eye disease. It may resolve
spontaneously when the systemic hyperthyroidism
is controlled or as natural course of spontaneous
remission of the eye disease. Prismatic correction is
helpful in patients with less than 3 prism diopters of
concomitant strabismus with good fusional capacity.
Surgical procedure like recession of the fibrotic muscle
(inferior rectus or medial rectus) should be done only
a) when the angle of deviation is stable for more than
6 months b) in chronic and inactive cases and c) after
orbital decompression surgery.45
Chemodenervation in thyroid myopathy Clostridium
Botulinum produces 7 endotoxin which are alphabeti-
cally numbered from A to G. Type A is used as
chemodenervation to decrease the strength of the
muscle. The recommended dose is 1.5 to 5 units of
toxin injected to the muscle. Action of the drug starts
within 1 to 3 days and lasts for about 3 months. The
action is in the motor end plate, i.e. at the neuromus-
cular junction. Instead of surgery the strabismus in
 Chapter 92: Thyroid Ophthalmopathy
thyroid ophthalmopathy can be treated by Botulinum
injection in the identified muscle.46-48 Botulinum toxin
can also be used to treat lid retraction which becomes
cosmetically unacceptable. The toxin is injected into
the Mullers muscle of the upper eye lid.45
Orbital Decompression
Orbital decompression is done in vision threatening
complication like optic nerve compression in thyroid
ophthalmopathy. This can be:
a. Medical decompression
b. Surgical decompression
Medical Decompression
This modality includes steroid therapy. Immuno-
suppressive drug therapy, and radiation therapy.
Steroid therapy Steroid has been used since 1950 for
orbital decompression but with variable results. A
high dose of steroid (150-300 mg) is found to be effec-
tive in some patients in reducing orbital inflam-
mation (The exact mechanism of action of steroid is
unclear–perhaps its anti-inflammatory and immuno-
modulatory action plays an important role. Steroid
also helps to reduce the deposition of mucco-
polysaccharides in the orbital tissue by the fibroblast.
The steroid therapy is mainly effective in:
i. Acute inflammatory eye symptoms of recent
origin.
ii. Thyroid optic neuropathy.
iii. In combination with orbital radiation or surgical
decompression.
However, the undesirable effects of long-term
systemic use of steroid like hypertension diabetes,
osteoporosis, peptic ulcer, hirsutism, infection, etc.
may limit the duration of therapy and may lead to
switch over to other measures for medical decompres-
sion.49-51
Immunosuppressive drugs A variety of immuno-
suppressive drugs have been used to treat thyroid
ophthalmopathy.52 In addition to cyclosporine, aza-
thioprine, cyclophosphamide and methotrexate have
been used in thyroid ophthalmopathy. Immunosu-
ppressive drugs seldom cure the disease but it is
usually helpful in relieving the soft tissue infla-
mmation, proptosis, and improving the extraocular
muscle dysfunction. The immunosuppressive drugs
work better if combined with steroids. For long term
maintenance cyclosporine in combination with
705
prednisolone is more effective than when either drug
given alone.53 The morbidity of immunosuppressive
drugs are many and should be given only in patients
with vision threatening complication which do not
respond to the standard treatment. The common
adverse effects of these agents are bone marrow
depression, carcinogenic effect, hepatotoxicity, renal
toxicity, gastrointestinal disturbance and infection.
Plasmapheresis is a plasma exchange therapy based
on the concepts of removal of humoral factor in an
autoimmune disease.54 However, its role in thyroid
ophthalmopathy is not yet established.
Orbital radiation is a safe and effective method of
orbital decompression in thyroid ophthalmopathy
and it has fewer side effects than steroid. Orbital
radiation is indicated in patients (a) not responding
to steroid therapy (b) when there are intolerable
steroid induced side effects and c) in patients where
steroid is contraindicated. Supervoltage radiation by
linear acceleration a total dose of 2000 rads
fractionated over 10 days is given at lateral field with
posterior angulations. Radiation is believed to
damage orbital fibroblast or lymphocytes. The effect
of radiation take few weeks to start and it may tend
to transiently increase inflammatory process so the
patients are to be maintain on steroids during the
first few weeks of radiation treatment. 55-57 It is
contraindicated in case of previous failed
radiotherapy and relatively contraindicated in
diabetes mellitus. The possible risks of radiation
therapy are radiation cataract, radiation retinopathy,
glaucoma, keratitis and mutagenic effects.
Surgical Decompression
The morbidity of surgical decompression is very high
and should be only done in case of acute thyroid
orbitopathy with vision threatening complication not
responding to non surgical therapeutic modalities.
Lately due to improvement of the technique it is also
performed in non vision threatening cases for
cosmetic improvement. The indication for surgical
decompression in thyroid ophthalmopathy are:
a. optic nerve compression
b. in ineffective medical treatment. The surgical
decompression may be done through one wall,
two, three or four walls of the orbital cavity.
Lateral wall orbital decompression ( Kronlein) The
lateral wall orbital rim consisting of frontal process
706 Section 6: Diseases of Orbit
of zygomatic bone, external angular process of frontal
and a small part of greater wing of sphenoid are
removed to accommodate the orbital content. This
procedure is not very popular because of its minimum
displacement of orbital content.58
Superior frontal decompression (Naffziger) This is best
done with the help of neurosurgeon through frontal
scalp incision. The orbital roof is removed so that
the orbital content herniates into the anterior cranial
fossa. This operation tends to produce pulsating
exophthalmos.59
Medial wall decompression This is done by removing
the ethmoidal air cells as well as part of the medial
wall and part of roof of the orbit so that the orbital
content expands into the potential space created by
it.
Inferior antral decompression Inferior orbital wall may
be removed alone or along with the medial wall
decompression, this is called antral-ethemoidal
decompression. This technique is commonly practiced
since it carries less morbidity and achieves a higher
degree of retradisplacement (3-16 mm) of the globe.
Three wall or four wall decompression is done in
cases of severe degree of exophthalmos with the help
of neurosurgeon but it has a high morbidity.59 The
main complications of orbital decompression are
meningitis, CSF-rhinorrhea, diplopia, blindness,
ptosis, epiphora, sinusitis, periorbital numbness,
globe malposition and recurrent optic nerve
compression. After the orbital decompression
surgery further medical treatment may be required
to control the disease process as the surgery has no
effect on the progress of the thyroid eye disease.
Additional surgery on extraocular muscles and eyelid
is often required to correct the postoperative
complication of orbital decompression surgery.60-62
Instead of operating upon the bony orbital wall,
the retrobulbar and peribulbar fat can be removed
through a surgical incision along the lid crease in the
medial third of the upper eyelid or lateral lower lid.
After opening the orbital septum, prolapsing orbital
fat is identified and using blunt surgical dissection
strands of fat are gently pulled out and excised. Fat
removal through inferotemporal incision is less
complicated and greater volume of fat can be remo-
ved. Proptosis of about 5 to 10 mm can be
reduced by this operation.62
REFERENCES
1. Harrison‘s Principle of Internal Medicine (14th ed). Mcgraw
Hill International Book Company: New York 1997;2012.
2. Ahuja MMS. Thyroid in textbook of medicine, Association of
Physicians of India, Bombay.
3. Devon Char. Thyroid eye disease (2nd ed). Churchill
Livingstone: New York, 1990.
4. Fruch BR. Graves eye disease, orbital compliance, and other
physical measurements. Trans Am Ophthalmol Soc 1984;
82:492.
5. Bartely GB, Gorman CA. Diagnostic criteria of Graves‘
ophthalmopathy. Am J Ophthalmol 1995;114:792.
6. Volpe R. The Pathogenesis of graves‘ disease: an overview.
Clin Endrocrinol Etab 1978;7:3.
7. Kriss Jp, Konishi J, Erman MM. Studies on the pathogenesis of
graves‘ Ophthalmopathy. Recent Prog Horm Res 1975;31:533.
8. Lawton NF. Diagnosis of dysthyroid eye.In Davidson SI (Ed):
Recent Advances in Ophthalmology, Churchill Livingstone:
New York 1983;99.
9. Kendler DL, Rootman J, HuberGK et al. A64kDA membrane
antigen is a recurrent epitope for natural autoantibodies in
patients with Graves’ thyroid and ophthalmic disease. Clin
Endocrinol (Oxf) 1991;35;539.
10. Wall JR, Salvi M, Bernad NF et al. Thyroid –associated
ophthalmopathy–A model for association of organ specific
autoimmune disorder. Immnunol. Today 1991;12;150.
11. Jakobiec FA, Jones IS. Orbital Inflammation. In Duane TD
(ed) Clinical Ophthalmology (2nd ed). Hagerstown, MD Harper
and Row, 1990.
12. WiesingaWM, Smit T, vander Gaag H ET AL. Clinical
presentation of Graves Ophthalmopathy. Ophthalmic. Res.
1989;21;73.
13. Bertelsen JB, Hegedus L. Cigarette smoking and thyroid,
Thyroid 1994;4:327.
14. Werner SC. Classification of the eye changes in Graves disease.
AM J Ophthalmol 1969;68;646.
15. Grove AS, Jr. Upper lid retraction in Graves disease,
Ophthalmology 1981;88:499.
16. Duke ElderS. System of Ophthalmology. St. Louis: CV Mosby
1971;13.
17. Small RG. Enlargement of Levator palpebrae superiorus muscle
fibers in Graves ophthalmopathy, Ophthalmology.
1989;96:424.
18. Gonnering RS. Pseudoretraction of the eyelid in thyroid-
associated orbitopathy. Arch Ophthalmol 1988;106:1078.
19. CrombieAL. The eye in thyroid disease. In Recent Advances in
Ophthalmology (Ed): PD Trevor Roper, Churchill Livingstone:
New York 1975;181.
20. Kanski Clinical Ophthalmology. Asystemic approach (2nd
edn). Butterworth Heinemann Ltd 1989;77.
21. Hulnagel TJ, Hicky WF, Cobbs WH et al: Immunohistochemical
and ultrastructural studies on the exenterated orbit of a patient
with Graves’ disease. Opthalmology 91;1:1081.
22. Char DH, Norman D. The use of computed tomography and
ultrasonography in the evaluation of orbital masses. Surv
Ophthalmol 1982;27:49.
23. Clagill WM. Excyclotropia in Dysthyroid Ophthalmopathy.
Am J Ophthalmol 1974;73:437.
 Chapter 92: Thyroid Ophthalmopathy
24. Bergen MP. A Literature review of the vascular system in the
human orbit. Acta Morphol Neerl Scand. 1981;19:273.
25. Sevel D. A reappraisal of the origin of human extraocular
muscles. Ophthalmology 1981;88:1330.
26. Gans G, Northcutt RG. Neural crest and the origin of vertebrates,
A new head Science, 1983;220:268.
27. Jensen SF: Endocrine Ophthalmoplegia. Acta Ophthalmol.
1971;9:479.
28. Dunnington JH, Burke RN. Exophthalmos due to chronic
myositis. Arch Ophthalmol 1993;30:446.
29. Lyons DE. Postural change in IOP in dysthyroid exophthal-
mos. Trans Ophthalmol Soc UK 1971;91:799.
30. Cheng H, Perkins ES. Thyroid eye disease and glaucoma. Br
Ophthalmol 1964;51:547.
31. Neigi JM, Rootman J et al. Dysthyroid Ophthalmopathy. The
crowed orbital apex syndrome, Ophthalmology 12988;95:11.
32. Smith BR, Hall R. Thyroid Stimulating immunoglobulins in
Graves disease Lancet 1974;2:427.
33. Hawkins BR, Cheah PS et al: Diagnostic significance of thyroid
microsomal antibodies in random selected population. Lancet
1980;2:1057.
34. Kumiko Kazua, Takishi Fuzikado et al. Value of Thyroid
stimulating antibody in the diagnosis of thyroid associated
ophthalmopathy of euthyroid patients. Br J Ophthalmol
1997;81:1080.
35. Char DH, Norman D: The use of computed tomography and
ulrasonography in evaluation of orbital masses. Survey
Ophthalmol 1082 ;27:49.
36. Enzamann DR, Donaldson SS, Kriss JP et al. Appearance of
Graves disease on orbital computed tomography J. Comput
Assit Tomogr 1976;3:815.
37. Char DH. Thyroid Eye Disease (2nd ed). New York: Churchill
Livingstone, 1990.
38. Morrice GD, Smith FW. Early experience with nuclear magnetic
resonance imaging in the investigation of ocular proptosis Trans
Ophthalmol Soc UK 1983;103:143.
39. Shammas JH. Pathological condition of orbit. In Atlas of
ophthalmic Ultrasonography and biometry. CV Mosby USA,
1989;230.
40. Forester JV, Sutherland GR, Mcdongall IB. Dysthyroid
ophthalmopathy; Orbital evaluation with B-scan ultra-
sonography J Clin Endocrinolonol.Metab.1977;45:221.
41 Hodes BI, Stern G. Contact B scan echographic diagnosis of
ophthalmoic graves disease. J Clin Ultrasound.1975;3:255.
42. Gay AJ, Wolkstein MA: Topical guanethedine therapy for lid
retraction.Arch.Ophthalmol.1987;76:364.
43. Putterman AM. Surgical treatment of thyroid related upper
lid retraction graded Mullers muscles excision and levator
recession, Ophthalmology 1982;88:507.
707
44. Grove AJ JR. Upper lid retraction and Graves disease
Ophthalmol 1981;88:499.
45. Scot WF, Thalaker JA. Diagnosis and treatment of thyroid
myopathy, Ophthalmology 1974;73: 437.
46. Dunn WJ, Arnoid AC, O’conner PS. Botulinum toxin for
treatment of dysthyroid ocular myopathy, Ophthalmology.
1986;99:470.
47. Leed Elson J, Vickerg S et al. Botulinum toxin for squint. Eye
1988;2:24.
48. Melling I, Hamilton P, Shone CC. Clostridum Botulinum toxin
nature and preparation for clinical use. Eye 1988;2:16.
49. Day PM, Caroll FD. Corticosteroid in the treatment of optic
nerve involvement with thyroid dysfunction Arch Ophthalmol
1968;79:279.
50. Brown J, Coburn JW, Wigod RA et al. Adrenal steroid therapy
of severe infiltrative ophthalmopathy of Graves disease Am J
Med 1984;34:786.
51. Apers RC, Oostterhius JA, Bierlaagh JJM. Indications and
results of Prednisolone treatment in thyroid ophthalmopathy.
Ophthalmologica 1976;173:163.
52. Wiesinga WM. Immunosuppressive treatment in Graves
ophthalmopathy. Thyroid 1992;2:229.
53. Prumed MF, Mourito MP et al. Prednisolone and cyclosporine
in treatment of severe Graves ophthalmopathy N Eng J Med
1989;321:1353.
54. Dandona P, Marshall N, Bidey S et al. Successful treatment of
exophthalmos and pretibial myxoedema with plasmaparesis
Br J Med 1979;1:374.
55. Prumed MF, Blank I, Mourito MP et al. Random double blind
trial of prednisolone versus radiotherapy in Graves
ophthalmopathy, Lancet 1993;342:1909.
56. Lliod W, LeoneCR. Supervoltage radiotherapy 36 cases of
Graves disease. Am J Ophthalmol.1992;113:374.
57. Breman MW, Leone CR, Janaki L. Radiotherapy for Graves
disease. Am J Ophthalmol 1983;96:195.
58. Knoll HA, Kawbara T. Dysthyroid ocular myopathy palliation
by lateral orbital decompression. Arch Ophthal-
mol.1966;76:244.
59. Wright JE. Malignant exophthalmos, In Davidson SI (Ed):
Recent Advances of Ophthalmology. Churchill Livingstone:
New York 1983;106.
60. Garrity JA, Fatonrrchi V, Burgtrath EJ et al. Results of orbital
decompression in 428 patients with severe ophthalmopathy,
Am J Ophthalmol 1993;76:205.
61. Trokel SC, CooperWC. Orbital decompression effect on motility
and globe position. Ophthalmology 1979;86:2064-70.
62. Trokel S, Kazim M, Moore S. Orbital fat removal. Decom-
pression for Graves’ Ophthalmopathy. Ophthalmology
1993;100:674.
 Chapter 93

Anatomy, Physiology and

Diseases of the Lacrimal System
AK Grover, A Bhatnagar, Sarmi Malik

ANATOMY OF LACRIMAL SYSTEM
The lacrimal apparatus consists of the lacrimal gland
with its ducts, puncta, canaliculi, lacrimal sac and the
nasolacrimal duct which opens into the inferior nasal
meatus.
Lacrimal Gland
The lacrimal gland is an exocrine gland situated in
the anterior and outer part of the roof of the orbit
which forms a concavity known as the fossa of the
lacrimal gland. It is in direct contact with the upper
and outer side of the eyeball. Anatomically it has two
parts incompletely separated by the levator palpebrae
muscle; a bigger orbital portion and a smaller
palpebral portion. The anterior portion of the
palpebral part can be seen through the conjunctiva in
the lateral portion of the superior fornix. 10 to 12 ducts
from both portions of the gland open into the
conjunctival sac just in front of the superior fornix.
Few ducts open into the lateral portion of the inferior
fornix also. The ducts from the orbital portion pass
through the palpebral portion and hence, removal of
the palpebral portion might result in loss of secretion
of lacrimal fluid. Few accessory small lacrimal glands
(glands of Krause and Wolfring) are present in the
conjunctiva in between the superior fornix and upper
convex border of the tarsal plate; these glands have
got no apparent nerve supply. Structure of the lacrimal
gland resembles that of the parotid gland. Surface of
the gland is lobular and is covered with fibrous fascia,
expansions from which go in between the lobules. The
acini consist of two layers of cells surrounding a central
canal. The outer layer cells are myoepithelial in
character and the inner layer of cylindrical cells are
secretory in nature.
Blood supply of the lacrimal gland is from the
lacrimal branch of the ophthalmic artery. Venous
blood drains into the ophthalmic vein.
Nerve Supply
The lacrimal gland has got (a) Sensory (b) Secreto-
motor and (c) Sympathetic supply.
Sensory supply comes through the lacrimal branch
of the ophthalmic division of the 5th cranial nerve.
Lacrimal nerve, the smallest of the three branches of
the ophthalmic nerve arises in the anterior part of the
middle cranial fossa and enters the orbit through the
superior orbital fissure in between the 4th nerve and
the ophthalmic vein and enters on the medial aspect
of the lacrimal gland. Before entering the gland it
receives a branch from the maxillary nerve.
Secretomotor Fibers
Parasympathetic preganglionic fibers arise from the
lacrimal nucleus in the pons near the glossopharyngeal
nucleus and pass along the pars intermedia of the 7th
nerve to the geniculate ganglion and without any relay
emerge from the under surface of the ganglion as the
greater superficial petrosal nerve (sympathetic) to
form the vidian nerve on the cartilage of foramen
lacerum; the fibers pass through the pterygoid canal
to join the sphenopalatine ganglion (Meckel’s
ganglion) which remains suspended from the
maxillary nerve. Postganglionic fibers from this
 Chapter 93: Anatomy, Physiology and Diseases of the Lacrimal System
ganglion pass to the orbit through the inferior orbital
fissure along with the zygomatic branch of the
maxillary division are transferred to the lacrimal twig
via an anastomotic twig.
Sympathetic Fibers
Postganglionic fibers come from superior cervical
ganglion and reach the lacrimal gland via deep
petrosal and sympathetic fibres around lacrimal artery
and nerve.
The lacrimal excretory apparatus consists of lacrimal
punctum, canaliculus, lacrimal sac and nasolacrimal
duct (Fig. 93.1).
Punctum One for each eyelid, the punctum situated
in, the medial part, appears as a raised papilla with a
dark central opening leading to the canaliculus. When
the lids are closed the upper and lower puncta do not
come in contact with each other but the upper
punctum lies just medial to the lower one. The puncta
are visible only after slightly everting the eyelids
because the upper puncta look downwards and
backwards. On movement of the eye lids the puncta
glide in the groove lateral to the plica semilunaris.
Canaliculi The canaliculi are embedded in the
substance of the pars lacrimalis of the lid margin.
Upper canaliculus is 8 mm and the lower one is 8.5
mm long. First 2 mm of the canaliculus is vertical and
the rest is horizontal which converge medially to unite
(in 90%) and the common canaliculus opens into the
middle of the lateral surface of the lacrimal sac.
Fig. 93.1: Anatomy of lacrimal excretory system
709
Lacrimal sac The lacrimal sac lies in the lacrimal
fossa in the anterior part of the medial wall of the orbit.
The fossa is formed by the frontal process of the
maxilla and the lacrimal bone. It is well demarcated
above and continues below with the nasolacrimal
canal. The anterior boundary of the lacrimal fossa is
formed by the anterior lacrimal crest which is
prominent in the lower part; but the upper part is not
palpable through the skin. Posterior lacrimal crest,
though well demarcated, cannot be felt through the
skin. Vertical suture line between the frontal process
of the maxilla and the lacrimal bone is slightly medial
to the middle of the floor of the fossa. This is of surgical
importance because in dacryocystorhinostomy
operation, the first bony opening is made along this
suture line. When filled with fluid the lacrimal sac is
1.5 mm long (vertically) and 5-6 mm wide. The upper
part of the fundus 1.0 of the sac extends 3 to 5 mm
above the medial palpebral ligament. The sac is
enclosed by a portion of the periorbita known as the
lacrimal fascia which splits at the posterior lacrimal
crest and enclosing the sac joins at the anterior lacrimal
crest. The anterior layer is known as the anterior
lacrimal fascia and the posterior one as posterior
lacrimal fascia; behind this fascia few fibers of Muller’s
muscle take origin from the posterior lacrimal crest.
Between the posterior surface of the sac and the
posterior lacrimal fascia there is a vascular plexus;
injury to this plexus during sac surgery leads to
troublesome bleeding. Anteriorly, the upper part of
the sac is in close contact with the medial palpebral
ligament so much so that the ligament may have to be
divided near its attachment to the anterior lacrimal
crest for complete mobilization of the sac. Some fibres
of the inferior oblique muscle arise from the lacrimal
fascia. Angular vein crosses the medial palpebral
ligament 8 mm from the inner canthus; however, the
position of the vein is not always constant and as such
it is a good practice to identify the vein before injecting
the anesthetic fluid.
Nasolacrimal Duct
Lacrimal sac is almost continuous with the naso-
lacrimal duct which is about 15 mm long. From the
point of junction with the sac the duct is directed
backwards, outwards and downwards; the course of
the duct may be represented on the skin surface by a
line joining the inner canthus and the first molar tooth
of the same side. In probing of the duct this point is
worth remembering. The duct opens into the inferior
nasal meatus beneath and lateral to the inferior
turbinate bone.
710 Section 6: Diseases of Orbit

The tear fluid secreted from the lacrimal gland is
poured into the lateral part of the upper fornix through
the ducts from where it spreads over the anterior
surface of the cornea and conjunctiva due to move-
ments of the eyelids. By capillary action very small
portion of the lacrimal fluid is directed to pass through
the punctum to the canaliculus and then to the sac;
but the major portion is evaporated from the exposed
portion of the globe. In reflex secretion the lacrimal
drainage system cannot manage to dispose off the
fluid and hence, it overflows the conjunctival sac. In
addition to patency of the nasolacrimal duct, tone of
the orbicularis oculi muscle is essential for proper
drainage of tear fluid. The lacrimal sac should dilate
during each contraction of the orbicularis oculi muscle
to swallow a gulp of tear fluid which then drains to
the nasal cavity mostly by gravitational force.
Development of the Lacrimal Apparatus
Lacrimal gland is developed from 8 to 10 epithelial
ingrowths from the upper temporal side of the
conjunctival sac at about the second month of
intrauterine life and these buds divide and redivide
to form the lacrimal gland. Full histological differen-
tiation takes place soon after birth. The lacrimal sac
and the nasolacrimal duct are developed from the cord
of the surface ectodermal cells which was cut off from
the surface during union of the lateral nasal and
maxillary process at about 10 mm stage (early 5th
week). By the sixth week of intrauterine life the
canaliculi grow into the lids from the upper end of
this cord. Canalization of the solid columns of cells
takes place by degeneration and shedding off of the
cells starting at about the 3rd month and completed
before birth.
sympathetic fibers control the basic secretors in lids
and conjunctiva. Jordan and Baum, who proposed that
all aqueous tear secretion is driven by stimuli, have
questioned this division of tear secretion into basic
and reflex. 2
Drainage of Tears (Fig. 93.2)
In the well-compensated eyes most of the tear volume
is lost to evaporation and only a small fraction drains
through the excretory system. The tears are conducted
to the lacrimal puncta in three ways (a) gravitational
fall at the lateral canthus to form the lower tear strip
(b) capillary attraction of tears into the punctum and
vertical limb of canaliculus (c) blink mechanism. Jones
developed the concept of lacrimal pump3 according
to which tears are propelled through the lacrimal
system by alternating negative and positive pressure
in the lacrimal sac. When the orbicularis muscle
contracts during the act of blinking, the punctum is
drawn nasally, the ampulla is compressed, and the
horizontal limb of the canaliculus is shortened, thus
driving tears into the lacrimal sac. This contraction of
orbicularis muscle also stretches the lateral wall of
lacrimal sac; the resultant negative intrasac pressure
sucks fluid into the sac during the contraction phase
of the blink. When the lids open, the orbicularis
muscle relaxes, the sac collapses and the positive
intrasac pressure forces tears down the nasolacrimal
duct. Classically, it has been believed that it is the
lower punctum and canaliculus, which is mainly
responsible for drainage of tears. However, recent
studies4 suggest an equal importance of both upper
and lower canaliculi in tear drainage. In addition, it
has been shown that in patients with abnormality of

PHYSIOLOGY OF LACRIMAL SYSTEM

Secretion of Tears
The neurogenic control of secretion of tears is best
understood in terms of Jones’ concept of “basic” and
“reflex” secretion. 1 The basic secretors are the
accessory lacrimal glands. The reflex secretion is a
function of the main lacrimal gland. Reflex secretion
may be of peripheral sensory origin, through fifth
nerve stimulation (cornea, conjunctiva, nose), or of
central sensory origin (retinal stimulation by bright
light or psychogenic stimuli). While the reflex
secretion is controlled by parasympathetic supply, the Fig. 93.2: Lacrimal pump mechanism
 Chapter 93: Anatomy, Physiology and Diseases of the Lacrimal System
the lower canaliculus, the upper canaliculus is able to
drain sufficient tears in 90% of them.5
SYMPTOMS OF LACRIMAL
SYSTEM DYSFUNCTION
Symptoms indicative of a lacrimal excretory system
dysfunction include epiphora, punctal discharge and
a mass or swelling in the region of medial canthus.
Excessive lacrimation can also occur with stimulation
of reflex arcs such as ocular irritation, dental, sinus or
ear disease.
INVESTIGATING THE LACRIMAL SYSTEM
Tests of Lacrimal Secretion
Schirmer Test
This is a useful test for estimating the rate of tear
production. Whatman 41 filter paper strips 5 mm x 35
mm are folded 5 mm from one end and inserted into
inferior fornix at the junction of middle and lateral
thirds of the lid and allowed to remain there for 5
minutes. During this time, the patient sits in a dimly
lit room with the eyes open and blinks normally. The
wetting of the filter paper strip is measured at the end
of 5 minutes.
Schirmer I test is performed without topical
anesthetic and a wetting of 10mm or more is
suggestive of a normal tear production. The basic
secretion test is performed in a similar way but after
instilling a topical anesthetic into the conjunctival sac.
This test gives an estimate of the basal tear production
(by accessory lacrimal glands) by eliminating sources
of reflex lacrimation. Thus, it differentiates between
pseudoepiphora and hypersecretion. Wetting of less
than 10 mm in 5 minutes suggests deficiency in basic
tear production.
Schirmer II test measures the reflex tearing after
anesthetizing the conjunctival sac; filter paper strips
are placed as before and the trigeminal nerve is
stimulated by applying a cotton applicator to the nasal
mucosa or with ammonia vapors. The amount of
wetting achieved in excess of that elicited by basic
secretion test represents the reflex secretion.
Although the Schirmer test is rapid, simple and
adequately repeatable in a given patient, its result
must be interpreted in light of the patient’s symptoms
and signs. Moreover, with increasing age there is a
decline in the rate of tear production.
711
Tear Break-up Time (TBUT)
This test assesses the deep mucinous layer of the tear
film. Deficiency of the mucinous component (pro-
duced by goblet cell of the conjunctiva) results in
symptoms of dry eye even in the presence of sufficient
aqueous tear component.
The test is performed as follows: One drop of 2%
sodium fluorescein solution is instilled into the
conjunctival sac. The patient is asked to blink several
times and then keep his eyes open. The cornea is
examined through the slit lamp and TBUT is measured
from the first blink until fluorescein free patches
appear on the corneal surface. Normally the TBUT is
15 seconds or more.
Tear Lysozyme Assay
This enzyme constitutes 21 % to 23% of total protein
content of tears. Its ability to inhibit the growth of the
bacterium Micrococcus lysodeikticus is used to assay
its level in tear fluid. Decreased concentration of tear
lysozyme is seen in hypersecretory states. However,
the levels are characteristically low in Sjögren’s
disease.
Tests of Lacrimal Excretion
Saccharin Test
In this test a drop of saccharine solution is instilled in
the conjunctival sac. If the lacrimal excretory passages
are normal, the patient will report a bittersweet taste
in his mouth within 20-30 minutes of instillation.
Jones’ Dye Tests
In this test a drop of 2% fluorescein solution is instilled
in the conjunctival sac and a cotton tipped applicator
is inserted under the inferior turbinate (anesthetized
by Lignocaine spray) after 1 minute and thereafter
every minute upto 5 minutes (Fig. 93.3). If the
excretory pathways are functioning normally, the
fluorescein stained solution will pass into the nose
within 5 minutes. However, failure to identify the dye
in nose may occur in upto 22% of normal subjects.6 In
some of the negative cases, blowing into a cotton pad
may show the presence of dye in the nasal secretion
reducing the number of false negative results. If this
test (Jones I test) is negative, Jones II test is performed.
The residual fluorescein solution is flushed from the
conjunctival sac and clear saline is flushed through
712 Section 6: Diseases of Orbit
Fig. 93.3: Jones dye test: Cotton-tipped applicator inserted
under the inferior turbinate
the lacrimal system with the help of a syringe with
cannula. If the fluid now recovered from nose is
stained with fluorescein then it indicates that the
passages are structurally patent and the dye had
reached upto the sac normally but a functional block
exists below the sac. However, if the fluid that enters
the nose is still clear it means that the dye never
entered the lacrimal excretory system (i.e. there is a
pump failure). If no fluid is recovered from the nose
on irrigation, it indicates an anatomical obstruction
in the pathway. Nearly 70% of obstruction in adults
occurs at the level of junction of sac and nasolacrimal
duct.
Fluorescein Dye Disappearance Test
After instilling a single drop of 2% fluorescein in the
conjunctival sac, the color intensity is graded after 5
minutes on a scale of 0 to 4. Normally the retained
fluorescein at the end of 5 minutes is not more than
grade 0 to 1. The advantage of this test lies in its
simplicity. It is especially useful in infants and
children.7
Syringing of Lacrimal Passages
This helps in diagnosing an anatomical block. After
anesthetizing the conjunctival sac with 4% Lignocaine
or Paracaine eye drops, the punctum is dilated with a
Nettleship’s punctum dilator. A lacrimal cannula with
a smooth blunt tip containing saline is introduced into
the lacrimal canaliculus 2mm downwards and then
turned medially (to lie in the horizontal limb of the
canaliculus). The irrigating solution is then injected
and any regurgitation of fluid from either punctum is
noted.
i. If there is no regurgitation and the fluid passes
down into the patients’ throat it indicates patency
of lacrimal excretory system.
ii. Regurgitation of mucoid or mucopurulent fluid
followed by clear fluid from the opposite punc-
tum is suggestive of a nasolacrimal duct block.
iii. Immediate regurgitation of clear fluid from oppo-
site punctum is seen in cases with common canali-
cular block.
iv. Clear fluid regurgitating from the same punctum
indicates a block in that particular canaliculus.
In such cases, syringing should then be attempted
from the other punctum.
Two important precautions to be observed during
syringing are (i) the tip of the cannula should be blunt
and smooth in order to prevent any damage and
subsequent stricture in the canaliculus; (ii) the tip of
the cannula should not be forced in any direction to
avoid forming false passage.
Probing
If syringing demonstrates an anatomical blockage in
the lacrimal excretory pathways, a Bowman’s lacrimal
probe can be passed to determine the exact site of
block. After anesthetizing the conjunctival sac and
dilating the punctum, the probe is passed into the
canaliculus (2 mm vertically and then turned medially
till it strikes the bone). If there is any obstruction to
the passage of the probe, its site is determined by
measuring the length of probe, which had gone in
before it encountered the obstruction. A “soft stop”
resistance to the probe is felt in cases of common
canaliculus block, while a “hard stop” is felt in cases
of nasolacrimal duct obstruction. When the probe
encounters resistance, it is grasped with a forceps at
the entrance to the punctum. The distance between
the end of the probe and the forceps is measured, to
determine the site of block.
Probing is also used therapeutically in cases with
congenital nasolacrimal obstruction (discussed later).
Dacryocystography
This technique utilizes a radiopaque dye to confirm
the level of the block. The details of its technique and
its interpretation have been discussed elsewhere.
(Chapter 94).
 Chapter 93: Anatomy, Physiology and Diseases of the Lacrimal System
Newer Investigative Modalities
A chemiluminescent evaluation of lacrimal drainage
system has been described8 that utilizes a material,
cyalume, injected with a sialography catheter to
demonstrate the structure and patency of outflow
passages. It eliminates any radiation exposure and
may also be used during surgery. Raflo, Chant and
Hurwitz9 have described a method for thermographic
evaluation of lacrimal passages. A mini rigid
endoscope, termed a dacryoscope, has been developed
to allow direct visualization of the interior and the
lining of lacrimal pathway.10 Dacryoscintigraphy11
requires instillation of a radioactive tracer dye, sodium
pertechnate into the tear film. The lacrimal area is
scanned with a gamma camera to follow the progress
of radioactive tracer into the canaliculi, the lacrimal
sac, nasolacrimal duct and nose. This test provides the
most physiological assessment of function of outflow
pathway. It is of special use in children and uncoope-
rative adults. Dutton12 has shown that standardized
echography may provide a simple, non-invasive
adjunctive technique for evaluating gross anatomic
structure of lacrimal system.
DISEASES OF THE LACRIMAL GLAND
Lacrimal gland enlargements may be caused by
inflammations or tumors of the gland. The latter has
been discussed in detail elsewhere (Chapter 95).
Inflammatory processes may be due to infections,
granulomatous diseases of unknown causes such as
Sarcoidosis, Sjögren’s syndrome and Benign lympho-
epithelial lesions.
Infection
Many viral infections may cause a sub-clinical lacrimal
gland enlargement. Most frequent and clinically
significant virus implicated is mumps, which is
associated with parenchymal inflammation domi-
nated by lymphocytes. Infrequently, the cyto-
megalovirus, herpes zoster and mononucleosis viruses
may cause dacryoadenitis.
Acute bacterial infections of lacrimal gland occur
rarely as a result of local extensions from skin or in
the course of bacteraemia. The gland may be affected
in chronic infection like tuberculosis and leprosy.
Non-infective Chronic Inflammations
Lacrimal gland enlargement may be seen in upto 7%
of patients with systemic Sarcoidosis. Therefore,
713
lacrimal gland biopsy is an important procedure to
confirm Sarcoidosis. The pathologic picture is
dominated by epitheloid granulomas with scattered
lymphocytes.
Inflammation of lacrimal gland is an integral part
of Sjögren’s syndrome. The ensuing decrease in tear
production leads to a dry eye condition known as
keratoconjunctivitis sicca.
Benign Lymphoepithelial Lesion
It is characterized by diffuse infiltration of lacrimal
and salivary glands by lymphocytes, unassociated
with systemic disease or symptoms of dry eye.
CONGENITAL ANOMALIES OF
LACRIMAL EXCRETORY SYSTEM
Congenital Nasolacrimal Duct (NLD) Block
Congenital NLD block is present in 2 to 4% of
otherwise normal newborns. In the most common
variation of congenital NLD block, the duct ends at
or near the vault of the anterior end of inferior nasal
meatus but fails to perforate the nasal mucosa
(imperforate Valve of Hasner). This results in a
persistent epiphora with or without acute dacryo-
cystitis.
In 80 to 90% cases, the residual membrane
spontaneously dissolves within 2 to 4 months after
birth. Majority of the persistent cases will respond to
conservative treatment with antibiotics and lacrimal
sac massage.
In a large majority of cases, the cause of failure of
conservative treatment is an improper technique of
sac massage. Therefore, it is imperative to explain to
the mother, the correct way of massaging the sac area.
She should be instructed to compress the sac by
applying pressure with the pulp of the index finger
and with firm, gentle pressure slide the finger down
for about one inch in the groove between medial
inferior orbital rim and nose. This is followed by
instillation of antibiotic drops in the conjunctival sac
and the procedure should be repeated 4 to 5 times
daily. In unresponsive cases, probing of the NLD is
required.
The duration for which sac massage should be tried
as the means for treating this condition is contro-
versial. In case sac massage is ineffective, probing of
the lacrimal passages is done.
714 Section 6: Diseases of Orbit
Technique of Probing
It must be done under general anesthesia to ensure
absolute immobility of the head. It is preferable to
probe through the upper punctum to eliminate any
inadvertent damage to the lower punctum and
canaliculus. After dilating the upper punctum,
syringing of the lacrimal passages are done to check
their patency. Once the NLD block is confirmed, a
Bowman’s lacrimal probe of appropriate diameter is
passed through the punctum and upper canaliculus
till it reaches the medial wall of the sac and lacrimal
fossa. The probe is held steady against the bony
resistance of the medial wall of orbit and slowly turned
into a vertical position. During this maneuver, it is
essential to maintain contact between the tip of the
probe and the lacrimal fossa. As the probe passes
down, slightly backwards and laterally, its tip will get
engaged in the NLD. The probe is then passed upto
the obstructed end of NLD and with a quick sharp
thrust it pierces through the imperforate membrane.
The patency of the passage can be confirmed by
syringing. The patient is put on topical antibiotic-
steroid drops for a week postoperatively.
Probing is absolutely contraindicated during the
acute phase of dacryocystitis because the edematous,
inflamed mucosa can get injured easily during the
procedure, leading to fibrosis and stricture.
The age at which sac massage should be abandoned
and probing tried is controversial. Proponents of early
intervention by probing (usually at 6-8 months) argue
that it provides symptomatic relief, prevents long-
term infection and saves the parents the task of
massaging the child’s eye for a long period of time.
The overall success rate for initial probing before
one year is more than 90%.13,14 In addition, the risk of
probing failure increases with age, doubling every 6
months.15 It has been reported that delay in probing
beyond 13 months is associated with a decreased
success rate.13-16 Early probing (below the age of 6
months) has also been found to be more cost
effective.17
On the other hand, proponents of later probing
(above the age of 6 months but below 1 year) report a
high degree of spontaneous resolution of the condi-
tion, thus obviating the need for any surgical
intervention. Robb followed a cohort of almost 5000
infants in whom 96% had spontaneous remission of
their obstruction by the age of 1 year.18 He noted no
significant decrease in the success rate of probing with
age upto 5 years. The probability of spontaneous
resolution in patients below the age of 14 months has
been found to be 1 in 3 cases.
Finally, it is for the surgeon and the parents to
decide on the appropriate timing of probing in the
child based on the knowledge of these studies.
Probing may be unsuccessful due to closure of the
new ostium, a narrow inferior meatus or a hyper-
trophied inferior turbinate. In such cases, several
surgical options are available including infracture of
the inferior turbinate, silicone intubation of the
lacrimal system and balloon catheter dilatation.
Infracture of the Inferior Turbinate
This method has been found to be useful in those
patients in whom ecurrence of dacryocystitis has
occurred following a successful syringing and
probing, and as a primary procedure in those patients
who have a hypertrophy of the inferior turbinate.
Silicone Intubation
Silicone intubation is thought to work by dilating areas
of stenosis in the lacrimal system. An advantage of
intubation is the maintenance of the normal anatomy
of the lacrimal system. It is performed under general
anesthesia. The tube attached to a metal probe is
inserted through the canaliculi into the nose. The ends
are either tied in several knots or sutured to the side
of the nose. Success rate of silicone intubation has
generally been reported to be from 80 to 90% in
congenital nasolacrimal duct obstruction.19-21
Potential complications include damage to the
lacrimal passage, creation of false passages, dacryo-
cystitis, extrusion of the tube, conjunctivitis, corneal
abrasions and epistaxis.
Balloon Catheter Dilatation
This is another procedure that can be done in case of
failed probing in congenital nasolacrimal duct
obstruction. The procedure and its results are
described later in the chapter.
Congenital Lacrimal Fistula (Lacrimal Anlage Duct)
Congenital fistula of the lacrimal sac is a result of
canalization of a strand of epithelial cord that extends
from the sac to the skin surface. This creates a fistula,
which opens on the skin below and medial to the lower
punctum.
 Chapter 93: Anatomy, Physiology and Diseases of the Lacrimal System
The fistulous tract is identified by passing a probe
through it and is dissected microsurgically upto the
medial canthal tendon; the duct is ligated, excised and
the skin incision closed. Occasionally, the fistula may
be associated with a nasolacrimal duct obstruction,
which may require appropriate management.
Punctal Atresia
Failure of the embryologic epithelial cord to open on
the eyelid margin results in an imperforate punctum.
The presumed location of the punctum can be
identified as a shallow dimple at the appropriate site
or by following the posterior lid margin until the
papilla is reached. An attempt can be made to pass a
probe through the atretic region to connect with the
canaliculus. An alternative approach is to dissect down
on the posterior aspect of the lid in an effort to cross
the canaliculus. If the opposing canaliculus is patent
a pigtail probe can be passed through the patent
portion of involved canaliculus. The surgeon can then
dissect down to the tip of the probe and intubate the
upper and lower canalicular system. The details of this
technique will be described later while discussing
management of canalicular lacerations.
ACQUIRED DISORDERS OF
LACRIMAL EXCRETORY SYSTEM
Punctal Stenosis
The punctum can get stenosed due to chronic
inflammation, cicatricial conjunctival disease, aging
or use of certain topical drugs. In the early cases simple
dilation of the punctum suffices but in advanced cases
a one-snip or three-snip operation is indicated. In some
patients one vertical snip with a Vanna’s scissors from
the punctum to the junction of the ampulla with the
canaliculus (Fig. 93.4) relieves epiphora; if this fails, a
Fig. 93.4: Single-snip procedure for punctal stenosis
715
3-snip procedure is done. In this technique 2 more
snips are made from the ampulla along the canaliculus
for 3mm and the third snip to join the previous two
snips, thus removing a triangle of tissue. These
procedures may be combined with silicone intubation
for a duration of 3 to 6 months to ensure maintenance
of patency.
Punctal Ectropion
Laxity of tissues with age coupled with a habitual
rubbing of eyes in a downward and outward direction
results in eversion of the lower punctum. Mild degrees
of eversion can be corrected by inducing fibrous
tissues contracture by focal cautery of adjacent inferior
tarsal border. In severe cases, conjunctivoplasty is
required to invert the lower punctum (Fig. 93.5). In
this procedure a horizontal tarsconjunctival ellipse,
5 × 8 mm, is resected inferior to the punctum. This
causes shortening of the posterior eyelid lamella
relative to the anterior lamella. Alternative techniques
include correction of medial canthal tendon laxity by
“tucking” and horizontal shortening of lower lid by
Smith’s lazy-T technique or shortening by lateral tarsal
strip procedure combined with conjunctivoplasty. A
rare cause of punctal ectropion is Centurion syndrome,
in which patients have epiphora since childhood and
a prominent nasal bridge.
Canalicular Laceration
Avulsion of lid at the medial canthus or deep
laceration in this region will result in complete
severance of the canaliculi. It is important never to
willingly sacrifice the upper canaliculus and it must
Fig. 93.5: Conjunctivoplasty for punctal eversion
716 Section 6: Diseases of Orbit

be repaired in the same way as a lacerated lower tubes may be passed into the nose by using Quickert-
canaliculus. Dryden probing system26 wherein the silicone tube is
fixed to a malleable probe which is passed into the
Repair of Single Canalicular Laceration inferior meatus through nasolacrimal duct and
recovered from there. The other end of the tube is also
The first step is to identify the two cut ends of the
passed into the nose from the opposite punctum
canaliculus. The lateral cut end is easily identified by
(Figs 93.6 to 93.10). This ensures retention of the probe
passing a lacrimal probe through the punctum. To
for the required period of time.
identify the medial cut end, the wound is examined
under magnification, preferably by an operating
microscope. The tiny opening of the cut canaliculus is
paler than the surrounding tissues. However, if the
cut end is not obvious, it is identified by pooling sterile
saline in the wound and then watching for bubbles
while injecting air through the opposite canaliculus
while a pressure is maintained on the lacrimal sac.
The use of a pigtail probe to identify the medial end
of lacerated canaliculus should be avoided because of
the risk of creating false passage and trauma to the
intact canaliculus. Once the 2 cut ends are identified, Fig. 93.7A: Malleable probe being brought down
a fine silicone tubing or the plastic tubing of a fine through NLD in the inferior meatus
intravenous catheter is threaded via the punctum
along both sections of the canaliculus. If tubing is not
available, a thick monofilament nylon suture is
threaded in the same way. The silicone tubing which
was passed through the lateral canaliculus is sutured
to the lid margin, so as to retain it in place. The silicone
tubing is left in place for at least 3 months with good
results22 (Fig. 93.6).
Some surgeons prefer a pancanlicular intubation
by encircling the 2 canaliculi.23,24
A common problem encountered with these
techniques is the extrusion of the silicone tube from Fig. 93.7B: The probe advanced anteriorly along
the intubated canaliculus. To aid in its retention, the the grooved director

Fig. 93.6: Silicone tube intubation for canalicular laceration.

The proximal end of tubing is tied to the lid margin to prevent Fig. 93.7C: The advancing tip of the probe
its extrusion brought out through external nares
 Chapter 93: Anatomy, Physiology and Diseases of the Lacrimal System 717

Fig. 93.7D: Probe and swedge-on silicone tubing Fig. 93.7E: Process repeated through opposing canaliculus
withdrawn from nose and ends of silicone tubing tied together within inferior meatus

A B

Figs 93.8A to C: Canaliculodacryocystorhinostomy (A) one end of silicone tube passed through the canaliculus, bony opening
and out through nose. The other end is also passed in the same way before suturing the anterior flaps (B) free ends of the tube
being sutured together (C) final postoperative appearance
718 Section 6: Diseases of Orbit
Figs 93.9A to C: Conjunctivo DCR (A) 23 G curved needle
being passed into the conjunctiva to enter in the lacrimal sac;
behind the anterior flap. (B) Graefe’s knife has been passed to
create the track for passing the flanged tube. The required
length of tube being estimated by passing a probe. (C) Flanged
polythene tube being passed over a lacrimal probe by the side
of Graefe’s knife
Fig. 93.10: Conjunctivo-DCR tube irrigation being
done to overcome mucus plugging
Repair of Both Upper and Lower
Canalicular Laceration
In such a situation, the proximal openings are isolated
by passing a Bowman’s probe through the puncta. At
least one of the distal cut ends of the canaliculus can
be located by using an operating microscope. A pigtail
probe can then be passed through it and out through
the distal cut end of canaliculus. A silastic tubing is
inserted over the pig-tail probe tip and passed through
the canaliculus by withdrawing the probe. The lateral
cut ends of the canaliculi are also intubated and a
nylon suture passed through the tube and tied so as
to retain the tube in place.
Canalicular Obstruction
Most commonly, it occurs following improper repair
of lid laceration involving the canaliculi. It can also
occur as a complication of DCR surgery, following
infection and as a congenital canalicular atresia. Choice
of surgical procedure for management of canalicular
obstruction depends on the site of block. Obstructions
located in the distal part of common canaliculus can
be treated by canaliculodacryocystorhinostomy.
Proximal common canalicular blocks and blockage of
individual canaliculus necessitate a conjunctivo-
dacryocystorhinostomy.
Dacryocystitis
It is the inflammation of the lacrimal sac and duct.
The highest incidence is seen in the 5th decade of life.
Females are affected in 80% cases due to narrow lumen
of the bony canal. An essential prerequisite for
 Chapter 93: Anatomy, Physiology and Diseases of the Lacrimal System
development of infection is stasis of sac contents. The
most common sources of infection are the nose,
paranasal sinuses and pericystic tissue.
Clinically, dacryocystitis can be classified into two
major types:
a. Chronic dacryocystitis: Characterized by persis-
tent epiphora and regurgitation of mucoid or
mucopurulent material on pressure over the sac
area. In some cases the sac becomes distended
and appears as a cystic swelling below the
medial palpebral ligament; this is called
mucocoele. Occasionally, the opening of
common canaliculus into the sac gets blocked
because of kinking of the lateral end of common
canaliculus; this results in the formation of an
encysted mucocele (Fig. 93.11).
b. Acute dacryocystitis: It occurs due to aggravation
of infection in a case of chronic dacryocystitis.
It is characterized by pain, redness and
tenderness over the sac area; the pus may burst
into the skin surface resulting in formation of a
lacrimal fistula.
Management of Acute Dacryocystitis
This includes institution of appropriate antibiotic
therapy systemically and locally coupled with warm
compresses over the inflamed area. Syringing or
probing of an acutely inflamed sac is strictly
contraindicated because of the risk of damage to the
inflamed mucosa resulting in a fibrotic stricture.
If untreated in early stage, acute dacryocystitis may
progress to form lacrimal abscess. In such cases,
Fig. 93.11: Encysted mucocele (left eye)
719
surgical drainage is indicated. The incision is made
3 mm medial to medial canthus and just below the
medial palpebral ligament. The tip of the knife is
carried posteriorly and downward to the most
dependent part of the sac. After drainage of the pus, a
thin rubber drain is inserted, antibiotic ointment
applied and the wound is bandaged. The rubber drain
is usually removed after 48 hours. In some cases, a
chronically discharging fistula may persist after
surgical drainage of lacrimal abscess or following its
spontaneous bursting through the skin. This requires
a fistulectomy with or without dacryocystorhinos-
tomy.
Management of Chronic Dacryocystitis
This is essentially surgical. The procedure of choice is
dacryocystorhinostomy (DCR) in an overwhelming
majority of cases.
Conventional Dacryocystorhinostomy
In this procedure, the tears are diverted from the
lacrimal sac into the middle meatus by forming an
anatomosis between the sac and the nasal mucosa,
thus bypassing the blocked NLD.
Preoperative Evaluation
A thorough rhinological check-up is important to
exclude the presence of a grossly deviated nasal
septum, nasal polyps or a hypertrophied turbinate,
all of which may lead to failure of surgery. Presence
of atrophic rhinitis would contraindicate a DCR and
a dacryocystectomy (DCT) should then be performed.
In all cases, bleeding during the surgery and early
postoperative period is a major concern and precau-
tions should be taken preoperatively. Bleeding time
and clotting time should be tested in all cases and the
patient be questioned regarding taking any drugs that
may alter blood coagulation, e.g. heparin, warfarin
sodium, aspirin and other nonsteroidal anti-infla-
mmatory drugs.
Nasivion nasal drops are started in the corres-
ponding nostril 2 to 3 days before the surgery. This
helps in maintaining hemostasis.
Type of Anesthesia
The surgery can be performed under general or local
anesthesia. If general anesthesia is being used,
hypotensive anesthesia may be used in selected cases
720 Section 6: Diseases of Orbit

to minimise bleeding. For local anesthesia, an crest; superiorly extends to the upper margin of medial
infratrochlear block is used. Two percent Lignocaine palpebral ligament; inferiorly, upto the opening of
containing adrenaline in a concentration of 1:200.000 NLD and posteriorly upto the posterior lacrimal crest
is used. The needle is entered just below the trochlea (Fig. 93.12C). While making the bony opening, great
and passed backwards along the junction of roof and
medial wall for 3 centimetres. One ml of the anesthetic
agent is injected and the needle withdrawn. The skin
over the anterior lacrimal crest, along the line of
incision, is also infiltrated with anaesthetic solution.
In addition, the nasal cavity is packed with a ribbon
gauze soaked in Lignocaine with adrenaline
(1:200,000) to anaesthetize the nasal mucosa. This also
serves the purpose of decongesting the nasal mucosa
and minimizing bleeding during surgery. While doing
the nasal packing it is important to pack the anterior
nasal cavity. For correct placement of the ribbon gauze,
nasal forceps is directed gently towards the medial
Fig. 93.12A: Skin incision for DCR
canthus. A forceful passage of the nasal forceps may
to avoid angular vessels
push it through the cribriform plate of the ethmoid
bone leading to postoperative CSF rhinorrhea. The
patient is placed with head end raised, to minimise
intra-operative bleeding.

Surgical Technique
The skin incision should be either within 3 mm of the
medial canthus or beyond 8-10mm from medial
canthus, so as to avoid cutting the angular vessels
(Fig. 93.12A); the incision is a curved one conforming
with the anterior lacrimal crest. It begins just above
the medial palpebral ligament and is deepened
through the orbicularis muscle to expose the anterior
lacrimal crest. The second type of incision is placed
about midway between medial canthus and bridge of
Fig. 93.12B: Periosteum being reflected laterally to
nose; it is a straight incision, about 2cm in length.
expose the anterior lacrimal crest
After exposing the anterior lacrimal crest, the
periosteum is incised and periosteal elevator used to
reflect it on the lateral side (Fig. 93.12B). The blunt
dissector is then used to separate the sac from the
lacrimal fossa, down upto the opening for the NLD
and posteriorly to the posterior lacrimal crest.
The next step is preparation of the bony opening.
Several ways are available to make this opening. A
quick way is to fracture the thin lacrimal bone of the
posterior half of lacrimal fossa using the small end of
the blunt dissector. During this procedure the dissector
must be oriented as parallel to the bone as possible to
avoid nasal mucosal damage. The process is initiated
with small punches and enlarged later with larger
ones. Ideally, the bony opening should extend Fig. 93.12C: Bony opening has been made while
anteriorly upto and involving the anterior lacrimal protecting the sac laterally
 Chapter 93: Anatomy, Physiology and Diseases of the Lacrimal System
care should be exercised to avoid damaging the nasal
mucosa; the introduction of bone punch closely
hugging the bone is important to avoid this damage.
Alternative techniques of making the bony ostium
are of using an electrically driven Stryker’s saw or by
a hand-driven or motor-driven trephine (Iliff, Arruga).
Next, the sac is opened to create the anterior and
posterior sac flaps. The lower most part of the sac
where it forms the nasolacrimal duct is given a small
incision. A lens hook is passed into the lumen of the
sac through the incision to confirm that the incision is
full thickness. One blade of a blunt-pointed scissors is
introduced into this small opening and the medial wall
of lacrimal sac is cut to create a larger posterior and a
smaller anterior sac flap. An alternative technique of
fashioning the sac flaps is by tenting the medial wall
of lacrimal sac over a probe passed through the
canaliculus. The medial wall is then incised over the
probe and cut from above downward with scissors.
The important thing is to open the sac right down to
the point where it forms the NLD, otherwise a small
cul-de-sac may be left in the lowest part of lacrimal
sac causing retention of mucopus and persistence of
the patient’s symptoms in spite of the patent
anastomosis.
The nasal mucosa is incised horizontally in the
upper and lower limit of the bony opening. A lens
hook may then be passed between the two openings
to lift the mucosa. These two incisions are joined by a
vertical incision at the desired position thus creating
a larger anterior and smaller posterior flap. Bleeding
from the nasal mucosa is prevented by packing the
area with a gauze soaked in adrenaline (1:200,000) for
few minutes.
The anterior and posterior flaps are sutured using
6-0 vicryl suture. The specially designed 5/8 circle
needles are particularly helpful for this purpose. The
anterior flaps are also anchored to the adjacent
periosteum to prevent them from falling backwards
and closing the anastomosis.
The incision is closed in layers using 6-0 vicryl for
the orbicularis muscle and 6-0 silk for closing the skin
incision.
Many surgeons advocate using some means to
maintain separation of the anterior and posterior flaps
for some time during the postoperative period. This
can be achieved by passing a silastic tubing through
the two canaliculi to emerge from the internal common
punctum. The two ends are passed through the bony
ostium and into the nose. A triple tie is placed in the
721
ends of the tubing and pulled to estimate the tension
of the loop of the medial canthal area. The two ends
of the silastic tubing are passed through another
slightly larger bore silastic tubing so as to hold them
in place. The anterior flaps of the sac and nasal mucosa
are then sutured together. This tubing may be
removed approximately 6 weeks postoperatively if
there was no common canalicular or punctum
problem at the time of surgery. Alternatively, a large
catheter can be passed through the DCR ostium and
into the nose to maintain the patency of the anas-
tomosis. The catheter is held in position by a single
absorbable suture to the anterior wall of the sac above.
The catheter is removed after 2 weeks when the
absorbable sutures have become friable.
Results of DCR
When properly performed, the success rates of DCR
have been reported to be as high as 94% to 99%.26, 27
Complications of DCR
i. Hemorrhage: Intranasal bleeding may occur from
the nasal mucosa, which requires nasal packing
for 24 hours.
ii. Failed DCR surgery: Causes and management of
failed DCR are discussed below:
Causes of Failure in DCR Surgery
i. Inadequate bony opening is, by far, the most
important cause for failed DCR.
ii. Anastomotic block may occur due to improper
suturing, redundant flaps, bony fragments,
postoperative hematoma or infection.
iii. Iatrogenic common canalicular obstruction may
at times be the cause of failure.
iv. Nasal pathology, which may have been over-
looked preoperatively, e.g. hypertrophied middle
turbinate, nasal polyps, etc.
Management of Failed DCR
All cases must be evaluated clinically by intranasal
assessment, irrigation of lacrimal passages, Jones’ dye
tests, probing and dacryocystography (DCG). The
choice of surgical procedure is made on the basis of
clinical observations.
In patients where regurgitation of mucopurulent
discharge is present and DCG shows presence of a
moderate sized sac, repeat DCR is performed with the
722 Section 6: Diseases of Orbit
passage of a ureteric catheter to maintain patency of
the anastomosis. In cases where the sac shows
intraluminal adhesions extending close to the common
canalicular opening, a silicone tube intubation of
passages is carried out alongwith the DCR.
In patients with common canalicular block the
procedure of canaliculodacryocystorhinostomy with
silicone tube intubation is preferred. However, in cases
with a proximal common canalicular block or
obstruction of individual canaliculi, the procedure of
conjunctivodacryocystorhinostomy is necessary.
OBSTRUCTION OF COMMON CANALICULUS
The exact level of obstruction in a case of common
canalicular block is determined by measuring the
distance of the obstruction from the punctal opening
by passing a probe. This is helpful in planning the
procedure to be performed. Preoperative evaluation
and type of anesthesia is the same as for conventional
dacryocystorhinostomy.
A probe is passed from each punctum to the site of
obstruction. A flimsy common canalicular obstruction
is often overcome by gentle pressure from the probe.
In this situation the passages are simply intubated with
silicone tubing (0.2 inch inner diameter. 0.37 inch outer
diameter; Dow corning) using a lacrimal intubation
set, both from upper and lower puncta; the nasal ends
being fixated by a larger tubing or tied together. Many
of the cases of common canalicular obstruction can be
managed by the above method. In cases where it is
not possible to overcome this obstruction by gentle
pressure, the procedure of canaliculodacryocystor-
hinostomy becomes necessary.
Canaliculodacryocystorhinostomy
The surgical procedure is carried out as a routine
dacryocystorhinostomy till the step of suturing of the
posterior flaps. Following the skin incision, dissection
is carried down to the level of medial palpebral
ligament (MPL) which is then incised from the
periosteum and retracted laterally. Probes are pushed
into both canaliculi until an obstruction is encoun-
tered. The common canaliculus is freed from posterior
limb of medial canthal tendon and all the tissues
between deep surface of MPL and the lacrimal sac are
cleared carrying the dissection to the level of posterior
lacrimal crest. All pericanalicular fibrous tissue is
excised thoroughly. It is helpful to do this surgery
under magnification. The most medial patent part of
common canaliculus is identified and opened. The part
is freed by circumferential dissection and intubated
from the punctum by two ends of a silicone tube. The
remaining obstructed portion is excised. The bony
opening is made as for a DCR surgery.
The common canaliculus is sutured to the flaps of
the lacrimal sac and DCR completed as usual. Where
lacrimal sac is obstructed, fibrosed or destroyed, the
common canalicular flaps may be sutured directly to
the nasal mucosa, using absorbable sutures. Silicone
tubes are passed through the rhinostomy and brought
out through the nose before suturing the anterior flaps.
The free ends of the tube are sutured together and left
in place for 3 to 12 months.
In this procedure it is important that the obstruc-
ting scar should be dissected from its most lateral
extension medially until patency is found. Very often,
the sac is also scarred and the patent canalicular
remnant must be anastomosed directly to the nasal
mucosa. However, a minimum of 8mm of patent
canalicular system must be present to allow this
anastomosis without undue tension. If less than 8 mm
of the canalicular system remains intact, the anas-
tomosis is too difficult and conjunctivodacryo-
cystorhinostomy should be considered. Recently it has
been suggested that in cases of proximal common
canalicular obstruction, where a conjunctivo-DCR is
necessitated, the procedure should be combined with
a canalicular reconstruction and silicone tube
intubation.29
Conjunctivodacryocystorhinostomy
Jones29 described a procedure to treat patients with
canalicular block by creating an artificial channel
between the conjunctival sac and the middle meatus.
The surgical technique is the same as in conven-
tional DCR procedure until the posterior sac and nasal
mucosal flaps are sutured. Thereafter the caruncle is
resected and a 23 gauge curved hypodermic needle is
entered in the conjunctiva 2 mm from the canthal
angle. It is directed in a plane, which will cause it to
enter into the lacrimal sac just below the canthal angle
and behind the anterior sac flap. With the needle in
place a narrow Graefe’s knife is passed in the same
plane after which the needle is withdrawn. The knife
is used to enlarge the passage to accommodate the
entry of the flanged tube. The length of the tube
required is estimated by passing a probe from the
conjunctiva to the nasal septum. A tube 2mm smaller
than this length is passed over a lacrimal probe wider
 Chapter 93: Anatomy, Physiology and Diseases of the Lacrimal System
end first and passed into the passage by the side of
Graefe’s knife.
It is important to ensure that the nasal end of the
probe is not abutting against the middle meatus. The
tube is anchored to the lower lid near the medial
canthus by a double arm suture. The anterior sac and
nasal flaps are sutured and DCR completed as usual.
Several materials have been tried to create the
artificial channel between conjunctival sac and nasal
cavity. Jones recommended using a polythene tube
intraoperatively, to be replaced by a pyrex glass tube
after the postoperative edema subsides because a glass
tube causes less irritation, possesses capillary
attraction and does not clog easily with secretions.29
Carrol and Beyer30 used a silicone tube hoping to
encourage development of an epithelialized track.
Grover and associates31 described use of a polythene
tube in order to overcome the difficulties in availability
of pyrex glass tubes. The polythene tube of required
size is fashioned from a scalp vein tubing by
momentarily flaming the proximal end repeatedly till
the desired width of flange is obtained. The results
are comparable to studies using pyrex glass tube.
However, mucus plugging remains a serious problem
with use of polythene tubes, requiring regular
irrigation of the tube.
An important aspect of postoperative care in all
patients is educating them regarding care of the tube
and prevention of its extrusion. A meticulous
postoperative care holds the key to success. Extrusion
of the tube, mucus plugging and granulation tissue at
conjunctival and nasal ends are the important
complications. Extrusions are managed by immediate
replacement.
Balloon Catheter Dilatation
Becker et al described this method, which is effective
in both congenital and acquired nasolacrimal duct
obstruction. The advantages of the procedure include
its simplicity, short time taken, easy repeatability and
requirement of only topical anesthesia in adults. The
procedure has been described as follows32: A lacrimal
probe is advanced through the lacrimal passages, into
the nose. A guide wire is then passed into the lacrimal
sac. A balloon catheter is guided over the wire and
inflated. This is done twice for 10 minutes each at 10
bars. Success rate has been reported to be 95% in a
group of 51 cases of congenital nasolacrimal duct
obstruction above the age of 1 year. Long-term success
723
rates in adults have been reported to be 70% in adults
(both partial and complete obstruction) and as high
as 85% when patients with complete obstructions were
excluded.33 Therefore, it is of much greater benefit in
patients with partial obstructions. This procedure may
be recommended as a primary procedure in those
patients who refuse an external dacryocystor-
hinostomy.
Antimetabolites in Lacrimal Surgery
Several modifications of dacryocystorhinostomy have
been described. Some authors have recommended the
use of Mitomycin C in a dose of 0.2 mg/ml. It is
applied as a cottonoid soaked in the solution, to the
osteotomy site as well as the anastomosed flaps. The
cottonoid is removed after 30 minutes transnasally.
The principle behind the use of Mitomycin C is its
antiscarring and antifibrotic effects, thus resulting in
a larger osteotomy size. It has been shown that the
intra-operative use of Mitomycin C effectively results
in a larger osteotomy size at 6 months follow-up.34 It
has been suggested that the use of Mitomycin C be
restricted to patients with previously failed dacryocys-
torhinostomy, as one of the commonest causes of
failure of conventional dacryocystorhinostomy is
fibrosis and closure of the osteotomy opening.
Endoscopic Nasal Lacrimal Surgery
Endoscopic surgery may be done in the case of a
primary dacryocystorhinostomy, in the revision of
failed dacryocystorhinostomy, and even for intubation
of the lacrimal system.
The potential advantages of endoscopically
assisted surgery include excellent hemostasis,
decreased postoperative pain, swelling and bruising.
Moreover, an external incision is avoided, thus
preventing scarring and webbing. There is minimum
distortion of the medial canthal anatomy.
As in a conventional dacryocystorhinostomy, an
osteotomy is made in the lacrimal bone. A variety of
tools have been used to make this opening, including
curette, punch, chisel, electric burr and lasers. The
lasers available for this purpose include Holmium
YAG and blue green Argon laser. These lasers are
suitable as they have sufficient power to penetrate the
bone.
An important step in the performance of an
endoscopic dacryocystorhinostomy is intubation of
the lacrimal system using silicone tubes. This step
724 Section 6: Diseases of Orbit
helps to maintain patency, as the flaps are not
anastomosed in this procedure.
There are definite disadvantages of endoscopic
surgery. Besides the high cost of instruments and
equipment, there is a steep learning curve. It has been
seen that on an average, endoscopic dacryocystor-
hinostomy takes longer time than a conventional one.
Some contraindications to the use of endoscopic
dacryocystorhinostomy surgery include lacrimal sac
tumours and dacryoliths and large abscesses of the
lacrimal sac. Preoperative diagnosis of these condi-
tions requires the routine use of a CT Dacryocysto-
graphy, increasing the effective cost of the procedure.
In a prospective randomized study to compare
external dacryocystorhinostomy to endonasal laser
dacryocystorhinostomy, there was a 91% success rate
for the external group while a 63% success rate for the
endonasal laser group.35 This is a significant diffe-
rence, especially considering that most studies report
higher than 90% success rates in primary external
dacryocystorhinostomy.
Transcanalicular YAG Laser in
Failed Dacryocystorhinostomy
A method that has been tried for the revision of failed
dacryocystorhinostomy is the use of transcanalicular
Nd YAG laser. Its success rate has not been found to
be comparable to that of external dacryocystor-
hinostomy. It is, therefore, unlikely to be adopted in
place of external dacryocystorhinostomy.
Dacryocystectomy
Dacryocystectomy is the surgical removal of the
lacrimal sac. Indications of dacryocystectomy include
elderly patients with chronic dacryocystitis without
epiphora and patients with lacrimal sac tumours.
The preoperative evaluation, type of anesthesia
and skin incision are the same as for DCR surgery.
The medial tendon is exposed and cut close to its
insertion into the bone. The lacrimal facia is cut and
the sac freed from the lacrimal fossa by blunt
dissection. The canaliculi are cut and the dome of the
sac is grasped and pulled forwards so that the sac is
freed posteriorly all the way down to the duct. The
junction of the sac and NLD is cut and the walls of
fossa are curetted thoroughly to get all the remnants
of the sac. The ends of the medial canthal tendon are
sutured together and the incision closed in layers.
REFERENCES
1. Jones LT. The lacrimal secretory system and its treatment.
Am J Ophthalmol, 1966;62:47.
2. Jordan A, Baum JL. Basic Tear Flow, does it exist? Ophthal-
miol 1980;87:920.
3. Jones LT. The cure of epiphora due to canalicular disorders,
trauma and surgical failure on the lacrimal passages. Trans
Am Acad Ophthalmol Otolaryngol 1962;66:5061.
4. Daubert J. Tear flow analysis in the upper and lower system.
Ophthal. Plast Reconstr Surg 1990;6(3):193.
5. William M Hart Jr (Ed). Adler’s Physiology of the Eye Clinical
Application (9th Ed). Harcourt Brace and Company: Asia PTE
LTD 1992.
6. FZappia R, Milder B. Lacrimal drainage function I. The Jones
fluorescein test. Am J Ophthalmol 1972;74:154.
7. McEwan CJ, Young JD. The fluorescein disappearance test
(FDT): An evaluation of its use in infants. J Paediatr
Ophthalmol Strabismus 1991;28:302.
8. Raflo GT. Assessment of efficacy of chemiluminescent
evaluation of lacrimal drainage system. Ophthalmic Surgery
1982;13:36.
9. Ralfo GT, Chant P, Hurwitz JJ. Thermographic evaluation of
lacrimal drainage system. Ophthalmic Surgery 1982;13:119.
10. Coehn SW, Prescott R, Sherman M. Dacryoscopy. Ophthalmic
Surgery 1979;10:57.
11. Rossomondo RM. Carlton WH, Trueblood JH: A new method
of evaluating lacrimal drainage. Arch Ophthalmol 1972;
88:523.
12. Dutton JJ. Standardised echography in the diagnosis of
lacrimal drainage dysfunction. Arch. Ophthalmol 1989;
197:1010.
13. Katowitz JA, Welsh MG. Timing of initial probing and
irrigation in congenital nasolacrimal duct obstruction.
Ophthalmology 1987;94:698.
14. Mannor GE, Rose GE, Frimpong-Ansah K et al. Factors
affecting the success of nasolacrimal duct probing for
congenital nasolacrimal duct obstruction. Am J Ophth
1999;127:616.
15. Paul TO, Shephard R. Congenital nasolacrimal duct
obstruction: Natural history and the timing of optimum
intervention. J Paediatr Ophthalmol Strabismus 1994;31:362.
16. El Mansoury J, Calhoun JH, Nelson LB, Harley RD. Results
of late probing for congenital nasolacrimal duct obstruction.
Ophthalmol 1986;93:105.
17. Kassoff J, Meyer DR. Early office-based versus late hospital-
based nasolacrimal duct probing. Arch Ophthalmol
1995;113:1168.
18. Robb RM. Success rate of nasolacrimal duct probing at time
intervals after 1 year of age. Ophthalmol 1998;105:1301.
19. Leone CR Jr, Van Gemert JV. The success rate of silicone
intubation in congenital lacrimal obstruction. Ophthalmic
Surgery 1990;21:91.
20. Ratliff CD, Meyer DR. Silicone intubation without intranasal
fixation for treatment of congenital nasolacrimal duct
obstruction. Am J Ophth 1994;118:781.
21. Pe MRL, Langford JD, Linberg JV et al. Ritleng intubation
system for treatment of congenital nasolacrimal duct
obstruction. Arch Ophth 1998;116:387.
 Chapter 93: Anatomy, Physiology and Diseases of the Lacrimal System
22. Kalra BR, Dayal Y, Grover AK, Betharia SM. A modified
approach to repair of lacerated canaliculus. Proc. Congress
of Asia Pacific Acad of Ophthalmology. New Delhi 1985.
23. Wallar RR. Treatment of acute eyelid trauma. J Trans Am
Acad Ophthalmol. Otolaryngol 1976;81:556.
24. Beard C. Repair of traumatic defects of the, lacrimal system
(acute). In Smith B and Converse JM (Eds): Proc. Second
International System on ‘Plastic and Reconstructive Surgery
of the Eye and Adnexa. St Louis: CV Mosby Co, 1967;171-
179.
25. Quickert MH, Dryden RM. Probes for; intubation in lacrimal
drainage. Trans Am Acad Ophthalmol Otolaryngol 1970;74:
431.
26. Mclachlan DL, Shannon GM, Flangan JC. Results of
dacryocystorhinostomy: analysis of reoperations. Ophthalmic
Surgery.1980;11:427.
27. Welham RAN, Henderson P. Failed dacryocystorhinostomy.
Trans Am Acad Ophthalmol and Otolaryngol 1974;78:824.
28. Steinsagir KO, Glatt HJ, Putterman AM. A I6-year study of
conjunctivo-DCR. Am J Ophthalmol 1990;109:387.
29. Jones LT. Conjunctivodacryocystorhinostomy. Am J
Ophthalmol 1965;59:773.
725
30. Carroll JM, Beyer CK. Conjunctivodacryocystorhinostomy
using silicone rubber lacrimal tubes. Arch Ophthalmol
1973;89:113.
31. Grover AK, Kumar S, Gupta AK, Rastogi A. Canalicular
obstruction—Is polythene tube conjunctivodacryocystor-
hinostomy the answer (A long term appraisal)? Proc. 49th
Annual AIOS Conference. Bangalore, 1991.
32. Becker BB, Berry FD, Koller H. Balloon catheter dilatation for
treatment of congenital nasolacrimal obstruction. Am J Ophth
1996;121:304.
33. Janssen AG, Mansour K, Bos JJ. Obstructed Nasolacrimal Duct
System in Epiphora: Long-term Results of Dacryocystoplasty
by Means of Balloon Dilatation. Radiology 1997;205:791.
34. Kao SCS, Liao CL, Tseng JHS et al. Dacryocystorhinostomy
with intraoperative mitomycin C. Ophthalmology 1997;
104:86.
35. Hartikainen J, Grenman R, Puukke et al. Prospective
randomized comparison of external dacryocystorhinostomy
and endonasal laser dacryocystorhinostomy. Ophthalmology
1998;105:1106.
 Chapter 94

Radiographic Study of
Lacrimal Passage
AS Mehrotra

SURGICAL ANATOMY OF LACRIMAL PASSAGE

The lacrimal passage consists of the following:

a. The upper passage which includes lid margins,
puncta, canaliculi, common canaliculus (sinus of
Maier and valve of Rosemuller).
b. The lower system comprised of lacrimal sac,
nasolacrimal duct, and valve of Hasner.
The canaliculus originates from puncta having a
vertical portion of 2.0 mm and a horizontal portion,
of 6 to 8 mm length, with diameter of 0.5 mm. The
superior and inferior horizontal portions unite
together to form a common canaliculus in 90 percent Fig. 94.1: Anatomy of lacrimal passage
of cases, which is also known as sinus of Maier, to DACRYOCYSTOGRAPHY (DCG)
open into lacrimal sac (Fig. 94.1).
Dacryocystography was first performed by Ewing in
The lacrimal sac is the widest portion of lacrimal
1909. It is helpful in documenting functional and
apparatus, with a vertical dilated part tapering below
morphological status of tear flow by visulizing the true
to continue as nasolacrimal duct which opens into the
dimension of the passages.
inferior nasal meatus. The average size of the sac and
the duct in infant and adult given below (in mm) is Types of Dacryocystography
different.
1. Plain dacryocystography (PDG)
Sac Duct 2. Distention dacryocystography (Fig. 94.2)
Width Length Width Length 3. Macrodacryocystography (MDCG) (Fig. 94.3)
Infant 2.5-3.5 10-11 2-3 14-16 4. Cinematography
Adult 2.5-4.5 10-15 4.2-4.4 16-22 5. Dacryoscintigraphy (DSG) (Figs 94.4A and B).
Nasolacrimal duct has few valves which check the
Radiopaque Dyes Used for Dacryocystography
flow of tear in reverse direction. At the upper end of
the duct there is a mucosal fold called the valve of The radiopaque dyes are:
Krause. Another valve, the valve of Hasner, is at the i. Lipoidal in water or lipoidal with olive oil
lower end of the duct. ii. Iodized oil
 Chapter 94: Radiographic Study of Lacrimal Passage
Fig. 94.2: Procedure of distention DCG
Fig. 94.3: The procedure of macrodacryocystography
727
A B
Figs 94.4A and B: Normal dacryoscintigraphy. (A) Canaliculi
(B) Sac and duct
iii. Neohydroil angiographin
iv. Dionosil aqueous
v. Conray
vi. Diagonal viscous.
Thin watery dyes are easy to inject but do not stay
in passage and come out through puncta. Oily
preparations stay well but require high pressure to
inject. They may not fill narrow passage like small
diverticulum. The viscous and water soluble contrast
media stay well as well as spread well to give better
contrast and they do not have globule formation.
Further, they are easy to inject and gives a good
radiographic contrast.
Techniques
Plain DCG
About 0.5 ml of dye is pushed into the sac through
lower puncta and canaliculus with a canula attached
to 2.0 ml syringe. The cannula is now removed and X-
ray of AP and lateral views are taken to visualize the
lacrimal passage.
Distention DCG
It is named so, because the passage is kept distended
throughout the procedure of taking the X-ray by
keeping the cannula in the canaliculus and pushing
the radiopaque dye in required quantity till X-rays
are taken.
Procedure After topical anesthesia punctum is
dilated; 20 or 22 G cannula is pushed into lower
canaliculus and connected through nylon tube to 2.0
ml syringe containing the radiopaque dye. The tube
is fixed on cheek or lower lid with adhesive plaster.
Required amount of dye, depending on the size of the
728 Section 6: Diseases of Orbit

sac, is pushed. Patient may be kept in sitting or supine to see for partial obstruction, if any, which will show
position. Water’s and lateral projection of X-rays are as a thin line of the contrast media in the passage below
taken (Fig. 94.2). the obstruction site.
In cases with patent passage the dye appears in
nasal passage within few seconds. In cases with Cinematography of Lacrimal System
partially blocked passage, which is usually at the level
It is just taking a series of X-rays after injecting the
of nasolacrimal duct, the dye may appear gradually
radiopaque dye. This gives a better idea of the
in nasal passage, either due to pressure with which it
condition of the sac and nasolacrimal duct. Partial
is pushed into the sac or with little massage over sac
obstruction, if any, can be visualized prominently. This
area. This procedure to study the lacrimal passage has
method requires a very well set radiodiagnostic unit.
few advantages over conventional DCG. Here due to
It is of research interest only.
constant distention of passage, exact idea of the size
of the sac, diverticula or false passage, and other
Dacryoscintigraphy (DSG)
details are easily detected.
This noninvasive technique is helpful in documenting
Macrodacryocystography functional as well as morphological status of tear
passage. Two drops of radio tracer Tc99m are used in
1. Canalicular diseases and obstructions are best seen
each eye. Series of images of both eyes are teken at
by magnification.
interval of 5 minutes for 35 to 40 minutes by Gamma
2. Details are enhanced by very good contrast
Camera fitted with pinhole collimeter which focuses
obtained from filtrations of large air gap as the film
the required area. In a normal dacryoscintigraph
is kept away from head.
lacrimal passages can be visualized due to appearance
3. Use of small focus of X-ray beam has given large
of tracer in nasal cavity (Fig. 94.4A and B) after
but a sharp image as there is no geometric
outlining the lacrimal sac and nasolacrimal duct. If
unsharpness.
there is obstruction in the passage, lacrimal sac cannot
The basic principle of the technique is the same as
be visualized. Persistent pooling of the radiotracer in
in distention DCG; only the method of taking the X-
lacrimal sac indicates, obstruction at sac nasolacrimal
ray is different. The film cassette is kept under the X-
ray table on a wooden stool with a stationary grid. duct junction.
The head of the patient is at a midway position This study also helps to differentiate epiphora due
(Fig. 94.3) between the film and X-ray tube. The focus to blockage from epiphora due to lid laxity in old age
film distance (FFD) should be 36 inches. For two times resulting from lacrimal pump dysfunction.
magnification, the object film distance should be 18
inches. Radiography in Operated Cases of Sac

FFD 36
After dacryocystectomy mucopurulent discharge may
_______________________
= _____
= 2 times. still be present if the sac is not completely removed or
Object-focus distance 18 after regeneration of the lacrimal sac. This can be
detected with radiographic study. Similarly, post-
Anteroposterior and lateral skiagrams are taken operative cases of dacryocystorhinostomy can be
immediately after injecting the contrast medium and assessed to find out the actual cause of nonfunctioning
a set of delayed films are also taken after 15-30 minutes of the ostium after the operation.
 Chapter 95

Lacrimal Gland Tumors

LC Dutta, KS Ratnakar

ANATOMY OF THE LACRIMAL GLAND
The lacrimal gland is an exocrine gland situated in
the anterior and upper part of the roof of the orbit
which forms a concavity known as the fossa for the
lacrimal gland. It is in direct contact with the upper
and outer side of the eyeball. Anatomically, it has two
parts incompletely separated by the levator palpebrae
superioris muscle, i.e. a bigger orbital portion and a
smaller palpebral portion. The anterior border of the
palpebral part can be seen through the conjunctiva in
the lateral part of the superior fornix. 10 to 12 ducts
from both the portions of the gland open into the
conjunctival sac just in front of the superior fornix.
Few ducts open into the lateral part of the inferior
fornix also. The ducts from the orbital portion pass
through the palpebral portion and hence, removal of
the palbebral portion might result in loss of secretion
of lacrimal fluid. Few accessory lacrimal glands
(glands of Krause and Wolfring) are present in the
conjunctiva between the superior fornix and the upper
convex border of the tarsal plate; these glands have
got no apparent nerve supply. Structure of the lacrimal
gland represents that of the parotid gland. Surface of
the gland is lobular and is covered with a fibrous
fascia, expansions from which go in between the
lobules. The acini consists of two layers of cells
surrounding a central canal. The outer layer cells are
myoepithelial in character and the inner layer of
cylindrical cells are secretory in nature.
Space Occupying Lesions of the Lacrimal Fossa
Space occupying lesions of the lacrimal fossa may be
due to noninfectious inflammatory process and
tumors arising from the lacrimal gland. Cystic
formations and dermoid of the lacrimal gland may
simulate a tumefaction process. Sometimes simple
dislocation of the palpebral part of the lacrimal gland
may be mistaken for a tumor. Most of the tumors of
the lacrimal gland are basically epithelial tumors or
mixed tumors and others are lymphomas and
adenocarcinomas. The simple classification of lacrimal
gland swellings:
1. Inflammatory swellings
2. Cystic process
3. Dermoid
4. Lymphoid swellings
5. Tumors:
a. Benign mixed tumor
b. Malignant mixed tumor
c. Adenocystic carcinoma
d. Other types of carcinoma.
Accurate histopathological classification suggested
by WHO is shown in Table 95.1.
Inflammatory Lesions
a. Acute inflammation of the lacrimal gland usually
occurs in children. It is characterized by pain and
swelling of the gland. The lid on the affected side
appears to be ptosed or it may simulate orbital
cellulitis. Acute dacryoadenitis develops as a
complication of measles or even acute conjunc-
tivitis.
b. Chronic dacryoadenitis is usually common in
adults and is characterized by a hard movable
lobulated mass with very little or no pain,
tenderness or edema. Granulomatous pathology
like tuberculosis or sarcoidosis are common cause
of chronic dacryoadenitis. This condition is to be
730 Section 6: Diseases of Orbit

Table 95.1: Histopathological classification
of tumors by WHO1
I. Epithelial tumors
A. Adenomas
1. Pleomorphic adenoma (Benign mixed tumor)
2. Other Adenomas
B. Mucoepidermal tumors
C. Carcinomas
1. Carcinoma in pleomorphic adenoma (Malignant
mixed tumor).
2. Adenoid cystic carcinoma
3. Adenocarcinoma
4. Others
II. Tumors and tumor-like lesions of hemopoietic or lymphoid
tissue
A. Tumor-like lesions of reactive lymphoid hyperplasia
B. Lymphoid lesions of intermediate nature
C. Malignant lymphoma
D. Systemic disease
III. Secondary tumors
IV. Inflammatory and other tumor-like lesions
A. Chronic dacryoadenitis
B. Benign lymphoepithelial lesions
C. Dacryops
D. Others
V. Other unclassified tumor-like lesions.
differentiated from tumors of the lacrimal gland.
However, before an invasive method of diagnosis
like fine needle aspiration cytology or surgical
biopsy is planned, it is better to give a course of
systemic antibiotic and steroid. If the therapeutic
trial fails then only invasive diagnostic procedure
should be undertaken.
Basically the lesions in the lacrimal gland fossa may
originate from the following:
a. Epithelial elements of the lacrimal gland, or
b. Primarily of the nonepithelial tumors.
EPITHELIAL LACRIMAL GLAND TUMORS
1. Dacryops
2. Pleomorphic adenoma (Benign mixed tumor)
3. Malignant tumor.
Dacryops or Ductal Cyst
It is a cystic dilatation of one of the lobes of the lacrimal
gland. The cyst is usually unilateral but may be
bilateral also.2 This commonly occurs in the age group
of 35 to 45 years. Clinically, it appears as a slowly
growing painless bluish mass in the superolateral
fornix at the site of the exit of the lacrimal ducts. It
may enlarge during crying or on exposure to irritants.
Treatment is surgical removal. Asymptomatic cases
may be marsupialized. Aspiration of the fluid from
the cyst may also be done but the condition usually
recurs after aspiration.
Pleomorphic Adenoma
(Originally called Benign Mixed Tumor)
Benign mixed tumor is the most common tumor of
the lacrimal gland.3 It is called mixed tumor because
it consists of two distinct elements— one element in
the epithelial lining of the duct and the other element
has an apparently mesenchymal appearance. The
stroma is formed by the outer layer of epithelium that
lines the duct. The typical age of presentation of
patients with mixed cell tumor is 35 years. It presents
as a painless swelling in the supratemporal region of
the anterior part of the orbit in middle aged persons.
The eyeball is displaced downward and medially
sometimes causing diplopia. The tumor is firm in
consistency with a lobulated surface. The tumors are
nonvascular and may contain cystic cavities. The
orbital lobe of the gland is most commonly involved;
palpebral lobe involvement is rare.4 After developing
from the orbital lobe the benign mixed tumor tends
to extend farther back into the orbit and may become
quite large. In some cases these lesions cause
indentation of the ocular wall, choroidal folds and
bony excavations. When involving only the palpebral
lobe, the lesion usually remains anterior and does not
cause bony deformities.5
Benign mixed tumors consists of epithelial and
connective tissue elements which vary in relative
amount, arrangement, and differentiation showing a
diverse but typical histological picture. Histological
appearance not only varies from patient to patient but
also in different parts of the same tumor. Tubular
structure of the epithelial element may be arranged
in an irregularly anastomosing pattern in myxoid
stroma which is rich in hyaluronidase resistant type
of acid mucopolysaccharide. The tubes or ducts are
lined by a double layer of epithelium. The inner layer
of epithelium secretes mucus or undergoes mucous
metaplasia and the outer layer forms myxoid, fibrous
or cartilaginous stroma. Pressure of the tumor on the
surrounding tissue creates a capsule like condensation
(pseudocapsule). The tumor almost always infiltrates
 Chapter 95: Lacrimal Gland Tumors
the pseudocapsule in some places. Therefore, there is
likelihood of recurrence of the tumor after shelling it
out by incising the pseudocapsule.
Diagnosis is confirmed by orbital imaging. CT scan
shows mass lesion accompanied by fossae formation
without any bony erosion.
Treatment
Benign mixed tumors should be excised with the intact
capsule. Surgical biopsy or FNAB should be avoided.
Incomplete excision or prior surgical biopsy may lead
to recurrence, sometimes with malignant
transformation.
Malignant Epithelial Lacrimal Gland Tumors
Malignant lacrimal gland tumors may start as
malignant or show malignant transformation on
benign mixed tumors. Further, it is not unlikely that
benign mixed tumor is associated with simultaneous
growth of adenoid cystic carcinoma. Other malignant
lacrimal gland tumors are pleomorphic adeno-
carcinoma and mucoepithelial carcinoma. Adenoid
cystic carcinoma is the most common variety followed
by pleomorphic adenocarcinoma.
The age group in which malignant mixed tumor
may occur is around 50 years. There is no sex
predilection. Adnexal cystic carcinoma occurs in
young adults with median age of 38 years.
The clinical features of all malignant lacrimal
tumors are more or less the same. Proptosis with
downward and medial displacement of the globe,
limitation of some ocular movements, ptosis, conjunc-
tival injection, and pain due to involvement of the
periosteum of the lacrimal fossa. The rate of growth
of de novo malignant tumors is rapid in comparison to
tumors transformed from benign lacrimal tumors.
Adenoid cystic carcinoma is the second most common
epithelial tumor and the most common primary
malignant tumor of the lacrimal gland. These tumors
are usually infiltrative, although in some cases they
can appear well circumscribed. The tumors have a
hard consistency and are nonvascular. These tumors
frequently affect the bone causing either excavation
or in some cases, extensive bony destruction.
Benign mixed tumors may be associated with
simultaneous growth of adenoid cystic carcinoma.
Malignant changes may first be detected when there
is recurrence after removal of benign mixed tumors.
731
Adenoid cystic carcinoma invades the perineural
lymphatics in the very early stage, hence its prognosis
is extremely poor. Systemic metastases, mainly in the
lungs, develops usually after 5 years of presentation
of symptoms. Characteristic swiss cheese histopatho-
logical appearance is due to the scattered island of
poorly differentiated small tightly packed epithelial
cells against the background of hyaline like stroma.
Lymphoma
Lymphoma of the lacrimal gland presents as a painless
mass involving the lacrimal fossa. The swelling can
be seen on the superolateral part of the fossa for the
lacrimal gland. It can also be palpable, rubbery, non-
tender mass fixed to the orbital margin. Lymphoma
may occur in adults of any age. It may be unilateral or
bilateral. It may be an isolated lesion of the lacrimal
gland or may be an association of systemic lympho-
proliferative disorder.
Differential Diagnosis of
Malignant Lacrimal Tumors
Dacryoadenitis In acute dacryoadenitis the history
is of short duration. It may be in terms of days rather
than in months. The upper lid becomes swollen and
reddish in color with some chemosis or conjunctivitis
with purulent discharge. The preauricular glands are
enlarged. This type of dacryoadenitis responds to
antibiotics unlike those secondary to mumps,
infectious mononucleosis, and herpes zoster.
Inflammatory pseudotumor of lacrimal gland This
is a painless condition. X-ray picture may not show
any abnormality, but CT scan demonstrates the size
and extent of the tumor.
Lymphomatous lesion Lymphomatous masses due
to reactive lymphoid hyperplasia or various types of
malignant lymphoma may occur in adults. The lesions
can be palpated in the region of the lacrimal gland
underneath the conjunctiva of the upper fornix
(Fig. 95.1).
Dermoid cyst Clinically it is difficult to differentiate
dermoid cyst from a tumor of the lacrimal gland. Plain
X-ray, CT scan, and MRI demonstrate the cystic nature
of the lesion with fluid inside it.
Sarcoidosis of the lacrimal gland is another
condition .
732 Section 6: Diseases of Orbit
Fig. 95.1: Lymphomatous swelling of the lacrimal gland
in a boy of 14 years. The right eye is pushed downward
Management and Prognosis of
Lacrimal Gland Tumor
Lesions of the lacrimal fossa present special problems
in diagnosis and management. Lesions conforming to
the clinical pattern of benign mixed lacrimal gland
tumors need not undergo incisional biopsy but require
an enblock excision with adjacent tissue through a
lateral canthotomy to ensure complete excision and
prevent late recurrence. Incisional biopsy is indicated
and should not be delayed in suspected infectious and
noninfectious inflammatory masses that have not
responded satisfactorily to medical therapy, and in
other lesions suspicious of being neoplastic but not
amenable to local excision.
Among the malignant neoplasms in the region of
the lacrimal gland the adenoid cystic carcinoma is
particularly vicious and metastasis is common. Only
slightly less malignant in terms of survival rate or
tumor free intervals are the malignant mixed tumors,
adenocarcinoma (Fig. 95.2), squamous cell carcinoma,
and mucoepidermoid carcinoma. These tumors
infiltrate the orbital tissue and periorbita that
surrounds the lacrimal gland; the adenoid cystic
carcinoma, in particular, may quickly spread into the
bone of the lacrimal fossa. Even though the tumor and
the surrounding mantle of normal lacrimal gland
including orbital and periorbital tissue are removed,
there may be undetected invasion of the neighboring
bone.
Fig. 95.2: Pulmonary metastasis (canon ball appearance) in
terminal stage of lacrimal gland adenocarcinoma in a man aged
31 years
The management of intrinsic neoplasms of the
lacrimal gland is of serious concern because some of
the most malignant primary tumors of the orbit occur
in the glandular tissue. The better surgical option is
to remove the tumor and adjacent adnexa in one stage
procedure, i.e. enblock resection of the lacrimal gland
with its periorbital base and surrounding bone. This
procedure minimizes seeding and provides a more
complete eradication of the neoplasm without losing
the eye, and assures a longer interval free of local
recurrence of metastasis.6
Exenteration of the orbit is logical in case of
malignant lacrimal gland tumor where there is orbital
infiltrate of tumor cells.
REFERENCES
1. International Histological classification of tumors No. 24
WHO. Histological classification of tumors of the eye and its
adnexa 1980;35.
2. Bullock JD, Fleishman JA, Russel JS. Lacrimal ductal cysts.
Ophthalmology 1986;93:1355.
3. Shields CL, Shields JA, Eagle RC, Rothwell JP. Clinicopatho-
logical review of 142 cases of lacrimal gland lesions. Ophthal-
mology 1989;96:431.
4. Awran J, Jakobiec FA, Krebs W. Benign mixed tumor of the
lacrimal gland. Clinical diagnosis and appropriate surgical
management. Ophthalmology 1988;95:90.
5. Jakobiec FA, Font RL. Orbit. In Ophthalmologic pathology:
In Spencer (Ed): A Atlas and Textbook (3rd ed): Saunders:
Philadelphia, 1986;3.
6. Shields CL, Shields JB. Lacrimal gland tumors. Intl
Ophthalmol Clinics 1993;33(3):181.
 SECTION 7: PEDIATRIC OPHTHALMOLOGY
INCLUDING STRABISMUS
Chapter 96
Neonatal Conjunctivitis
Samrat Chatterjee
Neonatal conjunctivitis or ophthalmia neonatorum is
defined by the World Health Organization as any
purulent conjunctivitis occurring within the first 28
days of life.1 It manifests as diffuse, nonfollicular, often
hyper-acute conjunctivitis where gram-stain of
conjunctival smear reveals at least one polymorpho-
nuclear leukocyte per high-power field.2 The impor-
tant causes are Neisseria gonorrhoeae, Chlamydia
trachomatis, Herpes simplex virus (HSV), other bacteria
like Staphylococcus aureus and Streptococcus pneumoniae.
Although neonatal conjunctivitis has been present
since antiquity it was only in 1750 that Quellmatz
linked the disease to maternal vaginal secretions.3 This
postulate was supported by Gibson (1807) and
Mackenzie (1830) and in 1841 Piringer confirmed it
by demonstrating the infective nature of vaginal
secretions. Later in 1879 Neisser identified gonococci
in both genital and conjunctival discharges. The
disease was attributed to gonococci till other causes
were recognized, the most important of which was
inclusion blenorrhea, caused by Chlamydia trachomatis.
The clinical features were described in detail by
Lindner in 1909 and the organism was isolated from
the conjunctiva in 1950s.3
The credit for preventing gonococcal neonatal
conjunctivitis goes to Karl Credé, a German ophthal-
mologist from Leipzig. In 1880, he introduced the
practice of disinfecting the conjunctival sac of the
infants immediately after birth with 2% silver nitrate
solution.4 This procedure remarkably reduced the
incidence of the disease in his hospital from 30-45 cases
per year to less than 1 case. This method which came
to be known by his name was actively adopted
worldwide. It remains till today a singular example
of the triumph of medicine in preventing blindness
and has been so effective that the concept of prophy-
laxis still continues.
ETIOPATHOGENESIS
The incidence of neonatal conjunctivitis is dependant
on the prevalence of sexually transmitted infection
(STI) in pregnant women and on the standards of
perinatal care.5 Gonorrhea started declining in the
developed countries during the mid-seventies and
eighties and there was a gradual rise in chlamydial
infections. In 2002, the rate of chlamydial infection
amongst women in United States was three times more
than that of gonorrhea.7 In developing countries, the
prevalence of gonorrheal and chlamydial infection is
estimated to be 2-40% and 6-45% respectively.8 In
India, Chlamydia trachomatis is the commonest STI
amongst women in prenatal clinics affecting 20-30%
cases.9,10
During the 19th century, in Europe, the prevalence
of gonococcal conjunctivitis among live births in
maternity wards exceeded 10%, produced corneal
damage in 20% and blindness in 3%.11 Nowadays it is
estimated that worldwide, 1000- 4000 newborn babies
become blind every year due to neonatal conjunc-
tivitis.11 The average incidence of neonatal conjunc-
tivitis reported from developed nations is generally
less than 12%.12-17 An accurate prevalence rate in
developing countries is difficult to estimate because
of inadequate reporting. Africa is the worst affected
with incidence ranging from 19-23%18,19 A 1997 survey
of blind schools in India estimated that 0.76% of
blindness amongst the inmates was because of
neonatal conjunctivitis.20
Currently Chlamydia trachomatis is reported more
often than Neisseria gonorrhoeae. Gonococcal neonatal
conjunctivitis is reported in 0.4 per 1000 live births in
734 Section 7: Pediatric Ophthalmology Including Strabismus
Belgium and 0.3 per 1000 live births in USA, while
chlamydia is reported in 5 to 60 per 1000 live births
in USA, 4 per 1000 live births in United Kingdom
and 40 per 1000 in Belgium. 11 Other studies
estimate the incidence of chlamydial conjunctivitis at
3-55%15-19,21-34 and of gonococcal conjunctivitis at
0-10%.15-19,21,22,26,29-33,35 Concurrent infections with
both have been reported in 1-4% of cases.18,19,21,22,26,31
The relative proportion of causative microorganisms
differ between countries, regions and cities and also
vary across cross-section of a population. In Kenya,
chlamydia was more commonly isolated from
conjunctival sacs of infants in a general maternity
hospital in Nairobi, while gonococcus was more
common in those born to mothers attending a sexually
transmitted disease clinic.19, 26 In United Arab Emirates
and India, microorganisms other than gonococcus and
chlamydia are isolated more often.33,36 In Singapore,
gonococcus was isolated in 68% of neonates with
conjunctivitis while chlamydia was detected in only
two cases.37
The transmission rate of Neisseria gonorrhoeae from
mother to infant is 30-42%19,38 and that of Chlamydia
trachomatis is 18-44%.19,39-41 In women infected with
both, the transmission rates are particularly higher for
gonococci, suggesting possible synergistic mecha-
nisms that enhance the efficiency of transmission and
virulence. 19 Vaginal delivery exposes the fetus to
microorganisms present in the maternal genital tract
and the surrounding skin.42 The fetus can also get
infected in utero by microorganisms ascending from
the vaginal cavity following prolonged rupture of
membranes.42 Infants delivered by cesarean section
also can develop chlamydial conjunctivitis.43
Important non-sexually transmitted pathogens
causing neonatal conjunctivitis are Staphylococcus
aureus, Streptococcus pneumoniae, Streptococcus viridans,
Hemophilus sp., Escherichia coli, Proteus sp, Klebsiella
pneumoniae, Enterobacter sp., Pseudomonas aeruginosa
and Serratia marcescens.13,14,25,28,44 These are usually
acquired after birth from nurseries, caregivers and
through unhygienic cultural practices. In many
instances no organism can be isolated from affected
neonates which may be due to differences in popu-
lation or culture techniques.13,15,19,30 Under normal
circumstances the infant’s conjunctival sac and eyelids
are colonized soon after birth by commensals like
Lactobacillus sp., Diphtheroids, Bacteroides, Staphylococcus
epidermidis and Propionibacterium sp. and also by
potential pathogens like Staphylococcus aureus and
Streptococci.45,46 These reflect the bacterial flora present
in the vagina and skin which are the sources of
contamination.
Factors that promote infection depend on the
immune status of the host and virulence of the
organisms. The natural defenses in the neonate are
not well developed. They lack specific immunity and
are unable to synthesize antibodies which they acquire
passively from the mother. Locally there is reduced
tear flow and low levels of IgA, lactoferrin and
lysozymes.14 The ocular surface is also susceptible to
injury during delivery. Neisseria gonorrheae possesses
pili, adhesion molecules and transmembrane proteins
that help it to attach to epithelial cells and penetrate
intact epithelium.47 Virulence is also promoted by
development of strains resistant to penicillin,
tetracycline and ciprofloxacin.2,48 Toxins and enzymes
from gram-positive and gram-negative bacteria
promote infection through direct effects. Chlamydia
possesses intrinsic mechanisms that protect it from
lysis within host cells.47
Although conjunctivitis is the commonest manifes-
tation in the newborns, Neisseria gonorrhoeae and
Chlamydia trachomatis also colonize the mucous
membranes of the pharynx, rectum, ear canal and
vagina.2,19,26 The extraocular sites act as sources of
repeated conjunctivitis and lower respiratory tract
infection like pneumonia.19,26
It has been estimated that in the United States the
seroprevalence of HSV 2 in women is 25.6%,49 and 1
in 2000 pregnant women have herpetic genital
infection during pregnancy, 50 of which 70% are
asymptomatic.51 Both HSV Type 1 and 2 can cause
neonatal conjunctivitis, but it is commoner with the
latter. Infection during third trimester is a significant
risk factor. The mode of transmission is either
transplacental or direct contact during vaginal
delivery or via contaminated amniotic fluid due to
prolonged labor after rupture of membranes. HSV-
Type 1 infection is however acquired from an
immediate family member with active infections like
cold sores or fever blisters. Shedding of the virus from
the cervix is rare and there are only 40-60% chances of
the mother transmitting the virus during vaginal
delivery.52
CLINICAL FEATURES
The clinical features of neonatal conjunctivitis are
rarely specific enough to suggest an etiologic diagnosis
(Table 96.1). Although the incubation period is helpful
 Chapter 96: Neonatal Conjunctivitis
Table 96.1: Differential diagnosis of ophthalmia neonatorum78,79
Etiology Onset Discharge
Silver nitrate 24-48 hours Mucopurulent
Neisseria gonorrhoeae 2-5 days Very purulent
Chlamydia trachomatis 5-12 days Mucopurulent
Bacterial 5-7 days Mucopurulent
Herpes Simplex 2-30 days Mucoid
in some instances, it may not be always reliable.
Clinical history should contain information related to
prenatal care of the mother including past and present
STI and their treatment, duration of ocular and
systemic symptoms, type of ocular prophylaxis and
any previous treatment of the conjunctivitis. The
clinician should also acquaint himself with local
cultural practices and be aware of any ongoing
infection in the nursery.
Chemical Conjunctivitis
Chemical conjunctivitis is a toxic reaction to silver
nitrate solution. It is reported in 2-90% of neonates
who receive it as a prophylaxis against infectious
conjunctivitis and is rarely seen with other
agents.18,21,53 It starts a few hours after instillation,
presenting usually within 24-48 hours after birth. It is
characterized by mild and transient conjunctival
congestion and tearing that resolves within a day or
two. The disease is rarely severe enough to cause
blindness though serious adverse reactions have been
reported following accidental over-dosages. 54
Evaporation of the solution during storage can
increase the concentration and cause toxicity.
Complications can be prevented by taking stringent
care in preparation and storage of the solution.
Chlamydial Neonatal Conjunctivitis
Chlamydial neonatal conjunctivitis appears between
5-14 days after birth and is bilateral in two thirds of
the cases.28 It is characterized by mucopurulent or
purulent discharge, lid edema, palpebral congestion,
chemosis, true or pseudomembranes, peripheral
punctate epithelial erosions and less commonly
subepithelial infiltrates with stromal haze. A follicular
response is absent as lymphoid follicles do not develop
before six to eight weeks after birth. If left untreated
the disease may persist up to three to twelve months
or more and long standing cases may present with
735
Corneal features
Epithelial keratopathy, corneal scarring
Ulcers, perforation, leucoma, conjunctival scarring
Epithelial keratopathy, pannus, conjunctival scarring
Epithelial keratopathy, ulcers
Corneal clouding, dendritic keratitis, stromal keratitis,
retinitis, encephalitis
follicular conjunctivitis. Late manifestations are
conjunctival scarring, superficial corneal vasculari-
zation, pannus and corneal scarring.55,56 Asymp-
tomatic infections with chlamydia with delayed
presentation can also occur even in those receiving
prophylaxis.57 Systemic manifestations like pneu-
monia presents usually between three weeks to three
months after birth, the onset of which is heralded by
fever and cough.28,40,58
Gonococcal Neonatal Conjunctivitis
Gonococcal conjunctivitis presents within two to five
days after birth with severe clinical features and
profuse purulent discharge.19,26 It can present even on
the first day if infection is acquired in utero. It can be
bilateral purulent conjunctivitis with severe conges-
tion and edema (Fig. 96.1). If untreated, it rapidly leads
to diffuse epithelial edema of the cornea giving it a
Fig. 96.1: A Nigerian infant with gonococcal neonatal
conjunctivitis. (Photograph courtesy: Dr Clare Gilbert, London
School of Hygiene and Tropical Medicine, London)
736 Section 7: Pediatric Ophthalmology Including Strabismus
hazy grayish appearance. Coarse infiltrates appear at
the limbus which can coalesce and enlarge to form
ulcers by the end of second or third week (Fig. 96.2).2
Untreated ulcers lead to corneal perforation with loss
of vision. The outcome is poor if treatment is not
initiated early.
Neonatal Conjunctivitis due to Other Bacteria
Although the onset of neonatal conjunctivitis caused
by other bacteria is usually later in the second or third
week after birth, the clinical features are often
indistinguishable from gonococcal or chlamydial
infection.28 The inflammation is usually less severe
than gonococcal conjunctivitis and is not much
different from that caused by chlamydia. They can
affect one or both the eyes with purulent discharge.
Systemic involvement is uncommon and is seen
with infection with Hemophilus influenzae, Pseudo-
monas, some gram-negative bacilli and meningococci.
Pseudomonas aeruginosa causes a purulent memb-
ranous conjunctivitis which may rapidly progress to
ulceration and is often associated with pneumonia.59
Herpes Simplex Neonatal Conjunctivitis
The clinical manifestations of neonatal herpes involve
the skin, eye, mouth, central nervous system and the
visceral organs. The most common presentation in the
acute stage is neonatal conjunctivitis, which usually
manifests between 6-30 days and can affect one or both
the eyes. There is edema of the eyelids with serous
discharge. This may be the only manifestation or there
Fig. 96.2: Gonococcal neonatal conjunctivitis with advanced
corneal ulceration. (Photograph courtesy: Dr Clare Gilbert,
London School of Hygiene and Tropical Medicine)
may be associated blisters on the skin or eyelid
margins. Microdendrites and geographic ulcers
characterize corneal involvement, which is the next
most common feature. Serious ocular complications
occur in approximately 60% of cases and include
necrotizing retinochoroiditis, retinitis, cataracts,
corneal scars, optic atrophy and phthisis. 60 The
disseminated form of the disease may involve the
central nervous system or visceral organs resulting in
death or long-term disabilities in the survivors.51,61
Laboratory Diagnosis
As the clinical features of neonatal conjunctivitis are
mostly non-specific, the etiologic agent can be
ascertained only through laboratory techniques. A
preliminary diagnosis is made on the basis of cytology
of conjunctival smears while culture of the organism
gives the definitive diagnosis.
As gonococci initially replicates within conjunc-
tival epithelial cells before being present in the
exudates,3 these cells are essential for cytology and
are better obtained by scraping the conjunctiva with
a metal spatula than a swab. Smears from the scrapings
are then stained with Gram, Giemsa or Papanicolau
stains. The pattern of inflammatory cells and presence
of inclusion bodies in Giemsa-stained smears may
indicate the diagnosis (Table 96.2). With Giemsa
staining, chlamydia inclusions appear in the cyto-
plasm of epithelial cells as distinct blue, purple, or
reddish purple granules (Fig. 96.3).55 The Gram stain
helps in distinguishing gram-positive and Gram
negative bacteria. Neisseria gonorrhoeae appear as Gram
negative diplococci within epithelial cells and
polymorphonuclear leucocytes (Fig. 96.4). The Gram
stain is extremely useful because it is a simple and
rapid technique with a sensitivity and specificity of
86% and 90% respectively.26,30
Table 96.2: Cytologic characteristic of
Giemsa-stained conjunctival smears 78,79
Etiologic agent Cytology
Chemical Neutrophils, few lymphocytes
Bacterial Neutrophils and bacteria
Chlamydial Neutrophils, lymphocytes, plasma cells,
Leber cells, intracytoplasmic basophilic
inclusions in the epithelial cells
Viral Lymphocytes, plasma cells, multinucleated
giant cells, intranuclear eosinophilic
inclusions
 Chapter 96: Neonatal Conjunctivitis
Fig. 96.3: Giemsa stain showing intracytoplasmic
inclusion bodies of Chlamydia trachomatis
Fig. 96.4: Gram stain showing numerous intracellular and extra-
cellular gram-negative diplococci which on culture was identified
as Neisseria gonorrhoeae (Photograph courtesy: Dr Savitri
Sharma, LV Prasad Eye Institute, Hyderabad)
737
Culture specimens are obtained with calcium
alginate swabs or a Dacron swab pre-wetted with a
sterile liquid broth and streaked over the media.
Besides the commonly used media like blood agar,
chocolate agar, thioglycolate or brain- heart infusion
broth and Saborauds dextrose agar, Thayer Martin
media which is specific for pathogenic Neisseria species
is used. Newer techniques like nucleic acid hybri-
dization (probe) and nucleic acid amplification tests
(NAAT) are increasingly being used to detect both
Neisseria gonorrhoeae and Chlamydia trachomatis with
satisfactory results.62-66
The gold standard for detecting Chlamydia
trachomatis has always been by cell (McCoy cells)
culture. Culture has a specificity of 100% but
sensitivity ranging from 70-90%.67 In cell culture, the
infected cells develop characteristic inclusion bodies
after 48-72 hours. The inclusion bodies are detected
by staining with fluorescein-conjugated monoclonal
antibody that is specific for the major outer membrane
protein.66 As culture has several disadvantages like
high cost, complexity of laboratory requirements,
transportation or storage difficulties and bacterial or
viral contamination, many non-culture tests for
detecting chlamydia have been developed (Table 96.3).
These are direct fluorescein antibody (DFA) test,68-70
enzyme immunoassays (EIA),71 nucleic acid hybridi-
zation tests,62and NAAT.39,63,72-74 Chlamydia trachomatis
can also be rapidly detected in the physician’s office
with the help of a monoclonal antibody based
membrane antigen capture EIA kit.77

Table 96.3: Various tests used for chlamydial detection

Test Sensitivity Specificity Predictive value
Positive Negative
Giemsa stain69 42 98 95 69
Direct fluorescent antibody test69,70 88-100 88-95 75-88 95-100
Detects chlamydia elementary bodies with fluorescent
monoclonal antibody. The stained smear is examined
under a fluorescent microscope
Enzyme immunoassay71 93-97 96-100 93-100 96-99
Uses polyclonal or genus-specific monoclonal antibodies
to detect chlamydia antigens by color change with a
spectrophotometer
Polymerase chain reaction73 92 100 100 98
Amplifies nucleic acid sequence
Chemiluminometric immunoassay75 83 100 100 92
Optical immunoassay76 10 93 83 100
Positive predictive value is the proportion of patients with positive test results who are correctly diagnosed.
Negative predictive value is the proportion of patients with negative test results who are correctly diagnosed.
738 Section 7: Pediatric Ophthalmology Including Strabismus
The presence of multinucleate giant cells or
koilocytic changes in Giemsa-stained conjunctival
smears indicate a possible viral etiology.78,79 Viral
antigens are detected by direct immunofluorescence
test or ELISA, the genomic material by PCR while
culture is done on appropriate cell lines. Additional
sources for specimens are vesicles on the skin and
mucosal surface.
TREATMENT
Treatment is initiated on the basis of clinical features
and conjunctival cytology and is modified according
to the clinical response and culture results (Fig. 96.5
and Table 96.4). It is prudent to hospitalize all affected
neonates for intensive medical care and close
monitoring for ocular and extraocular features like
pneumonia, sepsis, arthritis and meningitis. The
mother and her partner(s) need to be investigated for
STI and treated according to recommended guide-
lines. As gonococci and chlamydia frequently co-exists
it is essential to exclude dual-infection. Chlamydial
conjunctivitis has been reported in 12% of infants who
Fig. 96.5: Management of neonatal conjunctivitis (Adapted from
Guidelines for the management of sexually transmitted
infections, WHO 2001)85
Table 96.4: Treatment strategies for ON
Gonococcal neonatal conjunctivitis
Ceftriaxone, 50 mg/kg by intramuscular injection as a single
dose, to a maximum of 125 mg*
Alternative regimen
Kanamycin, 25 mg/kg by intramuscular injection as a single
dose to a maximum of 75 mg
or
Spectinomycin, 25 mg/kg by intramuscular injection as a
single dose to a maximum of 75 mg
Chlamydial neonatal conjunctivitis
Erythromycin syrup, 50 mg/kg per day orally, in 4 divided
doses for 14 days**
Alternative regimen
Trimethoprim 40mg with sulfamethoxazole 200mg orally,
twice daily for 14 days
Viral neonatal conjunctivitis
Acyclovir or Vidarabine, 30mg/kg/day by intravenous
injection in 3 divided doses for 10 days
plus
Topical Acyclovir 5 times daily or 1% Trifluorothymidine, 2
hourly
Bacterial conjunctivitis
Gram-positive: 0.5% erythromycin or 1% tetracycline, 4 hourly
Gram-negative: 0.3% gentamicin, 0.3% tobramycin or 0.3%
ciprofloxacin, 4 hourly
*Ceftriaxone should be cautiously given to hyperbilli-
rubinemic and premature infants.82
**Neonates treated with erythromycin should be followed for
signs of Infantile Hypertrophic Pyloric Stenosis.82
had been diagnosed and treated for gonococcal
neonatal conjunctivitis.80 Ocular examination should
be done as gently as possible to avoid injury to the
delicate ocular tissues. Proper precautions must be
taken by the examining ophthalmologist like using
protective plastic goggles while opening the eyelids
and frequent hand washings to limit spread of
infection. Ocular hygiene is of utmost importance and
includes frequent irrigation of the conjunctival sac
with saline and cleansing of the eyelids with
moistened cotton swabs. Dacryocystitis if present is
managed with lacrimal sac massage and topical
antibiotics.81
Chemical conjunctivitis requires no specific
treatment other than ocular hygiene as it resolves
spontaneously within twenty-four to forty-eight
hours.78,79 A presumptive treatment of gonococcal
infection is justified in neonates when gram-negative
intracellular diplococci are seen in conjunctival smears
 Chapter 96: Neonatal Conjunctivitis
and also in those born to mothers with gonorrhea and
have conjunctivitis but do not have gonococci in
Gram-stained conjunctival smears.82 The eyes are
cleansed frequently with saline to prevent corneal
complications. The recommended treatment is with
ceftriaxone, as a single intramuscular or intravenous
dose of 25-50 mg/kg, up to a maximum of 125 mg.82-86
Ceftriaxone has a rapid high peak serum levels and a
long half-life and is safe and highly effective in ocular
and extraocular gonococcal infection. 83 Penicillin
which was earlier the drug of choice is not recommen-
ded anymore because of the emergence of resistant
strains of gonococci. The alternative to ceftriaxone is
either kanamycin or spectinomycin.82,85 While being
cheaper and widely available in developing countries,
they are however less effective against systemic
infection.80,82,87 Kanamycin carries the risk of oto-
toxicity. Cefotaxime, a third generation cephalosporin
has also been reported to be effective in neonatal
infections with gonococci including penicillinase
producing strains. 87 Topical antibiotics alone are
inadequate and their use along with systemic
antibiotic has shown no additional benefit.85 Neonates
with epithelial defect, stromal infiltrate or stromal
thinning should be considered to have an infectious
keratitis. They require intravenous ceftriaxone, 50-80
mg/kg in two divided dosages for at least 3-6 days
and in addition topical antibiotics can be considered.88
Therapy can be adjusted according to the clinical
course and culture results.
The treatment of choice for chlamydial neonatal
conjunctivitis is erythromycin oral suspension
(ethylsuccinate or stearate) 50 mg/kg per day, in four
divided doses for 14 days. 82,85,89 Alternatively a
combination of trimethoprim 40 mg and sulpha-
methoxazole 200mg is given twice daily for 14
days.82,85 Topical therapy alone is not recommended
because it cannot eradicate extra-ocular infections like
pneumonia.90-92 There is no evidence that additional
therapy with a topical agent is of any benefit.90,91 Initial
treatment with erythromycin achieves a cure in 80%
of cases and the rest usually respond to a second
course.82 Infection in the mother is treated with a single
oral dose of azithromycin 1gm or doxycycline 100 mg
twice daily for 7 days.82
Conjunctivitis caused by bacteria other than
gonococci is treated with topical antibiotics. Topical
0.5% erythromycin or 1% tetracycline is used to treat
gram-positive bacteria while gram-negative orga-
nisms are treated with topical 0.3% gentamicin, 0.3%
739
tobramycin or 0.3% ciprofloxacin.28,78,79,93 Empirical
treatment is discouraged but where no laboratory
facilities exist, broad-spectrum antibiotics may be
used. Knowledge of commonly prevalent bacterial
species of the locality and their sensitivity pattern is
helpful in guiding initial therapy.
Viral neonatal conjunctivitis is treated with
systemic Acyclovir or Vidarabine 30 mg/kg/day in
divided doses.94 Topical acyclovir or trifluridine along
with cycloplegics are indicated in herpes kerato-
conjunctivitis. Topical corticosteroids are contra-
indicated in active epithelial disease.79
Prevention of Neonatal Conjunctivitis
There are four major strategies in control of neonatal
conjunctivitis and associated morbidity (Table 96.5).2,5
The first is directed at the community and aims at
reducing the spread of STI through programs
promoting safe sexual practices.82,84,85 The reduction
of STI prevalence in the population lowers the risk in
newborns. There is a need to educate mothers about
hygienic practices to prevent acquisition of post-
partum infections. Implementation requires a
coordinated effort between health professionals,
government and the community through integrated
program packages.85
Approximately 70% of chlamydial infections and
50% of gonococcal infections in women are asymp-
tomatic causing delay in diagnosis and treatment.7
Therefore a proactive approach involving screening
of women during pregnancy for genital infections can
prevent transmission to the newborn.95 Such screening
is routine in the prenatal clinics of many developed
countries. In developing countries where the need is
most, lack of diagnostic facilities and high cost makes
routine screening logistically and economically
prohibitive. However, the cost-effectiveness of
surveillance programs can be optimized by limiting
screening to high-risk cases (Table 96.6).2,5,11,12
The third component of prevention is ocular
prophylaxis at birth. It consists of instilling a safe an
Table 96.5: Control strategies for neonatal conjunctivitis
Primary prevention:
• Prevention of STI in the population
• Antenatal screening for STI
Ocular prophylaxis at birth
• Secondary prevention:
• Early detection and treatment of cases
740 Section 7: Pediatric Ophthalmology Including Strabismus
Table 96.6: High-risk groups
Pregnant women with STI
Pregnant women with vaginal discharge or dysuria
Pregnant women with multiple sexual partners
Pregnant women who have had sex with partners with STI
Women with no or incomplete prenatal care
Pregnant women with substance abuse
effective antimicrobial agent in the conjunctival sac
immediately after birth. Silver nitrate was the first
effective prophylactic agent. In United States, use of
silver nitrate which was mandated by the government
reduced the incidence of blindness due to gonococcal
conjunctivitis from 24% of the pre-prophylaxis era
(1906-1910) to 0.3% within a few decades.96 Similarly
later in Kenya, silver nitrate and tetracycline reduced
the transmission of gonococci by 83% and 93% and
chlamydia by 68% and 77% respectively.57 However
from the beginning, reports of chemical conjunc-
tivitis 18,21,53, and failures97,98 prompted the use of
alternatives like penicillin, erythromycin, tetracycline
and povidone iodine.
Various trials have compared silver nitrate,
erythromycin and tetracycline. 57,99-102 Although
erythromycin and tetracycline were found to be
effective in reducing the incidence, the difference in
comparison to silver nitrate was more often not
significant and none of the three were overwhelmingly
superior. 103 Prophylaxis against chlamydia was
singularly unsatisfactory.57,100,101 An ideal prophy-
lactic agent must have a broader antimicrobial
spectrum than currently used ones with high efficacy
against Chlamydia trachomatis, cause less resistance,
have no to fewer toxic reactions, be easy to store and
administer and be widely available at affordable
costs.104 One such antimicrobial that seems to fulfill
most of these criteria is 2.5% povidone iodine.
Povidone-iodine is an iodophore which slowly
liberates inorganic iodine and works by disrupting the
cell wall of microorganisms. It is reported to be
effective against gonococci, chlamydia and Herpes
simplex virus in concentrations of 1-5%.105 It has been
found to be effective in reducing bacterial counts 104
and also compare favorably to silver nitrate and
erythromycin in preventing chlamydial and gono-
coccal neonatal conjunctivitis.106 It is cheap and readily
available while bacterial resistance or toxicity at 2.5%
concentration is yet to be reported.104-107
The need for routine prophylaxis is dictated by the
risk of the disease and the resources available.54,96,108,109
In low-risk communities the benefit may be margi-
nal103 and many countries like Britain, Denmark and
Sweden have discontinued general prophylaxis and
instead have focused on early diagnosis and treat-
ment. 11 In high-risk communities the benefit of
prophylaxis outweighs the risk of toxicity or probable
failure. Currently various authoritative bodies
recommend use of a single drop of silver nitrate,
erythromycin or tetracycline (Table 96.7).82,84,85 The
drug needs to be applied immediately after birth as
the risk increases with delay.110 Additional protection
is recommended in infants of mothers with gonorrhea
in the form of a single intramuscular dose of
ceftriaxone (50 mg/kg, maximum 125 mg) or alter-
natively kanamycin or spectinomycin (25 mg/kg,
maximum 75 mg).82,85 Ocular prophylaxis with a
topical agent does not provide protection against
systemic infections.89,99 In India prophylaxis is not
routinely practiced. Instead, cleaning of the eyes with
sterile swabs and saline is emphasized and prophy-
laxis is reserved for only high-risk cases.111
Table 96.7: Prophylactic agents for
neonatal conjunctivitis*
A single application of either of the following is instilled in the
conjunctival sac after cleansing the eyes with sterile cotton swabs
wetted with saline
1% Silver nitrate solution
0.5% Erythromycin ointment
1% Tetracycline ointment
* Povidone iodine has not yet been recommended for prophylaxis by
the World Health Organization or Centers for Disease Control and
Prevention, Atlanta, GA though it is being used in some countries
like Mexico, Congo, Kenya, Tanzania and Thailand.
REFERENCES
1. Conjunctivitis of the newborn: Prevention and treatment at
the primary health care level. Geneva: World Health
Organization, 1986.
2. Laga M, Meheus A, Piot P. Epidemiology and control of
gonococcal ophthalmia neonatorum. Bull WHO 1989;67:471.
3. Thygeson P. Historical review of oculogenital disease. Am J
Ophthalmol 1971;71:975.
4. Credé K. Die verhutung der augenentzundung der neugebo-
renen. Archiv fur Gynaekologie 1881;17:50(English trans-
lation).
5. Foster A, Klauss V. Ophthalmia neonatorum in developing
countries. N Eng J Med 1995;332:600.
6. Cates W, Hinman AR. Sexually transmitted diseases in the
1990s. N Eng J Med 1991;325:1368.
 Chapter 96: Neonatal Conjunctivitis
7. Centers for Disease Control and Prevention. Sexually
Transmitted Disease Surveillance, 2002. Atlanta, GA: US
Department of Health and Human Services, Centers for
Disease Control and Prevention, 2003.
8. De Schryver A, Meheus A. Epidemiology of sexually
transmitted disease: The global picture. Bull WHO 1990;
68:639.
9. Rastogi S, Salhan S, Mittal A. Prevalence of chlamydia
trachomatis infection in pregnant women by Giemsa cytology
Indian Journal of Sexually Transmitted Diseases 1996;17:61.
10. Yasodhara P, Ramalakshmi BA, Naidu AN, et al. Prevalence
of specific IgM due to toxoplasma, rubella, CMV and C.
trachomatis infections during pregnancy. Indian Journal of
Medical Microbiology 2001;2:134.
11. Schaller UC, Klauss V. Is Credé prophylaxis for ophthalmia
neonatorum still valid? Bull WHO 2001;79:262.
12. Pierog S, Nigam S, Marasigan DC, et al. Gonococcal
ophthalmia neonatorum. Relationship of maternal factors and
delivery room practices to effective control measures. Am J
Obstet Gynecol 1975;122:589.
13. Prentice MJ, Hutchinson GR, Taylor-Robinson D. A micro-
biological study of neonatal conjunctivae and conjunctivitis.
Br J Ophthalmol 1977;61:601.
14. Pierce JM, Ward ME, Seal DV. Ophthalmia neonatorum in
the 1980s: Incidence, aetiology and treatment. Br J Ophthalmol
1982;66:728.
15. Jarvis VN, Levine R, Asbell PA. Ophthalmia neonatorum:
Study of a decade of experience at the Mount Sinai Hospital.
Br J Ophthalmol 1987;71:295.
16. Di Bartolomeo S, Mirta DH, Janer M, et al. Incidence of
chlamydia trachomatis and other potential pathogens in
neonatal conjunctivitis. Int J Infect Dis 2001;5:139.
17. Dannevig L, Straume B, Melby K. Ophthalmia neonatorum
in northern Norway. I Epidemiology and risk factors. Acta
Ophthalmol (Copenh) 1992;70:14.
18. Buisman NJ, Abong Mwemba T, Garrigue G, et al. Chlamy-
dial ophthalmia neonatorum in Cameroon. Doc Ophthalmol
1988;70:257.
19. Laga M, Plummer FA, Nzanze H, et al. Epidemiology of
Ophthalmia neonatorum in Kenya. Lancet 1986;2(8516):1145.
20. Rahi JS, Sripathi S, Gilbert C, et al. The importance of prenatal
factors in childhood blindness in India. Developmental
Medicine and Child Neurology 1997;39:449.
21. Armstrong JH, Zacarias F, Rein MF. Ophthalmia neonatorum:
A chart review. Pediatrics 1976;57:884.
22. Rees E, Tait IA, Hobson D, et al. Neonatal conjunctivitis
caused by Neisseria gonorrhoeae and chlamydia trachomatis.
Br J Vener Dis 1977;53:173.
23. Stenson S, Newman R, Fedukowicz H. Conjunctivitis in the
newborn: Observations on incidence, cause, and prophylaxis.
Ann Ophthalmol Mar 1981;13:329.
24. Persson K, Ronnerstam R, Svanberg L, Pohla M. Neonatal
chlamydial eye infection: An epidemiological and clinical
study. Br J Ophthalmol 1983;67:700.
25. Sandstorm KI, Bell TA, Chandler JW, et al. Microbial causes
of neonatal conjunctivitis. J Pediatr 1984;105:706.
26. Fransen L, Nsanze H, Klauss V, et al. Ophthalmia neonatorum
in Kenya: The roles of Neisseria gonorrhoeae and chlamydia
trachomatis. J Infect Dis 1986;153:862.
27. Barry WC, Teare EL, Uttley AH, et al. Chlamydia trachomatis
as a cause of neonatal conjunctivitis. Arch Dis Child
1986;61:797.
741
28. Rapoza PA, Quinn TC, Kiessling LA, Taylor HR. Epide-
miology of neonatal conjunctivitis. Ophthalmology 1986;
93:456.
29. Fransen L, Van den berghe P, Mertens A, et al. Incidence and
bacterial aetilogy of neonatal conjunctivitis. Eur J Pediatr
1987;146:152.
30. Winceslaus J, Goh BT, Dunlop EM, et al. Diagnosis of
ophthalmia neonatorum. Br Med J 1987;295:1377.
31. Mabey D, Hanlon P, Hanlon L, et al. Chlamydial and
gonococcal ophthalmia neonatorum in the Gambia. Ann Trop
Paediatr 1987;7:177.
32. Frost E, Yvert F, Ndong JZ, et al. Ophthalmia neonatorum in
a semi-rural African community. Trans R Soc Trop Med Hyg
1987;81:378.
33. Nsanze H, Dawodu A, Usmani A, et al. Ophthalmia
neonatorum in the United Arab Emirates. Ann Trop Pediatr
1996;16:27.
34. Serigwa A, Pratt BC, Eren E, et al. Ophthalmia neonatorum
in Bangkok: The significance of chlamydia trachomatis. Ann
Trop Pediatr 1993;13:233.
35. Friendly DS. Gonorrheal ophthalmia. Reappearance of an old
problem. Trans Am Acad Ophthalmol Otolaryngol 1970;
74:975.
36. Mani VR, Vidya KC. A microbiological study of ophthalmia
neonatorum in hospital-born babies. Journal of Indian
Medical Association 1997;95:416.
37. Ng SK, Au E, Thirumoorthy T. Ophthalmia neonatorum—
the Middle Road Hospital perspective. Ann Acad Med
Singapore 1987;16:645.
38. Galega FP, Heynmann DL, Nasah BT. Gonococcal ophthalmia
neonatorum: The case for prophylaxis in tropical Africa. Bull
WHO 1984;62:95.
39. Talley AR, Garcia-Ferrer F, Laycock KA, Essary LR.
Comparative diagnosis of neonatal chlamydial conjunctivitis
by polymerase chain reaction and McCoy cell culture. Am J
Ophthalmol 1994;117:50.
40. Schachter J, Grossman M, Sweet RL, et al. prospective study
of perinatal transmission of Chlamydia trachomatis. JAMA
1986;255:3374.
41. Chandler JW, Alexander ER, Pheiffer TA, et al. Ophthalmia
neonatorum associated with maternal chlamydial infections.
Trans Am Acad Ophthalmol Otolaryngol 1977;83:302.
42. Isenberg SJ, Apt L, Yoshimori, et al. Source of the conjunctival
bacterial flora at birth and implications for ophthalmia
neonatorum prophylaxis. Am J Ophthalmology 1988;106:458.
43. Givner LB, Rennels MB, Woodward CL, et al. Chlamydia
trachomatis infection in infant delivered by cesarean section.
Pediatrics 1981;68:420.
44. Mohile M, Deorari AK, Satpathy G, et al. Microbiological
study of neonatal conjunctivitis with special reference to
Chlamydia trachomatis. Indian J Ophthalmol 2002;50:295.
45. Isenberg SJ, Apt L, Yoshimori R, et al. Bacterial flora of the
conjunctiva at birth. J Pediatr Ophthalmol Strabismus
1986;23:284.
46. Franklin CH. Bacterial flora in infants encountered at time of
delivery. Am J Obstet and Gynecol 1948;56:738.
47. Watt PJ. Pathogenic mechanisms of organisms virulent to the
eye. Trans Ophthalmol Soc UK 1986;105:25.
48. CDC. Sexually Transmitted Disease Surveillance 2002
Supplement: Gonococcal Isolate Surveillance Project (GISP)
742 Section 7: Pediatric Ophthalmology Including Strabismus
Annual Report—2002. Atlanta, Georgia: US Department of
Health and Human Services, 2003.
49. Fleming DT, McQuillan GM, Johnson RE, et al. Herpes
Simplex Virus Type 2 in United States 1976 to 1994. New
Engl J Med 1997;337:1105.
50. Nahmias AJ, Josey WE, Naib ZM. Neonatal herpes simplex
infection. JAMA 1967;199:132.
51. Whitley RJ, Nahmias AJ, Visintine AM, et al. The natural
history of herpes simplex virus infection of mother and
newborn. Pediatrics 1980;66:489.
52. Nahmias AJ, Josey WE, Naib ZM, et al. Perinatal risk
associated with maternal genital herpes simplex virus
infection of fetus and newborn. Obstet Gynecol 1974;44:63.
53. Nishida H, Risemberg HM. Silver nitrate ophthalmic solution
and chemical conjunctivitis. Pediatrics 1975;56:368.
54. Dickmann WJ. The prophylaxis of gonorrheal ophthalmia
neonatorum. Am J Obstet Gynecol 1953;65:155.
55. Dawson CR. Lids, conjunctiva, and lacrimal apparatus. Eye
infections with chlamydia. Arch Ophthalmol 1975;93:854.
56. Chandler JW, Alexander ER, Pheiffer TA, et al. Ophthalmia
neonatorum associated with maternal chlamydial infections.
Trans Am Acad Ophthalmol Otolaryngol 1977;83:302.
57. Laga M, Plummer FA, Piot P, et al. Prophylaxis of gonococal
and chlamydial ophthalmia neonatorum. A comparison of
silver nitrate and tetracycline. New Eng J Med 1988;318:653.
58. McIntosh K. Community acquired pneumonia in children.
New Eng J Med 2002;346:429.
59. Traboulsi EI, Shammas IV, Rati HE, et al. Pseudomonas
aeruginosa ophthalmia neonatorum. Am J Ophthalmol
1984;98:801.
60. el Azazi M, Malm G, Forsgren M. Late ophthalmologic
manifestations of neonatal herpes simplex virus infection. Am
J Ophthalmol 1990;109:1.
61. Malm G, Forsgren M, el Azazi M, et al. A follow-up study of
children with neonatal herpes simplex virus infections with
particular regard to late nervous disturbances. Acta Paediatr
Scand 1991;80:226.
62. Dean D, Palmer L, Pant CR, et al. Use of a Chlamydia
trachomatis DNA probe for detection of ocular chlamydiae.
J Clin Microbiol 1989;27:1062.
63. Limberger RJ, Biega R, Evancoe A, et al. Evaluation of culture
and the Gen-Probe PACE 2 assay for detection of Neisseria
gonorrhoeae and Chlamydia trachomatis in endocervical
specimens transported to a state health laboratory. J Clin
Microbiol 1992;30:1162.
64. Buimer M, Van Doornum GJJ, Ching S. Detection of
Chlamydia trachomatis and Neisseria gonorrhoeae by ligase
chain reaction-based assays with clinical specimens from
various sites: Implications for diagnostic testing and
screening. J Clin Microbiol 1996;34:2395.
65. Van Dyck E, Ieven M, Pattyn S, et al. Detection of Chlamydia
trachomatis and Neisseria gonorrhoeae by enzyme immuno-
assay, culture and three nucleic acid amplification tests. J Clin
Microbiology 2001;39:1751.
66. Centers for Disease Control and Prevention. Screening tests
to detect Neisseria gonorrhoeae and Chlamydia trachomatis
infections—2002. MMWR 2002;51:3.
67. Centers for Disease Control and Prevention. Recommen-
dations for the prevention and management of Chlamydia
trachomatis infections, 1993. MMWR 1993;42.
68. Hawkins DA, Wilson RS, Thomas BJ. Rapid reliable diagnosis
of chlamydial ophthalmia by means of monoclonal antibo-
dies. Br J Ophthalmology 1985;69:640.
69. Rapoza PA, Quinn CT, Kiessling LA. Assesment of neonatal
conjunctivitis with a direct immunofluorescent momoclonal
antibody stain for chlamydia. JAMA 1986;255:3369.
70. Roblin PM, Hammerschlag MR, Cummings C, et al.
Comparison of two rapid microscopic methods and culture
for detection of chlamydia trachomatis in ocular and
nasopharyngeal specimens from infants. J Clin Microbiol
1989;27:968.
71. Hammerschlag MR, Roblin PM, Gelling M, et al. Comparison
of two enzyme immunoassays to culture for detection of
chlamydial conjunctivitis and respiratory infections in infants.
J Clin Microbiol 1990;28:1725.
72. Loeffelholz MJ, Lewinski CA, Silver SR, et al. Detection of
Chlamydia trachomatis in endocervical specimens by
polymerase chain reaction. Journal of Clinical Microbiology
1992;30:2847.
73. Hammerschlag MR, Roblin PM, Gelling M, et al. Use of
polymerase chain reaction for the detection of Chlamydia
trachomatis in ocular and nasopharyngeal specimens from
infants with conjunctivitis. Pediatr Infect Dis J 1997;16:293.
74. Elnifro EM, Storey CC, Moris DJ, Tullo AB. Polymerase chain
reaction for detection of Chlamydia trachomatis in conjunc-
tival swabs. Br J Ophthalmol 1997;81:497.
75. Dumornay W, Roblin PM, Gelling M, et al. Comparison of a
chemiluminometric immunoassay with culture for diagnosis
of chlamydial infections in infants. J Clin Microbiol
1992;30:1867.
76. Roblin PM, Gelling M, Kutlin A, et al. Evaluation of a new
optical immunoassay for the diagnosis of neonatal chlamydial
conjunctivitis. J Clin Microbiol 1997;35:515.
77. Hammerschlag MR, Gelling M, Roblin PM, et al. Comparison
of Kodak Surecell chlamydia test kit with culture for the
diagnosis of chlamydial conjunctivitis in children. J Clin
Microbiol 1990;28:1441.
78. Chandler JW. Neonatal conjunctivitis. Duane’s Ophthal-
mology CD Rom edition. Lippincot Williams and Wilkins,
2000.
79. Lindquist TD. Ophthalmia neonatorum. In Krachmer JH,
Mannis MJ, Holland EJ (Eds): Cornea. St Louis: Mosby.
1997;2:789.
80. Fransen L, Nsanze H, D’costa L, et al. Single-dose kanamycin
therapy in ophthalmia neonatorum. Lancet 1984;2(8414):1234.
81. Sandstorm I. Treatment of neonatal conjunctivitis. Arch
Ophthalmol 1987;105:925.
82. Centers for Disease Control and Prevention. Sexually
transmitted diseases treatment guidelines 2002. MMWR
2002;51(RR-6):1-80.
83. Laga M, Naamara W, Brunham RC, et al. Single-dose therapy
of gonococcal ophthalmia neonatorum with ceftriaxone. New
Eng J Med 1986;315:1382.
84. Canadian STD Guidelines 1998. Laboratory Centre for Disease
Control (LCDC) Expert Working Group on Canadian
Guidelines for Sexually Transmitted Disease. Ottawa,
Canada, 1998.
85. World Health Organization. Guidelines for the management
of sexually transmitted infections. WHO. Geneva 2001.
 Chapter 96: Neonatal Conjunctivitis
86. Conjunctivitis. Preferred Practice Pattern. American Academy
of Ophthalmology, 2003.
87. Lepgage P, Bogaerts J, Kestelyn P, Meheus A. Single-dose
cefotaxime intramuscularly cures gonococcal ophthalmia
neonatorum. Br J Ophthalmology 1988;72:518.
88. Ullman S, Rousel TJ, Forster RK. Gonococcal kerato-
conjunctivitis. Survey Ophthalmology 1987;32:199.
89. Lietman T, Whitcher JP. Chlamydial conjunctivitis. Ophthal-
mology Clinics of North America 1999;12: 21.
90. Heggie AD, Jaffe AC, Stuart LA, et al. Topical sulfacetamide
vs oral erythromycin for neonatal chlamydial conjunctivitis.
Am J Dis Child 1985;139:564.
91. Patamasucon P, Rettig PJ, Faust KL, et al. Oral v topical
erythromycin therapies for chlamydial conjunctivitis. Am J
Dis Child 1982;136:817.
92. Stenberg K, Mardh PA. Treatment of chlamydial conjunc-
tivitis in newborns and adults with erythromycin and
roxithromycin. J Antimicrob Chemother 1991;28:301.
93. Diamant JI, Hwang DG. Therapy for bacterial conjunctivitis.
Ophthalmology Clinics of North America 1999;12:15.
94. Whitley R, Arvin A, Prober C, Burchett S, et al. A controlled
trial comparing vidarabine with acyclovir in neonatal herpes
simplex virus infection. New Eng J Med 1991;324:444.
95. McMillan JA, Weiner LB, Lamberson HV, et al. Efficacy of
maternal screening and therapy in the prevention of
chlamydia infection of the newborn. Infection 1985;113:263.
96. Barsam PJ. Specific prophylaxis of gonorrheal ophthalmia
neonatorum. N Eng J Med 1966;274:731.
97. Pearson HE. Failure of silver nitrate prophylaxis for
gonococcal ophthalmia neonatorum. Am J Obstet Gynecol
1957;73:805.
98. Solomon E, Kramer B, Stein WW, Kohl SG. The incidence of
ophthalmia neonatorum without prophylaxis. Am J Obstet
Gynecol 1959;78:513.
99. Hammerschlag MR, Chandler JW, Alexander ER, et al.
Erythromyin ointment for ocular prophylaxis of neonatal
chlamydial infection. JAMA 1980;244:2291.
743
100. Hammerschlag MR, Cummings C, Roblin PM, et al. Efficacy
of neonatal ocular prophylaxis for the prevention of
chlamydial and gonococcal conjunctivitis. N Engl J Med
1989;320:769.
101. Chen JY. Prophylaxis of ophthalmia neonatorum: Compa-
rison of silver nitrate, tetracycline, erythromycin and no
prophylaxis. Pedtr Infect Dis J 1992;11:1026.
102. Bell TA, Grayston JT, Krohn MA, et al. Randomized trial of
silver nitrate, erythromycin, and no eye prophylaxis for the
prevention of conjunctivitis among newborns not at risk for
gonococcal ophthalmitis. Eye Prophylaxis Study Group.
Pediatrics 1993;92:755.
103. Moseley J. Ophthalmia neonatorum. In Wormold R, et al
(Eds): Evidence based ophthalmology, BMJ Books, 2004;71.
104. Isenberg SJ, Apt L, Yoshimori R, et al. Povidone-iodine for
ophthalmia neonatorum prophylaxis. Am J Ophthalmol
1994;118:701.
105. Beneveto WJ, Murray PM, Reed CA, Pepose JS. The sensitivity
of Neisseria gonorrhoeae, Chlamydia trachomatis and Herpes
Simplex Type II to disinfection with povidone-iodine. Am J
Ophthalmol 1990;109:329.
106. Isenberg SJ, Apt L, Wood M. A controlled trial of povidone-
iodine as prophylaxis against ophthalmia neonatorum. New
Eng J Med 1995;332:562.
107. Isenberg SJ, Apt L, signore MD, et al. A double application
approach to ophthalmia neonatorum prophylaxis. Br J
Ophthalmol 2003;87:1449.
108. Dillon HC. Prevention of gonococcal ophthalmia neonato-
rum. The New Eng J Med 1986;315:1414.
109. Chandler JW. Controversies in ocular prophylaxis of
newborns. Arch Ophthalmol 1989;107:814.
110. Muhe L, Tafari N. Is there a critical time for prophylaxis
against gonococcal neonatal conjunctivitis? Genitourinary
Med 1987;62:356.
111. NNF teaching aids on new born care. In Deorari AK (Ed).
Recommendation of National Neonatalogy Forum of India,
1998.
 Chapter 97
Amblyopia
JN Rohatgi
The term amblyopia literally means “dullness of
vision” derived from Greek (amblyos, dull; opia,
vision). Such an eye is generally described as one
which is structurally normal but functionally has
reduced visual acuity which may interfere with the
child’s educational progress and sporting abilities. It
may also affect the child’s self image, interpersonal
relationships and influence later life career choices.
It is the commonest cause of visual defect in a child
with a prevalence of 3% in UK population1 and despite
all out efforts there are still children growing up to be
amblyopic.2
Amblyopia results from unequal visual stimulation
during the sensitive period of visual development,
mostly from a squint or visual deprivation caused by
unequal refractive error. For most of the time this
functional amblyopia is unilateral. But one does come
across cases of bilateral amblyopia as seen in cases of
high hypermetropia in both eyes in the excess of +7 D
or associated with astigmatism in excess of 3 D.
Cases of uniocular amblyopia can be divided into
subgroups as in Table 97.1.
Table 97.1: Causes of amblyopia
Without squint
1. Straight eye amblyopia
a. With high hypermetropia
in the amblyopic eye-
anisometropic amblyopia.
b. With equal refractive
error in both eyes
c. With no significant refractive error
2. Amblyopia with squint
a. With central fixation
b. With or without significant
refractive error in the
amblyopic deviating eye
3. With eccentric fixation
Of the two groups, the straight eye amblyopia
group constitutes a large percentage of cases.
Straight Eye Amblyopia
The first group of straight eye amblyopia cases have
high hypermetropic refractive error in the amblyopic
eye. They have been variously called as suppression
amblyopia, straight eye amblyopia and anisometropic
amblyopia. Being asymptomatic such cases often go
unnoticed till the child has a routine school medical
examination. The mechanism of such an amblyopia is
different from the mechanism in cases of strabismic
amblyopia.
Hypermetropia in the order of 3.5 Spherical
diopters or astigmatism of 2 diopters in one meridian
are both risk factors for amblyopia.4 Increasing simple
astigmatism or oblique astigmatism and presence of
strabismus have high relative risk.
If a child is unable to accommodate equally with
each eye as happens in anisometropic hypermetropia
or if the accommodation does not achieve clear
definition as in unilateral astigmatism, the retinal
image of the more hypermetropic/astigmatic eye is
blurred. This blurred image acts as sensory obstruction
to binocular vision and is, therefore, suppressed. This
suppression begins when accommodation starts being
active, that is about the age of 2 to 3 years. The
sensitivity to develop suppression and amblyopia
gradually decreases till the child reaches 6 to 7 years
of age whereafter visual maturation is complete and
the retino-cortical pathways and visual centres may
become immune to abnormal visual input.
In myopia on the other hand, the more myopic eye
is used for near work and the less myopic eye for
distance work. Since both retinas continue to receive
 Chapter 97: Amblyopia
adequate stimulation, amblyopia does not develop.
In cases of high myopia and more so when one eye is
highly myopic (unilateral high myopia) the retina of
this eye is deprived of adequate vision and clarity and
amblyopia may develop in such an eye.
Amblyopia with Squint
Patients who constantly use one eye for fixation as in
unilateral squint (and as opposed to alternating
fixation pattern in case of alternating squint) are most
likely to develop strabismic amblyopia. Thus, one can
expect to find amblyopia more often in esotropes than
in exotropes.
In the majority of cases of concomitant squint
especially when one eye has a higher visual acuity,
this eye tends to be used in preference to the other.
This causes a conditioned inhibition in the neglected
deviated eye. This inhibition gradually becomes fixed
leading to the development of an obligatory inhibition
or amblyopia.
The earlier the age, at which inhibition first
becomes effective, the more profound is the
amblyopia. Thus, in a case of congenital squint, where
the inhibition is present since birth, vision in the
squinting or deviating eye will remain permanently a
bit more than perception of light.
On the other hand, if this inhibition of vision in
the squinting eye occurs after the age of 6 or 7 years
(when visual maturation is expected to be complete)
no such arrest of development or amblyopia is likely
to occur. In between, when amblyopia comes up about
the age of 3 to 4 years, (accommodative convergent
squint) recovery of vision is likely to take place upto
the level of normal for the age at which inhibition
commenced. This was earlier referred to as amblyopia
ex-anopsia (Amblyopia of diffuse or under stimulation
of the retina). Such stimulus deprivation amblyopia
is seen in children with opacities of the ocular media
like congenital or traumatic cataract, corneal leucoma
or following prolonged indiscriminate patching
(occlusion-amblyopia). It is not necessary that he
amblyopic eye show deviation or squint.
The depth of amblyopia and its recovery varies
depending on:
a. The degree of visual acuity attained before
inhibition became effective,
b. The period during which the extinction of vision
remained active and
c. The age at which amblyopia developed. Thus,
deep amblyopia is a disease of the young
745
children primarily those under the age of four
years. Most infants with amblyopia are detected
at the age of 2 to 3 years.
On the other hand, when deviation begins late say
after 7 to 8 years of age, habitual suppression is
difficult and amblyopia is less common. An adult with
a recent onset of deviation invariably complains of
diplopia and the absence of this complaint suggests
an earlier onset of the deviation.
Clinically
From a clinical point of view—a difference of two lines
on a visual acuity chart is commonly used a diagnostic
criteria for amblyopia. However, in a patient with
squint in whom the VA in the “Amblyopic eye” has
improved from 6/36 to 6/12, must still be considered
as amblyopic while visual acuity in the fixing sound
eye is 6/6.
Crowding Phenomenon
In patients with amblyopia, it is always of interest and
importance to compare the vision obtained with visual
acuity symbols presented in a row to that obtained
with isolated symbols like E on a uniform background.
According to Von Noorden,5,6 in some patients the
difference is quite startling such as when line acuity
of 6/36 responds to 6/6 symbols presented singly. This
is known as crowding phenomenon.
The presence or absence of the crowding
phenomenon has significant prognostic value,5 atleast
at the completion of treatment. If standard line acuity
is not or cannot be achieved, the probability is high
that the vision of the amblyopic eye will regress
significantly.
Fixation Pattern of Amblyopic Eye
There are cases of strabismic amblyopia where the
fixation is eccentric rather than being central. These
cases of eccentric fixation do not assume central
fixation even when the fellow eye is covered, that is
the amblyopic eye remains less deviated.
Classification of Fixation
Classification of fixation pattern in amblyopia is as
follows:
1. Central Fixation (Foveolar).
2. Eccentric Fixation (non-foveolar). Para-foveal
within 2° of the fovea.
746 Section 7: Pediatric Ophthalmology Including Strabismus
3. No fixation (erratic)—no definite area of fixation
around the true fovea.
— Paramacular: Between 2 to 4° away from the
true fovea.
— Centrocaecal: Greater than 4° between the
macula and the optic disk.
— Paracentral : Around the optic disk.
The prevalence of eccentric fixation in strabismic
amblyopia has been reported by different authors
varying from 23 to 82% (Harada and Hayashi 1958–
quoted from Von Noorden5).
For diagnosis and treatment of eccentric fixation,
Cover Test and Corneal reflex method can diagnose
only gross degree of eccentric fixation and thus, many
of these cases could remain undiagnosed and wrongly
treated.
With the help of a visuoscope–(A modified
ophthalmoscope), Cuppers first localized accurately
the eccentric fixation. A number of modern ophthal-
moscopes have a built-in fixation target that helps in
diagnosing the eccentric fixation. Once diagnosed,
Cuppers has used euthyoscope to dazzle the area of
eccentric fixation after first covering the foveal area.
By these exercises, the acuity of the area of eccentric
fixation is lowered and reduced compared to the VA
of the foveal area. And thus, eccentric fixation is
converted into amblyopia with foveal fixation.
Bangerter Pleoptophore
A fully controllable device dazzles out the area of
eccentric fixation while a black disk protects the fovea.
This is followed immediately by stimulating the fovea
by means of an intermittent light stimulus using small
optotypes. Once the patient is able to recognize the
foveal light stimulus, subsidiary instruments like
localizer, centrophore and separation—trainer take
over.
Visual Acuity
It has been stated that the visual acuity of an amblyopic
eye could be predicted from the position of eccentric
fixation but no direct relationship has yet been
established.
Steady eccentric-fixation is an unfavourable
prognostic sign whereas an unsteady or wandering
fixation is a favourable sign.
Pathogenesis of Amblyopia
Since the low vision of the amblyopic eye is not
explained by demonstrable acquired details, it is
important to investigate the visual function of such
eyes, For this, we have:
1. Objective method – Electrophysiological methods
and
2. Subjective method – Psychophysical methods.
In objective methods: Responses from the retina
and central nervous system are registered following
light stimulation.
These methods are:
1. Electroretinography (ERG) and
2. Central cerebral response (EEG and VER).
i. ERG: Defective retinal functions are
expressed in abnormal ERG responses. This
stimulated many investigators to record
ERG from amblyopic eyes. No significant
difference in the ERG of normal and
amblyopic eyes were recorded with single
light stimulus.
ii. EEG and VER: Here again, though anom-
alies in EEG recording of amblyopic patients
were reported by some investigators, others
reported negative or no significant findings.
As for VER—the overall impression given is that
VER responses are reduced in amplitude and are
delayed in appearance in cases of amblyopia. This
reduction of VER amplitude, however, cannot be
consistently co-related with the degree of amblyopia.
The findings that the visual function of amblyopic
eyes occasionally recovers partially or even completely
in adults after functional loss of the good eye or in
strabismus monkey after enucleation of the sound eye,
indicates that even in long-standing and deep
amblyopic cases the retino-striate connections of an
amblyopic are not irrevocably destroyed but become
dormant.
To sum up, amblyopia appears to be a cortical
inhibition of the highest function of pattern vision
without impairment of lower function of the light-
sense and spatial projection. Though amblyopia due
to an acquired lesion may occur, its incidence is
relatively rare and in these cases, the visual loss is
passive and irrecoverable.
The usual amblyopia in a squinting eye is active
and functional and of cerebral origin. The earlier it
develops, the more profound it tends to be and the
earlier the treatment is instituted, the greater the
amount of vision that can be reclaimed.
 Chapter 97: Amblyopia
Treatment
7 itself.2
In 1743 Buffon occluded the fixating eye (in case of
concomitant squint) to improve the vision in the
deviating eye because according to him poor vision
in the amblyopic eye was the cause of the deviation.
Once again with the concept of amblyopia as a
sensory adaptation to squint, patching was resumed
and has since remained the mainstay of amblyopia
treatment, both for strabismic amblyopia and also for
cases of straight eye amblyopia (anisometropic
amblyopia).
The use of contact lenses to improve visual acuity has
been thought of and practised in cases of
anisometropia from unilateral high myopia and also
in hypermetropia. This has been used and prescribed
along with occlusion and found to improve the visual
acuity in the myopic amblyopic eye upto 9 diopters.9
But before occlusion of the sound eye refractive error
(if any) should be assessed under cycloplegic
mydriasis and full refractive correction consistent with
the visual comfort of the child should be prescribed.
In a unilateral high hypermetropia, under-correction
may be necessary.
Occlusion Treatment
Occluding the sound eye forces the child to use the
amblyopic eye. In addition, it removes the inhibiting
stimuli to the amblyopic eye that arises from
stimulation of the fixating eye. It has to be recognized
that there is a critical period in early childhood during
which amblyopia must be identified, if treatment with
occlusion therapy (patching of the non-affected eye)
is to be successful.
Occlusion appears to be a simple procedure and
in many cases it is so. But the practical application of
this simple procedure is beset with many difficulties
more so in young children. By patching the sound or
unaffected eye during activities requiring sustained
attention and co-ordination such as playing, reading
and socializing that maximum gains in visual acuity
are made. Therefore periods of patching should be
encouraged by parents in which children play, read
and interact with others.10 Further, active and learned
co-operation of the parents are necessary; many a time
occlusion has been given up halfway considering it
as a useless time consuming procedure. The failure of
the treatment is greatly affected by lack of compliance.
The motivation of the patients (and their parents) to
protect themselves from the disease is often
747
outweighed by the adverse effect of the treatment
Methods of Occlusion
These are different ways for occluding the eye:
a. By attaching an occluder to the spectacle or pasting
a dark black paper on the spectacle lens so that no
light can pass through the paper and lens to the
eye.
b. By a piece of material that fastens directly onto the
skin.
The important point however, is that the
fixating eye should be occluded completely and
constantly during all waking hours. The child
should be re-examined at frequent intervals and
visual acuity of both the eyes be checked.
Sometimes, it so happens that the vision in the
fixating eye under occlusion goes down or it
becomes amblyopic. This, however, is reversible
and in such cases occlusion has to alternating—
alternate occlusion of the sound eye with occlusion
of the amblyopic eye.
Occlusion has got to be continued till the vision of
the amblyopic eye and its fellow eye becomes
equalized or until there is no improvement even after
three months of constant occlusion.
Results of Occlusion
Flynn et al 11 after extensive study of therapy of
amblyopia conclude “ factors that appeared closely
related to a successful outcome of patching therapy
were patients age and depth of visual loss before
treatment”. This further supports the value of early
detection and screening for amblyopia.
Marie12 clearly states that in terms of occlusion
duration, maximum improvement occurs in response
to 400 hours of occlusion wear and to full time
occlusion. She further states that occlusion is more
effective in the treatment of strabismic amblyopia and
spectacles alone and the effect is optimal within the
first six months of treatment.
The visual improvement in the amblyopic eye is
better in straight eye amblyopia cases than in cases
where amblyopia is associated with squint. This is
however not acceptable in all studies.
In suitable anisometropic amblyopia, where the
refractive difference does not exceed +4.0 dioptre, a
visual acuity of 6/9 may be achieved. The VA may
improve in these children upto the age of 15 to 16 years
748 Section 7: Pediatric Ophthalmology Including Strabismus
(sometimes even in college going students upto the
age of 20 years of age) whereas in squint amblyopia
cases, the visual acuity has practically no chance to
improve once the age of 6 to 7 years have passed
without any active treatment.
Amblyopia tends to recur until the child has
reached 8 to 10 years of age because of the persistence
of inhibitory effect from the fixating eye and it may
be necessary to resume occlusion. Such children who
are at risk of having recurrence of amblyopia, can be
helped by alternating penalization treatment.
Sneak or slowly increasing occlusion may be tried
in children between 2 to 4 years of age. In this method
graded papers are pasted on the spectacle lens
reducing the vision in the sound eye to a known extent
varying from 6/9 to 6/60. The purpose is to put the
good eye gradually at a disadvantage in order to
encourage the weak eye.
Occlusion in Squinting Eye with Eccentric Fixation
a. Many investigators are of the opinion that after two
years of age, occlusion of the sound eye is
contraindicated in amblyopes with eccentric
fixation, because it may reinforce anomalous
fixation behaviour. They suggest that instead, the
amblyopic eye should be occluded to break-up the
abnormal fixation behaviour. This is inverse
occlusion. However, other workers have reported
that the occlusion of the sound eye (direct
occlusion) is effective until 5 years of age regardless
of the fixation behaviour. To steer clear of the
controversy, many now use inverse occlusion only
during the initial phase of therapy of eccentric
fixation in children older than 5 years of age and
then switch on to occlusion of the sound eye.
b. Red filter treatment: Total occlusion of the sound eye
and application of a Red filter (Kodak Gelatine
Wratten filter-wave length 600-640 μm) on the glass
before the amblyopic eye is also recommended. It
is postulated that red light entering the amblyopic
eye (the filter cutting off the other wavelengths of
white light) is ineffective in stimulating the retinal
area of eccentric fixation which is predominantly
a rod populated area. Thus, a suitable red filter
motivates the child to use the fovea and inhibits
use of the eccentric-fixation area. Regular
examination has to be done to keep on studying
the change in fixation. Once, it has become para-
foveal or central, red filter is removed and
occlusion of the sound eye is continued till the VA
of the amblyopic eye improves. For this treatment,
the child must be highly co-operative.
c. Prisms: To break the eccentric fixation, use of Base-
in and Base-out prisms before the amblyopic eye
in combination with occlusion of the sound eye has
been suggested by various authors with varying
success. Base-out prism is put before the fixating
eye in convergent squint cases to align the deviated
eye with amblyopic and eccentric fixation and
thereby, create conditions more favourable for
foveal fixation. This method can be combined with
penalization.
d. Pleoptics: In1940 Bangerter began systemic active
treatment of amblyopia with eccentric fixation
using a method for which he coined a term
‘Pleoptics’. Using a pleoptophore (a modified
Gullstrand ophthalmoscope) and under direct
observation of the fundus, the eccentric-fixating
retinal area is dazzled with a bright light while the
fovea is protected with a disk projected onto the
fundus. This is followed by intermittent
stimulation of the macula with flashes of light. This
treatment continues until the central scotoma
diminished and fixation becomes central.
Bangerter invented and used a few other instru-
ments—(1946 and 1955) to improve the efficacy of the
treatment. Cuppers (1956 and 1963), at Geissen used
the physiological principle of the supremacy of the
foveal area over the retinal periphery. His instrument
is Euthyscope—(a modified ophthalmoscope) in
which a black disk protects the fovea while the reinal
periphery including the area of eccentric fixation is
dazzled with bright light. A negative after-image is
evoked and enhanced by flickering room illumination.
The clear spot in the centre of the after-image co-relates
to the position of the fovea which has regained its
functional supremacy over the eccentric fixating
retinal area at least till the exercise continues. Use of
Hadinger brushes (c0-ordinator) completes the
exercise.
But after a few years of great enthusiasm (1945–
1970) the pleoptic treatment of amblyopia with
eccentric fixation has waned for a number of valid
reasons. Pleoptic exercises are not practical because:
a. They can only be used in children above the
age of 6 or 7 years. Young children cannot co-
operate sufficiently.
b. These instruments and appreciation of after
image and concentration involved in the use of
co-ordinator and pleoptophore demand
 Chapter 97: Amblyopia
intelligence which is not available in many of
these young children.
c. Time consuming and financially taxing as these
exercises are, they do not appeal to parents for
positive are not many and hence, parental co-
operation is also poor.
In view of the difficulties encountered in children
with occlusion an alternate method suggested is
“Penalization”.
In this method Atropine 1% ointment is used in
the fixating sound eye (in order to blur vision in this
eye and thereby compel the amblyopic eye to fixate at
near) has been advocated often since first mentioned
by Worth in 1903. Along with atropinization of the
sound eye a miotic drop instilled at bedtime in the
amblyopic eye of hypermetropic children was
suggested by several authors.
The principle of penalization is to decrease or blur
near vision of the sound fixating eye by atropinization
(This also decreases distance vision). The amblyopic
eye with the use of a miotic drop starts seeing clearly
at near distance and thus gets exercised which can
improve its vision. Except in moderate or high
hypermetropia, atropinization does not sufficiently
decrease visual acuity of the sound eye so that the child
would prefer the amblyopic eye for fixation. Hence,
while not superior to occlusion, penalization is a useful
alternative treatment in patients with moderate
amblyopia.
CAM Treatment for Amblyopia
Campbell et at 13 proposed a new treatment for
amblyopia known as CAM (Cambridge stimulator).
In this procedure for a minimal time of 7 minutes a
day occlusion of the sound eye and simultaneous
stimulation (exercise) of the amblyopic eye with
slowly rotating high contrast grating of different
spatial frequencies is practised. The number of
sessions varies from 10 to 20 at a stretch. This may
have to be repeated at short intervals to sustain the
improvement of VA in the amblyopic eye.
The Rationale of CAM Treatment
Visual cortical cells selectively respond best to gratings
of certain size (spatial frequency), orientation and
contrast. As such a stimulus designed to exercise fully
the majority of visual neurones in the visual cortex
should contain high contrast gratings of different
frequencies and orientations. With this in mind, this
749
instrument was constructed in which sharp;
uminance-edged high contrast gratings were placed
and rotated so as to occupy all the orientational
positions.
A set of seven gratings of different spatial
frequencies is used. To begin with, the coarsest one is
placed on the CAM vision stimulator turntable and
the child is engaged in pencil games on a transparent
plastic plate over the rotating grating so as to
concentrate fixation. The non-amblyopic sound eye is
occluded during the treatment. After one minute of
using the first selected grating, the next finer grating
is placed on the turntable and the child directed to
play for another minute. After seven minutes of
treatment having used all the seven gratings, the child
is assessed for visual improvement and asked to return
in a few days. This treatment is however not claimed
to succeed in all cases of amblyopia. If there is no
improvement after three sittings one may have to give
up. Rohatgi and Chandra14 presented a study report
of 20 cases of amblyopia of the age group 5 to 16 years
using CAM stimulator which showed an improve-
ment of VA form FC 1 to 2 meters to 6/24 – 6/9
initially. And this could be sustained in at least half of
the cases when examined two years after the start of
the treatment with this instrument. The visual
improvement was found to be better in emmetropes
and hypermetropes (anisometropic-amblyopes) than
in those of strabismic amblyopia.
Levo-Dopa as an adjuvant to conventional
occlusion for the treatment of amblyopia has been
studied recently in amblyopic children below the age
of 12 years. A significant improvement in visual acuity
and contrast sensitivity was noticed. Levo-Dopa
(Carbidopa) (4:1) in doses of 2/0.5 mgm per kg body
weight was used for three weeks along with
conventional occlusion.
Epilogue
One would like to end the chapter by stating that
though no final and unanimous line of treatment has
yet been evolved for final treatment of amblyopia, may
it be strabismic, anisometropia, vision-deprivation
(Amblyopia ex-anopsia) and meridonial, we have the
obligation to treat these cases by the best appropriate
method to which one is used to, so that there is a
maximum improvement of the VA in the amblyopic
eye and maintain this improvement by supportive
therapy.
750 Section 7: Pediatric Ophthalmology Including Strabismus
REFERENCES
1. Thompson JR. The incidence and prevalence of strabismus—
A national audit. Eye 2002;16:522.
2. Gregson R. Why are we bad at treating amblyopia? Eye
2002;16:461.
3. Rohatgi JN, Mohanty KC. Trends in the management of
amblyopia. Proc All India Ophthalmol Soc 1972;29:117.
4. Wickham L. The assessment and management of strabismus
and amblyopia—A national audit. Eye 2002; 16:522.
5. Von Noorden GK. Binocular vision and ocular motility, The
CV Mosby Co: St Louis, 1990.
6. Von Noorden GK, Burian HM. Visual acuity in normal and
amblyopic patient under reduced illumination I Behaviour
of visual acuity with and without neutral density filter. Arch
Ophthalmol 1959;62:396.
7. Duke Elder WS. Textbook of Ophthalmology Henry Kimpton,
London, 1949;4.
8. Duke Elder WS. System of Ophthalmology. Ocular motility
and strabismus, Henry Kimpton, London 1965;6.
9. Roberts CJ, Adams GGW. Contact lenses in the management
of high anisometropic amblyopia. Eye 2002;16:577.
10. Lyle and Jackson. Practical Orthoptics in the Treatment of
Squint (5th edn). HK Lewis and Co: London 1967.
11. Flynn JT, Woodruff G, Thompson JR, et al. The theory of
amblyopia: An analysis comparing the results of amblyopia—
Therapy utilising two polled data sets. Trans Am Ophthalmol
Soc 1999;97:373. Quoted in Am J Ophthalmol 2000;12:831.
12. Marie Cleary. Efficacy of occlusion for strabismic amblyopia.
Can an optimal duration be identified. Br J Ophthalmol 2000;
84:957.
13. Campbell FW, Hess RF, Watson PG, et al. Preliminary results
of a physiologically based treatment of amblyopia. Br J
Ophthalmol 1978;62:748.
14. Rohatgi JN, Chandra Bimal. Trends in the management of
straight eye amblyopia. Proc 24th Intl Congress of Ophthal-
mol, Rome, 1986.
 Chapter 98
Nutritional Blindness: Vitamin A
Deficiency Disorders
Samar K Basak
Vitamin A deficiency (VAD) along with protein energy
malnutrition (PEM) causes severe blinding corneal
destruction. Most of the time, Vitamin A deficiency is
precipitated by PEM and other diseases which
precipitate malnutrition (e.g. diarrhea, measles,
malaria, or other acute illness in children. Diarrhea
causes malabsorption of vitamin A, High fever in
measles and malaria causes increased utilization of
vitamin A). Again malnutrition is caused by vitamin
A deficiency. Together, this blindness is termed as
‘nutritional blindness’, though the main factor is
vitamin A deficiency.
VAD is a systemic disease that affects the structures
and functions of all the epithelial cells and organs
throughout the body including the eye. The resultant
changes in epithelial architecture are termed as
“Keratinizing Metaplasia”. The characteristic ocular
manifestations of vitamin A deficiency ranging from
night blindness to corneal melting are termed as
“Xerophthalmia”. It is now becoming increasingly
apparent that VAD is responsible for a wide variety
of disorders. The new term vitamin A deficiency
disorders (VADD) is proposed as a comprehensive
term to cover all possible consequences of the lack of
dietary intake of vitamin A.
VAD should not be considered in isolation, but
recognized to occur together as in other nutritional
deficiencies. Children with corneal xerophthalmia
have consistently been observed to be stunted in
growth. Deficiency of two essential elements, iron and
zinc, have been highlighted along with VADD.
Vitamin A deficiency and iron deficiency anemia
tend to exist together in some children. Iron supple-
mentation along with vitamin A therapy is also
important to control nutritional anemia in children.
Many enzymes are zinc-dependent and among
them, retinal dehydrogenase is involved in rod
function. Some cases of night blindness resistant to
vitamin A supplement alone, may respond when zinc
is supplemented. In addition, zinc has beneficial effect
in diarrheal and some other infectious diseases. It is
probable that the mechanism of the mortality in those
children who had clinical VAD is in some way related
to impairment in their immune response to an
accompanying infectious disease. Follow-up over a
period of one year after the diagnosis of corneal
xerophthalmia only 40% survive. Of these survivors,
about 25% remain totally blind and 50-60% is partially
blind.
VADD may be divided into two distinct categories:
Primary VADD
— due to deficient dietary intake of vitamin A and
other micronutrients.
Secondary VADD
— due to some defect in absorption and utilization,
e.g.
• Malabsorption syndrome
• Chronic liver diseases
• Chronic pancreatitis
• Severe infections
• Enzymatic defect, etc.
752 Section 7: Pediatric Ophthalmology Including Strabismus
Global Prevalence of VAD
The WHO/UNICEF MDIS report (1995) estimated the
global prevalence of preschool children affected by
clinical VAD to be 3.3 million and sub-clinical VAD
to be 251 million.
In India, most recent survey (UNICEF MICS) on
clinical VAD has shown the prevalence of XN between
0-4 years is 0.6 to 2.8% and serum retinol level <0.70
μmol/L is between 16.9 to 63.8%.
It has been estimated that about 14,000 preschool
children suffer from vitamin A deficiency at any point
of time in India.
Epidemiology
It is important to understand that epidemiological
factors may vary considerably from place to place. So,
the interventions need to be appropriate for local
conditions.
Age
Preschool children are more vulnerable. Children
between 2-3 years are mostly affected.
Sex
Males are more susceptible to VAD than females.
Socioeconomic Status
There is a positive correlation with low socioeconomic
condition and VAD.
Physiological Status
Pregnant and lactating women are especially vulner-
able. Consequently, low vitamin A content (< 1.05
μmol) in breast milk contributes to increased
susceptibility of the infant.
Diet
“Rice-dependent” communities suffer mostly from
VAD. It is ironical that VAD occurs mainly in the moist
tropic where carotene is readily available to every
hand.
Season
VAD along with PEM is mostly seen in dry summer
season.
Breastfeeding
Breastfeeding is highly protective against xeroph-
thalmia. The composition of the weaning-diet is
obviously of great importance.
Cultural Factors
Customs practiced by a community is also important
in regards to dietary habits.
Infectious Diseases
The relationship is complex and bilateral. The
important diseases predispose to the development of
vitamin A deficiency are:
• Diarrhoeal diseases.
• Intestinal parasites—Giardiasis, Ascariasis and
Ankylostomiasis are mainly responsible for
reduced vitamin A absorption.
• Respiratory diseases—Pneumonia, whooping
cough, etc.
• Measles and associated conditions.
• HIV/AIDS—a recent entity may be a contributing
factor.
Protein Energy Malnutrition (PEM)
Corneal xerophthalmia is usually associated with a
severe degree of vitamin A deficiency which is often
accompanied by severe generalized PEM and severe
infection. Death is the most likely outcome at this late
stage, even in adequately treated patients. In fact,
death removes the problem of long-term care of the
blind survivors.
Vitamin A Deficiency Disorders Cycle (VADD Cycle)
This is to give some impression of the kind of
combinations of risk factors that conspire together at
different stages of the life to predispose to the
development of VADD (Fig. 98.1).
Major Signs and Symptoms of Xerophthalmia
(WHO Expert Group, 1982)
XN = Night blindness
X1A = Conjunctival xerosis
X1B = Bitot’s spot
X2 = Corneal xerosis
X3A = Corneal ulceration/Keratomalacia (<1/3
corneal surface)
X3B = Corneal ulceration/Keratomalacia (> 1/3
corneal surface)
XS = Corneal scar
XF = Xerophthalmic fundus
XN: Night blindness It is usually the earliest and most
prevalent manifestation of vitamin A deficiency;
sometimes termed as ‘Chicken eyes’ (chicken lack
 Chapter 98: Nutritional Blindness: Vitamin A Deficiency Disorders
Fig. 98.1: The vitamin A deficiency disorders (VADD)
rods, and are thus night blind). In night blindness, the
serum retinol level is usually between 10-20 mg/dL
(normal serum retinol level is > 25 mg/dL).
Night blindness responds rapidly within 24-48
hours to vitamin A therapy.
X1A and X1B: Conjunctival xerosis and Bitot’s spot
(Fig. 98.2) The conjunctival epithelium in vitamin A
deficiency is transformed from normal columnar to
stratified squamous with a resultant loss of goblet cells,
formation of a granular cell layer and keratinization
of the surface.
Fig. 98.2: X1B: Bitot’s spot
753
Conjunctival xerosis first appears at the temporal
side as an isolated oval or triangular patch, adjacent
to the limbus in the inter-palpebral fissure. It is almost
always present in both eyes. In some cases, keratin
and saprophytic bacilli accumulate on the xerotic
surface, giving it a foamy or cheesy appearance. These
lesions are known as Bitot’s spots.
Isolated, usually temporal, patches of conjunctival
xerosis or Bitot’s spots are some times encountered in
absence of active vitamin A deficiency. The only
certain means to distinguish an active lesion from an
inactive lesion is to observe its response to vitamin A
therapy.
Depending upon the response with vitamin A, Bitot’s spot
may be classified as:
1. Responsive and
2. Unresponsive type.
Responsive
• Subject usually a child of less than 6 years of age.
• With the maximum vitamin A dosage, response
usually evident within one week.
• Usually accompanied by generalized conjunctival
xerosis and night blindness.
• Males more commonly affected than females.
Unresponsive
• Commonly occur in children over 6 years and in
otherwise healthy adults.
• Usually a small, single spot.
• No accompanying evidence of VAD.
• Largely responsible for the apparent increase of
X1B prevalence with increasing age.
Active conjunctival xerosis and Bitot’s spot begin
to resolve within 2-5 days, and mostly disappear by
2 weeks.
X2: Corneal xerosis A hazy, lusterless dry appearance
of the cornea, is first seen near the inferior limbus.
Thick, keratinized plaques may form on the corneal
surface, and often more dense in the inter-palpebral
zone. Corneal xerosis responds within 2-5 days to
vitamin A therapy, and it returns to normal appea-
rance by 1-2 weeks (Fig. 98.3).
X3A and X3B: Corneal ulceration/Keratomalacia They
indicate permanent destruction of a part, or all the
corneal stroma, resulting in permanent structural
alteration. These ulcers are classically oval or round
“punched out” defects. The typical corneal ulcer is
754 Section 7: Pediatric Ophthalmology Including Strabismus

Fig. 98.4: X3B: Keratomalacia (> 1/3 corneal surface)

Fig. 98.3: X2: Corneal xerosis

inferonasal in position, about 1-2 mm in diameter and

0.25-0.50 mm in depth. Hypopyon may be present
with evidence of infection. The surrounding cornea is
usually xerotic. Perforation, if occurs, become plugged
with iris, thereby preserving the anterior chamber
(Fig. 98.4).
Corneal softening is due to a unique pathological
process termed colliquative necrosis. The stroma
becomes edematous. It is suspected that activation of
collagenases and other enzymes may be responsible,
but the precise pathogenesis is unknown. In some
cases, keratomalacia may proceed very rapidly,
noticeably within a matter of few hours, rather than
days (Fig. 98.5). This is especially true for very young
children (<1 year of age) and keratomalacia may
present without any evidence of xerosis of conjunctiva Fig. 98.5: Total keratomalacia with anterior
or cornea. staphyloma (left eye)
With therapy, superficial ulcers often heal with
surprisingly little scarring, but deeper ulcer with
perforation forms adherent leucoma. Sometimes, a
bigger perforation results with extrusion of intraocular
contents leading to phthisis bulbi or pseudo-cornea
leading to anterior staphyloma.
An emergency full course of vitamin A therapy
may still save the child’s eye to some extent.
XS: Xerophthalmic scar They are usually bilateral, and
indicate healed sequelae of prior corneal disease
related to vitamin A deficiency. They include nebula,
macula, leucoma, adherent leucoma, anterior staphy-
loma or phthisis bulbi (Figs 98.6 and 98.7).
The characteristic features of vitamin A Deficiency
related corneal scars (XS):
• Onset between about 2 months and 5 years.
• Accompanied at that time by severe PEM, measles,
severe diarrhea, respiratory infection. Fig. 98.6: Phthisis bulbi
 Chapter 98: Nutritional Blindness: Vitamin A Deficiency Disorders
Fig. 98.7: Bilateral phthisis bulbi
• Absence of trauma, or prolonged purulent
discharge.
• Location : typically nasal and inferior on the cornea
if only small part involved.
• Often bilateral, not necessarily equal in extent
(Fig. 98.8).
XF: Xerophthalmic (Uyemura’s) fundus Small white
lesions on the retina, seen in some cases of vitamin A
deficiency, are only of academic interest. They may
be associated with constriction of the visual fields.
ASSESSMENT OF VITAMIN A DEFICIENCY
(VAD) STATUS
Clinical (primary) Already discussed previously.
Fig. 98.8: XS: Bilateral corneal scar
755
Sub-clinical
• Dark adaptometry—Abnormal final rod threshold.
• Vision restoration test (VRT)—Delayed response
after blanching.
• Pupillary constriction—Failure of contraction in
low illuminations.
• Conjunctival impression cytology (CIC)—Abnor-
malities in epithelial and goblet cells pattern.
Biochemical Serum retinol (vitamin A)—
< 0.70 mmol/ml (20 mg/dL).
Treatment
Xerophthalmia is a medical emergency as it carries a
high-risk of corneal destruction and blindness, and/
or sepsis and death. Effective therapy is immediate
administration of massive doses of vitamin A with
concomitant treatment of underlying systemic illness
and protein energy malnutrition, and prevention of
any recurrence.
Treatment Schedule for Xerophthalmia
A. Vitamin A dose schedule for all age groups except
women of reproductive agea (WHO, UNICEF, IVACG
Task Force, 1997)
Timing Vitamin A dosageb
Immediately on diagnosis:
< 6 months of age 50,000 IU
6-12 months of age 100,000 IU
> 12 months of agea 200,000 IU
Next day Same age-specific dosec
At least 2 weeks later Same age-specific dosed
a. Caution: Women of reproductive age with night
blindness or Bitot’s spots should receive daily
doses =10,000 IU, or weekly doses of =25,000
IU, However, all women of reproductive age,
whether pregnant or not, who exhibit severe
signs of active xerophthalmia (i.e. acute corneal
lesions) should be treated as above.
b. For oral administration, preferably in an oil-
based preparation.
c. The mother or another responsible person can
administer the next-day dose at home.
d. To be administered at a subsequent health
service contact with the individual.
Because of the known teratogenic effects of large doses
of vitamin A, care has to be taken in the treatment of
xerophthalmia in pregnant women.
Active corneal lesion: Should receive full treatment.
756 Section 7: Pediatric Ophthalmology Including Strabismus
In XN and X1B: Should be treated with 10,000 IU daily
for 2 weeks or 25,000 IU weekly.
I/M injection of vitamin A (water-soluble)—100,000 IU is
given, when:
• the children can not swallow,
• in case of persistent vomiting,
• in severe mal-absorption syndrome or
• where the compliance is poor.
Oral administration is preferred, as it is safe, cheap
and highly effective even in presence of mild diarrhoea
(as it also helpful for healing of intestinal epithelium).
B. Medical status and diet: Proper treatment includes
rehydration, frequent feeding with easily digestible
and protein-rich food, and general supportive care.
Concurrent illness, e.g. respiratory infection, diarrhea,
worm infestation, etc. should also be treated.
C. Eye care: In case of corneal involvement:
1. Broad-spectrum antibiotic ointment e.g.
chloramphenicol or ciprofloxacin = 4 times
daily.
2. Atropine eye ointment = 2 times daily.
3. If secondary infection is present - second
antibiotic is added. Subconjunctival injection of
gentamycin and atropine may also be given.
4. Artificial tears (PVA or Povidone or both) eye
drop = 4-8 times daily.
D. Preventing recurrence: This is for the vulnerable
children by inexpensive, readily available vitamin A
rich diet. Periodic administration of a large dose of
vitamin A at an interval of 4-6 months is to ensure
adequate vitamin A store in children (see below).
Vitamin A Prophylaxis
Three main intervention strategies are:
a. Increasing the dietary intake of foods rich in
vitamin A and provitamin A.
b. Periodic administration of large doses of vitamin
A.
c. Administration of commonly consumable fortified
food items (vitamin A fortification).
Increased Intake of Dietary Vitamin A
Dark-green leafy vegetables—are usually the least
expensive; and most widely available source of
vitamin A. The daily requirement of vitamin A is
obtained from a handful of fresh spinach (65 gm) as
from a small portion of liver (65 gm), 4 medium-sized
hen’s eggs, 1.7 litre of whole cow’s milk, or 6 kg of
mutton.
The dark green leafy vegetables should be boiled,
shredded (mashed or sieved for the infants), and
should be combined with a small amount of edible oil
to improve vitamin A absorption.
Sources of Vitamin A
1. Vegetable sources: Dark-green leafy vegetables,
spinach, carrot, tomato, pumpkin, etc.
2. Animal sources: Liver, meat, cod-liver oil, shark-
liver oil, egg-yolk, etc.
3. Fortified food items: Vitamin A enriched commer-
cially available food items.
Daily Requirements
• School children, adolescent, and adults: 2250 IU
(750 mg).
• Children (0-4 years) : 1000-2000 IU (300-400 mg).
• Pregnancy and lactation : 3000-3500 IU (750 mg +
300 mg).
Functions of Vitamin A
In recent years knowledge of the functions of vitamin
A has increased greatly. In view of the fact that nuclear
receptors for retinoids have been identified in virtually
every type of cell, it could be argued that in some way
vitamin A plays a part in every bodily process. The
outlines of functions of vitamin A are :
1. Vision: Mainly under conditions of low illumi-
nation.
2. Cellular differentiation: In the form of retinoic acid,
it plays a very active role in cell differentiation
throughout the tissues and organs of the body.
3. Glycoprotein and glycosaminoglycan synthesis
4. Embryogenesis: Both severe vitamin A deficiency
and excessive dose of vitamin A in early pregnancy
cause malformations of the most organs of the
embryo.
5. Immune response: Non-specific but presumed to be
T-cell mediated.
6. Reproduction: May help in spermatogenesis and
prevent placental necrosis.
7. Hemopoiesis: May be required for iron metabolism
for full hematologic response.
8. Growth: Musculoskeletal growth of the body.
VISUAL CYCLE AND VITAMIN A
In the outer segment of rod in the retina, 11-cis retinal
combines with the membrane-bound protein, Opsin,
to form rhodopsin. It is involved in vision under
conditions of low illumination.
 Chapter 98: Nutritional Blindness: Vitamin A Deficiency Disorders
Similar complexes occur in cone cells to give there
specific iodopsins, with different absorption maxima,
resulting in blue, green and rod cones. These serve
color vision and vision in bright illumination. When
light strikes the retina, a series of biochemical changes
takes place, resulting in the generation of nerve
impulses.
Vitamin A, in the form of all-trans retinol is
delivered by the blood to retinal pigment epithelium
(RPE) where it is esterified for storage or isomerized
to 11-cis retinol which is then oxidized to II-cis retinol.
This is transported to the photoreceptor rods or
cones where it combines with the protein opsin to form
rhodopsin or iodopsin, respectively which is light
sensitive.
On exposure to light, 11-cis retinal is isomerized
back to all-trans retinal and the nerve impulse is
generated. On release from the protein all-trans retinal
is reduced to all-trans retinol and transported back to
RPE to complete the cycle.
Hypervitaminosis A (Vitamin A Toxicity)
Vitamin A toxicity may be either acute or chronic.
Acute toxicity usually follows a large single dose of
vitamin A. It is recognized by symptoms suggestive
of acute rise in intracranial tension—e.g. nausea,
vomiting and acute headache and in neonate, bulging
of the fontanels. These symptoms subside rapidly
without any permanent ill effects, provided no further
vitamin A is given.
The subjects are usually young children in a
supplementation program or Arctic explorers who
consumed large amount of liver of polar bear or seal.
Chronic toxicity is uncommon and may be very
difficult to diagnose. This may occur as a result of
dietary habit or regular use of vitamin A tablets. The
common symptoms are headache, vomiting, diplopia
(due to pseudo-tumor cerebri), alopecia, dryness of
mucous membrane, desquamation of skin, liver
damage including cirrhosis, hemorrhage or even
coma. In pregnant woman, it may cause teratogenic
effect to induce congenital malformation. If further
excessive vitamin A intake is not prevented, death may
result.
Periodic Supplementation
Oral administration of 200,000 IU vitamin A and half
this dose for children age 6-12 months, every
4-6 months will protect majority of the recipients from
757
diversifying VAA. This prophylaxis may be for entire
neighborhood (mass prophylaxis), or for high-risk
group (selective prophylaxis).
The high-risk conditions are:
• Children with severe PEM.
• Children with measles.
• Children with diarrhea, lower respiratory tract
infection, or other acute infection (e.g. malaria, chicken
pox, etc.).
They should receive a dose of 200,000 IU vitamin
A orally at the time of diagnosis by the pediatrician.
Children below 1 year should receive half of the above
dose; and children below 6 months old should receive
one-quarter.
High-dose universal-distribution schedule for preven-
tion of vitamin A deficiency (WHO, UNICEF, IVACG Task
Force, 1997)
• Infants < 6 months of agea
Non-breastfed infants 50,000 IU orally
Breastfed infants whose 50,000 IU orally
mothers have not received
supplemental vitamin A
• Infants 6-12 months of age 100,000 IU orally,
every 4-6 monthsb
• Children > 12 months of age 200,000 IU orally,
every 4-6 monthsb
• Mothers 200,000 IU orally,
within 8 weeks of
delivery
a. Programs should ensure that infants < 6 months
of age do not receive the larger dose intended for
mothers. It may therefore be preferable to dose
infants with a liquid dispenser to avoid possible
confusion between capsules of different dosages.
b. Evidence suggests that vitamin A reserves in
deficient individuals can fall below optimal levels
3-6 months following a high dose; however, dosing
at 4-6 months intervals should be sufficient to
prevent serious consequences of vitamin A
deficiency.
Fortification of Dietary Items
Fortification, the addition of selected nutrients to
common dietary items is a successful means of
protecting nutritional status of the children. Cooking
medium, milk, sugar, tea, cereal grains, bread, etc. may
be fortified with vitamin A.
The fortified foods should be inexpensive, stable
and virtually undetectable in food-vehicle selected,
and they should be acceptable to the community.
758 Section 7: Pediatric Ophthalmology Including Strabismus

New Plant Breeding and 5. Vitamin D — Zonular cataract.

Genetic Modification Papilledema (due to tetany).
6. Vitamin K — Hemorrhages in different
• To grow more high carotene containing foods. ocular tissues.
• Genetic modification of rice (Oryza sativa) to
provide β-carotene BIBLIOGRAPHY
1. McLaren DS, Frigg M. Sight and Life Manual of Vitamin A
Ocular Findings in other Deficiency Disorders (VADD), Task Force, Sight and Life (2nd
Vitamin Deficiencies edn). Switzerland, 2001.
2. McLaren DS. Towards the conquest of Vitamin A Deficiency
Vitamins Ocular manifestations Disorders (VADD). Sight and Life, Basel, 1999.
1. Vitamin B1 — Retrobular neuritis. 3. Rando RR. Retinoid isomerization reactions in the visual
(Thiamine) — Corneal hyposthesia. system. In: Vitamin A in Health and Disease, Marcel Dekker,
— Corneal and conjunctival New York, 1994;503-529.
4. Sommer A. Vitamin A deficiency and its consequences (3rd
degenerative changes.
edn). WHO, Geneva, 1995.
2. Vitamin B2 — Corneal vascularization
5. Sommer A, West KP Jr. Vitamin A deficiency: Health, Survival
(Riboflavine) Punctate epithelial keratitis.
and Vision. Oxford University Press, New York, 1996.
— Blepharoconjunctivitis. 6. WHO: Global prevalence of vitamin A deficiency. WHO/
3. Vitamin B12 — Retrobulbar neuritis. NOT/95.3,WHO, Geneva, 1995.
4. Vitamin C — Delayed wound healing. 7. WHO, UNICEF, IVACG Task Force. Vitamin A supplements.
Hemorrhage in the A guide to their use in the treatment and prevention of
conjunctiva, retina, or orbit. Vitamin A Deficiency and Xerophthalmia (2nd edn). WHO,
— Kerato—conjunctivitis. Geneva, 1997.
 Chapter 99
Congenital Glaucoma
B Sridhar Rao
Glaucoma in infants and children is commonly a
developmental disorder. The mechanism of glaucoma
in childhood is different from that of older patients.
Ophthalmologist must be familiar with the additional
information for the evaluation and care of childhood
glaucoma. Accurate diagnosis is helped by familiarity
with the different causes of childhood glaucoma.
SYMPTOMS AND SIGNS
The clinical presentation of childhood glaucoma varies
greatly depending on the degree of intraocular
pressure elevation and age of the child. Early diagnosis
can most often be made by the pediatrician or a general
practitioner who notices the early signs of the disease.
In the newborn, the diagnosis is suggested by diffuse
corneal opacification. Any corneal opacification in the
newborn is an indication to rule out glaucoma. These
newborns with dense opacities do not present the
subtle signs like corneal enlargement. Some children
are noticed to cover or rub the eyes due to the effects
of elevated intraocular pressure. Photophobia is one
of the most common symptoms at presentation and is
usually associated with clouding of the cornea and
related breaks in the Descemet’s membrane. Epiphora
is also evident. Abnormal corneal enlargement with
deep anterior chamber may be the first sign and is
strongly suggestive of congenital glaucoma. In
children over one year of age glaucoma generally
induces fewer signs and symptoms. In children
between one to four years, glaucoma may be missed
if it is not suspected from recognition of other
associated ocular or systemic anomalies. After four
years glaucoma is detected in the course of an
evaluation for decreased uncorrected visual acuity
related to myopia.
The optic disk is usually abnormal at the time of
diagnosis of congenital glaucoma with variable
amount of cupping. The cup enlargement is usually
in a concentric form. The neuroretinal rim remains
pink until the advanced stages, when pallor is noticed
temporally. The diameter of the optic nerve head
increases exaggerating the apparent cup size increase.
Though the anterior chamber deepens in congenital
glaucoma, some children with secondary glaucomas,
viz. with retinopathy of prematurity, nanophthalmos
and microphthalmos present with shallow anterior
chamber. Iris and anterior chamber angle anomalies
are also common in many types of primary and
secondary glaucoma and these need to be evaluated
thoroughly for proper management.
EXAMINATION TECHNIQUES IN CHILDREN
Examination of children in the clinic is often
incomplete, but is the first important step in noting
the signs and symptoms, presence of associated
systemic disease and ascertaining past history of
trauma as well as family history. External examination
may reveal conspicuous corneal signs like enlarge-
ment and lack of luster suggesting corneal edema.
Tonometry is very difficult except under a general
anesthesia in most children.
The accuracy of pressure measurements taken in
the office is affected by straining; while pressures
recorded under general anesthesia may be lower due
to the effects of some anesthetic agents.
Examination Under Anesthesia
Examination under anesthesia provides additional
important information. It is mandatory to follow a
routine, as mentioned below, so that nothing impor-
tant is missed.
760 Section 7: Pediatric Ophthalmology Including Strabismus

1. External examination
2. Intraocular pressure (IOP) measurement
3. Corneal diameter measurement
4. Gonioscopy
5. Ophthalmoscopy.

External Examination
This can be performed by using the loupe or hand
held microscope or more easily with the operating
microscope. The characteristic Haab’s striae which are
due to ruptures in the Descemet’s membranes are
usually evident. These are multiple curvilinear and
are horizontal or parallel to the limbus (Fig. 99.1).
These need to be distinguished from those caused by
trauma as in forceps delivery which are vertically
oriented in the cornea. It is important to distinguish Fig. 99.1: Slit lamp photograph showing Haab’s striae in
congenital glaucoma which are horizontally oriented
other conditions which may mimic, like corneal
dystrophy.
moderate miosis a clearer view is obtained by placing
the Koeppe’s lens and viewing the disk through this.
IOP Measurement
Careful documentation of the appearance of the disk
IOP measurement is best done with the Perkin’s hand helps to gauge the success of treatment on follow-up
held tonometer or with more recent digital instru- examinations. Refraction of both the eyes should be
ments like Tonopen which has a narrow tip for easier performed, as a progressive myopic change occurs
measurement. It is important to have the IOP with uncontrolled IOP.
measured with the child relaxed but the clinician
should remember that halothane anesthesia tends to CLINICAL TYPES OF CONGENITAL GLAUCOMA
lower IOP.
Glaucoma in children can be classified into the
It is good to have standard concentration of
following three major types:
halothane to help follow the IOP postoperatively.
1. Primary congenital glaucoma
2. Glaucoma associated with ocular anomalies
Corneal Diameter Measurement
3. Glaucoma associated with systemic anomalies.
This is done using a caliper taking care to avoid
parallax. The normal infant’s corneal diameter is 10.5- Primary Congenital Glaucoma
11 mm. At one year it is 11.5-12.00 mm and at 2 years It is the most common type of childhood glaucoma,
12.5 mm. A corneal diameter of 13 mm at any age and with an incidence of 1:15,000 live births. It most often
12 mm below the age of 1 year is suspicious of occurs sporadically, but is inherited by polygenic
abnormal enlargement. The horizontal corneal inheritance with a risk of approximately 5 percent in
diameter is the one generally chosen for measurement. siblings and offspring. Males are affected more
frequently than females. It can be detected at birth in
Gonioscopy one-third of the cases and the remaining by the age of
one year. Primary congenital glaucoma should be
This is done with smooth domed Koeppe’s lens.
differentiated from other primary types of glaucoma
Simultaneous goniolens in both eyes aids quick
that are usually recognized promptly at birth due to
comparison of both eyes in children with unilateral
striking corneal enlargement and severe diffuse
congenital glaucoma.
opacification of the cornea. This type of early onset
severe glaucoma is more often seen in India. 2
Ophthalmoscopy
Gonioscopy whenever possible reveals variable angle
This is best performed with the direct ophthal- anomaly. The longitudinal fibers of the ciliary muscle
moscope. In edematous cornea or in eyes with show trabecular insertion. The scleral spur is difficult
 Chapter 99: Congenital Glaucoma 761
to define as it is hidden by the overlying translucent
tissue in the angle recess consisting of uveal trabecular
meshwork and the iris processes (Fig. 99.2). There is
usually hypoplasia of anterior iris stroma and presence
of prominent radial iris vessels. The angle is wide with
no angle recess.
Primary congenital glaucoma is identified by signs
and symptoms of progressive corneal abnormalities
secondary to glaucoma. Visual loss occurs because of
corneal distortion resulting in astigmatism, corneal
opacification, ocular enlargement, and glaucomatous
optic atrophy.

Pathogenesis Fig. 99.2: Gonioscopic appearance of angle of the

anterior chamber in congenital glaucoma showing
Various theories have been postulated for the iridotrabecular dysgenesis with iris processes
causation primary infantile glaucoma. Barkan 3
attributed it to the persistence of fetal mesodern (uveal
meshwork) producing the classical Barkan’s mem-
brane which however is not seen histologically. Allen,
Burian, and Braley4 attributed incomplete cleavage of
fetal mesoderm from improper orientation of
developing ciliary muscle to produce congenital
glaucoma, hence called trabeculodysgenesis. Maum-
enee 5 administered that the anterior insertion of
longitudinal ciliary muscle fibers cause compression
of the scleral spur, trabeculum, and Schlemm’s canal.

Glaucoma Associated with Ocular Anomalies

The common ocular anomalies associated with Fig. 99.3: Slit lamp photograph of congenital ectropion
congenital glaucoma are: uveae with associated glaucoma
1. Anterior chamber cleavage syndrome—Axenfeld-
Rieger’s anomaly and Peter’s anomaly
2. Aniridia
3. Iridotrabecular dysgenesis and ectropion uvea
(Fig. 99.3)
4. Posterior polymorphous dystrophy.

Glaucoma Associated with Systemic Anomalies

1. Sturge-Weber syndrome (Fig. 99.4)
2. Neurofibromatosis
3. Rieger’s syndrome
4. Marfan’s syndrome.

Differential Diagnosis
The epiphora due to nasolacrimal obstruction must
be differentiated from tearing, secondary to congenital
glaucoma. However, both these conditions can coexist.
Corneal enlargement should be differentiated from Fig. 99.4: External photograph showing naevus-flammeus
megalocornea and high myopia. Corneal opacification involving left side of the face in Sturge-Weber associated
in congenital hereditary endothelial dystrophy and glaucoma
762 Section 7: Pediatric Ophthalmology Including Strabismus
mucopolysacchariodosis may mimic congenital glau-
coma. The Haab’s striae must be distinguished from
those caused by trauma of a forceps delivery, by the
absence of corneal enlargement and by their vertical
orientation.
Treatment
The treatment of primary congenital glaucoma is
primarily surgical. Medical treatment is mainly in
preparation for a definitive surgical treatment. Topical
carbonic anhydrase inhibitors and beta-blockers are
indicated. Barkan 6-9 introduced the technique of
goniotomy, marking the beginning of a new era in the
treatment of congenital glaucoma. The objective of
goniotomy is to remove the obstructing tissue that
causes aqueous obstruction and thereby restore the
access of aqueous to Schlemm’s canal. Goniotomy also
satisfies all the three major theories of congenital
glaucoma by the following:
1. Dividing persistent mesoderm (Barkan)
2. Completing angle cleavage (Allen, Burian, Braley)
3. Relaxing ciliary muscle (Maumenee).
Goniotomy requires good surgical skill and a clear
view of the angle of the anterior chamber and expertise
in direct gonioscopy. The procedure is done using a
Barkan operating gonioscopy lens for viewing the
angle through the operating microscope and a Barkan
or Swan goniotomy knife (Fig. 99.5). A superficial inci-
sion is made in the uveal trabecular meshwork
extending to about 120° of the angle. Preoperative
miotics and intraoperative viscoelastic help in safely
completing the procedure. The results of goniotomy
Fig. 99.5: Goniotomy procedure using the Hoskins-Barkan
goniotomy lens and a Swan goniotomy knife
reported by 12 authors, show a uniform success rate
of 80 percent in infantile glaucoma.10
The age of the patient when the glaucoma is recog-
nized appears to be most important. Haas11 has repor-
ted a success rate of only 55 percent with goniotomy
for congenital glaucoma recognized from birth
through two months of age. Similar low success has
been reported by Constenbader and Kwitko 12 in
children with congenital glaucoma recognized at 5
days of age or less. The severity of the filtration angle
defect determines the success rate of goniotomy.
Goniotomy is most successful, when the condition is
detected early and the surgery is performed between
1 month and 1 year of age. Over the age of 1 year the
success of goniotomy drops considerably.
External Trabeculotomy
External trabeculotomy or trabeculotomy ab externo,
occupies an important place in the treatment of
congenital glaucoma. This procedure was first
described by Burian,13 Allen,14 and Harms.15 The main
indications for trabeculotomy are eyes where corneal
haze precludes clear visualization of the angle for
goniotomy and eyes in which two goniotomies done
earlier have failed. However, reports of high success
of external trabeculotomy as a primary procedure for
congenital glaucoma have been published.16-19
The procedure is technically easier for an anterior
segment microsurgeon well versed in the anatomy of
the angle. It is important to remember that it is more
difficult to achieve a technically perfect procedure
with trabeculotomy than that with goniotomy. The
operation consists essentially of the introduction of
an appropriately constructed spatula into the
Schlemm’s canal or in the scleral groove and of
sectioning the trabecular meshwork and displacing
of overlying mesodermal tissue, thus giving the
aqueous direct access to outflow channels.
Procedure
The procedure consists of raising a lamellar scleral flap
after a fornix based conjuctival flap. The advantage of
having lamellar scleral flap is that the procedure can
be combined with trabeculectomy in severe cases with
cicatrized angle. The most important landmark is the
transition zone between the white sclera and the grey
limbus, the sclerolimbal junction (SLJ). In this area lies
the sulcus containing Schlemm’s canal. A radial
incision is made across the SLJ. The objective of this
radial incision is to cut the external wall of Schlemm’s
canal and to avoid entry into anterior chamber.
 Chapter 99: Congenital Glaucoma
Usually a distinct lumen is seen along with a drop of
aqueous or blood. If there is some doubt about the
exact location of Schlemm’s canal, a 5-0 or 6-0 nylon
suture is used to probe the cut edge to search it. The
internal arm of the trabeculotome (either Harms or
McPherson) is introduced into the canal using the
external parallel arm as a guide. Since, it is more
difficult for a right handed surgeon to introduce the
trabeculotome to the right of radial incision, this
should be done first while the anterior chamber is deep
and clear of blood. Once the trabeculotome is entirely
within the canal it is rotated into the anterior chamber
using the radial incision as the fulcrum (Fig. 99.6).
When about 80 percent of the internal arm is visible,
the rotation is reversed and the instrument is
withdrawn. The trabeculotome is then passed into
Schlemm’s canal on the other side of the radial incision
and similarly rotated into the anterior chamber. In
most cases the anterior chamber will shallow slightly
and a small amount of blood will appear.
The scleral flap is then sutured and with 10-0 nylon
suture followed by closure of conjunctiva in the usual
fashion. Goniotomy requires that the surgeon should
be adept in the study of visual distortion produced
by the operating gonioprism which does not occur
with external trabeculotomy. It appears that the
common characteristic feature of both external
trabeculotomy and goniotomy is to sever or change
the relationship between ciliary muscle and trabecular
meshwork. The success of trabeculotomy is not
dependent on the severity of the glaucoma, the corneal
diameter or the presence of corneal edema unlike a
goniotomy procedure.16 However, in patients with
cicatrized angle or iridocorneal dysgenesis or
associated ocular anomaly like aniridia, trabeculotomy
gives poorer results.16,17 If Schlemm’s canal could not
be properly cannulated or previous trabeculotomy
failed to control the IOP, the trabeculotomy shouls be
combined with a trabeculectomy.17 Trabeculectomy
alone is indicated when causation of open angle is
considered to be due to trabeculodysgenesis. Sood2
recommended a similar combined procedure since
patients seen in India have a more severe form with
early onset of glaucoma as well as their delayed
presentation. Luntz and Livingston20 have empha-
sized that the gonioscopic appearance of the angle is
a prognostic factor and the insignificant role of age at
onset and corneal diameter on the success of external
trabeculotomy.
763
Fig. 99.6: External trabeculotomy procedure. The internal arm
of the Harms trabeculotome (left) is introduced into the
Schlemm’s canal using the external arm as the guide and
rotated into the anterior chamber
Direct Goniotomy
Kwitko21 has described a direct goniotomy-gonio-
tripsy operation in severe cases with cloudy cornea.
This operation requires no viewing lens or a clear
cornea, yet the area involved causing obstruction to
the filtration angle is carefully removed under direct
visualization. This procedure carries a success rate of
about 40 to 50 percent in patients with extensive
abnormal development.
Other Procedures
Primary goniotrephine with scleral flap is another
surgical procedure and almost 80 percent success has
been claimed. In patients not responding repeatedly
to conventional procedures, filtration surgery with the
adjunctive use of antimetabolities like 5-Fluorouracil
or Mitomycin-C should be considered. Use of setons
like Molteno and Ahmed glaucoma valves23 can be
made to control the glaucoma in refractory cases.
These implants are well-tolerated by children. 22
Cyclodestructive procedures, like cyclophoto-
coagulation or cyclocryotherapy is reserved for
situations when the patient has very little visual
potential. Recently, there has been a report of
successful use of Q-switched Nd: YAG laser to achieve
a goniotomy in a 6-year old child with congenital
glaucoma, where surgical goniotomy controlled the
intraocular pressure for a few years.23 This has been
recommended in patients with isolated trabecular
dysgenesis.
764 Section 7: Pediatric Ophthalmology Including Strabismus
Follow-up
After satisfactory control of intraocular pressure the
corneal diameter stabilizes and glaucomatous cupping
reverses if the surgical success occurs within one year
of life. The cup size improvement occurs because the
connective tissue of the optic nerve head in the first
year of life is lacking in collagen allowing a more
elastic response to normalization of IOP.17 It is impor-
tant that after successful control of glaucoma following
surgery, the visual rehabilitation should include
proper treatment of amblyopia with refractive
correction and occlusion therapy wherever indicated.
All these patients should be monitored closely
throughout their life for a possible relapse with
recurrence of raised intraocular pressure.
Other Types of Congenital Glaucoma
Glaucoma associated with iridocorneal dysgenesis like
Axenfeld-Rieger’s anomaly, with marked anterior
synechiae and developmental iris anomalies as well
as lens opacification responds poorly. Glaucoma
associated with aniridia presents later in childhood
due to gradual increase in intraocular pressure caused
by obstruction of iris stump. When congenital
glaucoma complicates aniridia, the trabecular
meshwork is not obstructed by the iris stump.
Trabeculotomy or goniotomy is useful for this type of
glaucoma. Glaucoma associated with congenital
ectropion uvea is associated with iridotrabecular
dysgenesis, with dense iris processes obscuring the
angle. These patients also present later in life.
Sturge-Weber Syndrome
These patients have associated systemic defects and
problems. These include facial hemangioma, heman-
gioma involving leptomeninges, ocular manifestations
including glaucoma, prominent episcleral vessels and
choroidal hemangioma. Trabeculotomy combined
with trabeculectomy is recommended for this
condition.2,24 In patients with prominent episcleral
vessels intraoperative choroidal effusion can occur.25
REFERENCES
1. Krupin T, Feitl M, Roshe R. Halothane anesthesia and aqueous
humor dynamics in laboratory animals. Invest Ophthalmol
Visual Sci 1981;20:683.
2. Sood NN. Personal communication.
3. Barkan O. Pathogenesis of congenital glaucoma. Am J
Ophthalmol 1955;40:1.
4. Allen L, Burian HM, Braley AE. A new concept of the
development of the anterior chamber angle. Arch Ophthalmol
1955;53:783.
5. Maumenee AE. The pathogenesis of congenital glaucoma.
Am J Ophthalmol 1959;47:827.
6. Barkan O. Goniotomy for the relief of congenital glaucoma.
Br J Ophthalmol 1948;32:701.
7. Barkan O. Technique of goniotomy for congenital glaucoma.
Arch Ophthalmol 1949;41:65.
8. Barkan O. Goniotomy knife and surgical contact glass. Arch
Ophthalmol 1950;44:431.
9. Barkan O. Surgery of congenital glaucoma. Review of 196
eyes operated by Goniotomy. Am Ophthalmol 1953;36:1523.
10. DeLuise VP, Anderson DR: Primary infantile glaucoma
(congenital glaucoma). Surv Ophthalmol 1983;28:1.
11. Haas J. Principles and problems of therapy in congenital
glaucoma. Invest Ophthalmol 1968;7:140.
12. Constenbader FD, Kwitko MC. Congenital glaucoma. J Ped
Ophthalmol 1967;4:9.
13. Burian HM: A case of Marfan’s syndrome with bilateral
glaucoma with description of a new type of operation for
developmental glaucoma (trabeculotomy ab externo). Am J
Ophthalmol 1960;50:1187.
14. Allen L, Burian HM: Trabeculotomy ab externo. Am J
Ophthalmol 1962;53:19.
15. Harms H, Dannheim R. Epicritical consideration of 300 cases
of trabeculotomy “ab externo”. Trans Ophthalmol Soc UK
1969;89:491.
16. Luntz MH. Congenital infantile, and juvenile glaucoma.
Ophthalmology 1979;86:793.
17. Quigley HA. Childhood glaucoma: Results with trabeculo-
tomy and study of reversible cupping. Ophthalmology
1982;89:219.
18. Mandal AK, Gothwar VK, Bagga H et al. Outcome of surgery
on infants younger than one month with congenital glaucoma.
Ophthalmology, 2003;110:1909.
19. Anderson DR. Trabeculotomy compared to goniotomy for
glaucoma in children. Ophthalmology 1983;90:805.
20. Luntz MH, Livingston DG. Trabeculotomy ab externo and
Trabeculectomy in Congenital and Adult-onset glaucoma.
Am J Ophthalmol 1977;89:174.
21. Kwitko ML. The pediatric glaucomas. Glaucoma 1983;5:261.
22. Molteno ACB, Ancker E, Van Biljon G. Surgical technique
for advanced juvenile glaucoma. Arch Ophthalmol 1984;
102:51.
23. Coleman AL, Smyth RJ, Wilson MR et al. Initial clinical
experience with Ahmed glaucoma valve implant in pediatric
patients. Arch Ophthalmol 1997;115:186.
24. Board RJ, Shields MB. Combined trabeculotomy—trabeculec-
tomy for the management of glaucoma associated with
Sturge-Weber syndrome. Ophthalmic Surg 1981;12:817.
25. Hoskins HD Jr, Hetherington J Jr, Shaffer RN et al.
Developmental glaucomas: Diagnosis and classification in
symposium on glaucoma. Trans New Orleans Academy of
Ophthalmology. CV Mosby: St. Louis, 1981;172.
 Chapter 100

Glaucomas Associated with

Developmental and Congenital
Anomalies
S Choudhury, S Mitra

INTRODUCTION ANIRIDIA
The disorders to be discussed here have systemic Aniridia, first described in 1818 by Barratta,1 is a rare,
and/or ocular developmental anomalies associated bilateral developmental disorder, occurring in 1.8 per
with glaucoma, probably caused by developmental 100,000 live births. Aniridia can be classified into the
anomalies of the anterior chamber angle. These following three genetic types in a decreasing order of
developmental anomalies were traditionally thought prevalence:
to represent a mesodermal dysgenesis in the anterior 1. Isolated autosomal dominant aniridia (AN-1) with
ocular segment. More recent evidences suggest that complete penetrance and variable expressivity
the defect causing these abnormalities is probably of (approx. 85%). Gutbier first reported it in 1837. Two
neural crest origin. thirds of cases are familial, while one-third are new
Table 100.1 shows a classification of some ocular mutations or sporadic.
developmental abnormalities based on the major 2. Autosomal dominant aniridia (AN-2) associated
embryological layers involved. with Wilms’ tumor, genitourinary anomalies and
mental retardation (approx. 13%). The association
Table 100.1: Classification of ocular
with Wilms’ tumor was first reported in 1953.1
developmental anomalies
3. Autosomal Recessive Aniridia (AN-3) with
Sl. Clinical condition Embryologic layer cerebellar ataxia and mental retardation (approx.
N. involved 2%). This association, also known as Gillespie’s
1. Aniridia Neuroectoderm syndrome, was first described in 1965.2 The cere-
2. Peter’s anomaly bellar lesion can be documented by CT/MRI
3. Anterior segment First neural crest scanning.
mesenchymal dysgenesis mesenchymal wave
The presenting symptoms of aniridia may be
(ASMD)
4. Congenital hereditary photophobia, nystagmus, dimness of vision,
endothelial dystrophy (CHED) amblyopia and strabismus. The dimness of vision
5. Congenital hereditary stromal Second neural crest is usually progressive due to associated defects like
dystrophy (CHSD) mesenchymal wave corneal and lental opacities and angle closure
6. Axenfeld-Rieger syndrome Third neural crest glaucoma. Eighty six percent of the affected indi-
mesenchymal wave viduals show a visual acuity of 20/100 or less in
766 Section 7: Pediatric Ophthalmology Including Strabismus
the better eye. Presence of high refractive errors
lead to amblyopia and an absence of stereoacuity
is common in the patients with strabismus.
Clinical Findings
Corneal Abnormalities
Microcornea usually is associated with aniridia. 3
Sometimes a cellular infiltrate may develop between
the epithelium and Bowman’s layer as early as 2 years
of age.
Iris Anomalies
Most commonly iris appears as a small rudimentary
stump, but within isolated AN-1 families,4 an extreme
variablity ranging from rudimentary stumps to
minimal hypoplasia with round pupils can be seen.
Other additional abnormalities are persistent iris
strands, persistent tunica vasculosa lentis and
pupillary displacements. Iris fluorescein angiography
best demonstrates the vascular abnormalities even in
minimally affected patients.
Lens Abnormalities
Congenital abnormalities include cataracts (50-85%)
microphakia and lens subluxation (0-56%).5
Ptosis
It occurs more as a protective functional phenomenon
in response to photophobia. Ptosis may be due to
varying degree of decreased levator function.
Posterior Segment Abnormalities
Macular and/or retinal hypoplasia and optic nerve
hypoplasia (75%) are commonly encountered in AN-
1 and AN-2 patients, but are usually normal with AN-
3 group. There exists no correlation between the
amount of aniridia and macular hypoplasia.
Glaucoma
Glaucoma in aniridia has two closely related patho-
geneses.6 In AN-2 trabecular meshwork obstruction
is caused by developmental angle anomalies. In AN-
1 (and probably AN-3) the close apposition of the
rudimentary iris stump to trabecular meshwork leads
to angle closure glaucoma. Glaucoma usually
manifests in preadolescence or adolescence with a
highly variable incidence (6-75%).5
Recently it is being suggested that the pathogenesis
of aniridia (AN-1 and AN-2) is due to a primary
development arrest of neuroectoderm and a secondary
alteration of all three neural crest waves of mesen-
chyme. It may involve defective formation or excessive
regression of various layers of the anterior segment
caused by cellular or biochemical aberrations.
Pendular nystagmus in aniridia is the result of
gross visual defect caused by foveal hypoplasia.
Variable degrees of optic nerve hypoplasia are also
responsible for visual loss. Refractive error is another
cause of visual loss.
Management
Prognosis is slightly better in isolated AN-1 families
and in AN-2 patients with minimal iris anomalies.
a. For prevention of this developmental disorder of
the anterior segment genetic counseling is the most
significant measure.
b. Tinted or iris painted contact lenses can reduce
photophobia and also help decrease the nystagmus
when given in early infancy.
c. Correction of all refractive errors with occlusion
therapy for amblyopia, to achieve symmetrical
visual acuity, should be tried. In absence of macular
hypoplasia early squint correction will restore
binocularity.
d. Management of glaucoma.
Medical It is safe but often inadequate. Miotics are
used for their role on increasing outflow facility.
Patients often become refractory to the sympatho-
mimetics, beta-blockers and carbonic anhydrase
inhibitors.
Invasive surgical procedures It may give temporary
relief but often are met with disastrous complications.
Goniotomy may be the early therapeutic/prophylactic
procedure of choice.7,8 Chance of vitreous loss is
profound with filtering procedures. Trabeculotomy
is considered to be moderately safe and effective.
Noninvasive surgical procedures like laser therapy for angle
anomalies It shows initial success rate in lowering the
intraocular pressure followed by a marked rise.
Cyclocryotherapy may be the safest surgical proce-
dure for this condition, but single heavy treatment
may produce complications like uveitis, uveal
effusion, and prolonged hypotony.
AXENFELD-RIEGER SYNDROME
In 1920, Axenfeld1 described a white line near the
limbus on the posterior aspect of cornea with iris
 Chapter 100: Glaucomas Associated with Developmental and Congenital Anomalies
strands extending to it from the periphery and coined
the term “posterior embryotoxon of the cornea”.
Rieger1 in mid 1930s described similar cases with
additional iris changes like corectopia, atrophy and
hole formation. He named it “mesodermal dysgenesis
of the cornea and iris”. Several patients of this group
exhibited extraocular developmental lesions like
defects of teeth and facial bones. Various descriptive
terminology have failed to give a satisfactory collective
term for this condition and “Axenfeld-Rieger
syndrome” has been proposed to describe all clinical
variations within the spectrum of this developmental
disorder.
A positive family history with an autosomal
dominant mode of inheritance is found in many cases.
Rare cases may show chromosomal anomalies. No sex
predilection has been noted. The age of diagnosis of
the A-R syndrome ranges from birth to adulthood.
This is of autosomal inheritance pattern, but it may
also be sporadic.
Ocular Features
Presentations are typically bilateral and frequently
associated with secondary glaucoma (50%). Structures
most commonly affected are peripheral cornea,
anterior chamber angle and iris.
Cornea
Typical abnormality is an anteriorly displaced
prominent Schwalbe’s line, which is a characteristic
sign but is not pathognomonic. In 8 to 15 percent of
general population this isolated defect called
“posterior embryotoxon” can be detected. Cornea
otherwise is unaffected with the exceptions of
occasional altered shape or altered size, megalocornea
being more common. Nonspecific central corneal
opacities are very rarely observed.
Anterior Chamber Angle
Gonioscopy demonstrates the prominent Schwalbe’s
line suspended in some areas from the cornea
occasionally by a thin membrane.9,10 Tissue strands
ranging from threads to broad bands, bridge the
anterior chamber angle from the peripheral iris to the
prominent ridge extending for 15 degree angle
circumference. Beyond this the angle is open.
Trabecular meshwork is visible but scleral spur is
obscured by the insertion of the peripheral iris on the
posterior portion of the meshwork.
767
Iris
Abnormalities of the iris may vary from mild
peripheral anomalies (traditional Axenfeld anomaly)
to mild stromal thinning, marked atrophy with hole
formation, corectopia and ectropion of uveal pigment
(traditional Rieger’s anomaly). In corectopia, pupil is
displaced toward a prominent peripheral strand with
atrophy and hole formation in the quadrant away from
the direction of the corectopia. A very small number
of patients may show progressive central iris
abnormalities.9,11,12
Other reported ocular abnormalities may include
limbal dermoid, strabismus, cataracts, peripheral
spokelike transillumination defects of the iris, retinal
detachment, macular degeneration, chorioretinal
coloboma, choroidal hypoplasia and optic nerve head
hypoplasia.
Extraocular Features
Most commonly associated are dental and facial bones
development anomalies.
Dental Anomalies
These include microdontia (a reduction in crown size),
hypodontia (a reduction in numbers of teeth), and
oligodontia or anodontia (a focal absence).
Maxillary Hypoplasia
Maxillary hypoplasias with flattening of midface and
a receeding upper lip and prominent lower lip are
commonly found facial bone defects. Hypertelorism,
telecanthus and a broad flat nose have also been
reported.
More serious but rare anomalies are primary empty
sella syndrome9,13 and congenital parasellar arachnoid
cyst. Redundant periumbilical skin, hypospadius,
oculocutaneous albinism,7 cardiac anomalies, middle
ear deafness, mental deficiency and a multitude of
neurological and dermatological disorders can occur.
Histopathological Features and Mechanism
The prominent Schwalbe’s line consists of dense
collagen tissue and ground substance covered by
single layer of spindle shaped cells with a basement
membrane.9,10 The strands of tissue are made up of
iris stroma or a monolayered membrane of spindle
shaped cells. Peripheral to this, the iris generally
inserts into the posterior aspect of an incompletely
768 Section 7: Pediatric Ophthalmology Including Strabismus
developed trabecular meshwork. In cases with severe
glaucoma Schlemm’s canal may be rudimentary or
totally absent.
Based on these observations and recent concepts
of normal anterior segment development, it has been
postulated that a late prenatal developmental arrest
of certain anterior ocular structures derived from
neural crest cells is responsible for these changes.9,15
Primordial endothelium is retained over a portion of
the iris and anterior chamber angle forming the iris
strands. The zone of differentiation between corneal
endothelium and the anterior chamber angle is
abnormally anterior and an excessive basement
membrane deposition is seen in most cases. The
complete posterior migration of the anterior uvea is
also arrested resulting in high insertion of iris and
incomplete development of trabecular lamellae and
Schlemm’s canal. Aqueous humor outflow obstruction
is believed to occur due to this incomplete develop-
ment or due to the compression of the trabecular
meshwork by the tension of the abnormally inserted
uveal tissue.
The common embryogenic origin of the mesen-
chyme related to forebrain and pituitary, bones and
cartilage of upper face and dental papillae from the
neural crest cells explain the defects of these structures
in A-R syndrome patients.14 Differential diagnosis of
this syndrome is shown in Table 100.2.
Management
The primary aim in identifying a patient of A-R
syndrome is the early diagnosis and management of
the secondary glaucoma. Medical therapy is the first
modality of treatment except in infantile cases where
Table 100.2: Differential diagnosis of Axenfeld-Rieger syndrome
Name of the condition Similar features
Iridocorneal endothelial Iris and angle anomalies—
(ICE) syndrome both clinically and histopathologically
Posterior polymorphus Iris and angle anomalies in
dystrophy one variant
Peter’s anomaly Changes are similar to A-R
syndrome
Congenital iris hypoplasia Iris hypoplasia
Ectopia lentis et pupillae Corectopia
Iridoschisis Iris hypoplasia with associated
glaucoma
early surgery is indicated. Drugs reducing aqueous
production like beta blockers and carbonic anhydrase
inhibitors are more effective than miotics. Laser
procedures are usually unsuccessful. Surgical
procedures like goniotomy, trabeculectomy and
trabeculotomy are conventionally used; the last one
probably yields the best possible result.
PETER’S ANOMALY
Clinical Features
Peter’s anomaly is not only an isolated anterior
segment anomaly but occurs as a diverse pheno-
typically heterogenous condition associated with
multiple underlying ocular and systemic defects. It
may present with a congenital central corneal opacity
of variable density with a defect in the corresponding
posterior stroma and Descemet’s membrane asso-
ciated with synechia extending from the central iris
to the periphery of the corneal opacity. In the initial
stage of the diseased process raised intraocular
pressure may lead to corneal epithelial stippling which
subsides with the control of the intraocular pressure.
Sometimes a shallow anterior chamber is found due
to a central keratolenticular adhesion.
Most commonly associated anterior segment
anomalies include glaucoma (50-70%) and anterior
polar cataract. Less common findings are microcornea,
microphthalmia, cornea plana, sclerocornea, coloboma
of iris, corectopia, aniridia and Axenfeld’s
anomaly.16-18
Other Ocular Abnormalities
These are maldevelopment of the hyaloid system,
anterior staphyloma, anterior lentiglobus, micro-
Dissimilar features
• Unilateral
• No family history
• Onset in young adulthood
• Corneal endothelial abnormalities
• Corenal endothelial defects
• Central portions of cornea,
iris and lens involved
• No angle defects
• No angle anomalies
• Late onset in 6th or 7th decade of life.
 Chapter 100: Glaucomas Associated with Developmental and Congenital Anomalies
phakia, congenital aphakia, persistant hyperplastic
primary vitreous, coloboma of choroid and ciliary
body, retinal dysplasia and blue sclera.19-21
Pathogenesis
Pathogenesis of Peter’s anomaly is ill understood, but
more than one mechanism is responsible. Peter’s own
suggestion was an incomplete separation of the lens
vesicle from the surface ectoderm. Other hypotheses
are an intrauterine keratitis resulting in corneal
perforation and forward displacement of lens-iris
diaphragm, retrolenticular mass like persistent
hyperplastic primary vitreous or detached retina
pushing the lens forward, or zonular abnormalities
producing the corneal endothelial changes secon-
darily.
Mechanism of Glaucoma
The anterior chamber angle appears mostly normal.
But aqueous outflow obstruction is probably caused
by an accelerated senile trabecular meshwork
changes,22 secondary changes in anterior chamber
angle or neural crest cell dysgenesis of the anterior
chamber angle. A differential diagnosis has to be made
from other causes of newborn corneal opacities,
congenital glaucoma, birth trauma, and perforated
corneal ulcers with iris incarceration.
769
structural defects of the central nervous system,
amblyopia and postoperative complications like graft
failure, cataract, inoperable retinal detachment and
phthisis.24
GLAUCOMA IN PHAKOMATOSIS
Phakomatosis (Gr. phakos: birth mark) or dissemi-
nated hamartomas, are a group of hereditary disorders
which have important ophthalmological manifes-
tations. This group exhibits variable penetrance and
expressivity. The general classic features are the
following:
1. Hamartias, which are nontumorous growths of
skin and mucous membrane arising from the
normal inhabiting cells of the involved tissue.
2. Hamartomas, which are localized tumors arising
from normal inhabiting cells of the involved tissue.
3. True neoplasms arising from undifferentiated emb-
ryonic cells.
4. Other associated congenital abnormalities.
Association of glaucoma in phakomatosis is
quite common and diagnosis is often obvious with
the presence of buphthalmos in infancy or early
childhood, and an elevated intraocular pressure in
children and adults (Table 100.3).
Pathogenesis of glaucoma depends on multiple
mechanisms, but there are similarities among the

Management Table 100.3: Associations of glaucoma

with phakomatoses
Management is extremely difficult. An early diagnosis
has to be established with corneal diameter measure- Nature of associations Kinds
ments, intraocular pressure measurements with non- Commonly associated Encephalotrigeminal
contact tonometers, ultrasound and ERG evaluations, angiomatosis
and specular microscopy depending on availability. (Sturge-Weber)
Surgery for medically uncontrolled raised intraocular Occasionally associated a. Neurofibromatosis
(von Recklinghausen)
pressure has to be performed before attempting
b. Angiomatosis retinae
penetrating keratoplasty. Trabeculotomy is a better (von Hippel-Lindau)
choice, as goniotomy is very difficult to perform in c. Oculodermal melanocytosis
presence of corneal opacity. Results of penetrating (Nevus of Ota)
keratoplasty is extremely variable, a success rate of Rarely associated a. Basal cell nevus syndrome
2023 to 50 percent has been reported in 4 years, (first b. Tuberous sclerosis
graft survival rate). Optical iridectomy may be a safer (Bourneville)
c. Klippel-Trenaunay-Weber
surgical approach. As multiple procedures and
d. Diffuse congenital
adjunctive medical therapy are often required to hemangiomatosis
achieve adequate IOP control. Overall visual outcome Unassociated a. Ataxia telangiectasia
is guarded in children with Peter’s anomaly. Achie- (Louis-Bar)
ving a satisfactory visual outcome and preventing b. Racemose angioma of the
further visual loss is impeded by the presence of retina
congenital anterior and posterior segment anomalies, (Wyburn-Mason).
770 Section 7: Pediatric Ophthalmology Including Strabismus
syndromes. Ocular hypertension in neurofibro-
matosis and Sturge-Weber syndrome may be
caused by tissue hypertrophy and developmental
abnormalities. A neurofibroma, or neovasculari-
zation in Sturge-Weber or melanocytes in oculo-
dermal melanocytosis may occlude the anterior
chamber angle. A ciliary body or choroidal
neurofibroma, or an iris hemangioma may cause
the iris root to obstruct the angle.
Francois described the following three stages in the
pathogenesis of the phakomatoses:
a. Developmental stage at which the abnormal
gene functions—from the thirtieth day and the
third month25 to between the third and seventh
months of gestation.
b. An embryological differentiation of phako-
matosis based on the germinal layer affected
states—in neuroectodermal dysplasias, inter-
ference with the migration and differentiation
of embryonic neural cells and mesodermal
disorders with irregularity in the distribution
and structure of small vessels resulting in
abnormal proliferation of perivascular cells.
c. An interference with the process of induction
may result in multiple malformations.
Sturge-Weber Syndrome
The first case was probably reported by Schirmer in
1860. In 1887 Kalischer by autopsy confirmed the
association between facial and intracranial angiomas.
Radiological evidence of intracranial calcification was
demonstrated independently by Weber26 and Dimitri.
The syndrome has little familial tendency with no
sexual or racial predilection. Chromosomal abnor-
malities have been reported with the disorder and the
mode of inheritance may be a dominant trait with
incomplete penetrance.
Systemic Involvement
A variable sized, burgundy colored facial cutaneous
hemangioma (nevus flammeus, port wine stain),
usually unilateral is present at birth, involving the area
of distribution of the 1st and 2nd divisions of the
trigeminal nerve.27 Bilaterality is reported in 10 to
30 percent cases. A meningeal racemose hemangioma
usually occurs ipsilateral to the facial hemangioma
with progressive calcification in the subintimal layer
of the meningeal arteries. Seizures have been reported
in 85 percent of cases while 60 percent have intellectual
deficits. Classical Sturge-Weber called the trisympto-
matic form affecting the leptomeninges, eyes and face.
Facial involvement is common in the bisymptomatic
forms while monosymptomatic forms have also been
reported.
Ocular Involvement
Hemangiomas may occur in the lid, episclera, conjunc-
tiva, iris, and ciliary body. Exophthalmos may be
rarely produced by orbital involvement. Choroidal
hemangiomas occur in 40 percent of cases. Patholo-
gically these are thin walled blood filled sinuses lined
by a monolayered endothelium like the cavernous
hemangiomas. Exudative retinal detachment may
occur after a long period. Buphthalmos is a common
finding. Alexander and Norman28 reported buph-
thalmos ipsilateral to the nevus in two-thirds of this
series while one-third had glaucoma without buph-
thalmos. Numerous mechanisms postulated to explain
the pathogenesis are mostly of historical interest.
Vascular or mechanical theories offer more feasible
explanations. Mechanical theories are based on the
occlusion of the anterior chamber angle leading to
aqueous humor outlfow obstruction, raised intra-
ocular pressure and glaucoma. Vascular theories are
related to vascular malformations that might increase
production, decrease outflow or actually change the
components of the aqueous or interfere with the
extrascleral drainage route, thereby elevating the
intraocular pressure.
The most likely cause for a raised intraocular
pressure seems to be a combination of developmental
angle anomalies and an increased episcleral venous
pressure.
Management
Medical treatment in absence of buphthalmos consists
of beta blockers and carbonic anhydrase inhibitors in
cases with increase intraocular pressure with normal
outflow. If outflow is also reduced, miotics and
epinephrine are advised.
Surgical intervention is required in cases with
congenital glaucoma and cases unresponsive to
medical treatment. Various surgical procedures that
may be adopted are goniotomy, trabeculectomy,
trabeculotomy, argon–laser trabeculoplasty with none
showing any extra-advantage.
Neurofibromatosis
It is a neuroectodermal dysplasia characterized by
tumor-like formations derived from the proliferation
 Chapter 100: Glaucomas Associated with Developmental and Congenital Anomalies
of peripheral nerve elements. It was first reported by
von Recklinghausen in 1882. Incidence of the disorder
is 1 in 2500-3300 live births. Inheritence is autosomal
dominant with complete penetrance but variable
expressivity. Mental retardation and seizures may
occur while intelligence usually remains normal.
Systemic Involvement
Clinical presentation is the appearance of multiple
circumscribed areas of hyperpigmentation of the skin
accompanied by multiple dermal nodules and neuro-
fibromas. There may be involvement of the brain,
meninges, spinal cord and peripheral, cranial or
sympathetic nerves. Characteristic cutaneous manifes-
tations are cafe-au-lait spots which are circumscribed
brown macules typically located on the trunk.
Plexiform neuromas are large ramifying cords of
neurofibromas caused by enlarged nerves and
thickened peripheral sheaths.
Skeletal involvement is more common (29%)
whereas endocrine, vascular and visceral disturbances
are less common.
Ocular Involvement
Ocular tissues, involved in the decreasing order of
frequency, are the eyelids, orbit, uveal tissue, optic
nerve, retina, cornea, tarsal and bulbar conjunctiva.
Palpable string like swelling of plexiform neuromas
characteristically involves the lids. Combination of this
with facial hemihypertrophy and buphthalmos
constitutes Francois syndrome. Globe displacement
with proptosis is caused by orbital neurofibroma.
Rare manifestations include ectropion uveae,
Lische’s nodules at iris or heterochromia irides,
conjunctival nodules, scleral melanosis as well as
thickening of the choroid and ciliary body. Incidence
of uveal melanoma increases with this group of
patients.29,30 The association of neurofibromatosis with
congenital glaucoma was first reported in 1884 by
Schiess-Gemuseus. Glaucoma is almost always unila-
teral with characteristics of neurofibromatous involve-
ment of the upper lid. Incidence of glaucoma is about
50 percent of all eyes with plexiform neuroma. Buph-
thalmos in absence of raised intraocular pressure has
been reported. Developmental or mechanical abnor-
malities are most likely to be responsible for the
mechanism of glaucoma associated with neuro-
fibromatosis.
Management
Choice of the modality of treatment depends on the
age of onset, severity of the disease and mechanism
of glaucoma. Medical treatment is indicated in juvenile
771
or adult onset disease groups. The congenital variety
calls for surgical intervention. Any form of glaucoma
surgery can be performed, but angle closure from
choroidal enlargement may supervene even after
successful glaucoma surgery.
Klippel-Trenaunay-Weber Syndrome
Klippel and Trenaunay in 1890 and Weber in 1907 des-
cribed a syndrome characterized by a triad of
cutaneous hemangioma extending over the limbs,
varicosities in the affected limbs and hypertrophy of
bones and soft tissue.
Ocular findings include enophthalmos, conjunc-
tival telengiectasis, heterochromia irides, iris colo-
boma, retinal varicosities, choroidal angiomas,
Marcus-Gunn pupil, strabismus, glaucoma, and
buphthalmos.
von Hippel-Lindau Syndrome
In 1904 von Hippel described the progression of a
retinal hemangioblastoma and in 1926 Lindau
discovered angiomatous cysts of the cerebellum in
many cases of von Hippel’s disease. Secondary
glaucoma was first reported in 1930 by Ballantyne.
The disease is progressive if left untreated and
eventually may produce massive exudation, retinal
detachment and neovascular glaucoma. Heman-
giomas may require treatment with cryoapplication
and/or photocoagulation.
Tuberous Sclerosis
In 1881 Bourneville first described the disease. The
most frequent clinical manifestations consists of a triad
of epilepsy, adenoma sebaceum, and mental defi-
ciency. Classical ocular lesion is single or multiple
peripapillary astrocytic hamartoma. Secondary
glaucoma occurs rarely resulting from vitreous
hemorrhage, rubeosis iridis, and retinal detachment.
Oculodermal Melanocytosis
Unilateral, deep dermal pigmentation affecting the
area distributed by the first and second divisions of
the trigeminal nerve is the characteristic clinical
appearance. Apparent primary angle closure and open
angle glaucoma have been reported.
GLAUCOMA ASSOCIATED WITH
CONGENITAL DISORDERS
Fifty percent of all known syndromes or chromosomal
abnormalities may affect the eye, ocular adnexa, and
orbit. Glaucoma in these disorders may resemble
772 Section 7: Pediatric Ophthalmology Including Strabismus
primary congenital glaucoma, juvenile or adult onset
open angle glaucoma, primary angle closure glaucoma
or may be secondary to other ocular anomalies with
either an open or closed angle.
Glaucoma Associated with Systemic
Congenital Syndromes with known
Chromosomal Abnormalities
Various types of chromosomal defects are associated
with congenital glaucoma. These include trisomy 21,
trisomy 13, trisomy 18, Ullrich’s syndrome, de
Grouchy’s syndrome, Turner’s syndrome, Praeder-
Willi’s syndrome, etc. A plethora of systemic and
ocular manifestations with a wide variation in their
presentations may be evident.
The pathogenesis of glaucoma may be a poor
differentiation or immaturity of the anterior chamber
angle structures.
Glaucoma Associated with Systemic
Congenital Disorders of Unknown Etiology
Congenital or secondary glaucoma can be caused by
various conditions and syndromes like atopic
dermatitis, cystinosis, Lowe’s syndrome, Pierre-Robin
syndrome, Rubinstein-Taybi syndrome, Weber-
Christian syndrome, Stickler’s syndrome, Krause’s
syndrome, Osteogenesis imperfecta, etc. Secondary
glaucoma of atopic dermatitis may be corticosteroid
induced.31 Pupillary block glaucoma due to thickening
of iris due to cystine crystal deposition is found in
childhood cystinosis.32
Pierre-Robin Syndrome
Pierre-Robin syndrome is characterized by ocular dis-
orders like cataract, high myopia and retinal detach-
ment, microphthalmos, proptosis, ptosis and develop-
mental glaucoma.33 Mechanism of the congenital
glaucoma is not well understood; an anterior insertion
of iris may be responsible. Common systemic
manifestations are micrognathia, glossoptosis, cleft
palate, and cardiac anomalies.
Lowe’s Syndrome (Oculocerebrorenal Syndrome)
It is characterized by ocular, musculoskeletal and renal
anomalies and mental and growth retardation with a
high male preponderance.34 Cataract and congenital
glaucoma are the most common ocular abnormalities.
The lens is consistently small in dimension. The
congenital glaucoma may be secondary to the
microphakia or may be caused by congenital angle
abnormalities.35 The glaucoma may be controlled
successfully by goniotomy or trabeculotomy.
Rubinstein-Taybi Syndrome
(Broad Thumb Syndrome)
The most prominent abnormalities of this disorder are
broad thumbs and toes, mental and growth retar-
dation, high arched plate and cardiac anomalies.
Common ocular manifestations are lid colobomata,
cataract and congenital glaucoma.36 The juvenile
glaucoma caused by developmental anterior chamber
angle anomalies may be associated with this synd-
rome.37 Both goniotomy and trabeculectomy have
been reported as successful procedures in these
patients.
Glaucoma Associated with
Ocular Congenital Disorders
Congenital ocular anomalies which are associated
with developmental or secondary glaucoma include
conditions like persistent hyperplastic primary
vitreous, retinopathy of prematurity, microcornea,
megalocornea, cornea plana, iridoschisis, and
congenital ectropion uveae.
Microphthalmos
It can manifest in three different forms. A true form is
called nanophthalmos, or it may be associated with
cyst, or other systemic anomalies. Nanophthalmos is
associated with small axial length and corneal
diameter, narrow anterior chamber angle and
glaucoma. The glaucoma manifests between 3rd and
5th decade of life and is secondary to chronic angle
closure. Treatment of choice is medical or laser therapy
as surgical procedures are prone to develop compli-
cations.38,39
Microcornea
It is characterized by a corneal diameter of less than
10 mm. It may be found in patients with rubella
syndrome, persistent hyperplastic primary vitreous,
Rieger’s anomaly, nanophthalmos and micro-
phthalmos. Angle closure glaucoma can occur due to
narrow angles and shallow anterior chamber.
Glaucoma may also be due to trabeculodysgenesis.
Persistent Hyperplastic Primary Vitreous
It typically affects a microphthalmic eye unilaterally.
The basic pathogenesis involves a failure of atrophy
of the primary vitreous and its vascular structures. It
can present as leucocoria at birth resulting from a
retrolental fibrovascular mass. Angle closure glau-
 Chapter 100: Glaucomas Associated with Developmental and Congenital Anomalies
coma is due to contraction of this membrane, or
swelling and opacification of the lens, or vitreous
hemorrhage.
Early surgical intervention with lens removal,
vitrectomy and membrane excision may prevent the
progressive pathological changes.
Retinopathy of Prematurity
It is a typically bilateral and symmetrical disease asso-
ciated with a history of prematurity and oxygen
therapy of the newborn (This condition is described
in detail in Chapter 107).
Angle closure glaucoma may result from pupillary
block by a forward displacement of the lens and iris
caused by these retrolental fibrotic membranes. Iridec-
tomy may be helpful in relieving the pupillary block.
In selective cases removal of lens and the retrolental
membranes may be indicated.
REFERENCES
1. Ritch R, Bruce Shields M, Krupin T. The Glaucoma. Mosby
1989;2:869-71.
2. Gillespie FD. Aniridia, cerebellar ataxia and oligophrenia in
siblings. Arch Ophthalmol 1965;73:338.
3. David R, MacBeath L, Jenkins T. Aniridia associated with
microcornea and subluxated lenses. Br J Ophthalmol
1978;62:118.
4. Hittner HM, Riccardi VM, Ferd RE et al. Variable expressivity
in autosomal dominant aniridia by clinical, electro-
physiologic, and angiographic criteria. Am J Ophthalmol
1980;89:531.
5. Nelson LB et al. Aniridia: A review. Surv Ophthalmol
1984;28:621.
6. Margo CE. Congenital aniridia: A histopathologic study of
the anterior segment in children. J Pediatr Ophthalmol Strab
1983;20:192.
7. Banken O. Goniotomy for glaucoma associated with aniridia.
Arch Ophthalmol 1953;49:1.
8. Grant WM, Walton DS. Progressive changes in the angle in
congenital aniridia with development of glaucoma. Am J
Ophthalmol 1974;78:842.
9. Shields MB. Axenfeld-Rieger Syndrome: A theory of
mechanism and distinctions from the iridocorneal endothelial
syndrome. Trans Am Ophthalmol Soc 1983;81:736.
10. Wolter JR, Sandall GS and Fralich FB. Mesodermal dysgenesis
of anterior eye with a partially separated posterior
embryotoxon. J Ped Ophthalmol 1967;4:41.
11. Cross HE, Maumenee AE. Progressive spontaneous dissolu-
tion of the iris. Surv Ophthalmol 1973;18:186.
12. Gregor Z, Hitchings RA. Rieger’s anomaly: A 42-year follow-
up. Br J Ophthalmol 1980;64:56.
13. Kleinman RE, Kazarian EL, Raptopoulos V et al. Primary
empty sella and Rieger’s anomaly of the anterior chamber of
the eye: A familial syndrome. N Eng J Med 1981;304:90.
14. Lubin JR. Oculocutaneous albinism associated with corneal
mesodermal dysgenesis. Am J Ophthalmol 1981;91:347.
773
15. Shields MB, Buckley E, Klintworth GK et al. Axenfeld-Rieger
syndrome: A spectrum of developmental disorder. Surv
Ophthalmol 1985;29:387.
16. Kenyon KR. Mesenchymal dysgenesis in Peter’s anomaly:
Sclero-cornea and congenital endothelial dystrophy. Exp Eye
Res 1975;21:125.
17. Theodore FH. Congenital opacities of the cornea. Arch
Ophthalmol 1944;31:138.
18. Beauchamp GR. Anterior segment dysgenesis, keratolenti-
cular adhesion and aniridia. J Paediatr Ophthalmol Strabis
1980;17:55.
19. Harden AF, Mooney DJ. Congenital keratolenticular
adhesion. Am J Ophthalmol 1970;70:975.
20. Harris R, Brownstein S, Little J. Peter’s anomaly with
congenital aphakia. Am J Ophthalmol 1980;15:91.
21. Scheie HG, Xanoff M. Peter’s anomaly and total posterior
coloboma of retinal pigment epithelium and choroid. Arch
Ophthalmol 1972;87:525.
22. Kupfer C, Kuwabara AT, Stark WJ. The histopathology of
Peter’s anomaly. Am J Ophthalmol 1975;80:653.
23. Waring GO, Laibson PR. Keratoplasty in infants and children.
Trans Am Acad Ophthalmol Otol 1977;83:283.
24. Yang LL, Lambert SR. Peter’s anomaly: A synopsis of surgical
management and visual outcome. Ophthalmology Clinics of
North America 2001;14:467.
25. Mann I. Developmental Abnormalities of the Eye. London:
British Medical Association, 1957.
26. Weber FP. On the association of extensive hemangiomatosis
nevus of the skin with cerebral (meningeal) hemangioma.
Proc R Soc Med 1928;22:431.
27. Ehrlich LM. Bilateral glaucoma associated with unilateral
nevus flammeus. Arch Ophthalmol 1941;25:1002.
28. Alexendar GL, Norman RM. The Sturge-Weber syndrome.
Bristol, England: John Wright and Sons Ltd. 1960.
29. Gartner S. Malignant melanoma of the choroid in von
Recklinghausen’s disease. Am J Ophthalmol 1940;23:73.
30. Wiznia RA, Freedman JK, Mancini AD, et al. Malignant
melanoma of the choroid in neurofibromatosis. Am J
Ophthalmol 1978;86:684.
31. Amemiya T, Matsuda H, Uehara M. Ocular findings in atopic
dermatitis with special references to the clinical featrues of
atopic cataract. Ophthalmologica 1980;180:129.
32. Wan WL, Mincker DS, Rao NA. Pupillary block glaucoma
associated with childhood cystinosis. Am J Ophthalmol
1986;101:700.
33. Smith JL, Stowe FR. The Pierre-Robin syndrome (glossoptosis,
micrognathia, cleft palate): A review of 39 cases with
emphasis on associated ocular lesions. Paediatrics 1961;
27:128.
34. Fisher NF, Hallett J, Carpenter G. Oculocerebrorenal
syndrome of Lowe. Arch Ophthalmol 1967;77:642.
35. Walton DS. Congenital glaucoma associated with congenital
cataract. J Paediatr Ophthalmol 1972;15:221.
36. Roy FH, Summit RL, Hiatt RL et al. Ocular manifestations of
the Rubenstein-Taybi syndrome. Arch Ophthalmol 1968;
79:272.
37. Shihab ZM. Paediatric glaucoma in Rubenstein-Taybi
syndrome. Glaucoma 1984;12:288.
38. Calhoun FP. The management of glaucoma in nanophthal-
mos. Am J Ophthalmol 1979;88:572.
39. Polland ZF. Secondary angle closure glaucoma in cicatricial
retrolental fibroplasia. Am J Ophthalmol 1980;89:651.
 Chapter 101
Childhood Cataract and
Other Abnormalities of the
Crystalline Lens
Nitin K Dutta, LC Dutta
The crystalline lens is situated behind the iris and in
front of the vitreous. The volume of the adult lens is
212.9 mm3. The diameter is 9-10 mm and the thickness
4-5 mm at the center. It is held in place by the
suspensory ligaments of the ciliary body. The
suspensory ligaments extend from the apices of the
ciliary processes to be attached to the equator and
extreme periphery of the anterior and posterior
capsules in such a way that the suspensory ligaments
and the lens divide the eye into an anterior segment
containing aqueous humor and a posterior segment
containing vitreous humor.
Structure of the lens consists of:
a. Capsule
b. Subcapsular anterior epithelium
c. Lens fibers
d. Interfibrillar cement substance.
The lens capsule is ectodermal in origin. It is like
a basement membrane and the thickest of its type in
the body. The lens capsule is composed of a colla-
genous framework the interstices of which are filled
with mucopolysaccharides. The lens epithelium is
composed of a single layer of cuboidal epithelial cells
spread under the anterior lens capsule up to the
equator of the lens. The germinative zone of the lens
epithelium is located near the equator and from this
the dividing cells grow out and elongate in the
equatorial bow to form the lens fibers. The remainder
of the lens consists of the elongated lens fibers which
progressively lose most of their intracellular
organelles as they grow deeper into the lens cortex
and nucleus.
The lens contains 65 percent water and 35 percent
organic material mainly protein. Ninety percent of
the proteins are water soluble and they are divided
into three main types: Alpha, beta and gamma
crystallin. A relatively insignificant amount of lens
protein is insoluble. The transparency of the lens
depends upon the alpha and gamma crystallin
component.
The lens is made up of fibers, which are devoid
of intracellular organelles. The organelles present in
the cuboidal epithelial cells lying along the anterior
lens capsule take part in oxidative phosphorylation
and aerobic glycolysis; the remaining greater portion
of the lens particularly the nucleus is entirely
dependent on anaerobic glycolysis for metabolism.
The main essential process involved in metabolism
of the lens is provision of energy from carbohydrates
and provision of structural materials mainly from
amino acids.
The total lipid content of the lens is less than 1
percent of its protein content. More than half of the
fat of the lens is composed of phospholipids, which
is present in the cell membrane and in the intracellular
particulate matters like mitochondria and endo-
plasmic reticulum. The free fatty acid content is
 Chapter 101: Childhood Cataract and Other Abnormalities of the Crystalline Lens
extremely low and the lens does not get appreciable
amount of energy from metabolism of fat.
CONGENITAL ABNORMALITIES OF THE LENS
Congenital Aphakia
Congenital absence of the lens is probably a non-
existent entity, but is occasionally mentioned in
textbooks as a possible congenital abnormality.
However, primary aphakia may be due to defective
tissue migration from the surface ectoderm and
invagination during formation of the optic vesicle and
cup.
Persistent Hyaloid System
a. Persistence of the tunica vasculosa lentis is theo-
retically possible but is rarely described in
literature.
b. A fibrous band, remnant of the original hyaloid
artery, may be adherent to the posterior pole of
the lens and may extend through the vitreous
(Cloquet’s canal) up to the optic disk. Sometimes
the anterior part of the hyaloid artery may
disappear completely and the posterior part
remains adhered to the optic disk giving it a
corkscrew appearance.
Epicapsular Star
Some light brown granular star shaped deposits may
be present over the anterior capsule of the lens. Vision
is not affected.
Pigments over the Anterior Lens Capsule
Congenital clumps of pigment over the pupillary area
of the lens capsule is occasionally seen. Visual acuity
is not affected and it has got to be differentiated from
pigmentation over the lens capsule as seen after
healed iritis. In the latter condition, the pigment
particles are of various sizes and dispersed all over
the lens capsule with subcapsular lens opacity.
Coloboma
Coloboma of the lens is secondary to coloboma of
the iris and ciliary body. When, due to absence of
suspensory ligaments at the colobomatous area the
contour of the equator at the site is not maintained,
equatorial part at that site is not formed and the lens
margin becomes linear. This condition may be
associated with astigmatism.
775
Lenticonus
Cone shaped bulging of the anterior and/or posterior
pole of the lens is also a condition that is far less
common than is described in textbooks. This condition
may be associated with anterior or posterior polar
cataract. The eye becomes myopic.
Spontaneous Displacement of the Lens
In addition to hypermature cataract, there are a
number of disorders which may be associated with
spontaneous displacement of the lens. Simple ectopia
lentis is a bilateral genetically determined condition
with an autosomal dominant mode of inheritance.
When the lens is dislocated anteriorly or posteriorly,
in about one quarter of patients, secondary glaucoma
develops. Ectopia lentis et pupillae is a condition in
which the lens and slit-like pupil are displaced. The
exact cause of spontaneous dislocation is not known.
It is thought to be due to abnormal nature of collagen
all over the body. There is a group of three conditions
which is associated with spontaneous dislocation:
Marfan’s Syndrome
It is an autosomal dominated condition characterized
by a triad of skeletal, cardiovascular and ocular
abnormalities, which include general thinness and
elongation of the limbs, slender long fingers
(arachnodactily), sternal deformities, kyphoscoliosis,
joint hyperextensibility and decreased ratio of the
upper segment and lower segment of the body. A
long narrow face and a high arched palate are
common. Cardiovascular changes consists of abnor-
malities in the tunica media of the aorta and
pulmonary artery which may lead to development
of diffuse dilation or dissecting aneurysm. The lens
appears to be small and spherical and is most
commonly displaced temporally and upward. The
process of dislocation is a gradually progressive one.
In the early stages it may be asymptomatic but later
on defective vision occurs due to myopic astigma-
tism. When dislocation progresses to such an extent
that the edge of the lens is in the midpupillary space,
the phakic portion of the pupil becomes myopic and
the aphakic portion highly hypermetropic; this may
result in monocular diplopia and if the condition is
symmetrical in both the eyes then there is a theoretical
possibility of quadropia. In advanced stages the lens
may be dislocated into the vitreous cavity, but usually
776 Section 7: Pediatric Ophthalmology Including Strabismus

the subluxated lens becomes cataractous requiring Table 101.1 Some causes of congenital cataract
removal. High myopia, keratoconus, megalocornea
and blue sclera may be associated with this condition. Intrauterine infection
Rubella15
The angle of the anterior chamber frequently contains
Vaccinia
pectinate strands, iris processes or mesodermal tissue. Herpes simples virus14
Glaucoma may occur either as the result of these Toxoplasmosis
anomalies or following anterior or posterior Associated with ocular diseases
placement of the lens. There may also be associated Persistent hyperplastic primary vitreous
retinal detachment. Retrolental fibroplasias
Uveitis (Juvenbile rheumatoid arthritis)
Retinal pigmentary degeneration
Weill-Marchesani Syndrome
Aniridia
(Brachimorphis Spherophakia) Lenticonus
It is characterized by skeletal and ocular changes; Drugs and physical agents
Systemic corticosteroids
the skeletal changes are antithesis of those found in
Radiation
Marfan’s syndrome. The patient has a short stature Trauma
with short limbs and fingers, well-developed Intrauterine tumors
musculature and an abundance of subcutaneous fat. Associated with systemic syndromes
Eye affection consists of sphero or microphakia and Alport’s syndrome
subluxated lens is frequently found which occurs at Myotonic dystrophy
a later life than in Marfan’s syndrome. Anterior or Neurofibromatosis
Atopic dermatitis
posterior subluxation is associated with glaucoma.
Lowe’s syndrome
However, when the lens becomes spherophakic or Wilson’s syndrome
microphakic, it blocks the pupillary aperture obstruc- Turner’s syndrome
ting drainage of aqueous humor resulting in glaucoma Downs syndrome
inversus so named because mydriatic rather than
miotic will lower the intraocular pressure. Prominent
ocular manifestation is ectopia lentis. In 50 percent 7. Total cataract
of cases the displacement is noted by the age of 5 a. Soft
years. b. Membranous
8. Coraliform cataract
Homocystinuria 9. Blue dot cataract
Homocystinuria is an autosomal recessive hereditary 10. Cuneiform cataract
disease characterized by skeletal, cardiovascular, and
ocular involvement. There is bilateral downward Congenital Cataract
displacement of the crystalline lens. Secondary
Congenital cataracts are responsible for 10% blindness
glaucoma may be a common complication. Basically
in children worldwide. Its incidence is 0.4% of
homocystinuria is an effect of an inborn error of
newborns. The most common form of congenital
metabolism and is described in details elsewhere.
cataract is total soft cataract. Usually this type of
CONGENITAL OR DEVELOPMENTAL cataract has got strong hereditary character and is
CATARACT bilateral; it may also occur sporadically and may be
unilateral. It is difficult to determine the etiology of
It can be described on morphological basis depending sporadic case of bilateral congenital cataract not
upon the site of the opacity within the lens. associated with any other disease or ocular abnorma-
1. Coronary cataract lity. Unilateral congenital cataract should arouse
2. Anterior suspicion of some intraocular pathology. In complete
a. Polar pyramidal or total bilateral cataract, vision is grossly affected
b. Reduplicated so much so that nystagmus invariably develops if
3. Anterior subcapsular operation is not done before the age of six months.
4. Posterior polar Minute opacities that are present at birth, visible only
5. Sutural cataract
6. Lamellar or zonular
 Chapter 101: Childhood Cataract and Other Abnormalities of the Crystalline Lens
with the slit lamp microscope, without causing any
interference with vision are commonly seen and
normally remain stationary throughout life.
Blue Dot Cataract (Punctiform Opacity)
Small punctiform opacities scattered irregularly in the
central part of the lens are quite common. These
opacities can be seen with slit lamp or by any form of
oblique illumination and magnification. These minute
opalescent particles disperse the light irregularly in
such a way that the major part of the dispersed light
is made up of short blue and violet wavelengths and
hence, appear blue. These opacities do not interfere
with vision and do not progress.
Coronary Cataract
Coronary cataract involves the superficial layers of
the adult nucleus and the deeper layers of the cortex.
These juvenile or presenile discrete lens opacities are
typically arranged near the equator of the lens like a
crown and can be visualized when the pupil is fully
dilated. They are more or less stationary.
Anterior Polar Cataract
Anterior polar cataract sometimes develops when the
central part of the anterior capsule of the lens comes
2. Nuclear cataract This type of cataract involves the
in contact with the cornea. It is possible to occur in
cases of corneal perforation which heals sponta-
neously and immediately. Subcapsular lens opacities
also may occur due to the same cause and when both
of these two are present and separated by a small
3. Sutural cataract Tiny microscopic opaque dots are
gap of clear lens matter, it is known as reduplicated
cataract.
Posterior Polar Cataract
Usually it is associated with some remnant of hyaloid
system attached to the posterior pole of the lens. This
(Mittendorf’s dots) type of lens opacity is also more
or less stationary; as the opacity is right at the center
of the lens, vision is grossly affected.
Zonular Cataract
Zonular cataract is opacity of one zone or area of the
lens proper, the rest of the lens remaining transparent.
Zonular cataract may be classified according to the
systemic diseases like galactosemia which is an
zone involved.
inborn error of metabolism. This condition is charac-
1. Lamellar This is the commonest type of zonular
terized by nutritional failure, hepatosplenomegaly,
777
cataract and second commonest type of infantile
or congenital cataract. Lamellar cataract may be
present at birth or it may manifest during early
postnatal period. It consists of concentric zones
of lamellar opacities surrounding a core which is
clear, or almost so, enveloped by a clear cortex
externally. These concentric zones of
maldeveloped fibers result from some prenatal
or postnatal noxious factors active for a certain
period during the development of the lens.
Heredity plays an active role in formation of
lamellar cataract and transmission of autosomal
dominant type. Maternal malnutrition, viral
disease like rubella and measles and endocrine
disorders like hypoparathyroidism are
nonhereditary causes of lamellar cataract.
On examination with undilated pupil, lamellar
cataract cannot be distinguished from total
congenital cataract. When the pupil is widely
dilated, a central disk shaped opacity is seen in
the central part leaving the peripheral part of the
lens transparent. Few concentric rings of opacities
alternating with clear zones may be present and
radial bow shaped opacities run anteroposteriorly
at the periphery of the disk shaped opacity.
Lamellar cataract is almost always bilateral and
usually static.
embryonic or both the embryonic and fetal nuclei.
Under slit lamp it may appear as fine grains,
distinct dots or small lines of opacities in the central
part, the rest of the lens remaining clear.
situated in the Y sutures, commonly the anterior
sutures of the lens. Combined anterior and
posterior sutural cataract is known as stellate
cataract.
Congenital cataract may be associated with
hypoplasia of the mandibulofacial region. Treacher
Collins’ syndrome, a common form of mandibulo-
facial dysostosis, is associated with congenital
cataract, Down syndrome, characterized by
mongolism, is frequently associated with ocular
abnormalities; cataract frequently develops
toward the end of the first decade of life but
congenital cataract is also not uncommon.1,2
Cataract is also associated with some other
778 Section 7: Pediatric Ophthalmology Including Strabismus
cirrhosis of the liver, mental retardation and infantile
cataract which appears in the first year of life. The
lens opacity develops as an oil drop cataract and
progresses to involve the whole nucleus before it
matures. Normally, the galactose in the lens is
reduced to terminal products by a specific enzyme
known as aldose-reductase. In its absence, as occurs
in galactosemia, this substance is accumulated in the
lens which in turn imbibes water causing swelling of
the lens leading to final disruption of the lens fibers.
Nonhereditary congenital cataract may be due to
maternal malnutrition of different types and/or
infections like rubella, mumps, measles, influenza,
toxoplasmosis and herpes. Some ocular congenital
diseases may also be associated with congenital or
infantile cataract. Norrie’s syndrome is one such
disorder in which microphthalmia, retinal dysplasia
and cataract are often associated with mental retar-
dation and deafness.
Virus Induced Cataract
During the early months of pregnancy some viral
diseases may cause opacification of the lens. This fetal
involvement is due to the passage of the virus through
the placenta to the fetus. In maternal rubella,
congenital cataract was a common manifestation and
it accounts for 30 percent to 40 percent of congenital
cataract if the mother had suffered from rubella
during the first trimester of pregnancy. After
availability of Rubella vaccine in 1979, rubella cataract
is rare.
At the first week of intrauterine life, the human
lens appears as a sphere of epithelial cells. After a
few days, the cells on the posterior aspect of the
sphere elongate to fill the cavity. The elongated
primary lens fibers form the embryonic nucleus which
is surrounded by a capsule. By the ninth week of
pregnancy, the cells at the equator of the lens begin
to elongate to form the secondary lens fibers. By the
tenth week, the hyaloid vessels begin to degenerate,
which is complete by the twelfth week.
In rubella the lens develops areas of necrosis and
the cortical fibers may become partially cataractous
leading to total opacification. The appearance of
rubella cataract is sometimes pearly due to some clear
zones in between the opaque areas. Sometimes these
may be mistaken for a membranous cataract. How-
ever, actual membranous cataract may also result after
spontaneous absorption of the rubella cataract.
Rubella virus may be cultured from the aspirated lens
matter by needle aspiration. Therefore, it is important
to note that after surgery there may be postoperative
uveitis due to the rubella virus which may result in
poor visual outcome.
There have been several reports of cataract where
herpes simplex was thought to be the causative agent.
When the mother suffers from herpetic lesions during
the later months of pregnancy the virus may be
present in the fetal circulation to cause cataract. Viral
etiology of congenital cataract has been reported in
case of herpes zoster virus, cytomegalovirus,
echovirus and smallpox virus.
Congenital or infantile cataract may occur in
association with a variety of congenital abnormalities,
some of which are grouped together as syndromes.
Lowe’s Oculocerebral Syndrome
Lowe’s syndrome is an X-linked disorder with mental
retardation, renal tubular acidosis, aminoacidosis and
renal rickets. Congenital cataract, congenital
glaucoma and corneal keloids are the ocular
manifestations which may lead to blindness. The lens
is usually small and discoid and the cataract is total.
Female carriers may show focal dot opacities in the
cortex.
Alport’s Syndrome
Alport’s syndrome consists of a clinical triad of
hemorrhagic nephropathy, progressive sensorineural
deafness, characteristic ocular abnormality affecting
mainly the crystalline lens and the retina. Alport’s
syndrome is an X-linked hereditary syndrome and
approximate incidence is 1 in 5000 persons. Males are
more affected than females. In a small percentage of
cases it may be autosomal dominant. The key
pathologic process of the disease is abnormality in
the collagen of the basement membrane of the
structures of the body.
Congenital cataract and retinal involvement are
the two disease entities of the eye which develops in
Alport’s syndrome. Initial pathology is scanty collagen
in the basement membrane of anterior and posterior
capsule of the lens. The lens capsule becomes
extremely thin and attenuated. Due to repeated stress
during accommodation of the eye, the weakened
capsule bulges. If a small area of the capsule bulges
anteriorly it produces anterior lenticonus. Posterior
lenticonus may also develop due to cone shaped
bulging of the posterior capsule; but it is very
uncommon because the anterior vitreous face is just
adjacent to the posterior capsule and thus, cone
 Chapter 101: Childhood Cataract and Other Abnormalities of the Crystalline Lens
formation is prevented. There may be micro-rupture
of the lens capsule at the tip of the cone and lens
fibers come in contact with aqueous humor resulting
in opacification of the lens. When a larger area of the
anterior capsule bulges forwards it produces lenti-
globus.
Retinal involvement gives rise to flute retinopathy
in the mid-periphery of the fundus. As the flecks are
away from the macular area, central vision is not
affected.
Treatment of visually significant cataract might
need surgical intervention with intraocular lens
implantation and cataract operation.
Turner’s Syndrome
Congenital cataract occurs in Turner’s syndrome.
Other ocular manifestations in this syndrome may
be ptosis, strabismus, blue sclera corneal nebulae.
Cardiac, skeletal and renal abnormalities and
perceptive type of hearing loss may be present.
Myotonic dystrophy
Myotonic dystrophy causes wasting of muscles and
tonic relaxation of the skeletal muscles. Cataract may
779
be an early and prominent feature in 90% of patients
with the disease. Other ocular features include
hypotony, blepharitis and pigmentary retinopathy.
Early cataract formation is characterized by polychro-
matic dots and flecks in the superficial cortex. The
polychromatic luster is due to optical dispersion of
light through the multilamellar bodies in the
subcapsular cortex of the lens. There may be stellate
posterior subcapsular opacities also.
REFERENCES
1. Shaprio MB, France TD. The ocular feature of Down’s synd-
rome. Am J Ophthalmol 1985;99:659.
2. Cunha DA, Moreiere JBC. Ocular findings in Down’s syndrome.
Am J Ophthalmol 1996;122:236.
3. Lowe CU, Terry M, MacLaclan EA. Organic aciduria, decreased
renal ammonia production, hydrophthalmos and mental
retardation: A clinical entity. Am J Dis Child 1952;83:164.
4. Tripathi RC, Cibis GW, Tripathi BJ. Pathogenesis of cataract in
Lowe’s syndrome. Ophthalmology 1986;93:1046.
5. Tripathi RC, Cibis GW, Tripathi BJ. Lowe’s syndrome. Trans
Ophthalmol Soc UK: 1985;99:659.
6. Schartz H. Alport’s syndrome in a negro kindred. Am J
Ophthalmol 1971;71:1236.
7. Sohar E. Renal disease, inner ear deafness and ocular changes.
A new heredofamilial syndrome. AMA Arch Intern Med
1956;97:627.
 Chapter 102

Management of
Infantile-Pediatric Cataract
Suresh K Pandey, M Edward Wilson, Jagat Ram, Liliana Werner, David J Apple

Congenital, early developmental and traumatic
cataracts are common and represent an important
cause of visual impairment in childhood. The global
estimate of 1.5 million severely handicapped and blind
children is relatively small compared to the 17 million
blind adults due to cataract. Management of childhood
cataract is more challenging compared to cataract
management in adults.1,2
DIAGNOSIS OF PEDIATRIC CATARACTS
Congenital, developmental and traumatic cataracts
can have different morphological characteristics
(Figs 102.1 to 102.5, Table 102.1). Biomicroscopic
examination of the anterior segment should be
performed to evaluate the size, density, and location
of the cataract in order to plan the surgical procedure
and to determine the visual outcome. Fundus
examination should be carried out after pupillary
dilatation. A- scan ultrasound helps to measure the
axial length for calculating the IOL power and
monitoring the globe elongation postoperatively. For
an eye with total cataract, a B- scan evaluation is useful
to exclude vitreoretinal pathology. A history from the
parents is useful to determine whether the cataract
could be congenital, developmental or traumatic in
origin. One must ascertain if there is any history of
maternal drug use, infection or exposure to radiation
during pregnancy. Each child should be thoroughly
examined by a pediatrician to rule out systemic
associations, anomalies or congenital rubella.
Indications for Treatment
In order to avoid the development of deprivational
amblyopia, prompt diagnosis and treatment are
necessary for visually significant cataract in neonate,
infants or toddler.3 Indications for surgery in these
eyes include: cataracts of more than 3 mm in diameter
(visually significant), dense nuclear cataracts, cataracts

A B C

Figs 102.1A to C: Slit-lamp photographs of zonular cataracts, taken from 3 different cases.
Note that the lenticular opacity is occupying the central visual axis
 Chapter 102: Management of Infantile-Pediatric Cataract 781
Table 102.1: Characteristics of pediatric cataracts
Congenital/developmental Traumatic
Total/diffuse: Uncommon; rubella cataracts; bilateral; variable visual prognosis Total/diffuse
Anterior polar: Unilateral or bilateral; sporadic; opacity < 3 mm; Anterior subcapsular
usually non-progressive; good visual prognosis
Lamellar/zonular: Bilateral; partial; opacity 5-6 mm; good visual prognosis Posterior subcapsular
Nuclear: Autosomal dominant in many; bilateral (80%); non-progressive; Intumescent
opacity 3.5 mm; moderate visual prognosis
Posterior lentiglobus: Unilateral; good visual prognosis Ruptured anterior capsule with flocculent lens
matter in anterior chamber
Persistent hyperplastic primary vitreous (PHPV): Unilateral; sporadic Partially absorbed
and progressive; poor visual prognosis (when posterior segment
involvement present)
Etiology Etiology (blunt/penetrating trauma)
Idiopathic, hereditary, congenital rubella syndrome, Sport related Firecracker
galactosemia, Lowe’s syndrome, Bow and arrow Thorn
TORCH infection Sticks
Associated ocular findings Associated ocular findings
Strabismus, amblyopia, anisometropia, Corneal laceration(s), hyphema, angle
microphthalmia, microcornea, recession, vitreous hemorrhage, posterior
Peter’s anomaly, excessive elongation capsule rupture, retinal detachment,
of the globe Berlin’s edema

obstructing the examiner’s view of fundus or preven-
ting refraction of patient, if the contralateral cataract
has been removed and cataracts associated with
strabismus and/or nystagmus.3-5
When children beyond infancy present with dense,
central opacities of uncertain duration and Snellen
visual acuity cannot be accurately measured, surgery
is indicated within a few weeks of detection.6-8 Non-
surgical methods as patching or pharmacological
pupillary dilation can be useful to manage partial
cataracts.
The threshold for surgical removal of a partial
cataract in a child capable of Snellen visual acuity has
often been stated to be 20/70 or 20/80. Use of vision
charts, e.g. Lea Hyvarinen symbol charts, is extremely
useful in assessment of the visual status in a young
child unable to read. However, individual judgments
need to be made (especially in children too young for
Snellen visual acuity testing) based on documented
progression of the partial cataract and on the child’s
visual functioning, visual needs, and expected best
visual outcome. When possible, low contrast sensiti-

Figs 102.2A to C: Clinical photographs showing 3 different examples of bilateral total infantile cataracts. (A) Bilateral total
cataract in a 2-month-old male child, (B) Bilateral total cataract in a 5-month-old male child, and (C) Bilateral total cataract in a 9-
month-old female child
782 Section 7: Pediatric Ophthalmology Including Strabismus

A A

B B

Figs 102.4A and B: Pediatric uniocular cataracts following blunt

and penetrating trauma. (A) Slit-lamp photograph of the anterior
segment of a 6-year-old male child showing traumatic cataract
after blunt trauma (firecracker injury). Note the formation of a
posterior synechia at 3 o’clock position, (B) Slit-lamp photograph
of the anterior segment of a 7-year-old female child after the
repair of penetrating injury. Note the formation of a traumatic
cataract associated with an irregular pupil

vity testing may provide a helpful guideline for

C deciding either the need of cataract surgery or
Figs 102.3A to C: Examples of unilateral total pediatric
cataracts in 3 different children. (A) Unilateral congenital
cataract in a 2-month-old male child. Note the convergent
squint in the left eye probably secondary to deprivational
amblyopia, (B) Unilateral traumatic cataract in a 2-year-old
male child, and (C) Unilateral developmental cataract in a
5-year-old female child
treatment for posterior capsule opacification (PCO).
Optical Rehabilitation
Correction of pediatric aphakia can be accomplished
with spectacles, contact lenses, epikeratophakia or IOL
implants (Figs 102.6 and 102.7). Currently the contact
lenses (in infants) and IOLs (in older children) are
 Chapter 102: Management of Infantile-Pediatric Cataract 783

Fig. 102.5: Bilateral congenital cataract in a 10-year-old male

child associated left convergent squint. Note the associated
ocular anomalies (microphthalmos and microcornea)
preferred. In infants, whichever method of optical
correction is chosen, it is important to get a reasona-
bly well-focused image on the retinas as early as
possible.2,9-17
Fig. 102.6: Visual rehabilitation in an infant after bilateral
cataract surgery using aphakic glasses. Thick and heavy
aphakic glasses are not suitable for the infant’s nose and facial
structure. They are also cosmetically inferior to other modalities
(contact lenses/IOLs) of optical corrections

Aphakic Glasses
Spectacle correction is safest and their power can be
readily changed to compensate for ocular growth.
They can be worn at any age and not unduly
expensive. Their magnifying effect may improve the
child’s acuity and make microphthalmic eyes appear
normal size. Spectacles can be the only form of optical
correction that is available in a community and most
children using contact lenses should have a pair of
aphakic glasses as a ‘spare’, for when they are not able
to use contact lenses. Spectacles, however, have the
disadvantage of poor cosmesis and inferior optics (Fig.
Fig. 102.7: Use of Rigid Gas Permeable (RGP) contact lens
102.6). They cause alteration in the peripheral field of
for aphakic correction after surgery for traumatic cataracts in a
vision by inducing distortion and prismatic effects. 9-year-old child. Note the traumatic corneal scar inferonasally
An infant’s ear and nose are often too insubstantial to extending from 7 o’ clock to 1 o’clock and a large sector
support aphakic glasses. In addition, obtaining iridectomy from 4 o’clock to 10 o’clock. The visual acuity of the
centration with heavy aphakic glasses is difficult and eye was 20/40 with the RGP contact lens (Courtesy: Ashok
the optical center of the lens does not move with the Sharma, MD, Post Graduate Institute, Chandigarh, India)
eye. Although they provide a satisfactory correction
(RGP) lenses (Fig. 102.7), the hydrogel extended-wear
for many children with bilateral aphakia, aphakic
or daily wear lens, and the silicone lens. Most of the
spectacles are generally not suitable for children with
problems of aphakic spectacles can be overcome by
unilateral aphakia because of marked retinal image
the use of contact lenses, their power can also be easily
size disparity (approximately 30% magnification).
adjusted according to the growth of the eye.82,116
The RGP contact lenses have the advantage of low
Contact Lenses
cost and can be customized in regards to power and
There are three choices of contact lens type for base curve. Their disadvantage is that they must be
pediatric patients: the hard lens, including poly- removed daily and are more difficult for the parents
methylmethacrylate (PMMA) and rigid gaspermeable to insert. The hydrogel or soft contact lenses have
784 Section 7: Pediatric Ophthalmology Including Strabismus
comfort as their main advantage. These lenses are
tolerated in a wide range of base curvatures and thus
they are easily fitted. However, insertion difficulties
coupled with instability and fragility lead to high
damage and lens loss rates. Extended wear poly
HEMA lenses have proven to be the lenses of choice
for children with unilateral aphakia. They are fairly
stable with reduced lens loss rates.
Silicone contact lenses (Silsoft, Bausch & Lomb,
Rochester, NY) combine the best features of hard and
soft lenses. They are reported to mask up to 2 diopter
(D) of astigmatism in the adult. Like the hard lenses,
they are easy to handle, have a relatively low loss rate,
and can be fitted using either measurement or trial
techniques. Most children under the age of one year
can be fitted with a lens of 7.50 base curve. Older
children are most often fitted with a base curve of 7.70.
A fluorescein pattern may be used during the fitting
sequence as needed. Lens movement with blinking is
the most critical and important factor to evaluate
during fitting. If too much movement is seen, a steeper
lens can be tried. If little or no movement is seen, a
flatter lens is indicated.
Unique problems facing the fitter of contact lenses
in young aphakic children include their small eyes,
steep corneas, and high hyperopia. Their continuously
changing refraction, primarily related to an increasing
axial length and progressive corneal flattening
provides an additional challenge. Repeated insertion
and removal of a contact lens can be psychologically
traumatic to the child. The major disadvantage of
contact lenses for the correction of aphakia is the
frequency of lens loss. In addition to lens loss, non-
compliance is a major problem particularly in children
using contact lenses for correction of monocular
aphakia. About 44% of children with unilateral
aphakia wear their contact lens. Lens loss, conjunctival
erythema and poor fit reasons for noncompliance.
Noncompliance leads to increased amblyopia and
sensory strabismus. Other problems associated with
contact lens use, more commonly encountered in
developing country patients, who often come from
rural communities with poor socio-economic and
educational background, include infective keratitis,
corneal vascularization, hypoxic corneal ulcerations
and red eye without ulcerations.76
Epikeratophakia
Epikeratophakia was introduced in the early 1980s as
an alternative means of optically correcting aphakic
eyes. It is a refractive corneal surgical technique in
which a lathed lamellar corneal disk is sutured to the
front surface of the recipient’s cornea after removal of
the recipient’s epithelium. Epikeratophakia corrects
the refractive error by changing the anterior curvature
of the cornea. Advantages of this technique are that
no damage occurs to the recipient’s central cornea, it
is reversible, entirely extraocular, and may be
employed with cataract extraction or as a secondary
procedure. Problems like graft failure due to persistent
epithelial defects, infections or mechanical trauma are
common with this technique. In addition, sutures must
be removed after 3 weeks, often necessitating another
anesthetic procedure. Amblyopia therapy is generally
delayed until 4 to 6 weeks after the initial operation.
Epikeratophakia for correcting pediatric aphakia has
fallen into disuse due to the difficulty in achieving
the target refracting power and the prolonged haziness
of the host donor interface.
Intraocular Lens Implantation
Problems such as contact lens intolerance, downward
displacement of the contact lens with induced vertical
diplopia, aniseikonia (approximately 6% with contact
lenses), and traumatic corneal scars have prompted
some investigators to advocate IOL implants for
pediatric aphakia. IOL implantation in children during
the early years of implant use in adults resulted in
frequent complications secondary to poor lens design
and poor quality control but also to lack of present
refinements in the surgical technique. 9-18 There
continues to be some hesitation of some ophthal-
mologists to implant IOLs in the pediatric population
because of fear of the long-term effects of synthetic
material, the changing refractive status of the
developing eye and the increased inflammatory
response that occurs in pediatric eyes. As late as 1991,
IOL implantation in children was not well accepted,
especially by the pediatric ophthalmic community.
However, the 1990s brought major improvements in
IOL designs and surgical techniques better suited for
children’s eyes. In 1994, 46% of 234 pediatric
ophthalmologists responding to a survey conducted
by Wilson et al,19 indicated that they were currently
implanting IOLs in children. In addition, 27% of 1,039
adult cataract specialists were implanting pediatric
patients. The numbers are undoubtedly greater today.
Many surgeons who remained skeptical in the recent
past, have now become advocates of selective IOL use
 Chapter 102: Management of Infantile-Pediatric Cataract
in children. A growing number of case series have now
been published supporting the safety and effectiveness
of IOLs for children beyond infancy.
IOL implantation at the time of cataract surgery is
rapidly becoming the commonest means of optical
correction for children beyond infancy. An IOL can
provide a full time correction with optics that closely
simulates those of the crystalline lens. However,
concern still remains about the unknown risks of an
IOL over the long life span of a child. In addition,
predicting the refractive change of even older children
is difficult since individual variation is common.
IS IOL IMPLANTATION FEASIBLE FOR
INFANTILE CATARACTS?
In contrast to older children, there is no consensus
about when, if ever, to implant an IOL in the first 1 or
2 years of life. Increased tissue reactivity and marked
axial length and refractive changes have been cited as
contraindications to IOL use in the first 2 years of life.
However, Dahan and Salmenson 20 reported 13
patients who had posterior chamber IOLs implanted
at age 18 months or younger. With follow-up ranging
from 1.2 years to 4.5 years, the IOLs were well tolerated
with no additional surgical intervention needed.
Primary posterior capsulectomy and anterior vitrec-
tomy were performed in these patients at the time of
IOL placement. Vasavada and Chauhan21 evaluated
21 eyes of 13 infants between 2 and 8 months of age
who had primary posterior chamber IOL implantation
for congenital cataracts. Twelve eyes had a posterior
capsulorhexis or plaque peeling at the time of IOL
implantation and 1 eye had a vitrectomy. Follow-up
ranged from 6 months to 5 years. All eyes developed
one or more posterior synechiae and all, except one,
required secondary capsulectomy and vitrectomy
between 1 month and 1 year. Twenty eyes attained
stable IOL fixation and a clear visual axis in their series.
Patients with bilateral cataracts had greater visual
improvement than those with a cataract in 1 eye only.
Their findings revealed the benefits of posterior
capsulectomy and anterior vitrectomy if done in early
postoperative period. Other than a greater propensity
for PCO, the IOLs were as well tolerated in the infants
and toddlers as they were in the older children.
IOL Power Selection
Although aforementioned reports indicate that IOL
implantation is technically feasible even in early
785
infancy, some problems remain. Since the axial growth
of the eye is dramatic in early infancy, IOL power
selection is much more difficult. Keratometry, usually
very stable after eighteen months of age, still
undergoes rapid change in early infancy.
Knight-Nanan et al,22 recommend the use of an IOL
power which is lower by 6.00 diopters than one needed
for emmetropia to compensate for the expected
myopic shift when implanting infants younger than
one year of age. The residual refractive errors are
managed with spectacles. However, when an IOL is
implanted in the first month of life, we are often faced
with residual hyperopia as high as 10 diopters. A
contact lens may be needed for a few months until
the residual hyperopia decreases to the 4 to 6 diopters
range. Spectacles can then be more easily used. Since
contact lens wear is easiest in early infancy and much
more difficult as the toddler age is approached, this
treatment scheme has been successful.
For children beyond the age of 2, users data are
available to help the surgeon predict the growth of
the eye on average.23-27 When operating on children
between the ages of 2 and 8 years, many surgeons have
advised selecting an IOL power that will leave mild
to moderate hyperopia, milder with increasing age.
Postoperative refraction of +4.00 for children younger
than age two, +3.00 diopters for children age two to
four, +2.00 diopters for age four to six, +1.00 diopters
for age six to eight, and emmetropia for children older
than eight years of age at the time of implantation
should be taken as a guide line for IOL power
selection. Some authors have advocated aiming for
emmetropia regardless of age when operating beyond
age 2.
Modern theoretical IOL formulas are usually used
in adults to calculate the IOL power most likely to
achieve the desired postoperative refraction. In a
recent study2 we applied the Sanders-Retzlaff-Kraff
(SRK) II, SRK-T, Holladay, and Hoffer Q formulas for
47 consecutive IOL implantation in children. The eyes
were divided into short (less than 22 mm in axial
length) medium (axial length > 22 mm but less than
24 mm) and long (> 24 mm) groups.
IOL Size
The mean axial length of a newborn’s eye is 17.0 mm
compared to 23 to 24 mm in an adult. The pediatric
eye, especially in the first 1 to 3 years of life, is signifi-
cantly smaller than the adult. This leads to concerns
786 Section 7: Pediatric Ophthalmology Including Strabismus

with implantation of adult-sized IOLs in these IOLs in children was related in part to the perceived
patients. In an effort to determine the size of the pedia- need for an intact posterior capsule. Surgeons experi-
tric lens, Bluestein et al28 examined 50 fresh, non- enced in removing neonatal and infantile cataracts
preserved autopsy eyes from patients ranging in age feared returning to the days of dense secondary
from 1 day to 16 years. A variety of measurements membranes and frequent repeat surgeries. Technical
were made, including the anterior–posterior, vertical,
and horizontal lengths of the globe, corneal diameter,
lens diameter and the diameter of the zonular free
zone. This study revealed that most rapid lens growth
occurred during the period from birth to 2 years of
age.
Currently available adult-sized IOLs are slightly
oversized in relation to capsular bag measurements,
but may actually fit into eye in the first 2 years of life,
although possibly not in very small infantile eyes. The
small capsular bag may ovalize with these adult sized
IOLs. The possible consequences of implantation of
the adult-sized IOL in the relatively small capsular
bag of infants and young children are firstly, in
contrast to adult cataract surgery, dialing of the IOL
haptics into the capsular bag can be difficult in infants.
One of the IOL haptics will dial out of the capsular
bag rather than into it, leading to asymmetric (bag-
sulcus) fixation, which can lead to decentration of the
IOL. Secondly, implantation of an oversized IOL in
the capsular bag of an infant may cause marked
capsular bag stretching, resulting in posterior capsular
folds and striae. The lens epithelial cells may migrate
toward the visual axis, through the capsular folds,
leading to opacification of the posterior capsule.
Thirdly, implantation of an oversized IOL in the
capsular bag of an infant may cause zonular stress in
the direction parallel to the IOL haptics. The long-term
sequelae of the capsular bag stretching (and also the
zonular stress) in the axial growth of the globe remains
to be further investigated.
Some of the surgical steps are summarized in the
Figures 102.8A to C.
Figures 102.9A to 102.10G illustrate ovaling of the
capsulorhexis of rigid and foldable lenses in post-
mortem human eyes obtained from both group A and
B. Comparison of all six lens types within each group
of eyes, for difference in capsulorhexis ovaling and
capsular bag stretch, was significant (P < .001,
ANOVA).
Figs 102.8A to C: Gross photographs illustrating some of the
surgical steps used in the study evaluating capsular bag ovaling
SURGICAL TECHNIQUES and stretch of the capsular bag. (A) Anterior (or surgeon’s) view
Historical Perspective of the crystalline lens after removal of cornea and iris, (B)
Aspiration of soft lens substance in one quadrant, after
The initial reluctance of the pediatric ophthalmic hydrodissection, (C) capsular bag after complete cortical clean-
community to endorse primary implantation of PC- up
 Chapter 102: Management of Infantile-Pediatric Cataract 787
advances have now resulted in several options for capsular bag have resulted in a lower incidence of, or
opening the posterior capsule without eliminating the at least a delay in posterior capsule opacification.
possibility of IOL placement within the capsular bag. Table 102.2 summarizes the major advances
In addition, even when the posterior capsule is left influencing the pediatric cataract surgery procedure
intact, the combination of more complete cortical during the last three decades that considerably
removal and the presence of an intraocular lens in the popularized the use of IOL implantation in child-

Figs 102.9A to G: Evaluation of capsulorhexis ovaling and capsular bag stretch after implantation of rigid and foldable lenses.
Gross photographs from the left eye of a 5-month-old child (anterior view with retroillumination). (A) Empty capsular bag after
complete cortical clean-up, (B) Single-piece hydrophobic acrylic (AcrySof®) IOL, (C) Three-piece hydrophobic acrylic optic-
PMMA haptic IOL, (D) One-piece silicone-plate IOL, (E) One-piece PMMA optic-PMMA haptic IOL, (F) Three-piece silicone
optic-PMMA haptic IOL and (G) Three-piece silicone optic-polyimide haptic IOL

Figs 102.10A to G: Evaluation of capsulorhexis ovaling and capsular bag stretch after implantation of rigid and foldable lenses.
Gross photographs from the left eye of a 4-year-old child (anterior view with retroillumination). (A) Empty capsular bag after
complete cortical clean-up, (B) Single-piece hydrophobic acrylic (AcrySof®) IOL, (C) Three-piece hydrophobic acrylic optic-
PMMA haptic IOL, (D) One-piece silicone-plate IOL, (E) One-piece PMMA optic-PMMA haptic IOL, (F) Three-piece silicone
optic-PMMA haptic IOL and (G) Three-piece silicone optic-polyimide haptic IOL
788 Section 7: Pediatric Ophthalmology Including Strabismus

Table 102.2: Evolution of pediatric cataract surgery Harold Ridley33 in 1949, Peter Choyce34 reported the
Advances Year Author(s) implantation of an IOL in a 10-year-old child as early
as 1958. Binkhorst35-40 first implanted iridocapsular
First implant in a child 1958 Choyce34
fixated IOLs in children in 1959. Hiles, BenEzra and
for the aphakic correction
coworkers41-45 have extensively studied the use of
Manual aspiration of 1960 Scheie32 intraocular lens in pediatric cataract and their
congenital/juvenile complications. Use of a vitreous suction cutter to
cataract
perform a posterior capsulectomy and vitrectomy
Iridocapsular implant 1969 Binkhorst35 while removing a congenital or juvenile cataract was
Binkhorst intraocular 1977-82 Hiles31 advocated by Parks in 1983.46 This represents one of
lenses (IOLs) the major advances revolutionizing the cataract
surgery in infants. Although recurrent membrane
Posterior chamber 1982 Hiles33
formation had been very common after the infantile
IOLs
cataract surgery, second surgeries became rare.
Iris-claw lenses 1983 Singh Removal of all but 2 mm of the peripheral posterior
Pathophysiology 1977-85 Weisel/Raviola lens capsule with a vitreous suction cutter was
of amblyopia recommended as well as a generous anterior vitrec-
tomy. While this procedure reduced the risk of
Posterior chamber IOLs 1983-93 Sinskey/Hiles
amblyopia by virtually eliminating secondary
Posterior capsulotomy/ 1983 Parks membranes, it was incompatible with primary in-the-
anterior vitrectomy bag fixation of an IOL or secondary sulcus fixation of
an IOL. In consideration of secondary sulcus fixated
Epikeratophakia 1986 Morgan89
posterior chamber IOL at an older age, most pediatric
Retropseudophakic 1991 Mackool/ ophthalmic surgeons today modify the Parks proce-
vitrectomy via limbus Chhatiawala dure to leave enough residual capsule to support the
Retropseudophakic 1993 Buckley et al IOL when it is later placed in the ciliary sulcus.
vitrectomy + posterior
capsulectomy via pars Anesthesia
plana
Most pediatric cataract surgeries are done under
Primary posterior 1994 Gimbel/DeBroff63
general endotracheal anesthesia. Thus, the occurrence
capsulorhexis/optic
capture of vomiting in the early postoperative period is not
uncommon. This, along with inevitable rubbing of
IOL biomaterials/designs/ 1994 Wilson et al19
sizing in children
eyes, helps to justify the use of sutures to close the
surgical wound even if it appears to be self-sealing.
Primary posterior 1994-96 BenEzra/Cohen42 Children also have a very active Bell’s phenomenon
capsulotomy & anterior Koch/Kohnen if they become somewhat light under anesthesia. For
vitrectomy this reason, many pediatric surgeons still use a
Anterior capsulotomy 1994 Wilson et al19 superior rectus traction suture during cataract surgery.
for pediatric cataract (Vitrectorhexis)
surgery Auffarth et al47
Wound Construction
(Rabbit Model)
Heparin in BSS to decrease 1995 Brady et al78 Children have thin sclera and markedly decreased
postoperative inflammation scleral rigidity when compared with adults. Scleral
collapse results in increased vitreous upthrust (posi-
Dye-enhanced pediatric 2000 Pandey/
tive vitreous pressure). Collapse of the anterior
cataract surgery Werner72,73
chamber and prolapse of iris tissue are also much more
common when operating on pediatric eyes. Pediatric
ren.30,31 Scheie32 popularized the technique of manual cataracts can be removed through a relatively small
aspiration of congenital and juvenile cataracts. After wound, as the lens can be removed in toto since there
a successful implantation of an IOL in an adult by is usually no formed nucleus. Therefore, wounds
 Chapter 102: Management of Infantile-Pediatric Cataract
should be constructed to provide a snug fit for the
instruments that pass into the anterior chamber. When
an IOL is not being implanted, two stab incisions are
usually made at or near the limbus. These incisions
should not be larger than necessary for the instruments
being used. For instance, a micro vitreoretinal (MVR)
blade creates a 20 gauge opening that is ideal for a 20
gauge vitrector/aspirator to enter the anterior
chamber. A 20 gauge blunt tipped irrigating cannula
can also be used through a separate MVR blade stab
incision. If the instrument positions need to be
reversed, the snug fit is maintained. An anterior
chamber entry of 3 mm or less can facilitate manual
anterior capsulotomy and cortical aspiration with a
phacoemulsification or irrigation/aspiration hand-
piece. When a rigid IOL is being implanted, a scleral
tunnel wound is utilized most often. A half thickness
scleral incision is made initially approximately 2 or
2.5 mm from the limbus and dissected into clear
cornea. It is enlarged to the size necessary for IOL
insertion. Scleral tunnel wounds decrease the inci-
dence of iris prolapse into the wound during surgery
and assist the surgeon in preventing collapse of the
anterior chamber, which occurs with greater frequency
in the soft eyes of children. Unlike adults, scleral tunnel
incisions do not self-seal in children.47 According to
the study by Basti et al48 self-sealing wounds failed to
remain watertight in children below 11 years of age,
especially when an anterior vitrectomy was combined
with cataract extraction. In older (> 11 years) children
the wounds remained self-sealing. The authors
attributed this to low scleral rigidity resulting in fish
mouthing of the wound leading to poor approxi-
mation of the internal corneal valve to the overlying
stroma. Closure is recommended using a synthetic
absorbable suture such as 10-0 Biosorb or Vicryl. When
a foldable IOL is being implanted, a corneal tunnel is
preferred since it leaves the conjunctiva undisturbed.
The corneal tunnel should begin near the limbus (so-
called “near clear” incision) for maximum healing and
should be sutured with a synthetic absorbable suture.
While the temporal wound presents the same
advantages in children as it does in adults, the location
is more easily traumatized by children. The superior
approach allows the wound to be protected by the
brow and the Bell’s phenomenon in the trauma prone
childhood years. Both scleral tunnels and corneal
tunnels can be easily made from a superior approach
since children rarely have deep set orbits or over-
hanging brows. Locating the site of tunnel according
789
to the pre-existing astigmatism (e.g. temporally in
against-the-rule astigmatism) can help in reducing the
astigmatic component in the postoperative treatment
of amblyopia.
Viscoelastic Substances
A high molecular weight viscoelastic substance such
as sodium hyaluronate 14 mg/per ml (Healon GV®,
Pharmacia Corp. Peapack, NJ, USA) is most commonly
used in pediatric cataract surgery to effectively resist
the increased tendency for anterior chamber collapse
due to decreased scleral rigidity and a positive
vitreous pressure. This viscoelastic helps to maintain
a deep anterior chamber and a lax anterior capsule,
facilitating attempts at manual anterior capsulorhexis.
Also, the initially convex posterior capsule is effecti-
vely held back during IOL insertion. We have also
recently evaluated the use of viscoelastic with even
higher viscocity, sodium hyaluronate 23 mg/per ml
(Healon 5®, Pharmacia Corp. Peapack, NJ, USA)
during pediatric cataract surgery. This viscoadaptive
appears to be useful during various steps of pediatric
cataract surgery. Without a high molecular weight
viscoelastic, an IOL inserted in a manner acceptable
for an adult eye will result in inadvertent sulcus
placement secondary to the posterior vitreous
pressure and posterior capsule convexity. The
trabecular meshwork of children clears viscoelastic
substances more easily, on average, than in adults.
However, efforts should still be made to remove all
of the viscoelastic material since postoperative
intraocular pressure spikes have been documented
when Healon GV is inadequately removed.49
ANTERIOR CAPSULE MANAGEMENT
Manual Continuous
Curvilinear Capsulorhexis
Gimbel and Neuhann50 advocated continuous tear
anterior capsulotomy or CCC technique for small-inci-
sion adult cataract surgery in the mid-1990s. During
the same time, capsular bag fixation of a posterior
chamber IOL placed at the time of cataract surgery
became commonplace for children beyond age 2 years.
Because manual CCC had become the standard
anterior capsulotomy technique in adults, it was
naturally also applied to the pediatric age group, but
with mixed success.
790 Section 7: Pediatric Ophthalmology Including Strabismus
Figs 102.11A to H: Illustrations showing the push-pull
technique of CCC in the rabbit eye as a model for pediatric
capsulectomy. (A) The anterior capsule is punctured with the
cystotome to create a horizontal oval opening, (B-D) The
anterior capsule is grasped centrally with the capsulorhexis
forceps and the capsular flap torn towards 6 o’clock until half
circle is completed, (E-H) After a half circle is completed, the
capsular flap is torn back toward 12 o’clock. The capsule will
automatically tear to complete a full circle according to its elastic
properties (Modified from Auffarth GU, et al. Capsulorhexis in
the rabbit eye as a model for pediatric capsulectomy. J Cataract
Refract Surg 1994; 20:188-191, with permission).
Clinically, it became evident that the pediatric lens
capsule is more elastic than in adults and requires
increased force before tearing begins. Laboratory
investigations have now verified a markedly higher
fracture toughness and extensibility in pediatric
anterior capsule as compared to elderly adults. In
addition, reduced scleral rigidity results in posterior
vitreous upthrust when the eye is entered. This
vitreous “pressure” pushes the lens anteriorly and
keeps the anterior lens capsule taut. Surgeons found
more difficulty completing an intact circular capsulo-
tomy. The so-called “run-away rhexis” became all too
common. In addition, a capsulotomy that started out
small would end up much larger than intended. This
result was also due to the marked elasticity of the
child’s anterior capsule. Performing an intact CCC is
challenging in young children even for an experienced
surgeon as reported by Vasavada and Chauhan,21 in
a series of 21 eyes of 13 infants, where the authors
failed to create an intact CCC using manual techniques
in as high as 80% of the cases.
Surgical steps technique of continuous curvilinear
capsulorhexis in the rabbit eyes are shown in Figures
102.11A to H.
Figures 102.12A to F present illustrations, photo-
graphs and ultrastructural appearance of the manual
CCC technique, based on clinical and laboratory
studies done at the Storm Eye Institute.
Can-opener Anterior Capsulotomy
(Figs 102.13A to C)
To avoid the difficulties with CCC in children, some
surgeons have returned to the can-opener style
capsulotomy when operating on children (Fig.
102.13A). Wood and Schelonka compared the strength
and safety of a CCC with a can-opener capsulotomy
in a porcine model that closely resembles the high
elasticity of the human pediatric lens capsule.
Vitrector-cut Anterior Capsulectomy
(Vitrectorhexis)
An ideal anterior capsulotomy for children would
need to be easy to perform and yet have a low rate of
radial tear formation even as it is stretched and
deformed during cataract aspiration and IOL
placement. The manual CCC remains the gold
standard for resistance to tearing and should be
accomplished when possible. However, its completion
difficulty in children has prompted the development
and investigation of alternative techniques.
Vitrectorhexis in Pediatric Eyes
(Figs 102.14A to D)
When creating a vitrectorhexis, the following surgical
caveats are offered. Use a vitrector supported by a
Venturi pump. Peristaltic pump systems will not cut
anterior capsule easily. Use an infusion sleeve or a
separate infusion port, but with either approach,
 Chapter 102: Management of Infantile-Pediatric Cataract 791

A B

C D

E F

Figs 102.12A to F: Manual continuous curvilinear capsulorhexis (CCC) is gold standard when it can be successfully achieve.
(A) Technique of a manual CCC is illustrated. A bent needle cystotome usually is used to begin the capsulotomy by making a
linear cut near the center of the capsule. Capsulorhexis forceps are then used to tear the capsule in a circular fashion, (B) A
manual CCC is shown 4 years postoperatively. This child was 10 years old at the time of surgery. A manual tear capsulorhexis
was easily accomplished. The posterior capsule was left intact but has now received a YAG laser application, (C) Anterior (or
surgeon’s view) of crystalline lens in a human eyes obtained postmortem, aged 5-month. The cornea and iris are excised for
better visualization. (D) Creation of successful manual CCC in the same eye using capsulorhexis forceps. Note the smooth,
intact edges after a manual CCC (arrows). (E-F) Scanning electron micrograph of the capsule edge after a manual CCC and
implantation of a posterior chamber IOL in the capsular bag. Note the smooth edge of the anterior capsule edge following
manual CCC. (A, B, E, and F: Reproduced from Wilson ME. Anterior capsule management for pediatric intraocular lens implantation.
J Pediatr Ophthalmol Strabismus 36:1-6, 1999, with permission). (E-F: original magnification X5, X100, X500, respectively)
792 Section 7: Pediatric Ophthalmology Including Strabismus
A cutter on and increase the suction using the foot pedal
B escapes into the anterior chamber during the
C
Figs 102.13A to C: A can-opener anterior capsulotomy has
also been proposed by some investigators as an alternative to
manual CCC technique. (A) A can-opener capsulotomy is
illustrated. A bent needle cystotome is used to make jagged
punctures in the capsule. As these punctures are connected,
they form a circular opening. Capsular tags are created that
can promote radial tears. The sharp apex of each capsular tag
that points outward away from the center of the circle has been
shown to be an area of high-stress accumulation, making radial
tear formation likely, (B) Can-opener anterior capsulotomy in
the human eye obtained postmortem. Note the presence of
capsular tags (arrow), which can lead to radial tear formation,
jeopardizing successful in-the-bag fixation. The capsular bag
was stained using 0.1% trypan blue dye to enhance visualization
of the anterior capsular flap. (C) Scanning electron microscopy
of the anterior capsulotomy margin showing the presence of
capsular tag. (Reproduced from Wilson ME. Anterior capsule
management for pediatric intraocular lens implantation. J
Pediatr Ophthalmol Strabismus 36:1-6, 1999, with permission).
Original magnification X100
maintain a snug fit of the instruments in the incisions
through which they are placed. The anterior chamber
of these soft eyes will collapse readily if leakage occurs
around the instruments, making the vitrectorhexis
more difficult to complete.
A micro-vitreoretinal (MVR) blade can be used to
enter the eye. The vitrector and the blunt-tip irrigating
cannula (Nichamin cannula-Storz) fit snugly into the
MVR openings. Do not begin the capsulotomy with a
bent-needle cystotome. Merely place the vitrector,
with its cutting port positioned posteriorly, in contact
with the center of the intact anterior capsule. Turn the
until the capsule is engaged and opened. A cutting
rate of 150 to 300 cuts per minute and an aspiration
maximum of 150 to 250 (these settings are for the Alcon
Accurus and the Stortz Premier—adjustments may be
needed for other machines) are recommended. With
the cutting port facing down against the capsule, the
authors then enlarge the round capsular opening to
the desired shape and size. Any lens cortex that
vitrectorhexis is aspirated easily without interrupting
the capsulotomy technique. Care should be taken to
avoid leaving any right angle edges, which could
predispose to radial tear formation. The completed
vitrectorhexis should be slightly smaller than the size
of the IOL optic being implanted. Any capsular tags
or points created at the apex of a scalloped cut from
the vitrector are located in an area of low biomecha-
nical stress much like an irregular outside-in
completion of a CCC. These tags do not predispose to
radial tear formation as demonstrated by finite
element method computer modeling.
Bipolar Radiofrequency Capsulotomy
Radiofrequency diathermy capsulotomy, developed
by Kloti et al52 has been used as an alternative to CCC
for intumescent adult cataracts, and for cataract
surgery in children. The Kloti device cuts the anterior
capsule with a platinum-alloy-tipped probe (Figs
102.15A and B) using a high frequency current of 500
kHz. The probe tip is heated to about 160°C and
produces a thermal capsulotomy as it is moved in a
circular path across the anterior capsule. Small gas
bubbles are formed while the tip is active, but these
do not usually interfere with visibility during the
capsulotomy. Gentle pressure must be maintained on
the capsule with the tip as it moves either clockwise
or counterclockwise. If contact is too light or move-
ment too fast, skipped areas will result. If contact is
too firm or movement too slow, the tip will burn
through the capsule and enter the lens cortex. Subse-
 Chapter 102: Management of Infantile-Pediatric Cataract 793

Figs 102.14A to D: Use of vitrector for anterior and posterior capsulorhexis (termed as “vitrectorhexis”) has been extensively
studied in both clinical and laboratory setting. (A) A vitrectorhexis is illustrated. The side port cutting vitrector hovers over the
intact capsule. The capsule is aspirated up into the cutting port and a circular opening is fashioned. Although a scalloped edge
is created (left background), this edge folds back as viscoelastic is placed within the capsular bag (right foreground) to create a
smooth edge. Capsular tags made with the vitrector usually have an apex pointing toward the center of the capsular opening. As
opposed to can-opener capsulotomy tags, these do not represent areas of high-stress accumulation. The mechanical vitrector
cut capsulectomy works best on the elastic capsule of young children, (B) A vitrector-cut anterior capsulectomy is shown in this
pediatric autopsy eye from the Miyake-Apple posterior view, (C) The postoperative appearance of this vitrector-cut anterior
capsulectomy is smooth and round. The intraocular lens is well centered and placed completely within the capsular bag. (D)
Scanning electron micrograph of vitrectorhexis capsule edge. (Reproduced from Wilson ME. Anterior capsule management for
pediatric intraocular lens implantation. J Pediatr Ophthalmol Strabismus 36:1-6, 1999, with permission)

quent tip movement drags the capsulotomy edge

rather than cutting it, which may cause radial tearing.
However, the preferred rate of movement and
firmness of capsule contact is quickly learned after a
few cases. Even when performed perfectly, a dia-
thermy-cut capsulotomy can be seen to have coagu-
lated capsular debris along the circular edge. In
addition, this edge has been shown experimentally to
be less elastic than a comparable CCC edge. Since the
stretching force needed to break the edge of a
diathermy-cut capsulotomy is much reduced compa-
red to a CCC edge, surgical manipulations needed to
remove a cataract and place an IOL may result in more
radial tears when the diathermy is used. However,
the experimental measurements were all made on
adult autopsy globes. It is well known that the
pediatric capsule responds differently. In fact, Comer
et al62 reported no radial tears when using the dia-
thermy-cut capsulotomy in 14 eyes of 7 children whose
mean age was 23 months. Clinically, the diathermy
devise is useful in children for both the anterior and
posterior capsules. However, the diathermy edge tears
more easily than when vitrector or manual CCC
techniques are used.
Figs 102.15A and B: The Kloti radiofrequency diathermy. The
platinum alloy tipped probe directs a high frequency current of
Fugo Plasma Blade™ Anterior Capsulotomy 500 kHz. Under viscoelastic, the probe tip is placed in contact
The Fugo Plasma Blade™ has also been recently with the intact anterior capsule and moved in a circular path to
create a round opening. (A) Kloti radiofrequency diathermy
introduced as a radiofrequency unit that can be used
needle hand piece and (B) Kloti radiofrequency diathermy
to perform an anterior capsulectomy (Fig. 102.16). The needle. (Reproduced from Wilson ME. Anterior capsule
Fugo blade capsulotomy unit is a portable electronic management for pediatric intraocular lens implantation. J
system that operates on rechargeable batteries and Pediatr Ophthalmol Strabismus 36:1-6, 1999, with permission)
794 Section 7: Pediatric Ophthalmology Including Strabismus
Figs 102.16A to D:Anterior capsulotomy using the Fugo
Plasma Blade. (A-D) Show various steps of anterior
capsulotomy in a porcine eye model. (Modified from original
article: Roy H, MD. Course for Fugo blade is enlightening,
surgeon says. Ocular Surgery News, September 1, 2001, with
permission)
provides an alternative to capsulorhexis. This unit is
user friendly and may be clipped to the surgeon’s belt
or may rest on a countertop. The Fugo blade provides
an anterior capsulotomy that requires no red reflex
and usually require less than 10 seconds to perform.
The unit also allows the surgeon to easily revise the
size of the capsulotomy openings. The Fugo blade may
be particularly suited for the highly elastic capsule of
children. Because it cuts the capsule with a “plasma
blade”, it may not suffer from the tendency for skip
areas seen with Kloti radiofrequency device. However,
the edge of a Fugo blade capsulotomy will not likely
perform better than the Kloti diathermy edge when
stretched.
Lens Substance Removal
Pediatric cataracts are soft. Phacoemulsification is
rarely if ever needed. Lens cortex and nucleus usually
easily aspirated with an irrigation/aspiration or
vitrectomy handpiece. When using the vitrector,
bursts of cutting can be used intermittently to facilitate
the aspiration of the more “gummy” cortex of young
children. The phacoemulsification handpiece can also
be very useful when aspirating pediatric lens material.
Hydrodissection78,80 has been thought to be less useful
in children than in adults. However, a recent study
has shown the intraoperative benefits of performing
multiquadrant hydrodissection.54 The benefits are:
overall reduction in the operative time, and the
amount of irrigating solution used and facilitation of
lens substance removal. A fluid wave can sometimes
be generated in older children but not reliably in
infants and toddlers. Cortical material strips easily
from the pediatric capsule even in the absence of
hydrodissection. Attempts at hydrodelineation should
be discouraged in children since it does not aid in lens
removal and may lead to capsular rupture.
Primary Intraocular Lens Implantation
Capsular fixation of the IOL is strongly recommended
for children. 53,55 Care should be taken to avoid
asymmetric fixation with one haptic in the capsular
bag and the other in the ciliary sulcus. In contrast to
adults, dialing of an IOL into the capsular bag can be
difficult in children. An oversized IOL (adult IOL—
12 to 12.5 mm) along with the vitreous upthrust often
cause the IOL to vault forwards which results in its
dialing out of the capsular bag. On the other
hand, sulcus fixation of an IOL in a child appears to
be easy but the long-term consequence of contact with
vascularized uveal tissue is a cause for concern.
To minimize the iris-optic contact, lens decentration
and to reduce the possibility of erosion into the ciliary
body, prolapse of the optic through an intact ante-
rior or posterior capsulotomy is suggested when
sulcus fixation of an IOL in a child is necessary.
Secondary Intraocular Lens Implantation
The vast majority of children undergoing secondary
intraocular lens implantation have had a primary
posterior capsulectomy and anterior vitrectomy. If
adequate peripheral capsular support is present, the
implant is placed into the ciliary sulcus.67 Since the
sulcus is only 0.5 to 1.0 mm larger than the evacuated
capsular bag, most IOLs designed for capsular fixation
can also be placed in the ciliary sulcus. Viscodissection
is often all that is needed to break synechia between
the iris and residual capsule. Both the AcrySof™
acrylic lens and the all-PMMA lenses have been used
by the authors for sulcus fixation in the child. Our
current recommendations are to place an all-PMMA
heparin-surface-modified IOL rather than an acrylic
lens when sulcus placement is required. Prolapsing
the IOL optic through the fused anterior and posterior
capsule remnants is useful in preventing pupillary
capture and assuring lens centration. In some cases,
the anterior and posterior capsular remnants can be
 Chapter 102: Management of Infantile-Pediatric Cataract
dissected apart allowing the IOL to be placed in the
capsular bag.56 An exuberant Soemmering’s ring
formation will often separate the anterior and
posterior capsule leaflets and maintain the peripheral
capsular bag. This material can be aspirated cleanly
after the anterior capsule edge is lifted off the posterior
capsular edge to which it is usually fused.
When inadequate capsular support is present for
sulcus fixation in a child, implantation of an IOL is
not recommended unless every contact lens and
spectacle option has been fully explored. Although
their long-term safety is unknown, modern flexible
open loop anterior chamber lenses seem to be well
tolerated in children when their anterior segment is
developmentally normal. Scleral fixation of posterior
chamber IOLs in children have been well tolerated
according to some recent studies, but complications
such as pupillary capture, suture erosion and
refractive error from lens tilt or anterior/posterior
displacement have been reported.57-59 The ab-externo
approach is recommended for trans-scleral suture
placement in children.
Management of the Posterior Capsule
Management of the pediatric posterior capsule,
especially when implanting an IOL at the time of the
primary surgery remains controversial. 60 Several
surgical techniques have been used by various
surgeons to maintain the long-term clear visual axis.
PRIMARY POSTERIOR CAPSULOTOMY
AND ANTERIOR VITRECTOMY
Primary posterior capsulectomy and anterior vitrec-
tomy during pediatric lensectomy were popularized
by Parks in the early 1980s.46 This led to a dramatic
decrease in the need for secondary surgery for
congenital cataracts. Pediatric ophthalmologists are
accustomed to removing a portion of the posterior
capsule and the anterior vitreous at the time of
lensectomy. Adult cataract surgeons are often more
reluctant to perform a primary posterior capsulectomy
and vitrectomy for fear of the risk of retinal detach-
ment or cystoid macular edema will be increased. In
point of fact, these complications are exceedingly rare
after pediatric cataract surgery with or without a
primary capsulectomy 61 and vitrectomy. Neody-
mium: YAG laser posterior capsulotomy is usually
795
necessary in children when the posterior capsule is
left intact. This procedure also carries a risk of retinal
detachment and cystoid macular edema. In addition,
larger amounts of laser energy are often needed when
compared to adults and the posterior capsule opening
may close requiring repeated laser treatments or a
secondary pars plana membranectomy.
Dahan and Salmenson 20 have recommended
posterior capsulotomy and anterior vitrectomy in
every pediatric cataract patient younger than eight
years. Vasavada and Desai61 also advise anterior
vitrectomy along with primary posterior continuous
circular capsulorhexis (PCCC) in children younger
than 5 years of age. Metge and co-workers21 have
shown that a posterior capsulectomy without a central
vitrectomy did not prevent the development of a
secondary membrane. The opacification rate was not
significantly decreased by a posterior capsulectomy
alone. Only when an anterior vitrectomy was added
did the opacification rate fall. Vasavada and Trivedi,62
in a prospective and randomized study, have also
shown that visual axis obscuration by reticular fibrosis
of the anterior vitreous face occurred in 70% of those
eyes in which vitrectomy was not done following
PCCC. As opposed to this, no eye developed
visual axis obscuration when a PCCC was combi-
ned with anterior vitrectomy (Figs 102.17A and B).
Also, these eyes performed better for low contrast
sensitivity testing. All these results suggest that
anterior vitrectomy is not only beneficial but also
necessary in children aged 5 to 12 years.23
POSTERIOR CAPSULORHEXIS
WITH INTRAOCULAR LENS OPTIC CAPTURE
Gimbel and DeBrof 63-65 recommend performing a
posterior capsulorhexis with IOL optic capture. This
technique is designed to help prevent secondary
membrane formation without necessitating a vitrec-
tomy. 66It also ensures centration of the posterior
chamber IOL because the haptics remain in the
capsular bag and the optic is captured in the posterior
capsular opening (Fig. 102.18). Vasavada and Trivedi62
also reported a better centration of the IOL following
optic capture. However, they have also expressed
concern regarding the resultant increased predis-
position to uveal inflammatory sequelae. The same
authors,62 along with other surgeons67,68 have repor-
ted opacification of the visual axis despite optic
capture. Thus they recommend performing an anterior
796 Section 7: Pediatric Ophthalmology Including Strabismus
Figs 102.17A and B: Two different cases of in-the-bag IOL
fixation in combination with primary posterior capsulotomy and
anterior vitrectomy. (A) Clinical photograph post implantation
of an all PMMA IOL in which a primary posterior capsulotomy
with anterior vitrectomy were performed at the time of primary
surgery. The posterior capsule within the visual axis remained
clear 1-year postoperatively. Note however the presence of
some cell deposits on the IOL surfaces, (B) Acrylic (AcrySofTM)
IOL implanted in the capsular bag of a 4-year-old child. A primary
posterior capsulorhexis and anterior vitrectomy were performed.
This photograph was taken 1 year postoperatively. There are
several Elschnig pearls outside the IOL optic, but the visual
axis is clear. (Courtesy: AR Vasavada)
vitrectomy even when optic capture is utilized
through the posterior capsulorhexis.
Fig. 102.18: Photograph of an eye implanted with an acrylic
(AcrySofTM) IOL in the capsular bag. IOL optic capture through
a posterior capsulorhexis was performed during the primary
procedure. This photograph was taken at 1 month post-
operatively and shows well centered IOL and anterior and
posterior capsulorhexis edges. (Courtesy: AR Vasavada)
Neodymium (Nd):
YAG Laser Posterior Capsulotomy
Atkinson and Hiles, 69 on the other hand, recom-
mended leaving the posterior capsule intact even in
very young children and performing Neodymium:
YAG capsulotomy under a second general anesthesia
in the early postoperative period. Subsequently,
however, the same group reported a 41% need for
repeating laser capsulotomy when this protocol was
followed. Interestingly, Plager et al27 reported that in
their patients, the incidence of PCO began to increase
markedly at approximately 18 months after surgery,
independent of the age at the time of cataract
extraction. They recommended a primary posterior
capsulectomy and anterior vitrectomy at the time of
primary lens implantation in children who are not
expected to be suitable candidates for awake
Neodymium: YAG capsulotomy within 18 months of
surgery. IOL exchange, if needed later, will be more
difficult if optic capture has been used.
Options for Primary Posterior Capsulotomy
When a decision is made to perform a primary
posterior capsulotomy, several options are
available.64,70,71 The posterior capsular opening can be
made using a manual PCCC technique or using an
automated vitrector or the Kloti radiofrequency
bipolar unit. The manual technique and the mechani-
 Chapter 102: Management of Infantile-Pediatric Cataract 797
zed vitrector technique can each be performed either
before or after the intraocular lens has been placed in
the eye. When the vitrector is used after the IOL has
been placed, it is usually done via the pars plana. The
radiofrequency bipolar unit is not easily manipulated
beneath an IOL and is therefore usually performed
on the posterior capsule from an anterior approach
prior to IOL insertion. In most instances, an anterior
vitrectomy is performed simultaneously with the
posterior capsulectomy.

DYE-ENHANCED PEDIATRIC
CATARACT SURGERY
Use of capsular dyes such as 2% fluorescein sodium,
0.5% indocyanine green (ICG), and 0.1% trypan blue
for staining the anterior capsule, while performing
CCC in white/advanced adult cataract is well known.
We recently reported our experience of anterior
capsule staining for performing CCC in postmortem
human eyes with advanced/white cataracts.72 We also
reported the use of capsular dyes to enhance visualiza-
tion to learn and perform other critical steps of the
phacoemulsification procedure, and posterior capsul-
orhexis, respectively.73,74 According to our experimen-
tal studies, posterior capsulorhexis (with or without
the optic capture) is relatively easy to perform after
staining of the otherwise transparent posterior capsule
(Figs 102.19A and B). The procedure of optic capture
with or without anterior vitrectomy can also be
accomplished easily after staining the posterior Figs 102.19A to C: Photographs of a pediatric eye obtained
capsule. It is easier to localize an inadvertent tear of postmortem, taken from anterior (surgeon’s view) illustrating
the posterior capsule when staining of the posterior the use of the capsular dye to enhance visualization during
various steps of the pediatric cataract surgery. (A) Posterior
capsule has been utilized (Fig. 102.19C).
capsulorhexis after the staining of the capsular bag with trypan
blue, (B) Posterior capsulorhexis and optic capture of a foldable
PERIOPERATIVE AND IOL after the staining of the capsular bag with trypan blue, (C)
POSTOPERATIVE MEDICATIONS Visualization of a posterior capsule tear after staining of the
capsular bag with indocyanine green
The perioperative routine includes a drop of 5%
povidone iodine at the beginning and at the end of
the surgical procedure. It is better to avoid using a atropine is sometimes avoided when an IOL is placed
miotic at the completion of surgery since this can create in the ciliary sulcus to reduce the possibility of
increased anterior segment inflammation. Topical pupillary capture. Glasses or an eye shield is worn
steroid/antibiotic and atropine ointment are put in over the eye continuously for the first week.
the eye, and a light patch and fox shield placed over
the eye. Beginning the next morning, topical steroid POSTOPERATIVE COMPLICATIONS
drops six times a day and atropine 1% eyedrops once AND MANAGEMENT
per day for four weeks are recommended. A topical Complications associated with pediatric cataract
antibiotic is added for the first several days. The surgery continue to be a major concern for the ophthal-
atropine eyedrops regimen is stopped at four weeks mic surgeon. The risk of postoperative complication
and the topical steroid tapered and discontinued. The is higher due to greater inflammatory response after
798 Section 7: Pediatric Ophthalmology Including Strabismus

Figs 102.20A and B: Cataract surgery and in-the-bag fixation of posterior chamber IOLs in pediatric traumatic cataracts. (A)
Preoperative photograph of the anterior segment of a 6-year-old male child showing traumatic cataract and formation of posterior
synechia at 2.30 o’clock position. The visual acuity on presentation was 20/60, (B) Same eye 4 weeks postoperatively, showing
the clear visual axis after cataract extraction and capsular bag fixation of a posterior chamber intraocular lens. The best-corrected
visual acuity was 20/20

pediatric intraocular surgery.29 In many cases, these

complications may be the primary reason for a poor
visual outcome.
Capsular bag fixation of a PC-IOL was performed
in 10 eyes (group A) and in other 10 eyes (group B)
ciliary sulcus fixation was performed (Figs 102.20A
and B).

Uveitis
Postoperative anterior uveitis (fibrinous or exudative)
is a common complication due to increased tissue
reactivity in children. The reported incidence of
postoperative fibrinous anterior uveitis was 81.8%,
26.0% and 19.0%. 15,75 Uveitis results in fibrinous
membrane formation, pigment deposits on the IOL Fig. 102.21: Slit lamp photograph of a young child after ciliary
and posterior synechia formation (Fig. 102.21).76,77 sulcus fixation of a PMMA IOL. Note the formation of a
Frequent topical steroids and even systemic steroids membrane and multiple posterior synechiae
may be needed in selected cases to reduce uveitis-
A complete resolution of fibrin formation was seen in
related complications. Brady et al78 recommend five
90% of children after using 10 micrograms of
units of intravenous heparin in 500 ml of irrigating
recombinant tissue plasminogen activator (rt-PA). Of
solution. According to recent studies, implantation of
course modern surgical techniques that limit iris
heparin-surface-modified PMMA IOLs in children
manipulation and ensure capsular bag fixation of the
reduces postoperative inflammation. Mullaney et al79
reported dissolution of pseudophakic fibrinous IOL, have resulted in less postoperative inflammation
even in small children.
exudates with the use of intraocular streptokinase
(500-1000 IU) without any adverse effect. Similarly,
Corneal Edema
Klais and co-workers80 performed fibrinolysis in 11
eyes of 10 children who developed severe fibrin Transient corneal edema may occur in pediatric
formation despite intensive topical steroid therapy. cataract surgery but bullous keratopathy is a rare
 Chapter 102: Management of Infantile-Pediatric Cataract
complication. 81 Cataract surgery does not cause
significant endothelial cell loss in children. Reports
on corneal endothelial cell count in pediatric aphakia
and IOL implantation have shown no significant loss
of endothelial cells.21,82,83 Corneal decompensation
may occur if detergents (e.g. glutaraldehyde) are used
for sterilization of cannulas or instruments and are
not rinsed thoroughly before use in the anterior
chamber. Indeed, cannulas or tubing should not be
sterilized in glutaraldehyde solution as, even after
thorough rinsing, residual chemicals may remain.
Endophthalmitis
Endophthalmitis does occur after cataract extraction
in children. It is a rare complication and appears to
occur with the same frequency as in adult cataract
patients. The prevalence of endophthalmitis reported
by Wheeler and associates84 was 7/10,000 cases, after
pediatric cataract surgery. Common organisms are
Staphylococcus aureus, Staphylococcus epidermidis and
Staphylococcus viridence. Nasolacrimal duct obstruc-
tion, periorbital eczema and upper respiratory tract
infections are important risk factors.94
Techniques to avoid the complication of endoph-
thalmitis remain controversial in all cataract proce-
dures. Authorities advise the use of topical antibiotic
ophthalmic solutions applied to the cataractous eye
for 24 hours preoperatively. Other authorities empha-
size the need to use an undiluted povidone-iodine
(Betadine™) solution not only applied to the skin but
also instilled in the eye at the time of the operation to
reduce the bacterial flora in the operative field.
Identifying endophthalmitis in the young child is
often much more difficult than in the adult aphakic
patient. Careful slit-lamp examination may not be
possible, even with a hand-held device. It should be
recalled that the most likely time for endophthalmitis
to become clinically apparent in the postoperative
period is between 48 and 96 hours postoperatively.
Postoperative schedules for evaluating these patients
should be drafted with this fact in mind in this era of
ambulatory surgical therapy.
The risk of endophthalmitis may be lower than the
risks associated with general anesthesia in some
neonates. Therefore, some ophthalmologists have
opted to perform bilateral cataract surgery under one
general anesthesia in medically unstable infants. This
point remains controversial.
799
Noninfectious Inflammation
Jameson and colleagues85 have described a benign
syndrome of excessive noninfectious postoperative
inflammatory response in young aphakic children.
This syndrome presents with excessive photophobia,
tearing, and even inability to open the eyes postope-
ratively. It may persist for days or even weeks and
may preclude the early contact lens fitting that initiates
amblyopic therapy. It is not clear whether steroids
applied topically or injected into the sub-Tenon’s space
are efficacious in shortening this benign inflammatory
process.
POSTOPERATIVE COMPLICATIONS
INTERMEDIATE/LATE ONSET
Capsular Bag Opacification
Opacification of the capsular bag universally occurs
following pediatric cataract surgery. It includes
opacification of the anterior, equatorial and posterior
capsules. Excessive anterior capsule fibrosis and
shrinkage of the CCC opening can lead to difficulty
in examining the retinal periphery and occasionally
the decentration of the IOL.86 Figures 102.22A to C
shows examples of capsular bag opacification in 3
different pediatric cases.
PCO is the most common complication after
pediatric cataract surgery with or without IOL
implantation.11,87 A recent report has indicated an age
independent dramatic rise in the incidence of PCO
beginning at 18 months after surgery and reaching
nearly 100% over time.27 PCO is amblyogenic if it
occurs during the critical period of visual development
in the younger children. In cases of dense, thick PCO,
surgical posterior capsulotomy combined with
anterior vitrectomy may be required to prevent
amblyopia. Nd: YAG laser can also be used to perform
posterior capsulotomy when PCO is not dense (Fig.
102.23).64 The use of newer surgical techniques such
as primary posterior capsulotomy and anterior
vitrectomy, posterior capsulorhexis with optic capture
or posterior capsulotomy performed with endodia-
thermy of capsule have shown encouraging results in
maintaining a clear visual axis.44,51,70
Secondary Membrane Formation
Formation of secondary membranes is a common
complication of pediatric cataract surgery, particularly
after infantile cataract surgery.88-91 Nd: YAG laser
capsulotomy may be sufficient to open them in the
800 Section 7: Pediatric Ophthalmology Including Strabismus
Figs102.22A to C: Clinical photographs showing examples of
delayed postoperative capsular bag opacification (and its
sequelae) after pediatric cataract surgery. (A) Anterior capsule
opacification after phacoemulsification and implantation of an
AcrySof™ IOL in a 7-year-old child. Both eyes had a best-
corrected visual acuity of 20/40. (B) Dense anterior capsule
opacification after phacoemulsification and in-the-bag
implantation of a PMMA IOL in a 8-year-old child. (C) Superior
decentration of in-the-bag fixated posterior chamber IOL 5
months following cataract surgery secondary to asymmetrical
capsular bag fibrosis in a 5-year-old child
Fig. 102.23: Slit-lamp photograph of the anterior segment of a
7-year-old-male child 18 months following capsular bag fixation
of a posterior chamber intraocular lens. This patient required
Nd:YAG laser posterior capsulotomy for posterior capsule
opacification. There was also an opacification of the anterior
capsule including the capsulorhexis margin
early stage. More dense secondary membranes usually
need membranectomy and anterior vitrectomy.92
Pupillary membranes can occur postoperatively in
children whether an intraocular lens has been
implanted or not. Microphthalmic eyes with micro-
coria operated in early infancy are at greatest risk,
especially when mydriatic/cycloplegic agents have
not been used postoperatively. When an IOL is in
place, secondary membranes may form over the
anterior and/or posterior surface of the implant. The
incidence of secondary membranes after neonatal or
infantile cataract surgery has been reduced drama-
tically by the “no-iris-touch” aspect of the closed
chamber surgery, by applying topical corticosteroids
and cycloplegic agents at frequent intervals post-
operatively and by performing posterior capsulec-
tomy and an adequate anterior vitrectomy.
Pupillary Capture
Placing the IOL in the capsular bag helps to prevent
pupillary capture, a complication that is much more
common in children. It is associated with posterior
synechia formation and PCO. Incidence of pupillary
capture after pediatric cataract surgery varies from
8.5 to 41%. This was reported by several authors:
Vasavada and Chouhan21 in 33% (7 of 21 eyes), Basti
et al70 in 8.5% (7 of 82 eyes), Brady et al78 in 14.2% (3
 Chapter 102: Management of Infantile-Pediatric Cataract
of 20 eyes) and Bustos et al.93 in 10.5% (2 of 19 eyes).
Pupillary capture occurs most often in children
younger than 2 years of age, when an optic size less
than 6 mm is used and the lens is placed in the ciliary
sulcus. In a series of 20 cases of traumatic cataracts
with PC-IOL implantation in children, Pandey et al55
reported an incidence of pupillary capture as high as
40% in ciliary-sulcus fixated IOLs while none of the
eyes with in-the-bag fixation of the PC-IOL had this
complication (Figs 102.24A and B). Pupillary capture
can be left untreated if it is not associated with
decreased visual acuity, IOL malposition or glaucoma.
However, surgical repair recreates a more round pupil
shape and IOL centration. Fixation of PC-IOLs in the
capsular bag (whenever possible) is recommended to
decrease the incidence of this complication. Prolapsing
the optic of a secondary sulcus fixated IOL through
the anterior capsulorhexis opening can also prevent
pupillary capture.
Deposits on IOL Surface
Precipitates composed of pigments, inflammatory
cells, fibrin, blood breakdown products and other
elements, are often seen during the immediate
postoperative period on the surface of an IOL optic
implanted in a child (Figs 102.25A and B). The deposits
can be pigmented or non-pigmented but are usually
801
not visually significant. They occur much more
commonly in children with a dark iris, and when
compliance with postoperative medications has been
poor. Heparin-surface-modified IOLs have been
reported to decrease the incidence of these deposits.
The site of IOL implantation can also influence the
formation of deposits. Vasavada and Trivedi62 have
found that the incidence of deposits was higher in eyes
with the IOL optic captured through the PCCC in
comparison with in-the-bag fixated IOLs.
IOL Decentration
Decentration of an IOL can occur because of traumatic
zonular loss and/or inadequate capsular support.
Capsular bag placement of the IOL is the most
successful way to reduce this complication. Posterior
capture of the IOL optic also resulted in better
centration of the implanted IOL. Incidence of lens
malposition in pediatric eyes following posterior
chamber IOL implantation was reported as high as
40%.94 Asymmetric IOL fixation, with one haptic in
the capsular bag and the other in the ciliary sulcus
can also lead to decentration and should therefore be
avoided. Complete IOL dislocation can occur after
trauma. Explantation or repositioning of the IOL may
be necessary in some cases presenting with significant
decentration/dislocation.

Figs 102.24A and B: Pupillary capture and posterior capsule opacification after pediatric cataract surgery and IOL implantation.
(A) Slit-lamp photograph of the anterior segment of a 12-year-old-female child 13 months after ciliary sulcus fixation of a
posterior chamber intraocular lens. Note the marked pupillary capture of the IOL optic, extending from 12 o’clock to 5 o’clock
associated with pupillo—capsular synechia and marked posterior capsule opacification. Best-corrected visual acuity was 6/24
in this eye due to posterior capsule opacification. It required Nd: YAG laser posterior capsulotomy, (B) Clinical photograph of the
eye of a 10-year-old girl, post PMMA posterior chamber intraocular lens implantation. There is a marked pupillary capture. This
is associated with marked posterior capsule opacification. Attempt to perform Nd: YAG laser failed, resulting in multiple pits on
the IOL optic. This type of dense PCO is an indication of surgical posterior capsulotomy with anterior vitrectomy
802 Section 7: Pediatric Ophthalmology Including Strabismus
Figs 102.25A and B: Slit-lamp photographs showing pigment deposition surface of 2 different IOLs. This complication is not
uncommon after the pediatric cataract surgery and usually don’t cause a decrease in visual acuity (Courtesy: AR Vasavada)
Glaucoma
Pediatric aphakic/pseudophakic glaucoma remains
a challenge. Its etiology, pathogenesis, incidence,
onset, diagnosis, and successful treatment often
confuses the surgeon. The incidence of glaucoma
varies from 3 to 32%.95-100 Although microphthalmic
eyes appear to be at the highest risk, cataract surgery
before one year of age, congenital rubella, and poorly
dilated pupils are other important risk factors and
should alert the treating ophthalmologist.
Glaucoma occurring soon after surgery is usually
due to pupillary block or peripheral anterior synechia
formation. This form of glaucoma is rare in children.
Vajpayee and co-workers101 reported the development
of pseudophakic pupillary block glaucoma in 16
children after PC-IOL implantation leading to irrever-
sible visual loss in two of their patients. These authors
emphasized the necessity of stringent and frequent
follow-up for pseudophakic children. Peripheral
iridectomy may prevent pupillary block pseudo-
phakic glaucoma. For this reason, some authors
recommend that all children having PC-IOLs undergo
peripheral iridectomy when there is rupture of the
posterior capsule or zonular dehiscence, which may
predispose to vitreous plugging. The majority of
pediatric cataract surgeons, however, don’t routinely
perform peripheral iridectomy at the time of cataract
surgery.
The commonest type of glaucoma developing after
pediatric cataract surgery is open-angle glaucoma.
Unlike angle-closure glaucoma, which usually
develops soon after surgery, open angle glaucoma is
usually seen later, emphasizing the need for a life-long
follow-up of these children. The reported mean
interval from the time of cataract surgery until the
detection of glaucoma ranged from 6 years to as long
as 56 years.102 A deep anterior chamber, increased
pigmentation of the trabecular meshwork, and the iris
inserting into the posterior aspect of the trabecular
meshwork are generally seen during the gonioscopic
examination. Cataract surgery may accelerate the
development of glaucoma in certain eyes that are
predisposed to develop open angle glaucoma.
The diagnosis of glaucoma may be difficult to
establish in children after cataract surgery. Intraocular
pressure should be periodically recorded to detect and
treat this vision threatening complication. It may be
difficult to measure IOP with the child awake, and
view of the optic disk may be compromised by lens
remnants, miosis, and nystagmus. Further, it is
difficult to assess the visual field until later in
childhood. An excessive loss of hyperopia may be the
sign of glaucoma in children following cataract
surgery as noted by Egbert and Kushner.98
Retinal Detachment
The incidence of retinal detachment following
pediatric cataract surgery has been reported between
1 to 1.5%. The interval from infantile cataract surgery
to retinal detachment ranged from 23 to 34 years
according to some authors. 121 The significant risk
factors for occurrence of retinal detachment are high
myopia and repeated surgeries. Retinal detachments
following infantile cataract surgery are usually
secondary to oval or round holes along the posterior
vitreous base. These are difficult to repair in children
due to poor visualization. Most reported cases have a
history of multiple reoperations performed in the
 Chapter 102: Management of Infantile-Pediatric Cataract
years prior to the introduction of automated lensec-
tomy and vitrectomy. The incidence appears to be
decreasing as surgical techniques advance and evolve.
Cystoid Macular Edema
Cystoid macular edema (CME) is a rare complication
following pediatric cataract surgery probably due to
healthy retinal vasculature.103 Because of the difficulty
of performing fluorescein angiography during
infancy, surgeons seldom evaluate children for this
complication. Gilbard and co-workers104 reported no
CME in 25 eyes after pars plicata removal of congenital
cataracts. No subsequent paper has documented
clinically significant CME after pediatric cataract
surgery even when an anterior vitrectomy is per-
formed.
Hemorrhagic Retinopathy
This complication may occur following infantile
cataract surgery in up to one-third of eyes as reported
by Mets and Del Monte.105 It presents with flame-
shaped retinal hemorrhages and may be associated
with concurrent vitreous hemorrhage.108 The hemorr-
hages develop during the first 24 hours following
surgery, are non-progressive and resolve within few
weeks.106
Residual Refractive Error
Uncorrected aphakia after pediatric cataract surgery
can cause or worsen amblyopia. When a child is left
aphakic, every effort should be made to minimize time
intervals when the prescribed aphakic glasses or
aphakic contact lenses are not worn. Even short
intervals of uncorrected aphakia are potentially very
damaging to the prognosis.107-111 When an IOL is
implanted, a smaller amount of residual hyperopia
may be present. Correction of residual hyperopia and
any significant astigmatic error is necessary to
optimize visual development and recovery from
amblyopia. Some surgeons prefer to correct children
to emmetropia with an IOL even at young ages to
minimize the amblyogenic effects of residual hyper-
opia. Since young children’s eyes continue to grow
axially after cataract surgery and IOL implantation,
significant late myopia will be more and more
common as the years pass, especially if emmetropia
is achieved early in life with an IOL.112-114 Glasses or
contact lenses will be used for correction of secondary
myopia in most cases. However, the development of
803
new corneal and intraocular refractive procedures will
provide new options for correcting significant late
myopia.
PIGGY-BACK FOLDABLE
INTRAOCULAR LENSES IN INFANTS
Polypseudophakia (piggy-back IOLs) has been used
as a means to provide appropriate optical correction
for patients requiring high IOL power or for secondary
correction of an undesirable postoperative refraction
after cataract surgery. This procedure, called
“temporary polypseudophakia”, may help in the
prevention and treatment of amblyopia by avoiding
residual hyperopia.115 The posterior lens is implanted
in the capsular bag and the anterior lens is placed in
the ciliary sulcus. Within 12 to 24 months after the
primary surgical procedure, the lens implanted in the
ciliary sulcus is explanted/exchanged. To date, 15
infantile eyes have had this procedure successfully.
Management of Amblyopia
The postoperative compliant occlusion therapy of the
normal eye in cases of unilateral congenital, develop-
mental or traumatic cataract may be needed to reverse
or prevent amblyopia in visually immature children.
Pharmacological penalization may be useful in
children with amblyopia secondary to unilateral
aphakia. Wheeler et al found poor compliance of
amblyopia therapy in one–third of the children having
PC-IOLs. A best-corrected visual acuity of 20/40 or
better was achieved only in 33% of eyes in their series.
Noncompliance of occlusion therapy appears to be a
major barrier in achieving satisfactory visual outcome
during the treatment of amblyopia.116-123
SUMMARY AND CONCLUSIONS
Pediatric cataracts are common and represent one of
the most treatable causes of visual impairment in this
population. Management of cataract in children is
different from the adult, because of increased intra-
operative difficulties, propensity of postoperative
inflammation, changing refractive state of the eye,
difficulty in documenting anatomic and refractive
changes due to poor compliance, and a tendency to
develop amblyopia. Adoption of different techniques
for cataract surgery in children is a must due to a low
scleral rigidity, increased elasticity of the anterior
804 Section 7: Pediatric Ophthalmology Including Strabismus
capsule, and positive vitreous pressure. Early surgical
intervention and adequate visual rehabilitation is
necessary to avoid irreversible visual damage
secondary to amblyopia. Aphakic glasses are not
desirable for the long-term correction of pediatric
aphakia because of many disadvantages associated
with their use. Although contact lenses offer many
advantages over aphakic spectacles, there are
problems of infection, lens loss, and a low compliance.
Current practice for providing full time correction of
pediatric aphakia is shifting toward implantation of
intraocular lenses due to refined and perfected
microsurgical techniques, as well as the availability
of suitable rigid and foldable implant designs. Main
postoperative complications noted following pediatric
cataract surgery include fibrinous uveitis, pupillary
capture, aphakic glaucoma, pigment and cellular
deposits on the implants, posterior capsule opacifi-
cation or secondary membrane formation, and
residual refractory error. These side effects may
develop after many years. Therefore, it is crucial to
follow children closely on a long-term basis after
pediatric cataract surgery.
REFERENCES
1. Wilson ME, Pandey SK, Thakur J. Pediatric surgery in the
developing world. Br J Ophthalmol 2003;87,16.
2. Pandey SK, Wilson ME, Trivedi RH. Pediatric cataract surgery
and intraocular lens implantation: Current techniques,
complications and management. Intl Ophthalmol Clin
2001;41,175.
3. Cheng KP, Hiles DA, Biglan AW, Pettapiece MC. Visual
results after early surgical treatment of unilateral congenital
cataracts. Ophthalmology 1991;98:903.
4. France TD, Frank JW. The association of strabismus and
aphakia in children. J Pediatr Ophthalmol Strabismus
1984;21:223.
5. Gelbart SS, Hoyt CS, Jastrebeski G, Marg E. Long-term results
in bilateral congenital cataract. Am J Ophthalmol 1982;93:615.
6. Helveston EM. Infantile cataract surgery. Int Ophthalmol Clin
1977;17:75.
7. Nelson LB, Wagner RS. Pediatric cataract surgery. Int
Ophthalmol Clin 1994;34:165.
8. Nelson LB. Diagnosis and management of cataracts in infancy
and childhood. Ophthalmic Surg 1984;15:688.
9. Dahan E. Lens implantation in microphthalmic eyes of infants.
Eur J Implant Refract Surg 1989;1:9.
10. Dahan E, Salmenson BD, Levin J. Ciliary sulcus reconstruction
for posterior implantation in the absence of an intact posterior
capsule. Ophthalmic Surg 1989;20:776.
11. Davies PD, Tarbuck DT. Management of cataracts in infancy
and childhood. Trans Ophthalmol Soc UK 1977;97:148.
12. Drummond GT, Scott WE, Keech RV. Management of
monocular congenital cataract. Arch Ophthalmol 1989;107:45.
13. Gieser SC, Apple DJ, Loftfield K, et al. Phthisis bulbi after
intraocular lens implantation in a child. Can J Ophthalmol
1985;20:184..
14. Hing S, Speedwell L, Taylor D. Lens surgery in infancy and
childhood. Br J Ophthalmol 1990;74:73.
15. Keech RV, Toungue AC, Scott WE. Complications after
surgery for congenital and infantile cataracts. Am J
Ophthalmol 1989;108:136.
16. Menezo JL, Esteve JT, Perez-Torregrosa VT. IOL implantation
in children -17 years’ experience. Eur J implant Refract Surg
1994;6:251.
17. Menezo JL, Taboada JF, Ferrer E. Complications of intraocular
lenses in children. Trans Ophthalmol Soc UK 1985;104:546.
18. Wisniewska GM, Kaluzny J, Junk HL, Elicks I. Intraocular
lens implantation in children and youth. J Pediatr Ophthalmol
Strabismus 1999;36:129.
19. Wilson ME, Bluestein EC, Wang XH. Current trends in the
use of intraocular lenses in children. J Cataract Refract Surg
1994;20:579.
20. Dahan E, Salmenson BD. Pseudophakia in children:
precautions, techniques, and feasibility. J Cataract Refract
Surg 1990;16:75.
21. Vasavada A, Chauhan H. Intraocular lens implantation in
infants with congenital cataracts. J Cataract Refract Surg
1994;20:592.
22. Knight-Nanan D, O’Keefe M, Bowell R. Outcome and
complications of intraocular lenses in children with cataract.
J Cataract Refract Surg 1996;2:730.
23. Gordon RA, Donzis PB. Refractive development of the human
eye. Arch Ophthalmol 1985;103:785.
24. McClatchey SK, Dahan E, Maselli E, et al. A comparison of
the rate of refractive growth in pediatric aphakic and
pseudophakic eyes. Ophthalmology 2000;107:118.
25. McClatchey SK, Parks MM. Myopic shift after cataract
removal in childhood. J Pediatr Ophthalmol Strabismus
1997;34:88.
26. McClatchey SK, Parks MM. Theoretic refractive changes after
lens implantation in childhood. Ophthalmology 1997;
104:1744.
27. Plager DA, Lipsky SN, Snyder SK, et al. Capsular manage-
ment and refractive error in pediatric intraocular lenses.
Ophthalmology: 1997;104:600.
28. Bluestein EC, Wilson ME, Wang XH, et al. Dimensions of the
pediatric crystalline lens: Implications for intraocular lenses
in children. J Pediatr Ophthalmol Strabismus 1996;33:18.
29. Lambert SR, Buckley EG, Plager DA, et al. Unilateral
intraocular lens implantation during the first six months of
life. J Am Ass Pediatr Ophthalmol Strabismus 1999;3:344.
30. Hiles DA, Hered RW. Modern intraocular lens implants in
children with new age limitations. J Cataract Refract Surg
1987;13:493.
31. Hiles DA, Wallar PH. Visual results following infantile
cataract surgery. Int Ophthalmol Clin 1977;17:265.
32. Scheie HG. Aspiration of congenital or soft cataracts: A new
technique. Am J Ophthalmol 1960;50:1048.
33. Ridley H. Artificial intraocular lenses after cataract extraction.
St. Thomas’ Hospital Reports 1952;7(Series):12.
34. Choyce DP. Correction of uniocular aphakia by means of
anterior chamber acrylic implants. Trans Ophthalmol Soc UK
1958;78:459.
 Chapter 102: Management of Infantile-Pediatric Cataract
35. Binkhorst CD, Gobin MH, Leonard PA. Post-traumatic
artificial lens implants (pseudophakoi) in children. Br J
Ophthalmol 1969;53:518.
36. Binkhorst CD, Gobin MH, Leonard PA. Post-traumatic
pseudophakia in children. Ophthalmologica 1969;158
(Suppl):284.
37. Binkhorst CD, Gobin MH. Injuries to the eye with lens opacity
in young children. Ophthalmologica 1964;148:169.
38. Binkhorst CD, Greaves B, Kats A, Bermingham AK. Lens
injury in children treated with irido-capsular supported intra-
ocular lenses. J Am Intraocular Implant Soc 1978;4:34.
39. Binkhorst CD, Greaves B, Kats A, Bermingham AK. Lens
injury in children treated with irido-capsular supported intra-
ocular lenses. Doc Ophthalmol 1979;46:241.
40. Binkhorst CD. Iris-clip and irido-capsular implants
(pseudophakoi); personal techniques of pseudophakia. Br J
Ophthalmol 1967;51:767.
41. BenEzra D. Cataract surgery and intraocular lens implan-
tation in children. Am J Ophthalmol 1996;121:224.
42. BenEzra D, Cohen E, Rose L. Traumatic cataract in children:
Correction of aphakia by contact lens or intraocular lens. Am
J Ophthalmol 1997;123:773.
43. BenEzra D, Cohen E. Cataract surgery in children with chronic
uveitis. Ophthalmology 2000;107:1255.
44. BenEzra D, Cohen E. Posterior capsulectomy in pediatric
cataract surgery: The necessity of a choice. Ophthalmology
1997;104:2168.
45. BenEzra D, Paez JH. Congenital cataract and intraocular
lenses. Am J Ophthalmol 1983;96:311.
46. Parks MM. Posterior lens capsulectomy during primary
cataract surgery in children. Ophthalmology 1983;90:344.
47. Gimbel HV, Sun R, DeBrouff BM. Recognition and manage-
ment of internal wound gape. J Cataract Refract Surg
1995;21:121.
48. Basti S, Krishnamachary M, Gupta S. Results of sutureless
wound construction in children undergoing cataract
extraction. J Pediatr Ophthalmol Strabismus 1996;33:52.
49. Englert JA, Wilson ME. Postoperative intraocular pressure
elevation after the use of Healon GV in pediatric cataract
surgery. J Am Ass Pediatr Ophthalmol Strabismus 2000;4:60.
50. Gimbel HV, Neuhann T. Development, advantages, methods
of the continuous circular capsulorhexis technique. J Cataract
Refract Surg 1990;16:31.
51. Basti S, Greenwald MJ. Principle and paradigms of pediatric
cataract management. Indian J Ophthalmol 1995;43:159.
52. Kloti R. Anterior high frequency capsulotomy. Part I: experi-
mental study. Klin Monatsbl Augenheilkd 1992; 200:507.
53. Faust KJ. Hydrodissection of soft nuclei. J Am Intraocular
Implant Soc 1984;10:75.
54. Fine IH. Cortical cleaving hydrodissection. J Cataract Refract
Surg 1992;18:508.
55. Pandey SK, Ram J, Werner L, et al. Visual results and post-
operative complications of capsular bag versus ciliary sulcus
fixation of posterior chamber intraocular lenses for traumatic
cataract in children. J Cataract Refract Surg 1999;25:1576.
56. Sharma A, Basti S, Gupta S. Secondary capsule-supported
intraocular lens implantation in children. J Cataract Refract
Surg 1997;23:675.
805
57. Lam DS, Ng JS, Fant DS, et al. Short-term results of scleral
intraocular lens fixation in children. J Cataract Refract Surg
1998;24:1474.
58. Sharpe MR, Biglan AW, Gerontis CC. Scleral fixation of
posterior chamber intraocular lenses in children. Ophthalmic
Surg Lasers 1996;27:337.
59. Zetterstrom C, Lundvall A, Weeber H Jr, Jeeves M. Sulcus
fixation without capsular support in children. J Cataract
Refract Surg 1999;25:776.
60. Mackool RJ. Management of posterior capsule during
intraocular lens implantation. Am J Ophthalmol 1994;117:121.
61. Vasavada A, Desai J. Primary posterior capsulorhexis with
and without anterior vitrectomy in congenital cataracts. J
Cataract Refract Surg 1997;23 (Suppl):647.
62. Vasavada A, Trivedi R. Evaluation of optic capture along with
anterior vitrectomy in congenital cataracts. J Cataracts Refract
Surg 2000.
63. Gimbel HV, DeBroff DM. Posterior capsulorhexis with optic
capture: Maintaining a clear visual axis after pediatric cataract
surgery. J Cataract Refract Surg 1994;20:658.
64. Gimbel HV. Posterior capsulorhexis with optic capture in
pediatric cataract and intraocular lens surgery. Ophthal-
mology 1996;103:1871.
65. Gimbel HV. Posterior continuous curvilinear capsulorhexis
and optic capture of the intraocular lens to prevent secondary
opacification in pediatric cataract surgery. J Cataract Refract
Surg 1997;23 (Suppl):652.
66. Fenton S, O’Keefe M. Primary posterior capsulorhexis
without anterior vitrectomy in pediatric cataract. J Cataract
Refract Surg 1999;25:763.
67. Koch DD, Kohnen T. A retrospective comparison of
techniques to prevent secondary cataract formation following
posterior chamber intraocular lens implantation in infants
and children. Trans Am Ophthalmol Soc 1997; 95:351,
discussion 361.
68. Koch DD, Kohnen T. Retrospective comparison of techniques
to prevent secondary cataract formation following posterior
chamber intraocular lens implantation in infants and children.
J Cataract Refract Surg 1997;23 (Suppl):657.
69. Atkinson CS, Hiles DA. Treatment of secondary posterior
capsular membrane Nd:YAG laser in a pediatric population.
Am J Ophthalmol 1994;118:496.
70. Basti S, Ravishankar V, Gupta S. Results of a prospective
evaluation of three methods of management of pediatric
cataracts. Ophthalmology 1996;103:713.
71. Wang XH, Wilson ME, Bluestein EC, et al: Pediatric cataract
surgery and IOL implantation techniques: A laboratory study.
J Cataract Refract Surg 1994;20:607.
72. Pandey SK, Werner L, Escobar-Gomez M, et al. Dye-enhanced
cataract surgery. Part I. Anterior capsule staining for
capsulorhexis in advanced/white cataracts. J Cataract Refract
Surg 2000;26:1052.
73. Pandey SK, Werner L, Escobar-Gomez M, et al. Dye-enhanced
cataract surgery. Part III. Staining of the posterior capsule to
learn and perform posterior continuous curvilinear
capsulorhexis. Part III. J Cataract Refract Surg 2000;26:1066.
74. Werner L, Pandey SK, Escobar-Gomez M, Hoddinott DSM,
Apple DJ. Dye-enhanced cataract surgery. Part II. An
experimental study to learn and perform critical steps of
806 Section 7: Pediatric Ophthalmology Including Strabismus
phacoemulsification in human eyes obtained postmortem. J
Cataract Refract Surg 2000;26:1060.
75. Gupta AK, Grover AK, Gurha N. Traumatic cataract surgery
with intraocular lens implantation in children. J Pediatr
Ophthalmol Strabismus 1992;29:73.
76. Ram J, Pandey SK, Jain A, Gupta A. Intraocular lens
implantation in infantile cataract, In Pasricha JK (Ed): Indian
Ophthalmology: Year book, New Delhi, India, Aravali
Publishers 1998;123.
77. Ram J, Pandey SK, Jain AK, Gupta A. Visual results and
postoperative complications of PC-IOL implantation in
children, In Pasricha JK (Ed), Indian Ophthalmology: Year
book, New Delhi, India, Aravali Publishers 1998;132.
78. Brady KM, Atkinson CS, Kilty LA, et al. Cataract surgery and
intraocular lens implantation in children. Am J Ophthalmol
1995;120:1.
79. Mullaney PB, Wheeler DT, al-Nahdi T. Dissolution of
pseudophakic fibrinous exudate with intraocular strepto-
kinase. Eye 1996;10:362.
80. Klais CM, Hattenbach LO, Steinkamp GW, et al. Intraocular
recombinant tissue-plasminogen activator fibrinolysis of
fibrin formation after cataract surgery in children. J Cataract
Refract Surg 1999;25:357.
81. Rozenman Y, Folberg R, Nelson LB, Cohen EJ. Painful bullous
keratopathy following pediatric cataract surgery with
intraocular lens implantation. Ophthalmic Surg 1985;16:372.
82. Baker JD. Visual rehabilitation of aphakic children. Surv
Ophthalmol 1990;34:366.
83. Hiles DA, Biglan AW, Fetherolf EC. Central corneal endo-
thelial cell counts in children. J Am Intraocular Implant Soc
1979;5:292.
84. Wheeler DT, Stagger DR, Weakley DR, Jr. Endophthalmitis
following pediatric intraocular surgery for congenital
cataracts and congenital glaucoma. J Pediatr Ophthalmol
Strabismus 1992;29:139.
85. Jameson NA, Good WV, Hoyt CS. Inflammation after cataract
surgery in children. Ophthalmic Surg 1992;23:99.
86. Wheeler DT, Mullaney PB, Awad A, et al. Pediatric IOL
implantation. The KKESH experience. J Pediatr Ophthalmol
Strabismus 1997;34:341.
87. Apple DJ, Solomon KD, Tetz MR, et al. Posterior capsule
opacification. Surv Ophthalmol 1992;37:73.
88. Kugelberg U. Visual acuity following treatment of bilateral
congenital cataracts. Doc Ophthalmol 1992;82:211.
89. Morgan KS, Karcioglu ZA. Secondary cataracts in infants after
lensectomies. J Pediatr Ophthalmol Strabismus 1987;24:45.
90. Parks MM, Johnson DA, Reed GW. Long-term visual results
and complications in children with aphakia: A function of
cataract type. Ophthalmology 1993;100:826.
91. Zetterström C, Kugelberg. Bilateral blinding uveitis in a child
after secondary U, Lundgren B, Syren-Nordqvist S: After
cataract formation in the newborn rabbits implanted with
intraocular lenses. J Cataract Refract Surg 1996;22:85.
92. Menezo JL, Taboada JF, Ferrer E. Managing dense retro-
pseudosphakos membranes with a pars plana vitrectomy. J
Am Intraocular Implant Soc 1985;11:24.
93. Bustos FR, Zepeda LC, Cota DM. Intraocular lens implan-
tation in children with traumatic cataract. Ann Ophthalmol
1996;28:153.
94. Assaf AA, Wiggins R, Engle K, et al. Compliance with pres-
cribed optical correction in cases of monocular aphakia in
children. Saudi J Ophthalmol 1994;8:15.
95. Asrani SG, Wilensky JT. Glaucoma after congenital cataract
surgery. Ophthalmology 1995;102:863.
96. Brady KM, Atkinson CS, Kilty LA, Hiles DA. Glaucoma after
cataract extraction and posterior chamber lens implantation
in children. J Cataract Refract Surg 1997;23 (Suppl):669.
97. Chrousos GA, Parks MM, O’Neill JF. Incidence of chronic
glaucoma, retinal detachment and secondary membrane
surgery in pediatric aphakic patients. Ophthalmology
1984;91:1238.
98. Egbert JE, Kushner BJ. Excessive lodd of hyperopia: Presen-
ting sign of juvenile aphakic glaucoma. Arch Ophthalmol
1990;108:1257.
99. Simon JW, Metge P, Simmons ST, et al. Glaucoma after
pediatric lensectomy/vitrectomy. Ophthalmology 1991;
98:670.
100. Walton DS. Pediatric aphakic glaucoma: A study of 65
patients. Trans Am Ophthalmol Soc 1995;93:403.
101. Vajpayee RB, Angra SK, Titiyal JS, et al. Pseudophakic
pupillary block glaucoma in children. Am J Ophthalmol
1991;11:715.
102. Phelps CD, Arafat NI. Open-angle glaucoma following
surgery for congenital cataracts. Arch Ophthalmol 1977;
95:1985.
103. Pinchoff BS, Ellis FD, Helveston EM, Sato SE. Cystoid macular
edema in pediatric aphakia. J Pediatr Ophthalmol Strabismus
1988;25:240.
104. Gilbard SM, Peyman GA, Goldberg MF. Evaluation for
cystoid maculopathy after pars plicata lensectomy-vitrectomy
for congenital cataracts. Ophthalmology 1983;90:1201.
105. Mets MB, Del Monte M. Hemorrhagic retinopathy following
uncomplicated pediatric cataract extraction. Arch Ophthal-
mol 1986;104:975.
106. Christiansen SP, Munoz M, Capo H. Retinal hemorrhage
following lensectomy and anterior vitrectomy in children. J
Pediatr Ophthalmol Strabismus 1993;30:24.
107. Birch EE, Stager DR. Prevalence of good visual acuity
following surgery for congenital unilateral cataract. Arch
Ophthalmol 1988;106:40.
108. Birch EE, Stager DR. The critical period for surgical treatment
of dense, congenital, unilateral cataracts. Invest Ophthalmol
Vis Sci 1996;37:1532.
109. Birch EE, Swanson WH, Stager DR, et al. Outcome after very
early treatment of dense congenital unilateral cataract. Invest
Ophthalmol Vis Sci 1993;34:3687.
110. Burke JP, Willshaw HE, Young JD. Intraocular lens implants
for uniocular cataracts in childhood. Br J Ophthalmol
1989;73:860.
111. Catalano RA, Simon JW, Jenkins PL, Kandel GL. Preferential
looking as a guide for amblyopia therapy in monocular infan-
tile cataracts. J Pediatr Ophthalmol Strabismus 1987;24:56.
112. Eckstein M, Vijayalakshmi P, Killedar M, et al. Aetiology of
childhood cataract in south India. Br J Ophthalmol 1996;
80:628.
 Chapter 102: Management of Infantile-Pediatric Cataract
113. Huber C. Increasing myopia in children with intraocular
lenses: An experiment in form deprivation myopia? Eur J
Implant Ref Surg 1993;5:154.
114. Hutchinson AK, Drews-Botsch C, Lambert SR. Myopic shift
after intraocular lens implantation during childhood.
Ophthalmology 1997;104:1752.
115. Wilson ME, Peterseim MW, Englert JA, et al. Pseudophakia
and polypseudophakia in the first year of life. J Am Ass
Pediatr Ophthalmol Strabismus 2001.
116. Lloyd IC, Dowler JG, Kriss A, et al. Modulation of amblyopia
therapy following early surgery for unilateral congenital
cataracts. Br J Ophthalmol 1995;79:802.
807
117. Neumann D, Weissman BA, Isenberg SJ, et al. The effective-
ness of daily wear contact lenses for the correction of infantile
aphakia. Arch Ophthalmol 1993;111:927.
118. Griener ED, Dahan E, Lambert SR. Effect of age at time of
cataract surgery on subsequent axial length growth in infant
eyes. J Cataract Refract Surg 1999;25:1209.
119. Keech RV, Mutschke PJ. Upper age limit for the development
of amblyopia. J Pediatr Ophthalmol Strabismus 1995;32:89.
120. Taylor D. Monocular infantile cataract, intraocular lenses and
amblyopia (Editorial). Br J Ophthalmol 1989;73:857.
121. Taylor D. The Doyne Lecture Congenital Cataract: The
history, the nature, and the practice. Eye 1998;12:9.
122. Tytla ME, Lewis TL, Maurer D, Brent HP. Stereopsis after
congenital cataract. Invest Ophthalmol Vis Sci 1993;34:1767.
123. Verma A, Singh D. Active vision therapy for pseudophakic
amblyopia. J Cataract Refract Surgery 1997;23:1089.
 Chapter 103
Lens Subluxation and
its Management
Kasturi Bhattacharjee, Harsha Bhattacharjee, Pankaj Bhattacharyya
Ectopia lentis is defined as displacement or mal-
position of the crystalline lens of the eye. The first
description of the dislocated lens was made in 1749
by Berryat.1 But the term “Ectopia lentis” has been
introduced by Stellwag in 1856.2 When the crystalline
lens lies completely outside the patellar fossa it is
referred as dislocation or luxation of lens whereas
subluxation denotes the condition when the lens is
partially displaced but contained within the lens space.
ETIOPATHOGENESIS
Degree of zonular disruption or dysfunction, regard-
less of the cause, determines whether the lens is
subluxated or luxated; with the latter, the entire lens
may be in the anterior chamber (anterior luxation) or
may fall posteriorly into the vitreous cavity (posterior
Fig. 103.1: Superonasal lens subluxation
luxation). Subluxated lens may be tilted or displaced
slightly in anterior or posterior direction.
Clinical consequences of ectopia lentis are related
to the position or location of the lens (Figs 103.1 to
103.3). Anteriorly dislocated lens may lead to
secondary (pupillary) block glaucoma which could be
painful and potentially blinding. Corneal endothelial
damage and decompensation may follow an anteriorly
luxated lens-corneal touch. Cataract and phacolytic
uveitis are other sequelae of a luxated lens. Retinal
detachment is commoner in patients with heritable
ectopia lentis as in Marfan’s syndrome with homocys-
tinuria in about 10% of cases.
Children with heritable ectopia lentis may have a
high incidence of amblyopia and strabismus due to
early visual disturbances usually anisometropia.
Fig. 103.2: Inferonasal lens subluxation
 Chapter 103: Lens Subluxation and its Management 809

Fig. 103.3: Superior lens subluxation

Lens displacement can be best studied by classi-

fying the condition into heritable, acquired and Fig. 103.4: A family of Marfan’s syndrome
traumatic.
aneurysms. Mental retardation is not seen in Marfan’s
HERITABLE ECTOPIA LENTIS syndrome.
Ectopia lentis is seen in almost two third of cases
The heritable form of lens dislocation can be under
with Marfan’s syndrome. It is nearly always bilateral
two broad groups—(a) larger group of those asso-
and symmetric, usually superior and temporal,
ciated with other systemic and ocular anomalies, and
although variations are not infrequent (Fig.103.5).
(b) a smaller section presenting as lens dislocations
Zonular attachments are intact but stretched. At the
without any systemic anomalies.
same time, the zonules are strong and resist lysis in
HERITABLE ECTOPIA LENTIS ASSOCIATED the displaced area. Presentation is by the age of 5 years
WITH SYSTEMIC ANOMALIES in 50% of patients. The extent of dislocation remains
stable from early childhood. Progression is very rare.
Marfan’s Syndrome Maumenee has reported progression of lens displace-
Described by Marfan in 1896, this syndrome is ment in only 7.5% of 193 Marfanian eyes.4 She has also
characterized by a triad of skeletal, cardiovascular and
ocular anomalies. This condition has an autosomal
dominant heredity with variable expressivity, without
any racial or ethnic predilection3 (Fig.103.4).
However, about 15% of the cases present with no
family history and are believed to arise from new
mutations, 3 significantly attributed to increased
parental age. The exact molecular mechanism remains
unknown but faulty formation of collagen as well as
abnormality in fibrillin has been implicated.
The skeletal abnormalities comprise of thin and
elongated limbs, arachnodactyly present at birth, low
ratio between upper and lower segments of the body,
sternal abnormalities and kyphoscoliosis. There is
underdevelopment of the muscles predisposing to
hernias.
The cardiovascular abnormalities include atrial
dilatation, mitral regurgitation and dissecting Fig. 103.5: Ectopia lentis in Marfan’s syndrome
810 Section 7: Pediatric Ophthalmology Including Strabismus
identified increased axial length as a determinant
factor of lens displacement and retinal detachment in
Marfan’s syndrome.
The iris dilator muscle hypoplasia results in miotic
pupils with poor response to mydriatics. The patients
may be with high contribution from the lenticular and
axial components.5 Gonioscopy may reveal pectinate
ligaments, dense iris processes, peripheral mounds of
iris tissue and a broad trabecular meshwork.1
The patients present with variable degrees of
optical problems and refractive errors. Amblyopia
may ensue due to delayed and inadequate refractive
correction and may even be bilateral. Spectacle and
contact lens correction is satisfactory though some
cases may require lens extraction. Children may rarely
present with open angle glaucoma. Pupillary block
and angle closure glaucomas are reported with
luxation of the lens into anterior chamber. Retinal
detachment has also been reported.
Homocystinuria
This is an autosomal recessive disorder involving an
inborn error of metabolism of sulphur containing
amino acids—most importantly methionine and
characterized by excessive urinary excretion of
homocystine. There is deficiency of the enzyme cysta-
thione synthetase. Zonular fibers of the lens normally
have a high concentration of cystine. Deficiency of
cysteine in homocystinuria causes the zonules to be
brittle. Like Marfan’s, this condition also presents with
skeletal, cardiovascular and ocular abnormalities—but
with certain marked differences.
Skeletal abnormalities like arachnodactyly are
usually less marked than in Marfan’s syndrome. Most
patients are tall with an abnormal upper to lower
segment ratio. There is a high incidence of generalized
osteoporosis along with knock-knee, kyphoscoliosis,
and high arched palate.
Skin abnormalities include a characteristic malar
flush, a dry and fair skin,though not very evident in
the Asian skin colours, along with sparse hair.
Cardiovascular abnormalities are more marked
and often present dramatically. Blood coagulation
disorders and increased platelet stickiness are
responsible for thrombo-embolic phenomena occur-
ring in almost 50% of the cases. Myocardial infarction,
cerebrovascular accidents and pulmonary embolism,
all have propensity to occur at a relatively younger
age and may be potentially fatal in 40% of cases.
Surgery and general anesthesia predispose to
thromboembolism—a fact to be borne in mind by the
ophthalmic surgeon.
In contrast to Marfan’s syndrome, mental retar-
dation is seen almost in 50% of the patients with
homocystinuria and it tends to be progressive.
Ocular anomalies like lens dislocation, occurring
in almost 90% of cases, tends to be bilateral and
symmetric — usually inferior (Fig. 103.1) and nasal
(Fig. 103.2). It appears in infancy in about 30% and in
80% by 15 years of age. The lens is much more mobile
in this condition and thus progression is frequently
seen. In one series,1 almost 33% lenses in homocysti-
nuria progressed to total displacement into the
anterior chamber or vitreous. There is also a higher
incidence of associated complications seen in the form
of pupillary block glaucoma and retinal detachment.
Gonioscopic abnormalities are not seen.
The diagnosis of homocystinuria can be supported
by a positive brand reaction in urine. Cyanidenitro-
prusside test is used for the qualitative determination
of cystine in urine. Cystine is reduced to cysteine by
sodium cyanide and the free sulphydryl groups react
with nitroprusside to produce a red purple color.
Dietary titrations by reducing methionine content and
increasing cysteine may be beneficial in early cases.
Weill-Marchesani Syndrome
This condition has been attributed to both dominant
and recessive heredity in various reports. The
condition is a type of mesodermal dystrophy.
However, the presentation is a striking antithesis of
its counterparts—Marfan’s syndrome and homo-
cystinuria. The individual is short statured with spade-
like hands and feet, a condition referred to as
brachydactyly. There is overall brachymorphy with
large thoraces and stiff joints. Vascular, mental or
urinary abnormalities are not seen.
The characteristic ocular feature of microsphero-
phakia is considered a must for the diagnosis, so much
so that Weill-Marchesani syndrome is also referred to
as spherophakia. Ectopia lentis is seen in about 50%
of the cases and occurs later in life, usually in the early
twenties. Angle anomalies and retinal detachment has
also been reported in some studies.6
Hyperlysinemia
This is a rare, recessively transmitted lysine meta-
bolism disorder due to deficiency of the enzyme lysine
alpha ketoglutarate reductase. Affected individuals
 Chapter 103: Lens Subluxation and its Management
show mental retardation, muscular hypotony and lax
ligaments. Ocular features include microspherophakia
associated with ectopia lentis in some cases.
Sulfite Oxidase Deficiency
This is a very rare autosomal recessive disorder of
sulfur metabolism. Ectopia lentis is associated with
progressive muscular rigidity and severe mental
retardation. Affected individuals usually succumb by
the age of 5 years.
Ehlers-Danlos Syndrome
The condition, described separately by Ehlers and
Danlos, involves the integument, skeleton,viscera and
eye. Ocular manifestations predominate in two of the
seven phenotypes, described as ‘Ocular Ehlers Danlos
Syndrome’ (Fragilitas oculi). Scleral thinning, kerato-
conus, dislocated lens with micro and megalocornea,
strabismus, angioid streaks and retinal detachment
have been documented. Hyperstretchability of the
skin, hyperextensibility of the joints, hiatus hernia,
gastrointestinal tract diverticuli and cardiac valvular
defects are other associations.
Sturge-Weber Syndrome
This Dermato-oculo-neural syndrome described by
Sturge (1879) and Weber (1922) consists of facial nevus
flammeus, ipsilateral cavernous hemangioma of the
choroid, glaucoma, subluxated lens and meningial
hemangiomatosis.
Ectopia lentis has also been rarely reported in
Cruozon’s syndrome, Mandibulofacial dysostosis,
Refsum’s syndrome, Kniest syndrome, Conradi syn-
drome, Pierre-Robin syndrome and Wildervanck
syndrome.
Ectopia lentis has also been reported in the
following conditions:
Crouzon’s Syndrome
Congenital defects of the cranium (brachycephaly or
oxycephaly) are combined with characteristic facial
deformity of the face due to maxillary hypoplasia.
Mandibulofacial Dysostosis
This is also known as Treacher-Collins syndrome and
is characterized by hypoplastic or absent malar bones
and poorly developed zygomatic arches. These
patients have marked downward slant of the
811
palpebral fissures along with lid coloboma , depressed
cheekbones, deformed ears, large mouth and receding
chin.
Refsum’s Syndrome
A rare autosomal, recessively inherited syndrome
characterized by atypical pigmentary retinopathy
associated with night blindness, peripheral neuro-
pathy, and cerebellar ataxia. There are also reports of
posterior cortical lens opacities.
Conradi Syndrome
Both autosomal dominant and recessive inheritance
have been reported in the pathogenesis of this
condition characterized by congenital cataract,
mongoloid slant and infrequently, optic atrophy.
Extraocular manifestation is in the form of skeletal
deformities mainly involving cartilage.
Pierre Robin Syndrome
It is characterized by cleft palate, small mandible and
backward displacement of the tongue. Ophthalmic
manifestations include high myopia, cataracts,
strabismus and retinal detachment.
Wildervanck Syndrome
Also referred to as cervico-ocular-acoustic dysmor-
phia, this condition is comprised of Duane syndrome,
hearing loss and a deformity of the cervical spine
called Klippel-Feil anomaly. However, there may be
cases presenting without the complete triad.
Aniridia
A defect in the PAX 6 gene on chromosome 11 is the
cause of aniridia. It is a panocular, bilateral disorder.
Isolated aniridia may sometimes be complicated by
ectopia lentis (Fig. 103.6).
Heritable Ectopia Lentis Not Associated With clinically
detectable Systemic Anomalies.
Isolated Ectopia Lentis
It is rare and occurs early in life. There is bilaterally
symmetrical upward and temporal ectopia lentis. The
condition is accredited with an autosomal dominant
heredity (Fig. 103.7).
812 Section 7: Pediatric Ophthalmology Including Strabismus
Fig. 103.6: Ectopia lentis in aniridia
Fig. 103.7: Isolated ectopia lentis
Ectopia lentis et Pupillae
Also referred to as Familial Ectopia Lentis, this
autosomal recessive disorder is characterized by a
pathological association between the lens and the
pupil. The condition has often been reported as
bilateral and symmetrical 2 though asymmetrical
involvement is not infrequent7. Here both the pupils
and the lenses are ectopic with the pupillary displace-
ment in the direction opposite to that of the lens.
Cataract formation, glaucoma, severe axial myopia,
retinal detachment and abnormal iris transillu-
mination defects have been reported as associated
features.7
ACQUIRED ECTOPIA LENTIS
It is found to be frequently associated with or caused
by certain ocular conditions such as
• High myopia
• Pseudoexfoliation
• Perforation of a corneal ulcer
• Buphthalmos
• Coloboma of iris and choroids
• Long standing subacute endophthalmitis
• Mechanical effect of an intraocular growth
• Hypermature cataract
• Megalocornea
• Retinitis pigmentosa
• Syphillis/chronic uveitis
• Spontaneous lens dislocation- It is seen in elderly
individuals where progressive age related weake-
ning of the zonules first causes a tilting and is
gradually followed by complete dislocation of the
lens into the vitreous and rarely into the anterior
chamber (Fig.103.8).
TRAUMATIC ECTOPIA LENTIS
Trauma remains the predominant cause of acquired
lens subluxation/luxation, with an incidence varying
from 22-50%.8,9 Traumatic ectopia lentis, thus not only
deserves a mention as a distinct etiological entity in
lens subluxation but also merits a separate discussion.
A direct impact by a blunt object causes a dispro-
portionate lateral elongation of the globe resulting in
stretching and complete or partial snapping of the
zonules (Fig. 103.9).
A blow to the eye usually causes a subluxation. A
subluxated lens in the pupillary area gives rise to
optical discomfort of varying extent. A greater sub-
luxation makes the pupillary area partly phakic and
partly aphakic. The patient presents with monocular
diplopia and glare due to the gross disparity in the
refraction through the two zones in the pupil. A severe
injury involving rupture of the zonules may cause
displacement of the lens into the vitreous or anterior
chamber. Rarely, however, the lens may float on the
Fig. 103.8: Spontaneous dislocation of lens
into anterior chamber
 Chapter 103: Lens Subluxation and its Management
Fig.103.9: Traumatic lens subluxation
with rosette cataract
vitreous surface with vitreous herniation and irido-
donesis. Dislocated lens has been traced beneath the
retina and also subconjunctivally when the injury has
caused total rupture of the zonules.
Management of Ectopia Lentis
A detailed ocular examination should be conducted
in all cases of ectopia lentis. The most important being
assessment of visual function as ectopia lentis is a
potentially vision threatening condition. Visual acuity
varies with the degree and location of malposition of
the lens. The other ocular examination includes
evaluation of globe symmetry (e.g. strabismus,
secondary to amblyopia, enophthalmos seen in
Marfan’s syndrome), measurement of corneal
diameter (e.g. megalocornea associated with Marfan’s
syndrome), measurement of intraocular pressure,
refraction, slit lamp examination, funduscopy (retinal
detachment is a serious consequence of dislocated
lens) and echography (increased axial length found
in Marfan’s syndrome). Slit lamp examination should
be conducted initially in non-dilated pupil.10 In this
way phacodonesis, iridodonesis and increased
anterior chamber depth are more apparent. However
the extent of zonular dialysis and direction of lens
displacement are more clearly evident in dilated pupil.
Other signs usually associated with traumatic lens
subluxation are hyphema, iris sphincter lesion,
areflexic mydriasis, angle recession and herniation of
vitreous into the anterior chamber. All these are the
813
direct signs of lens subluxation, which can be
evaluated preoperatively. However, appearance of
radial folds on anterior capsule during initiation of
capsulotomy or capsulorhexis, irregular anterior
chamber depth and iridic flutter resulting from
inverted fluid infusion into vitreous body through the
area of zonular dehiscence are some of the indirect
signs of lens subluxation and are apparent intra-
operatively.
Ectopia lentis continues to be a therapeutic
challenge for ophthalmologists. The rational approach
would be to regard the eyes as sick and priority set
towards preservation of the globe and vision. As the
clinical presentation of ectopia lentis is varied, each
situation warrants a carefully analyzed management
undertaken with the rational goal in mind. Early
diagnosis and treatment of ectopia lentis in childhood
is important. Amblyopia is considered as the most
common cause of decreased vision in ectopia lentis.
Amblyopia may be prevented or minimized by
appropriate refractive correction through the phakic
or aphakic part of the pupil. If the edge of the
subluxated lens bisects the pupil, then theoretically
the phakic portion of the lens could be used for near
and the aphakic portion for distant vision.
Alternatively, the pupillary size can be altered to
achieve optical correction. Use of miotics improves the
vision with the stenopic effect and eliminates visual
aberrations. The pupil large size may be altered by
mydriatics, laser therapy or surgery to secure aphakic
refractive correction.11 Newer surgical procedures
have been tried to displace the lens from the visual
axis by using YAG laser on residual zonular fibres.12,13
These different nonsurgical procedures should be tried
first, especially in patients with systemic disorders like
homocystinuria who are at increased risk with general
anesthesia.14
In the past, surgical treatment of ectopia lentis has
been associated with high rate of complications and
poor visual outcome. Lens surgery is indicated in cases
with ectopia into the anterior chamber with corneal
touch, alteration of visual function, associated cataract,
lens-induced uveitis and recurring lens subluxation.
Surgical interventions have been associated with high
incidence of vitreous loss and retinal detachment
ranging from 11-30%.15,16 Different surgical techniques
like discission, aspiration, intracapsular removal and
inadvertent extracapsular removal have been descri-
bed with surgical complication rate upto 51% in
treating dislocated lens.15
814 Section 7: Pediatric Ophthalmology Including Strabismus

The introduction of automated vitrectomy has

resulted in manifold improvement in surgical
outcomes. Peyman et al in 197917 and Seetner and
Crawford in 198118 first reported the management of
ectopia lentis by pars plana lensectomy, demons-
trating good results and fewer complications. Though
the introduction of pars plana and limbal lensectomy
has improved the functional and anatomical prognosis
of these patients, the need to correct aphakia using
contact lenses was inevitable.
The advent of sophisticated surgical accessories
and advancement in surgical technologies have
brought important changes and predictable outcomes
of cataract surgery in the subluxated lens. The
Fig. 103.10: The standard ECR
introduction of the ‘Capsular Tension Ring’ (CTR) has
revolutionized the management of zonular dialysis.
In 1991 Hara et al introduced the concept of the the modified CTR, (MCTR),30 designed by Robert
‘Equator Ring’, ‘Endocapsular Ring’ (ECR) or Cionni may be used. Here the CTR is incorporated
‘Capsular Tension Ring’ to prevent capsular bag with fixation hook with an eyelet at the free end to
contraction. 19 They used flexible silicone rods provide scleral fixation without violating the integrity
designed on its undersurface with a groove. A of the capsular bag. Currently, there are three designs
posterior chamber IOL is inserted in the bag with the of modified CTR: Model 1-L has a single fixation hook,
IOL loops in the grooves. The capsular tension ring away from the insertion end of the ring (Fig. 103.11);
presses on the equatorial cells of the lens and prevents Model 2-C has the single fixation hook near the
their migration and proliferation. Many surgeons such insertion end of the ring (Fig. 103.12); Model 2-L has
as Liger et al,21 Cionni and Osher22, Colen23, Gimbel24, two fixation hooks and is very useful in patients with
Fine and Hoffman,25 Orbigozo,26 Tokudo,27 have made very significant zonular weakness (Fig. 103.13).
extensive study on CTR and used it for the manage-
ment of subluxated lenses. Surgical Technique
The advantages of CTR are manifold. It maintains
the circular contour of the bag despite zonular The CTR can be inserted into the capsular bag at any
dehiscence, prevents IOL decentration and also retards point after the capsulorhexis has been completed. The
the migration and proliferation of the lens equatorial rhexis must be started at the point where the zonules
cells, thereby preventing the capsular contraction
syndrome.
The CTRs are available in diameters of 12.5 to 14.5,
compressible to 10 mm or less. The size of the CTR is
estimated by measuring the corneal white-to-white
distance. Animal studies using the Miyaki technique
of observation proved that the size of the CTR is
important in preserving the shape of the capsular
opening and the bag.28
Though there are different designs, dimensions and
materials of CTR29, the standard CTR is made of
PMMA and designed as open loop with eyelets at
either end in order to aid manipulation (Fig. 103.10).
There are some situations where the standard CTR
cannot provide centering of the capsular bag. In such
situations of extensive zonular dehiscence, the use of Fig.103.11: MCTR model 1-L
 Chapter 103: Lens Subluxation and its Management 815
aspiration of the cortex or just before the IOL is
implanted. If introduced prior to phacoemulsification,
a safety suture can be looped through the leading
eyelet, such that if posterior capsular tear occurs, the
suture and the CTR can be retrieved. If the procedure
is uneventful, the suture is simply cut and removed.
During phacoemulsification and cortical clean up,
all the main parameters, i.e. ultrasound power, aspi-
ration flow rate, vacuum and infusion must be kept
extremely low. The irrigation and aspiration of the
cortex to be done gently and carefully safeguarding
the integrity of the zonules and the capsule. If the CTR
is trapped between the anterior and posterior cortex,
the aspiration of the cortex to be done in a tangential
manner starting from the equator.
Fig.103.12: MCTR model 2-C With moderate loss of zonular support, the conven-
tional CTR is very helpful. But in cases of profound
zonular dehiscence, adequate stabilization is difficult

A B

Fig.103.13: MCTR model 2-L

are intact, to minimize the traction. Rhexis is to be

followed by hydrodissection, preferably cortical C D
cleaving hydrodissection. If the rhexis is not conti-
nuous, the risk of tearing into the posterior capsule is
quite high.
Before introducing the CTR into the capsular bag,
a cohesive viscoelastic must be injected just below the
residual capsular ring to create a path for the CTR to
be inserted. The viscoelastic agent separates the cortex
away from the peripheral capsule, decreasing the E
chances of cortical entrapment. The CTR can be
introduced with smooth forceps through the main Figs 103.14A to E: Surgical technique of phacoemulsification
in subluxated lens: (A) Subluxated lens in the superotemporal
incision or through a side port corneal stab incision.
quadrant, (B) Corneal tunnel, (C) Cortical cleaving hydro-
A more controlled insertion can be achieved by using procedure and hydrodelineation, (D) Phacoemulsification—stop
a special injector called the Geuder Shooter. The and chop technique after ECR insertion, (E) Photoslit lamp
introduction of the CTR can be timed before phaco documentation—postoperative IOL centration in subluxated
(Figs 103.14A to E), during phaco, during the lens
816 Section 7: Pediatric Ophthalmology Including Strabismus

to achieve. To manage a situation with significant
zonular dehiscence, several surgeons have devised
different techniques of suturing the CTR to the scleral
wall. Use of MCTR, as described before, transscleral
suturing of the CTR provides adequate expansion of
the capsular bag and excellent centration of the IOL
(Figs 103.15A to D).
Another reported technique for the management
of lens subluxation in the case of non-availability of
CTR, or torn capsulorhexis, is to make two relaxing
incisions on the anterior capsule in the inferonasal and
inferotemporal quadrants. This creates a flap, which
is flipped over the area of lost zonules and sutured to
the scleral wall. However, the IOL needs to be placed
in the sulcus, which may jeopardize the long-term
stability of the IOL.
Thus, the management of subluxated lens with the
use of CTR during phacoemulsification is a safe
surgical procedure. It enhances intraoperative safety
and decreases vitreoretinal complications. Moreover,
it maintains the stability of the capsular bag and
prevents IOL decentration, providing good post-
operative visual rehabilitation.
In young children, regular assessment of ectopia
lentis with a prompt surgical intervention in cases with
significant uncorrectable optical error is of paramount
importance to prevent amblyopia.
REFERENCES
1. Cross HE. Ectopia lentis in systemic hereditable disorders.
Birth Defects 1974;10:113.

Figs 103.15A to D: Surgical technique of phacoemulsification in subluxated lens with the use of the Cionni ECR. (A) Subluxated
lens in Marfan’s syndrome. (B) Unexpanded capsular bag at the end of phaco procedures.(C)Insertion of Cionni ring. (D) Expansion
of the capsular bag following trans scleral suturing of the capsular ring
 Chapter 103: Lens Subluxation and its Management
2. Marfan AB. Un cas de deformation congenitale desquatyre
members, plus pronocee aux extremities, caracterisee par
Pallongement des os avec un certain degree d’amincessement,
Bull Soc Med Hop Paris 1986;13:220.
3. Pyerite RE, Mckusick VA. The Marfan’s syndrome: Diagnosis
and management. N Engl J Med 1979;300:772.
4. Maumenee IH. The eye in the Marfan’s syndrome. Trans Am
Ophthalmol Soc 1981;79:684.
5. Allen RA. Ocular manifestation of the Marfan’s syndrome.
Trans Am Acad Ophthalmol & Otolaryngol 1967;71:18.
6. Kanski J. Clinical Ophthalmology: A Systematic Approach,
Butterworth Heinemann. (4th edn), 1999;180.
7. Basic and clinical Science Course, American Academy of
Ophthalmology, Section 2001-2002;11:37.
8. Nirankari MS, Chaddah R. Displaced lens. Am J Ophthalmol
1967;63:1719.
9. Jaffe NS, Jaffe MS, Jafe GF. Cataract Surgery and its Complica-
tions. St. Louis, CV Mosby 1990;303.
10. Jofe M. Detection of lens subluxation in pseudoexfoliation.
Arch. Ophthalmol 1998;106:1032, (letter).
11. Whiting M. Congenital dislocation of the lens, Br J
Ophthalmol 1963;47;54.
12. Rosen PH, Dart JK, Turner GS. Neodymium YAG laser
zonulotomy. Arch Ophthalmol 1987;105:892.
13. Tchah H, Larson RS, Nichol BD et al. Neodymium YAG laser
zonulodialysis for treatment of lens subluxation: Ophthal-
mology 1989;96;230.
14. Nelson LB, Maumenee IH. Ectopia Lentis, Surv Ophthalmol
1982;27:14.
15. Tarrett W H. Dislocation of lens— a study of 166 hospitalized
cases, Arch. Ophthalmol 1967;78:289.
16. Cross HE, Jensen AD. Ocular manifestations in the Marfan’s
syndrome and homocystinuria. Am J Ophthlmol 1973;75:405.
17. Peymen GA, Raichand M, Goldberg MF, Ritacca D.
Management of subluxated and dislocated lenses with
vitriophage. Br. J Ophthalmol 1979;63:771.
18. Seetner AA, Crawford JS. Surgical correction of lens
dislocation in children. Am. J. Ophthalmol 1981;91:106.
19. Hara T,Hara T, Yamada Y. “Equatorial Ring” for main-
tainence of the completely circular contour of the capsular
817
bag equator after cataract removal. Ophthalmic Surg
1991;22:358.
20. Hara T. Equator ring to obtain complete circular contour of
the capsular bag equator and to prevent postoperative
posterior capsular opacification. Proc 3rd American
International congress on cataract, IOL and Refractive
Surgery, Seattle 1993.
21. Orbegozo J, Mendicute J, Salz A. Phacoemulsification and
management of the subluxated crystalline lens: Chapter
22,174; Phacoemulsification, Laser Cataract and foldable
IOL’s. Fine H, Agarwal A et al. First edition 1998: Jaypee
Brothers Medical Publishers (P) Ltd: India
22. Cionni RJ, Osher RH. Endocapsular ring approach to the
subluxated cataractous lens. J Cataract Refract Surg
1995;21:245.
23. Colin J. Endocapsular PMMA rings may help prevent some
complications in cataract surgery. Ocular Surgery News
1995;6:17.
24. Gimbel HV, Sun R, Heston JP. Management of zonular
dialysis in phacoemulsification and IOL implantation using
the capsular ring. Ophthalmic Surg Lasers 1997;28:273.
25. Fine J, Hoffman RS. Phacoemulsification in the presence of
pseudo exfoliation –challenges and options. J Cataract Refract
Surg 1997;23:160.
26. Orbegozo J, Araurhrri J, Saiz A. One option for coping with a
subluxated cataract. Ocular Surgery News 1997;8:12.
27. Tokuda Y. In the bag IOL suture fixation represents a new
approach to zonular dehiscence. Ocular Surgery News
1997;8:9.
28. Lee DH, Lee HY, Lee KH et al. Effect of a capsular tension
ring on the shape of the capsular bag opening and intraocular
lens. J Cataract Refract Surg 2001;27:452.
29. Assia EL ,Shelach M, Israel HM et al. Experimental studies
of capsular rings of soft Latex: J. Cataract Refract Surg
2001;27:457.
30. Cionni RJ, Watanabe TM. Congenital subluxation of the
crystalline lens and the surgical treatment. Buratto L, Osher
RH, Masket S. Cataract Surgery in Complicated Cases; Slack
Inc., 2000;15.
 Chapter 104
Ophthalmic Manifestations of
Inborn Errors of Metabolism
LC Dutta
Inborn error of metabolism was first designated by
Garrod in 1908 in describing the chemical pathology
of alkaptonuria which resulted from a hereditarily
determined deficiency of the specific enzyme normally
required for degradation of homogentisic acid in the
metabolism of phenylalanine and tyrosine. Now
hundreds of such inherited metabolic diseases are
recognized and new ones are continuing to be
described at a rapid rate. In approximately half of these
there is at least a partial understanding of the role of
specific protein which is altered either in quality or
quantity by genetic mutation to produce the derange-
ment of biochemical function which delineates the
phenotype of the disorder. Incidence of these diseases
varies from 1:500 (familial hypercholesterolemia) to
1:1,000,000 (alkaptonuria). Some produce clinical
manifestation at birth and others only in adult life.
Some are lethal regardless of treatment and others are
compatible with normal health and life span. Many
of the diseases of inborn error of metabolism have
important ocular manifestations including gross
defective vision. Even when the vision is not
significantly affected, the ocular manifestations serve
as a guide for diagnosis of the condition. Once the
diagnosis of the disease is made, dietary or detoxi-
cating treatment is undertaken. The progress or arrest
of the disease and the response to treatment can be
monitored by electrophysiological tests like ERG and
EOG. The main aim of treatment is to reduce the
concentration of injurious abnormal metabolite in the
body before they produce permanent toxic effect
particularly on the function of the nervous system.
Most of the inborn errors of metabolism have got
autosomal or X-linked recessive pattern of inheritance.
Hence early diagnosis may help in early and accurate
genetic counseling so that the parents can know the
possibility of having the next child being affected by
the same process. Early diagnosis also helps the
physician to avoid the exposure of his patients to
unnecessary risks from circumstances which are not
normally harmful. Some example of such conditions
are intravascular sludging in sickle cell anemia on
exposure to relative hypoxia in high altitudes and
thromboembolic episode in children with homo-
cystinuria during general anesthesia.
GALACTOSEMIA
Galactosemia is an autosomal recessive inborn error
of metabolism in which galactose metabolism is
abnormal. Normally galactose is derived from dietary
milk; the lactose is split by intestinal lactase into
galactose and glucose. After absorption through the
intestinal mucosa galactose is phosphorylated to
galactose-1-phosphate with the help of the enzyme
galactokinase. In the next phase of metabolism
galactose-1-phosphate is transformed into glucose-1-
phosphate with the help of enzyme galactose-1-
phosphate uridyl transferase. Therefore metabolism
of galactose may be hampered in two ways and hence
galactosemia may be of two types:1
a. Galactokinase deficiency.
b. Uridyl transferase deficiency.
Ocular manifestation of both the types of galacto-
semia mainly consists of opacification of the lens which
may initially be in the form of an oil droplet in the
lens capsule and later on if the condition remains
 Chapter 104: Ophthalmic Manifestations of Inborn Errors of Metabolism
untreated the whole lens becomes completely opaque.
It may appear within a few days or in the first few
weeks after birth and hence it has got to be differen-
tiated from congenital cataract. The cataract is usually
bilateral. At the beginning cataract appears as punctate
lesions in the fetal lens nucleus seen in slit lamp
examination. Galactosemic cataracts look mostly as a
zonular or more often as a nuclear opacity possibly
accompanied by some small cortical vacuoles or by
saucer-like anterior or posterior opacity. There is
always a clear zone between the surface of the lens
and the opacity. The cataract becomes rapidly
complete and at that stage it may be intumescent. In
addition to lenticular change there may be damage to
the nervous tissue and in advance stage may cause
death. In case of galactokinase deficiency galactosemia
there is associated galactosuria. In transferase
deficiency, children become ill from the age they start
drinking mother’s milk. In kinase deficiency, the
children ar entirely well except for cataract formation.
Galactose in the urine can be detected with various
reducing agents. Serum galactose level may be
measured by spectrophotometric and fluorometric
methods. Enzyme assay of blood is the most sensitive
test but it requires high laboratory technology.
Antenatal detection of galactosemia may also be done
by studying enzyme activity in cultured cells of
amniotic fluid obtained by embryocentesis.
Treatment
Treatment of galactosemia consists of total withdrawal
of galactose from diet. Adequate treatment in early
stage with lactose-free diet may lead to regression of
the lens opacities and even to their complete
disappearance. When opacification of the lens is not
likely to disappear then surgical intervention is
inevitable.
ALBINISM
Albinism is a very common ophthalmic manifestation
of inborn error of metabolism in which skin, hair and
uveal tract melanocytes fail to produce normal amount
of melanin.3
Clinical Classification of Albinism
1. Oculocutaneous albinism—skin hair and eyes are
affected.
2. Ocular albinism—primarily involves the eye.
3. Cutaneous albinism—eyes are not affected.
819
Out of these three, oculocutaneous albinism is the
most common. Whether it is ocular or cutaneous or
oculocutaneous the chemical pathology is the same;
this involves the pigment cells which are derived from
the developmental neural crest both in the skin as well
as in the eye. These cells, known as melanocytes, form
melanosomes which are packed with pigment
granules known as melanin. This melanin is formed
by the amino acid tyrosine which is converted by
tyrosinase to dihydroxyphenylalanine (DOPA) and
then to DOPA quinone. The role of tyrosinase in the
development of oculocutaneous albinism has been
clarified by the hair bulb incubation test. In this test
plucked hairs with the bulb intact from albino patients
are incubated with tyrosine solution. In one type of
oculocutaneous albinism there is no darkening of the
hair bulb after incubation and this is termed as
tyrosinase negative albinism. In the other form darkening
does occur indicating the ability of the melanocytes
to synthesize melanin in the presence of tyrosine
substrate and such cases are tyrosinase positive albinism.
Out of these two the former is more severe.
Ocular manifestations consist of affection of
eyebrows and eyelashes; the pupil appears to have
red glow in reflected light. However the appearance
of the iris may vary from light grey to blue in color or
it may be completely white with a pinkish tinge.
Severe photophobia with blepharospasm and nystag-
mus associated with severe refractive error are
common presentations of albinism.
Causes of Visual Disability in Albinism
Foveal hypoplasia is one of the main causes of visual
disability. Another cause is nystagmus which may be
congenital in origin. Nystagmus causes image destabi-
lization. Light entry through the hypopigmented
anterior segment and high light scattering the
hypopigmented fundus cause photophobia and may
contribute to decreased visual acuity.
In addition to the causes mentioned above, there
is high incidence of refractive errors of all types in
albinism. Unfortunately, accurate corrective measures
cannot be offered due to difficulty in fixation in
presence of nystagmus.
Albinism is an autosomal recessive form of
hereditary disease so much so that in some families
the hair bulb test may indicate tyrosinase negative
albinism in one member of the couple and the
tyrosinase positive form in the other, and their
children develop oculocutaneous albinism. In the
820 Section 7: Pediatric Ophthalmology Including Strabismus
carrier stage of albinism there may not be manifest
hypopigmentation in any of the pigmented structure
of the body but in the iris some amount of translu-
cency known as diaphanous iris is seen.
Chediak Higashi Syndrome
Chediak Higashi syndrome is a form of oculocuta-
neous albinism in which hair bulb test is positive. This
is autosomal recessive in nature and is characterized
by poor pigmentation of hair, skin and eyes. Ocular
manifestations are extreme photophobia, nystagmus
and pale blue iris. In young children death may occur
due to undercurrent infection and in older children
from multiple lymphoid infiltration.
Heredity of Albinism
Both tyrosinase negative and tyrosinase positive
albinism exhibit an autosomal recessive pattern of
inheritance and the gene loci are separate. Cases have
been described where both the husband and wife had
oculocuteneous albinism and yet they had normally
pigmented children2 and they themselves both being
from normally pigmented parent.
Management
Albinos have a variety of ocular problems related to
morphologic changes in the eye. The central vision is
usually poor and in histologic studies done in albinos
it is found that the retina is six to eight cells thick in
the macular area rather than containing only the
receptors. The photophobia is caused by the marked
pigment deficiency in the iris and retina. Nystagmus
and squint are usual associations. Since the albinos
have the same complement of premelanosomes as
normal individuals it appears that the deficiency in
melanin production is within the cell. In those albinos
who are tyrosinase negative there is probably no hope
for treatment; but in a tyrosinase positive albino,
feeding of large doses of tyrosine has been tried. Tinted
and photochromic lenses are useful. One may also use
contact lens with opaque scleral portion and painted
iris. A side effect which has been beneficial is that the
weight of the hard contact lens tends to reduce the
excursion of nystagmus.4 Nondevelopment of the
macula causes defective vision. In order to get the
benefit of magnification the patients hold the prints
quite close to the eye. Therefore, hand held magnifier
or even high powered presbyopic correction even in
children who are not of presbyopic group are very
effective. If the child is hypermetropic then presbyopic
correction is more effective. The correction should aim
at reading comfort at a distance of about four inches
from the eyes.5
CYSTINOSIS (CYSTINE-STORAGE
DISEASE; LIGNAC-FANCONI DISEASE)
Cystinosis is a rare autosomal recessive hereditary
disorder resulting from deposition of cystine crystals
in various tissues of the body including the eye. In
this inborn error of metabolism cystine is deposited
in the various tissues of the body due to abnormal
metabolism of methionine. This is an autosomal
recessive disease. The condition may be associated
with dwarfism, acidosis, hypophosphatemia and renal
glycosuria. Extraocular tissues where cystine deposi-
tion occurs are cells of reticuloendothetial system
including those of liver, spleen, lymph glands, kidney
and bone marrow. Ocular tissues affected are cornea,
conjunctiva, sclera, retina and uveal tract.6,7
Classification
Cystinosis may be classified into three types:
1. Infantile (nephropathic).
2. Juvenile (intermediate).
3. Adult (benign).
The infantile type is the most severe and it is
inevitably fatal probably due to damage caused to the
renal tissue; renal transplant may be necessary in these
cases. In juvenile type renal involvement is mild. The
adult type is very rare but prognosis of good.
Deposition of hexagonal crystals of cystine in the
ocular tissues occurs in all the three categories of the
disease. The characteristic refractile corneal crystals
are not present at birth, but are seen in first year of
life along with renal involvement. In slit lamp
biomicroscopy fine scintillating tinsel like crystals of
cystine can be seen dispersed throughout the cornea
and sclera. In the conjunctiva the crystals may appear
like chalky white precipitates aggregated around the
blood vessels with scattering refractile surface. In some
cases cornea may appear hazy because of dense
meshwork of polychromatic crystals present in the
stroma. Mild photophobia may occur but inflam-
matory signs are characteristically absent. Topical
instillation of 0.1% to 0.5% cysteamine eyedrops may
be effective in clearing the corneal deposits.
Retinopathy is a feature of the nephropathic type
in which areas of patchy depigmentation occurs
 Chapter 104: Ophthalmic Manifestations of Inborn Errors of Metabolism
associated with irregularly distributed pigment
clumps in the mid-peripheral part of part of the cornea.
These changes may precede the other ocular findings
by months. The crystals may be seen histologically in
conjunctival biopsy specimens. Since the crystals are
water soluble they will disappear if the tissue is
processed in routine methods. Therefore, frozen
section and minimal exposure to water during staining
are needed to demonstrate the crystals. Histo-
pathologic changes in retinal lesions include focal and
extensive retinal pigment epithelial degeneration and
loss of pigment granules.
Biochemical estimation of cystine concentration of
blood by colorimetry and photochromatography may
show abnormally high cystine level.
PROGRESSIVE HEPATOLENTICULAR
DISEASE (WILSON’S DISEASE)
Wilson’s disease is characterized by progressive
neurological impairment, ataxia, hepatosplenomegaly
and cirrhosis of the liver with Kayser-Fleischer ring
in the peripheral part of the Descemet’s membrane.
This golden greenish or brownish ring may not be
visible in the very early stage of the disease and it often
disappears with appropriate systemic treatment.
Rings may also be seen in relatives of individuals with
fully developed Wilson’s disease. The rings may be
occasionally unilateral or sometimes may be incom-
plete being present in upper and lower part of the
cornea. Double rings may also be seen. The rings may
be 2 to 3 mm in width. Under slit lamp microscope
(best seen against light colored irides) the ring is
composed of (copper containing) granules situated in
the Descemet’s membrane. Anterior capsular sun-
flower cataract is occasionally present.
This is an autosomal recessive disease with
deficiency of alpha-2-globulin ceruloplasmin which
has got the capacity of binding 98 percent of serum
copper and helps its excretion. As the free copper is
not bound with serum ceruloplasmin, wide spread
copper deposition occurs in the basal ganglia of the
brain, liver, spleen, kidney, cornea and many other
tissues of the body.
Biochemical diagnosis of Wilson’s disease consists
of estimation of serum ceruloplasmin concentration;
if it is less than 50 percent then it is suggestive of
Wilson’s disease. Though corneal deposits confirm the
diagnosis, its absence does not rule out the disease.
Treatment of Wilson’s disease is with chelating
agent like D-penicillamine in the dose of one to two
gm per day. The patient may recover dramatically
821
from ocular, neurological and hepatic lesions.
Prognosis without treatment is grave; death results
within five years or so. Successful homotrans-
plantation of liver was reported to have cleared the
ring completely after six years.8
ALKAPTONURIA
(OCHRONOSIS, OCULAR OCHRONOSIS)
Alkaptonuria is an inborn error or metabolism in
which there is inability to metabolize the amino acids
phenylalanine and tyrosine beyond the stage of
homogentisic acid (2,5-dihydroxyphenylacetic acid),
which is an intermediate product in the metabolism
of these substances. This error is due to absence of the
enzyme Homogentisic acid oxidase. Homogentisic
acid is excreted in the urine and when the urine is
kept in normal environment it turns black due to
oxidation of the acid producing a brown or blackish
discoloration. Alkapton means alkali; as the brownish
discoloration occurs when the urine becomes alkaline
on exposure to air, the disease is known as alkapto-
nuria. If the pH of urine remains on acidic side then
the color change may not occur. It is an autosomal
recessive disease.
In alkaptonuria homogentisic acid accumulates in
the connective tissue of the body where it undergoes
polymerization to form a black pigment specially
marked in the joint cartilages causing arthritis.
Cartilage of the nose and ears also may be affected;
the lesion consists of pigmentation of the sclera in the
form of a triangular patch in the interpalpebral area
near the insertion of horizontal rectii muscles. This is
known as Osler’s sign.
Sometimes the disease may first attract attention
in infancy by the staining of the underclothing. The
melanotic deposits may be evident by about middle
age. Diagnosis may be confirmed by serum chromato-
graphy.
HOMOCYSTINURIA
Homocystinuria is an autosomal recessive hereditary
metabolic disease in which the sulfur containing
amino acid methionine is not completely metabolized
due to absence or defective activity of the enzyme
cystathionine synthetase in the liver and appearance
of homocystine in urine. This enzyme normally
controls the formation of cystathione from homo-
cystine and serine which is an important step in the
cellular metabolic pathways between methionine and
cystine. This condition was simultaneously reported
822 Section 7: Pediatric Ophthalmology Including Strabismus
by Carson and Neil (1962)8 from Northern Ireland and
by Garritsen, Vaughn and Waisman (1962) from
Wisconsin. The main clinical signs in homocystinuria
are ocular and include ectopia lentis which occurs
usually within first decade of life but may also be
present at birth. Other associated ocular abnormalities
reported in homocystinuria are congenital cataract,
optic atrophy, microphthalmos, congenital glaucoma,
hyperplastic primary vitreous, myopia, aniridia,
retinoschisis, spherophakia, etc. Skeletal abnormalities
like genu valgum and osteoporosis are also common;
this may lead to fracture of femur. Mental retardation
is found in most of the patients.
The most typical cardiovascular feature is a
tendency to recurrent arterial and venous thrombosis
the cause of which is still unknown. Increased
stickiness of the platelets was thought to be a cause
but it is an inconstant finding. Such thrombosis is
common with dehydration, after venepuncture or
general anesthesia. Malar flush and fair hair are also
typical signs of homocystinuria.
About 5 percent of the cases of spontaneous
(nontraumatic) dislocation of the lens is due to
homocystinuria. Bilateral subluxation of the crystalline
lens occurs in two other rare metabolic conditions, viz.,
sulfite oxidase deficiency and hyperlysinemia, both
of which are also characterized by severe mental and
physical retardation. Marfan’s syndrome is a well-
known condition in which bilateral displacement of
the lens occurs in temporal and upward direction but
in these metabolic disorders including homo-
cystinuria, displacement is downward. In some cases
the displacement may be downward and medially and
exceptionally it may be upward and temporally. The
biochemical mechanism by which homocystinuria
causes ectopia lentis is not known. Lens zonule is a
collagenase resistant protein containing cystine and
hence zonular abnormality can be related to insuffi-
cient supply of this amino acid. Arachnodactyly with
long upper and lower extremities is a distinctive
feature in Marfan’s but may occur in homocystinuria
also. The Sternberg thumb sign is constant in Marfan’s
syndrome: when the thumb and the little finger of one
hand are clasped around the wrist of the opposite hand
of a patient with Marfan’s syndrome they overlap.
Again when the thumb is flexed across the palm under
the fully flexed fingers of the same hand, its tip extend
well beyond the ulnar border of the hand. These signs
demonstrate and the thinness of the wrists in Marfan’s
syndrome; these features may be absent in homo-
cystinuria.
Biochemical Tests for Homocystinuria
a. Homocystine in the urine is detected by sodium
nitroprusside test in which 5 ml of urine is mixed
with 2 ml of 5 percent sodium cyanide and after 10
minutes 2 to 4 drops of 5 percent sodium nitro-
prusside is added. If homocystine is present in
urine, a bright red color is seen. However some-
times false-negative results are possible. Moreover
the test is not conclusive because in addition to
homocystine, cystine also can cause coloration of
the urine. Silver diamine and nitroprusside gives
a greater specificity.
b. Estimation of homocystine in urine and methionine
and homocystine in plasma by using amino acid
analyzer.
c. Enzyme assay of cystathionine synthetase activity
in extracts of liver obtained by fine needle
aspiration biopsy.
Abnormality in Collagen Metabolism
Marfan’s Syndrome
Marfan’s syndrome is an autosomal dominant
abnormality of the collagen tissues of the body.
Systemic findings include increased height, long and
thin extremities, increased ratio of lower body to upper
body, increased length of the fingers. Elongated face
and high arched palate and kyphoscoliosis, hyper-
extensibility of the joints due to lax joint capsules,
ligaments and tendons are prominent features of the
disease.
Ophthalmic features include elongation of the
ciliary processes, flat ciliary body and poorly
developed circular and radial muscles of the iris. The
lens mat be small, spherical and may be subluxated
in 50 to 80% of patients. Subluxation is typically
bilateral and superotemporally. Zonules are visible
across the pupillary aperture— they appear stretched
but may also be broken. High myopia is a common
association of Marfan’s syndrome.
Stickler’s Syndrome
This autosomal dominant hereditary condition is due
to defective metabolism of collagen. Systemic abnor-
malities include laxity and hyperextensibility of the
joints, high palate, bifid uvula, mandibular hypoplasia
and deafness. Ocular involvements include congenital
cataract in about 50% of cases, progressive myopia of
about 8-18 D due to increased length of the eyeball,
 Chapter 104: Ophthalmic Manifestations of Inborn Errors of Metabolism
hypopigmentation of the fundus and straightening of
the retinal blood vessels. However scleral staphyloma,
lacquer cracks and choroidal neovascularized
membrane is rare in patients with Stickler’s syndrome.
Giant retinal tear with retinal detachment may also
occur.
Ehlers-Danlos Syndrome
This dominantly inherited condition also has decrea-
sed collagen and an increase in dermal elastic tissue.
In addition to laxity of the joints, there is increased
friability of the blood vessels causing aneurysm and
rupture of large blood vessels. The patients usually
die at around 15 years of age as a result of exsangui-
nations. Ocular findings are epicanthus, strabismus,
lens displacement, keratoconic myopia and myopic
staphylomas.
823
REFERENCES
1. Segal S. Disorders of galacotose metabolism. In Stanbury JB,
Wyngaavden JB, Fredrickson, DS (Eds): The Metabolic Basis
of Inherited Disease (3rd Ed). New York: McGrew Hill, 1972.
2. Trevor-Roper PD. Marriage of two complete albinos with
normally pigmented off springs. Br J Ophthalmol 1952;36:107.
3. Jay B, Carrot W. Albinism: Recent advances. Trans Ophthal-
mol Soc UK 1980;100:467.
4. Taylor WOG. Visual disabilities of oculocutaneous albinism
and their alleviation. Trans Ophthalmol Soc UK 1978;98:423.
5. Taylor WOG. Aiding the vision in albinism: Optical and non-
optical means considered. Trans Ophthalmol Soc UK
1985;104:309.
6. Cogan DG, Kuwabara T, Kinshita J et al. Ocular manifes-
tations of systemic cystinosis. Arch Ophthalmol 1956;55:36.
7. Wong VG, Lietman RS, Seegmiller JE. Alteration of pigment
epithelium in cystinosis. Arch Ophthalmol 1967;77:361.
8. Carson NAJ, Neill DW. Metabolic abnormalities detected in
a survey of mentally backward individuals in northern
Ireland. Arch Dis Child 1962;37:505.
 Chapter 105

Pediatric Orbital Space

Occupying Lesions
LC Dutta, Nitin K Dutta

The eye and ocular adnexa snugly fill the orbital
cavity; any change in volume of the orbital content
will cause proptosis. The basic causes of intraocular
space occupying lesions are almost the same both in
adults and children, but the spectrum may vary
widely. Table 105.1 gives an idea of various pediatric
space occupying lesions collected from three large
series published almost simultaneously by three
separate groups from different centers. The most
common pediatric lesions are of congenital-develop-
mental cystic tumors followed by lesions caused by
inflammatory processes.
an inclusion cyst and may present anywhere along
the suture lines around the frontal bone. Deeper
lesions within the orbit may present as an orbital mass
with diplopia and proptosis. 1 Another mode of
presentation of these tumors may be as orbital
inflammation after blunt trauma.
In the four angles of the orbital cavity, dermoids
are seen in the following order of frequency; upper
outer, upper inner, lower inner and lower outer.
Frontozygomatic suture line is the most common site
of dermoids. The size of the dermoid may vary from
the size of the fingertip to that of a clenched fist.3

CYSTIC TUMORS
Table 105.1: Pediatric Orbital space occupying lesions7
Dermoid/Epidermoid Cyst
Types of lesion Shields10 Rootman2 Bullock43
Dermoid cyst is the commonest form of orbital cyst
and encompasses about 10% of orbital cysts. It is a No of cases 250 210 121
form of developmental choristoma.1 Dermoid and Cystic lesions 130 27 48
epidermoid cysts are clinically almost the same: There
Inflammatory mass 41 55 2
is only histological difference between the two. 2
Epidermoid is a newer term replacing cholesteatoma. Dermolipoma 17 7 11
The distinction between dermoid and epidermoid is Vascular lesion 17 49 21
the type of tissue found associated with the cyst.
Rhabdomyosarcoma 10 5 3
Epidermoid cyst contains only stratified squamous
epithelium forming the wall of the cyst while dermoid Metastatic/secondary lesions 9 5 4
contains epidermal appendages including the hair Lacrimal gland lesions 6 2 3
follicles, sweat glands and sebaceous glands.
Lymphoid 6 0 5
Though the dermoids/epidermoids are congenital
cysts that become clinically apparent in later Optic nerve tumor 6 16 6
childhood and present as slowly growing unilateral Peripheral nerve tumor 4 9 9
painless firm mass. It may be mobile or fixed to the
underlying structures and free from skin. It occurs as Fibro-osseus tumor 3 15 6
 Chapter 105: Pediatric Orbital Space Occupying Lesions
Dermoids should be differentiated from cephalo-
cele or meningoencephalocele. It is customary to have
an X-ray as an initial measure to detect any gap or
deficient bone in case of encephalocele and meningo-
encephalocele. Frequently it is tempting to put a
needle to assess the nature of the content—but it
should never be done for two reasons: (a) If the needle
test confirms a dermoid, the toxic content of the cyst
released through the needle puncture point causes an
extensive uncontrollable inflammation of the orbital
tissue necessitating complete removal of the orbital
fibrofatty tissue. (b) If the lesion happens to be
cephalocele/meningoencephalocele, there is risk of
leakage of CSF and meningitis. Orbital radioimaging
like CT scan is the best investigation for diagnosis for
orbital space occupying lesions.
Microphthalmos with Cyst
This congenital anomaly of the globe is due to exteri-
orization of some neuro-ectodermal tissue through the
primary optic fissure during the second month of
intrauterine life. The neuro-ectodermal tissue prolife-
rates to form a cyst, the wall of which consists of an
inner layer of glial tissue and an outer layer of
fibrovascular tissue. The microphthalmic eye is
attached to the upper part of the cyst which gradually
increases in size and fill the whole orbital cavity.
Teratoma
Teratoma is a congenital condition. It is defined as a
tumor containing all the three germ cell layers—
ectoderm, endoderm and mesoderm. It is also called
a fetus in fetus. Teratoma may be present at any age
between fetal age to adolescence. Most are benign and
localized in the orbit4. It is a rapidly growing tumor
and though not clinically malignant, it very closely
simulates a malignant tumor. In adults the tumor
grows very slowly. More often, a true teratoma is
defined as a true neoplasm with structures developed
from all the three germinal layers.
Clinically it is manifested as a rapidly growing
orbital mass of varying size. Typically, an otherwise
normal full term infant develops an extremely rapidly
increasing proptosis. The eyelids become stretched
over a tense fluctuant or solid mass with elongation
of the palpebral fissure. There is no abnormality in
development of the eye. However, the eye may be
displaced or compressed by the tumor leading to
perforation and collapse. Clinically it is difficult to
differentiate it from other benign or malignant tumors.
825
Differential diagnoses include other congenital
abnormalities like dermoid, microphthalmos with
cyst, encephalocele, cystic eyes, neurofibroma,
neuroblastoma, other ocular diseases like retrobulbar
hemorrhage and hematoma. X-ray and CT shows
enlargement of the orbital cavity with soft tissue
shadow. Radiologically, the differential diagnosis
includes optic nerve glioma, meningioma and
rhabdomyosarcoma.
Histopathologically teratoma may be of solid or
cystic consistency. Rapid increase of the size of the
tumor is attributable to rapid enlargement and
distension of the cystic cavities within the tumor.5
Histopathological examination of the teratoma of any
part of the body usually shows simple type of tissue
like skin and its appendages, connective tissue,
muscle, cartilage and bone. Many complex and
differentiated tissues like brain, pancreas, parathyroid,
liver, mammary gland may be occasionally present6.
Treatment of teratoma is surgical removal; but not
infrequently the eye may also have to be salvaged
enucleated. Recurrence may occur due to incomplete
removal.
Cephalocele, Encephalocele,
Meningoencephalocele, Meningocele
This congenital condition common in the superoan-
teromedial aspect of the orbit, is due to outpouching
of brain matter with the meninges along the suture
lines between frontal, maxillary, ethmoid and lacrimal
bones. The cystic swelling extends either anteriorly
on to the face at the junction of the nose and eyebrow
or laterally into the orbital cavity. The cysts may be
bilateral. The eyeball is displaced downwards,
forwards and laterally when the cyst is located in the
superomedial part of the orbit. Clinically there may
be pulsatile exophthalmos when the cyst is big. A bruit
may be heard on auscultation over the closed eyelids.
Another diagnostic clinical sign is increase of the size
of the swelling during coughing, sneezing or crying.
The swelling may reduce in size on pressure but may
cause slowing of the pulse rate or even coma. Routine
X-ray may not show any bony defect but CT and MRI
can offer great help in diagnosis.
Differential Diagnosis
Differential diagnosis of a soft cystic swelling inside
the orbital cavity specially in the posterior part should
be meticulous. If any doubt exists then a fine needle
826 Section 7: Pediatric Ophthalmology Including Strabismus

aspiration biopsy may also be necessary. If the

aspirated material is clear and watery, then estimation
of sugar and protein content should be done just to
assess that it is not cerebrospinal fluid.

Treatment
Treatment of cephalocele should be attempted with
the assistance of a neurosurgeon. The cephalocele may
be excised after dividing the pedicle and the bony gap
may be closed by bone graft or synthetic material like
silastic plate.

Optic Nerve Tumors

Meningioma and glioma are the two tumors that arise
from the intraorbital part of the optic nerve. In a review
of literature Volve and Jakobiec reported that out of
643 cases of pediatric space occupying lesions only 30
cases had optic nerve tumor.7 Glioma of the optic
nerve in children is more common in contrast to
meningioma8 which is rare in pediatric age group. Not
infrequently 10-58% optic nerve gliomas are associated
with neurofibromatosis (von Recklinghausen’s
disease). Lewis et al 9 studying 277 patients with
neurofibromatosis found optic nerve glioma in 33
cases (15%). The diagnosis of glioma was confirmed
by CT of the optic nerve. The mean age of these
patients was 16 years.
Glioma of the optic nerve is a benign tumor
(pilocytic astrocytoma) arising from the astrocytes and
oligodendroglial cells of the optic nerve. 9,10 The
symptomatology consists of a triad of (a) slowly pro-
gressive, non-pulsatile, irreducible axial proptosis (b)
frequent presence of papilledema and optic atrophy
causing ultimate gross reduction of vision and (c)
ocular motility disturbance.10 The tumor grows along
the orbital part of the optic nerve and may grow in
size assuming a fusiform shape. The tumor can be pal-
pated if it grows towards the temporal side of orbital
cavity. Diagnosis is confirmed by MRI which may
show widening of the optic foramen (Figs 105.1A to C).

Differential Diagnosis
Meningioma and glioma are the two main tumors of
the intraorbital part of the optic nerve. Out of the two,
meningioma is more aggressive than glioma and
pediatric meningioma is more aggressive than adult
meningioma. But the incidence of meningioma in
pediatric age group is far less than the incidence of
glioma. Further, glioma of the intracranial part of the
Figs 105.1A to C: Optic nerve glioma on MR, postoperative
status: (A) Axial T1-weighted MR scan shows residual tumor
involving the right intracanalicular and intracranial optic nerve.
The mass is isointense to brain. Note widening of the optic
canal (arrows). (B) Coronal T1-weighted MR shows the enlarged
intracranial optic nerve involvement on the right (arrow). Note
normal intracranial optic nerve on the left (thick arrow). (C) Post-
contrast fat-suppressed image shows moderate inhomogenous
enhancement. (Courtesy Dr SK Handique)
 Chapter 105: Pediatric Orbital Space Occupying Lesions
optic nerve as well as of the optic chiasm may grow
into the orbit. The main differentiating CT scan sign
of meningioma of the optic nerve is erosion of the bone
forming the optic canal; bony erosion does not occur
in glioma.
Treatment
Surgical removal of the tumor is the only method of
treatment of glioma. However visual prognosis is poor
because the tumor involves all the optic nerve fibers.
Therefore excision of the whole tumor along with the
involved part of the optic nerve can be done through
the temporal aspect of the orbit without any hesitation
because the eye is blind. But the important aspect of
the surgery is that both ends of the optic nerve should
be tumor free.
Prognosis
Visual prognosis is poor. Operation is indicated for
cosmetic purpose only. Though pediatric glioma is a
benign tumor, adult glioma may be malignant. If the
tumor is not removed, risk of malignant change should
be kept in mind.
Rhabdomyosarcoma
Rhabdomyosarcoma is the most common primary
malignant soft tissue sarcoma of the orbit in children.
Its incidence is 4% to 10% of all childhood malignant
tumors11. It causes rapid progress of proptosis which
develops in days or weeks. Boys are more affected
than girls in the ratio of 5:3. The tumor may be
congenital – present at birth even with wide spread
metastases.12,13 But it may appear at any age upto 16-
18 years. Most common age of occurrence is 7-10
years.15,16 There is no hereditary tendency, but the
tumor has been reported in siblings. 14 Though
rhabdomyosarcoma is basically an orbital tumor,
sometimes it may develop in the adjoining structures
of the orbit such as ethmoid sinus or nasal cavity and
from there extend into the orbit causing initial
symptoms. Orbital rhabdomyosarcoma may develop
from any quadrant of the orbital cavity but supero-
nasal quadrant is the most common site of origin.
When it appears initially in the ethmoid sinus or nasal
cavity, the symptoms may be those of sinusitis with
nasal congestion and epistaxis followed by onset of
proptosis.
827
Fig 105.2: Rhabdomyosarcoma of the orbit in a 2-day old baby:
Axial CT scan shows a mass of soft tissue density filling most
of the left orbit. There is pressure effect on the globe. Note
widening of the superior orbital fissure (arrows) due to
intracranial extension (Courtesy DR SK Handique)
When rhabdomyosarcoma originates in the
anterior part of the eye it may start as a palpable or
visible mass under the conjunctiva with mild
proptosis. Associated ocular findings due to mechani-
cal pressure on the globe by the growing tumor may
be choroidal folds, papilledema and dilated tortuous
retinal veins. The tumor may start in the retrobulbar
space also; causing proptosis. During the rapid process
of growth, the tumor may erode through the spongy
bone of the medial wall of the orbit to the ethmoid air
cells. However, as mentioned above the reverse
process may also be possible viz. the tumor may
originate in the ethmoid sinus and extend to the orbit.
In the initial stage the regional lymph nodes are not
involved because the orbital tissue behind the orbital
septum does not have lymphatics. Distant metastases
in lungs and cervical lymph glands are via hemato-
genous spread. Bone metastasis is less common.
Pathology
Pathological definition suggests that rhabdomyo-
sarcoma is a malignant (sarcomatous) tumor arising
from the striated muscles. In fact, this highly malignant
childhood tumor may develop in any part of the body
where pluripoptential cells exist—even though that
area does not contain skeletal muscles. The cross
striation within the cytoplasm of the tumor cells is the
828 Section 7: Pediatric Ophthalmology Including Strabismus
characteristic diagnostic evidence of rhabdomyo-
sarcoma. But in standard hematoxylin eosin stain of
the histological slides the cross striations are not
discernable. Special stains like Masson trichromic stain
or phosphotungstic acid hematoxylin stain only can
show the cross striations. Therefore presence of
rapidly evolving spindle cells in histopathological
slides stained with hematoxylin eosin stain should be
considered as an evidence that the orbital malignant
tumor with characteristic clinical symptomatology in
rhabdomyosarcoma.
For prognostic purpose, histopathologically,
rhabdomyosarcoma is divided into four types on the
basis of the predominant cell type:
a. Embryonic type:17 Two-thirds of rhabdomyosar-
coma are of this type is composed of a loose
network of spindle shaped rhabdomyocusps with
hyperchromatic eosinophilic cytoplasm and
elongated central nucleus. On low power micro-
scopy they appear like parallel pallisading bands.
Cross-striations are difficult to be identified.
b. Alveolar type: This type is composed of poorly
differentiated cells arranged in groups along
fibrovascular septa resembling the alveoli of the
lungs. This type of rhabdomyosarcoma is most
malignant with worst prognosis.18
c. Pleomorphic type: The cells are longer than the
alveolar and embryonic subtypes and have
granular cytoplasm containing glycogen, This type
of rhabdomyosarcoma is typically a tumor of adult
skeletal muscle and that also vary rarely involves
the orbit.
d. Botryoid type: Botryoid type of rhabdomyosarcoma
is not very common in the orbit. This is a fleshy
tumor which looks like a bunch of grapes. The
tumor simulates genitourinary tumor in female
infants. The histopathologic examination shows
interlacing bundles of spindle cells with abundant
eosinophilic cytoplasm and elongated hyper-
chromatic nuclei. Clinically the tumor spreads in
the anterior part of the orbit as a polypoid grapelike
mass beneath the conjunctival epithelium.
Diagnosis
Based on the clinical features, if high clinical suspicion
of rhabdomyosarcoma exists, an incisional biopsy
should be performed as early as possible. Fine needle
aspiration cytology is not very reliable in confirming
rhabdomyosarcoma. Delay in performing biopsy may
be followed by rapid progression of proptosis even
over the weekend.
Radioimaging procedures mainly CT may reveal
any posterior extension of the tumor eroding the bone
with intracranial extension (Fig. 105.2).
Differential Diagnosis
In differential diagnosis of rhabdomyosarcoma, most
cases of proptosis in children should be considered.
These include orbital cellulitis, capillary hemangioma,
lymphangioma, metastatic neuroblastoma, dermoid
tumors, granulocytic sarcoma and optic nerve glioma.
Another orbital inflammatory condition known in the
past as orbital pseudotumor is presently called
‘idiopathic orbital syndrome’ comes into the group of
orbital mass in children.
The most common clinical entity to be differen-
tiated from rhabdomyosarcoma is cases of orbital
cellulitis specially those which result from infection
spreading from paranasal sinuses, specially ethmoid
sinusitis. Unlike in orbital cellulitis the skin of the child
overlying the tumor is not hot and the patient is
afebrile. However, subperiosteal abscess formation in
resolving stage or orbital cellulitis may be difficult to
detect clinically.
Radioimaging procedures viz. orbital CT and MRI
may help in the clinical diagnosis. Routine hemato-
logical examination and chest X-ray will help
differentiating rhabdomyosarcoma from other
diagnostic possibilities such as acute orbital cellulitis,
leukemia. Chest and bone X-rays will help detection
of distant metastasis. As rhabdomyosarcoma is a
rapidly growing malignant condition consultation
between ophthalmologists, otorhinologists, neuro-
logists, neurosurgeons and pediatric oncologists may
help in deciding its therapeutic modalities.20
Treatment
For the purpose of management rhabdomyosarcoma
can be divided into 4 types. (i) Localized tumor which
can be completely resected. (ii) Regional spread (can
be resected). (iii) Gross residual tumor after incomp-
lete resection. (iv) Distant metastasis – for treatment
with chemotherapy.
Surgical excision can be done if the tumor is well
circumscribed and if the excision can be done without
much tissue damage. In the past, when the tumor is
limited to orbital cavity without invading the bony
orbit, exenteration of the orbit was the treatment of
choice. However rhabdomyosarcoma is highly
 Chapter 105: Pediatric Orbital Space Occupying Lesions
radiosensitive and radiotherapy of 4000 to 6000 cGy
in divided doses over 5 to 6 weeks has been considered
a suitable treatment. Adjunctive chemotherapy along
with radiotherapy is indicated in cases with significant
extracranial spread. Chemotherapy is also indicated
in recurrent cases after radiotherapy.1 However visual
prognosis for the affected eye is poor. During
radiotherapy adequate protective measures should be
taken to prevent radiation damage to the unaffected
eye. Another reasonable recommendation by Shields
and Shields15 is to remove as much of the tumor as is
easily accessible without causing undue risk to the
eyeball, optic nerve and other neurovascular struc-
tures of the orbit with appropriate postoperative
radiation and chemotherapy.21 The aim of chemo-
therapy is to achieve maximal drug response with
minimum acceptable toxicity. Three drugs treatment
is a recent concept rendering maximum benefit. In
triple therapy vincristine sulfate, dactinomycin and
cyclophosphamid has been advocated.
Prognosis
Rhabdomyosarcoma responds well to radiotherapy.
Prognosis for life in patients with orbital rhabdo-
myosarcoma is good. According to Intergroup
Rhabdomyosarcoma Study Committee reviews. 127
cases confined to the eyelid and orbital regions
confirmed that recurrent tumor developed in about
9% treated patients and have 3-year survival rate.11
Advances in the treatment of rhabdomyosarcoma
with chemotherapy the survival rate in localized
rhabdomyosarcoma is more than 90% at 5 years.
METASTATIC TUMORS
The types of malignant tumor which metastatize in
adults and children are quite different. In case of
adults, the common primary tumors are breast (42%),
Lungs (11%), prostate (8%), melanoma (5%) and
unknown source are 11%.2 The spectrum of pediatric
primary tumors metastatic to the orbit is narrow. They
include neuroblastoma and Ewing’s sarcoma.
Medulloblastoma and Wilms’ tumor metastatize to the
orbit less frequently.23 Musarella et al24 reported that
20% of children with neuroblastoma had ocular
involvement with three-fourths having proptosis or
ecchymosis.
Neuroblastoma
Neuroblastoma is a disease of the infants and children.
It is a highly malignant tumor arising from the
829
embryonic neuroblastic sympathetic nervous tissue
usually arising from the adrenal medulla and very
rarely from the ganglia of the sympathetic trunk.
About 90% of cases occur before the age of 4-5 years.
Orbital metastasis is frequently seen with bony
metastasis in the skull. The malignant cells in the orbit
grow very rapidly to produce proptosis and changes
in the lids such as edema, swelling, puffiness and
echymosis. Proptosis is the usual feature but not
uncommonly the condition may simulate orbital
cellulitis, rhabdomyosarcoma and leukemia. The
proptosed eye may be displaced in any direction; it
will be axial if the neoplasm is in the soft tissues of the
posterior orbit or to one side or another in the direction
opposite to the metastatic colony. When the eye is
displaced the epibulbar tissue becomes chemotic and
congested and movements of the eyeball become
restricted.
Diagnosis is confirmed by cytological examination
after fine needle aspiration biopsy. Biochemical
examination of urine in respect of 4-hydroxy-3
methoxy mandelic acid may also throw some light on
the diagnosis of neuroblastoma. Microscopic picture
of neuroblastoma may show some similarity with
rhabdomyosarcoma, granulocytic sarcoma25, Burkitt’s
lymphoma and retinoblastoma.
Ewing’s Tumor
Ewing’s sarcoma of long bone can metastatize to the
orbit. But primary tumor may develop also from the
soft tissue or the bones forming the orbit. Ewing’s
tumor usually arises in the second decade of life.
Ewing’s tumor metastasis is usually unilateral.26 The
disease is characterized by sudden onset of proptosis
due to blood borne metastasis from the long bones.
The pathologic features are undifferentiated and
prognosis is poor in spite of combined treatment with
radiation and chemotherapy.27
Wilms’ Tumor
Wilms’ tumor or nephroblastoma is rare with
devastating prognosis. Orbital metastasis is common.
Leukemia and Lymphoproliferative Conditions
Leukemia is a common childhood disorder. In acute
lymphatic leukemia the eye and ocular adnexa are
commonly involved. Proptosis and limitation of ocular
movement are the clinical features of orbital metastasis
830 Section 7: Pediatric Ophthalmology Including Strabismus
of leukemia. Acute proptosis develops due to hemorr-
hage in the leukemic mass. Retinal hemorrhages and
choroidal deposits also are ocular features of leukemia.
Granulocytic sarcoma or the extramedullary form of
acute myeloblastic leukemia can also present as an
orbital mass.25 The average age of this condition is 7
and the condition may be bilateral. Histiocytosis X,
which includes three conditions—Hand-Schuller-
Christian disease, Leterrer-Siwe disease and eosino-
philic granuloma—is a pediatric disease causing
leukemia with orbital involvement occurs in 10% of
cases. The lesions are presumed to be due to the
accumulation of histiocytes of Langerhans type of cell.
The disease of the orbit involves the superolateral part
of the orbit with soft tissue tumor along with osteolysis
around the tumor. Prognosis of the disease in younger
children is poor. Mortality rate in children below
2 years is 60 percent.4
Orbital Varix
Orbital varix is a venous counterpart of the orbital
aneurysm. This pathological condition involves an
enlargement of a single or several venous channels.
This is a disease of the adult who complains of
intermittent exophthalmos in stooping position due
to stagnation of blood in the vessels. In children
proptosis may occur during crying. Foroozan et al28
described a case of extreme neonatal proptosis caused
by rupture of congenital varix confirmed by radio-
logical study and CT. Rosenblum and Zilkha29 reports
a case of sudden loss of vision in a child which was
confirmed to be due to bleeding from the varix. Shields
et al demonstrated orbital varix in a young person with
CT and Valsalva test.30
Lymphangioma
Lymphangioma of the orbit is a hamartomatous
growth of isolated lymph channels. However it is
considered to be unusual because the orbital tissue
behind the orbital septum is believed to be devoid of
lymphatic channels. Though clinically it may simulate
orbital varix, histopathologically the conditions are
separate entities. Orbital lymphangioma causes a slow
progressive proptosis.31-33 The diagnosis of lymph-
angioma may be suggested by CT scan but final
diagnosis is made by biopsy only. Histopathologically
lymphangioma consists of grape like cysts of various
sizes accounting for varied manifestations. The lesion
is not encapsulated and usually there are no well
defined margins. This characteristic allows the tumor
to interdigitate freely with normal tissue. The tumor
consists of a network of dilated endothelium lined
spaces with filmsy mural septa. The loose stroma
between the lymph channels may contain focal
lymphocytic infiltrates that can hypertrophy accoun-
ting for proptosis during an upper respiratory tract
infection.33 There are also many small blood vessels
in the septa and stroma which have little endothelial
support. There may be internal bleeding in the mass
leading to characteristic chocolate cyst formation. The
blood vessels of lymphangioma do not substantially
communicate with the systemic circulation.31 Unlike
an orbital varix, which is under normal venous
pressure, characteristic postural proptosis does not
occur in lymphangioma. Surgical management of
lymphangioma is difficult. Conventional surgical
excision is incomplete. Laser therapy has good
prospect.34
Capillary hemangioma also known as benign
hemangioma is a common vascular lesion in children.
Girls are more affected than boys in the ratio of 3:2.
Capillary hemangioma of the orbit is usually
unilateral. When confined to the orbital tissue the child
may present with proptosis and globe displacement.
Though extraocular muscles may be involved,
diplopia and ocular motility disturbances are not
present. Orbital capillary hemangioma may be
associated with refractive errors35. Axial myopia is
usually common due to lengthening of the eyeball by
the pressure exerted by the tumor. Due to similar
mechanism hyperopia and astigmatic errors are also
possible.36 Capillary hemangioma of the orbit may be
associated with Sturge-Weber syndrome. Differential
diagnosis from rhabdomyosarcoma. Diagnosis is by
USG, CT and MRI. Amblyopia and strabismus may
be the complications of capillary hemangioma.
Treatment
Intralesional injection of 40 mg triamcinolone and
6 mg preparation of equal parts of betamethasone
sodium phosphate and betamethasone sodium
acetate.
ORBITAL PSEUDOTUMOR
Pseudotumor is an idiopathic, noninfective, non-
tumoral inflammatory mass which may resolve
without any treatment or resolves quickly after
treatment with steroids.37 It may be a localized or a
diffuse mass commonly in the anterior part of the
 Chapter 105: Pediatric Orbital Space Occupying Lesions
orbital cavity more commonly overlying the paranasal
sinuses. The condition possesses all the criteria of
orbital space occupying lesions.
The condition is non-malignant in the sense that it
is not life threatening. On the other hand it is not
entirely innocent as a benign neoplasm because unless
treated timely, it may lead to blindness. Presently the
term pseudotumor is less accepted; rather it is called
a form of “orbital inflammatory syndrome” and is
described in acute, subacute and chronic stages.
Histopathologically it consists of hypocellular
polymorphous infiltrate composed of polymorphonu-
clear leukocytes, lymphocytes, plasma cells,
eosinophils38 and macrophages. In the chronic form
of pseudotumor, lymphoid follicles with germinal
centers also may be found on histopathological
examination.
Clinical features of orbital pseudotumor are pain
and swelling of the eye and anterior ocular adnexa.
Ptosis, proptosis, limitation of ocular movements are
common findings. Iridocyclitis2, scleritis and posterior
uveitis may also be associated with orbital pseudo-
tumor. Hematological investigation may show high
erythrocytic sedimentation rate (ESR). CT scan may
show enlargement of the belly of some extraocular
muscles.
Differential Diagnosis
Pseudotumor needs to be differentiated from orbital
cellulitis of infective origin specially those with
subperiosteal abscess after resolution of the active
inflammatory process. A meticulous history corrobo-
rated with physical examination and radio-imaging
procedures will help in confirmation of the diagnosis.
Xanthogranuloma and histiocytosis-X also come in the
differential diagnosis; but this can be confirmed only
by histopathological examination of biopsy specimen.
Treatment
Standard treatment for orbital pseudotumor is
systemic steroid 60-80 mg of prednisolone daily in
divided doses.40 the response to therapy is shown by
reduction of proptosis and improvement of ocular
motility. Steroid therapy is also used as a therapeutic
test to differentiate this condition from neoplastic
lesions. Non-steroidal anti-inflammatory drugs are
also tried but the results are not encouraging.
831
SECONDARY TUMOR
Secondary orbital tumors occur by direct extension
from the adjacent structures of the orbit including the
eyeball, nasopharynx, and paranasal sinuses. In
children common extension of tumor of intracranial
part of optic nerve and chiasm, malignant tumor
(Retinoblastoma) from retina, craniopharyngioma, etc.
Retinoblastoma is the most common malignant
tumor of childhood which freely extends beyond the
confines of the globe. The tumor extends through the
choroid and sclera to the orbital tissue41. It can also
extend along the optic nerve. Incidence of orbital
extension is variable. The incidence is likely to be much
higher in patients with less access to care and neglected
disease. The tumor reaches the orbit through the
connective tissue surrounding the vessels and nerves
that enter the sclera. Once the tumor grows out of the
sclera, the tumor cells grow as differentiated neuro-
blastic cells. The histopathological difference between
the primary tumor and the secondary and metastatic
tumor is that the Flexner Wintersteiner rosettes are
absent in secondary and metastatic retinoblastoma.42
REFERENCES
1. Sherman RP, Rootman J, Le Pointe J. Orbital dermoid. Clinical
presentation and management. Br J Ophthalmol 1986;101,726.
2. Rootman J. Diseases of the orbit: a multidisciplinary
approach. Philadelphia. Lippincot 1988.
3. Grave AS. Giant dermoid cyst of orbit. Ophthalmology
1979;86:1513.
4. Levin ML, Leone CR, Kineocid MC. Congenital orbital
teratoma. Am J Ophthalmol 1986;102:476.
5. Mamalis N, Garland PE, Argyle JC, Appla DJ. Congenital
orbital teratomas. A review and report of 2 cases. Surv
Ophthalmol 1985;30:41.
6. Ide CH, Davis WE, Black SPW. Orbital teratoma. Arch
Ophthalmol 1978;96:2093.
7. Volve NJ, Jakobeic FR. Pediatric orbital tumors. Inter
Ophthalmol Clinics 1992;32,1:223.
8. Henderson JW. Orbital tumors. New York. Theime Straton
1980;472.
9. Lewis RA, Gensen LP, Axelsen KA et al. von Recklinghausen’s
neurofibromatosis II. Incidence of optic glioma. Ophthalmo-
logy 1984;91:929.
10. Sheilds JA, Bakerwell B, Augusberger JJ et al. Orbital space
occupying lesions in children. A review of 250 case routine
biopsies. Ophthalmology 1986;93:379.
11. Wharam M, Beltangardy M, Haya D et al. Localized orbital
rhabdomyosarcoma. Ophthalmology 1987;94:251.
12. Knowks DM, Jakobeic FA, Potter G et al. Ophthalmic striate
muscle neoplasm. A clinicopathological study. Surv
Ophthalmol 1976;21:219.
832 Section 7: Pediatric Ophthalmology Including Strabismus
13. Abramson DH, Ellisworth RM, Tretter P et al. The traetmenmt
of orbital rhabdomyosarcoma with radiation and chemo-
therapy. Ophthalmology 1979;86:1330.
14. Howard GM, Castern VG. Rhabdomyosarcoma of the orbit
in brothers. Arch Ophthalmol 1963;70: 391.
15. Shields JA, Shields CL. Rhabdomyosarcoma of the orbit. Intl
Ophthalmol Clin 1993;33:303.
16. Shields JA, Blackwell B, Aushberger JJ et al. Space occupying
orbital masses in children. Areview of 250 consecutive
biopsies. Ophthalmology 1986;93:379.
17. Frayer WS, Enterlin HT. Embryonal rhabdomyosarcoma of
the orbit in children and young adults. Arch Ophthalmol
1959;62: 203.
18. Fekrat S, Mitter NR, Lemoy MC. Alveolar rhabdomyo-
sarcoma that metastatize in the orbit. Arch Ophthalmol
1993;111:1662.
19. EllenbogenE, Lasky MA. Rhabdomyosarcoma of the orbit in
the newborn. Am J Ophthalmol 1975;80:1024.
20. Manner GE, Rose GE, Plouman PN. Multidiscplinary
management of refractory orbital rhabdomyosarcoma.
Ophthalmology 1997;104:1198.
21. Haik BG, Jereb B, Smith ME et al. Radiation and chemo-
therapy of parameningeal rhabdomyosarcoma involving the
orbit. Ophthalmology 1986;93:1001.
22. Shields JA, Shields CL, Eagle RC et al. Orbital rhabdo-
myosarcoma. Arch Ophthalmol 1987;105:784.
23. Albert DM, Rubenstein RA, Scheie HG. Tumor metastasis to
the eye. Clinicval study in infants and children. Am J
Ophthalmol 1967;63:727.
24. Musarella MA, Chen HSL, DeBoer G, Galle BI. Ocular
involvement in neuroblastoma: Prosthetic implications.
Ophthalmology 1984;91:936.
25. Davis JL, Parke DW II, Front RL. Granulocytic sarcoma of
the orbit: A clinicopathological study. Ophthalmology
1990;92:1758.
26. Goldberg RA, Rootman C. Linc RA. Tumor matastasis to the
orbit,. Surv Ophthalmol 1990;35:1.
27. Volve NJ, Jacobeik FA. Pediatric orbital tumor. Intl
Ophthalmol Clin 1992;33:1.
28. Foroozan R, Shields CL, Shields JA et al. Congenital orbital
varices causing extreme neonatal proptosis. Am J Ophthalmol
2000;129: 693.
29. Rosenblum P, Zilkha A. Sudden visual loss secondary to an
orbital varix. Surv Ophthalmol 1978;23:49.
30. Shields JA, Dolinskas C, Augsburger JJ et al. Demonstration
of orbital varix with computed tomography and valsalva
maneuver. Am J Ophthalmol 1984;97:108.
31. Henderson JW. Orbital tumors. WB Saunders, Philadelphia,
1973.
32. Ilift WJ, Green WR. Orbital lymphangioma. Ophthalmology
1979;86: 914.
33. Jonas IS. Lymphangioma of the ocular adnexa. An analysis
of 62 cases. Trans Am Ophthalmol Soc 1959;57:602.
34. Kennerdel JS, Maroon JC, Garrity JA, et al. Surgical
management of orbital lymphangioma with carbon dioxide
laser. Am J Ophthalmol 1986;102:308.
35. Robb BM. Refractive errors associated with hemangioma of
eye lid and orbit in infants. Am J Ophthalmol 1977;83:52.
36. Stigmar G, Crawford JS, Ward CM et al. Ophthalmic sequele
of infantile hemangioma of the eyelids and orbit. Am J
Ophthalmol 1978;5:506.
37. Mombart SI, Schlngermann RO, Goldschmecling H et al.
Idiopathic pseudotumor in childhood. Ophthalmology
1996;103:2135.
38. Mottowlippa I, Jacobeic FA, Smith M. Idiopathic inflam-
matory orbital pseudotumor in childhood. Ophthalmology
1981;88:565.
39. Allen JC, France TP. Pseudotumor of the orbit and peripheral
uveitis. J Pediatri Ophthalmology.
40. Rootman J, Nugent R. The classification and management of
acute orbital pseudotumor. Ophthalmology 1982;89:1040.
41. Jacobeic FA, Rootman J, Jones JS. Secondary and metastatic
tumors of the orbit. In Duane TD (Ed) Clinical ophthalmology
Vol 2. New York, Harper & Row 1978.
42. Kincaid MC, Green VR. Ocular and orbital involvement in
leukemia. Surv Ophthalmol. 1983;27:211.
43. Bullock JD. Orbital tumors of childhood. Ophthalmology
1986;93:379.
 Chapter 106
Pediatric Posterior Uveitis
V Gupta, A Gupta
The age of the patient can be useful in establishing
the differential diagnoses of the uveitis because certain
causes of uveitis are more common among specific
age groups. Following are the uveitis commonly seen
during childhood.
1. Toxoplasmosis
2. Toxocariasis
3. Postviral neuroretinitis
4. Sarcoidosis
5. Masquerade syndromes
• Retinoblastoma
• Leukemia
• Juvenile xanthogranuloma
• Retinitis pigmentosa
• Intraocular foreign body
• Peripheral retinal detachment.
Toxoplasmosis and sarcoidosis are discussed in
detail elsewhere. Here we will discuss toxocariasis and
masquerade syndromes in detail.
TOXOCARA
Toxocara canis, i.e. dog roundworm is an important
cause of posterior uveitis with reduced visual acuity
in young patients. The disease is typically found in
children. The average age of presentation being 7.5
years (range 2-31 years).1
Life Cycle
The organism has a complete life cycle in dogs and
incomplete in humans (Fig. 106.1). In dog’s intestine
the ova hatch and second stage larvae pass through
the intestinal wall to various organs including liver
and lung from where they are coughed up, pass
through the trachea and are swallowed. These larvae
mature to adult worms in dog’s intestines and lay eggs
which are excreted in feces. In humans, however, the
ingested ova hatch into larvae in small intestines of
children from where they pass through the intestinal
wall and migrate to various organs like liver, lung,
brain, and eye. But the organism does not return to
the intestine, and therefore not shed in the feces.2
Clinical Presentation
Several ‘typical’ ocular presentations have been
described that can be classified as the following:
1. Chronic endophthalmitis
2. Posterior pole granuloma
3. Peripheral granulomatous inflammatory mass.
Chronic Endophthalmitis
This presentation is seen in slightly younger patients
(2-9 years).3 The first Toxocara canis endophthalmitis
was described histologically in 1950.4 The disease
mimics any chronic endophthalmitis, but, there is no
history of trauma or intraocular surgery. History of
pica, however, can be obtained in many children.5 The
anterior chamber may be quiet or associated with a
granulomatous response with keratic precipitates,
posterior synechiae, and hypopyon. The vitreous may
be hazy with dense cellular infiltrates and later on
cyclitic membranes may be formed. This would make
visualization of the retina difficult. Retina might show
the presence of an ill-defined yellowish white mass
or secondary retinal detachment. The vision is grossly
diminished in these eyes and prognosis depends upon
the amount of intravitreal organization that occurs
during acute inflammation.
Posterior Pole Granuloma
This form generally presents in children between 6-
14 years of age. It generally presents with vitreous haze
834 Section 7: Pediatric Ophthalmology Including Strabismus

Fig. 106.1: Life cycle of Toxocara canis

(Modified from Shields JA: Ocular toxocariasis: A review. Surv Ophthalmol 1984;28:361-81)

and signs of acute inflammation with a posterior pole
granuloma that presents as an elevated whitish mass
with overlying vitritis. These granulomas are mostly
white or gray in color, spherical, elevated and various
traction bands can be seen running from the granu-
loma to the surrounding retina (Fig. 106.2). The main
presenting feature in these children is decreased vision
or leukocoria and the prognosis is relatively good,
unless the central vision has already been lost.
Peripheral Granuloma
This form presents somewhat later in life as a whitish
lesion that is spherical and localized in the peripheral
fundus. At times, the inflammation may be much
severer and appear as ‘snowbank’ typically seen in
the intermediate uveitis, a condition which is bilateral
in majority of cases; toxocariasis is almost always
unilateral. There may be traction bands seen running
from this mass to the posterior pole of the retina or
the optic nerve and can result in macular dragging/
heterotopia, strabismus, and decreased vision.
Atypical Presentations
Rarley toxocara could present as the following:
1. Inflammation of optic nerve head, i.e. papillitis.
2. Diffuse unilateral subacute neuroretinitis syn-
drome.6
3. Diffuse chorioretinitis.
4. Exudative retinal detachment.
 Chapter 106: Pediatric Posterior Uveitis
Fig. 106.2: Posterior pole toxocara granuloma with
associated vitreous membranes
Differential Diagnosis
Ocular toxocariasis is one of the most important diffe-
rential diagnoses in cases of young children presenting
with leukocoria. Other causes include retinoblastoma,
persistent hyperplastic primary vitreous (PHPV),
retinopathy of prematurity (ROP), toxoplasmosis,
intermediate uveitis, Coats’ disease, familial exuda-
tive vitreoretinopathy, and other forms of endoph-
thalmitis and uveitis.
Retinoblastoma
It is of utmost importance to recognize and diagnose
this condition accurately as retinoblastoma is the most
important entity, that is frequently confused with
ocular toxocariasis. However, patients with retino-
blastoma are usually less than 2 years of age, signs of
vitreoretinal traction, inflammatory cyclitic memb-
ranes, and secondary cataract are absent in retino-
blastoma. In difficult cases, ultrasonogrpahy and
computed tomography may be helpful in demons-
trating intraocular tumors and calcification.
Retinopathy of Prematurity (ROP)
In both ROP and cicatricial toxocariasis, there is a
peripheral retinal mass with a fold of retina extending
between the focus of inflammation and the posterior
pole. However, there is invariably a history of
prematurity in ROP and the disease is diagnosed soon
after birth. Also, ROP is bilateral and toxocariasis is
almost always unilateral.
835
Coats’ Disease
Both Coats’ disease and ocular toxocariasis occur in
the same age group and are unilateral. However,
fundus in Coats’ disease shows the presence of
telangiectatic intraretinal vessels associated with
yellow intraretinal and subretinal exudates. Also,
vitreous in Coat’s disease does not show any sign of
inflammation or intravitreal membrane.
PHPV
It is diagnosed within first few weeks of birth, typically
in microphthalmic eyes. This presents as a retrolental
fibrous mass and can be distinguished easily from
toxocariasis.
Familial Exudative Vitreoretinopathy (FEVR)
This disease also has a fold of retina extending from
the posterior pole to the peripheral mass. This
peripheral mass is associated with anomalous vessels.
However, FEVR has a strong family association and
is almost always bilateral.
Pars Planitis
Pars planitis occurs in slightly older age group and is
bilateral in approximately 80 percent of the cases.
Pathology
Atypical lesion demonstrates a dead nematode in the
center encysted by granulomatous inflammation
comprising of eosinophils, epithelioid cells, lympho-
cytes, and plasma cells.
Laboratory Tests
ELISA Test
This is the most reliable test to detect toxocara
antibodies. In this, the 2nd stage larval secreted
antigen is first extracted and then used for detection
of antibodies in serum and aqueous/vitreous.
Intraocular fluids including aqueous or vitreous may
give a positive result even if the serum titers are
negative. A titer of 1:8 in serum is considered the most
sensitive and specific for the diagnosis of toxocariasis.
Cytology
Intraocular fluid, i.e. aqueous or vitreous may reveal
the presence of eosinophils. Maguire et al7 isolated
836 Section 7: Pediatric Ophthalmology Including Strabismus
the remnants of Toxocara organism from vitrectomy
specimens.
Treatment
Medical
The medical management of the disease involves the
use of steroids or antihelminthics. Periocular or
systemic steroids are used primarily to minimize the
sequelae of inflammation and are indicated in cases
of posterior pole granulomas or endophthalmitis.
However, the role of antihelmentics, like thiaben-
dazole or diethyl carbazine is not clear. These drugs
cause the death of intraocular larvae which causes
significant inflammation within the eye. If anti-
helmentics are used, they should be given in
combination with steroids which can combat the
severe inflammatory response caused by the death of
the larvae.
Surgical
Surgery has been suggested in the presence of
complications, like cataract, glaucoma, cyclitic
membranes, retinal detachment or macular traction.
The most common indication for pars plana vitrec-
tomy (PPV) in these cases is retinal detachment.8
Vitreous surgery is preferred to conventional scleral
buckling as the former helps in clearing-up of the
transvitreal membranes as well. Hagler et al8 operated
on 17 patients with retinal detachment and were able
to reattach retina in 12, while 15 had a stabilization/
improvement of the visual acuity. Belmont et al9 also
reported favorable outcome in those patients who
underwent pars plana vitrectomy.
Laser
Laser photocoagulation of the motile nematode has
been tried with an aim to destroy motile worm, which
is at least 3 mm from the foveola and approaching
fovea or optic disk. But laser itself might induce
inflammation that may require steroids.2
MASQUERADE SYNDROMES
These consist of a group of disease entities which are
primarily noninflammatory in nature but clinically
present and often misdiagnosed as chronic idiopathic
uveitis. It is of utmost importance to diagnose the
underlying cause, as many of these are malignant pro-
cesses that might be overlooked and thus mis-
managed. The most important of these entities that
are seen in pediatric age group are summarized in
Table 106.1.
Table 106.1: Disease entities masquerading as uveitis
Malignant Nonmalignant
1. Retinoblastoma 1. Intraocular foreign body
2. Leukemia 2. Peripheral retinal detachment
3. Medulloepithelioma 3. Retinitis pigmentosa
4. Juvenile xanthogranuloma 4. Postvaccination
Malignant
Retinoblastoma is the most common intraocular
malignancy in pediatric age group and must always
be ruled out in all the children of less than 5 years
presenting with uveitis. The presenting feature in these
children may be leukocoria, strabismus or signs of
intraocular inflammation. Intraocular inflammation
may present as anterior uveitis with pain and redness,
ciliary injection, and hypopyon. The hypopyon in
these has been found to be comprised of malignant
cells and also called ‘pseudohypopyon’.10 At times,
the inflammation may be severe enough to produce a
clinical picture mimicking ‘endophthalmitis’ or even
‘panophthalmitis’.
All these children with undiagnosed intraocular
inflammation and suspicion of retinoblastoma can be
diagnosed with the aid of an ultrasound or CT scan.
The presence of a mass with associated calcification
in the tumor is characteristic of retinoblastoma.
Leukemia
Acute myelogenous leukemia may also manifest as
uveitis in children. These leukemias may present as
anterior uveitis, iris heterochromia, spontaneous
hyphema or raised intraocular pressure.11,12 Posterior
segment examination would reveal characteristic
white centered hemorrhages and cotton wool spots.11
Rare manifestations include serous retinal detachment
and peripheral neovascularization. Optic nerve
involvement manifesting as optic nerve infiltration
and papilledema are other common manifestations.
The diagnosis is established by bone marrow biopsy
and peripheral blood smears.
Other tumors like medulloepithelioma and benign
lesions like juvenile xanthogranuloma can also
 Chapter 106: Pediatric Posterior Uveitis
masquerade as idiopathic uveitis.13 Juvenile xantho-
granuloma is seen in a child usually under one year
of age and presents with anterior chamber flare and
cells or spontaneous hyphema. The diagnosis is
confirmed by skin examination and iris biopsy if
needed.
Nonmalignant Diseases
A number of nonmalignant disease can masquerade
as idiopathic uveitis. An important entity in children
is the retained intraocular foreign body that might
elicit an anterior or posterior uveitis. It is important
to take a history of antecedent trauma in children with
uniocular idiopathic uveitis. Gonioscopic examination
might reveal a foreign body in the angle. Other cases
might need an X-ray, ultrasound or CT scan to confirm
the diagnosis.
Retinal detachment can also sometimes produce
intraocular inflammation that could be misdiagnosed
as uveitis and myopic degenerations too could
produce cream colored atrophic lesions mimicking
focal choroiditis.
Patients with retinitis pigmentosa might have
associated vitritis, posterior subcapsular cataract, and
cystoid macular edema and in cases where bone
spicule pigmentation is minimal, the underlying
diagnosis of retinitis pigmentosa may be missed.
Finally, uveitis may also occur after vaccination in
children.14
It is thus evident that a number of these diseases
can cause intraocular inflammation. In the absence of
correct diagnosis, these disorders could be inappro-
priately treated and thus should be considered in the
837
evaluation of all children with undiagnosed intra-
ocular inflammation.
REFERENCES
1. Brown DH. Ocular toxocara canis—A clinical review. J
Pediatr Ophthalmol 1970;7:182-91.
2. Shields JA. Ocular toxocariasis: A review. Surv Ophthalmol
1984;28:361-81.
3. Smith RE, Nozik RA. Uveitis. A Clinical Approach to
Diagnosis and Management (2nd ed) Baltimore: Williams and
Wilkins, 1989;135-40.
4. Wilder HC. Nematode endophthalmitis. Trans Am Acad
Ophthalmol Otolaryngol 1950;55:99-109.
5. Wilkinson CP. Ocular toxocariasis Chap. 93. In Ryan SJ (Ed):
Medical Retina. Mosby-year book, Inc. St. Louis, Missouri
1994;1545-52.
6. Gass JDM, Gilbert WR Jr, Guerry RK et al. Diffuse unilateral
subacute neuroretinitis. Ophthalmology 1978;85:521-45.
7. Maguire AM, Green WR, Michels RG et al. Recovery of intra-
ocular Toxocara canis by pars plana vitrectomy. Ophthalmo-
logy 1990;97:675-80.
8. Hagler WS, Pollard ZF, Jannett WH et al. Results of surgery
for ocular Toxocara canis. Ophthalmology 1981;88:1081-86.
9. Belmont JB, Irvine A, Benson W et al. Vitrectomy in ocular
toxocariasis. Arch Ophthalmol 1982;100:1912-15.
10. Rao NA, Forster DJ, Spalton DJ. Masquerade syndromes and
AIDS Chap 9. In Poods SM, Yanoff M (Eds): The Uvea, Uveitis
and Intraocular Neoplasms: Textbook of Ophthalmology
Mosby Wolfe 1992;2:9.1-9.6.
11. Kincaid MC, Green WR. Ocular and orbital involvement in
leukemia. Surv Ophthalmol 1983;27:211.
12. Ridgway EW, Jaffe N, Walton DS. Leukemic retinopathy in
children. Cancer 1976;38:1744.
13. De Barge LR, Chan CC, Greenberg S, et al. Chorioretinal, iris
and ciliary body infiltration by juvenile xanthogranuloma
masquerading as uveitis 1994;39:65-71.
14. Nussenblatt RB, Whitcup SM, Palestine AG. Uveitis
Fundamantals and Clinical Practice (2nd edn) Mosby-
Yearbook, Inc. 1996;385-95.
 Chapter 107
Retinopathy of Prematurity
S Natarajan, B Dutta
DEFINITION
Retinopathy of prematurity (ROP) is a vasoprolife-
rative retinopathy which occurs principally, but not
exclusively in premature infants.1
It occurs in the following two overlapping phases:
1. An acute phase in which normal vasculogenesis is
interrupted and a response to injury is observable
in the retina.
2. A chronic or late proliferative phase in which
membranes grow into vitreous causing tractional
retinal detachment, ectopia or scarring of macula
leading to severe visual loss.
More than 90 percent of ROP cases undergo spon-
taneous regression with minimal scarring and little
or no visual loss. Less than 10 percent of the involved
eyes develop significant cicatrization.
INTRODUCTION
The condition was first described by Theodore Terry,1
a pathologist and ophthalmologist from Texas, in 1942
in a six-month-old premature infant who had grayish-
white vascular membranes behind each lens. One eye
was enucleated to rule out retinoblastoma. The
histopathology showed that the retina was incorpo-
rated in fibrous tissue behind the lens and hence it
was called retrolental fibroplasia (RLF).2 Subsequently
RLF was more accurately characterized both clinically
and histologically as retinopathy of prematurity.
Campbell3 of Australia first brought to notice the
relationship of intensive oxygen therapy in infants and
the subsequent development of ROP. In 1952, Patz et
al4 identified the link between ROP and the high
concentrations of oxygen.
The first randomized prospective study carried out
by Kinsey5 clearly established that the incidence of
ROP was inversely proportionate to the birth weight.
Normal Vasculogenesis in ROP
Ashton6 postulated that at 16 weeks of gestation the
mesenchyme grows out of the optic disk in the form
of sheets or cords. This tissue is the precursor of the
capillary network that follows. The tissue penetrates
the nerve fiber layer and grows centrifugally reaching
the nasal ora serrata by 36 weeks of gestation and the
more distant temporal ora serrata by 40 weeks of
gestation. This probably accounts for the pre-
ponderance of the disease to the temporal retina. The
edge of this tissue has a delicate network of capillaries
resembling to chicken wires, which by proliferation
and remodeling results in mature arteries and veins
surrounded by a capillary network.
An incompletely vascularized retinal periphery is
one important factor for ROP development. A fully
vascularized retinal periphery is resistant to hypoxia.
Ashton6 and Patz4 worked out that high oxygen levels
obliterate the newly formed capillaries by damaging
the endothelium. The damage is either due to a direct
cytotoxic effect of oxygen or a secondary response to
the reduced retinal blood flow due to severe vaso-
constriction.
Abnormal Vasculogenesis in ROP
Pathogenesis starts in the following successive
stages:4,7
1. An injury from unidentified noxious agent which
destroys vascular endothelium at the primitive
capillary network and obliterates the network.
2. The mesenchymes and the mature arteries and
veins survive, and unite with one another via the
remaining few channels.
3. The mesenchyme stops its peripheral advancement
and piles up like a shelf forming the mesenchymal
A-V shunt. It demarcates the vascular from the
 Chapter 107: Retinopathy of Prematurity 839
avascular retina. This shunt is fed and drained by the disk. The nasal retina becomes thin due to traction
dilated irregular vessels which loose their clear causing retinal pigment epithelium migration and an
identity as arteries or veins. There are no capillaries albinotic appearance of the fundus (Fig. 107.1). As the
in this shunt, but has an irregular pattern of disease progresses the cicatrix leads to secondary
canalization like a hepatic sinusoid. The channels myopia, macular ectopia, vitreous traction and retinal
are lined by immature endothelial cells which stain detachment (Fig. 107.2). Late events include secondary
and leak dye profusely on fluorescein angiography. glaucoma, vitreous hemorrhage, synechiae formation,
The visual prognosis of the disease depends on the and phthisis bulbi. The scar tissue gets pulled up
extent and location of the shunt. The more posterior behind the lens and appears as a white fibrovascular
the location and greater the extent, the worse the mass.
prognosis. The shunt is usually on temporal side
in a wedge shape with its apex at the disk. CLASSIFICATION
4. Next follows a static period in which after a brief
ROP was classified before as active and cicatricial. To
period of few days to months no vasculogenic
diagnose and treat ROP at its earliest stage the inter-
activity occurs and this lasts for few days to
national system of classification was developed in
months. In the next stage the shunt tissues thicken
1984.8 This system provides a standardized frame-
and form a grayish color which change to pink,
work that can be used to follow clinical progression
salmon, and then red. It is during this period that
of the disease. The classification focuses on the
the real fate of the eye depends. If the cells of the
following three clinical parameters—the stage of
shunt divide and differentiate into normal capillary
vascular proliferation, the location of the disease, and
endothelium, then they will form primitive
endothelial tubes. This is called regression of ROP
which fortunately occurs in more than 90 percent
of cases.
5. Nearly 10 percent of cases which undergo extra-
retinal neovascular proliferation develop end stage
of the disease. In such eyes the primitive cells of
the shunt multiply and break through the internal
limiting membrane of the retina, but do not
differentiate into normal endothelium. They
instead, grow into the vitreous, over the surface of
the retina and ciliary body to the lens equator. It is
this lack of differentiation and destructive
proliferation which leads to formation of a memb-
rane and ultimately tractional retinal detachment. Fig. 107.1: Cicatricial ROP with fibrovascular
These events may occur over days, weeks or proliferation in temporal periphery
months.
When complete regression occurs the peripheral
retina is transparent and the AV shunt is demarcated
by an area of faint wrinkling and whitening of the
internal limiting membrane.
If regression is incomplete there is extensive
damage with a thin opaque retina and large areas of
scarring with capillary-free zones. The vasculature
extends into the retina as finger-like processes with
its own arteriole or venule and no capillaries in
between. Pigmentary changes and choriocapillaries
are seen in these capillary-free areas. As the scar in
the periphery contracts, it pulls along with the neuro-
sensory retina, blood-vessels, pigment epithelium and Fig. 107.2: Dragging of optic disk in cicatricial stage of ROP
840 Section 7: Pediatric Ophthalmology Including Strabismus
the extent of involvement. This system of classification,
which has been framed by 23 ophthalmologists of 11
countries is summarized below:9
Location of the Disease
For this purpose, the retina is divided into the
following three zones:
Zone I
The inner zone extends from the optic disk to twice
the disk-macular distance or 30 degrees in all
directions from the optic disk.
Zone II
This extends from the outer border of zone I to the
ora serrata on the nasal side and the equator on the
temporal side.
Zone III
The outer zone extends from the outer edge of zone II
in a crescentic fashion to the ora serrata.
The extent of the vascular involvement is simply
coded by the number of clock hours involved.
Stages of the Disease
Stage 1 (Demarcation line)
This line is a thin structure that separates the avascular
retina anteriorly from the vascularized retina
posteriorly. It is relatively flat, white in color and lies
in the plane of the retina. The retinal vessels leading
to this line show brush like endings (Fig. 107.3A).
Stage 2
The line of stage 1 has grown in height and width. It
occupies a volume and extends out of the plane of the
retina. The ridge may change its color from white to
pink and the vessels leave the plane of the retina to
enter it. Small isolated tufts of new vessels lying on
the surface of the retina may be seen posterior to this
ridge (Figs 107. 3B). Anterior to the ridge are the
spindle cells. The exact origin and the nature of these
cells are not known; these are glycogen-rich and are
believed to be the precursors to vascular development.
Stage 3 (Ridge with Extraretinal
Fibrovascular Proliferation)
To the ridge of stage 2 it is added the presence of extra-
retinal fibrovascular proliferative tissue which is
located posterior to it. The capillary plexus exits the
retina proper and extends through the internal
limiting membrane into the vitreous gel. This stage is
subdivided into three stages—mild, moderate, and
severe, depending on the amount of fibrovascular
proliferation (Fig.107.3C).
Stage 4 (Partial Retinal Detachment)
To the above stages is added partial detachment of
the retina (Fig.107.3 D), which may be due to exudative
effusion of fluid, traction or both. This stage is
subdivided into the following:
A. Extrafoveal retinal detachment which is a convex
tractional detachment which occurs in the peri-
phery without macular involvement (Fig. 107.4A).
B. Partial retinal detachment including the fovea. It
usually extends in the form of a fold from the disk
through zone I to involve zones II, and III (Fig.
107.4B).
Stage 5 (Total Retinal Detachment)
This detachment is always funnel shaped for descrip-
tive purpose. The committee divided the funnel into
an anterior and a posterior part.
Regressed ROP
Though not an integral part of the classification, the
committee recognizes that regression is the most
common outcome of ROP. Regression has a broad
spectrum of peripheral and posterior retinal changes
along with vascular changes.
Plus Disease
This is typified by increasing dilatation and tortuosity
of the retinal vessels of the posterior pole, iris vascular
engorgement, pupillary rigidity, and vitreous haze
and/or hemorrhage. Plus disease is a sign of poor
prognosis and may be associated with threshold or
prethreshold retinopathy of prematurity.
Threshold ROP
Threshold ROP is defined as stage 3 ROP involving
five or more contiguous or eight or more cumulative
clock hours, in the presence of congestion of the
posterior pole vessels— ‘plus disease.’
 Chapter 107: Retinopathy of Prematurity 841

A B

C D
Figs 107.3A to D: Stages of active retinopathy of prematurity: (A) Demarcation line, (B) Fibrovascular ridge,
(C) Extraretinal, fibrovascular, proliferation, (D) Retina detached inferiorly

Fig. 107.4A: Stage 4: Retinal detachment—ridge with Fig. 107.4B: Stage 4: Retinal detachment—fibrovascular
extrafoveal detachment ridge with foveal detachment

RISK FACTORS FOR ROP Delicate Balance

Birthweight and Gestational Age
Immaturity is the most important risk factor for ROP.
Infants weighing more than 1500 gm and gestation
period of more than 31 weeks rarely develop the
disease. Infant weighing less than 1000 gm and under
28 weeks of gestation are at highest risk for severe
ROP.
The balance between the oxidants and antitoxidants
in the retina is altered by the following:
a. Changes in oxygen tension—the percentage and
duration of oxygen therapy correlate with the
severity of ROP. However, ROP occurs even
without history of oxygen therapy.
842 Section 7: Pediatric Ophthalmology Including Strabismus
b. Endogenous antioxidant deficiency (vitamin E and
other natural antioxidants).
c. Endogenous oxygen released by macrophages in
sepsis.
d. Shifts in oxygen-hemoglobin dynamics due to
blood transfusions and intraventricular hemor-
rhage, shock or conditions requiring exchange
transfusions.
e. Hypercarbia or hypocarbia and prolonged parente-
ral nutrition.
Prolonged Intubation and Multiple Gestation
These are independent risk factors:
Despite an awareness of these factors, the incidence
of ROP has increased unavoidably as the survival of
premature infants has increased, especially in those
weighing less than 1000 gm at birth. However, there
has been reports of ROP in full term infants10 without
any risk factors and this is thought to be the occurrence
of active lesion in utero.
EXAMINATION FOR ROP
A detailed history should be obtained regarding birth
weight, gestational age, amount and duration of
oxygen exposure, presence or absence of anemia,
septicemia, respiratory distress syndrome and blood
transfusions.
Time of Examination
The first examination should be done at 3-4 weeks of
age in all high-risk premature babies and should be
repeated after every 2 weeks till the day of discharge.
If no sign of ROP are seen after discharge, follow the
infants monthly till the peripheral retina is fully
vascularized.11
Technique of Examination
Pupillary dilatation is done by instilling one drop of
2.5 percent phenylephrine and 1 percent cyclo-
pentolate twice at an interval of 10 minutes.11,12 Exami-
nation is performed by binocular indirect ophthalmo-
scope. The fundus examination should stress on the
following points:
Location of the vascular zone, state of vessels, pre-
sence of the ridge, amount of fibrovascular prolife-
ration, signs of plus disease, and evidence of early
cicatrization. Close monitoring of the baby’s vital signs
like pulse, respiration and abdominal girth should also
be done during the examination.
The clinical pattern of the disease can be divided
into acute ROP and chronic or cicatricial disease.11,13,14
Mild Acute ROP
In the early stage of ROP, a demarcation line appears
between the vascular (rearguard) and avascular
(vanguard) retina. The demarcation line is flat and
white and lies within the plane of the retina. This stage
may be transient, and this early stage of ROP is most
variably reported.
If ROP progresses, the demarcation line develops
into a thickened and pink structure that extends out
of the plane of the retina. This is known as the “ridge”
or “mesenchymal shunt.” Vessels from the posterior
retina enter the ridge and isolated tufts of vessels are
also seen in this region. In more than 80 percent of
patients, spontaneous regression occurs without any
residual scarring.
Severe Acute ROP
With progression of the disease, fibrovascular
proliferation into the vitreous continues and the poste-
rior surface of the ridge becomes ragged. Severe forms
of ROP do undergo regression but less frequently than
the milder forms.
With further progression of the disease, there is
dilatation and tortuosity of the vessels of the posterior
pole. Next, myofibroblasts from the ridge migrate to
the vitreous and forms a contractile fibrovascular
mass. This leads to vitreoretinal traction causing
retinal detachment. Peripheral tractional detachments
lead to total retinal detachments which funnels within
a short time. Subsequently, the funnel closes and forms
a mass behind the lens due to continued cellular
proliferation between the apposed layers of the retina.
Rush Disease
This is unusually an aggressive pattern of ROP that
usually manifests at an earlier age of 3 to 5 weeks.
These patients have birthweights below 1000 gm and
some of them proceed very rapidly to severe ROP and
retinal detachment.
Cicatrization
In milder cases, the sequelae to ROP include high
myopia, vitreoretinal membrances, and small areas of
 Chapter 107: Retinopathy of Prematurity
irregular pigmentation in the peripheral. Significant
retina changes include disk pallor and straightening
and dragging of vessels, including the macula, to the
periphery. Areas of avascular peripheral retina and
lattice degeneration with retinal holes are frequently
observed. Falciform retinal folds are seen in severe
cases.
In the most severe cases, the totally detached retina
transforms into a thickened mass behind the lens. Only
this form of the disease is now called “retrolental
fibroplasia” which was previously applied to the
entire disease process.
PREVENTION AND TREATMENT
Decreasing Risk Factors
A high quality of perinatal-neonatal care with close
monitoring of oxygen levels is essential.
Vitamin E
Vitamin E is a natural retinal antioxidant found in the
inner layers of the retina. During maturation, the
photoreceptors synthesize and secrete interstitial
retinol binding protein (IRBP). At 28 weeks of
gestation a critical amount of IRBP must be present in
order to transfer threshold levels of supplemental
vitamin E into the inner retinal layers. Vitamin E
protects the proliferating spindle cells in the nerve
fiber layer. The preterm infant is deficient in vitamin
E at birth owing to a 4:1 placental permeability factor
and low plasma lipid and lipoprotein levels. This
results in plasma levels of 0.4 mg/dl, in contrast to
the normal levels of 1-3 mg/dl. Moreover, vitamin E
levels drop quickly in unsupplemented preterm
newborns owing to lack of adipose tissue for storage.
If the environmental oxygen increases, IRBP does not
reach the ora serrata until 32 weeks of gestation and
thus, premature babies have extensive peripheral
retinal areas with low levels of vitamin E. This
facilitates extensive formation of gap junctions
between spindle cells of mesenchyme and abnormal
vasculogenesis. The use of vitamin E and its supple-
ments to decrease the severity of ROP, was first
described by Owens and Owens in 1949.15 Phelps and
Rosenbaum16 confirmed the result of the beneficial
effects of vitamin E on oxygen induced retinopathy
in kittens. But when controlled, masked, and
randomized trials17 were done, there was no statistical
significance between the treated and untreated
843
groups. The vitamin E analogue di-alfa tocopherol (20
mg/kg) was given by rapid intravenous infusion.
Though vitamin E therapy is considered to be
efficacious, questions arise about its risk-benefit ratio.
As the controversy over vitamin E continues, multi-
vitamin formulations used in neonatal care units are
now supplemented with adequate vitamin E to
maintain the plasma level of babies, close to the adult
physiological range.
In conclusion, although there is some evidence that
vitamin E administration may be helpful in ROP
prevention, the overall data from the prospective
studies are conflicting, and hence, the routine use of
vitamin E is not recommended.
Surfactant
Artificial lung surfactant are now being increasingly
used to prevent or treat respiratory distress in
newborns. Its effect on ROP is not known. But recent
studies suggest that the use of prophylactic exogenous
surfactant had a beneficial effect on the development
of cicatricial ROP.18
TREATMENT
Cryotherapy
The first report on cryotherapy for ROP was made by
Hindle and Leyton.19 They directly froze the fibro-
vascular ridge and the areas anterior and posterior to
it after using one or two rows of cryo application. Ben
Sira et al20 used the indirect method of cryo treatment
only to the anterior avascular retina avoiding the ridge
and the new vessels posterior to it.
The rationale behind cryotherapy was thought to
be the elimination of the production of a vaso-
proliferative factor produced by the avascular retina
in the periphery as in diabetic retinopathy. By ablating
the peripheral zone of avascular retina, cryotheraphy
destroys the source of the vasoproliferative factor and
the preretinal new vessels regress.
It is recommended that treatment should be
withheld till stage 3 ROP of international classification
and when confluent fibrovascular proliferations of
more than 3 to 6 o’clock hours are found.
Technique
Treatment is done when infants are between 7 and 20
weeks of age under GA. Using indirect ophthalmo-
844 Section 7: Pediatric Ophthalmology Including Strabismus
scope, cryo is applied to the entire avascular zone
anterior to the ridge. The thin mira retinal cryoprobes
are used with temperature settings of –25 to –55
degrees.
Effect
Within 24 hours the signs of plus disease usually
disappear, the vessels are less engorged and the pupil
less rigid. In the next couple of weeks, the neovascular
ridge involutes and normal blood vessels grow
between the nonconfluent cryoscars. About 3 weeks
later the retina looks normal except for the pigmented
cryoscars in the periphery.
Complications
Cryotherapy has the following complications:
a. Accidental freezing of the fibrovascular tissue can
occur resulting in retinal or vitreous hemorrhage,
which increases the chances of PVR.
b. Excessive pressure by cryoprobes may occlude the
central retinal artery or may cause bradycardia due
to oculocardiac reflex.
c. Macular coloboma-like lesions and macular
pigment abnormalities21 are found in very low
birth weight infants receiving cryotherapy. This is
probably related to a greater severity of ROP and
a greater amount of cryotherapy.
Multicentric Cryotherapy Trial for ROP
A multicenter, double-blind controlled study of cryo-
therapy for ROP was started in January 1986. The
secondary objective of the study is to examine the
natural history of the disease which is divided into
two phases.
Phase I22 began in January 1986 and ceased two
years later as it was found that cryotherapy did reduce
the incidence of adverse outcome from severe ROP
by about 50 percent compared to the untreated control
group. Phase II, which began in 1989 is designed to
monitor the long-term effects of cryotherapy on the
eyes of the randomized group during the first 6 years
of life. Secondly, some phase I study patients will be
followed up to gather information on the natural
history of ocular and visual development in very low
birth weight (VLBW) infants.
Design of Study
The report recommends that cryotherapy should be
considered for both eyes whenever stage 3+ ROP
involves the zone I of both eyes. The result showed an
unfavorable result in 25.7 percent of the eyes that
received cryotherapy compared with 47.4 percent of
the control eyes as regards the masked grading of
fundus photographs.
Cryotherapy reduces the risk of unfavorable retinal
and functional outcome from threshold ROP.23,24
Laser Photocoagulation
Photocoagulation was attempted earlier for peripheral
retinal ablation in ROP. As cryotherapy was easier to
perform in the nursery, photocoagulation fell out of
favor. With the advent of binocular indirect ophthal-
moscopic lasers, the interest in it has now increased.
Laser photocoagulation is especially advantageous
in zone I disease, where cryotherapy is technically
difficult. Laser treatment is less irritating, technically
easier to perform, and the scars are less pronounced25
and more discrete compared to cryocoagulation.
Moreover, laser therapy avoids the need of conjunc-
tival incision for zone I ROP as well as the intense
scleral depression required with the cryoprobe. In
some cases treatment of the most anterior retina with
laser is difficult where cryo helps.
There are published reports of cataracts26 requiring
surgery as a complication of laser surgery. Recently,
Diode laser is used which is as effective as cryotherapy
and has the added benefit of reducing myopia in the
treatment of ROP.27
Vitreoretinal Surgery
Pathophysiologically, proliferation of epiretinal glial
cells occurs in ROP stages 4 and 5. These epiretinal
membranes exert traction on the retinal periphery and
equatorial areas with the subsequent development of
retinal detachment.
Vitrectomy in Stages 4 and 5
Indications When the detachment in stage 4B and 5
is too severe to be relieved by scleral buckling alone,
vitrectomy must be done. Extensive bilateral near total
or total traction or sometimes rhegmatogenous detach-
ments, or a recent history of rapid progression to
complete detachment are surgical indications. Unilate-
ral total retinal detachments should be considered for
surgery only if there is a high likelihood that the retina
of the fellow eye also detaches (Fig. 107.5).
Eyes with severe subretinal membranes, exudate
or blood are considered to be inoperable. Functional
 Chapter 107: Retinopathy of Prematurity 845
improvement remains highly uncertain, however,
even if successful reattachment is achieved.
Prognostic factors The timing of surgery is from few
months to 2 years of age or more. Once detachment
has occurred reattachment should be done as soon as
possible. Prognosis is better with cases of deep anterior
chamber, shallow macular detachment, and good
mydriasis.
Preoperative evaluation It is important to determine
the extent of the disease and the presence of negative
prognostic factors. Ultrasonography may be done in
eyes with opaque media. Corneal edema and pupillary Fig. 107.5: Indications for surgery in ROP: Retinal concave,
block glaucoma have to be treated before vitrectomy. stable fibrous proliferation and normal vessel caliber

Surgical Technique
The goal of ROP surgery is complete removal of
preretinal tissue with release of traction.
There are two approaches to vitrectomy in
advanced ROP, i.e. closed and open-sky. There are
controversies as regards which method is superior.
Steve Charles28 recommended the closed technique in
1977. Schepens proposed open-sky vitrectomy due to
the technical difficulties with the former in which the
cornea is removed and stored during the period of
surgery in culture media.
Entry sites differ with different surgeons. However, Fig. 107.6: Entry sites in ROP
the entry site should be anterior to the pars plana. The or flat chamber a micro-iris spatula is used to separate
closer the incision to the limbus, lesser is the difficulty the iris from the cornea. (Fig 107.7).
in instrumentation. The further the incision is moved
posteriorly, the more is the risk of producing Retrolental plate It is important to recognize the diffe-
iatrogenic retinal tears. Ciliary body entry about 0.5 rence in appearance of the retina and the retrolental
mm posterior to the limbus is the safest (Fig. 107.6). plate. The retina is shiny and pale yellow, whereas
The incisions are made with single puncture using the plate is of a matte finish and white. The retina does
20 G, 1.4 mm lancet-tip microvitreoretinal (MVR) not touch the central area of the retrolental plate, the
blade. A 30-degree bent, 20 G blunt tipped cannula is
used at a site slightly superior to the middle of the
medial rectus. The cannula is attached to the limbus
with a single suture to prevent movement. Closed
vitrectomy is done using two or three ports but most
patients of ROP will require three ports for greater
flexibility in exchanging instruments. Coaxial
illumination of the microscope without a fundus
contact lens or wide-angle observation systems is used
due to the anterior location of the disease process of
the retina.
Lensectomy The lens though usually clear has to be
removed by an aspirating ultrasonic fragmentor with Fig. 107.7: Lensectomy showing continuous fragmentation
foot controlled delta (linear) suction. In case of PAS and simultaneous aspiration
846 Section 7: Pediatric Ophthalmology Including Strabismus

area of which varies according to the size of the

anterior funnel.28
Multiple radial incisions from the center are made
toward the equatorial area, creating a stellate appea-
rance. These must be of full-thickness cutting the
posteriort capsule, anterior hyaloid face, and posterior
hyaloid face exposing the pale retina underneath
(Fig. 107.8).
Delamination or peeling off the membrane Delami-
nation is the best method for removing the posterior
hyaloid face and epiretinal membrane.29 The memb-
ranes should be cut as closely to the retina as possible. Fig. 107.8: Stellate incisions in retrolental
membrane dissection
Hyaloid system remnants, frequently present may be
adherent to the retina complicating surgery (Fig 107.9).
Vitreous substitutes Usually infusion fluid is left in
the eye at the end of vitrectomy unless there is a retinal
break. Hyaluronic acid too has a low surface tension
and a high incidence of reproliferation and secondary
glaucoma, hence it is not used. Silicone oil again causes
corneal changes and is not a good choice. Air-gas
mixtures are better due to a 50 percent higher surface
tension than silicone oil. During fluid-gas exchange
the fluid is removed via a tapered extrusion needle
(Fig. 107.10).
Fig. 107.9: Delamination at cone vertex
Subretinal fluid drainage This is usually not necessary removing the hyaloid system
as the detachment is nonrhegmatogenous. If apposi-
tion cannot be achieved because of retinal shortening,
subretinal fluid drainage may help in attachment.
External drainage should be done by 25 G 5/8 inch
needle placed obliquely through the equatorial sclera.
A marked transretinal pressure gradient should be
avoided because it can cause relief tears of the retina.
Scleral buckling Scleral buckling is an accepted
modality of treatment in ROP with rhegmatogenous
retinal detachment but the timing of its use in non
rhegmatogenous detachment is more controversial.
In this procedure, an encircling band is placed at
the site of the highest ridge elevation and cryotherapy Fig. 107.10: Internal fluid gas exchange
is done along with scleral buckling. Drainage of the
of the subretinal fluid in order to prevent the intrusion
subretinal fluid may be necessary. If nondrainage is
of the band as the child’s eye grows. This division of
used, a paracentesis of the anterior chamber is done
the band is usually done after 3 months of encirclage.32
for the maintenance of a normal intraocular pressure.
Resolution of the subretinal fluid may take several
Complications During Surgery
months. Scleral dissection is usually not performed.
One potential problem with scleral buckling in Iatrogenic retinal breaks, hemorrhage, and corneal
such small eyes is globe constriction by the band as clouding may occur. The corneal endothelium of the
ocular growth proceeds. To prevent this, the band infants is very vulnerable and the cornea may cloud,
around the eye may be divided, after the absorption necessitating open-sky vitrectomy.
 Chapter 107: Retinopathy of Prematurity
Results
The visual success rate is about 10 percent less than
anatomic success rate and depends on visual criteria.
Minimum visual criteria are ability to pick up small
objects and ambulate without striking obstacles in
familiar surroundings. A few older children can read
large print. The parents are informed that none of the
children will attain reading visual levels.
Poor visual recovery is associated with irreversible
photoreceptor degeneration, failure of photoreceptor
development, amblyopia, retinal hypoxia, CNS chan-
ges, and subretinal blood even though the retina is
attached.
RECENT ADVANCES REGARDING ROP
1. X-linked familial exudative vitreoretinopathy has
phenotypic resemblances to ROP and has been
associated with mutations in the Norrie’s disease
gene in some cases. It is postulated that missense
mutations in the third axon of the Norrie’s disease
gene may play a role in the development of severe
ROP in premature infants.29
2. “Down regulation of vascular endothelial growth
factor (VEGF) expression by hyperoxia may be
partly responsible for the vaso-obliteration and
cessation of normal retinal blood vessel growth
observed in premature infants in whom ROP
develops. Hyperoxia also has the potential to be
used therapeutically to downregulate VEGF
expression in hypoxic retina in the hope of limiting
the neovascular complications of ROP”. An
explanation of the pathogenesis of ROP has been
suggested based on these findings about the
regulation of VEGF expression in the retina.30
3. There had been researches regarding the possible
role of magnesium and copper deficiency in the
pathogenesis of ROP. Liposomes were found in the
retina in cells morphologically resembling micro-
glia. Delivery of superoxide dismutase to the retina
via long-circulating liposomes was found to be
beneficial. Therefore, it is believed that supple-
mentation of endogenous antioxidants in the
oxygen retinal tissue is probably a promising
therapeutic strategy.31
SUMMARY
In the past two decades there has been significant
changes in our understanding of ROP. While ambient
847
oxygen was formerly thought not to be of pathogenic
significance, it now appears that oxidative processes
in the immature retina may be of vital importance in
the development of ROP. Although major advances
in instrumentation now allow strict monitoring of
oxygen administration to the premature infant, ROP
is a multifactorial disease and probably cannot be
completely prevented. However, treatment techniques
including vitamin E supplementation, photocoagu-
lation, cryotherapy, and vitreoretinal surgery now
allow the ophthalmologist to intervene with some
hope of success in preventing blindness at almost
every stage of the disease.
REFERENCES
1. Terry TL. Extreme prematurity and fibrovascular overgrowth
of persistent vascular sheath behind each crystalline lens. Am
J Ophthalmol 1942;25:203.
2. Flynn JT. Acute proliferative retrolental fibroplasia: Evolution
of the lesion. Graefes Arch Klin Exp Ophthalmol 1975;195:101.
3. Campbell K. Intensive oxygen therapy as a possible cause of
retrolental fibroplasia: A clinical approach. Med J Aust
1951;2:48.
4. Patz A, Hoeck LE, De La Cruz E. Studies on the effect of high
oxygen administration in retrolental fibroplasia: Nursery
observations. Am J Ophthalmol 1952;35:1248.
5. Kinsey VC, Arnold AJ, Kalina RE, et al. PaO2 levels and
retrolental fibroplasia: A report of the co-operative study.
Paediatrics 1977;60:655.
6. Ashton NW. Oxygen in growth and development of the
retinal vessels. Am Jr Ophthalmol 1966;62:412.
7. Kushner BJ, Essner D, Cohen I et al. Retrolental fibroplasia
II: Pathological correlation. Arch Ophthalmol 1977;95:29.
8. Committee for the Classification of Retinopathy of Prema-
turity: An international classification of retinopathy or
prematurity. Arch Ophthalmol 1984;105:906.
9. Committee on Classification of Retinopathy of Prematurity:
An international classification of retinopathy of prematurity.
Arch Ophthalmol 1984;102:1130.
10. Kushner BJ, Gloeekner E. Retrolental fibroplasia in full-term
infants without exposure to supplemental oxygen. Am J
Ophthalmol 1984;97:148.
11. Ben Sira I, Nissenkorn I, Kremer I. Retinopathy of prema-
turity. Surv Ophthalmol 1988;33:1.
12. Majima A, Takahastri M, Hibino Y. Clinical observation of
photocoagulation on retinopathy of prematurity. Jpn J Clin
Ophthalmol 1976;30:93.
13. Biglan AW, Cheng KP, Brown DR. Update on retinopathy of
prematurity. Int Ophthalmol Clin 1989;29:2.
14. Flynn JT, Bancalari E, Bachynski BN et al. Retinopathy of
prematurity: Diagnosis, severity, and natural history.
Ophthalmology 1987;94:620.
15. Owens WC, Owens EU. Retrolental fibroplasia in premature
infants II: Studies on the prophylaxis of the disease. The use
of alfa tocoferol acetate. Am J Ophthalmol 1949;32:1611.
848 Section 7: Pediatric Ophthalmology Including Strabismus
16. Phelps DL, Rosenbaum A. Vitamin E protection in experi-
mental retrolental fibroplasia in kittens. Clin Res 1876;
24:194A.
17. Finer NN, Shindler RF, Grant G. Effect of intramuscular
vitamin E on frequency and severity of retrolental fibroplasia:
A controlled trial. Lancet 1982;1:1087.
18. Pennefather PM, Tin W, Clarke MP et al. Retinopathy of
prematurity in a controlled trial of prophylactic surfactant
treatment. Br J Ophthalmol 1996;80(5):420.
19. Hindle NW, Leyton J. Prevention of cicatricial retrolental
fibroplasia by cryotherapy. Can J Ophthalmol 1978;13:277.
20. Ben Sira I, Nissenkorn I, Grunwald E, et al. Treatment of acute
retrolental fibroplasia by cryopexy. Br J Ophthalmol
1980;64:758.
21. Saito Y, Hatsukawa Y et al. Macular coloboma like lesions
and pigment abnormalities as complications of cryotherapy
for retinopathy of prematurity in very low birth weight
infants. Am J Ophthalmol 1996;122:299.
22. Cryotherapy of Retinopathy of Prematurity Co-operative
Groups. Multicenter trial of cryotherapy for retinopathy of
prematurity: Preliminary results. Arch Ophthalmol 1988;
106:471.
23. Cryotherapy for Retinopathy of Prematurity Co-operative
groups. Three-month outcome multicenter trial of cryo-
therapy for retinopathy of prematurity. Arch Ophthalmol
1990;108:195.
24. Cryotherapy for Retinopathy of Prematurity Co-operative
Groups. One year outcome: Structure and function.
Multicenter trial of cryotherapy for retinopathy of prema-
turity. Arch Ophthalmol 1990;108:1048.
25. Laatikainen L, Mattila J, Karna J. Combined use of argon laser
photocoagulation and cryotherapy in the treatment of
retinopathy of prematurity. Acta Ophthalmol Scand
1995;73(4):333.
26. Chriastiansen SP, Bradford JD. Cataract in infants treated with
argon laser photocoagulation for threshold retinopathy of
prematurity. Am J Ophthalmol 1995;119(2):175.
27. Knight-Nanan DM, O’Keefe M. Refractive outcome in eyes
with retinopathy of prematurity treated with cryotherapy or
diode laser: 3-year follow-up. Br. J Ophthalmol 1996;
80(11):998.
28. Charles Steve. Retinopathy of Prematurity in Vitreous
Microsurgery. William’s and Wilikins: Baltimore, London,
Los Angeles, Sydney, 158-71.
29. Shastry BS, Pendergast SD et al. Identification of missense
mutations in the Norrie disease gene associated with
advanced retinopathy of prematurity. Arch Ophthalmol
1997;115(5): 651.
30. Pierce EA, Foley ED et al. Regulation of vascular endothelial
growth factor by oxygen in a model of retinopathy of
prematurity. Arch Ophthalmol 1997;115(3):427.
31. Caddell JL. Hypothesis. The possible role of magnesium and
copper deficiency in retinopathy of prematurity. Magnes Res
1995;8(3):261.
32. Trese MT. Vitreoretinal surgery for advanced retinopathy of
prematurity: Medical and surgical retinal advances,
controvesies and management 1994;39:471.
 Chapter 108
Retinoblastoma
Ramesh Murthy, Santosh G Honavar, Milind Naik, Vijay Anand, P Reddy
This highly malignant tumor is the most common
intraocular malignancy in children with a reported
incidence averaging about 1 in 15,000 to 1 in 18,000
live births.1 This lies second only to malignant mela-
noma of the uvea as the most common malignancy of
the eye.
HISTORY
Petras Pawius from Amsterdam described the tumor
as early as 1597.2 In 1809, James Wardrop referred to
the tumor as fungus hematodes and suggested
enucleation as the mode of management. 3 However
von Graefe pointed out the need to remove a long
section of the optic nerve at the time of enucleation.4
EPIDEMIOLOGY
There is no racial or sexual predisposition or any
predilection for the right eye or left eye. Though
mostly unilateral, it is bilateral in 25 to 35% of cases.5
AGE AT DIAGNOSIS
The average age at diagnosis is 18 months, unilateral
cases being diagnosed later at 23 months and bilateral
cases earlier at 12 months.5
PATHOGENESIS
Initially thought to be derived from the glial cells this
was called a glioma of the retina by Virchow (1864).
Flexner (1891) and Wintersteiner (1897) believed it to
be a neuroepithelioma because of the presence of
rosettes. Later there was a consensus that the tumor
originated from retinoblasts and the American
Ophthalmological Society officially accepted the term
retinoblastoma in 1926.6
GENETICS
The suspicion that retinoblastoma could be hereditary
arose quite late in the history of the disease. Stallard
in 1962 reported on an infant with retinoblastoma with
deletion of one of the D Group chromosomes, which
included chromosome 13, 14 and 15. 7 Later this
chromosome was identified to be chromosome 13 and
the syndrome named as the 13-deletion syndrome. The
locus of deletion was the 14 band on the long arm (q)
of the 13th chromosome. An intact gene protects
against the development of retinoblastoma. This is a
recessive tumor suppressor gene and for retino-
blastoma to occur both the genes at the loci should be
damaged.8
The 13-q deletion syndrome may be associated
with many other phenotypic abnormalities, which
include microcephaly, broad nasal bridge, hyper-
telorism, microophthalmos, micrognathia, lowset ears,
anal and genital malformations and mental retar-
dation.
Out of the newly diagnosed cases of retinoblastoma
6% have a family history (familial) while 94% do not
have a family history (sporadic). Approximately 15%
of unilateral sporadic retinoblastomas are caused by
germinal mutations affecting only one eye. The
remaining 85% are nonhereditary. Bilateral retino-
blastomas represent germinal mutations in 100% of
cases.9
In 1971, Knudson proposed the 2 hit hypothesis.10
He stated that for retinoblastoma to develop 2 chromo-
somal mutations are needed. In the case of hereditary
retinoblastomas, the initial hit is a germinal mutation,
which is inherited and found in all cells. The second
hit or mutation develops in somatic retinal cells
leading to the development of retinoblastoma.
850 Section 7: Pediatric Ophthalmology Including Strabismus

Therefore hereditary cases are predisposed to the

development of second non-ocular tumors like
osteosarcoma. In unilateral sporadic retinoblastoma,
both the hits occur during the development of the
retina and are somatic mutations. Therefore there is
no risk of second nonocular tumors.

CLINICAL FEATURES
The most common presenting signs and symptoms
include:
1. Leukocoria/cat’s eye reflex 56%.
2. Strabismus 20%, exotropia 11%, esotropia 9%.
3. Red painful eye with glaucoma 7%.
4. Poor vision 5%.
5. None 3%.
6. Orbital cellulitis 3%.
7. Unilateral mydriasis 2%.
8. Heterochromia iridis 1%.
9. Hyphema 1%.
10. Strange expression 0.5%, nystagmus 0.5%, not
eating 0.5%, failure to thrive 0.5%, white spots
on the iris 0.5%.11
Early Lesions
These are likely to be missed, unless an indirect
ophthalmoscopy is done under anesthesia especially
in familial cases. However the child may present with
a strabismus if the tumor involves the macula or with
reduced visual acuity. The tumors are transparent or
white fluffy masses of the retina and become more
white as the tumor grows.
Moderately Advanced Lesions
These usually present with leukocoria due to the
reflection of light by the white mass in the retrolental
area. As the tumor grows, 3 patterns are usually seen
(Fig. 108.1).
1. Endophytic in which the tumor grows into the
vitreous cavity. A white hazy mass fills the entire
vitreous cavity and vitreous seeds occur. The
tumor may extend into the anterior chamber and
form anterior chamber tumor deposits forming a
pseudohypopyon. The retinal vessels are not seen
on the tumor surface.
2. Exophytic in which the tumor grows towards the
subretinal space in which retinal vessels are seen
over the tumor. Retinal detachment usually occurs
and this condition may simulate Coats’ disease.
Fig. 108.1: Differential diagnosis of leukocoria
3. Diffuse infiltrating in which the tumor cells show
a horizontal growth on the retina. This can mimic
endophthalmitis. Usually there is a delay in
diagnosis and this is seen in older children.
Spontaneous hyphema results from bleeding from
the new vessels of the iris. New vessels develop due
to posterior segment ischemia caused by the tumor.
Any child with a spontaneous hyphema without
trauma needs ultrasound examination to rule out
retinoblastoma. Vitreous hemorrhage may sometimes
occur from a necrotic tumor.
Pseudohypopyon could occur and may simulate
intraocular inflammation but conjunctival injection or
other inflammatory signs are usually absent. Preseptal
or orbital cellulitis may occur in cases with necrotic
retinoblastomas and may be associated with extra-
ocular extension.
Advanced Lesions
These show optic nerve extension, orbital extension
or distant metastasis. Retinoblastoma can spread
through the optic nerve with relative ease especially
once the lamina cribrosa is breached. Orbital extension
may present with proptosis and is most likely to occur
at the site of the scleral emissary veins. Distant
metastasis is most likely to the brain, skull, distant
bones and the lymph nodes.
Retinocytoma
This is the benign counterpart of retinoblastoma which
is also called as retinoma.12 It is a homogeneous, small,
gray, slightly elevated tumor with normal caliber
blood vessels leading into the tumor with varying
 Chapter 108: Retinoblastoma 851
degrees of proliferation and migration of RPE in areas
underlying or adjacent to the tumor. The eye is
functional with clear media and no retinal detachment.
This tumor also has a similar inheritance pattern like
retinoblastoma.
Spontaneously regressed retinoblastoma. Retino-
blastomas are known to undergo severe inflammation
followed by phthisis bulbi. In any child with a phthi-
sical eye of uncertain cause this should be considered.

PATHOLOGY
Gross
They appear as chalky white tumors with foci of
calcification (Fig. 108.2). An endophytic retinoblas- Fig. 108.2: Two endophytic tumors in the fundus, one of
toma produces vitreous seeding while an exophytic them showing the presence of calcification
tumor produces retinal detachment. Some tumors
have both the components, while others are totally
calcified due to marked necrosis.
(released after tumor necrosis) can be found in the
walls of the lumen of blood vessels.
Microscopy
Retinocytomas show well differentiated retino-
Low Power blastoma cells with smaller and less hyperchromatic
nucleus, abundant cytoplasm without mitotic figures
On low power basophilic areas of tumor are seen along
or necrosis.
with eosinophilic areas of necrosis and more baso-
philic areas of calcification within the tumor.
DIFFERENTIAL DIAGNOSIS
OF RETINOBLASTOMA
High Power
Various conditions can simulate retinoblastoma and
Poorly differentiated tumors consist of small to
lead to an erroneous diagnosis (Figs 108.3 and 108.4).
medium sized round cells with large hyperchromatic
The enucleation rates for these ‘pseudoretino-
nuclei and scanty cytoplasm with mitotic figures.
blastomas’ was 27% in 1977, however with newer
Well differentiated tumors show the presence of
diagnostic tools this is much lower. 13
rosettes and fleurettes. These can be of various types:
These conditions can be classified as follows.
1. Flexner-Wintersteiner rosettes consist of columnar
cells arranged around a central lumen. This is
Classification14
highly characteristic of retinoblastoma and is also
seen in medulloepithelioma. Hereditary
2. Homer Wright rosettes consist of cells arranged
1. Norrie’s disease
around a central neuromuscular tangle. This is also
2. Congenital retinoschisis
found in neuroblastomas, medulloblastomas and
3. Incontinentia pigmenti
medulloepitheliomas.
4. Dominant exudative vitreoretinopathy.
3. Pseudorosette refers to the arrangement of tumor
cells around blood vessels. They are not signs of
Developmental Abnormalities
good differentiation.
4. Fleurettes are eosinophilic structures composed of 1. Persistent hyperplastic primary vitreous
tumor cells with pear shaped eosinophilic pro- 2. Congenital cataract
cesses projecting through a fenestrated membrane. 3. Coloboma
Rosettes and fleurettes indicate that the tumor cells 4. Retinal dysplasia
show photoreceptor differentiation. In addition 5. Congenital retinal fold
basophilic deposits which are precipitated DNA 6. Medullated nerve fibers.
852 Section 7: Pediatric Ophthalmology Including Strabismus

Inflammatory Conditions
1. Ocular toxocariasis
2. Congenital toxoplasmosis
3. Congenital CMV retinitis
4. Herpes simplex retinitis
5. Metastatic endophthalmitis
6. Orbital cellulitis (Fig. 108.3).

Tumors
1. Retinal astrocytic hamartoma
2. Medulloepithelioma
3. Glioneuroma.

Miscellaneous Conditions
Fig. 108.3: This child presented with features of orbital cellulitis
1. Coats’ disease
in the left eye which on further investigation was diagnosed as
2. Retinopathy of prematurity retinoblastoma
3. Rhegmatogenous retinal detachment
4. Vitreous hemorrhage
5. Perforating ocular injury.
In a study of 500 patients by Shields et al,15 referred
with a diagnosis of retinoblastoma, 58% were found
to have retinoblastoma, while 42% had pseudo-
retinoblastomas. The 4 most common pseudoretino-
blastomas were PHPV (27.8%), Coats’ disease (16%),
ocular toxocariasis (15.6%) and retinopathy of
prematurity ( 4.7%)

HEREDITARY CONDITIONS
Norries’s disease is X linked recessive, occurs in males
and is clinically apparent at birth. There is a bilateral
white retrolental mass with elongated ciliary processes
and total retinal detachment. Mental retardation is
usually associated with this condition.
Congenital retinoschisis is an X linked recessive disorder
occurring in males with the presence of retinoschisis
and a stellate pattern at the fovea and occasional Fig. 108.4: Children with atypical presentation are also more
likely to have extraocular spread. CT scan of the same child in
vitreous hemorrhage. Incontinentia pigmenti is
Figure 108.3 showing the presence of a parasellar lesion
characterized by proliferative retinal vascular
abnormalities, total retinal detachment, cataract and
RPE changes. Familial exudative vitreoretinopathy is a eye with occasional cataract. There is a retrolental mass
bilateral condition in which there is peripheral retinal into which the ciliary processes and peripheral retina
avascularity and fibrovascular proliferation leading is drawn. A persistent tunica vasculosa lentis is seen
to retinal detachment and subretinal exudation. in some cases. Congenital cataract usually becomes
apparent at an earlier age than retinoblastoma and
there may be a history of maternal rubella or trauma.
DEVELOPMENTAL ABNORMALITIES
A retinochoroidal coloboma may mimic retino-
PHPV is usually unilateral and presents a few weeks blastoma but can be differentiated by indirect
after birth. There is a white reflex in a microphthalmic ophthalmoscopy. Retinal dysplasia is characterized by
 Chapter 108: Retinoblastoma
a malformed detached retina with other ocular
abnormalities.
Congenital retinal fold consists of a ridge of abnormal
retina, glia and blood vessels extending from the optic
disc to the peripheral retina.
Medullated nerve fibers are seen as yellow white
fluffy thickening of the nerve fibre layer and if exten-
sive may cause leukocoria.
INFLAMMATORY CONDITIONS
Ocular toxocariasis is caused by the larva of the dog
tapeworm Toxocara canis. There could be a history of
contact with puppies or features like eosinophilia. A
large retinal inflammatory mass could be present with
severe cellular reaction and vitreous traction bands
appearing like endophthalmitis or it may present as a
solitary subretinal granuloma with much lesser
vitritis. Eventually traction occurs with formation of
a secondary falciform fold, retinal detachment and
secondary cataract. Serological tests like ELISA may
be helpful in making the diagnosis. The aqueous to
plasma LDH is more than 1.0 and phosphoglucose
isomerase is more than 2.0.15 Congenital toxoplasmosis,
congenital CMV retinitis and HSV retinitis may produce
severe inflammation with presence of vitreous cells
and mimic retinoblastoma. Serology is useful in
making the diagnosis. Orbital cellulitis may suggest
retinoblastoma, however ethmoid sinus infection is
usually associated.
TUMORS
Retinal astrocytomas can mimic a retinoblastoma. The
calcification is usually yellow; while in retinoblastoma
it is chalky white. In addition, these are usually
associated with tuberous sclerosis or neurofibro-
matosis.
Medulloepithelioma is usually unilateral and affects
older children. It can produce a yellow pink intra-
ocular mass with leukocoria.
MISCELLANEOUS
Coats’ disease is a unilateral vascular disorder
characterized by retinal telangiectasia, intraretinal
exudation and exudative retinal detachment occurring
in young boys less than 10 years of age. Aneurysmal
dilatation of the retinal blood vessels is present with
occasional non-rhegmatogenous exudative retinal
detachment and refractile particles, which correspond
853
to cholesterol crystals. NVI, hyphema and total retinal
detachment may develop which may mimic retino-
blastoma. Fluorescein angiography and ultrasound
examination are useful in differentiation from retino-
blastoma. Fluorescein angiography shows abnormal
leakage and retinal telangiectasia. Ultrasound
examination shows absence of a distinct tumor and
echoes of moderate reflectivity corresponding to
cholesterol crystals. In retinopathy of prematurity a
history of premature delivery and receiving oxygen
is usually forthcoming. This is a bilateral condition
characterized on fundus examination by vitreoretinal
traction and pigmentary changes. Rhegmatogenous
retinal detachment can usually be differentiated from
retinoblastoma based on B-scan which shows absence
of tumor.
Diagnosis
The diagnosis of retinoblastoma is difficult because
of numerous conditions which may mimic retino-
blastoma. However with a high index of suspicion and
using an array of diagnostic tools one can diagnose
retinoblastomas.
History
When a child less than 3 years of age presents with a
white pupillary reflex (leukocoria), strabismus or a red
inflamed eye, retinoblastoma must be ruled out. A
careful history can help rule out the mimics of retino-
blastoma. The antenatal and neonatal histories are
important. A history of prematurity, oxygen exposure,
exposure to puppies or kitten, neonatal infection,
trauma and maternal rubella should be enquired as
these indicate conditions other than retinoblastoma.
Retinal dysplasia is known to run in families. A
detailed family history including any loss of eyes or
deaths of children in the family should be sought.
Clinical Features
Any child presenting with leukocoria, squint or a red
eye needs further evaluation, as these could be the
presenting features of retinoblastoma. Less commonly
the child could present with hyphema, glaucoma,
rubeosis, phthisis bulbi or even with proptosis.
Multiple white or pink tumors in one or both eyes are
almost always retinoblastomas in children less than 5
years of age. A large unilateral tumor with a lumpy
calcified consistency is virtually diagnostic.
854 Section 7: Pediatric Ophthalmology Including Strabismus

External Ocular Examination

A white pupillary reflex is usually seen (Fig. 108.5).
Anterior segment examination by slit lamp bio-
microscopy may rarely show the presence of pseudo-
hypopyon or tumor seeds and hyphema. Iris neo-
vascularisation could be present.

Examination under Anesthesia

Any child presenting with leukocoria necessarily
needs a dilated fundus examination under anesthesia.
The intraocular pressure is measured and the anterior
segment should be examined for neovascularization,
pseudohypopyon, hyphema, and anterior chamber
inflammation. Bilateral fundus examination with 360
degrees scleral depression is mandatory. Direct
visualization of the tumor by an indirect ophthalmo-
scope is diagnostic of retinoblastoma in over 90% of
cases.16 Based on the indirect ophthalmoscopy find-
ings, the tumors are graded according to the Reese-
Ellsworth classification (Table 108.1).
Investigations
Ultrasonography is useful in the diagnosis of
retinoblastoma. A-scan shows high internal echoes
within the tumor and rapid attenuation of the normal
orbital pattern. B-scan shows a rounded or irregular
intraocular mass with numerous highly reflective
echoes within the lesion representing typical intra-
lesional calcification. These focal echoes, which
represent calcification, persist even when the
sensitivity is lowered. Computed tomography scores
over ultrasound as it can delineate extraocular
extension of tumor and detect the presence of an
associated pinealoblastoma. Magnetic resonance
imaging is specifically indicated if optic nerve invasion
or intracranial extension is suspected. On fluorescein
angiography the small intraretinal tumors show
minimally dilated feeding vessels in the arterial phase,
mild hypervascularity in the venous phase and late
staining of the mass. Larger tumors show dilated
feeding vessels and veins.
Laboratory tests like testing for elevated aqueous
enzymes like lactate dehydrogenase and phos-
phoglucose isomerase have a minimal role to play in
the diagnosis.
Management
Early diagnosis and recent advances in management
have improved the prognosis of this potentially fatal
Fig. 108.5: Leukocoria is a common presentation of retinoblas-
toma. This photograph shows a white reflex in the left eye of
the child
Table 108.1: Reese-Ellsworth classification
Group 1: Very favorable
1. Solitary tumor, less than 4 disk diameter in size, at or
behind the equator.
2. Multiple tumors, none over 4 disk diameters in size,
all at or behind the equator.
Group 2: Favorable
1. Solitary tumor, 4 to 10 disk diameters in size, at or
behind the equator.
2. Multiple tumors, 4 to 10 disk diameters in size, behind
the equator.
Group 3: Doubtful
1. Any lesion anterior to the equator
2. Solitary tumors larger than 10 disk diameters behind
the equator.
Group 4: Unfavorable
1. Multiple tumors, some larger than 10 disk diameters
2. Any lesion extending anteriorly to the ora serrata
Group 5: Very unfavorable
1. Massive tumors involving over half the retina.
2. Vitreous seeding
tumor. The survival rate has improved from 30% in
the 1930s to nearly 95% in the 1990s.
It is important to recognize the common pseudo-
retinoblastomas, which include persistent hyperplastic
primary vitreous, Coats’ disease and ocular toxo-
cariasis before embarking on the definitive treatment
of retinoblastoma.
The primary goal of management of retino-
blastoma is to safeguard the life of the child. Salvage
of the eye and vision are the secondary and tertiary
 Chapter 108: Retinoblastoma
goals respectively. The management involves a
multidisciplinary approach with a team comprising
of an ocular oncologist, pediatric oncologist, radiation
oncologist, radiation physicist, pathologist and
geneticist.
The most important factors that must be consi-
dered in the treatment are the tumor size, number,
location, and laterality, condition of the other eye,
threat of metastasis, risk for second malignant
neoplasms and systemic status of the patient.
The treatment modalities currently available can
be classified as focal, local, and systemic, and include
cryotherapy, laser photocoagulation, thermotherapy,
plaque brachytherapy, external beam radiotherapy,
enucleation, orbital exenteration, and chemotherapy.
CRYOTHERAPY
Cryotherapy is performed for small equatorial or
peripheral retinoblastomas measuring upto 4 mm in
basal diameter and 2 mm in thickness. Tumor
destruction is usually achieved with 2-3 sessions of
triple freeze thaw cycles at 1-month intervals. The
complications include transient serous retinal
detachment, retinal tear, preretinal fibrosis and
rhegmatogenous retinal detachment.
LASER PHOTOCOAGULATION
This modality of managing retinoblastoma has been
sidelined with the advent of thermotherapy. This is
usually done for small posterior tumors 4 mm in basal
diameter and 2 mm or less in thickness. The treatment
is directed to delimit the tumor and coagulate the
blood supply to the tumor by surrounding the tumor
with two rows of overlapping laser burns. The scar
produced is consequently much larger than the tumor
itself. The recurrence rate after treatment is as high at
20-30%. The common complications include transient
serous retinal detachment, vascular occlusion, retinal
traction, retinal hole and preretinal fibrosis.
THERMOTHERAPY
Thermotherapy is the delivery of heat using infrared
radiation. The goal is to reach a subcoagulative
temperature range of 40 to 60 degrees C, thus sparing
the retinal vessels of photocoagulation. Transpupillary
thermotherapy using infrared radiation from a
semiconductor diode laser has become a standard
practice. The large-spot-adapted indirect ophthalmo-
855
scope, operating microscope with a laser delivery
system, or the transscleral route using a diopexy probe
can be used to deliver it. The tumor is heated till it
turns a subtle gray. Shields et al in their series could
achieve complete tumor regression in 86% of tumors
using 3-4 sessions of thermotherapy. 17 The chief
complications of thermotherapy are focal iris atrophy,
peripheral focal lens opacity, retinal traction, retinal
vascular occlusion and transient localized serous
retinal detachment.
Thermotherapy alone can be performed for small
tumors, measuring up to 4 mm in basal diameter and
2 mm in thickness. However, its major application is
as an adjunct to chemoreduction. Heat has been
observed to have a synergistic effect with chemo-
therapy facilitating greater uptake of the platinum
group of drugs. This combination has been termed
chemothermotherapy.
PLAQUE BRACHYTHERAPY
Retinoblastoma is a radiosensitive tumor. In plaque
radiotherapy or brachytherapy, a radioactive implant
is placed on the sclera over the base of the tumor to
irradiate the tumor transsclerally. The goal is to deliver
a radiation dose of 4000-5000 cGy to the apex of the
tumor. The radioactive materials used commonly are
125
Iodine and 106Ruthenium.
The advantages of plaque brachytherapy are the
focal delivery of radiation with minimal damage to
the “normal” structures, minimal periorbital tissue
damage, minimal cosmetic abnormality, lesser risk of
second malignant neoplasms in the irradiated area,
and shorter duration of treatment.
Plaque brachytherapy can be performed as
primary or as secondary treatment. It is generally
reserved for tumors less than 16 mm in diameter and
8 mm in thickness, ideally situated > 3 mm from the
optic nerve and fovea. It is most successful as
secondary treatment in those eyes that fail to respond
to cryotherapy, laser photocoagulation, thermo-
therapy, and chemoreduction, and is less successful
in those that fail to respond to external beam
radiotherapy.18 In one series, 90% of the eyes destined
for enucleation could be salvaged with plaque
brachytherapy.19 The radiation associated problems
of papillopathy and retinopathy usually become
clinically manifest at about 18 months after irradiation.
Custom designs of plaques have reduced the incidence
of radiation-induced complications.
856 Section 7: Pediatric Ophthalmology Including Strabismus
EXTERNAL BEAM RADIOTHERAPY (EBRT)
This modality was started by Reese and Verhoeff and
has been used extensively in the past in the manage-
ment of retinoblastoma. Either the whole eye
technique or the lens sparing technique can provide
EBRT. The results of EBRT are gratifying (Table 108.2).
EBRT, however, has some long-term complications
such as impedance of orbital growth, midfacial
dysmorphism, chronic dry eye, cataract, retinopathy
and optic neuropathy. EBRT has been shown to induce
second malignant neoplasms (SMN) in the field of
irradiation. The 30-year cumulative incidence of SMN
in patients of bilateral retinoblastoma increases to 35%
in patients who received EBRT compared to 6% in
those who did not.20Abramson21 found that the risk
for SMN was greater in children less than 12 months
of age.
EBRT was conventionally indicated for moderately
advanced unilateral or bilateral retinoblastoma. It has
now been observed that the combination of chemo-
therapy with local treatment is usually successful in
salvaging eyes with Reese Ellsworth group 1 to 4
retinoblastomas (Table 108.2). Presently EBRT is
indicated in eyes where chemoreduction and local
therapy has failed, and in rare situations when
chemotherapy is contraindicated because of poor
systemic status. EBRT scores over enucleation in that
it can help salvage the eye. However, an enucleation
done after a failed EBRT may lead to socket contraction
and poor cosmesis. The decision, therefore, has to be
individualized in discussion with the patient’s family.
EBRT is also used as a standard adjunct following
enucleation in patients with retinoblastoma with
involvement of the optic nerve transection, scleral
infiltration, and orbital extension.
ENUCLEATION
Just about 3 decades ago, a majority of patients with
unilateral retinoblastoma and the worse eye in
bilateral retinoblastomas underwent primary enuclea-
tion. However the advent of chemotherapy has
changed this radical management of retinoblastoma.
Chemotherapy with local therapy can prevent
enucleation in a majority of Reese-Ellsworth groups
1-4 tumors, while enucleation may be necessary in
about 50% patients with Reese-Ellsworth group 5
tumors. Enucleation is thus the second or third line of
management and is reserved for patients who fail focal
therapy, chemotherapy, and/or EBRT. However, eyes
Table 108.2: Eye salvage rates with external beam
radiotherapy and chemoreduction
RE group Ellsworth Hungerford Shields
1977 1995 1997
EBRT EBRT CRD + SALT
I 91% 100% 100%
II 83% 84% 100%
III 82% 43% 100%
IV 62% 43% 100%
V 29% 66% 78%
with neovascularization of iris, secondary glaucoma,
anterior chamber tumor invasion, tumors occupying
>75% of the vitreous volume, necrotic tumors with
secondary orbital inflammation, and tumors asso-
ciated with hyphema or vitreous hemorrhage where
the tumor characteristics can not be visualized are
primarily managed by enucleation.
Minimum-manipulation surgical technique should
be necessarily practiced. It is important not to
accidentally perforate the eye. The sclera is thin at the
site of muscle insertions and the rectus muscles have
to be hooked delicately. It is important to obtain a long
stump of the optic nerve ideally more than 15 mm,
but never less than 10 mm. Use of an enucleation spoon
and a heavy scissors results in reduced space for
manipulation and a shorter optic nerve stump. A
straight blunt tip tenotomy scissors should be used
for the medial approach and a gently curved blunt tip
tenotomy scissors for the lateral approach. The optic
nerve should be traced to the orbital apex with the
scissors tip straddling the nerve and cut a little away
from the apex to preserve structures passing through
the superior orbital fissure. A snare or a clamp should
not be used during optic nerve transection as it may
induce crush artifacts making histopathological
examination of the cut end for tumor invasion difficult.
Orbital implants were earlier thought to interfere
with the detection of recurrence and impede EBRT.
However imaging allows detailed evaluation in spite
of the presence of an orbital implant. The orbital
implant promotes orbital growth, provides better
cosmesis and enhances prosthesis motility. The
various implants available could be non-integrated
like PMMA or silicon or bio-integrated like hydroxya-
patite or Medpor. Bio-integrated implants are avoided
in situations where postoperative adjunctive EBRT
may be necessary.
 Chapter 108: Retinoblastoma 857
ORBITAL EXENTERATION
Orbital exenteration is rarely performed for retino-
blastomas. It is usually done for orbital recurrence
after the child has received the maximum dose of
radiation and chemotherapy.

CHEMOTHERAPY (Fig. 108.6)

Systemic Chemotherapy
With the advent of chemotherapy, radical methods of
management like enucleation have been relegated to
the second or third place. The introduction of newer
chemotherapy protocols has dramatically improved
the prognosis for life, eye salvage, and residual vision.
Chemotherapy could be local or systemic. Local
chemotherapy is under trial. The role of systemic
chemotherapy in the management of retinoblastoma
includes chemoreduction, adjuvant chemotherapy,
and treatment of metastasis.
Chemoreduction, defined as the process of
reduction in the tumor volume with chemotherapy
so that it becomes amenable to cure by local therapy,
has become an integral part of the current manage-
ment of retinoblastoma. With chemoreduction and
sequential aggressive local therapy (SALT), it is now
possible to salvage many an eye and maximize
residual vision. There are different protocols in
chemotherapy. The commonly used drugs are
vincristine, etoposide and carboplatin, for 6 cycles
(Table 108.3).
In patients with Reese-Ellsworth groups 1-4,
chemoreduction coupled with SALT can minimize the
need for enucleation or EBRT without significant
systemic toxicity.22 Shields et al observed a globe Fig. 108.6: Shows a tumor touching the foveola at presentation
salvage rate of 100% using chemoreduction and (top). There was remarkable tumor shrinkage after 3 cycles of
adjuvant treatment in Reese-Ellsworth groups 1 to 4.23 chemotherapy (middle). With 6 cycles of chemotherapy and
Chemotherapy alone is however not curative and transpupillary thermotherapy, there was complete tumor
must be associated with intensive local therapy. regression (bottom). The resulting scar was much smaller than
the original tumor with the foveola fully exposed, thus
Table 108.3: Chemoreduction regimen and doses for maximizing visual potential
intraocular retinoblastoma
In high dose chemoreduction, the dose of etoposide
Day 1: Vincristine + Etoposide + Carboplatin
and carboplatin is increased (Table 108.3). This is
Day 2: Etoposide indicated in Reese-Ellsworth group 5 tumors, recur-
Standard dose: (3 weekly, 6 cycles): Vincristine 1.5 mg/m rences, and metastasis. The recent application of high
(0.05 mg/kg for children < 36 months of age and maximum dose chemotherapy is in the management of orbital
dose < 2 mg), etoposide 150 mg/m2 (5 mg/kg for children <
extension of retinoblastoma. Our unpublished early
36 months of age), carboplatin 560 mg/m2 (18.6 mg/kg for
children < 36 months of age) results indicate good response to a combination of
initial 3 cycles of high dose chemotherapy, followed
High-dose (3 weekly, 6-12 cycles): Vincristine 0.025 mg/kg,
Etoposide 12 mg/kg, Carboplatin 28 mg/kg by enucleation, orbital EBRT, and continued chemo-
therapy for 12 cycles.
858 Section 7: Pediatric Ophthalmology Including Strabismus
Standard dose adjuvant chemotherapy can be
administered post enucleation in patients with high
risk histopathologic characteristics that predispose to
metastasis. The histopathologic high risk factors have
been mentioned in Table 108.4. Honavar et al observed
that the incidence of metastasis was 4% in the group
which received post enucleation adjuvant therapy
compared to 24% in the group which did not.24 High-
dose adjuvant chemotherapy is indicated in patients
with extraocular extension of retinoblastoma, and
those who have optic nerve invasion to transection.
Patients with tumor cells in the cerebrospinal fluid
get intrathecal methotrexate in addition to high-dose
adjuvant chemotherapy.
It is important to be aware of the adverse effects
and interactions of chemotherapeutic agents, which
include myelosuppression, febrile episodes, neuro-
toxicity and non-specific gastrointestinal toxicity.
Chemotherapy should be given only under the
supervision of an experienced pediatric oncologist.
Periocular Chemotherapy
Carboplatin delivered subconjunctivally has been
demonstrated to be efficacious in the management of
retinoblastoma especially in the presence of vitreous
seeds because it can penetrate the sclera and achieve
effective concentrations in the vitreous cavity.
However the response may be short lived with tumor
recurrences. This modality is currently under trial.
Follow up Schedule
The usual protocol is to schedule the first examination
3-6 weeks after the initial therapy. In cases where
chemoreduction therapy has been administered, the
examination should be done every 3 weeks with each
cycle of chemotherapy. Patients under focal therapy
are evaluated and treated every 4-8 weeks until
complete tumor regression. Following tumor regres-
sion, subsequent examination should be 3 monthly for
the first year, 6 monthly for three years or until the
child attains 6 years of age, and yearly thereafter.
Genetic Counseling
This is often neglected in the management of
retinoblastoma. In patients with a positive family
history, 40% of the siblings would be at risk of
developing retinoblastoma and 40% of the offspring
of the affected patient may develop retinoblastoma.
In patients with no family history of retinoblastoma,
Table 108.4. Histopathologic high-risk
factors predictive of metastasis
• Anterior chamber seeding
• Iris infiltration
• Ciliary body infiltration
• Massive choroidal infiltration
• Invasion of the optic nerve lamina cribrosa
• Retrolaminar optic nerve invasion
• Invasion of optic nerve transection
• Scleral infiltration
• Extrascleral extension
Table 108.5: Current suggested protocol
A. Intraocular tumor, Reese-Ellsworth Groups 1 to 4,
Unilateral or Bilateral
1. Focal therapy alone for smaller tumors if the standard
tumor size indications are satisfied.
2. Standard 6 cycle chemoreduction and sequential
aggressive focal therapy for larger tumors and all
tumors located in the macular area.
3. Consider focal therapy for small residual tumor, and
plaque brachytherapy/EBRT for large residual tumor
if bilateral, and enucleation if unilateral.
B. Intraocular tumor, Reese-Ellsworth Groups 5A and 5B,
Unilateral
— Primary enucleation
C. Intraocular tumor, Reese-Ellsworth Groups 5A and 5B,
Bilateral
1. High dose chemotherapy and sequential aggressive
focal therapy.
2. Consider focal therapy for small residual tumor, and
plaque brachytherapy/EBRT for large residual tumor.
D. Advanced intraocular tumor, unilateral or bilateral, with
neovascularization of iris, anterior segment seeds, iris
infiltration, necrotic retinoblastoma with orbital inflam-
mation, media opacity precluding tumor visualization, and
eyes with no visual potential.
— Primary enucleation
E. Extraocular tumor
1. Baseline CT scan/MRI, bone marrow and cerebro-
spinal fluid cytology.
2. Intrathecal methotrexate if cerebrospinal fluid is
positive for tumor cells.
3. High dose chemotherapy for 6 cycles, followed by
enucleation or exenteration, external beam radio-
therapy, and continued chemotherapy for 12 cycles.
F. High risk factors on histopathology
1. Standard 6-cycle adjuvant chemotherapy.
2. High dose adjuvant chemotherapy and orbital external
beam radiotherapy in patients with scleral infiltration,
extraocular extension, and optic nerve extension to
transection.
 Chapter 108: Retinoblastoma
if the affected child has unilateral retinoblastoma, 1%
of the siblings are at risk and 8% of the offspring may
develop retinoblastoma. In cases of bilateral retino-
blastoma with no positive family history, 6% of the
siblings and 40% of the offspring have a chance of
developing retinoblastoma.
In summary, the current trend is to provide an
individualized (Table 108.5) multispecialty manage-
ment for patients with retinoblastoma. The recent
advances in the management of retinoblastoma have
yielded gratifying outcome in terms of preservation
of life, salvage of the eye, and optimal residual vision.
REFERENCES
1. Bishop JO, Madsen EC: Retinoblastoma. Review of current
status. Surv Ophthalmol 1975;19:342.
2. Albert DM: Historic review of retinoblastoma. Ophthal-
mology 1987;94;654.
3. Wardrop J: Observations of fungus hematodes or soft cancer.
Edinburgh : Archibald Constable & Co, 1809.
4. von Graefe A: Enucleation ou exeneration du globe del’oeil.
Ann Oculistique 1884;93:250.
5. Shields JA, Shields CL. Intraocular Tumors – A Text and Atlas.
WB Saunders Company 1992;18:306.
6. Jackson E: Report of the committee to investigate and revise
the classification of certain retinal conditions. Trans Am
Ophthalmol Soc 1926;24:38.
7. Stallard HB: The conservative treatment of retinoblastoma.
Trans Am Opththalmol Soc UK 1962;82:473.
8. Murphree AL, Benedict WF: Retinoblastoma: Clues to human
oncogenesis. Science 1984;223:1028.
9. Shields JA, Shields CL. Intraocular Tumors—A Text and
Atlas. WB Saunders Company 1992;19:337.
10. Knudson AG: Mutation and cancer: Statistical study of
retinoblastoma. Proc Natl Acad Sci USA 1971;68:820.
11. Abramson DH, Frank CM, Susman M, Whalen MP, Dunkel
IJ, Boyd NW 3rd. J Pediatr 1998;132 (3 Pt 1):505-8.
859
12. Gallie BL, Phillips RA, Ellsworth RM et al. Significance of
retinoma and phthisis bulbi for retinoblastoma. Ophthal-
mology 1982;89:1393.
13. Margo CE, Zimmerman LE: The accuracy of clinical diagnosis
in children treated by enucleation. J Ped Ophthalmol Strab
1983;20:227.
14. Shields JA, Shields CL. Intraocular Tumors—A Text and
Atlas. WB Saunders Company 1992;20:342.
15. Felberg NT, Mc Fall R, Shields JA: Aqueous humor enzyme
patterns in retinoblastoma. Invest Ophthalmol 1977;16:1039.
16. Ellsworth RM. The practical management of retinoblastoma.
Trans Am Ophthalmol Soc 67: 462, 1969
17. Shields CL, Santos MC, Diniz W et al. Thermotherapy for
retinoblastoma Arch Ophthalmol 1999;117:885.
18. Shields CL, Shields JA, Cater J et al. Plaque radiotherapy for
retinoblastoma, long-term tumor control and treatment
complications in 208 tumors. Ophthalmology 2001;108:2116-
21.
19. Shields JA, Shields CL, Hernandez JC et al. Plaque radio-
therapy for residual or recurrent retinoblastomas in 91 cases.
J Pediatr Ophthalmol Strabismus 1994;31:242.
20. Roarty JD, Mc Lean IW, Zimmerman LE. Incidence of second
neoplasms in patients with retinoblastoma. Ophthalmology
1988;95:1583.
21. Abramson DH, Frank CM. Second non ocular tumors in
survivors of bilateral retinoblastoma; a possible age effect on
radiation-related risk. Ophthalmology 1998;105:573.
22. Friedman DL, Himelstein B, Shields CL et al. Chemoreduction
and local ophthalmic therapy for intraocular retinoblastoma.
J Clin Oncol 2000;18:12.
23. Shields CL, Shields JA, Needle M et al. Combined chemo-
reduction and adjuvant treatment for intraocular retino-
blastoma. Ophthalmology 1997;104:2101.
24. Honavar SG, Singh AD, Shields CL et al. Post enucleation
adjuvant therapy in high risk retinoblastoma. Arch
Ophthalmol 2002;120:923.
25. Hungerford JL, Toma NMG, Plowman PN, Kingston JE.
External beam radiotherapy for retinoblastoma: I, whole eye
technique. Br J Ophthalmol 1995;79:112.
26. Ellsworth RM. Retinoblastoma. Modern problems in
ophthalmology. 1977;96:1826.
 Chapter 109
Infantile Nystagmus
LC Dutta
Nystagmus is defined as involuntary oscillatory move-
ment of the eyes in all or some fields of gaze. True
nystagmus should be differentiated from nystagmoid
or myoclonic movements of the eyes which occur in
extreme deviation of the eyes as in opticokinetic
nystagmus or in some muscular pathology. Basically
from the clinical point of view there are two types of
nystagmus: (a) one is ‘pendular’ in which both the
phases of movement are of equal speed, (b) ‘jerky’
nystagmus in which there is quick speed in one phase
and slow speed in the other phase. This is called Jerky
nystagmus. From the plane of movement of the eyes
the nystagmus may be horizontal, vertical or rotatory.
Again depending upon the amplitude of movement,
nystagmus may be divided into fine, medium and
coarse. When the excursion is less than 3 degrees it is
called fine type, between 5 and 15 degrees medium
Fig. 109.1: Classification of nystagmus
type and more than 15 degrees in coarse type. Rate of
nystagmus is inversely proportionate to its amplitude;
faster the rate the smaller the amplitude and vice versa.
In some cases the amplitude may be so small that it
can be detected only by seeing the movement of the
optic disk with slit lamp biomicroscope or ophthalmo-
scope. This type of nystagmus is called jelly nystag-
mus.1 The nystagmus is abolished during sleep.
Etiological classification of nystagmus is conge-
nital and acquired type. Congenital nystagmus is
sometimes hereditary and may be present at birth but
parents may not be aware of it until the child is several
months old.2 Congenital nystagmus again may be of
central origin or secondary to lack of fixation due to
some ocular diseases like achromatopsia, hypoplasia
of the optic nerve, ocular or oculocutaneous albinism,
macular defects, etc. (Fig. 109.1). Congenital nystag-
 Chapter 109: Infantile Nystagmus
mus is usually jerky and horizontal, although vertical
and rotatory types are not uncommon. History of
oscillopsia (apparent movement of the objects) is
usually absent. Intensity of nystagmus can be
voluntarily reduced by the patient by inducing
excessive convergence. Congenital nystagmus may be
superimposed by a latent component usually asso-
ciated with esotropia.
Spontaneous congenital nystagmus is present at
birth but may be detected after about six months after
birth. However, on electro-nystagmography (ENG)
the nystagmus can be detected soon after birth though
clinically no nystagmus is visible. It may so happen
that in parents of infants with congenital nystagmus,
ENG tests may be positive even though they have no
clinical nystagmus.
ELECTRO-NYSTAGMOGRAPHY (ENG)
The principle of electro-nystagmography consists of
picking up of the corneoretinal potentials of both eyes
by two electrodes applied as near as conveniently
possible to the left and right inner canthi. Special
devices can record the amplitude and the concomitant
gaze positions of the eyes simultaneously. Fixation and
nystagmus can be dissociated by eliminating the
former by closing the eyes or by testing the subject in
total darkness. ENG permits not only further exact
observations of frequency, amplitude and direction
of the nystagmus but it also provides a permanent
objective recording of these ocular movements for
future reference.
Early onset nystagmus includes all nystagmus with
an onset before six months of birth. This group is
divided into:
a. Sensory defect nystagmus (SDN) associated with
demonstrable anterior visual pathways defect as
indicated in the classification.
b. Congenital idiopathic nystagmus (CIN). This
includes nystagmus not associated with any
demonstrable visual or neurological impairment.
c. Neurological nystagmus (NN) occurs in tumors of
the visual pathway (glioma of the optic nerve, optic
chiasm) bony tumor pressing on the anterior visual
pathway, optic atrophy, etc.
SENSORY DEFECT NYSTAGMUS
Sensory defect nystagmus is the most common form
of early onset nystagmus which may be present after
a few days to a few months after birth. In a study of
early onset nystagmus in children Weiss and
861
Table 109.1: Characteristics of congenital nystagmus2
Manifest Latent or manifest-latent
Mostly pendular Jerking
No change on uniocular Increases on uniocular
occlusion occlusion
Direction independent of Fast phase towards fixating eye
fixating eye
Infrequently associated Almost always associated
with infantile esotropia with infantile esotropia
Binocular visual acuity is Binocular visual acuity is better
same as monocular visual than monocular visual acuity
acuity
Biersdorf3 reported that nystagmus due to sensory
defect constitute 91% of infantile nystagmus. This is
the most common type of nystagmus associated with
a wide range of local extraocular or intraocular diseases
some of which are mentioned in Table 109.1. A short
discussion of few of the conditions are given below.
CATARACT
Congenital cataract is the most common cause of
sensory defect nystagmus. Cataract needs surgical
intervention at the earliest possible time; but surgery
in newly born babies is not possible due to obvious
reasons. The operation can be delayed for a couple of
months; if it is further delayed then nystagmus is
inevitable. When the nystagmus is established,
cataract operation even with intraocular lens implan-
tation, fails to restore vision and nystagmus persists.
CORNEAL OPACITY
Congenital corneal opacity or corneal dystrophy is
another condition in which development of nystagmus
can be theoretically prevented by keratoplasty. But in
practice it is not possible to perform keratoplasty
during infancy—and hence nystagmus is inevitable.
Other causes of sensory defect nystagmus are early
hereditary or degenerative conditions of intraocular
structures. These include developmental defects like
coloboma of choroids-retina, optic nerve dysplasia and
aniridia. Heredofamilial genetic disorders that include
ocular or oculocutaneous albinism 1 and Leber’s
heredofamilial congenital amaurosis is also respon-
sible for sensory defect nystagmus. Retinopathy of
prematurity causes nystagmus in advanced stages of
the disease.
862 Section 7: Pediatric Ophthalmology Including Strabismus
CONGENITAL IDIOPATHIC NYSTAGMUS (CIN)
This group of nystagmus is diagnosed after exclusion
of Sensory Defect Nystagmus (SDN) and nystagmus
due to neurological disorders. Visual acuity in this
group of nystagmus is moderately affected. CIN can
be divided into two subgroups: (a) Typical, and (b)
Atypical.
Typical Congenital Idiopathic Nystagmus
Typical type is purely conjugate and horizontal. Both
eyes show similar intensity and plane of nystagmus
even on depression and elevation. The intensity is
decreased on convergence or with voluntary eyelid
closure and it may increase on rest period and decrease
on active period. There is a region of gaze direction
where the nystagmus is minimal or absent. This null
region is usually eccentric. A peculiar head turn has
got to be adopted by the patient to attain the least
intensity of the nystagmus. In such stage the nystag-
mus may be masked by the head turn and may remain
undetected for years. On the other hand in course of
time this type of nystagmus often subsides. In CIN
optokinetic nystagmus cannot be demonstrated. CIN
may have hereditary tendency—X-linked with
variable expressivity and incomplete penetration.4
Atypical Congenital Idiopathic Nystagmus
Atypical congenital idiopathic nystagmus may be
monocular or when binocular may be asymmetrical .
Head tilt or head turn and a head shaking is present.
As monocular nystagmus is common in neurological
nystagmus, it is important to conduct all the neuro-
radiological imaging procedures and electrophysical
tests like electroencephalogram (EEG), Visually
evoked potential (VER) and electronystagmogram
(ENG).
Neurological Nystagmus
When the nystagmus is asymmetrical or unilateral,
neurological disease should be considered as a cause
of nystagmus.5 Visual pathway disease giving rise to
nystagmus include glioma of the chiasm and optic
nerve, craniopharyngioma and other tumors and bony
anomalies pressing on the optic nerve. Schuman et
al6 reported a case (5-year-old boy) of monocular
vertical nystagmus due to glioma of the optic chiasm
which was confirmed by radiological diagnostic
procedures. This patient was initially diagnosed as
spasmas nutans nystagmus. Tumors of the anterior
visual pathways initially can produce quivering
movements of the eyeball prior to causing nystagmus.
Systemic diseases causing neurological nystagmus are
Down’s syndrome and hypothyroidism. Monocular
nystagmus is sometimes associated with epileptic
seizures. Cerebral palsy is a prominent cause of
neurological nystagmus. Black7 in a study of 120 chil-
dren of cerebral palsy between the age of 6 to 16 years
found 15.8% to have nystagmus. The lesions in these
cases were presumed to be in the cerebellum. The
nystagmus was primarily found in ataxic and spastic
type of cerebral palsy. Common types of nystagmus
were jerky horizontal and pendular.
See-saw nystagmus is extremely rare in children. In this
condition, one eye goes up and the other moves
down—it is a disjunctive pendular movement.
Torsional movement of the eyes are associated with
vertical movement; intorsion associated with upward
and extorsion associated with downward movement.
Nystagmus Compensatory Mechanism
Some patients with manifest congenital nystagmus can
decrease the amplitude and frequency of nystagmus
by blocking or dampening mechanism. This mecha-
nism is effected by increasing the innervational inputs
to bring one or both eyes towards a position that can
reduce or suppress the innervational impulse that
causes the nystagmus. The purpose of the dampening
of the nystagmus is to improve the visual acuity.
Patients with manifest congenital nystagmus are
able to decrease nystagmus by convergence or version
innervation or by moving their eyes into a null zone.
Congenital nystagmus decreases with convergence
and visual acuity may improve dramatically at near
fixation. But it is not clear how this improvement
occurs because no clear correlation exists between the
decrease of nystagmus intensity during convergence
and the improved visual acuity.8 However ophthalmic
surgeons have taken advantage of this beneficial effect
of convergence on nystagmus by inducing conver-
gence artificially with prisms or by creating exotropia
surgically to improve visual acuity also at distance
fixation.
Latent Nystagmus
It is a type of congenital jerky nystagmus which
develops when one eye is occluded, as in doing a
routine “cover test”. Often there is no clinically detec-
table nystagmus when both eyes are kept open. When
 Chapter 109: Infantile Nystagmus
either eye is closed , both the eyes develop nystagmoid
jerks (the eye behind the occluder also moves synchro-
nously with the uncovered fixating eye). The nystag-
mus has a slow and a fast component. The fast phase
beating towards the side of the fixating eye. The
etiology of latent nystagmus is unknown. It is seen in
pediatric patients specially in those having congenital
infantile esotropia. Due to induced nystagmus in the
uncovered eye, visual acuity decreases when either
eye is covered. Occasionally latent nystagmus may be
superimposed on a manifest nystagmus, i.e. amplitude
of the manifest nystagmus will increase and visual
acuity will decrease on covering either eye.9 Therefore
this subclass of congenital nystagmus is also called
manifest-latent nystagmus.
Infantile esotropia is frequently present in patients
with latent nystagmus. Therefore strabismus amblyo-
pia is likely to develop. As such it may be inferred
that amblyopia may be an accompaniment of latent
nystagmus.10
SPASMUS NUTANS
Spasmus nutans is another type of transitory acquired
horizontal pendular type of nystagmus beginning
during the first 18 months after birth and invariably
disappearing by the third year of life. This nystagmus
is associated with tilting of head, head-nodding and
occasionally torticollis.11 The nystagmus is of fine
intensity and of small amplitude. Though usually
horizontal it may be rotatory or vertical. Intensity of
nystagmus may vary in different gaze positions. The
condition is likely to be confused with congenital
nystagmus. The etiology of this acquired rare type of
nystagmus in children is not clear but it is reported to
be more common in children who are kept in ill
ventilated rooms with inadequate illumination. A
recent study12 comparing spasmus nutans nystagmus
with idiopathic infantile nystagmus reveals that low
socioeconomic status appears to be responsible for
development of spasmus nutans.
MANIFEST CONGENITAL NYSTAGMUS
Some patients with manifest congenital nystagmus are
able to decrease nystagmus by converging or version
innervation or by moving their eyes into a null zone.
Congenital nystagmus decreases with convergence
and visual acuity improves dramatically. This
beneficial effect can help the ophthalmologist in
medical management of congenital manifest nystag-
863
mus. Convergence is induced artificially by intro-
ducing necessary prismatic effect in spectacles.
MANAGEMENT
The aim of treatment of nystagmus is to stabilize the
eyes to improve visual acuity and decrease oscillopsia;
in the case of a neutral zone in a secondary gaze
position with compensating head posture, to shift the
neutral zone towards the primary position.
All patients require refraction and spectacles if
necessary; patients with astigmatism and aniso-
metropia are best benifitted. However, it is a difficult
task to asses the accurate spectacle power when the
amplitude of the nystagmus is very high. Contact lens
is more effective than spectacle correction because
along with excursion of the globe during the
nystagmus the contact also moves hence optical
aberrations are not likely to occur in contact lens wear;
but while using spectacle correction optical aberration
is common. Use of high power minus lenses stimulate
accommodative convergence and may improve visual
acuity while at distance fixation by nystagmus
dampening effect. Surgical treatment of nystagmus is
described in the Chapter 110.
REFERENCES
1. Walsh FB, Hoyt WF. Clinical Neurophthalmology (3rd edn)
1-3, William and William and Wilkins Co. 1969.
2. Simon JW, Kandel GI, Krobel GB et al. Albinotic characteristic
in congenital nystagmus. Am J Ophthalmol 1984;97:320.
3. Weiss AH, Binsdorf WR. Visual sensory disorder in congenital
nystagmus. Ophthalmology 1989;96:517.
4. Waggoner RW. Sex linked hereditary nystagmus. Am J
Ophthalmol 1942;25:177.
5. Farmer J, Hoyt CS. Monocular nystagmus in infancy and early
childhood. Am J Ophthalmol 1984;98:504.
6. Schuman JA, Shults W, Jones JM. Monocular vertical
nystagmus as an initial sign of chiasmal glioma. Am J
Ophthalmol 1979;87:87.
7. Black P. Visual disorder associated with cerebral palsy. Br J
Ophthalmol 1982;66:46.
8. Von Noorden GK, La Roche R. Visual acuity and motor
characteristics in congenital nystagmus. Am J Ophthalmol
1983;95,748.
9. Dell ‘Osso LF, Schmidt D, Daroff RB. Latent, manifest-latent
and congenital nystagmus. Arch Ophthalmol 1979;97:1877.
10. Von Noorden GK, Avilla CO, Sidicaro R. Latent nystagmus
and strabismic amblyopia. Am J Ophthalmol 1987;103:87.
11. Arviol E, Mittal S. See-saw nystagmus. Trans Ophthalmol
Soc UK. 1970;09.
12. Wizlow SS, Reinecke RD, Bocarnee M, et al. Comparative and
Socioeconomic Study of Apasmas Nutans and Infantile
Nystagmus. Am J Ophthalmol 2002;133:256.
 Chapter 110
Nystagmus Surgery:
Current Concepts
Elizabeth Joseph
Although nystagmus surgery was described in 1953
by Kestenbaum, and several modifications were
suggested later by several others, the surgical treat-
ment of nystagmus is still not very popular. More than
45 different types of nystagmus have been described
depending on its pathophysiology. Congenital
nystagmus is the most common of all the different
types of nystagmus. Majority of the congenital nystag-
mus are associated with a compensatory head posture.
COMPENSATORY HEAD POSTURE
Some patients with congenital nystagmus adopt a
compensatory head posture if the null zone is in one
of the lateroversion postions. The patient keeps the
head and the eyes in such a position so as to enable
the eyes to be in the null zone of nystagmus, so that
binocularity is maintained and visual acuity is
increased. There may be head tilt, chin-elevation or
depression or a face-turn or a combination of some of
these positions. These awkward head positions are
often cause for social embarrassment.
Principle of Nystagmus Surgery
The principle of nystagmus surgery for congenital
nystagmus with ocular torticollis essentially consists
of shifting of the null point to the primary position by
recession or resection of extraocular muscles.
History of Nystagmus Surgery
In 1953 Kestenbaum recommended shifting the eyes
away from the null point by performing an equal
amount of recession and resection in one eye followed
by the same in the other eye after a period of
stabilization. Kenstenbaum advocated 7 mm recession
and 7 mm resection. Later on Pratt Johnson suggested
symmetric surgery on all four horizontal rectus mus-
cles if no other strabismus was present. He recom-
mended 5 mm surgery on all horizontal rectus muscles
to correct 30 prism diopter of face-turn, 6 mm surgery
for 40 prism diopter, and 7 mm surgery for 50 prism
diopter of head-turn. Later on, it was understood that
the pulling power of lateral rectii is less than that of
MR. In 1960, Parks modified Kestenbaum procedure
in such a way that the four horizontal rectii received
different amount of surgery. The medial rectus of the
adducted eye would be recessed 5 mm and the lateral
rectus resected 8 mm. The abducted eye would have
a recession of lateral rectus muscle by 7 mm and
resection of medial rectus by 6 mm. This modification
of Parks became known as “Classic Maximum”
procedure. In classic maximum procedure a total of
13 mm of surgery is done in either eye and is divided
into 5,6,7 and 8 mm. The largest amount goes to the
resected lateral rectus.
Current Concept
The current concept of nystagmus surgery is that the
amount of surgery should be titrated according to
head posture.
The classic maximum procedure of 5,6,7 and 8 mm
is done for nystagmus with compensatory head-
posture between 15°-30°. When the face-turn is more
than 30°, the surgery is to be augmented by 40 percent.
A 60 percent augmentation leads to measurements of
8,9,6,11.2 and 12.8 mm, which are converted to 8,9,5,11
and 13 mm, respectively.
 Chapter 110: Nystagmus Surgery: Current Concepts 865
Measurement of Torticollis
There are several methods of measuring torticollis. A
perimeter can be used to measure head-turn, with the
patient fixing the central accommodative target. A
plastic protractor with two extended arms can be used
very easily (Figs 110.1 and 110.2). The protractor with
the two extended arms is placed on the patient’s head.
The patient is seated 6 meters from a Snellen’s chart
and is asked to fix at the smallest possible letter so
that the compensatory head-turn is manifested. The
observer stands adjacent to the patient and places one
arm of the protractor in the direction of the patient’s
face-turn; the second arm is aimed directly at the
fixation target. The degree of face-turn (Fig. 110.3) can
be directly read on the protractor. This can be used to Fig. 110.3: Preoperative picture showing
measure chin-elevation or depression by placing the face-turn in congenital nystagmus

protractor adjacent to the face or head with one arm

placed on a perpendicular plane with the second arm
parallel to the axis of the patient’s head (Fig. 110.4 and
110.5).

Face-turn 15°-30° Recess MR 5 mm Recess LR 7mm

(Classic maximum) Resect LR 8 mm Resect MR 6 mm
Total 13 mm Total 13 mm
Face-turn 30°-40° Recess MR 7 mm Recess LR 10 mm
(40% augmentation) Resect LR 11 mm Resect MR 8 mm
Total 18 mm Total 18 mm
Fig. 110.1: Photograph showing the measurement Face-turn more than 40° Recess MR 8 mm Recess Lr 11 mm
of torticollis (60% augmentation) Resect LR 13 mm Resect MR 9.5 mm

Fig. 110.4: Surgical guidelines: Face-turn

to right—eyes turn to left

Classic maximum Recess LR 7 mm Recess MR 5 mm

Resect MR 6 mm Resect LR 8 mm
40% augmentation Recess LR-10 mm Resect MR 7 mm
Resect MR 8 mm Resect LR 11 mm
60% augmentation Recess LR 11 mm Recess MR 8 mm
Resect MR 9.5 mm Resect LR 13 mm

Fig. 110.2: Photograph showing the measurement of the Fig. 110.5: Surgical guidelines: Face-turn to left—
degree of torticollis eyes turn to right
866 Section 7: Pediatric Ophthalmology Including Strabismus

Surgical Result (Figs 110.6 and 110.7)

After nystagmus surgery the compensatory head
posture will be well-corrected. When the null point is
shifted to the primary position the patient will keep
the head-straight. The intensity of nystagmus will be
diminished. Spontaneous improvement in visual
acuity is noted in some, probably due to reduction in
the amplitude of nystagmus. Those who are spectacle
users, can now use the optical center of the spectacle
and hence the vision will be improved. In addition to
all these, the correction of compensatory head posture
has a significant implication on the overall quality of
life due to the psychological and social factors

Fig. 110.7: Postoperative picture showing torticollis corrected

involved. There are no significant changes in the bino-

cular vision and double vision or mobility problems
are not encountered. Mild limitation of duction may
occur after augmented procedures.

BIBLIOGRAPHY
1. Paul R, Mitchell MD. Surgical management of nystagmus.
Oph Clinics NA, 1992.
2. Noorden GK, von MD. Binocular vision and ocular motility.
VI Edition.
3. Pratt Johnson JA. Results of surgery to modify the null zone
position in congenital nystagmus. Can J Ophthal 1991;
Fig. 110.6: Preoperative picture showing occular torticollis 26(4):219-23.
 Chapter 111
Evaluation of Strabismus
TN Surendran, Manjula Sridhar
Strabismus (syn: Squint) is one of the most common
childhood problems. As one is aware, it is extremely
difficult to examine the child; a tactful examination
with appropriate history is necessary to arrive at a
diagnosis and management of the squint.
The order of examination is usually as follows:
a. History taking and observation
b. Visual acuity estimation
c. Dynamic refraction
d. Ductions and versions
e. Measurement of angle of deviation and face
turn
f. Sensory tests
g. Special tests like forced duction test and force
generation test
h. Cycloplegic refraction and fundus evaluation.
HISTORY TAKING
History taking (Table 111.1) should be done by the
ophthalmologist himself/herself because it provides
an opportunity to observe the child’s visual behavior.
Along with this observation it is useful to review child-
hood photographs especially when the parents are not
sure about when the onset was first noticed.
VISUAL ACUITY ESTIMATION
In infants visual acuity can be assessed by fixation
pattern,1,2 by making the child lock his eyes onto a
toy and then moving the toy in various directions. In
infants with manifest squint, occlusion of the good eye
will make the child cry or prevent the occlusion if the
vision is poor in the squinting eye. The child has
obvious fixation preference. Better methods of
assessing vision in infants are optokinetic nystagmus,3
force choice preferential looking test, and visual
evoked potential.4
In preschool children visual acuity5 can be esti-
mated by Allen’s cards, Sheridan-Gardiner test,
illiterate E and Landolt rings. In school going children
the Snellen’s optotype for distance and the Jaeger’s
card for near is used. In cooperative children the
visuoscope3 can be used to diagnose foveal or eccentric
fixation. Central foveal vision is usually 6/12 or better.
In eccentric fixation vision is 6/60 or worse.
MONOCULAR VS BINOCULAR VISION
In children with face turn binocular visual acuity
should be estimated by allowing the child to adopt
the face turn. In intermittent exotropes monocular
visual acuity 6 is better than binocular vision. In
intermittent exotropia, accommodative convergence
is exerted to control the deviation which blurs the
vision under binocular condition. In latent nystagmus7
binocular vision is better than monocular vision. While
assessing monocular vision instead of occluding the
other eye, high plus lens is used to fog the vision.
DUCTIONS AND VERSIONS
Ductions are tested by covering one eye and have the
patient make command or pursuit movements,
bringing the eye to the farthest possible in the direc-
tions right, left, up, down, up and right, up and left,
down and right, and down and left. The examiner
should observe whether movements are excessive or
lag in any direction.
Versions are tested by placing the penlight in the
midline of the patient’s eye and move it in various
directions keeping the penlight in the midline so that
the corneal reflections are seen in both the eyes.
If abduction is normal, the corneal limbus should
touch the outer canthus. If the limbus passes that point
and some of the cornea is hidden, abduction is
868 Section 7: Pediatric Ophthalmology Including Strabismus

Table 111.1: Points to history taking and observation excessive. In maximal adduction an imaginary vertical
History regarding the squint itself line through the lower lacrimal punctum should
• Age at which squint was first noticed coincide with a boundary line between the inner third
• Onset was gradual or sudden and outer two-third of the cornea.
• Squint is constant or intermittent
• Types of squint—inward or outward deviation Limbus Test of Motility of Kestenbaum
• One eye always squints or does it alternate
• Precipitating factors like fatigue, viral illness, day dreaming The test is performed by holding a transparent
in children with intermittent squint. millimeter ruler horizontally in front of the cornea. In
History regarding subjective ocular complaints measuring abduction, the location of the nasal limbus
• Blurred vision point is noted on the ruler in primary position and in
• Presence of double vision maximum abduction. The difference gives the degree
• Headache/asthenopia of abduction in millimeters.
• Presence of face turn/head tilt.
Adduction is measured by determining the
Other relevant history
position of the temporal limbus in primary position
• Preceding ocular problem
• Head injury
and in adduction.
• Viral illness To measure elevation and depression, hold the
• History of blinking or closing one eye. ruler vertically and measure the difference between
Maternal and birth history the superior and inferior limbus from primary position
• Maternal illness during pregnancy and in maximal elevation and depression. Normal
• Prolonged labor values are 10 mm for adduction, abduction, depres-
• Use of forceps during delivery sion, and 5-7 mm for elevation.
• Prematurity
Neonatal history Oblique Dysfunction (Fig. 111.1)
• Birth weight
• Developmental milestones When noting for oblique dysfunction use the occluder
• General health of the child for partition of the two eyes. The eye in abduction can
Drugs fixate a target light so that the adducting eye is free to
• Allergy to pharmacologic agents like atropine manifest oblique dysfunction.
• Enquiry regarding the use of echothiophate iodine in the
recent past as it can cause scoline apnea during usage of MEASUREMENT OF VERGENCE
succinyl choline in general anesthesia
Family history* Measurement of Nearpoint of Convergence
• Refractive error Objective method The near point of convergence (NPC)
• Squint.
is determined by placing a fixation object at 30 to 40
Treatment history cm in the midplane of the patient’s head. The patient
• Glasses
1. When prescribed
2. Glasses worn constantly
3. Effect glasses had
4. Date of last refraction
• Occlusion therapy
1. Types of occlusion
2. When worn.
• Penalization
• Surgery
1. When performed
2. Performed on which eye
*
Family history not only includes parents and siblings but
also uncles, aunts and cousins. If there was a squint in the Fig. 111.1: Oblique dysfunction: Occluder is placed as a
family, the type of squint and the treatment instituted with partition between the two eyes. Right eye is manifesting inferior
the resulting outcome should also be elicited oblique over action. Left eye is fixating light in abduction
 Chapter 111: Evaluation of Strabismus 869
is then asked to maintain fixation on the object. The
object is moved toward the eye until one eye loses
fixation and turns out. The distance at which this
occurs is the NPC. It is measured using the Prince’s
rule. NPC should be at least 8 to 10 cm.
Subjective method It is performed in the same way. The
end point is measured when the patient experiences
double vision.
Motor tests

MEASUREMENT OF ANGLE OF
DEVIATION AND FACE TURN
Measurement of the angle of squint is done for both
distance (6 m) and near (33 cm). Always use an
accommodative target for the patient to fixate on.
For distance, the Snellen’s optotype is used (one
line above the patients best corrected visual acuity,
i.e. the 6/9 line in a patient with 6/6 vision). For near
the optotype in the Jaeger’s card is used. In case of
children, small cartoon figures can be used (any
picture with fine detail). Never use penlight because
it is the least accommodative target and if the child
does not fixate properly, the angle of squint can never
be accurately measured.
A. Light reflex test
1. Qualitative tests (Hirschberg’s test)
2. Quantitative test (Modified Krimsky test)
B. Cover test
1. Qualitative tests
a. Cover test: Tropia
b. Cover-uncover test: Phoria
c. Alternate cover test: Phoria + Tropia
2. Quantitative tests
a. Prism bar cover test: Phoria + Tropia
b. Simultaneous prism cover test: Tropia
Hirschberg’s Light Reflex Test (Fig. 111.2)
It gives a fair estimate of the angle of deviation. The
test is done only for near because the examiner must
observe the corneal light reflex (Purkinje Sanson
image-I) from behind the light source. The patient is
asked to fixate on a light source at 33 cm and the
position of the light reflex is noted in both the eyes. If
it is situated at the edge of pupil it is 15°, at the midway
between the pupillary margin and the limbus—30°,
and at the limbus—45°, Beyond the limbus it is more
than 45° (1° = 2 prism diopters and hence the angle of
deviation in prism diopters can be obtained; 1 mm of
decentration of light reflex is equal to 7° of squint).
Fig. 111.2: Hirschberg’s light reflex test: (A) Light reflex is
centered in both the eyes. Patient is orthophoric. (B) Temporal
decentration of light reflex. Patient has right esotropia. (C) Nasal
decentration of light reflex. Patient has right exotropia. (D) Lower
decentration of light reflex. The patient has right hypertropia
In esodeviation the light reflex is decentered in tem-
poral direction, in exodeviation it is decentered in
nasal direction, and for vertical squints it is decentered
above or below the pupil.
Krimsky Test (Figs 111.3A and B)
It is a modification of the Hirschberg’s test. A prism is
placed in front of one eye, (usually dominant). with
the base oriented appropriately to neutralize the
deviation.
A penlight is shined into both the eyes until the
light reflex is symmetrically centered.
Angle Kappa
Angle kappa8 is the angle formed by the pupillary axis
and the visual axis. Positive angle kappa is associated
with out-turning of the eyes and negative angle kappa
with inturning of the eye. Normally all patients have
a small positive angle kappa. Pathologically positive
angle kappa occurs when the macula is displaced
temporally in disease such as retinopathy of pre-
maturity (ROP). A negative angle kappa is caused by
nasal displacement of the fovea toward the optic
nerve.
870 Section 7: Pediatric Ophthalmology Including Strabismus
Figs 111.3A and B: Krimsky test: (A) Patient is made to fixate
on a target with fine detail juxtaposed next to a light source. (B)
Prism is placed in the front of the fixating eye until the light
reflex is centered in the squinting eye
All the tests described below are done for distance
and near. The prerequisites for these tests are patients’
cooperation, good fixation in both eyes, and normal
ocular motility.
Cover test (Fig. 111.4) Cover test is used to detect
tropias. Patient is asked to fixate at the accommodative
target and then one eye is covered. The uncovered eye
is looked for any movement. The following conclu-
sions can be drawn if the uncovered eye shows:
1. Inside movement—indicates exotropia
2. Outside movement— indicates esotropia
Patient is made to fixate on a target with fine detail
juxtaposed next to a light source
3. Downward movement— indicates hypertropia
4. Upward movement— indicates hypotropia.
Cover-uncover test It is used to detect phoria. The
covered eye is just uncovered to see for movement.
Fig. 111.4: Cover test: When occluder is placed in front of the
nonsquinting eye, the squinting eye moves out (if estropia) to
take up fixation
The following conclusion can be drawn with different
movements:
1. Outside movement—esophoria
2. Inside movement—exophoria
3. Vertical movement—vertical phoria.
Alternate cover test The cover is rapidly alternated
between the eyes and make sure that the occluder is
placed before each eye for more than 2 seconds to
disrupt fusion. Alternate cover test brings out the total
deviation—tropia plus phoria.
Prism bar cover test (Fig. 111.5) Prism bar cover test
quantitatively measures the total deviation. Prisms
should always be placed with the apex pointing
toward the deviation. Never stack prisms because it
gives an under estimation of the angle of deviation.
When prisms are being changed, always make sure
that the other eye is covered. Place the prism appro-
priately in front of one eye and then perform the
alternate cover test until there is no refixation
movement. This quantitatively measures the angle of
deviation.
Measurement of Incomitant Deviations
In incomitant squints, secondary deviation is more
than the primary deviation (secondary deviation is
when the paretic eye is fixing). When measuring
primary deviation place prisms in front of the paretic
eye until there is no refixation movement.
When measuring secondary deviation place prisms
 Chapter 111: Evaluation of Strabismus 871
appropriately in front of the nonparetic eye until there
is no refixation movement.

Face Turn and Head Tilt

It points out to the presence of nystagmus or incomi-
tant deviation. The degree of face turn can be assessed
by using the torticollimeter of Sradj.

SENSORY TESTS
• Stereoacuity estimation
• Diplopia test
• Suppression
• Anomalous retinal correspondence
• Haploscopic tests

Stereoacuity Estimation
Stereopsis is the highest grade of binocular vision.
Horizontal separation of two similar images stimulates
noncorresponding retinal points within the panums
fusional area that results in stereopsis.
This image disparity is measured as an angle in
seconds of an arc. In patients with bifoveal fusion the
stereopsis is 40 to 50 sec of an arc. In patients with
peripheral fusion the stereoacuity is only 8 to 30 sec
of an arc.
Stereopsis can be assessed in children who are two
years of age and older.

Lang’s Two-pencil Test
This is one of the oldest and most popular test. The
examiner holds a pencil vertically in front of the
patient. The patient’s task is to touch the upper tip of
the examiner’s pencil with one swift movement from
above; patient passes this test when stereopsis is
present.
This test also helps to differentiate between ano-
malous retinal correspondence from suppression. A
person with obvious squint is made to perform the
two-pencil test under monocular and binocular
conditions. A person with suppression may perform
this test in both conditions. A person with anomalous
retinal correspondence passes this test only under
binocular condition.
Titmus Stereo Test
The titmus fly9 which is in the form of a vectograph is
used in children.
The child is made to wear the polarizing glass and
is asked to pinch the wings of the fly. A child with
Larger prism 20 PD is placed in front of the left eye and alternate cover
testing now reveals no shift in eye position as the deviation is completely
neutralized
Fig. 111.5: Prism alternate cover test for esotropia 40 PD
stereopsis will be able to pinch the wings slightly
above the plane of the fly due to three-dimensional
effect. It shows the presence of gross stereopsis of 3000
seconds of an arc.
It also has three rows of animals, one animal in
each row can be appreciated by a person with
stereopsis. The stereopsis are 400, 200, 100, seconds of
arc in the three rows.
Last the titmus test contains nine sets of 4 circles
arranged in the form of a lozenge. In this sequence, the
upper, lower, left or right circle is disparately imaged
at random with thresholds from 800 to 40 sec of arc.
The disadvantage of titmus stereo test is that it
provides monocular clues and even a stereoblind
observer may get it right. Random dot sterograms and
TNO test are completely devoid of monocular dues
and they are a better assessor of stereoacuity.
872 Section 7: Pediatric Ophthalmology Including Strabismus

Diplopia Tests • Exotropia with NRC—crossed diplopia with the

red light seen opposite to the red filter
The basis of diplopia test is that one fixation target is
• Strabismus with suppression results in perception
used that is seen by both eyes. In patients with straight
of a single red or white light
eyes, the target image will fall on both foveas, but in
• In patients with strabismus and anomalous retinal
strabismic patients the target image falls on the fovea
correspondence—the pseudofovea in the deviated
of the fixing eye and on an extrafoveal point in the
eye functionally corresponds to the true fovea of
nonfixing (squinting) eye.
the fixing eye and hence the patient will see a single
The various dissociating diplopia tests 10 in
pink light.
descending order of dissociation are
Anomalous retinal correspondence (ARC) can be
• Maddox rod
identified by neutralizing the angle of deviation with
• Dark red filter
prism. If neutralization results in diplopia then the
with room lights off
patient has ARC. The diplopia that occurs is of para-
• Worth 4-dot
doxical nature. Esotropia and ARC result in crossed
with room lights on
diplopia after neutralization of the deviation with
• Bagolini striated lenses.
prism. Exotropia and ARC result in uncrossed
Red Filter Test (Figs 111.6A and B) diplopia.
Put a red glass over one eye and direct the patient to Worth 4-Dot (Fig. 111.7)
fixate a white light source.
The various responses are as follow: It consists of two green lights, one red light and one
• Straight eye with NRC (Normal retinal corres- white light. The patient wears red and green glasses
pondence)—one pinkish-red light is seen usually with the red glass in front of the right eye and
• Esotropia with NRC—uncrossed diplopia with the views the worth 4-dot at 1/3rd of a meter (flash light)
red light seen in the same side as the red filter or at 6 m (light box).

Figs 111.6A and B: Diplopia testing using red filter: (A) Uncrossed diplopia with esotropia. (B) Crossed diplopia with exotropia
 Chapter 111: Evaluation of Strabismus
Fig. 111.7: Worth four-dot test
The WFDT are separated by 6° at near and by 1.25°
at distance. Worth 4-dot performed in dark is more
dissociating than in light because of the absence of
peripheral fusion clues. The following conclusions can
be drawn:
1. Normal fusion—subject sees 4 lights, 2 red and 2
green or 1 red light, 2 green lights and 1 light that
flickers between red and green. This light that
flickers is the white light that is seen by both eyes.
The flickering is due to color rivalry.
2. Acquired strabismus and diplopia—5 lights, 2 red
and 3 green.
3. NRC and exotropia—crossed diplopia.
4. NRC and esotropia—uncrossed diplopia.
5. Acquired strabismus and suppression—report
either 3 green lights or 2 red lights depending on
which eye is fixing.
6. Alternate fixation—describe seeing 2 red lights
alternating with 3 green lights.
873
7. Monofixational syndrome (Central suppression
scotoma less than 6 degrees with peripheral
fusion)—fuse near WFDT which subtends 6 degree
because the dots fall outside the scotoma. Suppress
distance WFDT which subtends 1.25° as they fall
within the central scotoma.
Bagolini Lens (Fig. 111.8)
Bagolini striated lenses are lenses that have fine
striations that produces a streak at 90° to the striations
when the patient views a point source of light. The
lenses are placed over each eye with the striations
oriented obliquely at 45 and 135 degrees.
• Straight eyes and NRC and those with harmonious
ARC report seeing a cross
• Large regional suppression—see only one line
• Monofixation syndrome—a cross is seen but there
is a central gap in one line
• NRC and estropia—uncrossed diplopia with
V pattern
• NRC and exotropia—crossed diplopia with A
pattern.
Maddox Rod Test
It consists of multiple cylindrical high plus lenses
stacked on top of each others.
When a patient views a light source through the
maddox rod, a linear streak is seen that is oriented
90° to the cylindrical ribs of the maddox rod.
Fig. 111.8: Bagolini testing
874 Section 7: Pediatric Ophthalmology Including Strabismus
Single maddox rod test (Fig. 111.9A) The maddox rod
is placed over one eye and asking the patient to view
a penlight. To detect horizontal deviation the streak
is vertical and for vertical deviations the streak should
be horizontal. The maddox rod is so dissociating that
it causes even patients with normal bifoveal fusion to
manifest their phoria.
Double maddox rod test (Fig. 111.9B) With the double
maddox rod test the patient is asked to align the two
lines of the maddox rod in a parallel fashion. Patients
without torsion will see parallel lines and patients with
Fig. 111.9A: Single maddox rod test
Fig. 111.9B: Double maddox rod test
torsion will see one line slanted inward or outward
depending on intorsion or extorsion and the other line
as a horizontal line.
Haploscopic Test
Haploscopic tests have two fixation targets one for
each eye and the targets are moved separately to align
with the fovea. Examples are Lancaster red-green and
Hess chart.11
Hess Chart (Fig. 111.10)
Patient is made to sit at 50 cm from the chart. The room
lights are dimmed. Patient is made to wear red-green
goggles. Red before the right eye and green before the
left eye first and then it is switched over.
The patient fixates on the red dot of light projected
by the examiner. The patient then directs the green
light given to him to align with the examiners light.
The patient perceives a single streak of light as each
light falls on the corresponding fovea even though the
streaks are separated. All the points in the Hess chart
are plotted with the red goggle before the right and
green before the left and then the glasses are alternated
and points are charted.
Hess chart gives the following information:
1. The eye with paresis or restriction.
2. Underaction and overaction of muscles.
3. Angle of deviation.
It is a reliable and repeatable source of information.
Less screen is another form of Haploscopic test
where a mirror is used to dissociate the eyes. In
 Chapter 111: Evaluation of Strabismus 875

Fig. 111.11: Amblyoscope—testing a patient with normal

retinal correspondence and orthotropia

Fig. 111.10: Hess chart

contrast the Hess chart uses complementary colors to

dissociate the eyes.

Normal and Anomalous

Retinal Correspondence
Corresponding retinal points are points that are
physiologically linked to the same binocular cortical
cells.
NRC is correspondence between corresponding
retinal points.
ARC is correspondence between non-corres-
ponding retinal points.

Amblyoscope (Figs 111.11 to 111.13)

Amblyoscope or synoptophore provides a haplo-
scopic12 view allowing presentation of images to each
eye independently. The transparent picture slides are
reflected by the mirrors situated at the elbow of the
arms of the amblyoscope. The arms of the amblyo-
scope can be moved to align the stimulus targets with
each fovea. Fig. 111.12: Harmonious ARC and right esotropia or 20 PD
876 Section 7: Pediatric Ophthalmology Including Strabismus
Fig. 111.13: Unharmonious ARC and 30 prism
diopters of esotropia
Subjective angle Amount in degrees the examiner must
move the amblyoscope arms to allow the patient to
see the two pictures are being superimposed.
Objective angle It is assessed by alternating the target
presentation from right eye to left eye and moving
the arms of the amblyoscope until there is no refixation
eye movement. The objective angle equals the
deviation as measured by alternate cover test.
Patients with harmonious ARC have a significant
objective angle but subjective angle is 0. The
displacement of the pseudofovea from the true fovea
is called the angle of anomaly. In harmonious ARC,
the angle of anomaly is equal to objective angle.
In patients with unharmonious ARC, the pseudo-
fovea is located in a position that does not fully
compensate the objective deviation. The difference
between the objective and subjective angle gives the
angle of anomaly.
After Image Test (Fig. 111.14)
The fovea of each eye is marked individually with a
linear streak of light that is masked in the middle. This
produces an after image that lasts appropriately for
ten seconds and has a break in the center.
Fig. 111.14: After image test
In NRC whether the patients is orthotropic or stra-
bismic, a cross is perceived by the patients with a break
in the center. In ARC with heterotropia, a paradoxical
after image is perceived. In esotropia, a crossed after
image and in exotropia an uncrossed after image.
SPECIAL TESTS
AC/A Ratio
It is the amount of change in convergence for a specific
amount of change in accommodation. The most
commonly used method is the lens gradient method.
The other methods are heterophoria method, distance-
near method. We will deal with the lens gradient
method.
The Lens Gradient Method
In this test accommodation is changed by having a
patient view an accommodative target through
supplemental plus or minus spherical lens.
 Chapter 111: Evaluation of Strabismus
A plus lens relaxes accommodation and a minus
lens increases accommodation. It is measured by
assessing the deviation at a set distance with and
without supplemental lenses and dividing the
difference by the lens power used:
Deviation without lens – Deviation with lens
___________________________________________________________
AC/A =
Lens power in diopters
Four Base-out Test (Fig. 111.15)
The test is performed by placing a four PD prism base
out in front of one eye. This induces fusional conver-
gence in normal individuals, i.e. a version movement
of both eyes in the direction of the apex of the prism
and second, a fusional vergence movement of the eye
without the prism in toward the nose.
Patients with monofixation syndrome have a small
central scotoma and hence do not show movement
when the four PD prism is placed over the nondo-
minant eye. The prism in front of the fixing eye results
only in version movement in monofixaters.
Forced Duction Test
It is performed under topical anesthesia in cooperative
adults when there is limited duction. In pediatric
patients it is performed under general anesthesia.
Instruct the patient to look in the direction of limited
duction. The technique is to grasp the eye at the
limbus, slightly proptose and rotate the eye in the field
of limited ductions. This will distinguish between
paresis or tightness due to contracture which causes
the limited duction. If it is possible to move the eye in
the field of limited duction then it is confirmatory of a
paresis, otherwise it is a suggestive of a contracture.
Forced duction test is considered positive when
contracture is present.
Muscle Force Generation Test
This is used to assess the rectus muscle strength. The
eye is anesthetized with topical anesthetic and the eye
is grasped at the limbus in the same fashion as in
forced duction testing. The patient is asked to look in
the field of limited movement and the eye is held in
primary position. The examiner feels the force
generated by the muscle as a tug and compares this
with the normal muscle from the unaffected eye. This
test is useful in assessing the amount of muscle
function.
877
Fig. 111.15: Four base-out prism test: (A) Right eye has
suppression scotoma with no motor fusion. A 4 PD base-out
prism in front of the right eye has no effect on eye movements;
the image moves within the suppression scotoma. (B) Placing
4 prism base-out in front of the left eye result in a version
movement with both eyes moving in the direction of the apex
of the prism, but since there is no fusion there is no convergence
movement
Cycloplegic Refraction
It is a must in every new strabismic patient. One
percent homatropine eye drops or 1 percent cyclo-
pentolate can be used for cyclopegic refraction.
Atropine 1 percent instilled twice daily for three days
before cycloplegic refraction is the best form of
cyclopegia.
FUNDUS EVALUATION
It is a useful indicator of torsional changes.13 In normal
persons the fovea is located between the midpoint and
the lower border of the optic disk. In patients with
extorsion, the fovea is shifted below the inferior border
of the optic disk and in intorsion, fovea is higher than
the midpoint of optic disk.
REFERENCES
1. Nelson, Calhoun, Harely. Pediatric Ophthalmology (3rd edn).
WB Saunders Company 1991;4:94.
2. Wright KW, et al. Reliability of fixation preference test in
diagnosing amblyopia. Arch Ophthalmol 1986;104:549.
3. Joyce Mein and Roger Trimble. Diagnosis and Management
of Ocular Motility Disorders (2nd edn). Blackwell Scietific
Publication 4: 53, 59.
4. Sherwin J Isenberg. The Eye in Infancy (2nd edn). St. Louis,
Mosby 1994;13:157.
878 Section 7: Pediatric Ophthalmology Including Strabismus
5. David Abranhms. Duke-Elders Practice of Refraction (10th
edn). Churchill Living Stone, 20:145.
6. Noorden GK von. Binocular Vision and Ocular Motility, 5th
edn. St. Louis: Mosby 1995;15:59.
7. Burde RM, Savino PJ, Trobe JD. Clinical Decisions in
Neurophthalmology (2nd edn). St. Louis: Mosby 1992;6:201.
8. Noorden GK von. Binocular Vision and Ocular Motility, 5th
edn. St. Louis: Mosby 1995;11:165.
9. Elkington AR, Frank HJ. Clinical Optics, 2nd edn. Blackwell
Scientific Publication 1:11.
10. Wright KW. Pediatric Opthalmology and Strabismus, 11:163.
11. Joyce Mein and Roger Trimble. Diagnosis and Management
of Ocular Motlity Disorders, 2nd ed. Blackwell Scientific
Publication 5:83.
12. Worth and Chavesses Squint T Keith Lyle CBE. State of
sensory correspondence, 237.
13. Eustis HS, Nussdorf JD. Inferior oblique overaction in
infantile esotropia. Fundus extrosion as a predictive sign. J
Paediatr Ophthalmol Strabismus 1996;33:85.
 Chapter 112
Sensory Adaptation in
Concomitant Squints
J N Rohatgi
The presence of a manifest squint or deviation causes
confusion and diplopia.
Different objects are imaged on corresponding
retinal points (the two foveae) and, therefore, are seen
in the same visual direction and overlap. This causes
confusion. Identical objects are imaged on disparate
retinal areas (fovea of the fixing eye and peripheral
retina of the deviating eye) and are, therefore, seen in
different visual directions, that is, these are seen as
two, i.e. diplopia.
Confusion is not often reported voluntarily but
when patients do notice overlap of the different foveal
images, they find it very distressing. On the other
hand, diplopia is a common complaint. This occurs in
every patient who has adequate vision in each eye and
in whom an acute relative deviation of the visual axes
has developed.
To avoid these—confusion and diplopia—the
visual system has at its disposal two mechanisms, i.e.
suppression and development of anomalous retinal
correspondence (ARC). And closely related to
suppression is another mechanism, that is, amblyopia
whereby the vision in the deviating eye is reduced.
These three help the patient to gain comfortable single
monocular vision or an anomalous form of binocular
single vision. These, thus, constitute nature’s way of
adapting to the altered situation caused by deviation
of one eye, uniocularly or alternatively.
DIPLOPIA
In a convergent squint, the fixation object is viewed
by the fovea of the nonsquinting or normal eye, while
in the deviating eye its image is formed on a point in
the peripheral retina, nasal to the fovea. This results
in cerebral impression of a false object situated on the
temporal side of the true object. This is a homonymous
diplopia or uncrossed diplopia. The angle between the
line of projection of the stimulated retinal point of the
squinting eye and the assumed line of projection of
the fovea of the squinting eye is equal to the angle of
squint (deviation).
In a divergent squint, the fixation object is viewed
by the fovea of the normal or nonsquinting eye and
by a peripheral retinal point situated on the temporal
side of the fovea of the squinting eye. This latter point
being situated on a part of the retina which normally
received stimuli from objects in the nasal part of the
visual field, causes cerebral impression of a second
object situated on the nasal side of the true object. This
gives a crossed or heteronymous diplopia. True image
is the image of the nonsquinting normal eye and false
image is the image of a squinting eye.
Diplopia is binocular; that is, both eyes (the fixing
eye and the deviating squinting eye) have to see to
cause diplopia. But a different type of diplopia also
exists, the uniocular diplopia which has nothing to
do with the concomitant squint except occasionally
during treatment of strabismic amblyopia.
SUPPRESSION
One of the means by which double vision and
confusion could be avoided is suppression. The image
of an object formed on the retina is not perceived but
is mentally ignored or neglected, partly or completely.
The process of suppression is the result of a cerebral
inhibition to give the fovea of the normal (non-
880 Section 7: Pediatric Ophthalmology Including Strabismus
squinting) eye complete dominance so that it forms
the center of attention and the patient adjusts himself
to the environment by means of a uniocular type of
perception. There is active inhibition of the image from
the squinting eye in the cerebral centers and, as such,
the visual acuity of this eye suffers causing a more or
less perceptual blindness.
Such suppression is of the following two types: (a)
Facultative, and (b) Obligatory inhibition.
Facultative Inhibition
In this, suppression of the image from the squinting
eye occurs so long as the eye is deviating. The moment
this eye takes up fixation, the inhibition of the image
(or visual impression) of the eye disappears and there
is an immediate return of more or less normal visual
function. This is typically seen in an alternating squint
where suppression is transferred, immediately from
one eye to the other on changing fixation. In this way
each eye retains good visual function.
Obligatory Inhibition
So long as a squinting eye is deviating, there is
suppression from this eye. Even when the squinting
eye is forced to take up fixation, the suppression
persists. It is typically seen in a case of uniocular
convergent squint, where the nondeviating normal eye
is chosen for fixation (because it has a better visual
acuity) and the squinting eye continues to have
suppression which in due course becomes obligatory
and fixed.
In the early stages of the development of a
uniocular squint, the inhibition is facultative and, as
time goes on and there is no treatment to correct the
deviation, the inhibition becomes obligatory with the
suppression of the image from this eye at cortical level.
This in turn leads to a consequent diminution of the
visual function and visual acuity of the deviating eye.
Young child In a young child where the binocular
reflexes are still in a state of flux, there is a rapid
transition from the facultative to the obligatory stage
of inhibition. But in an older child (where these reflexes
have become well-established), this is not feasible and
the obligatory inhibition may be minimal.
If a child is born with squint or he develops the
deviation in the early months after birth, the presence
of deviation precludes the development or further
development of central vision. This failing of vision is
called amblyopia of arrest. And this happens in a case
of congenital uniocular squint. On the other hand, in
cases of uniocular squint developing after birth or in
the first few years of life, there is loss of all or part of
the vision which had developed prior to the onset of
deviation. This is amblyopia of extinction along with
amblyopia of arrest.
Eccentric fixation Following obligatory inhibition, the
fixation of the squinting eye may suffer. A nonfoveal
retinal receptor in the squinting eye assumes a foveal
or straight-ahead form of projection and becomes the
point of reference around which the other retinal
receptors are ranged as a result of a change in the
spatial projection of all the receptors. This eccentric
retinal point has been termed as a false-macula or false-
fovea or pseudofovea and has less visual acuity value.
In abnormal retinal correspondence also (vide
infra), a point in the squinting eye other than the fovea
takes up fixation as an adaptation to produce binocular
single vision (BSV). This is pseudofovea.
ABNORMAL/ANOMALOUS
RETINAL CORRESPONDENCE
The third type of sensory adaptation of a squinting
eye is the development of abnormal retinal corres-
pondence (ARC). It is an abnormality of binocular
visual function which occurs in some cases of
concomitant squint as an adaptation to the ocular
deviation in an attempt to avoid diplopia and
confusion. Chavasse (1939) wrote “The first sign of
ARC is the ability to project correctly in spite of the
deviation of one eye” (that is, to project correctly in
relation to the body in space). It is an attempt to restore
some semblance of binocular vision. ARC presumably
adopts the sensory visual system to the abnormal
motor condition created by the deviation in an effort
to restore some semblance of binocular cooperation.
Abnormal retinal correspondence is of two types:
1. Harmonious ARC, and
2. Unharmonious.
Harmonious ARC
In a squinting eye the image of the object of fixation
falls on a point nasal or temporal to the fovea
depending on the type of squint, convergent or
divergent. In harmonious ARC, the angle of anomaly
and angle of squint are equal. The angle or anomaly
is the difference between the subjective and objective
angle of squint (Fig. 112.1).
 Chapter 112: Sensory Adaptation in Concomitant Squints
Fig. 112.1: RL convergent squint with harmonious ARC
Unharmonious ARC
Normally, a fixation object is viewed or appreciated
by the fovea of the normal eye and by a point other
than the fovea (on nasal side to it, in convergent squint)
of the squinting convergent eye. When harmonious
retinal correspondence develops, this point of
abnormal correspondence assumes the straight-ahead
(foveal) fixation to give rise to binocular single vision.
In unharmonious type of ARC a point on the retina
between the fovea and this abnormal point of fixation
on the retina (in the squinting eye) takes on the
function of straight-ahead (foveal) fixation. Thus the
angle of anomaly is smaller than that in a case of
harmonious ARC, that is, it is not true angle of squint.
Clinically ARC is likely to develop in the following
conditions:
i. Concomitant convergent squints of low to
moderate degree, the condition being less likely
to be found in deviations greater than +20° to
+25°.
ii. Convergent squints of early onset that is up to
the age of three years and infantile esotropia
specially when treatment has been neglected.
Cases of squint in which ARC is unlikely to occur
i. ARC is generally not found in cases of primary
divergent squints irrespective of the age. In these
881
cases there is no visual reward from abnormal
retinal correspondence. Also in divergent squints
many cases are intermittent to start with and by
the time the deviation becomes constant, the
binocular single visual function develops.
ii. Cases of convergent squint of late onset, say after
the fifth year. In these cases chances are that
binocular reflexes, have fully developed and as
such they cannot be easily replaced by abnormal
reflexes.
iii. Convergent squint cases with deviation greater
than +25° to +30° or more. In these cases, the
image in the deviating eye is formed in the
peripheral retina; hence, poorly defined and as
such easily suppressed.
iv. Cases of convergent squints of variable angle of
deviation. In such cases, a single area cannot be
established as pseudofovea.
Detection of ARC
A variety of methods and tests have been described
for detecting the presence of this binocular anomaly.
Of these the following are in common practice:
Examination on major amblyoscope The objective and
subjective measurements of the deviation are made.
In objective measurement using foveal-sized pictures
(in the slides) say lion before the left eye (fixing eye)
and the cage before the right eye (the deviating eye),
the left tube is set at zero on the scale and the right
tube (with the deviating eye) is moved till the corneal
reflex in this eye appears in the center of the cornea as
in the left eye. At this point both the pictures; the lion
and the cage are seen at the same time but not
superimposed indicating lack of normal retinal
correspondence. This movement of the right tube
(deviating eye) gives the objective angle. In the
subjective method, the patient moves the tube (in front
of the deviating eye) till the cornea reflex for this eye
appear in the center of the cornea and he feels that the
lion is well inside the cage.
Angle of anomaly The difference between the subjective
angle and the objective angle is known as the angle of
anomaly or the angle of adaptation.
The ARC found on examination may be unstable
and variable and amenable to treatment or it may be
stable and constant and thus difficult to eradicate. On
further examination, if the patient has a good power
of fusion, nothing need be done to treat such case of
ARC.
882 Section 7: Pediatric Ophthalmology Including Strabismus
The after-image test Extensively used by Bielschowsky
(1938), is accepted as the best method of ascertaining
the sensorial relationship between the two eyes
(Described in detail in Chapter 111).
Demonstrating after-image test It could be carried out
on a synoptophore using after-image slides, or by
using a cylindrical glass tube one foot in length
containing a glowing filament. Around the center of
the tube there is a black band with a fixation spot. The
tube is attached to its stand in such a way that it could
be rotated from the vertical into the horizontal
position. One can also use an electronic flash device.
Striated glass test of Bagolini (1958) Striated glass lenses
have been used for demonstrating the presence of
ARC. On looking a spotlight through a plain glass
which is striated (as in a maddox rod), the spotlight
appears to be transected by a clear linear streak of light.
One such striated glass is put in front of right eye and
the other in front of left eye in a trial frame, in a way
that the streaks of the two glasses appear to be at right
angle to each other. With such an arrangement the
linear streak of light (of the spotlight) presented to
one eye is at right angle to that presented to the other
eye. A person with normal binocular vision or normal
retinal correspondence will see the two lines making
a cross and bisecting each other at the center of the
spotlight. A patient with manifest deviation who
describes a cross cutting the light but not as to center,
indicates the presence of harmonious abnormal retinal
correspondence.
When such a patient sees two spotlights each with
its separate streak of light, it indicates normal retinal
correspondence or unharmonious ARC. Prisms may
be used to joint the two images (if possible) and the
patient is asked to state when this occurs. In the case
of unharmonious ARC the angle of anomaly is the
difference between the strength of the prisms used for
the objective and subjective tests. If the patient sees
only one streak of light, it indicates that dense control
suppression is present.
Treatment of ARC
It is generally accepted that ARC is a well-established
adaptation which may follow the development of a
squint. It is a condition which can become so firmly
fixed that eradication is often impossible. A
harmonious type of ARC counteracts diplopia and
confusion and provides a useful form of binocular
vision. Hence, in a large number of cases it is
uneconomical to attempt to treat and it is doubtful if
the effort is really worthwhile.
In early cases, when ARC is still in the developing
state, occlusion of the sound eye may arrest its
progress and reduce its stability. Occlusion helps
prevent as well as to cure or lessen the abnormal retinal
correspondence.
Orthoptic exercises and surgical correction of the
deviation do help. von Noorden postulates the
following three stages: (1) Correspondence remained
anomalous, (2) Rivalry occurred between normal and
abnormal correspondence, and (3) Normal
correspondence was re-established in favorable cases,
but not all cases go through these three stages.
The present trend is to accept a small angle
(cosmetically inconspicuous) residual strabismus with
ARC as an acceptable or even desirable end stage of
therapy in infantile esotropia requiring no further
treatment except for a co-existing amblyopia. In
acquired squint late in childhood it may need to be
treated.
Orthoptic treatment It is a long drawn affair to eradicate
abnormal retinal correspondence and with a variable
success rate. Therefore many do not subject their cases
to orthoptic treatment. Stimulation has to be foveo-
foveal, foveal-psuedofoveal with dissimilar and
similar images.
AMBLYOPIA
Habitual suppression of one eye results in amblyopia.
Amblyopia is derived from a Greek word meaning
blunting of vision. Such as eye is generally described
as one which is structurally normal but functionally
has reduced visual acuity. And this reduced visual
acuity cannot be fully improved with glasses.
This blunting of vision or poor visual acuity in an
eye may be associated with an organic lesion or is
without any detectable organic lesion. The latter is
pure amblyopia while the former with organic lesion;
as for example, amblyopia with congenital cataract or
that caused by toxic substances.
The condition of functional amblyopia may be
explained by unilateral suppression of foveal vision
and is unilateral. But one may come across cases of
bilateral amblyopia as in cases of high hypertropia in
both eyes in excess of +7.00 diopter or associated with
astigmatism in excess of +3 diopter.
 Chapter 112: Sensory Adaptation in Concomitant Squints 883
In a large percentage of cases of amblyopia, the Table 112.1: The causes of amblyopia
reduced visual acuity in the amblyopic eye is
Amblyopia without squint Amblyopia with squint
associated with deviation (squint) in that eye. Hence, (Straight-eye amblyopia) (with central (With eccentric
we can divide cases of uniocular amblyopia into two fixation) fixation)
subgroups Table 112.1 (Rohatgi, 1968):
Of the two groups, the straight-eye amblyopia a. With high hypermetropia With or without significant
in the amblyopic eye- refractive error in the
group constitutes a large number of such cases. anisometropic amblyopia amblyopic deviating eye
b. With equal refractive error
Straight-Eye Amblyopia in both eyes
c. With no significant
The first group of straight-eye amblyopia cases have
refractive error
high hypermetropic refractive error in the amblyopic
eye. They have been variously called as suppression
In the majority of cases of concomitant squint
amblyopia, straight-eye amblyopia and anisometropic
specially when one eye has a better visual acuity, this
amblyopia. Such cases often go unnoticed till the child
eye tends to be used in preference to the other. This
has a routine school medical examination. The
causes a conditioned inhibition in the neglected
mechanism of such an amblyopia is different from the
deviated eye. This inhibition gradually becomes fixed
mechanism in cases of squint amblyopia.
leading to the development of an obligatory inhibition
Such an amblyopia is obligatory in type but more
or amblyopia.
amenable to treatment than amblyopia in a case of
The extent to which this inhibiting of vision occurs
strabismus. Synoptophore examination may show
and the amount of vision which can be reclaimed,
good binocular function (simultaneous macular
varies with the following:
perception, fusion and full steropsis with little or no
1. The degree of visual development obtained before
suppression).
inhibition became operative.
If a child is unable to accommodate equally with
2. The length of time during which it remained active,
each eye as happens in anisometropic hypermetropia
and
or if the accommodation does not achieve clear
3. To some extent on the mental make up of the child.
definition as in unilateral astigmatism, the retinal
Further, the earlier the age at which inhibition first
image of the more amblyopic eye is blurred. This
became operative, the more profound is the amblyo-
blurred image is a sensory obstruction to binocular
pia. Thus, in a case of congenital squint, where the
vision and is, therefore, suppressed. This suppression
inhibition is present from birth, vision in the squinting
begins when accommodation starts being active that
eye will remain permanently a little more than
is about the age of 2 to 3 years. The sensitivity to
perception of light. On the other hand, if this inhibition
develop amblyopia gradually decreases until the child
of vision in one eye (squinting eye) occurs after the
reaches 6 to 7 years of age when visual maturation is
age of 6 years or so (when the visual acuity has fully
complete.
developed), no such arrest of development on amblyo-
At first the inhibition is probably facultative and
pia is likely to occur. In between, when amblyopia
in the nature of a central scotoma but habitual disuse
comes up about the age of 3 to 4 years, (accommo-
renders it obligatory. Distortion of objects does not
dative convergent squint) recovery of vision is likely
occur as it sometimes does in the amblyopia of squint
to take place up to the level, normal for the age at
with myopes unless the myopia is of high degree. Both
which inhibition commenced. This was earlier referred
retinae receive adequate simulation and amblyopia
to as amblyopia exanopsia (amblyopia of disuse)
does not develop.
which as would be mentioned later on, is not entirely
correct.
Amblyopia with Squint
In addition to the process of developmental arrest
Patients who constantly use one eye for fixation (as in mentioned above, any vision which has not become
unilateral squint) and as opposed to alternating permanently established and reached the state of an
fixation pattern (in case of alternating squint) are most unconditioned fixation, may be actively suppressed—
likely to develop or acquire strabismic amblyopia. One (Amblyopia of extinction).
can expect to find amblyopia far more often in For example visual acuity may have developed as
esotropes than in exotropes. low as 6/12 when an obstacle interferes with further
884 Section 7: Pediatric Ophthalmology Including Strabismus
normal development. The visual acuity may after a
period of disuse of the eye deteriorate to 6/24. This
drop is called the amblyopia of extinction. Thus, if a
child’s eye is bandaged (for a month or two as is done
for occlusion therapy to improve vision in the
deviating eye) the vision in that eye may drop, to
recover again when the obstacle is removed.
The depth of amblyopia and its recovery varies
depending on the following:
a. The degree of VA attained before inhibition became
effective.
b. The period during which the extinction of vision
remained active, and
c. The age at which amblyopia developed. Thus deep
amblyopia is a disease of the young; primarily
those under the age of four years.
Diagnostic Criteria
Clinically, a difference of two lines on a visual acuity
chart (Snellen’s chart) without any organic case is
commonly used as a diagnostic criteria for amblyopia.
However, in a patient with squint in whom the visual
acuity in the “amblyopic eye” has improved from
6/36 to 6/12 must still be considered amblyopic when
visual acuity in the fixing second eye is 6/6.
Crowding phenomenon In patients with amblyopia, it
is always of interest and importance to compare the
vision obtained with visual acuity symbols presented
in a row to that obtained with isolated symbols like E
on a uniform background. According to von Noorden,
in some patients the difference is quite startling such
as when a line acuity of 6/36 responds correctly to
6/6 symbols presented singly. This is known as
crowding phenomenon.
Fixation Pattern of Amblyopic Eye
There are cases of squint amblyopia where the fixation
is eccentric rather than being central. These cases of
eccentric-fixation do not assume central fixation even
when the fellow eye is covered, that is the amblyopic
eye remains more or less deviated.
Bangerter’s classification of fixation pattern in
amblyopia is as follows:
1. Central fixation.
2. Eccentric fixation (non-foveolar).
3. No fixation around the true fovea.
Parafoveal—within 2° of the fovea.
Para macular—between 2° to 4° away from the true
fovea.
Centrocecal—greater than 4° between the macula
and the optic disk.
Paracentral—around the optic disk.
Cover test and corneal reflex method It can diagnose only
gross degree of eccentric fixation and thus, many of
these cases can remain undiagnosed and wrongly
treated in absence proper diagnostic instruments with
the help of visuoscope (a modified ophthalmoscope).
Cuppers first localized accurately the eccentric
fixation. A number of modern ophthalmoscopes have
a built-in fixation target that helps in diagnosing the
eccentric-fixation. Once diagnosed, Cuppers had used
euthyscope to dazzle the area of eccentric fixation, after
first covering the foveal area. By these exercises, the
acuity of the area of eccentric fixation is reduced
compared to the VA of the foveal area. And thus
eccentric fixation amblyopia is converted into
amblyopia with foveal fixation.
Bengerter Pleoptophore This fully controllable device
dazzles out the area of eccentric fixation while the
fovea is protected by a black disk. This is followed
immediately by stimulating the fovea by means of
intermittent light stimulus. Once the patient is able to
recognize the foveal light stimulus, subsidiary instru-
ments like localizer, centrophore, and separation
trainer take over.
Treatments
In 1743 Buffon recommended patching of the fixating
eye (in a case of concomitant squint) to improve the
vision in the deviating eye; according to him poor
vision of the amblyopic eye was the cause of the
deviation. The concept of amblyopia as a sensory
adaptation to squint, patching was re-introduced and
has since remained the mainstay of amblyopia
treatment, both for the strabismic amblyopia as well
as for cases of straight-eye amblyopia.
But before occlusion of the sound eye, refractive
error (if any) should be assessed under cycloplegia
and full refractive correction consistent with the visual
comfort of the child should be prescribed. In an
unilateral high hypermetropic under-correction is
recommended.
Occlusion treatment Occluding the sound eye forces
the child to use the amblyopic eye. In addition it
removes the inhibiting stimuli to the amblyopic eye
that arise from stimulation of the fixing eye.
It appears to be a simple procedure and in many
cases it is so. But the practical application of this simple
 Chapter 112: Sensory Adaptation in Concomitant Squints 885
procedure is beset with many difficulties more so in are at risk of having recurrence of amblyopia, can be
young children. helped by alternating penalization.
Many different ways for occluding the eye are as Sneak or slowly increasing occlusion may be tried
follows: in children between 2 to 4 years of age. In this method
a. Attaching an occluder to the glass or pasting the graded papers are pasted on the lens reducing the
lens with a dark black paper so that no light can vision in the good eye to a known extent varying from
get through the paper and glass to the eye. 6/9 to 6/60. The purpose is to put the good eye
b. A piece of material that fastens directly to the skin. gradually at a disadvantage in order to encourage the
The important point, however, is that the fixating weak eye.
eye should be occluded completely and constantly
during all woken hours. The child should be re- Occlusion in Squinting Eye with Eccentric Fixation
examined at frequent intervals and vision of both eyes
a. Many investigators are of the opinion that after two
be tested. Sometimes, it so happens that the vision is
years of age occlusion of the sound eye is contra-
the fixating eye under occlusion goes down or it
indicated in amblyopes with eccentric fixation,
becomes amblyopic. This, however, is reversible and
since it may reinforce anomalous fixation behavior.
in such cases occlusion has to be made alternate
They suggest that instead the amblyopic eye
occlusion of sound eye with occlusion of the amblyopic
should be occluded to break up the abnormal
eye.
fixation behavior. This is inverse occlusion.
Occlusion has to be constant until the vision of the
However, other workers have reported that the
amblyopic eye and its fellow eye becomes almost
occlusion of the sound eye (direct occlusion) is
equalized or until there is no improvement even after
effective until 5 years of age regardless of the
three months of constant occlusion, whichever in
fixation behavior. To steer clear of the controversy,
earlier.
many now use inverse occlusion only during the
The visual improvement in the amblyopic eye is
initial phase of therapy of eccentric fixation in
better in cases of straight-eye amblyopia than in cases
children older than 5 years of age and then switch
where amblyopia is associated with squint. In suitable
on to occlusion of the sound eye.
cases of anisometropic amblyopia where the refractive
b. Prisms—to break the eccentric fixation, use of
difference does not exceed +4.0 diopter, a visual acuity
prisms—base in and base out, before the amblyopic
of 6/9 may be achieved. Further unlike cases of
eye in combination with occlusion of the sound eye
concomitant squint, the VA may improve in these
has been suggested by various authors with
children up to the age of 15 to 16 years (sometimes
varying degrees of success. Prism-base-out before
even in college going students up to 20 years of age)
the fixating eye in convergent squint cases to align
whereas in squint amblyopic cases the visual acuity
the deviated eye with amblyopic and eccentric
has practically no chance to improve once the age of 6
fixation and thereby create conditions more
to 7 years has passed without any active treatment.
favorable for foveal fixation.
Amblyopia tends to recur until children have
reached 8 to 10 years of age because of the persistence
CAM Treatment for Amblyopia
of inhibitory effect from the fixating eye and it may
be necessary to resume occlusion. Such children, who See Chapter 97. Ed.
 Chapter 113
Introduction to
Heterophoria
SK Narang, S Narang, Priya Narang
Normally the two eyes maintain an oculomotor
apparatus in a perfect equilibrium so that both eyes
remain parallel when looking at a distant object and
remain directed upon the fixation point for looking
near object even when their activity is dissociated by
the withdrawal of the controlling influence of fusion.
This maintenance is without effort for all direction of
gaze and all physiological distances of the fixation
point. If eyes are in such a state they are said to be
orthophoric. Orthophoria, like emmetropia, contrary
to expectation is uncommon. When fusion reflexes are
partially or totally removed and the visual axes do
not remain in such a position that the two images of
the object of regard fall on the two foveae there is
imperfect muscular balance. With imperfect muscular
balance the desire for binocular balance may act as a
stimulus and turn the eyes in a position so that the
visual axes lie in alignment. Such a state of muscular
imbalance is termed as heterophoria. A heterophoria
of long-standing puts considerable fatiguing strain or
in some debilitating conditions the ocular musculature
cannot cope with this strain, in these conditions a
heterophoria may be converted into a heterotropia.
Heterophoria is also known as latent squint.
ETIOLOGY
The causes of basic deviation whether it is phoria or
tropia are the same. They may be enumerated as
follows.
Mechanical
Muscle origin and insertions have been blamed for
basic deviation but no concrete proof is available to
justify this factor.
Innervational
Defective innervation may to a certain extent be
responsible for phorias and is probably due to
anomalous central distribution of the individual tonic
reciprocal innervation to the muscles of the two eyes.
Refraction Errors
Refractive errors may be responsible for deviations.
In moderate hypermetropia, the patient has to use his
accommodation even for distant and more so for near,
so he develops esodeviations as convergence goes
hand in hand with accommodation. On the other hand
myope has not to use accommodation even for near;
hence he is likely to go for exodeviations. Whether
the role of refractive errors is primary or secondary,
is still debatable as there may be many cases of refrac-
tive errors who do not develop deviations.
AC/A Ratio
Whenever a person accommodates he converges also.
The normal value varies from 3 to 5:1. However this
ratio may be abnormal in some individuals. There are
two main methods for measuring this ratio, viz. gra-
dient and heterophoric method. High AC/A ratio
leads to esodeviation and low one, to exodeviation. It
plays more evident role in esodeviation.
Position of Macula
There may be variation in anatomical position of the
macula in relation to the optic axis of the eye.
 Chapter 113: Introduction to Heterophoria
Weakness of Muscles
There may be weakness of the muscles which may be
congenital or may develop after prolonged illness
leading to deviations. Usually its role is secondary, so
that phoria is converted into tropia.
Psychic Patients
Higher incidence of deviations have been reported in
mentally ill patients. Exact mechanism in these patient
is not known.
Brain Trauma
Many a time deviation has been reported for the first
time after brain trauma.
Genetic Factors
Genetic factors may be playing some roles in
deviations which have not been well-understood. But
families have been reported with deviations in
different members.
CLASSIFICATION
Heterophoria can be classified as the following:
Exophoria
It is a condition where the visual axes tend to deviate
outward. It is more common than esophoria in general
population because essentially it is an exaggerated
position from the normal. Most of the time it is asso-
ciated with convergence insufficiency but not always.
Esophoria
In this, visual axes of the two eyes tend to deviate
inward usually seen in moderate hypermetropia.
Hyperphoria
It is defined as a condition in which the visual axes
tend to deviate upward in relation to the visual axes
of the other eye. So accordingly if the right axis
deviates upward or the left, it is called right or left
hyperphoria. Nowadays we use the terminology right
over left (R/L) or left over right (L/R) according to
which eye goes up.
SYMPTOMS
The symptoms of heterophoria are closely associated
with symptoms of the refractive errors and closely
887
resemble them. Beside the symptoms of blurring of
vision, asthenopia, headache, itching, burning and
smarting of the eyes, the patient may complain of
occasional diplopia, dizziness and vertigo. Persistent
asthenopia after correction of the refractive error
should be thoroughly investigated for any muscular
imbalance. The symptoms are more marked after a
day’s continuous work. Students usually have the
symptoms after reading continuously for an hour or
so.
EXAMINATION OF PHORIA
Before one undertakes to examine a case of hetero-
phoria one should obtain a complete, precise, and
detailed history of the patient which includes volun-
tary information and information obtained by close
questioning.
Refraction
Patient’s refractive error should be checked under
cycloplegia especially for astigmatism. It should be
prescribed to the patient. If the symptoms disappear
no further treatment is required.
Ocular Movements
All the movements should be checked especially the
horizontal movements up to the extreme gaze.
Cover Test
The cover test should be done both for the distant and
near objects. A note is made for the direction of devia-
tion, degree of deviation (with PBCT), and whether
the recovery of alignment is slow or rapid.
Convergence Test
Roughly the convergence can be measured by holding
a pencil or a finger at a distance of 30-40 cm and
bringing it near to the patient’s eyes. The object should
be kept at the level of the eye of the patient till the eye
develops diplopia or one eye deviates.
Livingston’s binocular gauge is an instrument for
measuring near point of convergence and accommo-
dation more accurately. Major amblyoscope can be
used for degree of convergence and divergence.
Maddox Rod Test
It consists of several red glass rods or grooves set in a
metallic disk which can be put in a trial frame. It
888 Section 7: Pediatric Ophthalmology Including Strabismus
converts the image of a spotlight into a redline at right
angles to the direction of the grooves. Under these
circumstances the phoria is converted into tropia and
deviation is measured by putting prisms in the other
eye. The test can be repeated with the Maddox tangent
scale. The scale is so marked that direct readings can
be obtained. The scale is marked for testing at 5 meters
and 1 meter.
Maddox Wing
It is an important instrument for the assessment of
heterophoria for the near work. The instrument is
simple but not as accurate as with rapid alteration, a
semblance of alignment can be given in spite of its
absence. Heterophoria may produce defects of
binocular function like suppression which can be
found by synoptophore, Bagolini’s striated glasses and
Worth’s four-dot test.
MANAGEMENT
Before treating phoria, refraction under cycloplegic is
essential and patient must be made to use glasses.
Symptoms might be due to refractive error and it may
disappear. Heterophoria is only treated if it is
producing symptoms.
Orthoptics
Many a time exophoria is associated with convergence
insufficiently. These are the best cases for orthoptic
treatment (convergence and range of convergence).
Atleast some degrees of binocular function should be
present for the result with orthoptics to be good, other-
wise it may harm the patient. Vertical phorias need
surgical management.
Surgery
Those cases which do not get relief with orthoptics in
reasonable time and the patients with no binocular
functions but with large degree of deviations need
surgery. Similarly the patients developing secondary
convergence insufficiency during the course of
orthoptic treatment need surgery. Bimedial resection
should be attempted in exophoria with convergence
insufficiency. Other principles of surgery should be
adhered to as in cases of horizontal tropia.
Prisms
If orthoptics fail and surgery is not possible because
of patient’s refusal or general condition is not good,
prisms can be prescribed. The following two types of
prisms can be given:
Relieving Prisms
Relieving prisms are prescribed in a way that base of
the prism is opposite to the direction of deviation, e.g.
base in in exodeviations and base-out in esodeviations.
Prisms should be divided between the two eyes.
However, the disadvantage of using prism is that the
amount of prism keeps on increasing as the time passes
(eating of prisms).
Exercising Prisms
These are given for exercises. Prisms are prescribed
in the opposite direction of the relieving prisms (Base-
out in exo).
Postoperative orthoptics may be tried to achieve
binocular functions in suitable cases in the form of anti-
suppression exercises (on chieroscope or synopto-
phore) and convergence exercises in exophoria. Home
exercises can be given for longer periods.
 Chapter 114

Esodeviations
Sabi Pandey

Esodeviations are caused by innervational or mecha- Table 114.1: Classification of esodeviations1

nical factors or a combination of both. An esodeviation
I. Comitant esodeviation
may be controlled by fusional divergence (esophoria) A. Accommodative
intermittently controlled (intermittent esotropia) or 1. Refractive (normal AC/A ratio)
manifest (esotropia). Other variable characters of 2. Nonrefractive (high AC/A ratio)
esodeviation other than the etiology include their 3. Partially accommodative
state of comitance, the presence of sensorial B. Nonaccommodative
adaptations, the age of the patient at the onset of the 1. Infantile
2. Acquired
deviation, the mode of onset, the size of the angle of
a. Basic
strabismus, and the state of fixation (unilateral or b. Nonaccommodative convergence excess
alternating). c. Esotropia in myopia
Thus esodeviations are difficult to classify and are d.Acute esotropia
never very accurately classified; however, a simple e. Divergence insufficiency
classification is made in Table 114.1. f. Cyclic esotropia
C. Microtropia
ACCOMMODATIVE ESOTROPIA D. Nystagmus blockage syndrome
II. Incomitant esodeviation
Refractive Accommodative Esotropia A. Paralytic
(Normal AC/A Ratio) B. Nonpralytic or nonparetic
1. A and V pattern esotropia
Clinical Characters
2. Retraction syndrome
Generally the onset of accommodative esotropia 3. Mechanical restrictive esodeviation
whether refractive or nonrefractive is common in a. Congenital fibrosis
b. Acquired restrictive, e.g. trauma excessive
children of 2 to 3 years of age, but occasionally the
surgery
onset may be delayed up to adolescence or adulthood
or may appear as early as during infancy, because it III.Secondary esodeviation
has been shown that accommodation may reach adult A. Sensory
B. Consecutive
level by four months of age.2,3
The ocular deviation in these patients is variable common. These asthenopic symptoms may be in the
being more for near than far distance. The variability form of occasional diplopia or closing of one eye on
of the angle depends upon the general state of the near work.
patient, (i.e. alert of fatigue) and the amount of The deviation is usually moderate in amount
accommodation exerted at a given moment. The ranging about 25-30 PD and these patients are usually
evolution of accommodative esotropia is gradual and high hypermetropes ranging between +3.00 to +10.00
the patients pass through a stage of intermittent diopters, about +5.00 diopters on an average.
strabismus; therefore asthenopic symptoms are The mechanism is that it has two etiological
890 Section 7: Pediatric Ophthalmology Including Strabismus

components, i.e (1) uncorrected hypermetropia,

(2) insufficient fusional divergence. An uncorrected
hypermetropia forces the patient to exert excessive
accommodation in order to have a clear the retinal
image, thus evoking excessive convergence. This itself
does not cause strabismus if the amplitudes of fusional
divergence is sufficient to cope with the increased
convergence tonus in which case the deviation would
remain esophoria. When motor fusion is inadequate,
however, the eosdeviation becomes manifest.

Treatment
Full correction of the hypermetropic refractive error
as determined by cycloplegic refraction is all that is
required in these patients. Patients who have near
worn glasses may require a brief period of atro-
pinization to relax the accommodation before the
glasses are tolerated. The cycloplegic refraction
should be repeated annually and glasses adjusted;
surgery or miotics are contraindicated in lieu of
glasses. The glasses produce a sharp retinal image
and assist in producing a proper balance between
accommodation and convergence.

Prognosis
The prognosis for restoration of normal binocular
function in refractive accommodative esotropia
usually is excellent when normal binocular functions
have existed before the onset of the deviation. But
when this type of esotropia is of early onset bifoveal
fusion does not develop (monofixational syndrome
of Parks).4
Nonrefractive Accommodative
Esotropia (High AC/A ratio)
Clinical Characters
This variety of esotropia is characterized by deviation
which is more for near than for distance (Figs 114.1A
to D). It may be present in patients with moderate
degree of hypermetropia, emmetropia or even
myopia; but hypermetropia is more common aver-
aging about +2.00 diopters.
Although esodeviation develops in early child-
hood, it may also manifest in adulthood and these
patients have an abnormally high AC/A ratio. The
diagnosis is based on the presence of a significant
esodeviation at near fixation on an accommodation
target with refractive error fully corrected. The
Figs 114.1A to D: Nonrefractive accommodative esotropia. (A)
Fixing at distance—low convergence. (B) With bifocal glasses
fixing at distance with upper segment eyes straight. (C) With
upper segment fixing at near—low convergence. (D) With bifocal
segment fixing at near eyes straight
reason for this is that children with accommodative
esotropia may manage to keep their eyes aligned at
near fixation by accommodating only partially or none
at all. The use of fixation target that requires full
accommodation to identify small details will eliminate
this frequent cause of diagnostic errors. There would
be a less esodeviation at near fixation with a +3.00
spherical lens.
Confusion may arise when diagnosing esotropia
with high AC/A ratio and an esotropia with a ‘V’
pattern if the angle of strabismus is measured at
distance fixation with eyes in primary position and
with the gaze lowered at near fixation. In esotropia
with a ‘V’ pattern the deviation increases charac-
 Chapter 114: Esodeviations
teristically only on downgaze regardless of whether
the patient fixates at near or distance. With an
accommodative esotropia the deviation will increase
at near fixation regardless of the position of the eyes
at which the strabismus is measured.
Hypoaccommodative Esotropia5
It is defined as an esotropia greater at near than at
distance fixation, unrelated to an uncorrected hyper-
metropic refractive error and caused by excessive
convergence from an increased accommodative effort
to overcome a primary or secondary weakness of
accommodation.
Clinical Characters
It was Costenbader in 1958 who first drew attention
toward this form of esotropia. It is characterized by
a small refractive error, a remote near point of
accommodation, a small deviation at distance
fixation, but a large esotropia at near fixation. He
stated that routine testing of the near point of
accommodation in strabismic patients revealed a
surprisingly large number in whom the near point
was recessed further that one would expect from the
patients age. These patients must exert an excessive
accommodation to clear their vision at near and in so
doing, exhibit excessive and undesirable convergence.
Clearly, this form of esotropia is accommodative, even
though its mechanism differs from refractive and
nonrefractive accommodative esotropia.
Mechanism It is not related to the underlying
refractive error. It is linked with an abnormal
synkinesis between accommodation and
accommodative convergence. The effort to
accommodate elicits an abnormally high
accommodative convergence response.
Treatment
Since the near deviation is the primary obstacle to
normal binocular vision in these patients of non-
refractive accommodative esotropia, they may be
placed on bifocals or miotics. Contraindications for
treatment with bifocals are the presence of amblyopia
and the reduction but not complete elimination of
esotropia at near fixation.
We determine the power of the bifocals by adding
plus lenses on the distance correction of the patient,
beginning with +1.00 D sph and increasing the power
891
in +05.0 D sph stepwise to a maximum of +3.00 D sph
and then measuring the angle each time a stronger
lens is added. In most of the patients with high AC/
A ratio a stepwise decrease in the angle of near
fixation is noted as the lens power is increased until
a point is reached at which the esotropia becomes
sufficiently small to be overcome by fusional
divergence. Only the minimal power which converts
an esotropia to esophoria is prescribed because of
the following: (1) Excessive relaxation is prevented,
(2) Some of the burden of keeping the eyes straight
is put on the patient which is the goal of all forms of
nonsurgical treatments.
The success of bifocal therapy depends largely on
the proper bifocal segment. A straight-top bifocal
segment cutting through the midpupillary plane when
the child looks straight-ahead is ideal bifocal and may
cause fusional amplitudes to develop spontaneously
in many patients after which the power of the bifocals
may be reduced stepwise and eventually disconti-
nued. We attempt to wean the patient from the bifocal
segment by 10 years of age. If a patient still depends
on bifocal to maintain fusion during the early teens
or if fusional control of the near deviation is no longer
possible, surgery is indicated,6 i.e. recession of both
medial rectus muscles. During the course of bifocal
treatment, cycloplegic refraction should be repeated
at least twice a year and the distance and near
correction adjusted if the refractive error has
changed.
Miotic topical drops such as echothiophate iodide
(phospholine iodide) have been shown to correct or
improve hypermetropic accommodative esotropia
and high AC/A ratio esotropia. Phospholine iodide
inactivates cholinesterase and is a parasympa-
themimetic. When given topically, it affects the iris
sphincter and ciliary muscles, causing miosis and
pharmacologic accommodation and has no effect on
extraocular muscles. Because miotics are anti-
cholinesterase, acetylcholine emitted at the ciliary
body lasts longer and produces more accommodation
for a given amount of innervational stimulation. Thus
a small amount of accommodative effort results in a
large amount of accommodation. By reducing the
amount of accommodative effort necessary to provide
a clear retinal image, miotics also reduce the amount
of associated convergence. Miotics7 therefore truly
reduce the AC/A ratio and over convergence
associated with hypermetropic accommodative
esotropia and high AC/A ratio esotropia.
892 Section 7: Pediatric Ophthalmology Including Strabismus
When using miotics, it is preferable to start with
a low dose of phospholine iodide (0.03%) one drop
every morning. If this dose is not sufficient to correct
the esotropia it may be increased 0.124 percent
phospholine iodide twice daily.
Adverse effects of miotics8 Phospholine iodide given
topically does have a systemic effect also as it lowers
the cholinesterase activity in the blood several weeks
later. This is significant in those who will undergo
surgery under general anesthesia with succinyl-
choline, because the effect of succinylcholine will be
prolonged resulting in prolonged respiratory para-
lysis. Succinylcholine should be avoided if phospho-
line iodide has been used 6 weeks prior to surgery.
Systemic side effects of miotics may include brow
aches, headaches, nausea, and abdominal cramps.
Ocular side effects include iris cysts along the
pupillary margin in 20-50 percent of cases which can
occur anytime between several weeks to several
months after treatment. Iris cysts tend to regress after
the topical drug has been withdrawn, but in some
cases may persist for several years. Phenylephrine
along with phospholine iodide may prevent iris cysts.
Other rare and unusual complications include lens
opacities, retinal detachment in adults, and angle
closure glaucoma.
Partial Accommodative Esotropia
An esotropia is partially accommodative when
accommodative factors contribute to but do not
account for the entire deviation.
Clinical Characteristics
Esodeviation of refractive or nonrefractive accommo-
dative etiology does not always occur in their ‘pure’
forms. A residual esotropia may exist despite full
correction of a hypermetropic refractive error or
prescription of bifocals or miotics, or both. As a
matter of fact the majority of patients with exotropia
have a mixed type, that is partially accommodative
and partially nonaccommodative. This is especially
so in infantile esotropia.
At times in a child with infantile esotropia an
accommodative element becomes superimposed on
the deviation as the child grows older; often accom-
panied by a large hypermetropia than was first
measured. Indeed, it may be the rule that the
nonaccommodative element occurred early in infancy
whereas the accommodative component is a later
acquisition. The presence of nonaccommodative
element should always raise the question that the
basic refractive error is not fully corrected, cycloplegic
refraction should be done to rule out this possibility.
In most instances, the deviation is probably
congenital with an accommodative element becoming
superimposed as the child grows older, but in other
cases a nonaccommodative element develops after
initial alignment of the eyes with glasses or bifocals.
We can only postulate that increased convergence
tonus or mechanical factors such as secondary
contracture of the medial rectus muscles, conjunctiva
or Tenon’s capsule may play a role.
Treatment
Amblyopia should be corrected by occlusion and a
fully hypermetropic correction should be prescribed.
When undertaking surgery only the nonaccommo-
dative component of the deviation should be treated
surgically.
Standard surgery It is based on the deviation measured
when the patient is wearing full hypermetropic
correction. The target angle is usually an average of
the near and distance deviation with correction.
Standard surgery results in a relatively high
undercorrection rate.
Augmented surgical formula There are various
formulae to augment the amount of surgery in order
to reduce the high number of cases of undercorrection
associated with standard surgery. The target angle
can be determined in a number of ways. Wright9
suggests the target angle between the near deviation
with correction and near deviation without
correction. The near deviation is used because it is
the largest angle and this is most affected by bimedial
recession. Operation for an angle larger than the angle
with near correction helps reduce the number of
undercorrection. If a slight over correction occurs,
one can reduce the hypermetropic correction to
stimulate accommodative convergence to correct the
consecutive exodeviation. Using this augmented
surgery formula; one would operate for 40 PD if the
angle measured 50 PD at near without correction and
30 PD at near with correction.
Prism adaptation10 Another method for augmenting
surgery in patients with partially accommodative
 Chapter 114: Esodeviations
esotropia is prism adaptation. Prism adaptation
consists of prescribing press-on base-out prisms for
residual esotropia after prescribing full hypermetropic
spectacle correction. The patient returns back in two
weeks for a follow-up if the esotropia has increased
the prisms are increased. This continues at 1-2 weeks
interval until the deviation has stabilized. The surgeon
operates on the full prism adapted angle as deter-
mined by the press on prisms. Operating on the larger
adapted angle reduces the under correction rate.
Results of a multicenter study on prism adaptation
showed that standard surgery resulted in approxi-
mately 75 percent successful correction and operating
on the prism adapted angle resulted in 85 percent
success rate.
ESSENTIAL INFANTILE ESOTROPIA
It is defined as a manifest esodeviation with an onset
between birth and 6 months of age. In these cases
the etiology is obscure 11 and it should be
differentiated from other forms of esodevition with
an onset at about that time. It occurs usually as an
isolated problem in an otherwise healthy child;
however, it can be associated with systemic diseases
such as Down syndrome, albinism, and cerebral
palsy. The differential diagnosis of esotropia
occurring in infancy includes Mobius syndrome,
congenital fibrosis syndrome, Duane’s retraction
syndrome, and sixth nerve palsy. One type of
esotropia, easily confused with congenital esotropia,
is infantile accommodative esotropia. These two
entities may be difficult to separate as many infants
with classical congenital esotropia are significantly
hypermetropic (average +2.50 D) and accommodative
esotropia can occur under six months of age. A
combined mechanism is probably the most common
form.
Normal neonatal alignment12 It is well-known that
newborn usually do not have straight-eyes. Approxi-
mately 30 percent of normal neonates have straight-
eyes, approximately 69 percent have an exotropia or
a variable angle strabismus and less than 1 percent
have esotropia and the esodeviation usually resolves
by 2 months of age. Therefore, any ocular deviation
persisting beyond 3 months of age requires an
ophthalmic check-up.
Clinical Features
Parents of children with infantile esotropia13 usually
893
state that the esotropia has been present since birth,
but in most cases it is impossible to know the time of
true onset. In most cases the esotropia is acquired in
the first few months of life, with the angle of deviation
gradually increasing over time. Infantile esotropia is
often a large esodeviation which is constant and
measures between 30 to 70 PD. The deviation is
usually stable and there is no significant difference
in the angle over near and distance deviation, thus
denoting a normal AC/A ratio.
There is a small subset of infants who develop a
relatively small variable esotropia with minimal
hypermetropia. These are difficult to manage because
of variable angle of deviation and poor compliance
with low powered hypermetropic spectacles in this
young age group. The size of the deviation is
unrelated to the size and type of the refractive error.
Patients with infantile esotropia show some limitation
of abduction. In these cases, it is important to verify
the abduction deficit by vestibular stimulation with
the doll’s head maneuver or spinning the infant. Vesti-
bular stimulation is best performed in infants by
gently spinning of child. Spinning a child stimulates
a vestibular movement to the opposite direction of
the spin, and a refixation saccade in the same direction
as the spin. In infants the vestibular reflex may be
immature and the infant will show a tonic deviation
in the direction of the spin. Many children who show
an abduction deficit to voluntary abduction have full
abduction by vestibular stimulation. If the abduction
deficit persists, assess lateral rectus function by
examining the abduction saccade. If there is brisk
abduction saccade, then the lateral rectus is func-
tioning and the limited abduction is restrictive,
probably secondary to tight medial rectus muscle. A
slow or absent abduction saccade indicates a weak
lateral rectus, possibly caused by a 6th cranial nerve
palsy or a Duane’s syndrome.
Amblyopia occurs in approximately 40-50 percent
of children with infantile esotropia. Anisometropia
is the second most common cause of amblyopia 13 It
is generally agreed that amblyopia, unless treated
and cured early in life, is a severe obstacle to the
return of normal binocular functions. Patients may
alternate fixation or show fixation preference for one
eye. Strong fixation preference for one eye indicates
significant amblyopia and should be treated by
patching the preferred eye before strabismus surgery.
Some patients with limited adduction adopt a face
turn with the fixing eye in adduction. These patients
894 Section 7: Pediatric Ophthalmology Including Strabismus
show cross-fixation and fixate with the right eye for
objects in the left visual field and fixate with the left
eye for objects in the right visual field. Cross-fixation
was once seen as a sign of equal vision but it has
been reported that cross-fixators can have mild
amblyopia.14 Patients truly have equal vision if they
can hold fixation with either eye through smooth
pursuit, without refixating to the fellow eye. In some
patients the anomalous head posture is associated
with latent or manifest latent nystagmus and the
patient turns the head toward the side of the fixating
eye which gains optimal visual acuity in a position of
adduction.
Other motor anomalies associated with infantile
esotropia include inferior oblique overaction in about
70 percent of cases and dissociated vertical deviation
in 78 percent of cases and a latent nystagmus in
approximately 50 percent of cases. These three
associated findings may occur individually or in any
combination. Another associated finding which has
more recently been described is persistent smooth
pursuit asymmetry.15 Monocular nasal to temporal
smooth pursuit is inaccurate and lags behind the
fixation target in normal infants under 3 months of
age, while temporal to nasal pursuit is better and
more accurate. This asymmetry of monocular eye
movement normally disappears by approximately 6
months of age. Patients who have disruption of
binocular visual development as in cases of infantile
esotropia, amblyopia or unilateral cataracts retain
smooth pursuit asymmetry throughout life.
Treatment
The treatment of infantile esotropia is usually surgical.
Occasionally infants with small angle esotropia
(under 30 PD) may be corrected by hypermetropic
spectacle alone and glasses should be tried in all these
cases if hypermetropia of +2.00 D or more is present.
In patients with large angle esotropia (40 PD or more)
hypermetropic spectacle correction usually does not
straighten the eyes. However, the glasses are given
if the refractive error is greater than +3.00 D. In these
cases, glasses should be tried and if a residual
strabismus persists, surgery should be performed for
an angle of deviation between the deviation with and
without spectacle correction.
It is important to fully treat amblyopia before
performing surgery with the end point of patching
being “holds fixation well” with either eye by fixation
preference testing.16 If amblyopia is ignored before
surgery, the chances of obtaining binocular vision are
poor. The only situation when surgery is indicated
before amblyopia therapy is in case of tight medial
rectus muscle which causes the eye to be buried at
the medial canthus even when the good eye is
patched. This blocks the vision of the amblyopic eye
and makes amblyopia therapy impossible. This
unusual problem is termed as strabismus fixus and is
most frequently associated with congenital fibrosis
syndrome or rarely Ciancia syndrome.
The standard surgical approach for cases of
infantile esotropia is bilateral medial rectus reces-
sion.17 If the near deviation is larger than the distance
deviation, then the amount of surgery is usually based
on the near deviation as bilateral medial rectus
recession has a more effect on near deviation. We
should always aim at a slight overcorrection in cases
with fusion potentials. Producing an initial exode-
viation allows the infant with fusion potentials to use
fusional convergence to align the eyes.18 On the other
hand, a small residual esotropia cannot be fused
because of weak fusional divergence. Exotropia is
present in about of 70 percent of normal newborns
and those infants normally converge this exodeviation
to align their eyes during the first 6 months of life.
Older patients with irreversible amblyopia should
have surgery restricted to their amblyopic eye by a
recess/resect procedure.
Timing of Surgery and Treatment Goal
The goal of surgery for infantile esotropia has been
to establish the monofixational syndrome by
correcting the esotropia to within 8-10 PD of
orthophoria between 6 months and 2 years of age. A
recent study 19 has shown that over 80 percent of
patients of infantile esotropia showed peripheral
fusion and monofixation if the eyes were straightened
to within 8 PD by 2 years of age. Patients aligned
after 2 years of age had less than 20 percent chances
for peripheral fusion.
Despite the theoretical advantages of mono-
fixation,20 the overall success rate with infantile eso-
tropia is generally poor with most patients requiring
more than one surgery if follow-up is greater than
5 years. Long-term motor and sensory stability is also
lacking in these patients even if initial alignment is
within 8-10 PD of orthophoria and even if peripheral
fusion is obtained. In addition most of these patients
with infantile esotropia also develop motor sequelae
such as dissociated vertical deviations, inferior
 Chapter 114: Esodeviations
oblique overaction, latent nystagmus and smooth
pursuit asymmetry whether or not they achieve
monofixation. Surgery is advocated when the
following criteria are met:
1. Demonstration of a stable and sufficiently large
deviation.
2. Absence of an accommodative factor.
3. Alternating fixation pattern after treatment of
amblyopia.
4. Identification of the nature of the associated motor
anomalies.
Very early surgery Experimental studies21 have shown
that even 2-3 weeks of prism induced esotropia in
infant monkey will cause permanent loss of binocular
cells and fusion. Therefore, the basic science research
by Crawford and von Noorden suggests that the
classical approach to waiting until the child is over 6
months of age to operate, by itself may preclude
normal bifoveal fusion in children who truly have
the onset of esotropia at or shortly after birth.22
Chemodenervation Botulinum toxin injection22 into the
medial rectus has been mentioned as an alternative
to surgery. The theoretical advantage would be to
create an incomitant deviation so the patient could
adopt a face turn and obtain fusion. This is a good
theoretical strategy; however, there are some
problems involved with the use of botulinum toxin
including secondary ptosis and the temporary effect
of the botulinum injection. The treatment of choice
in cases of infantile esotropia still remains surgery;
however, investigations continue regarding the use
of botulinum toxin.
ACQUIRED NONACCOMMODATIVE ESOTROPIA
This variety includes all forms of nonaccommodative
esodeviation with onset after 6 months of age. The
onset is insidious and the esotropia may evolve after
a period of intermittency. Since normal binocular
functions have existed before the onset of the disease,
therefore in these patients the prognosis for norma-
lization of binocular functions is better than in those
with infantile esotropia, provided treatment is started
without delay.
Basic Esotropia
In this group those cases are included who developed
esotropia with onset after 6 months of age, but usually
limited to childhood. Characteristically an accommo-
dative factor is absent, the refractive error is insignifi-
895
cant and the near deviation approximately equals to
the distance deviation. At the onset the deviation is
smaller than in patients with infantile esotropia but
the angle then gradually tends to increase. It is
debatable whether this increase reflects the patients
effort to avoid diplopia or is indicative of secondary
anatomic changes in the medial rectus muscle. But
since the eyes diverge out under general anesthesia
and the forced duction tests are negative, it is
therefore mainly an innervational anomaly rather than
a mechanical restriction. Because parents usually
associated onset of deviation with some exogenous
factor like injury, illness or emotional upset in a
child,24 Costenbader postulated that such patients
have an excessive convergence tonus that is controlled
initially by fusional divergence but is disrupted easily
y these exogenous factors. Therapy consists of
elimination of amblyopia followed by surgical
correction. A slight surgical overcorrection should
always be aimed at as it results in a higher incidence
of fusion postoperatively.25
Nonaccommodative Convergence Excess
Clinical Characteristics
In addition to accommodative convergence excess
caused by high AC/A ratio, another clinically similar
but etiological different form of esotropia exists,
which occurs mainly in patients who are
hypermetropic or emmetropic as in the case of
accommodative esotropia. The onset is early in life,
occurring between 2 and 3 years of age. Such patients
at distance are orthophoric or have a small angle
esotropia and a large esotropia at near fixation in
contradistinction to esotropia with a high AC/A
ratio; however, relaxation of accommodation by
bifocal or its facilitation by miotics have little, if any,
effect on the near deviation. The AC/A ratio when
measured by the gradient method, may be normal
or abnormally low. The condition differs from the
hypoaccommodative esotropia of Costenbader in
such that the near point of accommodation is within
the normal range. Thus excessive convergence in
these patients must be on the basis other than
accommodation, perhaps from tonic innervation.
Clearly, an abnormal distance-near relationship
in the angle of esotropia is not always caused, as has
been assumed by a high AC/A ratio. Therefore
determining the AC/A ratio by comparison of
distance-near relationship (heterophoria method) is
896 Section 7: Pediatric Ophthalmology Including Strabismus
likely to miss the diagnosis of nonaccommodative
convergence excess.
Treatment
Since bifocals or miotics are ineffective in controlling
the deviation at near, surgery must be considered
for the nonaccommodative component of the
anomaly. The surgical management is rather
controversial; some recommend a bilateral medial
rectus recession alone or in combination with
posterior fixation sutures, 26 but this has been
surprisingly ineffective in controlling the near
deviation in the long run. An unconventionally large
recession of both the medial rectus muscles (5-8 mm)
is under consideration.
Microtropia
Ultra small angles of strabismus may escape diagnosis
by ordinary methods of examination and frequently
are overlooked. The cover test may be negative or
the fixation movement of the deviated eye may be
absent or so small that it defies detection by the
examiner when the sound eye is covered. Since
amblyopia is a regular feature of microtropia such
patients are often subjected to be extensive occlusion
therapy or neurological examination to establish the
cause of reduced visual acuity in one eye.
Diagnosis
Since the cover test is negative and the fixation
movement of the deviated eye is so small it may
escape the examiner’s eye. In all other cases the
diagnosis is clearly established by a very small
fixation movement (flick) of the deviated eye upon
covering the fixating eye. When the cover test is
negative, however, special diagnostic procedures
must be used to differentiate a microtropia from other
nonstrabismic conditions causing decreased visual
acuity in one eye. A cycloplegic refraction should be
carried out in such cases because microtropia is
frequently associated with anisometropic amblyopia.
Examination of the fixation pattern will tell us about
whether foveolar or parafoveolar fixation is present.
The finding of nonfoveolar fixation in an amblyopic
eye establishes the diagnosis of microtropia.
Identification of microtropia is more difficult in
isometropic patients and in those with minute degree
of fixation anomalies, for the mere presence of
fixation spot scotoma diagnosed with Bagolini lenses,
polarized visual acuity charts or the 4-prism base-
out or base-in prism cover test, does not establish
that the underlying cause is functional as in
microtoropia or organic. Also stereoacuity is reduced
not only with functional amblyopia but also when
foveal function is reduced by organic lesions. The
finding of a minute angle of anomalous retinal
correspondence clearly identifies the patient as having
microtropia, even when the results of the cover test
are negative or the amplitude of the fixation
movement of the amblyopic eye is too small to be
detected when the sound eye is covered.
A microtropia should always be suspected in
unilateral decrease of visual acuity for which no
organic cause can be found in patients without stra-
bismus or history of such and without significant
refractive errors or anisometropia.
Treatment
Microtropia in older children or adults does not
require any treatment; if treated for the elimination
of central scotoma they may develop intractable
diplopia. Such patients have nearly normal binocular
vision with good peripheral fusion amplitudes. In
young children up to is controlled initially by fusional
divergence but is disrupted easily by these exogenous
6 years of age, attempt should be made to treat
amblyopia. If significant anisometropia is present then
we occlude the fixating eye and give full refractive
correction. At times in some of these patients the
fixation of amblyopic eye changes from parafoveal
to central and steady fixation, and visual acuity
improves to 6/6, retinal correspondence becomes
normal, and stereoacuity improves from 100 to 40
seconds of arc.
REFERENCES
1. Noorden von GK. Binocular Vision and Ocular Molitily (5th
edn), 1996.
2. Archer SM, Sondhi N, Helveston GM. Strabismus in infancy
Ophthalmology. 1989;96:133.
3. Baker JD, Parks MM. Early onset accommodation esotropic.
Am J Ophthalamol 1980;90:11.
4. Park MM. The monofixational syndrome. Trans Am
Ophthalmol Soc 1969;67:609.
5. Muhlendyck H-Personal Communications.
6. Ludwiz IH, Parks MM, Getson PR. Long-term results of bifocal
therapy for accommodative esotropia. J Pediatric Ophthalmol
and Strabismus 1989;26:264.
7. Abraham S. Present status of miotic therapy in nonparalytic
 Chapter 114: Esodeviations
convergent strabismus. Am J Ophthalmol 1961;51:1249.
8. Wright KW. Pediatric Ophthal and Strabismus, (2nd edn),
1995.
9. Wright KW, Bruce Lyle L. Augmented surgery for esotropia
associated with high hypermetropia. J Pediatric Ophthal and
Strabismus 1993;30:167.
10. Prism Adaptation Study Group. Efficacy of Prism adaptation
in the surgical management of acquired esotropia. Arch
Ophthalmol 1990;108:1248.
11. Helveston EM. The 19th Annual Frank Costenbader Lecture:
The origins of congenital esotropia. J Pediatric Ophth and
Strabismus 1993;30:215.
12. Sondhi N, Archer SM, Helveston EM. Development of normal
ocular alignment. J Pediatric Ophthal and Strabismus 1988;
25: 210.
13. Beck RW. Pediatric Eye Diseases Investigation group. Arch
Ophthalmol 2002;120,281.
14. Dickey CF, Hetyz Hs, Stewart SA. The diagnosis of amblyopia
in cross-fixation. J Pediatric Ophthal and Strabismus 1991;
28:171.
15. Demur JL, Noorden GK von. Optokinetic asymmetry in
esotropia. J Pediatric Ophthalmol and Strabismus 1988;25:286.
16. Wright KW, Edelman PM, Walonker E. Reliability of fixation
preference testing in diagnosing amblyopia. Arch Ophthalmol
1986;104:549.
17. Kushner BJ, Morton GV. A randomized comparison of surgical
procedure for infantile esotropia. Am J Ophthalmol 1984;98:50.
897
18. Wright KW, Edelman PM, Jurry. A high grade stereoacuity
after early surgery for congenital esotropia. Arch Ophthalmol
1994;112:913.
19. Archer SM, Helveston EM, Miller KK, et al. Stereopsis in normal
infants and infants with congenital esotropia. Am J Ophthalmol
1986;101:591.
20. Helveston EM, Eills FD, Plager DA, et al. Early surgery for
essential infantile esotropia. J Pediatric Ophthalmol and
Strabismus 1990;27:115.
21. Ing MR. Early surgical alignment for congenital esotropia. Trans
Am Ophthalmo Soc 1981;79:625.
22. Arthur BW, Smith JT, and Scott WG. Long-term stability of
alignment in the monofixation syndrome. J Pediatric
Ophthalmology and Strabismus 1989;26:224.
23. Magoon EH, Scott AB. Botilinum toxin chemotherapy in infants
and children an alternative to excisional strabismus Surgery. J
Pediatric and Strabismus 1987;110:119.
24. Clark AC, Nelson LB, Simon JW, et al. Acute acquired constant
esotropia. Br J Ophthalmol 1989;73:636.
25. Dankner Sr, Mash AJ, Jampolsky A. International surgical
overcorrection of acquired esotropia. Arch Ophthalmol
1978;96:1848.
26. Leitch RJ, Burke JP, Strachan IM. Convergence excess esotropia
treated surgically with faden operation and medial rectus
muscle recession. Br J Ophthalmol 1990;79:278.
 Chapter 115

Exodeviation
Kamlesh, S Dadeya

INTRODUCTION Intermittent exotropia It is an exodeviation which is

intermittently-controlled by the fusion mechanisms to
An old dictum says, “Strength lies in unity.” This is
keep the eye properly aligned.
also applicable to eyes. A perfect alignment of both
eyes is mandatory for proper binocular vision, if one Exotropia It is a manifest exodeviation which is not
eye deviates from the other, then strabismus results controlled by the fusion mechanisms so that the eyes
and if the eye deviates outward, it is called exotropia. are never properly aligned.
Strabismus results not only in mechanical misalign-
ment, but also in physiological changes such as ETIOLOGY
suppression, defects of visual acuity, fusion, stereo-
Exodeviations are caused by mechanical and innerva-
scopic vision and convergence. Exodeviations are
tional factors and the most important factor being
much more common in the intermittent form. A
altered equilibrium between convergence and
patient may exhibit a manifest exotropia during one
divergence. Refractive status of the eyes also plays
examination, and at another time an exophoria or
some role in the pathogenesis of exodeviation, e.g. in
intermittent exotropia may be present. Indeed it is
uncorrected myopia. There is understimulation of
common to observe rapid switching from one phase
convergence, which may cause an exodeviation.
to the other during the same examination. For this
Similarly, if very high degree of hypermetropia
reason, it is often impossible to distinguish clearly
remains uncorrected, such patients make no effort to
between exophoria and exotropia or from a clinical
accommodate and exodeviation may develop because
point of view, to consider them as different entities.
of understimulation of convergence.
Therefore exophoria, intermittent exotropia, and
exotropia will be discussed together, but efforts will
be made to point out distinguishing features among CLASSIFICATION
these conditions. The extent to which an exodeviation
Duane has classified exodeviation into following
is controlled by fusion depends not only on the size
types:
of the angle of deviation, but also to a large extent, on
the general health, alertness, attention span, and level Basic exodeviations Distance deviation and near
of anxiety of patient. deviation are equal.
DEFINITION Divergence excess The exodeviation is 15 PD greater
An exodeviation is a latent or manifest divergence of at distance than at near fixation.
visual axes. Variations in fusion capabilities give rise
to three commonly recognized forms of exodeviation. Convergence insufficiency Near deviation is 15 PD grea-
ter than distance deviation.
Exophoria It is a latent exodeviation which is
controlled by the fusion mechanisms so that under Simulated divergence excess Actually it is a basic type
normal binocular vision the eyes remain properly of deviation, but static deviation at near fixation is
aligned. obscured by factors such as persistent convergence.
 Chapter 115: Exodeviation
Prism bar cover test will show that it is divergence
excess type of deviation, but after occlusion test near
and distance deviations are equal.
PREVALENCE
Exodeviations occur more frequently than esodevia-
tions in India. The ratio between exodeviation and
esodeviation is 3:1 in India and in western world it
is 1:3.
Age of Onset and Natural History
Majority of exodeviations develop before the age of 3
years. In a series of 400 patients with intermittent
divergent squint, deviation was present within 2 years
of age in 350 patients and only in 10 patients exotropia
developed after the age of 5 years. Although it is not
always possible to ascertain by history; whether
constant exotropia was present at birth or occurred
shortly after birth but most of the patients present
initially with exophoria that deteriorate later into
intermittent or constant exotropia (Table 115.1).
Presbyopia, tonic convergence, development of
suppression, and increased divergence of orbits in
children with advancing age are the factors which
influence progression of exophoria.
Sex distribution Exodeviation are more common in
females. In the above series, ratio of M:F was 1:2.
Refractive error Exodeviations are equally seen in
myopia and hypermetropic patients, although uncor-
rected myopia and high uncorrected hypermetropia
by understimulation of convergence may play some
role in pathogenesis of exodeviation.
Sign and symptoms Eye strain, blurring of vision,
difficulty with prolonged reading, headache, micro-
psia, and diplopia are common symptoms in patients
Table 115.1: Natural history of exotropia
1. Exophoria at distance, orthophoria at near
2. Intermittent exotropia at distance orthophoria/
exophoria at near
3. Exotropia at distance, exotropia or intermittent
exotropia at near
4. Exotropia at distance as well as near
Note: Patient may present in any stage
899
of exodeviation. Photophobia is a symptom commonly
seen in patients of intermittent divergent squint,
reason being when child is outdoor and looking at
infinity, there are no clues to stimulate convergence
and bright light dazzles the retina so fusion is
disrupted, causing the deviation to manifest. It is also
called diplopia phobia.
OCCLUSION TEST
Aims
i. To determine maximum amount of deviation.
ii. To differentiate simulated divergence excess from
true divergence excess.
In this test we occlude, one eye of patient for
24 hours and we measure prism bar cover test (PBCT)
for near and distance after 24 hours of occlusion. In
simulated divergence excess type of exophoria, after
occlusion deviation for near and distance is equal,
while in true divergence excess type it will be more
for distance than for near. Most important precaution
that should be kept in mind is to place prism before
other eye before removing occlusion.
Treatment
Refractive error Myopia should be fully-corrected in
exodeviation. Hypermetropic refractive error should
be fully-corrected in exodeviation taking special
precaution in presbyopic patient in whom weakest
bifocal lens should be prescribed and if by this, patient
is not satisfied, base-in prism should be prescribed
for near vision.
Prisms These should be used only in overcorrected
exotropes and in preoperative period to reinforce
fusion. They can control deviation upto 15 PD devia-
tion.
Orthoptics Troutman recommends orthoptic therapy
in all types of divergent squint and Burian clearly
contradicts orthoptic therapy. In authors’ opinion
orthoptic exercises are preserved for cases of conver-
gence insufficiency and postoperative cases in which
suppression persists.
High minus lens These lenses can be used in cases of
exodeviation with high AC/A ratio, where they
decrease an exodeviation by stimulating accommo-
dative convergence.
900 Section 7: Pediatric Ophthalmology Including Strabismus

Table 115.2: Signs of progression Indications for Surgery

1. Exotropia occurs more than 50% of waking hours. 1. Manifest deviation at birth
2. Exotropia with asthenopia. 2. Presence of diplopia phobia
3. Presence of suppression
3. Presence of suppression.
4. Intermittent divergent squint with signs of pro-
4. Increase in the size of basic deviation. gression (Table 115.2).
5. Development of secondary convergence insufficiency.
Note: If surgery is indicated for functional reasons deviation Age for Surgery
should be more than 15 PD and if for cosmetic reasons
Details of surgical procedures are elaborated in
deviation should be more than 25D.
Chapter 121.
 Chapter 116

A and V Syndrome
JN Rohatgi

A simple observation that a horizontal deviation may V-pattern

increase or decrease with the eyes in upward and
V-esotropia/esophoria The convergent deviation is
downward gaze was not taken care of or attached
greater when looking directly downward than when
clinical significance in management till 1948, when
looking directly upward.
Uretts-Zavatia (quoted in Noorden’91) published his
first paper. In his paper, the author emphasized the V-exotropia/exophoria The divergent deviation is
importance of measuring the angle of deviation (in considerably greater on looking directly upward than
cases of strabismus) in the straight upward and when looking directly downward.
downward positions of gaze in addition to the usual
measurement in the primary straight-ahead position.
Three years later, in 1951 Urist1 drew attention to cases
of horizontal concomitant squint with secondary
vertical deviations. In 1957 Albert2 suggested the
excellent descriptive terms of A-pattern and V-pattern.
These deviations have also been described as A and
V phenomena or A and V syndrome. They indicate
that there is a considerable difference in the angle of
the horizontal deviations on looking upward (supra-
version) as compared to when looking downward
(infraversion).
A-pattern indicates a considerable increase in the
angle of convergence (or decrease in the angle of Fig. 116.1: A syndrome (Engene R Folk)
divergence) with upward gaze and V-pattern indicates
those cases showing a considerable increase in the
angle of convergence (or decrease in the angle of
divergence) on downward gaze (Figs 116.1 and 116.2).
A working classification of these patterns is as
follows.

A-pattern
A-esotropia (esophoria) In A-esotropia/esophoria the
convergent deviation increases in direct upward gaze
and decreases in downward gaze.
A-exotropia (exophoria) In this case the divergent devi-
ation increases in downward gaze than when looking
directly upward. Fig. 116.2: V syndrome (Engene R Folk)
902 Section 7: Pediatric Ophthalmology Including Strabismus
Besides these, there are patients who may show
no deviation or only a small deviation in the primary
straight—ahead position, but may show exotropia
both in the upward and downward gaze (X-pattern).
Again exotropia may be present only in the upward
gaze (Y-pattern) or in downward gaze (Lambda
pattern, inverted Y). They are considered as modifi-
cations of the classical A-and V-pattern (Noorden).10
A certain degree of V-deviations are considered
physiological—when we look upward (supraversion),
there is a slight relative divergence and when we look
downward (infraversion), there is a slight relative
convergence. And so it has been suggested that in
order to be labeled as cases of V-phenomena, the diffe-
rence in the angle of deviation on looking up and
down should be atleast 15 PD (prism diopter) whereas,
in cases of A-phenomena this difference should be
atleast 10 PD.
ETIOLOGY
The exact pathophysiology of cases of A-V syndrome
is conjectural. The following three groups of etiological
factors are described:
i. The horizontal school of Urist3-5 (1951-1958)
ii. Vertical school of Brown6 (1963), and
iii. Oblique school.
Brown2 was of the opinion that A-and V-patterns
may be caused by primary anomalies in the func-
tioning of vertical rectus muscles. But since overaction
and underaction of the oblique muscles are frequently
associated with A and V syndrome, it soon came to
be realized that the vertical and oblique muscles jointly
are responsible for these changes in the angle of
deviation when looking upward and downward.
Hence, it is suggested that the etiological factors could
be discussed into two groups of (i) horizontal school,
and (ii) vertical school, combining the vertical and
oblique schools in one. These are as follows:
The Horizontal School of Urist3-5 (1951-58)
Urist thought that A- and V-patterns/syndromes are
the results of abnormal action of the horizontal rectii
muscles. According to him, overaction of the lateral
rectus muscle causes an increased relative divergence
when looking upward (upward gaze) and an over-
action of the medical rectus muscle causes increased
relative convergence in downward gaze.
Similarly an underaction of the lateral rectus
muscle may cause an increased relative convergence
in upward gaze and an underaction of the medial
rectus muscle may cause an increased relative diver-
gence in downward gaze. And thus, the V-pattern
(exophoria/esotropia) is the result of an overacting
medial rectus muscle and the V-pattern exophoria
(exotropia) is the result of an overacting lateral rectus
muscle. On the other hand, an underacting lateral
rectus muscle causes A-esophoria (esotropia) and an
underacting medial rectus muscle causes A-exophoria
(exotropia).
The Vertical School
According to this, these A- and V-pattern cases result
from a symmetrical underaction of the vertically acting
muscles (Lyle).7
In V-phenomenon, it seems likely that the basic
defect is weakness of superior oblique muscle with a
consequent overaction of the inferior rectus in the
opposite eye. This takes the eye downward. As supe-
rior oblique muscle is weak its tertiary action of
abduction is decreased, the eye remains relatively
more convergent and adducted facilitating the
depression of the globe by an overacting inferior rectus
muscle. The ipsilateral inferior oblique overacts
causing as abduction of the globe on elevation in a
relatively less convergent or more divergent position
in upward gaze (inferior oblique secondary action is
elevation and tertiary action abduction). And thus, one
gets a V-phenomenon with esophoria/esotropia.
The A-pattern similarly can be explained on the
basis of a weak inferior oblique muscle with conse-
quent overaction of the superior rectus muscle in the
other eye (Contralateral synergist muscle). A weak
inferior oblique favors adduction (or less abduction,
the tertiary action of inferior oblique) and a overacting
superior rectus favors abduction and elevation. So the
eye tends to converge in adduction (A-esotropia/
esophoria). At the time, an overacting superior oblique
in the same eye (ipsilateral anatagonist muscle) causes
abduction of the eye in depression. This produces A-
extropia/exophoria.
Thus, a combination of vertical and oblique
muscles overaction and underaction can explain the
A- and V-pattern. To explain these on the basis of only
the vertical rectii muscles or only on the basis of the
oblique muscles, under and overaction is rather
puzzling or mind boggling and a pure academic
exercise.
 Chapter 116: A and V Syndrome 903
Combined Patterns A case of convergent squint showing a V-pattern
may be mistaken as a case of accommodative
These patterns are the result of combined abnor-
convergence excess type of deviation and vice versa
malities of action of the horizontal and vertically acting
for in both of these conditions in distance fixation
muscles.
(looking slightly upward) there may be binocular-
It seems likely that when these patterns are present
single vision whereas, in near fixation in the reading
to a slight degree, the cause is an abnormal action of
position looking slightly downward there may be a
the horizontal rectii and it is also possible that an
manifest convergent squint.
abnormality of both the vertical and horizontal
It is also possible that the V-pattern in divergent
muscles may be operative in certain cases. It has been
strabismus (V-exotropia) may be confused with diver-
pointed out that the A-pattern tends to occur in people
gence excess type of exotropia in which a wider diver-
with a mongoloid type of face with high cheekbones
gence of the visual axes is prone to occur in upward
and palpebral fissure with upward slope.
gaze.
The shape of the orbit in this type of anomaly of
Hence, the deviation should be measured in three
the skull may predispose to a relative underaction of
sets: (i) in primary position looking straight-ahead,
the inferior oblique with overaction of the superior
(ii) looking slightly upward –25° of upward gaze, and
oblique thus, resulting in relative divergence in
(iii) looking slightly downward –25° of downward
looking downward.
gaze.
On the other hand the V-pattern may occur in
Ocular movements have to be carefully analyzed
people with antimongoloid face, flat cheek bones and
in all the cardinal positions to detect any paresis of a
palpebral fissure with downward slope in which the
horizontal or vertical ocular muscle. For this an
shape of the orbit may predispose to a relative
examination on Hess screen may also be utilized.
underaction of the superior oblique with overaction
AV-pattern in which the difference in deviation
of the inferior oblique thus, resulting in relative
between upward and downward gaze is 15 PD or
divergence on looking upward.
more should be considered a significant vertical
incomitancy. On the other hand an A-pattern (which
Anomalies of Muscle Insertion is never found as a normal variant) a limit of 10 PD
has been set beyond which an A-pattern is thought to
Weiss (1966) attributed8 the A- and V-pattern to the
be significant. Thus, an A-exotropia with only 15 PD
action of the abnormally inserted superior and inferior
deviation in downward gaze and 5 PD in primary
rectus muscles and the upshoot and downshoot in
position may interfere with normal binocular vision
adduction to the action of the abnormally inserted
and needs treatment.
medial rectus muscle.
Chin-elevation and depression with a horizontal
The clinician is thus, in lurch about the patho-
deviation should be carefully looked for. Thus, one
genesis of the A- and V-pattern and, therefore,
with A-esotropia and V-exotropia may hold his chin
confused about surgical decision when planning
in an elevated position and conversely a child with V-
operation in these cases. Should primary surgical
esotropia and A-exotropia may show chin-depression.
procedure be performed on oblique muscles or should
horizontal muscles be operated on before the oblique
TREATMENT
muscle? His own clinical judgment is the best arbiter
in such a situation. Treatment is indicated when binocular vision is distur-
bed. This is more common in cases of A-exotropia and
CLINICAL FEATURES AND DIAGNOSIS V-esotropia, and the treatment is surgery.
It may not be indicated for the single purpose of
An increase of deviation in downward gaze (with A-
decreasing a cosmetically acceptable deviation in
exotropia and V-esotropia) may cause discomfort
upward gaze, in a patient, who is asymptomatic with
during reading or in near work. On the other hand,
his eyes in the primary straight-ahead position and in
an increase of deviation in the upward gaze (V-
the downward gaze.
exotropia) may not be evident to the patient since little
or no interference with binocular single vision would Corrective unilateral or bilateral surgical procedures These
occur in the functionally more important primary or are for horizontal squints combined with, preceded
downward position of viewing. by or followed by weakening and strengthening
904 Section 7: Pediatric Ophthalmology Including Strabismus

procedures on the oblique muscles and have proved 2. In cases of exotropia (divergent position of the eye):
effective in most patients with A and V syndrome to a. V-exotropia—it is again clinically more common.
correct the vertical incomitance. A recession of lateral rectus along with raising
its insertion, along with medial rectus resection
Transposition of horizontal and vertical rectii muscles The
and lowering its insertion.
effect of surgery on horizontal rectii can be enhanced
b. A-exotropia—it is less frequent clinically. The
or decreased in upward and downward gaze by
deviation can be corrected by lateral rectus
vertical transposition of the insertion of the horizontal
recession. This may be combined with medial
rectii muscles. This technique was described by Knapp
rectus resection and raising its insertion.
(1969).10
Thus it can be said as follows:8
Thus, when the insertion of the medial rectus is
a. When the overaction of a muscle is to be
lowered its horizontal action decreases in downward
neutralized, besides recession, move the
gaze. As for the lateral rectus, when its insertion is
insertion in the direction in which weake-
raised, the horizontal action is decreased in elevation.
ning or neutralization is required (decreased
In practice, therefore, based on theoretical consi-
action).
derations, one can proceed as follows:
b. When the underaction has to be strength-
1. In cases of exotropia, convergent position of the
ened, besides resection move the insertion
eye:7
in the direction opposite in which strength-
a. V-esotropia (clinically more commonly met
ening is required (increase in action or more
with)—a recession of the medial rectus along
effectivity), and
with lowering its insertion. This may be
c. When performing resection/recession
combined with resection of lateral rectus and
procedure on a patient who also has a small
raising its insertion.
to moderate vertical deviation, both hori-
b. A-esotropia—a recession of medial rectus along
zontal muscles may be shifted vertically.
with raising its insertion. This may be combined
This approach can treat the vertical compo-
with resection of lateral rectus and lowering its
nent or deviation without altering the effects
insertion.

Table 116.1: Summary of surgical treatments of A-V pattern9

A-esotropia: Resection Resection Resection Move LR Antero Temporal
or tucking of IO Lateral insertion Position Transplant
IO Rectus downward of SO of SR
Tenotomy
SO
A-exotropia: Resection — Resection Move MR — Medial transplant
of IR of MR insertion IR
Tenotomy upward
SO
V-esotropia: Resection Antero Recession Medial Antero Temporal
of IO or position MR Rectus position Transplant
myectomy of IO insertion of IO IR
Resection muscle down
or tucking
of SO
V-exotropia: Recession — Recession LR Move — Medial transplant
myectomy LR of SR
IO insertion
Resection upwards
of SR
Note: MR—medical rectus muscle; SO—superior oblique muscle; LR—lateral rectus muscle; IO—inferior oblique muscle
 Chapter 116: A and V Syndrome
of the procedure for the eso or exodeviation.
The muscles are moved upward, if the eye
is hypodeviated and downward if the eye
is hyperdeviation. The amount of movement
upward and downward shall not exceed one
half of muscle width.
But since, in these cases of A and V syndrome, the
oblique muscles along with the vertical rectii also play
an important role, each case has to be analyzed to
ascertain the action of horizontal, vertical, and oblique
muscles and surgery is planned accordingly.
Thus, in cases with inferior oblique overaction
along with horizontal rectii as in cases of V-exotropia
and V-exotropia, one could proceed as follows:
i. In cases of V-esotropia and overacting inferior
oblique, an inferior oblique weakening procedure
will diminish the V-pattern in upward gaze,
combined to this a weakening procedure on
the medical rectus may be all that is necessary to
bring the eye to normal parallelism (MR-
recession and downward displacement of its
insertion).
On the other hand, in cases of V-exotropia,
a weakening procedure on inferior oblique
muscle decreases the deviation in upward gaze
and this, may be sufficient to create a satisfactory
functional result. If however, there is a left over
significant amount of exodeviation in primary
and downward positions of gaze, surgery on
horizontal muscle becomes a necessity—lateral,
rectus recession and if necessary also an upward
displacement of the lateral, rectus insertion.
ii. In cases of A-esotropia with superior oblique
overaction, a weakening procedure on superior
oblique may be necessary and thereafter, to
prevent exotropia in downward gaze or in
primary position, horizontal muscle surgery has
905
to be done. Resection of the lateral rectus and
lowering of its insertion.
In cases of A-exotropia, again with superior
oblique overaction, bilateral weakening proce-
dure on superior oblique along with surgery on
horizontal muscle may be performed— resection
of MR and upward displacement of its insertion.
And hence to achieve success in these cases one
has to carefully evaluate and analyze the degree
of deviation in the primary straight-ahead
position and on looking upward and downward
before deciding whether to tackle the horizontal
muscle only or to have a two stage surgery on
the horizontal muscles and involving the vertical/
muscle also, as the case may warrant.
Stanworth9 A (1968) has very lucidly described the
possible surgical treatment about the A and V
syndromes (Table 116.1).
REFERENCES
1. Urist MJ. Recession and upward displacement of the medial
rectus in A-pattern exotropia. Am J Ophthalmol 1968;65:765.
2. Albert DG. Personal communication in PARKS-MM: Annual
review strabismus. Arch Ophthalmol 1957;58:152.
3. Urist MJ. Horizontal squint with secondary vertical deviation.
Arch Ophthalmol 1951;46:245.
4. Urist MJ. Surgical treatment of esotropia with bilateral
elevation in adduction. Arch Ophthalmol 1952;47:270.
5. Urist MJ. The etiology of the so-called A and V syndrome.
Am J Ophthalmol 1958;46:835.
6. Brown HW. Vertical deviations in symposium strabismus.
Trans Am Acad Ophthalmol Otolaryngol 1963;57:157.
7. Lyle and Jackson. Practical Orthoptics in the Treatment of
Squint (5th edn). London: HK Lewis and Co, 1967.
8. Noorden, Cunter KV. Binocular Vision and Ocular Motility
(4th edn). St. Louis: The CV Mosby Co, 1990.
9. Stanworth A. A and V syndrome. Br J Orthopt 1969;26:12.
10. Knapp P. A and V pattern. In Symposium on Strabismus
Transaction of the New Orleans Academy of Ophthalmololgy
St. Louis: The CV Mosby Co, 1971.
 Chapter 117
Management of Double
Elevator Palsy
Kamlesh, S Dadeya
Double elevator palsy (DEP), a common cause of hypo-
deviation is defined as the inability to elevate the
paretic eye from any position of gaze provided
ductions of the eye are normal in all other positions of
gaze. There is paresis of superior rectus and inferior
oblique of the same eye. This may be associated with
ptosis. When patient fixates with the paretic eye,
normal eye will be hypertropic and when patient
fixates with normal eye, the paretic eye will take a
hypotropic position. Indeed double elevator palsy is
a misnomer and the generalized weakness of elevation
is caused by superior rectus palsy of long-standing,
the deviation having spread throughout the entire
upward field of gaze and inferior rectus having
becoming contracted.
The etiology of DEP is poorly understood. The 3rd
cranial nerve divides into two portions in orbit, supe-
rior and inferior divisions. The superior division
supplies the SR and LPS, while inferior division supp-
lies the inferior rectus, inferior oblique, and MR. Thus
a supranuclear lesion is thought to be responsible for
this disorder. Nowhere else in path of 3rd cranial nerve
could a single lesion explain this condition. Rarely,
this disorder might be an acquired entity.
CLASSIFICATION
From the management point of view double elevator
palsy is divided into following 3 types:
1. Those that have inferior rectus restrictions as a pro-
minent feature. These are diagnosed by the
following:
a. Positive forced duction to elevation.
b. Normal force generations.
c. Normal saccades of superior rectus muscle.
2. Those that have elevator weakness. These are diag-
nosed by the following:
a. Free forced duction.
b. Reduced forced generation.
c. Reduction in saccadic velocities to up-gaze.
3. Combination of these cases have positive forced
duction and also weakness of the elevators of eyes.
These are diagnosed by the following:
a. Positive forced duction to elevation.
b. Reduction in force generations.
c. Reduction in saccadic velocities into elevation.
CLINICAL CHARACTERISTICS
i. Limitations of elevation in up, up and left, and
up and right both on versions and ductions.
ii. Large hypotropia in primary position.
iii. Chin up position.
iv. Combination of ptosis and pseudoptosis.
v. Inferior rectus restriction: In cases that have
inferior rectus muscle restriction there is often an
extra or deeper lower lid fold on that side. Bell’s
phenomenon is usually asymmetric. The eye
having inferior rectus restriction has a very poor
or absent Bell’s phenomenon as compared to the
eyes without the inferior rectus muscle restriction.
Treatment of DEP is surgical. Patient must have a
deviation in the straight-ahead position before surgery
is contemplated. From the point of view of manage-
ment, if inferior rectus restriction is present, recession
of involved inferior rectus is usual approach. Vertical
 Chapter 117: Management of Double Elevator Palsy
deviation of 15 PD (mean) is corrected by recession of
inferior rectus, if deviation is still uncorrected Knapp’s
procedure in 2nd stage can be carried out which
corrects 22 PD (mean) of vertical deviation. Both
procedures (inferior rectus recession and Knapp’s)
should not be done in the same sitting, as a matter of
principle, in order to avoid anterior segment ischemia.
If restriction is not present and only vertical deviation
is present a transposition of medial rectus and lateral
rectus toward superior rectus (Knapp’s) is a comm-
only practiced method. Knapp’s procedure is
ungraded and unpredictable. The transposition can
be effective, but patient does lose some ability in
adduction and abduction in extreme positions of gaze
which can be avoided if recession of yoke muscles,
i.e. SR and IO is carried out. SR is recessed 5 mm and
inferior oblique 8 to 10 mm. However in cases in which
horizontal deviation is present along with vertical
deviation following approaches are available to
ophthalmologists:
1. Knapp’s procedure after recession and resection
of medial and lateral rectus respectively (one
stage).
2. Above procedure in two stages as advised to avoid
anterior segment ischemia.
3. Horizontal deviation can be corrected by surgery
on fellow eye and only Knapp’s procedure in eye
with DEP for vertical correction.
4. Authors’ modified Knapp’s procedure.
The authors have modified Knapp’s procedure for
cases of DEP associated with horizontal deviation,
reason being in such cases if Knapp’s procedure is
carried out, the horizontal muscle cannot be used for
correction of horizontal deviation. This is because, it
is not possible to recess or resect the transposed
muscle, recession would negate the benefit of opera-
tion; and resection is nearly impossible because the
transposed muscle is already stretched maximally. In
the authors’ modified technique the medial and lateral
rectii are divided into two equal parts by splitting
them lengthwise for a distance of 15 mm. The superior
parts of both the muscle are used only for transposition
907
procedure and the inferior halves for the correction
of horizontal deviation. In this technique the amount
of vertical correction in primary gaze obtained is
independent of the size of the preoperative deviation
and is not fully predictable for any given patient. By
this procedure 28 PD (mean) of vertical deviation and
22 PD (mean) of horizontal deviation is corrected. By
this technique repeat surgery for residual horizontal
deviation is possible. When hyperdeviation is
accompanied by ptosis, muscle problem should be
corrected before ptosis. In many patients who have
had ptosis surgery followed by muscle surgery, ptosis
procedure was found to be inadequate and a 2nd one
was required. Ptosis should be done at least 6 months
after squint surgery. Surgeon should strive for
undercorrection of ptosis, keeping in view, the danger
of exposure keratitis secondary to the loss of protective
Bell’s phenomenon.
DIFFERENTIAL DIAGNOSIS
1. Blow-out fracture of orbital floor—history of
trauma, positive forced duction test, demonstrable
fracture and entrapement of muscle on CT scan will
point toward blow-out fracture.
2. Congenital fibrosis syndrome of inferior rectus—
positive family history, strongly positive forced
duction test, associated other ocular anomalies will
differentiate this condition from DEP.
3. Endocrine myopathy—systemic features, positive
forced duction test and increase IOP in upgaze will
point towards endocrinal myopathy.
4. Acquired restrictive, mechanical pathology of infe-
rior rectus like cysticercosis, myosititis, but in these
conditions forced duction test will be positive.
BIBLIOGRAPHY
1. Knapp P. Surgical treatment of double elevator palsy. Trans
Am Ophthalmol Soc 1969;67:304.
2. Lee JP, Collin JRO, Timmes C. Elevating the hypotropic globe.
Br J Ophthalmol 1986;70:26.
3. O’Conner R. Tendon transplantation in ocular muscle
paralysis. Am J Ophthalmol 1935;18:813.
 Chapter 118
Vertical Strabismus
JN Rohatgi
The diagnosis and management of vertical strabismus
need special care as there are many facts which still
elude explanation.
Bielsckowsky1 classified these deviations into the
following four groups:
1. Purely concomitant vertical deviations or hyper-
tropia.
2. Paralytic vertical deviations.
3. Dissociated vertical deviations (DVD).
4. Vertical deviations due to mechanical factors
(Endocrine myopathy, orbital floor fracture, etc.).
Of these, purely concomitant vertical deviations
(the primary type) are not common. To find a patient
with a significant vertical deviation of the same
magnitude in all positions of gaze with either eye
fixating is unusual.
Some of the characteristic features of these
concomitant vertical deviations are as follows:2
1. The deviation is generally smaller in magnitude.
2. Sensory adaptations like amblyopia and abnormal
retinal correspondence (ARC) are less frequent as
most of these cases are intermittent in nature.
3. Those which are of a permanent type may be
associated with a compensatory tilting of the head
toward the side of hypotropic eye to counter-
balance the vertical displacement of the images in
the two eyes and bring them to the same level.
4. Hyperdeviation of only 2 to 3 PD can cause head-
ache, eyestrain, diplopia or blurred vision specially
in cases of intermittent type wherein the fusional
ability (which is sufficiently strong to maintain the
visual axes in alignment) may fail under abnormal
demand.
Etiology
Etiology of a true concomitant vertical strabismus is
not clear. Some of the cases started as a paretic
deviation, which with the passage of time acquired a
concomitant look. In others, it was inferior oblique
muscle overaction with a concomitant convergent
strabismus. In a few, it has been caused by anatomical
or mechanical factors of abnormal innervation. As far
as anatomical factors are concerned, one may refer to
the asymmetry of the orbit or displacement of the
globe by a space-occupying lesion. Again the anatomy
of the vertical muscle may be anomalous, causing an
imbalance between the elevator and depressor
muscles from variations in their insertions, or presence
of abnormal attachments and bands.
Treatment
In cases of vertical strabismus the treatment is
generally surgical though in some cases, the use of
prism with base-up or down may temporarily help
relieve the symptoms.3 In those where the vertical
deviation is less (up to 10 to 12 prism diopter)—
lowering the horizontal muscle insertions of the
hypertropic eye or raising the insertions of the hypo-
tropic eye may help. In some of these cases, associated
with long-standing horizontal deviation, the hori-
zontal muscle is dealt with first and this may be
enough to eliminate the vertical component of
deviation with the passage of time.
But in those where the deviation is purely vertical
in nature, operative interference has to take care of
the superior/inferior rectus muscle keeping in mind
that postoperative insufficiency in elevation is
 Chapter 118: Vertical Strabismus
relatively unimportant as compared to inadequate
depression.
DISSOCIATED VERTICAL DEVIATION (DVD)
The other names for this condition are alternating
sursumduction, dissociated vertical divergence and
alternating hypertropia/hyperphoria. This is an ano-
maly in which dissociation as by covering an eye
causes the covered eye to deviate markedly upward
under the cover and as soon as the cover is removed,
the elevated eye comes down and while doing so it
may shoot further down to become hypotropic before
coming back to normal horizontal alignment with the
fellow eye after a few seconds.
It may occur as an isolated phenomenon in patients
in whom binocular functions are normal, but is found
more often in association with exotropia (especially
infantile esotropia or exotropia.4
The anomaly may not give rise to any subjective
symptoms. It is also known as alternating hyper-
tropia/hyperphoria. Frequent elevation may cause
subjective symptoms like blurred vision, difficulty in
focusing or headache.
Etiology
Various theories have been put forward to explain this
condition:5
a. It is due to an exaggeration of the normal tendency
for the eyes to deviate upward.
b. The underlying cause is bilateral paresis of the
depressor muscles either the superior oblique or
the inferior rectus or both.
The second factor thus, divides such cases of
dissociated vertical deviation into two groups: 5
paralytic and nonparalytic. The paralytic cases show
a compensatory head posture (CHP).
Examination
1. Cover test—the covered eye slowly deviates
upward to a variable extent. On removal of the
cover there is a recovery movement downward
which occasionally may be excessive before the
final movement to gain fixation. Each eye may
show such an updrift under cover.
2. Ocular movements—may show a defect of eleva-
tion or depression of one or both eyes in one of the
oblique positions accompanied by a corresponding
overaction of the synergistic muscle of the other
eye.
909
3. Since a number of such cases coexist with esotro-
pia/exotropia—mostly infantile esotropia—
binocular function is defective. Others with no
horizontal deviation may show normal binocular
single vision although there is a strong tendency
for suppression.
4. In those with poor binocular single vision an
increasing head-tilt toward the shoulder on the side
of the fixing eye and decreasing on tilting the head
toward the shoulder on the side of the nonfixing
eye may be seen. The nonfixing eye is hypertropic.
5. Diplopia—occasionally presents.
Differential Diagnosis
It may be necessary to differentiate cases of horizontal
concomitant deviation with upshoot of the inferior
oblique muscle in adduction from cases of alternating
hypertropia. In the later case, the covered eye becomes
elevated in abduction, primary position and adduc-
tion, whereas in those with inferior oblique over
action, the eye becomes elevated primarily in
adduction and never in abduction. This is obvious and
covering of the eye is not necessary.2
Treatment
As patients with DVD usually are asymptomatic, the
upshoot of the eye under cover may not pose any
problem but where the patient is conscious and
cosmetically disturbed, surgical correction has to be
taken recourse. This may be a recession of the superior
rectus muscle or a combined recession of the superior
rectus and recession of the inferior oblique muscle.6
In the nonparalytic group, where there is an asso-
ciation of alternating convergent strabismus or a
constant divergent sign, the treatment is mostly
surgical. In such cases, correction of the horizontal
deviation may appear to lessen the frequency and
degree of vertical deviation. Later on, where necessary,
bilateral superior rectus recession may be necessary
to reduce the extent of the vertical deviation.
STRABISMUS SURSOADDUCTORIOUS
It is a type of vertical deviation with overaction of the
inferior oblique muscle. A clinical condition with a
marked upshot. On Adduction there is left hypertropia
when the eye deviate to up and right position
(dextroversion) and right hyopertropia when the eyes
in conjugate movement move up and left (Levo-
version). In the primary position looking straight-
910 Section 7: Pediatric Ophthalmology Including Strabismus
ahead, there is no vertical deviation. This condition
may be unilateral or bilateral.
It may be an isolated phenomenon when associated
with esotropia (mostly congenital esotropia). It may
be assumed that in the adducted eye (esotropic eye)
the inferior oblique muscle (being a stronger muscle
than its counterpart the superior oblique) has a
mechanical advantage and the adducted eye shoots
up. But no such explanation is available to explain the
upshoot of the inferior oblique in cases where there is
no esotropia or paresis/paralysis of the ipsilateral
superior oblique or contra lateral superior rectus.
Strabismus sursoadductorious is better left alone
for it is not much of a cosmetic problem. Surgery is
indicated when the hypertropia produced by the
overacting inferior oblique muscle presents an
obstruction to fusion in lateral gaze or a V-pattern
exists.
Guibor7 suggested that all possible nonsurgical
treatments be attempted before operating the inferior
oblique muscle.
NONCOMITANT VERTICAL DEVIATIONS
Besides the concomitant hypertropia/hyperphoria
cases of noncomitant vertical deviations are more
commonly seen. They may be broadly grouped into:
(i) Primary vertical strabismus, and (ii) Secondary
vertical strabismus.5
In the primary noncomitant group we may have
cases like the following:
1. Paresis of an elevator or depressor of one eye.
2. Paralysis of both elevators or depressors of one eye.
3. Bilateral paralysis of the same muscle in each eye.
4. Mixed or multiple paresis—paresis of an elevator
of one eye and a depressor of the other eye.
If a purely vertical deviation which was originally
latent, becomes manifest in childhood due to decom-
pensation, it will tend to be accompanied by a conver-
gent squint because of the strong power of conver-
gence present. If, however, exophoria existed
previously, the accompanying horizontal deviation
may be divergent.
The Secondary Vertical Strabismus
A typical example is when there is elevation in
adduction in a case of convergent squint brought
about by the overaction of ipsilateral inferior oblique.
This is the concomitant type which has already been
mentioned earlier. The secondary variety of non-
comitant type of inferior oblique overaction is caused
by paresis or paralysis of the antagonist such as
superior oblique muscle in the same eye or contra-
lateral synergist, the superior rectus in the other eye.
Cases of A and V syndrome can also be cited as cases
of secondary vertical strabismus wherein as a result
of relative strength in adduction/abduction, cases of
convergent/divergent horizontal strabismus tend to
have elevation/depression in certain positions of gaze.
In primary vertical squints, the horizontal
deviation does not vary whether the gaze is directed
straight up, straight-ahead or straight-down whereas
horizontal deviation varies in a case of horizontal
squint with a secondary vertical component.
A compensatory head posture is evident in cases
of primary noncomitant vertical squint whereas this
is not shown in a secondary vertical squint.
Treatment
Treatment of vertical squints is largely a surgical
problem. In secondary cases correction of the
horizontal deviation is all that may be necessary—the
vertical component disappearing after some time. In
primary noncomitant vertical squint cases, operation
may have to be done on both horizontal and vertical
muscles at the same time. Some prefer to operate on
horizontal first, and the vertical muscle is taken care
of in the second sitting.
The superior oblique is the only vertical muscle
that has its innervation from a single nerve (the
trochlear nerve) and as such the most common paretic
hyperdeviation results from a palsy of the fourth
cranial nerve.
The amount of vertical deviation is greater in the
early onset cases and less in the acquired ones.
Traumatic cases complain of diplopia. The most sign
in congenital cases is the position of one eye being
higher than the other.
Double Elevator Palsy
It is a common cause of hyperdeviation. Examination
reveals a paresis of the superior rectus and inferior
oblique muscles of the same eye. Ptosis may be an
associated finding. The child generally walks with the
head elevated slightly to maintain binocular single
vision.
An occasional association in such cases may be
Marcus-Gunn jaw-winking phenomenon.
The etiology is difficult to explain. The treatment
is surgical correction though seldom indicated,
because a number of such cases have binocular single
 Chapter 118: Vertical Strabismus
vision in the primary straight-ahead position and are
aware of diplopia only on looking up.
Special Group
There is a special group of situation in which a patient
may have a vertical deviation in thyroid myopathy.
The patient cannot elevate the eye above midline in
the field of action of the superior rectus. The condition
is bilateral, though to start with, there may be gross
asymmetry. Some of these cases may also show
esotropia or limitation of movement in adduction
(abduction/elevation).
The pathology is perhaps due to fibrosis of the
extraocular muscles—inferior, superior and/or
medical rectus. Of these fibrosis of the inferior rectus
is more common. At times the inferior rectus is just a
tight band that can actually indent the sclera.
Blow-out Fracture
As a result of blunt injury to the eye, the orbital floor
gives way. The inferior rectus and occasionally the
inferior oblique are trapped in the fracture. Limitation
911
of the action of the superior and inferior rectus and
occasionally of the inferior oblique results. There may
also be relative enophthalmos.
The eye may be straight in the primary position or
the patient may have a hypertropia with diplopia in
the up and down positions.
REFERENCES
1. Bielschowksy A. Disturbances of the vertical motor muscles
of the eye. Arch Ophthalmol 1938;20:175.
2. Noorden GK von. Binocular Vision and Ocular Motility:
Theory and Management of Strabismus (3rd edn). St. Louis:
The CV Mosby Co, 1985.
3. Duke-Elder S, Wybar K. System of Ophthalmology: Ocular
Motility and Strabsmus St. Louise: The CV Mosby Co 1973;6.
4. Helveston EM. Dissociated vertical deviation: A clinical and
laboratory study. Trans Am Ophthalmic Soc 1980;78:734.
5. Lyle T, Keith and Wybar Kenneth. Practical Orthoptics in the
Treatment of Squint. London: HK Lewis and Co Ltd, 1967.
6. Knapp P. Dissociated vertical deviation. In Fells P (Ed):
Second Congress of the International Strabismological
Association, Marseilles, 1976.
7. Guibor GP. Synkinetic overaction of the inferior oblique
muscle. Am J Ophthalmol 1949;22:100.
 Chapter 119
Special Forms of Strabismus
LC Dutta, NK Dutta
The clinical entities of this group include Duane’s
retraction syndrome, Brown syndrome, myasthenia
gravis and myopathy in Graves’ disease.
DUANE’S RETRACTION SYNDROME
(STILLING-TURK-DUANE’S SYNDROME)
Duane’s retraction syndrome (DRS) is a congenital eye
movement disorder characterized by retraction of the
eyeball and narrowing of the palpebral fissure on
attempted adduction, abduction or both. These are
also accompanied with vertical eye movement
disorders on attempted adduction. It is commonly a
unilateral condition but in about 20 percent of the cases
it may be bilateral.1 When unilateral, the left eye is
affected in two thirds of cases. The condition is found
in both the sexes, but incidence is slightly more in
females.2,3 It is mostly a sporadic condition but 5
percent of cases are reported to have autosomal
dominant type of heredity.
Cases having the various features of DRS were
published by several authors during the late 19th
century,4 viz. Henk (1879), Stilling (1887), Sinclair
(1895), Bahr (1896) and Turk (1899). Abraham Duane5
in 1905 critically analyzed 54 cases of such anomalies
described in the literature and summarized with
probable etiopathogenesis and management of such
cases. Since then Duane’s name has been attached to
the syndrome, but in Europe it is still referred to as
the Stilling-Turk-Duane’s syndrome. Duane defined
the following six abnormalities in the affected eye:
a. Decreased abduction
b. Decreased adduction
c. Retraction of the globe during adduction
d. Oblique elevation or depression on adduction
e. Deficient convergence
f. Narrowing of the palpebral fissure on adduction.
The etiopathogenesis of DRS was not identified
even up to the 70th year after Duane described the
clinical features in 1905. The following abnormalities
were thought to be the cause of DRS:
a. Fibrosis of lateral rectus muscle due to some sort
of trauma during delivery6
b. Posterior insertion of medial rectus muscle7
c. Adhesion of medial rectus to the medial orbital
wall
d. Absence or malformation of the 6th cranial nerve.8
Introduction of electromyography for testing the
neuromuscular functions has thrown some light on
the etiopathogenesis of DRS.7 Electromyographic
(EMG) study of ocular muscles in DRS revealed that
all the features of the syndrome were either due to
paradoxical innervation of the horizontal rectii
muscles resulting from nondevelopment or mal-
development of supranuclear or infranuclear path-
ways of the 6th cranial (abducens) nerve.9,10 Blodi et
al even demonstrated misdirection of the nerve to
medial rectus muscle to the ipsilateral lateral rectus
muscle suggesting that co-innervation of horizontal
muscles may be the main cause of DRS.11 Based on
clinical, EMG and anatomical findings DRS is
classified into 3 types as shown in Table 119.1.
Bilateral DRS
Basically, bilateral DRS is Type III Duane’s retraction
syndrome. In this condition either eye cannot be
abducted beyond the mid-vertical axis, thus causing
limitation of both abduction and adduction with
retraction of the globe and narrowing of the palpebral
fissure on attempted adduction. Additionally there
may be slight downward movement of each globe on
attempted adduction.
 Chapter 119: Special Forms of Strabismus 913
Table 119.1: Three types of Duane’s retraction syndrome
Clinical EMG findings Anatomical findings
Type I
a. Marked limitation or complete a. Medial rectus muscle normal activity. Partial double innervation of lateral
absence of abduction. b. Lateral rectus muscle with minimum rectus muscle.
b. Normal or slightly defective activity on attempted abduction and peak
adduction. activity on adduction
c. Widening of the palpebral fissure
on abduction.
d. Narrowing of the palpebral fissure
and retraction of the globe on
attempted adduction.
Type II
a. Limitation or complete absence a. Lateral rectus muscle with peak activity on Dual innervation of lateral rectus muscle,
of adduction with exotropia of both abduction and attempted adduction. both by the 6th and 3rd nerve.
the affected eye. b. Normal activity of medial rectus muscle.
b. Abduction is normal or slightly
limited.
c. Narrowing of the palpebral
fissure and retraction of the
globe on attempted adduction.
Type III
a. Limitation or absence of both a. Simultaneous activity of the medial and Absence of abducens nerve with oculomotor
abduction and adduction. lateral rectus muscle on both attempted innervation of lateral rectus muscle.
abduction and adduction.
b. Narrowing of the palpebral b. Complete absence of normal agonist-
fissure and retraction of the antagonist relationship.
globe on attempted adduction.

From autopsy of a case, Hotchkiss et al8 confirmed
that abducens nerve was absent in each eye and one
of the branches of the inferior division of the
oculomotor nerve supplied the inferior and medial
aspect of the lateral rectus muscle. The region of the
muscle innervated by the branch from the oculomotor
nerve was found to have healthy well-formed muscle
bundles and the remaining poorly innervated part was
fibrotic. The medial rectii of both eyes were normal in
size and structure. Electromyography suggests that
globe retraction is due to contraction of the horizontal
rectii muscles because there is simultaneous activity
of the medial and lateral rectus muscles on both
abduction and adduction. The agonist-antagonist
relation of the muscles is completely abolished.
Both systemic and ocular malformations can be
found in patients with DRS. Ocular congenital
abnormalities include microphthalmos, various
degrees of persistent hyaloid system, choroidal
coloboma, dysplasia of iris stroma, epibulbar tumor,
heterochromia irides, dystrichiasis, congenital ptosis,
crocodile tear and nystagmus.12,13 Systemic anomalies
include skeletal anomalies of the vertebral column like
cervical spina bifida, extremities and digits or trunk
as well as neurological abnormalities including
deafness, Goldenhar’s syndrome, cleft palate,
malformation of the external ears, and anomalies of
limb, feet and hands. Therefore it is necessary to have
a complete systemic examination in all cases of DRS
because about 30 to 50 percent of patients with DRS
have associated congenital defects involving ocular,
auricular, and neural structures.13
Pseudo-Duane’s Syndrome
(Acquired Retraction Syndrome)
As already described, DRS is a congenital anomaly.
Several cases having acquired clinical features of globe
retraction and narrowing of the palpebral fissure on
abduction have been described.14 These are called
acquired retraction or Pseudo-Duane’s retraction
syndrome. Smith and Damasat15 reported a case who
had left trigeminal rhizotomy for tic douloureux;
postoperatively the patient developed ipsilateral 6th
nerve palsy with typical findings of DRS. Another
reported case of acquired DRS occurred following
914 Section 7: Pediatric Ophthalmology Including Strabismus
lateral orbitotomy (Kronlein’s operation) for caver-
nous hemangioma of the orbit.16 A case of pseudo-
Duane’s retraction syndrome was also reported to be
due to entrapment of the medial rectus muscle in
fracture of the medial wall of the orbit.17 The fourth
case in the chronology of acquired retraction
syndrome was described by Baker and Robertson18
in a patient with rheumatoid arthritis. The patho-
genesis of this condition is considered to be due to
myopathy or vasculitis with collagen vascular disease.
Treatment of DRS
Presence or absence of binocular vision and quality of
binocular vision are the main considerations to decide
upon surgical treatment of DRS. If fusion can be main-
tained with mild or moderate head turn, surgery may
not be necessary. The aims of surgery are as follows:
1. Elimination or improvement of unacceptable head
turn.
2. Elimination or reduction of significant mala-
lignment of the eyes.
3. Reduction of severe retraction of the globe.
4. Improvement of upshoots or downshoots.
Types of Surgery
Surgery cannot eliminate the abnormal eye move-
ments because it cannot cure the fundamental error
of innervation. Duane initially practiced horizontal
muscle recession surgery for his cases and this is still
done with some success.19 The muscle to be recessed
is selected by evaluating the direction of gaze with
the greatest limitation of movement and by the
presence or absence of esotropia or exotropia. If
limitation of abduction with esotropia is present then
the medial rectus muscle of the involved eye is
recessed with posterior fixation suture operation of
the contralateral medial rectus muscle. On the other
hand, in limitation of adduction with exotropia, the
lateral rectus muscle needs recession. In cases of severe
globe retraction, recession of both horizontal rectus
muscles of the affected eye may be considered. The
amount of recession is determined by preoperative
measurements of deviation in primary position as well
as limitation of ocular movements on duction, version,
and forced duction test. The recession may be done
by adjustable suture technique.
Temporal displacement of vertical rectii muscle In paralysis
of 6th (abducens) nerve and in Duane’s I retraction
syndrome, the eyeball cannot be abducted beyond the
midline. Resection of the lateral rectus muscle cannot
move the eyeball laterally, instead it will produce
retraction of the globe causing enophthalmos. MH
Gobin in 1972 performed temporal displacement
(transposition) of the vertical rectii muscles. In this
operation the tendon of insertion of the superior and
inferior rectus muscles is first disinserted. Then the
temporal end of the tendon of insertion of the superior
rectus is attached to the upper border of tendon of
insertion of the lateral rectus and likewise the medial
(nasal) end of the superior rectus is attached to the
temporal site of the original insertion of superior
rectus. Similarly for the inferior rectus, the lateral end
of the tendon of the tendon of insertion of the muscle
is attached to the lower border of tendon of insertion
of lateral rectus and the medial end of the tendon of
inferior rectus muscle is attached to the site of
attachment of the lateral end of its original attachment.
It is claimed that20-22 in 73 percent of cases abnormal
face-turn is eliminated after this operation. In addition,
abduction ability was increased and the binocular
diplopia free field size was enlarged in all patients.
However there is a great risk of anterior segment
ischemia after simultaneous surgery on multiple
rectus muscles. Therefore the surgery on lateral rectus
muscle should be done first and on medial rectus
muscle, if necessary, should be done at a later stage.
Along with vertical rectii transposition, recession
of the medial rectus by about 4 mm is necessary.
Posterior fixation suture (Faden’s operation) may also
be useful instead of recession of medial rectus.23 There
is no rigid rule regarding surgical treatment of
retraction syndrome. Therefore an individualized
approach is recommended taking into account the
coexisting vertical and horizontal deviation.
BROWN SYNDROME (SUPERIOR
OBLIQUE MUSCLE SHEATH SYNDROME)
Harold Whaley Brown24 first described this syndrome
in 1950. It is a form of ocular motility disorder
characterized by passive as well as active limitation
of elevation of the eyeball in adduction. In normal
conditions when the eye moves upward and inward,
the superior oblique muscle relaxes and its tendon
slides smoothly through the trochlea. When the
superior oblique muscle cannot relax or the passage
of the tendon through the trochlea is restricted, then
elevation of the eyeball in adduction is impaired.
The following two types of Brown’s syndrome
have been identified:25
 Chapter 119: Special Forms of Strabismus
a. True Brown syndrome,
b. Simulated Brown syndrome.
True Brown syndrome In this syndrome the movement
of the eye is limited in adduction so that the eye cannot
voluntarily be raised over the mid-horizontal plane.
There is little or no overaction of the homolateral
superior rectus muscle. Usually slight downshoot of
the eye and the widening of the palpebral fissure
occurs on adduction.
Further, true Brown syndrome is divided into the
following:
i. Typical—without coexisting limitation of the
homolateral superior rectus muscle,
ii. Atypical with significant limitation of superior
rectus muscle.
Simulated (pseudo) Brown syndrome Posterior part of
the superior oblique muscle and its tendon is
thickened or too firmly attached to its posterior sheath.
The causes of this pathology include extension of
inflammatory process from coexisting inflammation
of adjoining paranasal sinuses, mainly ethmoid sinus
to the sheath and tendon-trochlea complex causing
sort of tenosynovitis. Orbital floor fracture, surgery
on paranasal sinuses, surgery on superior oblique
muscle tendon and rheumatoid arthritis also can cause
simulated Brown syndrome.26-28
Recent studies have shown that the restriction of
the movement is neither due to defect in the muscle
and tendon nor in the tendon sheath; but it is in the
tendon-trochlea complex.29,30 The condition may be
congenital and acquired as explained above.26-28 It may
be constant, recurrent or intermittent. In the inter-
mittent type a click is audible when the tendon passes
through the trochlea. The congenital etiology was
initially thought to be due to paralysis of inferior
oblique muscle with secondary shortening of superior
oblique tendon sheath during development of the
eye.31
Clinical Features
The following are the characteristic clinical features
of Brown syndrome.24,31
1. Absence of elevation on adduction.
2. Normal or near normal elevation in the primary
position or abduction.
3. Positive forced duction test (restriction of passive
elevation).
4. Occasional widening of the palpebral fissure in
adduction.
915
5. Divergence on upward gaze.
6. Abnormal head posture (common in congenital
form of Brown syndrome) face-turn and chin-up
position.
7. Diplopia may be a common symptom but is
avoided by abnormal head posture.
8. Suppression amblyopia develops if diplopia
cannot be avoided by abnormal head posture.
Differential Diagnosis
Conditions to be differentiated from Brown syndrome
include double elevator palsy, blow-out fracture of the
orbit, ipsilateral inferior oblique paralysis with supe-
rior oblique overaction and Duane’s retraction
syndrome.
Double elevator palsy is characterized by limitation
of elevation on primary position and in abduction as
well as in adduction. Ptosis may also be present.
Superior oblique overaction can cause hypotropia on
adduction and resemble Brown syndrome. But
primary superior oblique overaction does not occur,
it may be due to inferior oblique paralysis. Forced
duction test may be of help in differentiating these
two conditions. Duane’s retraction syndrome can
resemble Brown syndrome but is distinguished by
characteristic globe retraction and narrowing of the
palpebral fissure on attempted adduction in the
former.
Management of Brown Syndrome
Spontaneous resolution of Brown syndrome can occur
specially in some of the acquired and intermittent
cases. In persistent cases surgery should be considered.
Before planning any surgery, the status of binocular
single vision and degree of anomalous head posture
should be assessed carefully. Initially in all cases of
Brown syndrome, diplopia tends to develop in early
stage and this can be avoided by assuming anomalous
head posture—(chin-up and face-turn) or by suppres-
sion of vision in one eye, commonly the involved eye.
In mild cases diplopia may not be present in primary
position but occur on attempt to elevate the involved
eye in adduction. Such patients may learn to avoid
diplopia by avoiding this position of gaze. When the
eye is hypotropic in primary position or if abnormal
head posture is cosmetically unacceptable then
surgery is indicated. However in recurring or
intermittent case, the cause may be due to some degree
of stenosing tenosynovitis at the tendon-trochlea
complex. These patients respond well with medical
916 Section 7: Pediatric Ophthalmology Including Strabismus
treatment. Brown himself advocated and practiced
stripping of the sheath of the tendon leaving the
tendon intact.24 This operation was based on the
misconception that the pathogenesis of the syndrome
was contraction of the sheath of the superior oblique
tendon. During the immediate postoperative period
the result was very satisfactory. But recurrences were
common and forced duction test became positive
again. Hence this procedure was abandoned.
The present trend of treatment is to weaken the
superior oblique tendon. The surgical procedures to
weaken the tendon are as follows:
1. Tenotomy—this improves the patient’s field of
binocular single vision, head posture, and
version.32,33 Simultaneous tenotomy and inferior
oblique recession also tried by Parks and Eustis
who claimed 94 percent success with 14 mm
recession.34
2. Weakening of the muscle can also be achieved by
recession of the site of original insertion of superior
oblique muscle tendon.35
3. Excision of the tendon, i.e. tendenectomy.
4. Lengthening of the tendon by a piece of silicon also
has been tried.36,37
5. Based on the study of the anatomy and physiology
of the trochlea, the latest surgical treatment of
Brown syndrome suggested by Mombaerts and
associates is luxation or trochlear luxation.
Acquired Brown syndrome and superior oblique
muscle overaction can be treated by this opera-
tion.38 Unlike weakening the muscle action by
operations like tenotomy, lengthening of the
tendon or recession of tendon insertion, dislocation
of the trochlea will produce the same effect of
weakening the muscle action and this will negate
hypotropia of the eyeball on the affected side.
MYASTHENIA GRAVIS
Myasthenia gravis is usually a disease of elderly
people but adolescents may also suffer from the same.
Myasthenia gravis is characterized by easy fatigability
of the striated muscles. About 60 percent of patients
with myasthenia gravis present with ocular symptoms
like ptosis and diplopia; 90 percent of patients with
the disease get ptosis and/or diplopia. In other words
diplopia and ptosis may be the earliest manifestation
of myasthenia and other muscles like those involved
in respiration and mastication are affected later. Some
authors tend to consider that ocular myasthenia is a
separate entity but about 80 percent of such cases
develop generalized myasthenia usually within two
years.
Though myasthenia gravis is considered as an
autoimmune disease the basic pathology is at the
myoneural junction of the affected muscle. About 8
percent of patients with active generalized myasthenia
gravis have circulating antibodies against human
acetylcholine receptors of the postsynapytic memb-
rane of the neuromuscular junction. Acetylcholine,
which is the pharmacological transmitter at the
neuromuscular junction, is destroyed immediately
after its formation by an unknown and abnormal
substance imposing a curare-like block. Anticholine
esterase drugs may rectify the condition by preserving
the action of acetylcholine.
In general small muscles are affected first, viz,
ocular muscles and lumbricales. Initially, patients
complain of inability to write or do any work where
finger muscles are involved. Ptosis and diplopia may
appear at a later stage. These symptoms may appear
or become more toward the end of the day when the
muscles are fatigued.
In suspected cases the symptoms can be aggra-
vated by exerting more muscle work, viz. when
suspected patients are asked to look up and down
quickly, repeatedly and continuously for a minute or
so, the degree of ptosis will be more pronounced and
the diplopia may also be aggravated after moving the
eyeballs from side to side for one minute. Not
infrequently, the patients may present with features
of heterophoria, most commonly exophoria. The
characteristic feature of diplopia is that it is irregular,
i.e. does not conform to paralysis of any single muscle.
Pupillary muscles are never affected. An emotional
upset, upper respiratory tract infection, and pregnancy
may aggravate the onset of myasthenia.
Myasthenia is common in females in the second
and third decades of life but the age of onset of
symptoms may extend from infancy to old age.
Neonatal myasthenia also may be seen in babies born
to mothers suffering from myasthenia gravis.
The thymus gland is found to be enlarged in 10
percent of cases of myasthenia gravis. The condition
improves after thymectomy in 50 percent of cases.
Some of the thymus glands harbor thymoma while in
others there is lymphatic hyperplasia. It may be
possible that some factors derived from the thymus
gland may be responsible for deranged neuro-
muscular transmission. It is essential to exclude
thymus gland swelling by radioimaging procedures.
 Chapter 119: Special Forms of Strabismus
Along with the ocular muscles, facial, laryngeal
and the muscles of mastication may be affected leading
to difficulty in swallowing and breathing.
Diagnosis
Diagnosis of myasthenia gravis is made from the
clinical features suspicious of the disease entity.
Diagnosis can be aided by the following tests:
Pharmacological Test (Tensilon Test)
Steps of the test are as follows:
1. Extent of the ptosis and ocular motility defect
evaluated objectively.
2. Atropine sulfate 0.3 mg injected intravenously
before injection of endrophonium chloride.
3. 10 mg of Tensilon (endrophonium chloride) in 1
ml of solution is taken in a tuberculin syringe.
Initially 2 mg (0.2 ml) is injected intravenously. The
patient is observed for 30 to 60 seconds. This
fractional dose test has the following two purposes:
a. If the patient shows improvement of signs, i.e.
disappearance or decrease of ptosis and imp-
rovement of ocular motility then the full dose
need not be injected.
b. The other significance is that some patients may
develop side effects like bradycardia, abdo-
minal cramps, and rarely syncopal episodes
with respiratory arrest. If the fractional test dose
does not show any relief of symptoms or there
is no sign of any systemic side effects then the
remaining 0.8 ml is injected and the end point
is observed.
Tensilon Test (Negative)
If the Tensilon test is negative, then 2 mg of neo-
stigmine may be injected intramuscularly; but at least
10 minutes prior to neostigmine injection 0.3 mg of
atropine sulfate should be injected intramuscularly to
prevent intestinal cramps and other side affects of
neostigmine. In case of myasthenia, the symptoms are
relieved (neostigmine test and Tensilon test should
not be done on the same day).
Electromyography (EMG)
EMG in myasthenia gravis shows a gradual fatigue
and decline of potentials in the affected muscle.39,40
The restoration of normal potential following injection
of Tensilon or Prostigmin confirms the diagnosis.
917
Diagnosis of the disease with EMG can be done even
before its clinical manifestations appear.
Ocular Tonography
Intraocular pressure suddenly goes up due to the
contraction of the extraocular muscles after Tensilon
injection. It is suggested that Tensilon tonography may
be a sensitive test for diagnosis of myasthenia gravis.
Treatment of Myasthenia
In most of the cases, surgical treatment is not indicated
in this condition. Systemic anticholine esterase sub-
stances also do not have desired effect on myasthenic
diplopia. Local application of such drugs was
advocated in the past in the form of drops, especially
to treat myasthenic ptosis. Levator function is
improved to some extent. In troublesome diplopia,
occlusion of one eye can be tried. Muscle surgery may
be indicated in rare instances of myasthenic patients
with long-term and stable paralysis of a muscle or a
group of muscles.40
Medical treatment of myasthenia gravis consists
of anticholine esterase drugs. Neostigmine (Prostig-
min) 15 mg or pyridostigmine bromide (Mestinon) 60
mg tablet improves neuromuscular transmission
within 15-20 minutes with a maximum effect in 2 hours
and the action lasts for about 4 hours. Hence, the drug
has got to be administered six hourly. Steroid therapy
helps to some extent in some cases. Prednisolone 15-
20 mg per day may gradually be increased up to 60
mg. This may be combined with anticholineesterase
drugs. Another form of treatment recommended is
plasmapheresis to remove antiacetylcholine anti-
bodies. Surgical removal of the thymus gland is
indicated if thymus tumors are detected by CT scan.
Cyclic Strabismus
In his book on strabismus Von Noorden refers to a
case report by Windsor and Berg:58 “ A 10-year-old
boy following an injury to the left trochlear region had
left hypertropia with vertical diplopia and no head
tilt. After medication with phenobarbitone, the left
hypertropia was constant. But when the drug was
discontinued, the cycle returned”. The cause and
mechanism of this type of strabismus is intriguing.
Another report59of two cases due to central nervous
disease was published in 1987.
918 Section 7: Pediatric Ophthalmology Including Strabismus
Cyclic heterotropia commonly occurring every 48
hours or 72 hours or even 96 hours have been reported.
Electroencephalogram should be abnormal during the
heterotropic period and normal in the non-hetero-
tropic period. The periodic systemic phenomena
during the heterotropic period includes sweating,
raised body temperature and pulse rate. Another
peculiar aspect is that some reported patients have
strong family history of manifest strabismus.
REFERENCES
1. Kirlkham TH. Anisometropia and amblyopia in Duane’s
syndrome. Am J Ophthalmol 1970;64:774.
2. Isenbery S, Urist MJ. Clinical observation in 101 consecutive
patients with Duane’s retraction syndrome. Am J Ophthalmol
1977;84:419.
3. Ahluwalia BK, Gupta NC, Goel SR et al. Study of Duane’s
retraction syndrome. Acta Ophthalmologica (Copen)
1988;66:77.
4. Kowal VO, McKeown CA. Duane’s syndrome. Intl Ophthal-
mol Clinic 1992;32:51.
5. Duane A. Congenital deficiency of abduction associated with
impairment of adduction, retraction movements, contraction
of palpebral fissure and oblique movements of the eye. Arch
Ophthalmol 1905;34:133.
6. Gifford H. Congenital defects on abduction and other ocular
movements and those relating to birth injury. Am J
Ophthalmol 1974;58:293.
7. Huber A. Electrophysiology of the retraction syndrome. Br J
Ophthalmol 1974;58:293.
8. Hotchkiss MG, Miller NR, Clark AW et al. Bilateral Duane’s
retraction syndrome. Arch Ophthalmol 1980;98:870.
9. Scott AB, Wong GY. Duane’s syndrome: An electro-
myographic study. Arch Ophthalmol 1972;87:140.
10. Strachan IM, Brown BH. Electromyography of extraocular
muscles in Duane’s syndrome. Br J Ophthalmol 1972;56:594.
11. Blodi FC, Allen MW, Yarbrough JC. Duane’s syndrome: A
brain stem lesion. Arch Ophthalmol 1964;72:171.
12. Ahluwalia BK, Gupta NC, Goel SR et al. Study of Duane’s
retraction syndrome. Acta Ophthalmol logica 1972;88:635.
13. Pfaffenbach DD, Cross HE, Kearns TP. Congenital anomalies
in Duane’s retraction syndrome. Arch Ophthalmol 1972;
88:635.
14. Osher RH, Schatz NJ, Duane TD. Acquired orbital retraction
syndrome. Arch Ophthalmol 1980;98:1798.
15. Smith RS, Damasat M. Acquired retraction syndrome after
6th nerve paralysis. Neurology 1973;14:147.
16. Sood GC, Srinath B, Krishnamoorthy G. Acquired Duane’s
retraction syndrome following Kronlein’d operation. EENT
J 1975;54:308.
17. Duane T, Schatz NJ, Caputo AR. Pseudo-Duane’s retraction
syndrome. Trans Am Ophthalmol Soc 1976;74:122.
18. Baker RS, Robertson WC Jr. Acquired Duane’s retraction
syndrome in a patient with rheumatoid arthritis. Ann
Ophthalmol 1980;12:269.
19. Pressman SH, Scott WE. Surgical treatment of Duane’s
syndrome. Ophthalmology 1986;93:29.
20. Gobin MH. Aspects of horizontal muscle surgery, particularly
in Duane’s syndrome. Trans Ophthalmol Soc UK 1972;92:685.
21. Gobin MH. Surgical management of Duane’s syndrome. Br J
Ophthalmol 1974;58:301.
22. Molarte AB, Rosentrum AL. Vertical rectus muscle transplan-
tation surgery for Duane’s syndrome. J Paed Ophthalmol
Strabismus 1990;27:171.
23. Noorden GK von. Indications of posterior fixation operation
for strabismus. Ophthalmology 1998;85:512.
24. Brown HW. Congenital structural muscle anomalies. In Allen
JH (Ed): Strabismus Ophthalmic Symposium1. St. Louis: The
CV Mosby Co. 1950;205.
25. Brown HW. True and simulated superior oblique tendon
sheath syndrome. Doc Ophthalmol 1973;34:123.
26. Blanchand CL, Young LA. Acquired inflammatory superior
oblique sheath syndrome: Report of a case following frontal
sinus surgery. Arch Ophthalmol 1973;110:120.
27. Stanford-Smith JH. Superior oblique sheath syndrome and
its relationship to stenosing tenosynovitis. Br J Ophthalmol
1973;57:589.
28. Wright KW, Silverstein D, Marrone AC et al. Acquired inflam-
matory superior oblique sheath syndrome: A clinico-
pathological study. Arch Ophthalmol 1982;100:1752.
29. Helversten EM, Merrium WW, Ellis FFD et al. The trochlea:
A study of the anatomy and physiology. Ophthalmology
1982;87:124.
30. Wilson ME, Eustis HS, Parks MM. Brown’s syndrome. Survey
Ophthalmol 1989;34:153.
31. Brown HW. Isolated inferior oblique muscle paralysis:
Analysis of 97 cases. Trans Am Ophthalmol Soc 1957;53:415.
32. Crawford JS, Orton RB, Labow Daily L. Late results of
tenotomy in true Brown syndrome.Am J Ophthalmol
1980;89:824.
33. Crawford JS. Surgical treatment of true Brown syndrome. Am
J Ophthalmol 1976;81:289.
34. Parks MM, Eustis HS. Simultaneous superior tenotomy and
inferior oblique recession in Brown syndrome. Ophthalmo-
logy 1987;94:1043.
35. Caldoria JAF. Graduated recession of superior oblique
muscle. Br J Ophthalmol 1975;59:553.
36. von Noorden GK, Oliver P. Superior oblique tenotomy in
true Brown syndrome. Ophthalmology 1982;89:303.
37. Wright KW. Superior oblique silicone expander for Brown
syndrome and superior oblique overaction. J Paed Ophthal-
mol Strabismus 1991;28:101.
38. Mombaerts I, Koomect L, Everhand-Halmy’s et al. Superior
oblique luxation and tendon luxation as new concepts in
superior oblique muscle weakening surgery. Am J Ophthal-
mol 1995;120:83.
39. von Noorden GK. Binocular Vision and Ocular Motility (4th
ed). St. Louis: CV Mosby 1990;419.
40. Leopold H, Dedges TR, Montana J et al. Local examination
of agents in ocular myasthenia gravis. Arch Ophthalmol
1960;63:544.
41. Breinin SM. Electromyography: A tool in ocular and neuro-
logic diagnosis. 1. Myasthenia gravis. Arch Ophthalmol
1957;57:161.
42. Teasdall RD, Scar SM. Myasthenia Gravis: Electromyographic
evidence of myopathy. Am J Ophthalmol 1962;54:541.
 Chapter 119: Special Forms of Strabismus
43. Glaster J. Graves’ ophthalmopathy (editorial) Arch Ophthal-
mol 1984;101:1448.
44. Kroll AJ, Kuwabara T. Dysthyroid ocular myopathy:
Anatomy, histology, and electron microscopy. Arch
Ophthalmol 1966;76:244.
45. Magora A, Chaco J, Zauberman H. An electromyographic
investigation of ophthalmoplegia in thyrotoxicosis. Arch
Ophthalmol 1968;79:170.
46. Schultz RO, Van Allen ME, Blodi FC. Endocrine ophthal-
moplegia with an electromyographic study of paretic
extraocular muscles. Arch Ophthalmol 1960;63:210.
47. Ormond JN. Management of squint in dysthyroid diseases.
Trans Ophthalmol Soc UK 1981;101:284.
48. Trokel SL, Hital SK. Recognition of diferential diagnosis of
enlarged extraocular muscles in computed tomography. Am
J Ophthalmol 1979;87:503.
49. Byrne SF, Green RL. Ultrasound of the Eye and Orbit. St.
Louis: Mosby Year Book 376-78.
50. Grover AS. Upper lid retraction and Graves’ disease. Ophthal-
mology 1981;88:499.
919
51. Goldstein JE. Paresis of superior rectus muscle associated with
thyroid dysfunction. Arch Ophthalmol 1964;72:5.
52. Hurwitz J, Birt D. An individualized approach to orbital
decompression in Graves’ orbitopathy. Arch Ophthalmol
1985;103:660.
53. Bouzas AG. Endocrine ophthalmopathy: The Montgomery
Lecture 1980. Trans Ophthalmol Soc UK 1980;100:511.
54. Miker JE, Van Hunwan W, Ward R. Surgical correction of
hypoptropia associated with thyroid dysfunction. Arch
Ophthalmol 1968;74:170.
55. Scott AB, Rosenbaum AL, Collins CC. Pharmacological
weakening of extraocular muscles. Invest Ophthalmol Vis Sci
1973;12:924.
56. Scott AB. Botulinum toxin treatment of strabismus. Am
Orthop 1985;35:28.
57. Resenbaum AL. The current use of botulinum toxin therapy
in strabismus. Arch Ophthalmol 1996;114:213.
58. Windsor CE, Berg EF. Cicardian heterotropia. Am J
Ophthalmol 1969;67,656.
59. Pillai P, Dhand UK. Cyclic esotropia with central nervous
system disease. Report of two cases. J Pediatr Ophthalmol
Strabismol 1987;24,239.
 Chapter 120
Nonsurgical Treatment of Squint
Kamlesh, S Dadeya
Ideal goal of any therapy in squint is to have straight-
eyes with all levels of binocular vision with patient
functioning as if there had been no deviation. We
rarely achieve such results. Keeping in view of the
above limitation in the mind following nonsurgical
modalities have been tried with limited success. But
nonsurgical treatment cannot be ignored rather
nonsurgical treatment is very important and must be
tried before any surgical treatment, in order to achieve
the goals mentioned above (for both functional and
irreversible or constant and stable cosmetic results,
i.e. alignments). The following are some of the impor-
tant nonsurgical treatment modalities which are
summarized with their importance.
REFRACTIVE CORRECTION
An accurate cycloplegic refraction is essential in all
patients with childhood strabismus. Ideally, refraction
should be carried out under atropine in all children
below the age of 7 years. The first basic step of any
form of treatment is proper prescription of glasses. In
all patients who are under the age of 7 years, full
cycloplegic refraction should be prescribed (i.e. we
have to deduct only for working distance, i.e. +1.5 D).
In accommodative esotropia up to the age of 7 years
full refractive correction should be given and after that
refraction should be carried out every 6 months and
any change in power should be adjusted. Refraction
usually stabilizes by the age of 12 years and maximum
tolerable amount of plus power should be ordered.
Myopia and astigmatic refractive error should also be
fully corrected.
On the other hand in exodeviation, slight over
correction of myopic refractive error is occasionally
helpful in controlling exodeviation. Since correction
of hypermetropia will decrease the demand on
accommodative convergence and thus increases
exodeviation, each patient should be evaluated on an
individual basis. We do not correct hypermetropic
refractive error up to 2.0 diopter in children up to the
age of 5 years. In older patients hypermetropic
refractive error should be corrected in order to avoid
asthenopic symptoms, and in presbyopic age group
weakest bifocal should be prescribed. Glasses help in
maintaining proper balance between accommodation
and convergence and are stimulus for fusion by
creating a sharp image on retina.
BIFOCALS
Bifocals should be prescribed children, who are
orthophoric at distance after wearing full cycloplegic
correction and have an esotropia at near fixation that
can be converted into esophoria or orthophoria by
means of additional plus lenses. Bifocals should not
be prescribed in presence of amblyopia.
How to Determine Power of Bifocals
Patients is given full refractive correction. The
deviation is measured with glasses for distance and
near and we add +1.0 lens and determine the deviation
at near and go on adding up to +3.0 Ds till such point
is reached at which esotropia can be overcome by
fusional divergence. Only weakest lens power that
converts esotropia to esophoria is prescribed.
Mechanism of Action
Bifocals remove the need of accommodate by
peripheral mechanism without altering AC/A ratio.
Proper bifocal Specific instruction should be given for
standard-sized bifocal (segment height at lower lid
border) to optician for that purpose, otherwise bifocals
will render no benefit to patient.
 Chapter 120: Nonsurgical Treatment of Squint 921
Withdrawal of bifocal Repeat refraction should be done Convergence Excercise
and any change should be adjusted. Bifocal strength
The patient is asked to look at a distance object and
should be reduced step-by-step and bifocals should
with his gaze still fixed, base-out prisms, initially weak
be completely withdrawn by the age of 12 years. Some
and gradually increasing in strength, are placed before
patients may require additional orthoptic therapy to
the eye at interval of 5 seconds, the patient being
strengthen fusional divergence and if fusion is no
encouraged to fuse the 2 images into one. These
longer possible for near, bilateral medial rectus
exercises are initially done for distance and then object
recession should be carried out.
is brought nearer and exercise at the near-point and
MIOTICS far-point are alternated. If by these measures there is
no relief, base-in prisms should be prescribed in
Mechanism of Action
spectacles for near work.
1. Miotics induce accommodation without conver-
gence by peripheral mechanism. Treatment of Heterophoria
2. The concurrent miosis may assist by increasing the
depth of focus. a. Orthoptic exercise
b. Relieving prisms.
Drug used Phospholine iodide 0.03 percent is preferred
drug because of longer duration of action. Orthoptic exercise These are done with adverse prisms,
Indications i.e. exercises are done against prisms, with their base
turned toward the direction of deviation; with head
i. Accommodative squint with convergence excess
maintaining it’s original position, the object is then
ii. Residual esotropia
carried to the sides and exercise is repeated, until the
iii. Consecutive esotropia
patient can secure a single image in all parts of room
iv. Amblyopia.
in spite of the action of prisms.
Side Effects
Systemic Relieving prisms While strengthening muscles of
1. Respiratory paralysis inadequate strength by the above exercises, is the
2. Perspiration rational treatment, relief of symptoms, may be
3. Nausea achieved by prescription of relieving prisms) which
4. Vomiting correct the defect optically, the base of prism is placed
5. Salivation in the direction of action of the muscle, which is to be
6. Diarrhea aided; and its apex, toward that of the antagonistic
7. Abdominal cramps muscle which is to be neutralized. Prisms are
8. Jaundice. combined with the lenses to correct the optical error
and should be divided equally between the two eyes.
Local
1. Iridocyclitis Palliative
2. Acute congestive glaucoma
Here, there is no curative value; the prisms merely
3. Cataract
alleviate the symptoms:
4. Retinal detachment
5. Iris cysts.
Small residual deviation Till such time as fusion has
Atropine Guibor and Methy recommends atropine in developed sufficiently to allow the patient to
all children of esotropia before age of 6 year, but we overcome the deviation without their aid.
do not recommend use of atropine for treatment of
esotropia. Phorias Where orthoptic treatment has failed and in
which operation is contraindicated.
Prisms
Prisms can be used for therapeutic purposes in Muscle palsies Where surgery is contraindicated or
following conditions: patient is waiting for surgery.
922 Section 7: Pediatric Ophthalmology Including Strabismus
BOTULINUM TOXIN
Mechanism of Action
It exerts its effect by rapidly and strongly binding to
the presynaptic nerve terminal of cholinergic axons.
It is then internalized into intracellular compartment
where it inhibits the released acetylcholine containing
vesicles.
Indications
a. Antagonist muscle in paralytic strabismus.
b. Postoperative small angle residual deviation.
c. Strabismus following retinal detachment surgery.
d. Exotropia of less than 40 PD in poor surgical candi-
dates.
Contraindications (Relative)
a. Restrictive strabismus
b. Squint secondary to an over recessed or slipped
muscle
c. Antagonist muscle not intact
d. Deviation of more than 40 PD.
ORTHOPTICS
The following are the definite indications for orthoptic
therapy:
1. Increasing fusion range in cases of the following:
a. Heterophoria
b. Convergence insufficiency
c. Small residual angle of squint.
2. Antisuppression exercise
3. Pleoptic treatment
4. Treatment of abnormal retinal correspondence.
Heterophoria
The targets of synoptophore are set at an angle at
which patient can fuse, and the arms of instrument
are diverged (for divergence) or converged (for
convergence) until diplopia occurs. By this method
fusion range of patient is increased and patient is
relieved of symptoms due to heterophoria.
Convergence Insufficiency
Orthoptics is only method by which patient with
convergence insufficiency will find relief. In advanced
stages suppression should be treated first. After
suppression has been eliminated, the patient is told
to converge on an approaching object, such as pencil,
while a red filter is placed in front one eye. These
exercise are followed by training of fusional conver-
gence with base-out prisms and by treatment using
major amblyoscope. Base-out prisms may also be used
during reading.
Antisuppression Training
Suppression is patient’s defence against diplopia.
Principle of antisuppression therapy is to bring image
formed on suppressed retinal area back into conscious-
ness. Retina of deviated eye can be stimulated by
moving the visual target on the major amblyoscopic
back and forth across the suppression scotoma.
MANAGEMENT OF AMBLYOPIA
Amblyopia, a unilateral or bilateral decrease of visual
acuity caused by formed visual deprivation and/or
abnormal binocular interaction for which no organic
cause can be detected by physical examination of the
eye and which in appropriate cases is reversible by
therapeutic measures at appropriate time. The basic
principle in treating amblyopia is to restore vision by
promoting use of the amblyopic eyes which can be
achieved in following ways:
1. Occlusion treatment
2. Penalization
3. Pleoptics
4. Red filter treatment
5. CAM visual stimulators
6. Drugs (levodopa and carbidopa).
Occlusion Treatment
This is the most effective method of treatment of
unilateral amblyopia. By occluding better eye,
amblyopic eye is forced for use and occlusion also
prevent any inhibitory stimuli to amblyopic eye that
arises from stimulation of the fixating eye.
Types of occlusion (1) Conventional, (2) Inverse.
Nature of occlusion Total occlusion excluding all light
and form.
Partial occlusion Allowing appreciation of form, but
decreasing its acuity.
The best result in term of speed of recovery is
attained with total occlusion given full-time. Periodic
observation of the occluded eye, particularly its visual
acuity determination is essential, so as to prevent
occlusion amblyopia.
Occlusion-induced Amblyopia
The chance of occlusion-induced amblyopia is age-
related and may be seen in children up to age of 6
 Chapter 120: Nonsurgical Treatment of Squint
years. To prevent occlusion-induced amblyopia,
alternate occlusion of the sound eye with occlusion of
the amblyopic eye is preferred. The schedule for
alternation varies according to age. The ratio of
occlusion is 1:1 for a child of less than one year of age.
Then it is increased by 1 for each year till age of 6
years. After age of 6 years the risk of occlusion
amblyopia is particularly negligible, so constant
occlusion of the normal eye can be given for quicker
recovery. However, proper follow-up with visual
acuity check-up in each eye separately at each visit, is
mandatory.
The occlusion therapy should be continued till the
visual acuity of the amblyopic eye equalizes with the
sound eye or there is no further improvement of vision
following 3 months use of proper occlusion. Once the
visual acuity equalizes with the fixating eye, occlusion
therapy should not be stopped immediately. If
stopped immediately there is chances of recurrence
of amblyopia.
A special form of occlusion therapy used in cases
of eccentric fixation is inverse occlusion. As its name
suggests, occlusion is primarily given to the amblyopic
eye. von Noorden recommends that inverse occlusion
may only be tried in the initial phase of therapy of
eccentric fixation in children older than 5 years of age,
but in children below the 5 years of age conventional
occlusion therapy is preferred. In children older than
5 years, inverse occlusion of the eye with eccentric
fixation is given along with pleoptic therapy. Once
fixation becomes central in the amblyopic eye one can
switch over to conventional occlusion to reinforce the
central fixation and further improve vision of
amblyopic eye.
Penalization Therapy
The principle of penalization is the use of lenses or
drugs to blur the visual acuity of the better eye and to
augment the visual acuity of the amblyopic eye. This
method of amblyopia therapy is beneficial in children
who do not tolerate occlusion therapy.
Types of Penalization
Distance penalization Overcorrection of the better eye
(in a hypermetropic patient) or undercorrection (in a
myopia eye), so as to force the amblyopic eye to be
used for distance. This is the method most commonly
used for penalization.
923
Near penalization Use of cycloplegics in the better eye
with full correction to the amblyopic eye.
Total penalization Addition of strong convex lens to
the better eye, so that amblyopic eye sees for both
distance and near.
Pleoptics
Basic aim is to suppress the eccentric fixating area with
simultaneous stimulation of the fovea. Pleoptic
therapy is limited adolescent and cooperative patients.
As long-term results are not encouraging, this method
of therapy is gradually becoming obsolete.
CAM Visual Stimulator
Campbell and his coworkers in Cambridge designed
this apparatus to treat amblyopia by intense visual
stimulation for short period of time. Cortical cell
responds to specific line orientations and to certain
spatial frequencies. Therefore different spatial
frequencies ensured that large range of cortical
neurons was stimulated. Grating of different contrast
and spatial frequencies are rotated in front of
amblyopic eye, while the other eye is occluded for 7
minutes. The results are not so encouraging.
BIBLIOGRAPHY
1. Burian. Use of bifocal spectacles in the treatment of accommo-
dative esotropia. Br Orthopt J 1956;13:3.
2. Goldstein JH. The role of miotics in strabismus. Surv
Ophthalmol 1968;13:31.
3. Guibor GP. The use of atropine in the treatment of motor
defects. In Allen JH (Ed): Strabismus Ophthalmic Symposium
St. Louis: The CV Mosby Co, 316, 1950.
4. Kamlesh et al. Levodopa/carbidopa in treatment of
amblyopia proceedings of AIOS New Delhi, 1997.
5. Miller JE. A comparison of miotics in accommodative
esotropia. Am J Ophthalmol 1960;49:1350.
6. Rativ E. Results obtained with red filter method in the
treatment of amblyopia with eccentric fixation. J Pediatr
Ophthalmol 1966;3:28.
7. Ron A. Penalization treatment of amblyopia: A follow-up
study of 2 years in older children. J Pediatr Ophthalmol Strabis
1982;19:137.
8. Schlossman A. Prognosis, management and results of pleoptic
treatment. Int Ophthalmol Clin 1961;1:829.
9. Scott A. Botulinium toxin injection of the eye muscles to
correct strabismus. Trans Am Ophthalmol Suc 1981;79:734.
10. Scott AB, Rosenbaum A, Collins CC. Pharmacological
weakening of extraocular muscles. Invest Ophthalmol Vis Sci
1973;12:924.
11. Scott WE. Office Use of Prisms in Symposium on Strabismus:
Transactions of the New Orleans Academy of Ophthal-
mology. St. Louis: The CV Mosby Co. 1978;91.
 Chapter 121

Surgical Treatment of Strabismus

Vinita Singh

INTRODUCTION single vision. Strabismus surgery has primarily a

“mechanical” effect, to alter the position of the globe
Strabismus surgery is one of the frequent types of
in the orbit and to realign the visual axes. It has no
ophthalmic surgery, second only to cataract extraction.
direct “sensory” or “innervational” effects. These are
Yet the variability in the surgical results, which is
secondary to binocular sensory adaptations of the eyes
seemingly beyond the surgeon’s control is a cause of
to the surgically created new stimulus situation, which
dilemma amongst most ophthalmologists. Some of
is expected to restore comfortable binocular single
this variability can rightly be attributed to unpredic-
vision and strengthen binocular functions. When
table patient responses, but a substantial amount can
functional recovery is difficult or impossible then
be attributed to measurement and judgment errors
cosmetic reasons call for a surgical intervention.
and variations in surgical technique. With advances
In order to avoid postoperative frustration, the
in diagnostic methods, better understanding of
purpose and achievable realistic goal should be clearly
different forms of strabismus, functional interplay
defined prior to surgery. While a successful cosmetic
between various muscle groups, availability of better
appearance can almost always be obtained with
and safer suture materials and needles, surgical
strabismus surgery, functional cures are more difficult
procedures have changed remarkably specially with
and sometimes impossible.1 Complete functional cure
reference to performance of bolder surgery and an
implies freely mobile eyes, with ability to maintain
attempt to correct large deviations and combined
ocular alignment in all directions of gaze and have
horizontal and vertical deviations with one stage
binocular single vision with fusion and stereopsis.
procedure. Use of adjustable sutures permits bolder
Achievement of at least some degree of binocularity
and more accurate surgery in unpredictable situations.
is an important part of the goal, both functionally and
Strabismus surgery is distinct, firstly because
cosmetically, for the ability of the patient’s both eyes
movement of the tissue is the essential component of
to work together stimulates them to remain aligned
the final goal of the surgery and, secondly, because at
and hence ensures stability of the surgical result.
present time and in the near future there is a small
chance that further surgery may be necessary. It is INDICATIONS FOR SURGERY
therefore important to design the surgical technique
Surgical treatment should be considered in carefully
so as to avoid excessive restrictions on the eye,
selected patients, in whom the deviation precludes the
minimally disturb the strength and leverage of
development of binocular functions or interferes with
muscles, preserve tissue planes, and maintain a record
comfortable binocular vision in the practical field of
of preoperative details thus allowing necessary
fixation.
surgical reintervention to be easily accomplished.
Strabismus surgery is indicated to restore ocular
alignment for functional as well as cosmetic reasons.
AIMS OF STRABISMUS SURGERY
Misalignment of the eyes can be a considerable social
The aim of surgery for strabismus is to restore the and emotional handicap, and strabismus surgery for
alignment of the visual axes so as to facilitate binocular cosmetic reasons alone is certainly justified. It is also
 Chapter 121: Surgical Treatment of Strabismus
indicated to correct abnormal compensatory head
postures, even in the absence of obvious strabismus.
PATIENT EVALUATION
When the need for surgery has been established,
evaluation of the patient is done for the following:
i. To define the fusion potential and the achievable
realistic goal in terms of stability of ocular align-
ment, binocularity, and restoration of ocular moti-
lity. This should be clearly communicated to the
patient and the attendants, so as to avoid postope-
rative frustrations to both, the surgeon as well as
the patient.
ii. To determine the most appropriate surgical
approach. To alter the position of the eyes, the
action of a muscle can be weakened, strengthened
or modified by altering its position on the globe.
These procedures may be performed singly or in
combination. To determine the most appropriate
surgical approach and muscle or muscles to be
operated upon, it is necessary to carefully assess
all the clinical findings and then decide the type
and amount of operation on an individual basis
rather than routinely applying one or the other
procedure.
The following factors influence the above:
The age of onset, presentation, and duration of squint It is
generally agreed that children with congenital strabis-
mus should be treated as early as possible if there is
to be any chance of gaining even limited binocular
vision.1,2 When strabismus is acquired or intermittent,
the chances of regaining at least some binocular vision
with appropriate treatment are generally higher.
The potential for restoration of binocular vision
decreases with increased duration of strabismus.
Untreated infants lose this potential quickly, whereas
strabismic adults and older children retain at least
some potential for binocular vision for many years.
Visual acuity Uncorrected and corrected visual acuity
should be evaluated for each eye separately as well as
binocularly. All attempts should be made to attain
equal or near equal vision in both eyes. This is impor-
tant for achieving predictable and stable surgical
results.2 In the presence of intractable amblyopia the
surgical results are unpredictable, for the eye may
have a tendency to revert back to its original position,
or the deviation may get over corrected. In such
patients the aim is to have a cosmetically acceptable
residual angle which is slightly convergent.
925
Binocular functions Extraocular muscle surgery can
only restore the alignment of the two eyes but the most
important component of the neuromuscular apparatus
that maintains this position is the binocular fusion
faculty. If the estimate of the state of fusion faculty,
called the fusion potential, is high then even an
approximate surgical correction may be sufficient to
achieve stable ocular alignment with binocular single
vision. If on the other hand the estimate of the fusion
potential is low then the postoperative ocular
alignment may be unpredictable and unstable.3
The fixating eye Preoperatively, wherever possible, an
attempt should be made to make the patient able to
alternate. If monocular surgery is planned in the
absence of amblyopia then it is preferred to operate
on the dominant eye, as this is the eye that governs
the binocular motor reflexes.3
Angle of strabismus Although the degrees of correction
per millimeter of muscle surgery is variable, the
amount and behavior of the preoperative angle of
strabismus is an important deciding factor for the
surgical approach and the amount of surgery. The
deviation is measured for near and distance fixing each
eye, and in various directions of gaze. It is attempted
to correct the deviation present when the preferred
eye is used, as this is the eye that governs the
innervations being sent to each eye.3 Medial rectus
surgery is preferred if the near deviation is signifi-
cantly more and lateral rectus surgery is considered
when the distance deviation is more. A or V pattern
with horizontal strabismus can be corrected by combi-
ning recess/resect surgery with up/down displace-
ment, slant procedures or oblique muscle surgery.
Surgery is aimed to correct the basic deviation,
regardless of whether it is intermittent or constant.2
Refraction Any clinically significant refractive error is
corrected and a period of several weeks is allowed for
adaptation to the new optical correction before
determining the amount of deviation that needs to be
corrected surgically.1
Ocular motility A preoperative estimation of both
uniocular (ductions) and binocular (versions)
movements is necessary to plan the surgery so as to
normalize the excursions of the eyes and as far as
possible to symmetrize and restore ocular alignment
in all directions of gaze.2
Diplopia charting Diplopia charting is helpful in identi-
fying the areas of maximum diplopia, under or
overacting muscles and deciding the most appropriate
926 Section 7: Pediatric Ophthalmology Including Strabismus

surgical procedure which would restore binocular

single vision in maximum area of practical binocular
field.
Forced duction test Forced duction test is performed to
assess the passive movements. If it reveals mechanical
restrictions, not anticipated preoperatively, the
original surgical plan may have to be modified on the
table at the time of surgery.
It is obvious from the above account that due to
several variables affecting the surgical plan and
outcome, we cannot have a blanket formula applicable Fig. 121.1: Topographic arrangement of muscle origins in
to every patient. However, if surgery is planned on the annulus of Zinn (Right orbit)
the basis of individual findings in each patient, and
supported by appropriate pre and postoperative nasal orbital wall to reach the trochlea. It becomes
binocular training, then a high percentage of merely tendinous approximately 10 mm behind the trochlea.
immediate satisfactory cosmetic realignments would After passing through the trochlear pulley it courses
change into lasting good results. posteriorly and laterally to penetrate the Tenon’s
capsule about 3 mm nasal to the superior rectus. As it
ANATOMICAL CONSIDERATIONS passes under the superior rectus it fans out on its way
to its broad (7-15 mm) insertion onto the superior
Before discussing the surgical procedures it is
temporal quadrant posterior to the equator of the
necessary to consider some anatomical aspects that
globe (Figs 121.2 and 121.3). The broad insertion gives
are important for safety and success of extraocular
the superior oblique its three functions, viz. incyclo-
muscle surgery. As ocular motility is an important
torsion, depression, and abduction. The fibers anterior
outcome in strabismus surgery it is essential to know
to the equator cause incyclotorsion and those posterior
and respect the structures that allow it. The movement
to the equator cause depression and abduction.
of the eye within the orbit is brought about by six
Hooking the compact superior oblique tendon in the
extraocular muscles, four rectii and two obliques for
sub-Tenon’s space nasal to the superior rectus, prior
each eye. In addition, an intricate fascial network,
comprising of Tenon’s capsule, intermuscular septum,
and muscle capsule separates the globe from the
orbital fat and provides smooth slippery surfaces for
free movement of the globe within the sub-Tenon’s
space.4 Scarring of any of these structures will result
in restricted motility. Let us first study the location of
the extraocular muscles on the globe and the tissue
planes that must be passed to reach them and restored
during surgery so as to minimize complications and
allow free ocular motility.

Extraocular Muscles
The four rectii originate in the orbital apex at the
annulus of Zinn (Fig. 121.1), then pass forward though
the orbital fat and sub-Tenon’s space and insert onto
the sclera. The usual insertion width and limbus to
insertion distance of the extraocular muscles are
illustrated in Figure 121.2.
The superior oblique is the longest and the thinnest
extraocular muscle. It originates from the Annulus of Fig. 121.2: Sites, shapes and average sizes of insertions of
Zinn (Fig. 121.1) and then courses forward along the extraocular muscles of the right eye
 Chapter 121: Surgical Treatment of Strabismus 927

Fig. 121.4: Inferior view of right orbit

Fig. 121.3: Superior view of right orbit

to its fanning out will prevent the risk of incomplete

capture of the tendon.5
The inferior oblique originates from the anterior
nasal orbital floor just posterior to the orbital margin
and passes posteriorly and laterally, penetrating the
Tenon’s at the lateral border of the inferior rectus. In
the sub-Tenon’s space it continues in the same
direction around the globe (Fig. 121.4), passing under
the lateral rectus to reach its insertion into the sclera
just anterior to the macular area (Fig. 121.2). The poste-
rior fibers are responsible for elevation and abduction
and the anterior fibers for excyclotorsion.
Fig. 121.5: Fascia covering the eye and extraocular muscles
Fascial Coverings
The fascial coverings around the globe and extraocular performed on the anterior portion of the muscle
muscles comprise of the Tenon’s capsule, inter- contained within the sub-Tenon’s space.4
muscular septum, muscle capsule, and orbital fat
(Fig. 121.5). Intermuscular Septum
The intermuscular septum is a sheet of thin trans-
Tenon’s Capsule
parent, avascular tissue extending from a muscle’s
Tenon’s capsule is a dense white avascular fascial layer capsule to the capsule of adjacent extraocular muscle.
of elastic connective tissue surrounding the eye and It lies between the anterior Tenon’s capsule and the
extraocular muscles in the anterior orbit, and the globe sclera and forms a fascial plane joining the extraocular
in the posterior orbit. The extraocular muscles muscles. Anteriorly it fuses with the Tenon’s capsule
originate outside the Tenon’s capsule and penetrate about 3 mm from the limbus. This combined fascial
it prior to the insertion onto the globe. The rectii enter plane then fuses with the conjunctiva about 1 mm from
the Tenon’s posterior to the equator while the obliques the limbus. This has important implications for the
enter it anterior to the equator of the globe. The muscle strabismus surgeon.4 While doing the forced duction
capsule is attached to a sleeve of Tenon’s capsule at test it is safer to grasp the conjunctiva near the limbus
its point of penetration, allowing movement of the where a stronger structure exists. This minimizes the
muscle through the Tenon’s capsule. The inner surface chance of conjunctival tear. An incision at the limbus,
of the Tenon’s capsule is smooth and opposed to the where these three structures are fused, will imme-
sclera, posteriorly, and muscle capsule and inter- diately expose the correct plane for hooking the
muscular septum, anteriorly. Strabismus surgery is muscle. Whereas in a posterior incision the conjunc-
928 Section 7: Pediatric Ophthalmology Including Strabismus

tiva, Tenon’s and the intermuscular septum will have
to be passed separately to reach the correct plane for
extraocular muscle surgery.
Muscle Capsule
Surrounding each muscle and its tendon is an
avascular connective tissue capsule. It provides a
smooth surface to the extraocular muscle. Its inner
surface is associated intimately with muscular blood
vessels. Opening of the muscle capsule may result in
hemorrhage in the surgical field; it would also leave
an exposed muscle surface thus increasing the risk of
adhesions.
There are attachments between the muscle capsules
of the oblique and the rectus muscles as they cross.
The medial rectus, the strongest extraocular muscle,
has a relatively straight course, and has no direct
capsular attachment to an oblique muscle. It is,
therefore, at the greatest risk of slipping back into the
posterior orbit through the Tenon’s.4
A potential space exists between the muscle and
its capsule. It is therefore possible for a muscle to slip
within its own capsule. Care must therefore be taken
to pass the muscle suture through the entire thickness
of the muscle substance rather than superficially
where it may engage only the muscle capsule and
subsequently result in slippage of the muscle.7
Check Ligaments
These are sheets of elastic connective tissue extending
from the muscle to the overlying Tenon’s. These are
seen easily during surgery when Tenon’s capsule is
retracted to expose a rectus muscle that has been
hooked. These have to be severed to allow free
mobility of the muscle postoperatively in its altered
position.2
adhesions, causing the eye to be pulled in a deviated
position with restricted motility.8 Subsequent surgery
to restore the fascial planes is difficult and almost
always unsuccessful.
Capsulopalpebral Fascia
and Ligament of Lockwood
It originates from the terminal fibers and tendon of
inferior rectus, runs forward and divides into two
around the inferior oblique, fuses with the orbital sep-
tum prior to its insertion onto the tarsus of the lower
lid (Fig. 121.6). It acts as a lower lid retractor.9 While
operating on the inferior rectus, failure to sever its
attachments to the capsulopalpebral fascia will result
in a change of the height of the lower lid leading to a
change in the width of the palpebral aperture.
The blending of the sheaths of the inferior oblique
and inferior rectus muscles and their extensions to the
sheaths of medial and lateral rectus, tarsal plate of
lower lid and orbital septum forms a suspending
hammock to support the eyeball and is termed
suspensory ligament of Lockwood.10
SURGICAL TECHNIQUES
Anesthesia
The extraocular muscles can be operated upon
painlessly under local anesthesia, hence general
anesthesia is required only for small children and
apprehensive or nervous older children and adults.
After topical anesthesia with 4 percent lidocaine, an
equal mixture of 2 percent lidocaine with adrenaline
and 0.5 percent Bupivacaine with hyaluronidase 25
IU/mL is infiltrated in the retro or peribulbar space.
Facial block is usually not required.

The Orbital Fat

The orbital fat and its framework of connective tissue,
septa, provides a firm cushion to support the globe
and yet allows it to move freely within the orbit.
Anteriorly it comes forward to about 10 mm of the
limbus. The Tenon’s capsule separates it from the
muscle capsule and the intermuscular septum. An
inadvertent opening of the Tenon’s more than 10 mm
from the limbus will allow the orbital fat to herniate
in the sub-Tenon’s space, where it tends to incite
intense inflammatory reaction resulting in scaring and Fig. 121.6: The capsulopalpebral fascia
 Chapter 121: Surgical Treatment of Strabismus
Exposure of the Muscle
The eye is rotated in the direction opposite to the
muscle to be operated, with the help of one or two-
stay sutures at the limbus or a conjunctial fixation
forceps. The muscle insertion is approached through
transconjunctival incisions directly near the muscle
insertion or indirectly in the fornix or in the limbus
(Fig. 121.7). Each has its advantages and disadvan-
tages.
At the limbus the three tissue planes the conjunc-
tiva, Tenon’s and the intermuscular septum are fused
into one hence can be dealt by a single incision; besides,
the limbal incision, described by von Noorden,11 has
the added advantage that the bare sclera closure or
conjunctival recession can be performed. As the limbal
approach involves no or minimal dissection between
the conjunctiva and the Tenon’s, it incites minimal
tissue reaction postoperatively. In the more posterior
conjunctival incision, described by Swan and Talbot,12
the Tenon’s has to be incised and restored as a separate
layer. It has the advantage of simplicity, in that it
provides easier access and better exposure for poste-
rior surgery and muscle displacement procedures and
the disadvantage that it requires meticulous identifi-
cation and restoration of tissue planes in order to
prevent unwanted adhesions and a bad scar. The
fornix incision described by Parks,13,14 has the advan-
tage that it does not leave a scar visible in the palpebral
aperture, causes least discomfort to the patient, allows
three adjacent muscles to be approached through one
incision, in fact all the six extraocular muscles can be
tackled through two fornix incisions (the inferior
rectus, lateral rectus, and inferior oblique through the
lower temporal fornix and the superior rectus, medial
rectus and superior oblique through the upper nasal
fornix) and permits any necessary subsequent surgery
to be comfortable, as it leaves no conjunctival or
Tenon’s scar directly over the muscle. It has the
disadvantage of complexity, as it requires identifi-
cation and meticulous dissection of tissue planes.
After the sub-Tenon’s muscle plane has been
reached, the muscle along with its capsule is hooked.
A second hook is passed under the insertion from the
other side to ensure that the complete muscle is
engaged. The insertion is cleared. The muscle is stret-
ched on the hook and freed by severing its fascial
connections as far back as the white condensation of
the Tenon’s appears. The check ligaments are already
severed by dissection up to this point. Usually this
point is 9-10 mm behind the muscle insertion. 15
929
Fig. 121.7: Conjunctival incisions for
extraocular muscle surgery
Dissection beyond this point may result in herniation
of the orbital fat. The muscle should be freed of its
fascial connections without disturbing its capsule.
While clearing the superior rectus muscle care must
be taken to avoid injury to the levator muscle and the
superior oblique tendon and while clearing the inferior
rectus care must be taken to free it from the fascial
connections and the capsulopalpebral fascia in order
to maintain the level of the lower lid.
Once the muscle and its insertion has been isolated
and cleared the required surgical procedure can be
performed.
SURGICAL PROCEDURES
The horizontal rectii are by far the most commonly
operated extraocular muscles, the vertical rectii and
the oblique follow. The surgical procedures on the
extraocular muscles can be grouped as follows:
1. Weakening operations
2. Strengthening operations
3. Operations to modify the action of an extraocular
muscle.
Weakening Operations
Since Dieffenbach introduced tenotomy to weaken the
action of an extraocular muscle in 1839, great strides
have been accomplished in the field of surgery on
extraocular muscles. The unavoidable outcome of
tenotomy was a large number of overcorrections with
little to undo it. Except for unusual cases, tenotomies
have been largely replaced by recessions.
930 Section 7: Pediatric Ophthalmology Including Strabismus

Recession (Figs 121.8A to C)

The muscle insertion is secured by sutures to a
predetermined location, on the sclera, behind its
original insertion. Unlike free tenotomy this procedure
permits grading the weakening effect, prevents
excessive retraction of the muscle and leaves the
muscle in a position that it is available for any neces-
sary subsequent surgery. The weakening effect of
recession is due to loss of contractile force due to
shortening of the muscle, reduction in the arc of
contact and necessary disruption of some of the
supporting structures during surgery.2
Recession of rectii The recession of the medial rectus
should be restricted to a maximum of 6 mm. Larger
recessions of 6 to 8 mm are often required on the lateral
rectus. In adults with large exodeviations exceeding
70 PD as much as 10 to 12 mm lateral rectus recession
can be done with nil to minimal restriction of
abduction, postoperatively. Even though this places
the insertion behind the anatomic equator there is
sufficient arc of contact to allow the muscle to exert
rotational force. To retain sufficient arc of contact and
to ease placement of sutures while performing large
recessions hang back (HB) and hemihang back (HHB)
techniques of recession can be adapted.
Recessions of 5 to 6 mm can be safely performed
on the vertical rectii. Provided necessary precautions
are taken and the amount of surgery is not excessive,
the procedure is effective and free from complications.
Due to close relationship between the superior rectus
and levator of the upper lid and between the inferior
rectus muscle and capsulopalpebral fascia of the lower
lid, great care must be taken in dissecting the muscles
from all the fascial connections.
Recession of inferior oblique Weakening of the inferior
oblique can be achieved by recessing it to a point 3-4
mm inferolateral to the lateral border of inferior rectus Figs 121.8 A to C: Recession of left medial rectus
insertion (Figs 121.9A and B). The reduction in a
hyperdeviation by this procedure is 8 to 12 PD. It can a new focal insertion anteriorly. At this new insertion
also be recessed to a point 8 mm inferoposterior to the superior oblique no longer acts as a depressor.
the lower border of the lateral rectus insertion. Postoperative limitation of depression has been
Selective weakening of its elevation action can be observed with recession of the superior oblique.17 It
achieved by anteroplacement of its insertion.16 is therefore important to replace the tendon posterior
to the equator, which is difficult.
Recession of superior oblique Though weakening the
superior oblique by recession, has the theoretical Hangback and hemihang back recession 18 Both these
advantage of providing a graded effect it has the techniques of recession weaken the action of an extra-
disadvantage that it changes the basic mechanics of ocular muscle. The muscle is recessed and suspended
its actions. It collapses its broad insertion and creates with the help of sutures in both procedures. In HB the
 Chapter 121: Surgical Treatment of Strabismus 931

Fig. 121.10A: Hangback recession of left lateral rectus

Fig. 121.9A and B: Right inferior oblique recession

sutures pass through the original insertion stump and

in HHB from the sclera posterior to the insertion, half
way between the original insertion and the proposed
site of recession (Figs 121.10A and B). 6-0 vicryl or
ethibond sutures can be used. Both these procedures
have the advantage that the arc of contact is minimally
disturbed and the risk of scleral perforation is minimal
as the posterior awkward suture placement is avoided. Fig. 121.10B:Hemihang back recession of left lateral rectus
Larger recessions can therefore be safely performed
without disturbing the ocular movements.

Marginal Myotomy
A marginal myotomy is performed by severing the
muscle fibers at the upper and lower borders (Fig.
121.11). It effects actual weakening of the muscle by
reducing the number of contractile elements without
changing its arc of contact. This procedure has been
found highly effective in further reducing the action
of an already maximally recessed rectus muscle or one
that cannot be recessed. The reduction of the deviation
by this procedure, on a rectus muscle, has been Fig. 121.11: Marginal myotomy
estimated to be about 10 to 16 PD. This procedure can
be done on the superior and inferior oblique muscles
Myectomy of a inferior oblique muscle at its origin
also.16,17,19
through a skin incision has largely been abandoned.
Myectomy or tenotomy of an inferior oblique muscle
Tenotomy or Myectomy
is usually performed through a conjunctival incision
Free tenotomy on rectii is performed only in unusual about 8 mm from the limbus, in the inferotemporal
cases such as lateral rectus tenotomy in III N paralysis quadrant between its insertion and the inferior rectus
and inferior rectus tenotomy in thyroid myopathy. insertion. Though the choice as to the best procedure
Tenotomy is also performed as a weakening proce- for inferior oblique weakening is unclear, a recession
dure on the oblique muscles in patients with cyclo- of the inferior oblique is preferable in most cases, as
vertical paralysis, A/V patterns, or primary oblique this procedure permits subsequent handling of the
muscle overaction. muscle if need arises.1 An overcorrection following
932 Section 7: Pediatric Ophthalmology Including Strabismus

weakening of the inferior oblique is rare, but may

occur if performed on a normally or minimally
overacting muscle.2
Tenotomy of the superior oblique muscle is usually
performed midway between the insertion and the
trochlea where the tendon is compact, through a
conjunctival incision in the upper nasal quadrant
medial to the superior rectus insertion (Fig. 121.12). A
weakening operation on an overacting superior
oblique reduces hypodeviation in its field of action. It
is also effective in reducing incyclotropia and A-
pattern.20 Fig. 121.12: Tenotomy of right superior oblique

Posterior Fixation Suture (Faden Operation)

Posterior fixation suture (faden operation) or retro-
equatorial myopexy. It is performed by suturing a
rectus muscle to the sclera behind the equator (Fig.
121.13A).
In principle this decreases the leverage between
the center of rotation and the line of pull by shortening
the effective arc of contact in the direction of action of
the muscle producing a selective weakening in the
direction of primary action of the muscle without
disturbing the ocular balance in other positions of gaze
(Fig. 121.13B).2,21 Because this procedure does not
affect the primary ocular position, it must be combined
with a recession where there is need to correct a
deviation in the primary position.
The posterior fixation suture has been successfully Fig. 121.13A: Posterior fixation suture of the
tried wherever a selective weakening, in the direction right superior rectus
of action of the muscle, is required such as a paretic
strabismus on the yoke muscle, dissociated vertical
deviations, nystagmus blockage syndrome, conver-
gence excess type of esotropia, and Duane’s retraction
syndrome.

Botulinum Toxin to Weaken the Action of a Muscle

Weakening the action of an extraocular muscle by
chemically denervating the motor nerve terminals is
an accepted method of treatment in selected patients
of strabismus. Botulinum toxin A is injected trans-
conjunctivally under local anesthesia, into the belly
of the extraocular muscle about 2.5 mm from its
insertion. This approximates the location of the motor
end plate; here it inhibits the release of neuro- Fig. 121.13B: Posterior fixation suture of the SR muscle
transmitter acetylcholine leading to functional
denervation of the extraocular muscle. An electro-
myography (EMG) needle connected to an audible needle.
EMG amplifier is helpful in guiding the injection Two nanograms of botulinum toxin reconstituted
 Chapter 121: Surgical Treatment of Strabismus 933
in nonpreserved saline in the dilution of 1-12 units/
0.1 mL is the commonly used dose. The drug induced
weakness or paralysis of the extraocular muscle lasts
for 2-8 weeks or more. This usually results in
permanently changed ocular alignment as the injected
muscle lengthens and its antagonist contracts.
Extrajunctional actetylcholine receptors may develop
in the atrophied muscle leading to reinnervation,
reversal and eventual recovery of the drug induced
paralysis. Repeat injections can be given when
necessary.22
A deviation of less than 35 PD can be corrected to
within 10 PD or less in most of the patients. Over Fig. 121.14A: Resection of left lateral rectus
corrections are rare. The results in esotropia are
generally better than in exotropia. Botulinum toxin
has been successfully used in selected patients of
paralytic squints, postoperative adjustment of under
or overcorrections, esotropia of less than 40 PD in poor
surgical candidates and in strabismus following retinal
detachment surgery.22,23

Strengthening Operations
The action of a muscle can be enhanced by shortening
it so that the tension and hence the pull caused by it
increases. This can be achieved in a controlled manner
by resecting or plicating a precalculated length of the
muscle or its tendon; it can also be achieved by Fig. 121.14B: Left lateral resection
advancing the muscle insertion. Excessive resection
may mechanically restrict the movement of the globe
in the opposite direction and, therefore must be
avoided.

Resection Operation
A precalculated length of the muscle is resected and
the cut end is stitched to the site of the original
insertion (Figs 121.14A to C). When combined with a
recession of the ipsilateral antagonist it has a
stabilizing effect on the result and enhances the
amount of correction. Though it improves the action
of the resected muscle, resection alone has little or no Fig. 121.14C: Resection of left lateral rectus
effect on the primary ocular position.1,2 Resection of
one or both medial rectii has therefore been success- Vertical rectus muscles Resection procedures can be
fully used for treatment of selected cases of primary performed on the vertical rectii with precautions
convergence insufficiency. similar to that for recession techniques. The minimal
and maximal amounts of resection are 4 mm and 6
Horizontal rectus muscles The minimal amount of
mm, respectively.
resection on the horizontal rectii is 4 mm and the
maximal amount is 7 mm on the medial rectus and 10 Inferior oblique muscle Due to the proximity of its
mm on the lateral rectus. insertion to the fovea, resection procedure on the
inferior oblique muscle is technically difficult and
934 Section 7: Pediatric Ophthalmology Including Strabismus
risky. Besides, the procedure has been found to be
ineffective in improving ocular motility in the field of
action of this muscle; it is therefore not recommended.
Alternatively, whenever the need for such a surgery
is felt weakening of the yoke muscle, i.e. the superior
rectus of the other eye has been found to be effec-
tive.2,15
Superior oblique muscle Shortening of the superior
oblique tendon by plication is effective in improving
depression of the adducted eye and counteracting
excyclotropia. It is preferable to do plication of the SO
tendon (tenoplication) through a transconjunctival
route in the upper temporal quadrant (Fig. 121.15).
The plication can be performed in the upper nasal
quadrant also, but the risk of capture of the tuck in
the trochlea and restriction of oblique elevation
postoperatively is higher. To prevent this the plication
should be done near the nasal border of the superior
rectus while using the upper nasal approach.15
Selective strengthening of the intorsion action can
be achieved by selective plication of only the anterior
fibers of the SO tendon.15
Combined Weakening-Strengthening Operations
Weakening of a muscle combined with strengthening
of its antagonist in the same operative session adds
greatly to the effectiveness of each procedure and
postoperative stability of the ocular alignment. Resec-
tion alone is usually not enough for treatment of
manifest tropia. The corrective effect of a resection
procedure on the ocular deviation seen in the
immediate postoperative period gradually reduces
during the next 6 weeks.
Adjustable Sutures
Adjustable sutures can be placed after recessing or
resecting a muscle. Several techniques of placing
adjustable sutures have been described.24,25 After
suturing the muscle to the sclera the sutures are
brought forward and tied in a bow-tie fashion so that
the effect of surgery can be modified in the immediate
postoperative phase by pulling on or loosening the
sutures, the former being simpler. It is therefore
desirable to leave the muscle more posterior than
finally desired so that any adjustment will involve
tightening the sutures and advancing the muscle. To
leave the suture loose for readjustment in a resection
procedure, more than the precalculated amount of
Fig. 121.15: Tenoplication of right superior oblique
muscle, has to be resected. Adjustable sutures are
therefore, better used with a recession procedure.
An attempt to modify the result of surgery in the
immediate postoperative phase implies that the imme-
diate postoperative ocular position is predictive of the
final outcome. This however, is not the case except
for large under and overcorrections that often tend to
persist. Moreover, precise evaluation of ocular
alignment and suture adjustment in the immediate
postoperative phase is difficult and impractical in
children. Their routine use is therefore not recom-
mended, but they may be of value in adults and older
children with an added factor for unpredictability of
outcome such as previous operations, scarring,
contracture or endocrine myopathy.
Operations to Modify the Action of an Extraocular
Muscle (Muscle Transposition Operations)
The action of an extraocular muscle can be modified
by shifting its insertion so that the direction of the pull
caused by it is altered. The raising or lowering of
horizontal rectus insertions and nasal or temporal
transposition of vertical rectus insertions are perfor-
med in selected cases for correction of A/V patterns,
vertical deviations, and for enhancing the effect of
horizontal corrections. The raising or lowering of a
horizontal rectus insertion has a weakening effect on
its horizontal action in up or down gaze, respectively,
in favor of its vertical action in the direction of the
shift.26 The amount of up or down displacement may
vary from 5 mm to full tendon width (about 11 mm)
in nonparalytic squints to transfer of a rectus insertion
to the insertion of another muscle in paralytic squints.
In nonparalytic squints a 5 mm up or down displace-
 Chapter 121: Surgical Treatment of Strabismus 935
ment of horizontal rectii has been found to be effective
with no torsional effects or limitation of ocular
motility.

Paralytic Strabismus
Muscle transpositions are effective in restoring some
degrees of motility in the field of action of the paretic
muscle, for example, some restoration of elevation by
transposition of medial and lateral rectus insertions
to that of superior rectus in elevator paralysis (Fig.
121.16A) and transposition of superior and inferior
rectus insertions to the lateral rectus in VI nerve palsy. Fig. 121.16A: Up-transposition of medial and lateral rectus
To overcome the risk of anterior segment ischemia, for elevator paralysis right eye
while combining muscle transpositions with resection
of the paralyzed muscle, partial tendon widths can be
sutured to the paralyzed muscle (Figs 121.16B and C).
This is known as the Jensen’s procedure.
In desperate situations of IIIrd nerve palsy the
tendon of the superior oblique can be used to aid
adduction by transplanting it either to the medial
border of the superior rectus or to the medial rectus
after freeing it from the trochlear tunnel. The former
procedure is simple but results in excessive intorsion,
the latter requires extensive dissection.15
These procedures should not be performed if there
is limitation of passive movement and mechanical
factors are responsible for the limitation of movement. Figs 121.16B and C: Transposition of lateral halves of SR
and IR to LR in right LR paralysis (Jensen’s procedure)
Correction of A/V Patterns
the medial rectii have to be shifted toward the apex
The muscle utilized for correction for A/V patterns
and the lateral rectii have to be shifted toward the base
depends upon the over or underacting muscle respon-
of the A or V (Figs 121.17A and B).
sible for the pattern of the deviation (Fig. 121.17A) ‘A’
While doing recess/resect procedures on the
exotropia is the one that needs to be treated most
horizontal rectii, A-V patterns can be corrected by
frequently. The A/V patterns respond satisfactorily
weakening or strengthening the upper and lower
to weakening procedures on the overacting superior
borders by different amounts and suturing the muscle
and inferior obliques respectively.2,16,20 The other
in a slanting manner (Fig. 121.17B).27 The direction of
muscles are utilized when obvious oblique over or
the slant depends upon the pattern of the deviation.
underactions are not present.
The muscle insertion is made parallel to the limbs of
For correction of A/V patterns, the insertion of a
the A or V (Fig. 121.17C).
horizontal muscle is moved in the direction in which
it is desirable to most decrease its horizontal action
and in the direction opposite that in which one wishes
its horizontal action to be more effective. 2,19 An
updisplacement of the lateral rectus results in a
relative decrease in its abduction action in the upgaze
and a reduction of V pattern, and a down displacement
to a reduction of A-pattern. Similarly an up or down-
displacement of the medial rectus results in reduction
of A or V-pattern, respectively. It helps to remember,
that to correct a vertical incomitance (A/V patterns) Fig. 121.17A: Etiology and correction of A-V patterns
936 Section 7: Pediatric Ophthalmology Including Strabismus
Fig. 121.17B: Correction of V esotropia
Fig. 121.17C: The placement of slanting insertions for
correction of A-V patterns
Anteroplacement of Obliques
The muscle insertion can be transposed so as to
selectively alter the action of a muscle. Antero-
placement of the obliques selectively weakens their
vertical action in favor of the torsional action.
Sagittalization by lateral and anterior advancement
of only the anterior fibers of the superior oblique
insertion (Fig. 121.18) enhances its torsional action
without affecting its depression action.15,19 These
procedures are not required very frequently but have
proven to be of value in carefully selected patients.
Use of Plastic Materials
Plastic materials such as supramid sheaths or tubes
are used during strabismus surgery in selected cases
for following purposes:
i. To prevent adhesions and preserve muscle
function after isolation of the muscle from scar
tissue in reoperations.2
ii. To add to the Tendon length. 4 to 7 mm long strip
of the silicone band is used as a sheath expander
Fig. 121.18: Anteroplacement of half of the
right superior oblique tendon
for elongating the superior oblique tendon in
Brown syndrome.28
AMOUNT OF OPERATION
The surgical results depend upon several variables
described earlier and on the surgical technique,
manner in which the muscle is exposed, how
thoroughly it is freed, how the muscle sheath is dealt
with, placement of sutures and other factors. Each
surgeon must therefore establish through experience
the approximate effectiveness of his technique. In
addition, a number of unknown mechanical and
innervational factors remain, so that an identical
surgical procedure on different patients may have
different results; hence the surgical strategy has to be
planned individually for each patient. Although the
surgical result and its stability is dependent upon
several variables and it is difficult to arrive at a
mathematical formula, it is essential to have some
guidelines as to what result to expect from a particular
surgery, in order to be able to plan the surgery to be
undertaken.
Surgery is planned with the aim of symmetrizing
the action of the extraocular muscles rather than
performing symmetrical surgery; hence ductions,
versions, gaze incomitance, and deviation for near and
distance fixation must be considered. The larger the
deviation the greater will be the effect of same amount
of surgery. In older children and adults larger
operations are required than in younger children with
a comparable deviation. Recession is more effective
than resection in reducing a deviation. A graded
combination of resection with recession has an added
mechanical advantage and a stabilizing effect on the
surgical result. Due to the difference in the anatomical
direction and the arc of contact of the horizontal rectii,
recession procedure is more effective when performed
 Chapter 121: Surgical Treatment of Strabismus
on the medial rectus and resection is more effective
when performed on the lateral rectus.19 The result of
surgery on the vertical rectii is more predictable. The
amount of correction also depends upon the strength
and the thickness of the operated muscle. It is expected
to get a correction of 3 to 5 PD and 3 to 4 PD per mm
of recession of medial and lateral rectus, respectively,
and 6 PD per mm recession of the vertical rectii, 2 to 3
PD and 2 to 4 PD per mm of resection of medial and
lateral rectus, respectively, and 4 PD per mm resection
of the vertical rectus.19
On the basis of clinical experience the following
guidelines have been found to be useful:
Horizontal Deviations
The amount of correction usually obtained by minimal
and maximal amount of bimedial or bilateral recession
is 15 to 20 PD and 30 to 40 PD, respectively,2 being
lesser by bilateral rectus recession. The amount of
correction usually obtained by minimal and maximal
amount of recess/resect operation in one eye is 20 to
25 PD and 40 to 50 PD, respectively,2 being lesser in
exodeviation. In consideration with other individual
variables Table 121.1 is helpful in planning the
surgery:
Cyclovertical Deviations
Small degrees (less than 8 PD) of hyper/hypotropia
can be safely ignored while operating on large
937
horizontal deviations. Comitant hypo or hyperdevi-
ations of 10 to 14 PD can be eliminated by raising or
lowering the insertions of the horizontal rectii while
performing surgery for horizontal deviation. 1
Adjustable sutures may be particularly helpful to
eliminate troublesome diplopia in down gaze due to
residual small tropias.
The results of surgery on the vertical rectii are more
predictable than on the horizontal rectii (Table 121.2).
Many methods for surgical correction of disso-
ciated vertical deviations have been tried, with
nonconsensus as to the best approach. Large (7-12 mm)
recessions of the superior rectus muscles with or
without a faden procedure have been found to be
effective.1,2 Large resections of the inferior rectus
muscles29 and recess-resect procedures on the vertical
rectus muscles30 have been tried with varying degrees
of success.
Overacting oblique muscles are weakened by one
of the appropriate procedures described earlier.
Weakening procedures on the superior and inferior
oblique muscles usually do not affect the horizontal
alignment in primary position.31,32 The surgery to
correct the oblique muscle over or underaction,
usually takes care of the associated cyclodeviation
also. In rare situations, when a cyclic deviation is
symptomatic in the absence of a vertical or horizontal
deviation, such as in cases of mild superior oblique
paresis, selective torsional effect can be obtained by

Table 121.1: Horizontal deviation (Individual variables)

Esodeviation Exodeviation
Surgery MR rec MR rec/LR res LR rec LR rec/MR res
Deviation
< 30 PD 5-6 mm OE 4 mm/5-6 mm OE 5-7 mm BE 5-7 mm/4-5 mm OE
4 mm BE
30-45 PD 5 mm BE 5-6 mm/6-7 mm OE 8-10 mm BE 7-8 mm/5-6 mm OE
> 45-60 PD 6-7 mm BE 5-7 mm/8-10 mm OE 10-12 mm BE 8-10 mm 5-7 mm OE
> 60 PD MR rec 5-6 mm BE+LR res 8-10 mm OE LR rec 8-12 mm BE + MR res 5-6 mm OE
or MR rec 5 mm BE+LR res 7-8 mm BE or LR rec 7-10 mm BE + MR res 5-6 mm BE
• When 3 or 4 muscle surgery is planned, it is preferred to proceed in a stagewise manner, particularly in younger patients.
• The amount of surgery on the medial and lateral rectii and which muscle to be tackled first is determined on the basis of near
and distance deviations, gaze, and vertical incomitance, if any.
• When persistent esotropia is associated with conjunctival fibrosis then MR recession may have to be combined with conjunctival
recession.
• If esodeviation is significantly more for near than for distance then bimedial recession may have to be combined with faden
on the medial rectii.
• For A-V patterns surgery may have to be modified as discussed in the text
938 Section 7: Pediatric Ophthalmology Including Strabismus
Table 121.2: Expected corrections
Amount of hypertropia Choice of surgery
15-20 PD SR rec 4-6 mm OE
or IO rec OE
20-30 PD SR rec 4-6 mm + IR res 4-6 mm OE
or SR rec 4-6 mm + IO rec OE
Alternating SR rec 5-7 mm OE/BE
sursumduction with faden if necessary
shifting only the anterior portion of the superior
oblique insertion, the sagittalization or modified
‘Harada-Ito’ procedure.1
Paralytic Squint
The aim of treatment in a case of paralytic squint is to
restore comfortable binocular vision, without the
necessity for adoption of compensatory head posture,
over as large an area of central and lower part of the
binocular visual field as possible, and to make the
ocular movements of both eyes as symmetrical and
equal as possible.
Surgical intervention is considered when the ocular
deviation becomes stationary that is there is no
regression or progression and the underlying disease
causing the palsy is no longer active.
The secondary effects of a paralysis or paresis of
an extraocular muscle are as follows:
i. Overaction of contralateral synergist (the yoke
muscle) with its hypertrophy.
ii. Overaction of the ipsilateral (direct) antagonist
due to unopposed action and secondary contrac-
ture.
iii. Inhibitional paresis of the antagonist of the
overacting synergist in the other eye.
The aim of surgery is to restore and symmetrize
ocular movements, to eliminate compensatory head
posture and restore ocular alignment as far as possible.
If a small residual deviation is unavoidable, then it is
better that it be in the upper and not in the lower or
central part of the visual field.
The surgery for paralytic squint is planned on the
basis of secondary over and underactions; one or
several of the following operations may have to be
performed in a stepwise manner:
i. Recession of the overacting contralateral syner-
gist.
ii. Recession of the overacting (or fibrotic) ipsilateral
antagonist.
iii. Strengthening of the weak, palsied muscle by
resection and/or transplanting tendons of adja-
cent muscles for example superior and inferior
rectus to the palsied lateral rectus (Fig. 121.16).
If there is no contracture of the ipsilateral
antagonist then the yoke muscle is weakened first,
whereas inthe presence of a contracture the ipsilateral
antagonist is weakened prior to tackling other
muscles.19 The amount of correction depends upon
the degree and duration of palsy and secondary effects
on other extraocular muscles.
Special Forms of Strabismus
A special therapeutic challenge exists in certain special
forms of strabismus. Some of these are Duane’s
retraction syndrome, superior oblique sheath syn-
drome, strabismus fixus, congential fibrosis syndrome,
and thyroid myopathy. Apart from their individual
features each of them has considerable amount of
restrictive element. The associated retraction and
palpebral fissure width changes add to the cosmetic
problem. Surgery usually fails to restore complete
ocular motility and binocular single vision over the
entire area of binocular field; it is therefore, indicated
only when there is a significant deviation in the
primary position or an uncomfortable compensatory
head posture. 33 The aim of surgery is to restore
cosmetic appearance, ocular alignment and bino-
cularity in primary gaze and as large area of visual
field as possible and to eliminate compensatory head
posture. The general principles for planning the
surgery are similar. The clinical evaluation of the
restriction is confirmed by a forced duction test and
surgery is done primarily to release the restriction and
then to restore the ocular alignment. Strengthening
the antagonist of a fibrotic or a cocontracting muscle
in an attempt to correct the ocular alignment, without
releasing the restrictive element is unlikely to give
satisfactory result; on the other hand, it may aggravate
the retraction and the cosmetic problem. For example,
in Duane’s retraction syndrome with limitation of
abduction, limitation and retraction of globe in
adduction, a positive forced duction test for lateral
rectus, medial rectus resection on an exotropic eye is
likely to enhance the retraction with no or minimal
effect on the ocular alignment whereas a medial rectus
recession on an esotropic eye may improve the ocular
alignment without any effect on the rectraction. A
recession of both horizontal rectii 34 graded in
accordance with the primary ocular position has been
 Chapter 121: Surgical Treatment of Strabismus
found to be effective in restoring ocular alignment in
primary position, eliminating compensatory head
posture and minimizing globe retraction. It has also
been found to be effective in controlling vertical
leashes (vertical slipping of tight muscles) often
associated with Duane’s syndrome.35 Satisfactory
results have been reported with posterior fixation
sutures with or without recession of the horizontal
rectii.36
The indications and aims of surgery for superior
oblique sheath syndrome are same as discussed above.
Dissection and release of a tight superior oblique
sheath has been found to have good but not lasting
results. 37 Superior oblique tenotomy with all its
disadvantages has therefore, been advocated.38 This
may lead to superior oblique paralysis in the long run,
requiring subsequent surgery to weaken the contra-
lateral inferior rectus.2 Recently there are reports of
satisfactory results with tendon lengthening proce-
dures.38
Suturing the Muscle to the Sclera
The muscle is restitched to the sclera at the desired
site by means of the preplaced muscle sutures at the
upper and lower borders of the cut edge (Fig. 121.8C).
An additional suture is used to secure the center of
the cut edge (Fig. 121.14C) and restore the natural
curve of the muscle insertion. While suturing the
muscle at the desired site a small 1.5 to 2 mm
superficial bite in the sclera is all that is necessary and
this avoids the danger of penetrating the globe. In a
resection procedure, a bite only through fibers left at
the original insertion stump is not enough and should
include the superficial sclera as well (Fig. 121.14B).
Closure of the Wound
It is preferable to close the Tenon’s capsule separately
using minimal absorbable sutures. Separate closure
of the Tenon’s ensures normal anatomical covering of
the sclera and prevents adhesions of the bulbar
conjunctiva to the sclera. Sometimes in a limbal
incision separate closure of the Tenon’s may not be
necessary. The conjunctiva should be closed accurately
taking care to avoid leaving exposed tags of Tenon’s
as these tend to form granulomas. 15 The suture
material for conjunctival closure is entirely the
surgeon’s choice. Absorbable sutures incite more
tissue reaction than nonabsorbable silk sutures, but
are preferred by some, particularly in small children,
939
as they do not have to be removed. However, the tissue
reaction with silk sutures is distinctly lesser and we
do not find their removal a problem.
Irrespective of the exposure, suturing and closure
techniques, it is important to obtain hemostasis, to
handle tissues with gentleness with regard for tissue
planes. This adds to the postoperative patient comfort
and success of the surgery.
Postoperative Care
Period of hospitalization after strabismus surgery
depends upon the time that the effect of general anes-
thesia lasts. Most in town patients, operated under
local anesthesia can leave the hospital the same day
and out of town patients can leave the next day.
Postoperatively the patient is examined 24 hours,
7 days and 6 weeks after surgery. Conjunctival sutures
are removed on the 7th postoperative day. Dressing
is kept on the operated eye for 24 hours. It may be
done for 48 hours in patients with bare sclera closure.
Patching of both eyes has no benefit and is very
distressing to the patient hence should not be done.
Topical corticosteroids plus antibiotics are used for
2 to 4 weeks postoperatively. Systemic antibiotics are
used for 3 to 5 days and anti-inflammatory drugs are
used as and where required.
Postoperatively the patient should wear the
necessary refractive correction as soon as the dressing
is removed. Minor adjustments in the spectacle power
postoperatively may help the patient to exercise better
binocular control and overcome small residual
deviations. Wherever planned, postoperative ortho-
ptics should be started as soon as the tissue reaction
has subsided, this is frequently within two days and
certainly within one week.
COMPLICATIONS
Preoperative
Preoperative complications during strabismus surgery
are few and mostly can be prevented or satifactorily
dealt with if proper care and respect for tissue and
tissue planes are exercised.
Excessive bleeding Excessive bleeding is usually not a
problem if appropriate surgical planes are identified.
If bleeding is a repeated problem with a surgeon then
careful self reassessment of the technique is called for
Occasionally excessive bleeding may result from
cutting a conjunctival vessel, attempting dissection
940 Section 7: Pediatric Ophthalmology Including Strabismus
between muscle fibers and muscles sheath or from
accidentally cutting into the muscle during exposure.
Sometimes the scleral muscle stump bleeds after the
muscle has been cut. When it does occur it can usually
be managed satisfactorily by proper sponging and
cautery. Control of bleeding is essential before
continuing with the operation since organization of
the hematoma and subsequent scarring will unfavo-
rably influence the surgical result.
Scleral perforation Scleral perforation is extremely rare
with the use of modern fine spatulated needles.
Usually the size and shape of the needles permit them
to perforate the sclera without causing retinal holes.
In case, it is suspected, the site should be examined
carefully by thorough indirect ophthalmoscopy
through dilated pupils.
Lost muscle Muscle may be lost due to a broken suture
or rarely by cutting it on the wrong side of the clamp.
Usually it can be grasped and resutured. If it has
slipped more posteriorly then it can usually be grasped
through the opening in the muscle sheath. While
looking for a posteriorly slipped muscle do not look
back along the globe itself for that is not the natural
direction of the muscle.13 It is headed toward the
orbital apex which is directly posterior for the medial
rectus, nasal for the lateral rectus, inferior for the
superior rectus and superior for the inferior rectus.
Blind grasping and suturing of unidentified tissue
to the globe will result in unwanted restrictions of
ocular motility and should not be done. If the muscle
cannot be found then the globe should be fixed by
traction, with scleral stay sutures, in the direction of
the contraction of the lost muscle, for example, full
adduction in case of a lost medial rectus.15 The eye
should remain in this position for 2 weeks. If no
function is observed after that time then the case
should be dealt like any other paralytic squint. Resec-
ting and suturing the Tenon’s to the muscle stump
has also been recommended in case of a lost muscle.2
Oculocardiac reflex It is a transient phenomenon which
results from pulling on the muscle specially the medial
rectus. It results in vagal stimulation leading to brady-
cardia. Usually the cardiac rhythm is restored imme-
diately affect the pull on the muscle is relaxed. It can
be minimized or prevented by atropine injection and
to some extent by retrobulbar block.
Anatomical variations in the extraocular muscles These
are rare. When found the variation should be doubly
confirmed with the known landmarks and carefully
recorded by a photograph or sketches. If a muscle is
found to be absent and the absence conforms to the
ocular movements, the surgery is as for any paralytic
squint. Most variations are iatrogenic, stemming from
prior surgery. A good perioperative record of previous
surgical procedures will prevent most surgical
surprises.
Postoperative
Postoperative complications with strabismus surgery
are few and trivial. The agony due to them can usually
be minimized with good patient communication
regarding what he should expect as to discomfort,
redness, discharge, vision and position of eyes.
Overcorrections and undercorrections Small over and
undercorrections are not uncommon and are usually
compensated for by a patient with reasonable
binocular potential. Large overcorrections and
undercorrections cause serious concern to the patient
and his relatives. A large deviation in the early
postoperative phase with inability to bring the eye
even to the midline suggests a slipped muscle and calls
for immediate exploration and resuturing of the
muscle. Once the possibility of a slipped muscles is
ruled out it is desirable to reassure the patient, wait
and watch, continuing the appropriate conservative
treatment with spectacles, prisms or alternate
occlusion as and where indicated. In some of these
patients there is a reduction in this untoward result;
hence there is no need for immediate resurgery.
Usually it is preferable to wait for at least 6 weeks
before considering reoperation. While reoperating on
overcorrections, an attempt to undo the previous
surgery is not always the best option.2 Other muscles
can be operated upon with equal or more ease and
effectiveness.
Diplopia Patients operated for comitant heterotropia
often are troubled by postoperative diplopia which
occurs in response to the newly acquired position of
the eyes. It may persist from a few days to weeks or
oven months. Its duration depends upon the patient’s
ability to ignore it and hence is more prolonged and
troublesome in adults. It usually disappears with time.
When the residual deviation is too small for resurgery
persistent troublesome diplopia can be relieved with
prisms. Alternate occlusion often helps the patients
to learn alternate suppression.
Decreased muscle function Minimal limitation of action
of an operated extraocular muscle may appear in the
 Chapter 121: Surgical Treatment of Strabismus
immediate postoperative phase. This is probably due
to excessive handling of the muscle or splinting of the
eye by the patient due to postoperative pain and
inflammation. It usually recovers in a week or two.
Severe limitation of movement on the other hand may
indicate a slipped muscle, and calls for careful
examination and necessary intervention.
Infection Serious complications related to infections
leading to endophthalmitis, orbital cellulitis or suture
abscess have been reported but are extremely rare.2
Allergic reactions Mild to moderate allergic reactions
to suture material are more common than infections
and may present as ocular discomfort, conjunctival
congestion, chemosis and swelling of lids during 6-8
weeks after surgery. Treatment with topical cortico-
steroids is usually enough. Localized granulomas may
appear 2-4 weeks after surgery. Treatment is by topical
corticosteroids. Occasionally excision may become
necessary.
Conjunctival cysts Occasionally, small conjunctival
cysts filled with clear fluid may form. These can
usually be evacuated by a needle puncture.
Corneal dellen Corneal dellen may appear as whitish
elevated areas near the margin of the cornea specially
when limbal incision is used. They are due to
interruption in the tear film. They can be prevented
by proper closure of the limbal wound and resection
or recession of any excessive conjunctiva to prevent
tissue elevation near the limbus.2 They can be relieved
by pad and bandage.
Anterior segment ischemia Anterior segment ischemia
is a very rare but serious complication. It occurs due
to disruption of blood supply to the anterior segment,
as a result of injury to the anterior ciliary arteries when
3 or 4 rectii are operated upon in one sitting. Adults
are more susceptible than children.
Ischemia manifests within 24 hours of surgery as
corneal edema, haze, Descemet’s folds, mild keratic
precipitates and cells in aqueous. Segmental iris
atrophy, distorted pupil and cataract appear late.
Treatment consists of intensive topical and systemic
corticosteroids.
RESULT
The aim of all strabismus surgery is mechanical resto-
ration of ocular alignment to facilitate and strengthen
binocular functional cure which is more difficult and
sometimes impossible.1 Untreated infants lose the
941
potential for binocular development rapidly; hence to
achieve good or at least some degree of binocular
vision in children with congenital strabismus surgical
alignment should be aimed as early as possible
preferably by the age of 18 months. 1,2 When the
strabismus is acquired or intermittent, chances of
regaining binocular vision with appropriate ocular
alignment are greatly increased. The potential for
binocular restoration however, decreases with
duration of strabismus.
Due to the complexity of the sensory and motor
neuromuscular apparatus of the eyes, the variability
in results is unavoidable even in most experienced and
skillful hands, but it can be minimized by attention to
detail in preoperative evaluation and surgical
technique. Finally, the visibility of the result, in terms
of cosmetic appearance and properly functioning eyes,
is most gratifying to the patient and his relatives and
gives a satisfaction akin to that achieved after
successful cataract surgery. Fortunately, an unsatis-
factory cosmetic appearance can usually be corrected
with further surgery unless a disastrous step has been
taken during previous surgery.
Though some recent studies claim less variable
results by incorporating axial length measurements
in planning the amount of surgery,39,40 there is still a
long way to go in the understanding of various factors,
and the pursuit to improve functional results and
minimize variability of the motor results after
strabismus surgery continues.
REFERENCES
1. Guyton DL. Strabismus surgery: Rob’s and Smith’s operative
surgery. Ophthalmic Surgery (4th edn). 1984;85.
2. von Noorden Gunter K. Principles of surgical treatment:
Binocular vision and ocular motility. Theory and Manage-
ment of Strabismus (3rd edn) 1985;448.
3. Knapp P. The Surgical Treatment of Strabismus: Strabismus
Ophthalmic Symposium 1958;377.
4. Schnall BM. Anatomical considerations in strabismus surgery.
Ophthalmology Clinics of North America 1992;5:1,1-8.
5. Parks MM. Superior oblique tendon surgery. Atlas of
Strabismus Surgery. Philadelphia: 1983;S182.
6. Park MM. Extraocular Muscles: Duane’s Clinical Ophthal-
mology, 1986;1:1-3-12.
7. Bloom JN, Parks MM. The etiology, treatment and prevention
of the slipped muscle. Journal paediatric Ophthalmol
Strabismus 1981;18:6.
8. Parks MM. Causes of adhesive syndrome: Symposium of
strabismus. Transactions of the New Orleans Academy of
Opthalmology 1978;269.
9. Hawes MJ, Dortzobach RK. The microscopic anatomy of the
lower lid retractors. Arch Ophathalmol 1982;100:1313.
942 Section 7: Pediatric Ophthalmology Including Strabismus
10. von Noorden Gunter K. Summary of the gross anatomy of
the extraocular muscles: Binocular vision and ocular motility,
theory and management of strabismus (2nd edn) 1985.
11. von Noorden Gunter K. The limbal approach to surgery of
the rectus muscles. Arch Ophthalmol 1968;80:94.
12. Swan KC, Talbot T. Recession under Tenon’s capsule. Arch
Ophthalmol 1954;51:32.
13. Parks MM. Fornix incision for horizontal rectus muscle
surgery. Am J Ophthalmol 1968;65:907.
14. Parks MM. Surgical approach to the extraocular muscles:
Symposium on strabismus. Transactions of the New Orleans
academy of Opthalmology 1978;178.
15. Spaeth GI. Extraocular muscles: Ophthalmic surgery
principles and practice. 1982;653.
16. Parks MM. The weakening surgical procedures for elimi-
nating over action of the inferior oblique muscle. Am J
Ophthalmol 1972;73:107.
17. Wright KW. Surgical management of superior oblique
overaction and Brown syndrome. Ophthalmology Clinics of
North America V, 1992;1: 67.
18. Potter WS, Nelson LB. Suspension recession: Hang back and
hemihang back techniques in strabismus surger. Semin
Ophthalmol 1990;5:193.
19. Roper Hall MJ. The extraocular muscles: strabismus and
heterophoria. Stallard’s eye surgery 163-85, VII ed. 1989.
20. Parks MM. Bilateral superior oblique tenotomy for A-pattern
strabismus in patients with fusion. Binocular vision 1988;3:39.
21. von Noorden GK. Posterior fixation suture in strabismus
surgery: Symposium on strabismus. Transactions of the New
Orleans Academy of Ophthalmology 1978;307.
22. Wagner RS. The role of botulinum for strabismus. Ophthal-
mology Clinics of North America 1992;1:105.
23. Scott AB. Botulinum toxin treatment of strabismus. American
Academy of Ophthalmology Clinical Modules for Ophthal-
mologists 1989;7:1.
24. Jampolsky A. Adjustable strabismus surgical procedures:
Symposium on strabismus. Transactions of the New Orleans
Academy of Ophthalmology 1978;321.
25. Kraft SP, Jacobson ME. Techniques of adjustable suture
strabismus surgery. Ophthalmic Surg 1990;21:633.
26. von Noorden Gunter KA and V Patterns: Binocular vision
and ocular motility, theory and management of strabismus.
1985;338, III ed.
27. Boyd TAS, Leitch GT, Budd GE. A new treatment for A and
V patterns in strabismus by slanting muscle insertions. Can J
Ophthalmol 1971;6:170.
28. Wright KW. Surgical procedure for lengthening the superior
oblique tendon. Invest Ophthalmol Vis sci 1989;30(Suppl):377.
29. Parks MM. Personal communications, Oct 5; 1973 quoted in
von Noorden’s Binocular vision and ocular motility, theory
and management of strabismus. 1985;332 III ed.
30. Knapp P. Dissociated vertical deviations: Second congress
of the international strabismological association. Marseilles.
1976;185.
31. Diamond GR, Parks MM. The effect of superior oblique
weakening procedures on primary position horizontal
alignment J of Paediatric Ophthalmol and Strabismus
1981;18:35.
32. Stager DR, Parks MM. Inferior oblique weakening proce-
dures: Effect on primary position horizontal alignment
Archives of Ophthalmol 1973;90:15.
33. von Noorden Gunter K. Special forms of strabismus:
Binocular vision and ocular motility, theory and management
of strabismus III ed. 1985;379.
34. Papst W, Stien HJ. Zur chirugischen behandlung paradoxen
innervation. Ber Dtsch Ophthal Ges 1970;70:345.
35. Jampolsky A. Surgical leashes and reverse leashes and reverse
leashes in strabismus surgical management. Transactions of
the New Orleans Academy of Ophthalmology 1978;244-52-
68.
36. Spielmann A, Lagrange B, Laurent M. Le syndrome de
retraction de Stilling Duane, Etiopathogenie clinique.
Regulation motrice par la Faden operation de Cuppers sur
I’oeil sain, associe ou non a la chirugie de I’oeil atteint. J Fr
Orthopt 1976;8:105.
37. Brown HW. True and simulated superior oblique tendon
sheath syndrome. Doc Ophthalmol 1973;34:123.
38. Crowford JS. Surgical treatment of true Brown syndrome.
Am J Ophthalmol 1976;81:289.
39. Gillies WE, Hughes A. Results in 50 cases of strabismus after
graduated surgery designed by A scan ultrasonography. Br J
Ophthalmology 1984;68:790.
40. Kushner BJ, Lucchese NJ, Morton GV. Variations in axial
length and anatomical landmarks in strabismic patients.
Ophthalmology 1991;98:400.
 SECTION 8: NEUROOPHTHALMOLOGY

Chapter 122

Anatomy of Visual
Sensory System
G Natchiar, Subhuram

The visual system, as a whole, may be called “a little of the retina, optic disk, optic nerve, and other portions
brain”: developmentally, morphologically and of the anterior visual pathways can produce direct or
functionally, it is an outgrowth from the central retrograde changes in the nerve fiber layer of retina
nervous system. The visual sensory system comprises which can be seen with a direct ophthalmoscope.
of retina, optic nerve, optic chiasm, optic tract, lateral
geniculate bodies, optic radiation and the visual OPTIC DISK
cortex.
The optic disk is the exit side of all axons of the
ganglion cell . It is located 3 to 4 mm nasal to the fovea,
RETINA
and is about 1.5 mm in diameter, representing 5 to 7
The retinal ganglion cell is the neuro-ophthalmic degrees of visual space. As there are no photoreceptors
starting point of the visual sensory system. Each overlying the disk, it is projected into visual space as
ganglion cell sends a single nerve fiber through the an absolute scotoma, the blind spot of Mariotte, in the
optic disk, optic nerve, optic chiasm, and optic tract temporal visual field.3
to synapse in the lateral geniculate body. Ganglion
cells subserving central vision send their axons
directly from the foveal area to the temporal aspect of
the optic disk, thus forming the papillomacular
bundle. Fibers from the peripheral nasal ganglion cells
enter the nasal portion of the optic disk directly.1 Fibers
from the peripheral temporal retina enter the superior
and inferior poles of the optic disk (Fig. 122.1).
Temporal retinal nerve fibers arising near the
horizontal meridian run directly toward the disk until
approximately 4 mm temporal to the fovea, where they
diverge around the papillomacular bundle to become
part of the superior and inferior arcuate nerve fiber
bundles.2 However, the nerve fibers from the retinal
periphery may pass through the center of the nerve
and the peripapillary fibers to the periphery of the Fig. 122.1: Arrangement of optic nerve fibers in the retina
nerve. Alternatively, the fibers from the retinal (1) Optic disk, (2) Macula, (3) Maculopapillar bundle,
periphery pass to the periphery of the nerve and the (4) Juxtapapillar bundle (nasal fibers), (5) Nasal fibers,
peripheral fibers to the center of the nerve. Diseases (6) Temporal fibers (arcuate fibers)
944 Section 8: Neuroophthalmology
Optic Nerve
The optic nerve contains approximately 1.2 million
nerve fibers and may be divided anatomically into
four parts: (a) intraocular, (b) intraorbital, (c) intra-
canalicular, and (d) intracranial. The intraocular
portion is only 1 mm long and the fibers are non-
myelinated in most individuals; diameter of this
portion is 1.5 mm. The orbital portion is 20 to 30 mm
long and has a diameter of 3 to 4 mm; the increase in
diameter is due to acquisition of a myelin sheath. The
orbital optic nerve follows a sinusoidal course and
appears straightened when there is proptosis. The
optic nerve consists of bundles of myelinated axons
with interspersed connective tissue septae that contain
blood vessels. The nerve is surrounded by three layers
of meninges.
The optic nerve enters the optic canal at the apex
of the bony orbit. The optic canal measures 4 to 9 mm
in length and 4 to 6 mm in width. Along with the optic
nerve in the canal transmits the ophthalmic artery,
some filaments of the sympathetic carotid plexus and
extensions of intracranial meninges that form the
sheaths of the optic nerve. In the canal, (Fig. 122.2),
the dura of the optic nerve and the periosteum of the
bone are fused; however, the space between the pia
and the arachnoid of the optic nerve communicates
with the intracranial subarachnoid space and contains
cerebrospinal fluid (CSF). After the optic nerve fibers
leave the canal, they converge at the optic chiasm. This
intracranial portion of the optic nerve is generally
between 10 and 16 mm in length. Above the intra-
cranial portion of the optic nerves lie the frontal lobes
of the brain, the olfactory tracts, and the anterior
cerebral and anterior communicating arteries. The
lateral aspect of the optic nerve is often immediately
adjacent to the internal carotid artery as it emerges
Fig. 122.2: Optic nerve and its coverings
from the cavernous sinus. Inferiorly, posterior ethmoid
and sphenoid sinus cells are adjacent to the nerves.
OPTIC CHIASM
Fibers from the two optic nerves join in the optic
chiasm. In the chiasm, a hemidecussation of the nerve
fibers occurs so that all visual information to both eyes
from the right visual space is relayed to the left cerebral
cortex, while all visual information from the left visual
space is relayed to the right cerebral cortex. Fibers from
the ganglion cells temporal to the fovea of each eye
which serve the nasal visual field, do not cross and
reach the ipsilateral optic tracts. Fibers from the nasal
side serving the temporal field cross in the chiasm to
the contralateral optic tract.
Macular fibers constitute a large portion of the optic
chiasm. Nasal, crossed macular fibers decussate in the
posterior portion of the chiasm. Fibers from the lower
nasal quadrant, after decussating, cross over to the
opposite side; some of its fibers loop (convex forward)
into the contralateral optic nerve at its junction with
the chiasm (Fig. 122.3). This loop has been called von
Willebrand’s knee. It is because of these anterior loops
that lesions of the terminal optic nerve of one side
affect both visual fields. Upper nasal quadrant fibers
pass backward to form loops in the beginning of the
ipsilateral optic tracts and these cross in the posterior
inferior portion of the optic chiasm to enter the medial
and inferior portions of the contralateral optic tract.
The posterior loops are less prominent than the
anterior ones.
The optic chiasm is contiguous with the anterior-
inferior floor of the third ventricle. It measures about
Fig. 122.3: Arrangement of the optic nerve
fibers in the chiasm
 Chapter 122: Anatomy of Visual Sensory System 945
8 mm in its anteroposterior direction, 12 mm wide and
4 mm thick. The chiasm lies over the body of the
sphenoid bone, and lies about 5 to 10 mm above the
pituitary gland (Fig. 122.4).
The space between the chiasm and the pituitary,
the inferior chiasmatic cistern, ensures that mild
suprasellar extensions of pituitary tumors do not
easily result in visual field defects. The optic chiasm
lies above the dorsum sella in most patients (80%);
however, it may lie more posteriorly (postfixed 10%)
or anteriorly (prefixed 10%) (Fig. 122.5). This varia-
bility in position helps explain the various types of
visual defects seen in patients with tumors in this area.

OPTIC TRACTS
The optic tracts begin at the posterior aspect of the
optic chiasm. They diverge and continue posteriorly
around the cerebral peduncles to terminate in the
lateral geniculate bodies. Each tract contains visual Fig. 122.5: Normal, prefixed and postfixed
and pupillomotor fibers, both crossed (nasal retinal chiasm in relation to the chiasm
fibers from the contralateral eye) and uncrossed
(Fig. 122.6). Here fibers that originate from ganglion
(temporal retinal fibers from the ipsilateral eye). All
cells in the retina synapse with visual fibers that will
primary visual fibers in the optic tracts synapse in the
form the geniculocalcarine radiations and terminate
lateral geniculate body; pupillomotor fibers project
in the occipital cortex. The lateral geniculate body is a
through the brachium of the superior colliculus to the
portion of the thalamus. It is separated into six layers.
pretectal nuclei in the midbrain.
Ipsilateral retinal ganglion cells synapse in layers two,
LATERAL GENICULATE BODY (LGB) three and five; contralateral cells synapse in layers one,
four and six. In the lateral geniculate body a 90°
The lateral geniculate body is the termination of all
afferent fibers of the anterior visual pathways

Fig. 122.4: Relative position of the chiasm with Fig. 122.6: Lateral geniculate body with the optic nerve fibers
the pituitary gland of optic tract and optic radiation
946 Section 8: Neuroophthalmology

rotation of fibers occurs so that nerve fibers from (area 18) and peristriate cortex (area 19). These
superior retina lie not superiorly but medially in the adjacent areas are essential for integration of visual
lateral geniculate body, while nerve fibers from image.
inferior retinal lie laterally. Rotation occurs again after
fibers leave the LGB so that superior and inferior BLOOD SUPPLY OF THE VISUAL PATHWAYS
retinal fibers subsequently lie superior and inferior in
The optic nerve, chiasm and the tract are covered by
the optic radiations and cerebral cortex.
pia mater. Those portions of the chiasm and the tract
that are adherent to the base of the brain are not
OPTIC RADIATIONS
covered by pia. The blood vessels to the nerve fibers
Because of the configuration of the temporal horn of pas through pial septa in the form of a pial network.
the lateral ventricle, superior fibers that leave the The orbital portion of the optic nerve is supplied by
lateral geniculate body proceed directly posteriorly branches of the ophthalmic artery (Fig. 122.7) which
to the occipital cortex. Inferior fibers, however, must leave the brain while the artery is still in the optic canal.
loop around the ventricular system into the temporal The orbital portion is supplied by two groups of
lobe. The inferior fibers are also extremely close to the vessels.
sensory and motor fibers of the internal capsule. A a. The anterior optic nerve arteries enter the nerve
small infarct, tumor, or an abscess here can cause a sheath along with the central retinal artery. Some
contralateral hemianopic visual field defect as well as of these arteries enter the pia dividing into
contralateral hemiparesis. The inferior fibers that loop branches which run forwards, backwards and
around the temporal horn are known as Meyer’s loop. circularly and anastomose with the vessels of the
The most anterior fibers are found approximately 5 cm pial network to supply the nerve fiber.
from the tip of the temporal lobe. The optic radiations b. The posterior arteries of the optic nerve, about 20
contain three main groups of fibers. The superior in number, pierce through the dural sheath
portion contains fibers serving the inferior visual field. individually and are distributed to the middle and
The inferior portion contains inferior fibers serving posterior third of the nerve. The optic nerve is
the superior visual field. The central portion contains entirely supplied by these vessels and after piercing
the macular fibers. the dural sheath there is no anastomosis between
the branches. For practical purposes, these twigs
OCCIPITAL CORTEX behave as end arteries inside the nerve.
The visual (projection) cortex is also called the striate
cortex or area 17 and is situated along the superior
and inferior lips of the calcarine fissure. The major
portion of the occipital cortex is concerned with
macular vision. The occipital tip serves the macula and
extends variably on to the lateral aspect of the occipital
lobe. More peripheral visual field projects to visual
cortex that lies more anteriorly, along the medial side
of the occipital lobe. The visual fields of the two eyes
do not completely overlap. In fact, there is a temporal,
peripheral region of approximately 30° that is
monocular in each eye. The nerve fibers corresponding
to this retinal region are located, as a group, in the
most anterior visual cortex. It is in this region that
lesions may produce a purely monocular visual field
defect being postchiasmal. The field defect associated
with lesions in this area is called “the temporal crescent
syndrome”. More often, the temporal crescent is
spared after occipital damage. The resultant hemi- Fig. 122.7: PCA: Posterior ciliary artery; ON: Optic nerve; PIA:
anopia may give the appearance of being incongruous. Pia mater; A: Arachnoid; D; Dura mater; Col Br: Collateral
Adjacent to the striate cortex are the parastriate cortex branch; R: Retina; C: Choroid; S: Sclera; CZ: Circle of Zinn
 Chapter 122: Anatomy of Visual Sensory System 947
cerebral, anterior choroidals and anterior and poste-
rior communicating arteries (Fig. 122.8). Sometimes
the middle cerebrals may also take part. As many as
11 arteries take part in blood supply to the chiasm.
Immediately posterior to the chiasm, the anterior
part of the optic tract is supplied from an anastomotic
plexus formed by branches of anterior cerebral,
internal carotid, anterior choroidal, internal carotid
and posterior cerebral arteries. The rest of the optic
tract is supplied by branches from anterior choroidal.
Lateral aspect of the lateral geniculate body receives
nutrition from the anterior choroidal arteries and the
remaining portion from the posterior cerebral artery.
Optic radiation and visual cortex receive blood supply
from the calcarine branch of the posterior cerebral
artery; posterior limb of the internal capsule including
the commencement of the optic radiation is supplied
by the anterior cerebral artery.

REFERENCES
Fig. 122.8: Blood supply of the visual pathways 1. Pollack SC, Miller NR. The retinal nerve five layer. In
starting from the retina up to the occipital cortex Ophthalmol Clin 1986;26:201.
2. Hoyt WF, Sahlicke B, Ecklhoff RJ. Funduscopic appearance
of optic nerve-bundle defect. Br J Ophthalmol 1972;56:577.
Blood supply to the chiasm comes from the 3. Hayreh SS. Anatomy and physiology of the optic nerve head.
neighboring vessels namely, internal carotid, anterior Trans Am Acad Ophthalmol Neurolaryngolol 1974;78:240.
 Chapter 123
Neuroophthalmological
Evaluation
LC Dutta
HISTORY TAKING
A detailed carefully history taking is an unavoidable
exercise prior to neuroophthalmological examination.
Brain tumor causing increased intracranical pressure
may reduce or completely abolish consciousness or
the tumor arising from the vital areas of the brain may
cause motor or sensory aphasia; in such cases and in
very young children second hand history has to be
obtained from close relatives or companions or from
parents in case of children. The chief complaints of
neuroophthalmological disorders may be visual
deficit, diplopia and sensory disturbances like pain,
headache, numbness, etc.
Visual Deficit
A history of loss of central vision should be made well
differentiated by the patient from field defect. The state
of vision may also provide information of great value.
Occurrence of diplopia is usually readily remarked.
Next frequent complaint is transient attacks of loss or
fogginess of vision. Loss or defect of field of vision is
not a common and correct history. In homonymous
field defect most of the patients complain as loss of
vision of right or left eye depending upon respective
homonymous hemianopia. Some patients may be able
to detect right homonymous hemianopic defect when
patient finds difficulty in reading a book (in case of
Urdu or Persian language book difficulty is encoun-
tered in left homonymous hemianopia). In bitemporal
hemianopic defects patients usually give the history
of bumping against the objects around him while
moving around.
Careful history taking may even help in localizing
the lesion; loss of vision in one eye suggests a lesion
in the visual pathways in front of the chiasm as in optic
neuritis or tumor of the optic nerve. The early stages
of progressive loss of vision are not easy to detect.
Photopsia or seeing of sparks, lightning, luminous
sparks, etc. in one eye are usually symptoms of retinal
disease but when it is in both the visual fields then
one should consider it as a manifestation of some sort
of disorder of central nervous system. Sometimes
visual hallucinations are early symptom of occipital
or temporal lobe tumors.
When the patient’s chief complaint is decreased or
loss of central vision, some leading questions by the
physician might bring out more information about the
history. One should ascertain whether the visual
disturbance is in one eye or in both the eyes. Uniocular
visual loss is commonly due to lesion of one optic
nerve. If bilateral then the lesion may either be in both
the optic nerves or in the chiasm or beyond. Sometimes
patients with homonymous visual field defects will
complain unilateral visual loss implicating the eye
ipsilateral to the field defect. In order to determine
whether the problem is truly uniocular, it is essential
to know from the patient if he tested himself by
covering either eye. This is essential to know whether
the visual defect is monocular or binocular.
Another important point is to assess whether the
visual loss was of gradual or sudden onset. In
compressive lesions due to tumor or a mass there will
be gradual loss of vision and in circulatory distur-
bances of the optic nerve it is apoplectic in nature. It
is sometimes difficult to obtain this information
 Chapter 123: Neuroophthalmological Evaluation
because slowly progressive visual loss in one eye is
frequently discovered by the patient only when
covering the unaffected fellow eye inadvertently. They
may interpret this as sudden visual loss.
Diplopia
Diplopia is a common but disturbing symptom about
which the patients complain of visual loss in very early
stage of neuroophthalmological disorder. In early
stage of paralysis of rectii muscles, specially the
horizontal rectii, diplopia may not be present in
primary position but occurs in extreme deviation of
the eyes. Another oculomotor disorder is nystagmus;
and only in gross nystagmus of early onset patient
complains of movement of objects which is called
‘oscillopsia’.
Along with the history of neuroophthalmological
complaints, past medical history should be enquired
in detail. If the patient is under treatment, the nature
and dose of medication should be ascertained.
Personal history related to food habit, smoking,
addiction to drugs and alcohol, drug allergy, family
history of hypertension, diabetes, etc. should be
elicited.
History about Sensory Disturbances
Migraine and intracranial space occupying lesions are
the common causes of headache; the differentiating
point between the two is that migrainous headache is
almost always on one side of the head and lasts for a
day or two to appear again after days or weeks.
Headache due to raised intracranial pressure is almost
constant and gradually increases in intensity radiating
allover the head. The headache in brain tumor is due
to stretching of the meninges and is mediated through
the branches of the ophthalmic division of the
trigeminal nerve. Other neuroophthalmic causes of
headache are trigeminal neuralgia and lesions of the
Gasserian ganglion like herpes zoster ophthalmicus.
In the history of the ailment some patients will
often mention observations they have made while
looking at the mirror; these may play considerably
important role during the course of physical exami-
nation. Widening of the palpebral fissure associated
with drawing of the contralateral angle of the mouth
is a diagnostic sign of facial nerve paralysis. Wide
palpebral fissure also occurs in exophthalmos whereas
narrowing of the palpebral fissure is a sign of Horner’s
syndrome or paralysis of levator palpebrae superioris
muscle. Twitching of the orbicularis oculi muscle or
949
spasmodic contraction of muscles of facial expression
supplied by the facial nerve is more felt than seen by
the patient.
TESTING OF VISUAL FUNCTION
Testing of central visual acuity It is one of the most
important examinations in any kind of neuroophthal-
mological disorder. Central visual acuity is always
determined to its best-corrected level. This vision must
be recorded with the patients’ refractive error
corrected with glasses or with the help of a pinhole.
Color vision It should be tested with Ishihara color
vision testing plates; but Farnsworth Munsell 15 Hue
or 100 Hue test is a more sensitive and accurate
method. In this test the patient is required to rearrange
the 15 or 100 randomly presented color chips in a
regular color sequence. Each eye should be tested
separately. Acquired defects of color vision commonly
occur in patients with diseases of the optic nerve or
the anterior part of the visual pathways caused by
compression, toxin or demyelinating lesions.1 A rough
and ready method of assessment of gross color defect
is to have the patient view a red object (e.g. a pencil)
first with one eye then with the other eye and ask the
patient with which eye the color appears to be deeper.
By testing central vision field with Amsler-Landolt
grid one can detect central scotoma and meta-
morphopsia; with red colored grid relative scotoma
also can be detected in early stage of retrobulbar
neuritis and toxic neuritis.
PHOTOSTRESS TEST
Photostress test is an important test to differentiate
between decreased vision due to macular or optic
nerve lesion. To perform this test the patient is
examined in a dimly illuminated room. First the best-
corrected vision is recorded separately for each eye.
Then covering one eye, patient is asked to look directly
into an illuminated hand light held quite close to the
uncovered eye for ten seconds. Soon after removing
the light source the patient is asked to read the letters
of the Snellen’s test chart and vision is recorded. After
the dazzling due to the light, the vision is temporarily
blurred and it takes some time to recover from the
dazzle. In diseases of the optic nerve the recovery time
is not much prolonged—it is less than a minute. With
macular lesions like central serous choroidoretino-
pathy the recovery time may be three minutes or even
longer.2
950 Section 8: Neuroophthalmology
FUNCTIONAL VISUAL LOSS
Subjective visual loss which is not attributable to any
organic cause is called functional visual loss. When a
patient pretends or feigns visual loss for secondary
gain it is called malingering. If the patient is unaware
that the visual difficulty is non-organic it is called
hysterical. Hysterical amblyopia is usually bilateral
and commonly associated with photophobia and
blepharospasm. A diminution of vision in one eye may
be associated with hysterical blindness in the other
eye.
Organic bilateral blindness with clinically normal
eyes is rare; when the pupillary reactions are normal
and without any past history of hemianopia, bilateral
amaurosis is almost always functional. When a
functional visual loss is suspected, diagnosis must be
based on proving that the patient has better vision than
his subjective responses indicate. Patients with
functional amaurosis are difficult to be examined
because they are uncooperative, defensive and
sometimes hostile. The examiner should have patience
and perseverance in examining such patients. The aim
of the ophthalmologist should be to document better
visual acuity than the patient feigns to have.
History of complaints of the patient should be
taken with an aim to flaw the patient’s objective.
Persistent questioning may show that the patient
changes the story. Another point to be observed while
taking history is that the patient makes visually
elicited movements as if he fixates on objects in the
room. Before starting the ocular examination, a malin-
gerer or a hysteric patient should be asked to walk
into a room where some obstacles like stool, chairs,
etc. are placed; malingerers almost never hit the
obstacles except very softly. The hysterical patients
frequently avoid the objects altogether.
Testing of menace reflex if done properly is a good
method to confirm that the patient is not blind but
this should be done abruptly and unexpectedly;
because if the patient is prepared then the reflex may
be suppressed. Another test for bilateral blindness is
to ask the patient to write his name in a piece of paper.
Truly blind persons do so with little difficulty.
Performing proprioceptive test by asking the patient
to touch the tip of his nose with his index finger also
may fool the patient because the patient with
functional disease may mistake this to be a visual task
and pretend inability to perform it.
Testing of patients complaining of monocular
blindness as opposed to decreased vision is somewhat
easier. The tests for this purpose are:
Producing optokinetic nystagmus in each eye separately The
production of optokinetic nystagmus in a functionally
blind eye is evidence of intact vision in that eye.
Mirror test A mirror is held in front of the allegedly
blind eye of the patient while the opposite eye is
occluded. When the mirror is tilted vertically and then
horizontally then entire environment visible in the
mirror will correspondingly tilt. Along with this there
will be coincident movement of the eyes. This suggests
that the eye is not actually blind.
Prism test A prism is introduced in front of the blind
eye while the patient is reading. After removal of the
prism if there is refixational movement of the eyes then
there is binocular vision which prove that the alleged
blindness is functional.
FRIEND test As red and green are complementary
colors, when red and green glasses are put in front of
right and left eye respectively the patient will see the
whole word as FRIEND. Thus, in functional unilateral
blindness the patient will see the whole word but in
true unilateral blindness he will see either FIN or RED
depending upon whether the right or left eye
respectively is truly blind.
Pitiably enough, the most experienced ophthalmo-
logists may fail to detect a malingerer who has visited
and been examined already by several ophthalmo-
logists. On the other hand, cases like squint amblyopia
or anisometropic amblyopia may be wrongly disposed
off as functional amblyopia if one does not examine
the patient methodically.
EXTERNAL EXAMINATION OF THE EYE
As in other cases, neuroophthalmological cases also
should be examined in a properly illuminated area.
Size of the palpebral aperture is an important point to
be ascertained. Normally when a person looks straight
ahead the lower lid margin just grazes the 6 O’clock
position of the limbus and the upper lid covers the
cornea from 11 O’clock to 1 O’clock position. When
the upper lid covers about half or more of the upper
part of the cornea there is ptosis either due to paralysis
of levator palpebrae superioris muscle supplied by the
3rd cranial nerve or paralysis of the Müller’s muscle
 Chapter 123: Neuroophthalmological Evaluation
of the upper lid supplied by the cervical sympathetic;
differentiation of the two is made by the size of the
pupil which is dilated in the former and constricted
in the latter condition. Widening of the palpebral
fissure, on the other hand may be due to (a) sympa-
thetic stimulation, causing upper lid retraction,
(b) exophthalmos, and (c) paralysis of the facial nerve.
In the newborn babies the margin of the upper lid lies
well above the cornea; it descends in youth until it
reaches the normal position in adolescence. If the
eyeball is normal in size and position, and if the margin
of the upper lid rests at or above the limbus exposing
a strip of white sclera above the limbus when the eyes
are directed straight forward then lid retraction is
present. Spastic lid retraction is due to spasm of the
levator palpebrae superioris muscle. Paradoxical lid
retraction occurs in Marcus Gunn jaw winking
syndrome.
Ocular posture is another important aspect of
neuroophthalmological examination. By ocular
posture we mean three conditions:
a. Position of the eyeball in respect of the bony orbit
whether there is exophthalmos, enophthalmos and
horizontal or vertical displacement. In addition to
orbital lesions, intracranial space occupying lesions
also may produce exophthalmos; sometimes it may
be pulsating as in caroticocavernous fistula or in
dehiscence of the superior orbital wall.
b. Ocular deviation due to paralysis of extraocular
muscle.
c. Nystagmus of various degrees and types (see
Chapter 107).
Ocular Motility
Prior to testing for ocular motility preliminary obser-
vation should be made to see if there is any obvious
deviation of the eye, and to ascertain whether the devi-
ation is constant or intermittent, uniocular, alternating
or there is any head tilting or tendency to close one
eye suggesting diplopia. Next, the motility of the eyes
is tested to note the excursions of the eyes in six cardi-
nal positions by asking the patient to follow a small
fixation object. Observation is to be made whether
there is deficient or excessive movement in any direc-
tion suggesting underaction or overaction of a parti-
cular muscle. There may be primary underaction or
weakness of muscle due to actual paralysis of the
affected muscle. Primary overaction of a particular
muscle does not occur; it is secondary to weakness of
951
the contralateral synergistic muscle. In case of paresis,
the affected eye shows some limitation of movement.
In slight degree of paresis or during the recovery
period of paresis although the eye may complete its
excursions the weakness of the muscle may be mani-
fested by slight nystagmoid movements as the limit
of its range is approached (deviational nystagmus).
Gaze Palsy: Abnormality of Conjugate
Movements of the Eye
Gaze palsies are disturbances of the higher centers
involving movements which combine the two eyes
into a single visual organ to produce uniform
movements of the eyes in space. Gaze palsy is inability
to look in a given direction or to converge the eyes in
fixing a near object. For example, when converging at
near object the medial rectii muscles do not contract
or looking to the right, the right lateral rectus and left
medial rectus do not contract simultaneously, but
when testing the individual muscles for different
movements no restriction of movements is detected.
For clinical purpose the gaze palsy is subdivided into
horizontal, vertical and vergence types.
There are four different types of horizontal gaze
movements: (a) optically induced, (b) command, (c)
pursuit, and (d) vestibular movements.
The optically induced movement is tested by
attracting the attention of the patient by showing a
flashlight from temporal side; the eyes will move to
that side to change the point of light focus from the
periphery of the retina to the foveal area. Command
movements are tested by asking the patient to look to
the right or to the left. For testing the pursuit
movement an object like a pen or pencil is moved from
right to left and the patient is asked to follow the object.
Vestibular movement is tested by passively moving
the patient’s head to the right and left and the compen-
satory eye movement to the opposite direction is
assessed.
Vertical gaze palsies are detected by patient’s
inability to look up or down. In vergence gaze palsy
the patient may complain of diplopia—crossed dip-
lopia for convergence gaze palsy and homonymous
diplopia for divergence gaze palsy. Gaze palsies may
be caused by cortical and supranuclear lesions. Multi-
ple sclerosis, polio, encephalitis, vascular disorder and
brain tumors affecting the midbrain, pons and cerebral
hemispheres may also cause gaze palsy. Gaze palsy
has got some localizing value. An isolated palsy of
952 Section 8: Neuroophthalmology
the voluntary and command movements with preser-
vation of the other movements is suggestive of a lesion
in the gaze center of the frontal lobe or in the corres-
ponding internal capsule. In unilateral lesion the gaze
palsy is toward the side of the lesion. Horizontal gaze
palsy is associated with ipsilateral facial palsy and
hemiparesis or hemiplegia. Gaze palsy due to cortical
lesion is usually transitory because it is compensated
by the opposite lobe; in case of lobectomy, gaze palsy
is sometimes not detected.
Horizontal gaze palsies of all forms (optically
induced, pursuit, command and vestibular move-
ment) are lost in lesion in the supranuclear horizontal
gaze centers situated at the pons adjacent to posterior
longitudinal bundle and the resulting gaze palsy
defect is toward the side of the lesion. The supra-
nuclear gaze centers of both the sides in the pons are
situated close together; thus bilateral horizontal gaze
palsies are much more common. The centers for
vertical gaze movement and vergence movement are
situated at a higher level; therefore in pontine lesions
these movement are not affected. The nuclei of the 6th
and 7th nerves as well as the pyramidal tract are in
close proximity with the horizontal gaze center. This
is known as Foville-Millard-Gubler syndrome.
COVER TEST
Cover test is important to detect any latent deviation
of the eye and also to differentiate between paralytic
and non-paralytic squint. The patient is directed to
fix at a test object and while he is doing so an opaque
card is placed before one eye and then transferred
quickly to the other eye. When neither eye deviates
when covered or uncovered the condition is called
orthophoric, i.e. no phoria or no squint either manifest
or latent. If each eye deviates when covered and
returns to the fixing position when uncovered, a squint
is present. The deviation of the squinting eye behind
the cover is called ‘primary deviation’. When the
squinting eye takes up fixation the deviation of the
non-squinting eye is known as ‘secondary deviation’.
If both deviations are equal then the squint is nonpara-
lytic or concomitant. If the secondary deviation is
greater than the primary one the squint is paralytic. If
the primary is greater than secondary then the squint
is due to spasm of the muscle concerned.
Along with the examination for ocular motility to
find out any weakness of muscles, it is worthwhile to
revise the history of diplopia. Most of the patients with
horizontal rectii paralysis do not complain of diplopia
but they avoid diplopia by assuming compensatory
head posture; on the other hand the common
complaint is blurred vision or difficulty in seeing in
certain direction of gaze. Nevertheless when there is
some symptoms suggesting diplopia more detailed
information should be sought for by the following
leading questions:
a. What the patient means by diplopia. Is it seeing
one object twice? For example when a pen or pencil
is shown does it becomes two? Next point is to
differentiate between monocular and binocular
diplopia. Asking the patient to close either eye
alternately, it has got to be confirmed whether
diplopia persists. It is important that during the
examination, a strong vigil is kept so that the
patient does not take up an abnormal head posture
to compensate the diplopia. Common causes of
monocular diplopia are early stage of cataract
formation, subluxation of the lens, high degree of
astigmatism and essential atrophy of iris leading
to polycoria.
b. Next step is to ascertain which muscle is at fault to
cause diplopia. In doing motility test the patient is
instructed to identify whether the objects are
horizontally or vertically displaced and in which
direction maximum separation of images occurs.
For example, in paralysis of right lateral rectus
maximum separation of images will be on moving
the eyes toward right hand side of the patient.
Sometimes it may be difficult to ascertain which
muscle is at fault especially in cases of vertical rectii
and oblique muscles. In such cases, when the patient
appreciates diplopia in any one or more of the cardinal
positions of the eye, then the examiner covers one of
the (patient’s) eyes and ask which image disappears.
The principle is that the distant image belongs to the
paralyzed eye. To cite an example, when looking down
and to the left, muscles implicated are inferior rectus
of left eye and superior oblique of right eye. In order
to pinpoint the muscle at fault patient is asked which
image disappears when one eye is closed.
PUPILS AND PUPILLARY REACTIONS
Examination of the pupil should be performed in a
dim, uniformly illuminated room using bright source
of examining light. Diametrically, normal size of the
pupil is 3 to 4 mm. If the size is less than 2.5 mm then
it is called miotic pupil and more than 4.5 mm
diameter is called mydriatic pupil. Owing to the
refraction through the corneal surface, which acts as
 Chapter 123: Neuroophthalmological Evaluation
a magnifying glass to enlarge the size of the pupil by
about 1/8 (the actual pupillary diameter is 3.5 mm)
to appear clinically to be 4 mm. Normal pupil is central
in position with circular regular margin reacts to light
directly and consensually and to accommodation and
convergence. During testing the light reaction the
patient should look straight ahead to avoid accommo-
dation convergence pupillary reaction.
The size and reaction of the pupil is the result of
compromise between the adrenergic (sympathetic)
and cholinergic (parasympathetic) systems which
dilate and constrict the pupil, respectively. In sympa-
thetic hyperactivity, viz. emotion, fear, thyrotoxicosis,
etc. pupil is dilated. Pupil is bigger in size in myopic
than in hypermetropic eyes probably due to the fact
that in myopia accommodation is not exerted but in
hypermetropia it is essential. In elderly persons pupil
is smaller than in young persons due to the rigidity of
the collagenous tissue of the iris stroma. It is smaller
in new-born babies not due to the fact that dilator
953
pupillae is not functionally developed—the neonates
prefer to sleep after birth and during sleep the pupil
is constricted.
PUPILLARY DILATOR PATHWAY
Nervous pathway of sympathetic supply to the dilator
pupillae muscle of the iris starts from the hypo-
thalamic nucleus from where the first neuron travels
through the tegmentum of the brainstem into the
spinal cord terminating in the ciliospinal center of
Budge (Fig. 123.1).
The second neuron (preganglionic fiber) passes
from this center through ventral spinal roots and white
rami communicantes of C8 to T2 and forms the para-
vertebral sympathetic cords. The pupillodilator fibers
pass to relay in the superior cervical ganglion from
where the postganglionic fibers pass mostly as the
sympathetic plexus around the branches of internal
carotid artery including the ophthalmic artery. Within

Fig. 123.1: Ocular sympathetic pathways: (A) First order neuron from the hypothalamic center to the ciliospinal center of Budge,
(B) Second order neuron takes a circuitous course through the chest along the carotid system to superior-cervical ganglion,
(C) Third order neuron starts from this ganglion and distributed along the branches of external carotid artery and to the orbit via
the ophthalmic artery and first division of the trigeminal nerve
954 Section 8: Neuroophthalmology
the cavernous sinus the pupillodilator fibers leave the
carotid plexus and pass along with the fibers of the
oculomotor nerve and the ophthalmic division of the
trigeminal nerve to enter the orbit with its nasociliary
branch.
PUPILLOCONSTRICTOR PATHWAY
(Figs 123.2 and 123.3)
The pupillary light reflex is mediated by retinal
receptors which cannot be differentiated from the
visual rods and cones. The afferent fibers pass along
with the visual fibers in the optic nerve and partially
cross in the chiasm; while the visual fibers terminate
in the lateral geniculate body, the pupillary fibers
continue their course in the tract and from the
posterior part of the tract enter the superior brachium
conjuctiva and passing into the midbrain lateral to the
superior coliculus to reach the pretectal nucleus; then
these fibers partially cross to reach the Edinger-
Westphal nucleus of the same and opposite side via
the medial longitudinal bundle. The afferent fibers
from the Edinger-Westphal nucleus pass into the third
Fig. 123.2: Pupilloconstrictor fiber
nerve, then along with its branch to the inferior oblique
muscle to reach the ciliary ganglion where they make
a cell station. Then via the medullated postganglionic
fibers of short ciliary nerves pierce the globe around
the optic nerve to course forward between the sclera
and choroid to supply the sphincter pupillae muscle.
The center for near reflex is ill defined but is probably
located in the peristriate area; stimulation of this area
results in pupillary constriction particularly that
involved in the near reflex.
ADIE’S SYNDROME
Adie’s syndrome includes tonic pupil associated with
absent deep tendon reflexes of lower extremity. Tonic
pupil is dilated, reaction to light is poor, extensive but
slow and long-lasting pupillary constriction with near
vision, and frequently disturbance in accommodation.
The condition is usually unilateral. The reactions to
light in the affected eye, both direct and consensual
are delayed, slight or absent. The consensual light
reaction in the other eye is normal. The direct reaction
may be stimulated after a period of stay in the dark.
 Chapter 123: Neuroophthalmological Evaluation
Fig. 123.3: Oculomotor nerve and ciliary ganglion showing its afferent and efferent branches
The morphologic changes of the pupil may be seen as
segmental loss of pupillary ruff. The loss of tone within
the iris stroma in denervated areas of the iris may
result in a loss of the radial arrangement so that the
iris pillars point toward areas of intact sphincter. This
type of pupillary constriction is known as vermiform
pupillary reaction on near vision may appear to be
completely absent but after prolonged near fixation
contraction occurs very slowly and ultimately the size
of the affected pupil may be smaller than the fellow
one; on relaxation of convergence, dilatation is again
slower and takes a long time to restore to its original
size. There are however atypical forms of Adie’s pupil
particularly when it is bilateral and it is not so easy to
differentiate it from the other pupillary anomalies.
Topical instillation of 2.5 percent methacholine
(mecholyl) usually causes constriction of Adie’s pupil
but not of normal pupil.
The site of lesion of Adie’s pupil may be in any
region of the pupillary pathways starting from the
hypothalamus to the musculature of the iris. The
various forms of lesions in the oculomotor nerve
starting from its nucleus to any position of its distal
portion like clivus ridge, cavernous sinus, superior
orbital fissure or orbital apex syndromes may give rise
to Adie’s syndrome.
ARGYLL ROBERTSON PUPIL (ARP)
(Argyll Robertson)
Argyll Robertson pupil is characterized by absence of
light reflex whereas pupillary constriction to accom-
modation and convergence reflex is maintained. The
size of the pupil is less than 3 mm. Though ARP is a
typical pupillary sign of neuro-syphilis, it was
described long before the syphilitic involvement of
central nervous system was described. The exact site
of lesion for ARP has not been definitely known but it
955
is presumed to be due to involvement of the inter-
nuncial neuron between the pretectal nuclei and
Edinger-Westphal nucleus. Interruption of these
neurons results in loss of light reflex without affecting
pupillary constriction during accommodation and
convergence. Moreover the fibers which are respon-
sible for pupillary near response are situated ventral
to the pupillary light fibers. Along with the inter-
nuncial neuron there is involvement of the fibers
which subserve the inhibitory activity over Edinger-
Westphal nucleus which results in excessive sympa-
thetic activity causing miosis.
Argyll Robertson pupil also may occur in a great
variety of nonsyphilitic conditions affecting the inter-
nuncial fibers. Some of them are neoplasms around
the aqueduct, encephalitis lethargica, multiple
sclerosis, polio-encephalitis, trauma, etc. Typical ARP
is always bilateral, miotic, having irregular margin,
occasionally with patches of iris atrophy and does not
dilate fully after instillation of mydriatic.3
Hutchinson’s Pupil
Hutchinson’s pupil is a dilated pupil which occurs in
cerebral injury or hemorrhage, cerebral abscess,
cerebral edema and tumor. It is a diagnostic sign of
extradural or subdural hemorrhage. Hutchinson’s
pupil has got three stages:
1. Initial stage of miosis due to irritation of the
ipsilateral III nerve.
2. Dilatation of the ipsilateral pupil which still reacts
to light and convergence though the patient is
drowsy.
3. True Hutchinson’s pupil which is dilated with loss
of all the reflexes and the patient shows increasing
drowsiness progressing to coma. During this stage
there may be some paresis of the extraocular
muscles supplied by the III cranial nerve. In the
956 Section 8: Neuroophthalmology
terminal stage the contralateral pupil becomes
dilated and fixed. It is a grave prognostic sign—its
development is an indication of cerebral decom-
pression.
The genesis of Hutchinson’s pupil in raised intra-
cranial pressure may be due to two causes:
a. Herniation of the temporal lobe into the
tentorial hiatus where the III nerve is impinged,
or
b. The III nerve may be pressed against the
ipsilateral ridge of the tentorial notch or the
nerve may be compressed immediately after its
emergence from the cerebral peduncle either by
the posterior cerebral or superior-cerebellar
artery. Due to the pressure there may be
interference with the intraneural or perineural
blood circulation; and therefore, the pupillary
sign may be reversible if treatment is instituted
at an early stage.
WERNICKE’S HEMIANOPIC PUPIL:
HOMONYMOUS HEMIANOPIC
PUPILLARY RIGIDITY
Homonymous hemianopia is due to lesion in the
visual pathway beyond the chiasm either in the optic
tract or in optic radiation. If the lesion is located
between the chiasm and the point where the pupillary
reflex fibers branch off just distal to the lateral
geniculate body, there is an impairment of pupillary
reaction. Neither pupil will react if the light falls on
blind retinal halves but both pupils will react if the
light falls on the intact halves. If the lesion in the
afferent pathway occurs proximal to the optic nerve,
the pupillary reflexes as well as vision are lost on
stimulation of the blind halves of the retina. If the
lesion is in the visual pathways beyond the terminal
portion of the optic tract where the pupillary fibers
are separated from the visual fibers then there will be
hemianopic field defect, but a lesion in the pupillary
pathways beyond this point results in a hemianopic
pupillary paralysis without hemianopia.4
The Wernicke’s sign is of importance in cases of
homonymous hemianopia due to tumor to localize the
lesion whether it is in the optic tract or optic radiation.
It is nevertheless difficult to demonstrate hemianopic
pupillary rigidity due to the difficulty in focusing the
light strictly on one half of the retina. Moreover, the
nasal half of the retina always shows more distinct
pupillomotor effect than the temporal half.
MARCUS GUNN PUPILLARY SIGN
When optic nerve of one eye has been damaged
anywhere between the globe and the chiasm then
under uniform illumination of the face the pupil of
the affected eye will be larger with the normal eye
covered than the pupil of the normal eye with the
affected eye covered. The pupillomotor strength of the
involved eye with identical illumination is weaker
than that of the healthy eye. If vitreous or lental opacity
is ruled out to be cause of visual diminution then
positive Marcus Gunn sign is a definite proof of
retrobulbar interference in conductivity of the optic
nerve of the affected side.
Pupil in Horner’s Syndrome
Horner’s syndrome is characterized by unilateral
ptosis, miosis, enophthalmos, hemifacial anhydrosis
and hypopigmentation of the iris on the affected side.
Ptosis is due to paralysis of the Muller’s muscle of the
eyelid and miosis due to paralysis of the dilator
pupillae muscle. Cause of enophthalmos is again due
to paralysis of the vestigial fibers of the sheet of smooth
muscle supporting the eyeball. Hemifacial anhydrosis
is caused by the paralysis of the sympathetic
secretomotor fibers supplying the sweat gland.
Vasoconstriction is presumed to cause iris depig-
mentation.
The main cause of Horner’s syndrome is pressure
on the sympathetic trunk in its course from the cervical
to the thoracic region. The clinical conditions that
cause Horner’s syndrome include enlarged hyaloid /
cervical lymph glands, dislocation of first rib, apical
carcinoma of lung (pancoast tumor), aneurysm of arch
of aorta, left ventricular hypertrophy, following
lobectomy (of lung) operation, disseminated sclerosis
and vascular lesions affecting the hypothalamico-
spinal tract. Pediatric Horner’s syndrome may be
either congenital or acquired. Rarely, Horner’s syn-
drome in newborn may be caused by birth trauma to
the brachial plexus.
CORNEAL SENSITIVITY
Corneal sensitivity is tested easily by asking the
patient to look straight ahead or slightly upward and
touching in turn the central and peripheral parts of
the cornea with a moist twisted wisp of cotton. When
the sensation is normal the patient will instantaneously
close the lids when the cotton wisp touches the cornea.
Sometimes it may be necessary to keep the palpebral
 Chapter 123: Neuroophthalmological Evaluation
fissure opened by fingers of one hand of the examiner
while the cotton wisp is hold in the other hand; the
force of the closure reflex of the lids can be felt with
the fingers. The direct and consensual corneal reflex
should be assessed to find out if there be any weakness
of any of the facial nerves. Sensation of both cornea
should be compared by subjective and objective
findings: the patient should be asked in which side
the sensation is felt more. In some local conditions like
herpetic keratitis, herpes zoster and after injury there
may be hyposthesia of the cornea. In testing corneal
sensation it is important to differentiate fifth (sensory)
from seventh (motor) nerve impairment of corneal
reflex specially in cases of brainstem lesion. Unilateral
loss or diminution of corneal sensation is an important
sign of a tumor of cerebellopontine angle. In orbital
apex syndrome, cavernous sinus syndrome and
superior orbital fissure syndrome corneal sensation
is diminished along with varying degree of impair-
ment or loss of function of 2nd, 3rd, 4th and 6th
nerves.5
957
OPHTHALMOSCOPY
Examination of the fundus is one of the most impor-
tant clinical investigations in neuroophthalmic dis-
orders. Hyperemia of the optic disk, papilledema,
neuroretinal edema and optic atrophy are some of the
signs which are considered to be of importance not
only to indicate the nature of the neuroophthalmo-
logical pathology but also in assessment of prognosis
and localization of the lesions.
REFERENCES
1. Griffin JF, Wray SH. Acquired colour vision defects in
retrobulbar neuritis. Am J Ophthalmol 1978;86:193.
2. Glaser JS, Savino PJ, Sumers KO. The photostress recovery
test in the clinical assessment of visual function. Am J
Ophthalmol 1970;83:255.
3. Huber A. Eye Symptoms in Brain Tumour. CV Mosby
Company, 1971.
4. Duke-Elder S, Scott GI. System of ophthalmology. Neuro-
ophthalmology 12: Henry Kimpton, 1971.
5. Walsh FB, Hoyt WF: Clinical Neuro-ophthalmology, Ed 3,
Vol 1-3; Williams and Wilkins, Co. 1969.
 Chapter 124

Normal and Abnormal Pupils

G Natchiar, Subhuram

The size of pupil is determined by a number of factors Sympathetic Pathway

including age, level of alertness, level of retinal illumi-
The pathway is anatomically less well-defined but
nation,1 and the amount of accommodative effort.
probably originates in the posterior hypothalamus.
Change in pupillary diameter is influenced by para-
Fibers descend in an uncrossed fashion, undergoing
sympathetic and sympathetic pathways.
multiple synapses in the mesencephalon and pons to
terminate in the intermediolateral cell column of the
PUPILLARY PATHWAYS spinal cord at levels C8 to T2 (ciliospinal center of
Budge). Pupillomotor fibers exit from the spinal cord
Afferent Limb
The pupillary response to light probably originates in
the same rods and cones that provide visual signals
to the occipital cortex. Afferent pupillomotor fibers
travel via the optic nerves and cross at the chiasm.
After traversing the optic tracts they exit just before
the lateral geniculate body to enter the brain stem via
the brachium of the superior colliculus (Fig. 124.1).
Pupillomotor fibers form synapses in specific pretectal
nuclei; these pretectal nuclei then project to both
ipsilateral and contralateral Edinger-Westphal nuclei
in the oculomotor nuclear complex.

Parasympathetic Pathway
The efferent pupillary fibers exit the midbrain with
the third nerve. Initially these fibers are located on
the superior surface of the nerve, where they are
vulnerable to compression by aneurysms at the
junction of the posterior communicating and internal
carotid arteries, as well as by uncal herniation. As the
third nerve courses forward in the subarachnoid space
and cavernous sinus, the pupillary fibers move down
around the outside of the nerve to enter the inferior
division, to finally synapse at the ciliary ganglion.
Postganglionic fibers are then distributed to the iris Fig. 124.1: Anatomy of the pupillary constriction
sphincter and ciliary body via the short ciliary nerves. pathways (parasympathetic)
 Chapter 124: Normal and Abnormal Pupils 959
mainly at the T1 level and enter the cervical sympa- are several clinical syndromes in which pupillary
thetic chain at the level of the inferior cervical ganglion light-near dissociation is important (Parinaud, Argyll
(superior portion of the stellate ganglion), ascending Robertson, Adie’s amaurotic pupils). Clinically, if the
via this chain to synapse in the superior cervical pupils constrict well to light stimuli, there is little need
ganglion (Fig. 124.2). to test the near reflex. A poor near response in the
Postganglionic fibers travel with the internal presence of a good light response implies a lack of
carotid artery to enter the cranial vault. In the effort by the patient.
cavernous sinus these fibers have the carotid and join
the ophthalmic division of the trigeminal nerve to AFFERENT PUPILLARY DEFECTS
enter the orbit through the superior orbital fissure.
Shining a light in one eye of a normal subject causes
Sometimes sympathetic fibers travel with the sixth
both pupils to constrict.2 The pupillary reaction in the
nerve briefly before attaching to the first division of
illuminated eye is called the direct response, and the
the fifth nerve in the cavernous sinus.
reaction in the other eye is the consensual response
Sympathetic fibers reach the ciliary body and the
(Fig. 124.3). Because of the hemidecussation of afferent
dilator of the iris by passing through the nasociliary
pupillomotor fibers in the chiasm, and because there
nerve and the long ciliary nerves.
is another hemidecussation of the pupillomotor fibers
in the brain stem, the direct and consensual pupillary
Accommodation
responses are equal. When the light is shown in the
The near synkinesis consists of accommodation of the normal eye, both pupils will constrict, then redilate
lens, convergence, and miosis. The anatomic pathway
for pupillary constriction to near effort are less well-
defined than for the light reflex, but it is clear that the
two pathways are dissociated in the midbrain. There

Fig. 124.2: Origin and course of the Fig. 124.3: Pupillary light reflex
ocular sympathetic supply and swinging light test
960 Section 8: Neuroophthalmology

slightly. When the light is swung to the diseased eye,
the initial constriction will be decreased or absent, and
more redilation will occur. The diseased eye has a
relative afferent pupillary defect (also called the
Marcus Gunn pupil). The test used to detect the abnor-
mality is called the alternating (or swinging) light test.
The relative afferent pupillary defect (RAPD) is one
of the most important signs in neuro-ophthalmology.3
It provides objective evidence of disease affecting the
anterior visual system. Unilateral optic nerve disease
almost invariably causes an RAPD, bilateral optic
nerve disease causes an RAPD when the nerves are
not equally affected. Retinal disease causes an RAPD
proportional to the amount of visual loss; a small
macular lesion may not cause a pupil defect, but a
large macular lesion will usually cause such a defect.
An RAPD is not usually seen with cataract, acute
papilledema, refractive error, functional visual loss,
or cortical lesions. Optic tract lesions cause RAPDs if
there is more visual field loss in one eye than in the
other; because the temporal visual field is larger than
the nasal field, complete tract lesions are associated
with an RAPD in the contralateral eye.
RAPDs can be quantified by using neutral density
filters of increasing density to dim the light in front of
the better eye. The resultant number can be used to
follow a patient, and is very useful in correlating the
pupil findings with the rest of the eye examinations
in order to make a diagnosis. For example, a patient
with unilateral optic neuritis will have a denser pupil
defect than a patient with macular disease whose
visual acuity loss is similar. Afferent pupillary defects
occur when pupillomotor pathways are involved
between optic tract and Edinger-Westphal nucleus.
Three different syndromes are clinically important.
Argyll Robertson Pupils
This rare syndrome occurs in some patients with
tertiary syphilis involving the central nervous system.
The pupils are small (less than 2 mm) and often irre-
gular. They do not react to light, but the near response
is normal, one of the few situations in which a 1 mm
pupil reacts briskly. Iris atrophy frequently occurs;
portions of the iris transilluminate; dilatation is poor
after instillation of mydriatics. When vision is good,
this combination of findings is virtually pathogno-
monic of CNS syphilis.
A more common pupillary manifestation of
syphilis is a large, irregular pupil with a poor light
response and variably preserved near response.
Without special tests this particular appearance cannot
reliably be distinguished from conditions such as
Adie’s tonic pupil. When such a pupil is found a serum
FTA/ABS should be part of evaluation.
Parinaud’s Dorsal Midbrain Syndrome
Pupils in this condition are large, with poor light
response and good near response. Associated findings
include upward gaze paralysis, convergence-retrac-
tion nystagmus (best seen in attempted upgaze), small
amplitude skew deviation and lid retraction (Collier’s
sign). The most common cause is pineal region tumor;
other causes include stroke, multiple sclerosis and
hydrocephalus.
Pretectal Afferent Pupillary Defects
Occasionally a pretectal lesion will be predominantly
unilateral or will involve one side more than the other.
The effect of such a lesion on the pupillary responses
will be similar to that of an optic tract lesion, e.g. an
isolated pretectal lesion on the right will cause a
relative afferent pupillary defect in the left eye.4
LESIONS OF THE PARASYMPATHETIC SYSTEM
Third Nerve Palsy
Pupillary involvement in third nerve palsy is usually
accompanied by ptosis and limitation of ocular move-
ments. Pupillary dilatation may be the only sign of
third nerve palsy in two clinical situations: uncal
herniation and basal meningitis. Pupillary involve-
ment helps diagnose acute third nerve palsies. When
the pupil is involved an aneurysm at the junction of
the internal carotid and posterior communicating
arteries must be excluded. If the pupil is spared and
all other functions of the third nerve are completely
paretic, an aneurysm is not the cause.
Traumatic Mydriasis
Blunt traumas to the eye cause mydriasis by damaging
the pupillary sphincter. Notches in the pupillary
margin can be seen.
Pharmacologic Mydriasis
When mydriatic medications are accidentally or
intentionally instilled in the eye the pupil becomes
markedly dilated and reacts poorly to light and near.
Putting pilocarpine 0.5 or 1 percent in an eye with
 Chapter 124: Normal and Abnormal Pupils
mydriasis from third nerve palsy or Adie’s syndrome
will cause marked pupillary constriction (in Adie’s
syndrome painful ciliary spasm may be induced), but
in pharmacologic mydriasis the constriction will be
minimal.
LESIONS OF THE SYMPATHETIC SYSTEM
A lesion at any point along the sympathetic pathway
results in Horner’s syndrome, with ptosis and miosis
on the same side. The light and near reactions are
intact. The ptosis is caused by paresis of Muller’s
muscle. There is apparent enophthalmos, but exoph-
thalmometry readings are equal. When the lesion is
congenital, iris heterochromia will develop with
affected side usually being lighter. With CNS lesions,
anhidrosis affects the entire ipsilateral side of the body.
With second neuron lesions anhidrosis affects the
ipsilateral face and with postganglionic lesions
anhidrosis is either absent or limited to the forehead.
Confirmation of the diagnosis of Horner’s syndrome
may be done with topical cocaine 4 to 10 percent.5 In
a normal eye, the pupil will dilate but in Horner’s
syndrome the pupil will dilate poorly, since little or
no norepinephrine is being released into the synaptic
cleft. Localization of the lesion producing Horner’s
syndrome can be further refined by the use of
hydroxyamphetamine (Paredrine) 1 percent which
acts by releasing norepinephrine from the presynaptic
terminal. In a normal eye, paredrine will dilate the
pupil but in postganglionic Horner’s syndrome the
nerve terminal will have degenerated, and paredrine
will cause poor dilatation. In a preganglionic Horner’s
syndrome the postganglionic neuron will usually be
intact, and paredrine will dilate the pupil.
Localization of the lesion causing Horner’s syn-
drome is important. Preganglionic Horner’s syndrome
may be caused by CNS lesions, apical lung tumors
(Pancost tumors), thoracic aortic aneurysms, or trauma
to the brachial plexus. Isolated postganglionic
Horner’s syndrome is often benign. Postganglionic
Horner’s syndrome with ipsilateral headache has
961
several causes. Patients with typical cluster headaches
may develop Horner’s syndrome on the ipsilateral
side during an acute attack. The Horner’s syndrome
often resolves but may become permanent after
repeated attacks. Patients with spontaneous dissection
of the carotid artery often present with ipsilateral head
pain and Horner’s syndrome. This condition must be
recognized since stroke is a possible complication.
Patients with Raeder’s paratrigeminal syndrome are
usually aged males who present with Horner’s
syndrome and daily unilateral headaches.6 Congenital
Horner’s syndrome is usually caused by birth trauma
to the brachial plexus. Another cause of Horner’s
syndrome in childhood is neuroblastoma arising in
the sympathetic chain.
Simple Anisocoria
About 25 percent of individuals have noticeable
differences in pupillary diameter when comparing one
eye to the other. The condition is more common in
older adults. Usually the difference in pupil size is
less than a millimeter. Problems in diagnosis occur
when there is congenital or senile ptosis on the side of
the smaller pupil. The pupils in simple anisocoria
dilate after cocaine instillation, and there is no
dilatation lag.
REFERENCES
1. Cox TA. Pupillography of a relative afferent pupillary defect.
Am J Ophthalmol 1986;101:320.
2. Thompson HS, Corbett JJ, Cox TA. How to measure afferent
pupillary defect. Surv Ophthalmol 1981;26:39.
3. Thompson HS, Montague P, Cox TA. The relationship
between visual acuity, pupillary defect and visual field loss.
Am J Ophthalmol 1982;3:681.
4. Ellis CJ. Afferent pupillary defect in pineal region tumour. J
Neurol Neurosurg Psychiatr 1984;47:739.
5. Grimson BS and Thompson HS. Drug testing in Horner’s
syndrome. In Graser JS, Smith JL (Eds): Neuroophthalmology.
St. Louis: CV Mosby and Co. 8:265.
6. Grimson BS, Thompson HS. Raeder’s syndrome: A clinical
review. Surg Ophthalmol 1980;24:199.
 Chapter 125
Chiasmal Lesions:
Chiasmal Syndromes
LC Dutta
The lesions that affect the optic chiasm may be divided
into groups depending upon the site at which the
nerve fiber damage occurs to produce characteristic
field defects. Clinically, the conditions may be
classified according to the site of the lesion. One in
four of the intracranial tumors arise from the chiasmal
region. The clinical conditions include the following:
1. Inflammatory Chiasmal basal arachnoiditis or
chiasmal arachnoiditis or chronic chiasmal
arachnoiditis.
2. Neoplastic:
a. Intrasellar lesions:
i. Pituitary tumor
ii. Infraclinoid aneurysm.
b. Suprasellar lesions:
i. Meningioma of tuberculum sellae
ii. Glioma of the chiasm
iii. Supraclinoid aneurysm
iv. Craniopharyngioma (intrasellar also).
c. Parasellar tumor:
i. Meningioma of the sphenoid ridge
ii. All the tumors of the middle fossa and caver-
nous sinus.
Chronic Chiasmal Arachnoiditis
Infection of the leptomeninges commonly from
hematogenous source is due to syphilis, tuberculosis
or as a part of cerebral infection like encephalitis. Due
to inflammatory exudates the fine structure of the
arachnoid membrane is altered and it becomes
adherent to the pia inside and dura outside. Inflam-
matory products of pia-arachnoiditis and interstitial
neuritis exert pressure upon the nerve fibers causing
to visual field defect.
Symptoms of chiasmal arachnoiditis are variable.
In the acute stage headache is the early symptom.
Central visual acuity may be normal; in advanced
cases, depending upon the extent of atrophy of the
nerve fibers there may be various grades of visual loss.
Concentric constriction of visual field is the usual
finding but there may be central, paracentral or
cecocentral scotoma also. Pale optic disk with visual
loss and concentric contraction of the field of vision
are suggestive evidence of chiasmal arachnoiditis.
Pituitary Tumor
Pituitary body and the hypothalamus form a control
unit for the endocrine system of the body. Hypo-
thalamus is a small specialized area at the base of the
brain lying superior and posterior to the optic chiasm
and superior to the pituitary gland. The pituitary
gland is just below the base of the brain and is
connected by the pituitary stalk with the tuber
cinerium of hypothalamus. Pituitary is a reddish gray
somewhat ovoid body measuring about 12 mm in its
transverse and 8 mm in anteroposterior diameter. It
is located in the hypophyseal fossa of the sphenoid
bone which is roofed by a circular fold of dura mater
termed as the diaphragm sellae. The upper surface of
the body of the sphenoid is called sella turcica because
it resembles a Turkish saddle and the posterior part
of this region is hollowed to form the pituitary fossa.
Posterior to the fossa a plate of bone projects upward
and forward to form the dorsum sellae. The superol-
ateral angle of dorsum sellae is expanded to form the
posterior clinoid process. Laterally the pituitary fossa
is related to the internal carotid artery. Anterior clinoid
process is at the lateral side of the fossa. Diaphragma
 Chapter 125: Chiasmal Lesions: Chiasmal Syndromes
sellae which roofs the pituitary fossa is pierced by a
small central aperture through which the infundi-
bulum passes downward and forward. The infundi-
bulum separates the anterior part of the upper surface
of the hypophysis from the optic chiasm. Cavernous
sinus and optic chiasm are intimately related on either
side of the pituitary fossa.
Neoplasms affecting the pituitary body may be of
three types:
a. Adenoma
b. Adenocarcinoma
c. Metastatic tumor.
Adenoma is the most common tumor of pituitary
gland. Depending upon the staining character of the
cells the adenoma may be chromophobe and chormo-
phil; the latter may be again acidophilic or basophilic.
Chromophobe Adenoma
It comprises 75 to 80 percent of all the tumors of the
gland typically in adults of about 30 years of age. It is
called chromophobe because of the absence of
acidophilic or basophilic granules in the cytoplasm of
the cells. Non-ophthalmic clinical features are
amenorrhea, impotence and loss of libido, decreased
metabolic rate with weight gain and adiposity.
Acidophil Adenoma
It accounts for about 20 percent of pituitary tumors
and develops from the eosinophilic cells of the anterior
lobe of the pituitary gland. It frequently occurs in
females. Due to endocrine hyperfunction in young
individuals it causes gigantism and in adults acro-
megaly characterized by enlargement of hands and
feet, prominence of jaw, thick tongue, deep voice,
amenorrhea and loss of libido.
Basophil Adenoma
It is rare. Its incidence is about 2 percent or less. The
typical feature of this tumor is Cushing’s syndrome
which is characterized by adiposity, moon-face,
hypertension and hypogonadism.
Mixed Adenoma
It consists of both chromophobe and acidophil cells.
Frequency of mixed adenoma is about 7 percent. Due
to the combined effect of the two types of tumor there
is a tendency for extensive growth with endocrine
activity.
Adenocarcinoma and metastatic tumors of the
pituitary gland are very rare. These are rapidly
growing tumors. The neoplasm invades the base of
963
the skull and floor of the sella and spreads into the
brain. Carcinoma of the breast is the most common
neoplasm to metastasize in the pituitary gland.
Clinical picture It may vary depending upon the nature
of the tumor and its pressure upon the adjoining
structure. When the pituitary fossa is shallow then
expansion of the tumor is easy. If the fossa is deep
then the tumor tends to grow laterally toward the
cavernous sinus. Though, in general, pituitary tumor
grows slowly sometimes a sudden enlargement may
occur as in pituitary apoplexy. This type of episode
occurs when either there is hemorrhage inside the
tumor or infarction of the vessels in the pituitary stalk
leading to acute necrosis. Sometimes there may be
formation of an abscess in the adenoma. Sudden
blindness and paralysis of extraocular muscles are
features of pituitary apoplexy.
The clinical picture of pituitary tumor is classified
into: (a) Endocrine disorder, (b) Pressure symptoms,
and (c) Neuroradiological findings. Endocrine
disorders have been indicated earlier. Symptoms
related to endocrine disorders are more common in
male than in female. In general, ophthalmic mani-
festations do not present with endocrine disorders.
Headache and visual defect are the main features
of pressure effect. Headache is due to expansion of
the diaphragm sellae. Sometimes there may be severe
headache with bitemporal distribution. When the
tumor bursts through diaphragm sellae then the
headache subsides or diminishes in intensity only to
return soon associated with vomiting due to raised
intracranial pressure as a result of extension of the
tumor out of the pituitary fossa.
Field Changes (Fig. 125.1)
Pituitary adenomata typically exert their pressure in
the midline from below. There may be variation of
exact sites of nerve fiber compression depending upon
whether the chiasm is prefixed with short optic nerves,
in the midline position or postfixed with long optic
nerves. Classical field defect is a symmetrical
bitemporal hemianopia. When the chiasm is pressed
from below the defect in the field commences in the
periphery of the upper temporal quadrant then
involves the lower temporal field to produce the
typical bitemporal hemianopia frequently leaving
behind a temporal island, and finally moves upward
in the nasal field to produce complete blindness. As a
rule the pressure is never exactly median so that one
eye field defect commences and progresses before the
other eye, hence the defects are asymmetrical on the
two sides. A typical pituitary tumor field is an initial
964 Section 8: Neuroophthalmology
Fig. 125.1: Progressive stages of visual field defect of the right
eye: Starting with superior temporal defect leading to complete
blindness corresponding to the growth of the tumor
peripheral depression first for color in one upper
temporal quadrant only. The gradual loss of one
temporal field with similar loss following on the other
side to attain bitemporal hemianopia. In actual
practice the defects produced by large tumor vary
from no defect to combination of unilateral or bilateral
field defects in all quadrants. Reasons for the irregular
patterns include variations in the position of the
chiasm above the sella and variable compromise of
blood vessels supplying the optic chiasm.
Other pressure effects consist of disturbance of III,
IV, and VI nerves, nystagmus, abnormal pupillary
reflexes, trigeminal neuralgia, some degree of exoph-
thalmos and pressure effects on the hypothalamus.
Ophthalmoscopy
Atrophy of the optic disk is a distinct ophthalmoscopic
finding of pituitary tumor. Disk changes may vary
from slight pallor in early stages to complete papery
white primary looking optic atrophy.
Radiological Studies
Initial radiological studies should be a high quality
plain picture preferably with coned down lateral and
frontal view of the sella turcica. An increase in size or
apparent erosion of the sella turcica is often the
most common radiological sign of pituitary tumor.
However, conditions like craniopharyngioma, menin-
gioma, epithelial or other cysts in that area, metastatic
deposit of breast carcinoma, granuloma and empty
sella syndrome should be considered in differential
diagnosis of pituitary adenoma. CT scan and MRI are
better radioimaging procedure. Radioimaging shows
ballooning of the sella without any sign of erosion of
bone forming the boundary of the pituitary fossa.
Surgical intervention becomes necessary in case of
cerebrospinal rhinorrhea.
Empty Sella Syndrome
It describes a non-tumorous enlargement of the sella
turcica that may be misdiagnosed as a pituitary tumor.
Empty sella syndrome may be primary or secondary.
Primary one occurs when the arachnoid diverticulum
enlarges to such an extent that the sella becomes
enlarged and the pituitary is compressed against the
floor of the sella. The subsequent remoulding of the
pituitary fossa and flattening of the pituitary gland
constitute the radiological entity although it is worth
mentioning that the pituitary fossa is not invariably
enlarged. There is no apparent pituitary, sphenoid
sinus or intracranial disease. Some empty sella
develop secondary to infarction or regression of a
tumor due to which the sella was enlarged. The
secondary empty sella syndrome may also result after
treatment of pituitary tumor, suprasellar colloid cyst
of the 3rd ventricle, primary sella arachnoid cyst and
benign intracranial hypertension.
About 90 percent empty sella are found in obese
women. Non-ophthalmic manifestations consist of
headache, recurrent epistaxis, cerebrospinal fluid
rhinorrhea and nasal discharge.
Ocular manifestations are visual field defect, loss
of central vision and bilateral optic atrophy. Bitempo-
ral contraction of visual field is the characteristic field
change but generalized peripheral contraction or
unilateral temporal contraction of visual field also may
occur. Visual loss may be secondary to traction on the
hypophyseal stalk which pulls down the floor of the
third ventricle.
Craniopharyngioma
(Suprasellar or Rathke’s Pouch Cyst:
Hypophyseal Duct Tumor: Adamantinoma)
Development of the pituitary gland starts as an
outgrowth from the stomatodeum (of the pharyngeal
pouch) near the cephalic end of the neural tube. As
development advances, the outgrowth becomes
spherical and gets detached from the stomatodeum;
this finally becomes the anterior lobe of pituitary. The
sphenoid bone appears between the pituitary body
and the stomatodeum. The posterior lobe is formed
 Chapter 125: Chiasmal Lesions: Chiasmal Syndromes
from downgrowth from the neural epithelium. It is
possible that during the developmental process some
of the cells of the stomatodeum may remain which
later give rise to neoplastic formations which is
commonly known as craniopharyngioma. The epithe-
lial remnants are usually present above the diaphrag-
ma sellae anterior to the infundibulum; therefore,
craniopharyngiomata are primarily suprasellar
tumors but may occasionally be intrasellar also. The
neoplasm varies considerably in size from a small cyst
of the size of a pea to an enormous solid calcified
multicystic mass of the size of a fist containing dark
albuminous fluid and cholesterol. The intrasellar type
may be primary or may result from invasion from the
suprasellar one.
Craniopharyngioma is predominantly a tumor of
childhood but due to its silent nature and slow
progress its manifestations may sometimes appear
quite late in life. In children and adolescents the patient
may present with headache and vomiting. When
circulation of cerebrospinal fluid is impeded due to
invasion of the third ventricle by the tumor then
internal hydrocephalus develops. Impaired develop-
ment of the pituitary gland may produce various
grades of endocrine disturbance. In adults the
presenting symptoms are similar to those of adenoma
of the pituitary gland. Occasionally the clinical
features may be confused with those of retrobulbar
neuritis. In children the predominant sign of increased
intracranial pressure is choked disk which may
ultimately produce optic atrophy. In adults visual field
defect with papery white disk having clear-cut margin
may sometimes be associated with paresis of the third
and sixth cranial nerves.
Radiological features are erosion of the anterior
and posterior clinoid processes and dorsum sellae
from above; hence, dorsum sellae may appear to be
compressed. In intrasellar craniopharyngioma pitui-
tary fossa is enlarged as in adenoma of pituitary gland.
Shadow of calcification in craniopharyngioma is a
diagnostic radiological sign. The calcification may
vary from small flecks to enormous calcareous masses.
Sometimes a faint calcified shadow above the sella
may be due to an aneurysm of the internal carotid
artery.
Treatment of craniopharyngioma is surgical removal;
recurrent cases may be treated by radiation therapy.
Visual prognosis depends upon early diagnosis and
surgery. Though, it is rare for the atrophic nerve fibers
to regenerate, there may be slight visual improvement
after successful surgical removal. Malignant change
also may take place if the tumor is not completely
removed.
965
Meningioma of the Tuberculum Sellae
This suprasellar meningioma arises from the dura
mater of the tuberculum sellae and its adjoining bony
landmarks including the anterior clinoid process and
medial part of the sphenoid ridge. Growth of these
mulberry-like tumors is less rapid than meningioma
arising from other parts of cranial dura. These menin-
giomas do not occur in en-plaque form and are rarely
in the midline. Therefore, classical chiasmal symptoms
are rarely seen. The first sign is always a significant
unilateral loss of visual acuity. Sometimes the vision
in one eye may be completely lost without any
manifestation or any sign in the other eye. In compa-
rison to craniopharyngioma the asymmetry of the
visual field defect in meningioma of tuberculum sellae
is more pronounced. Amaurosis in one eye with
temporal hemianopia of the other eye is the most
characteristic and frequent sign.
Fundoscopy shows unilateral primary looking
optic atrophy with clear-cut disk margin or optic
atrophy may be more pronounced in one side than in
the other. In meningioma arising from the medial part
of the sphenoid ridge Foster Kennedy syndrome, viz.
optic atrophy in one eye and papilledema of varying
degrees in the other eye, may be seen.
Diagnosis It depends upon field defect with radio-
logical evidence of normal pituitary fossa and negative
endocrinological abnormality. However, in late stage
of the disease there may be decalcification or erosion
of the anterior and posterior clinoid processes. CT scan
and MRI provide accurate diagnosis.
Glioma of the Optic Nerve and Chiasm
This condition may be associated with neuro-
fibromatosis (von Recklinghausen’s disease). Glioma
is a tumor derived from the astrocytes (hence, some-
times called astrocytoma) and oligodendroglial cells
of the optic nerve. Glioma may be primarily in the
optic nerve or in the chiasm; sometimes glioma of the
optic nerve may extend to the optic tract or vice versa.
As opposed to meningioma, glioma is common in
children. The tumor is a smooth or nodular elastic
mass enclosed within the dura. As such it is not a
malignant tumor.
Presenting symptom of glioma of the optic nerve
is unilateral visual loss. In glioma of the optic chiasm
there is hemianopia of various grades. When the optic
nerve is involved in primary glioma then proptosis
develops in fairly late stage. It may be considered as a
generalized statement that in glioma of the optic
nerve visual loss is early and proptosis develops later,
whereas in meningioma proptosis is an early
966 Section 8: Neuroophthalmology
manifestation and visual defect occurs late. Limitation
of ocular movement in advance stage of glioma of
optic nerve is mechanical and not due to paralysis of
extraocular muscles.
The points of diagnostic importance are the radio-
logical findings. When the tumor extends forward then
the optic foramen is enlarged. Unilateral enlargement
of the optic foramen is a sign of glioma of the optic
nerve, whereas in case of glioma of the optic chiasm
both the optic foramen may be enlarged. In chiasmal
glioma there may be deformation of the sella turcica
in the shape of an omega or pumpkin resulting from
destruction of the anterior clinoid process by the tumor
which spreads along the optic nerve toward the orbit.
Removal of glioma of optic nerve involving the
chiasm should be by a combination of transfrontal and
orbital approach; when the investigations reveal that
the tumor is limited to the orbital portion of the optic
nerve then lateral orbitotomy may be sufficient to
remove the tumor. In other words when there is
enlargement of the optic foramen then complete
removal of the tumor may not be possible by orbital
route.
Though visual improvement is not possible alone
general prognosis of glioma of the optic nerve is good.
As the tumor is benign, question of secondary
metastasis does not arise. But if the tumor is allowed
to grow in size then intracranial pathology is bound
to occur due to pressure effects with grave conse-
quence.
Sphenoidal Ridge Syndrome:
Superior Orbital Fissure Syndrome
Superior orbital fissure is almost triangular in shape
formed by the greater (inferior) and lesser (superior)
wings of sphenoid. Medially the base of the triangle
is formed by the body of sphenoid; laterally a portion
of frontal bone is wedged at the apex between the
lesser and greater wing of sphenoid. The spine for the
lateral rectus projects into the fissure dividing it into
a wider posteroinferomedial end which lies below the
optic foramen and transmits all the important vessels
and nerves of the orbit except the optic nerve and
ophthalmic artery while the lateral narrower limb is
virtually occluded by dura mater. These structures
may be divided into two sets: one set within the
annulus or between the two heads of lateral rectus
muscle consisting of superior division of 3rd nerve,
the nasociliary nerve and sympathetic root of the
ciliary ganglion, the inferior division of 3rd nerve and
6th nerve and sometimes the ophthalmic vein or veins
in that order from above downward. 4th, frontal and
lacrimal nerves, superior ophthalmic vein and the
recurrent lacrimal artery pass through the fissure
above the annulus.
Sphenoidal ridge syndrome or superior orbital
fissure syndrome is mainly due to meningioma of the
sphenoidal ridge. Depending upon the clinical
features the meningioma of the sphenoidal ridge may
be divided into three types:
a. From the outer third of the ridge—the symptoms
of meningioma of this portion are predominantly
non-ophthalmic and include headache, epileptic
fits, and facial palsy due to pressure effect on the
neighboring brain tissue.
b. From the middle one-third.
c. From the inner one-third.
Meningiomas arising from the middle and inner
one-third produce mostly ocular symptoms which are
more marked in the latter than in the former type. In
addition to the general signs of increased intracranial
pressure such as headache, nausea and vomiting,
unilateral slowly progressive visual loss the patients
may complain of cloudy, indistinct or blurred vision
or appearance of fog or shadow. Due to involvement
of the oculomotor nerves diplopia is a common
symptom.
Meningioma of lesser wing of sphenoid extending
into the superior orbital fissure produces superior
orbital fissure syndrome which is characterized by
involvement of oculomotor, trochlear and abducens
nerves associated with unilateral proptosis. When the
meningioma does not extend to the orbital fissure
there will be only ipsilateral optic atrophy; if the tumor
assumes a considerable size contralateral papilledema
develops due to raised intracranial pressure caused
by the increasing size of the tumor. Papilledema does
not develop in the eye with optic atrophy. This is
known as Foster Kennedy syndrome. Frequently, it
becomes difficult to decide whether ocular motility is
restricted due to paralysis of the nerves or due to
mechanical restriction resulting from extension of the
meningioma in the orbital cavity producing exoph-
thalmos. Exophthalmos is an important and common
ocular sign of meningioma of the lesser wing of
sphenoid. However the degree of exophthalmos may
be variable depending upon the degree of extension
of the tumor into the orbit. Exophthalmos may be due
to interference with venous drainage and stasis as well
as due to invasion of the orbit by the tumor. As a result
of chronic venous stasis the lids show a characteristic
type of brawny edema and there may be congestion
and dilatation of the conjunctival and episcleral blood
vessels.
 Chapter 125: Chiasmal Lesions: Chiasmal Syndromes 967
Various degrees and varieties of field defects also Increased intracranial pressure will produce papill-
may be demonstrated in meningioma of sphenoidal edema only on the healthy unaffected eye and there
ridge depending upon whether and how much will be no papilledema on the side with optic atrophy.
pressure is exerted upon the optic nerve. Mild The value of Foster Kennedy syndrome is lessened
concentric contraction of the visual field or enlarge- by the fact that even tumors of the third ventricle or
ment of the blind spot may be due to papilledema the cerebellum can cause similar symptoms by remote
resulting from raised intracranial pressure. Monocular effect as for example via an internal hydrocephalus
nasal or temporal hemifield defect may develop and dilatation of the third ventricle. In nontumoral
depending upon the site of involvement of the optic cases also, as in chiasmal arachnoiditis, Foster
nerve. Kennedy syndrome may develop.
Pupillary disturbance is another important sign
and it may be either due to lesion of the afferent fibers Cavernous Sinus Syndrome
of the optic nerve or a lesion of the efferent pupillo-
Any lesion in the neighborhood of the cavernous sinus
motor fibers of the oculomotor nerve and hence there
may produce pressure effects on the III, IV, VI and
may be disturbance of direct and consensual pupillary
first and second divisions of the trigeminal nerve.
reaction to light on the side of the tumor which may
Causes of cavernous sinus syndrome are:
even assume the form of a dilated fixed pupil.
a. Cavernous sinus thrombosis
Radiological appearance of sphenoid ridge menin-
b. Aneurysm of internal carotid artery
gioma depends upon the type of the meningioma.
c. Lateral extension of pituitary adenoma
There may be osteomatous reaction of the lesser wing
d. Meningioma of middle cranial fossa
of sphenoid in cases of meningioma en plaque and
c. Trigeminal neurinoma.
demineralization of the bone around the optic foramen
In lesions of the anterior part of the cavernous sinus
showing osteoporosis in cases of vascularized
in addition to the oculomotor nerves only the first
meningioma. Carotid angiography helps to confirm
division of the trigeminal nerve is involved and in
the type and site of the tumor. Commonly the
posterior lesions both the first and second divisions
ophthalmic artery is seen to be greatly enlarged to cope
are involved. Of the three oculomotor nerves the sixth
with increased blood supply to the meningioma. CT
nerve is most vulnerable in this region because it
scan of the optic canal is helpful to differentiate glioma
traverses through the sinus unlike the other nerves
from meningioma of the optic nerve. In the former
which are on the lateral wall of the sinus (Fig. 125.2).
condition the optic canal is enlarged but in the latter
it is narrowed due to osteomatous thickening.

Foster Kennedy Syndrome

Combination of optic atrophy in one eye and papill-
edema in the other eye is known as Foster Kennedy
Syndrome. This is an important neuro-ophthalmo-
logical feature of basofrontal intracranial space occu-
pying lesion. The conditions which produce Foster
Kennedy syndrome include.
a. Meningioma of the olfactory groove and of the
floor of the anterior cranial fossa, sphenoidal ridge
and suprasellar meningioma.
b. Craniopharyngioma with forward extension.
c. Glioma of the intracranial portion of the optic nerve
and
d. Saccular and fusiform aneurysm of the internal
carotid artery.
Mechanism of production of the syndrome is that
at the initial stage the intracranial portion of the optic
nerve, i.e. the portion between the chiasm and the optic
foramen undergo atrophic change by a tumor situated
at the base of the brain with a backward extension. Fig. 125.2: Schematic diagram showing the
An atrophic optic nerve cannot develop edema. structure related to the cavernous sinus
968 Section 8: Neuroophthalmology

Orbital Apex Syndrome ridge syndrome (medial one-third) and superior

In orbital apex syndrome in addition to the III, IV, VI
and first division of V nerve, optic nerve is also
involved.
Central scotoma simulating retrobulbar neuritis,
edema of the optic nerve head or optic atrophy are
the various features of optic nerve involvement.
Sometimes there may be field defects. Exophthalmos
also develops in case of tumorous etiology. The causes
of orbital apex syndrome may be hemorrhage,
inflammation or neoplasm.
Superior Orbital Fissure Syndrome
There is very little difference between the orbital apex
syndrome, cavernous sinus syndrome, sphenoidal
orbital fissure syndrome. The main principle of
classifying these syndromes is that when the structures
i.e. III, IV, V and VI nerve course anteriorly, they get
separated from each other; in the superior orbital
fissure the two divisions of the third nerve remain
quite apart. Therefore in superior orbital fissure
syndrome the paralysis of the structures supplied by
the 3rd cranial nerve becomes regional rather than
according to the nerve supply. The levator palpebrae
superioris, superior rectus and superior oblique
muscles sometimes are simultaneously involved.
Exophthalmos may be a prominent feature even
without any visual defect in the early stage.
Differential diagnosis of the chiasmal syndromes
Table 125.1.

Table 125.1: Differential diagnosis of chiasmal syndromes (modified from Walsh)

Pituitary adenoma Meningioma Craniopha- Glioma of Aneurysm Chiasmal
of tuberculum ryngioma chiasma arachnoiditis
sellae
Age 30-50 30-50 Mostly Children As a rule, All ages
children, also adults
adults
Eye ground Primary optic Primary optic In children Primary optic Normal disk Unilateral or
atrophy atrophy, often papille- atrophy. or optic bilateral optic
more on one edema, in atrophy. atrophy or
side. adults optic papilledema.
atrophy.
Visual field Symmetrical Asymmetrical Asymmetrical Unilateral or More or less Central
bitemporal chiasmal bitemporal bilateral distinct scotomas,
hemianopia syndrome, hemianopia temporal bitemporal concentric
often amaurosis visual field hemianopia contraction,
of one eye with defects. (fluctuations) unilateral or
temporal bilateral
hemianopia of hemianopia.
the other
Endocrine Hypopituitarism, None Hypopituita- None or None None
signs hyperpituitarism, rism, perhaps hypopituita-
or mixed. also hypothala- rism
mic signs
Localization Sellar Suprasellar Intrasellar and Suprasellar Suprasellar Optic and
supraseller (supraclinoid chiasmal
(polyuria, aneurysm), arachnoid.
polydipsia, etc) intrasellar
(infraclinoid
aneurysm).
X-ray Ballooning of Sella normal, Suprasellar Unilateral or Often, Negative
findings sella, thinning of hyperostosis calcifications bilateral negative,
floor of sella, of tuberculum widening of occasionally
erosion of clinoid sellae optic annular
processes. foramen. calcium shadows
 Chapter 126

Visual Field Defects

G Natchiar, Subhuram

OPTIC NERVE
The arrangement of nerve fibers in the distal portion
of the optic disk corresponds generally to the
distribution of the fibers in the retina. The papillo-
macular fibers occupy a large portion of the temporal
portion of the disk. Because of this, the fibers from the
temporal retina are squeezed into the superior and
inferior poles of the disk. Approaching the optic
foramen, the macular fibers take a more central
location in the optic nerve, and the fibers from the Fig. 126.1: Various forms of scotoma. Dark area—blind spot;
retina assume a more temporal location in the nerve. hatched area—scotoma
The major volume of the optic nerve is occupied solely
by macular fibers. Visual field defects produced by
optic nerve lesions take several forms.1

Central Scotoma
When unilateral, this field defect is characteristically
found in patients with optic neuritis and compressive
lesions of the optic nerve. When bilateral, differential
diagnosis should include nutritional deficiencies, toxic
optic neuropathies, and hereditary disorders.

Cecocentral Scotoma
This field defect is classically found in patients with
toxic optic neuropathies but can be produced by an
optic pit with serous retinal detachment (Figs 126.1 Fig. 126.2: Cecocentral scotoma
and 126.2). (left eye foveal vision spared)

Arcuate Scotoma
This field defect is produced by selective damage to
the nerve fibers comprising the superior and inferior
arcuate nerve fiber bundles (Fig. 126.3). Patients with
glaucoma or ischemic optic neuropathy often develop
such defects. Anomalies such as optic pits, optic disk
drusen and chronic papilledema may also cause such
defects.
Altitudinal Visual Field Defect
This defect is usually caused by ischemic optic neuro-
pathy (Fig. 126.4).
970 Section 8: Neuroophthalmology

Fiber damage at the anterior angle of the chiasm Lesions

Fig. 126.3: Arcuate scotoma in right eye as an early field
defect in primary open angle glaucoma
like aneurysm of the anterior communicating artery
and meningioma of tuberculum sellae can produce
an anterior chiasmal syndrome in which there is a
combination of loss of visual acuity and visual field
in one eye with a superior temporal defect in the
opposite eye (junctional scotoma) due to damage to
the ventral crossing fibers that have looped onto the
opposite optic nerve2 (Fig. 126.5).
Fiber damage in the body of the chiasm Lesions damaging
the body of the chiasm produce relative or absolute
bitemporal hemianopias, e.g. pituitary adenoma,
craniopharyngioma, supraseller meningioma.
Fiber damage in the posterior angle of the chiasm Lesions
affecting this region destroy posterior macular
crossing fibers resulting in bitemporal hemianopic
scotoma, e.g. craniopharyngioma, pituitary adenoma
when the chiasm is prefixed (Fig. 126.6).

Fig. 126.4: Altitudinal visual field defect

in ischemic optic neuropathy Fig. 126.5: Junctional scotoma due to anterior chiasmal lesion:
Loss of central visual acuity in one eye and superior temporal
It should be remembered that all of these visual defect in the other eye
field defects can be produced by retinal lesions.
Investigation of any patient with a visual field defect
must include a careful examination of the retina.

Optic Chiasm
Lesions arising in the vicinity of the chiasm produce
certain types of field defects by means of compression
as well as by involvement of the blood vessels
supplying the chiasm. The precise field defect depends
on the location of the optic chiasm with respect to the
sella turcica (normal, prefixed or postfixed) and the
direction of the growth of the lesion.
Lesions that affect the optic chiasm may be divided
into groups according to the site at which nerve fiber
damage occurs and the visual field defect that is Fig. 126.6: Bitemporal hemianopia due to chiasmal
produced. pressure by pituitary adenoma
 Chapter 126: Visual Field Defects 971
Fiber damage to the optic tract Sellar and suprasellar
lesions that expand posteriorly (typical example is
craniopharyngioma) may compress fibers of the optic
tract, resulting in an homonymous hemianopia.
Binasal hemianopia due to lateral chiasmal compression3
(Fig. 126.7) This is rare. Lateral compression of the
chiasm can be caused by aneurysm of one carotid
compressing the chiasm against opposite carotid
artery. Bilateral compression is also possible by
atherosclerotic, inelastic carotid arteries. However,
binasal defects are usually due to a disease process at
the level of the optic disk such as glaucoma.

OPTIC TRACT
Visual field defects due to retrochiasmal lesions
generally tend to be homonymous, i.e. they occur in Fig. 126.8: Tendency for homonymous hemianopia due to
each eye on the same side of visual space4 (Fig. 126.8). unilateral retrochiasmal lesion
The similarity between the defects in each eye is
termed congruity. An essential feature of retro-
chiasmal lesions is their respect for the vertical midline
(Fig. 126.9). Nerve fibers from corresponding retinal
elements in each eye are not closely aligned in either
the optic tract or lateral geniculate body.
For this reason, visual field defects due to lesions
in these regions are generally relatively incongruous
homonymous hemianopias.

RETROGENICULATE LESIONS
Homonymous hemianopias produced by lesions in
the temporal lobe tend to be slightly incongruous and

Fig. 126.9: Incongruous homonymous hemianopia in

anterior tract lesion

denser above (Fig. 126.10). Homonymous hemi-

Fig. 126.7: Binasal hemianopia due to chiasmal pressured
from temporal side (atherosclerotic internal carotid arteries)
anopias produced by lesions in the parietal lobe tend
to be relatively more congruous and either complete
or denser below. The common lesions are infarctions,
tumors and abscesses. Lesions in the temporal or
parietal lobes that produce visual field defects also
produce other neurological signs and symptoms that
often help to localize the causative lesion. Temporal
lobe lesions often cause seizures and formed visual
hallucinations. Parietal lobe lesions may have
associated hemiparesis, visual perceptual difficulties,
agnosias, right-left confusion and acalculia.
Abnormalities in optokinetic nystagmus may occur
if optomotor pathways in the posterior cerebral
972 Section 8: Neuroophthalmology
Fig. 126.10: Incongruous homonymous hemianopia in
anterior part of the retrogeniculate lesion (optic radiation)
hemisphere are damaged. When these pathways are
interrupted, the optokinetic nystagmus will be
abnormal when targets are rotated toward the lesion
(opposite the hemianopia). In most instances, the
combination of a homonymous hemiamopia and
optokinetic nystagmus asymmetry suggests a parietal
lobe lesion. In the occipital cortex, fibers from
corresponding retinal elements of the two eyes lie
extremely close together. For this reason, homo-
nymous hemianopias resulting from lesions in this
region are extremely congruous. 5 There may be
sparing of the macula. Besides from producing visual
field defects, lesions of the visual cortex may produce
uniform visual hallucinations (Fig. 126.11).
In addition to homonymous hemianopias and
scotomas, there are specific visual field defects
classically associated with occipital lobe lesions.
The checkerboard field Caused by bilateral, incompletely
homonymous hemianopias, superior on one side and
inferior on the opposite side.
Bilateral homonymous hemianopia with macular sparing
(keyhole field) Although this appears to be a true
tubular field, careful visual field testing along the
vertical midline will establish the true nature of the
defect—there will usually be a vertical step.
Fig. 126.11: Extremely congruous homonymous hemianopia
with sparing of macula due to lesion in the most posterior part
of the visual pathways (occipital cortex)
Bilateral homonymous altitudinal defects These are
usually inferior, caused by infarction or trauma to both
superior occipital lobes.
Cortical blindness This is a syndrome of complete
blindness associated with normal pupillary responses.
Anton’s syndrome (denial of blindness) is occasionally
associated with cortical blindness.
The Riddoch phenomenon is perception of moving
targets but not static targets; this finding is most
prominent with retrogeniculate lesions.
REFERENCES
1. Natchiar G. Visual field defects in intracranial lesions. In
Ramamurthi S, Tandon PN (Ed): Textbook of Neurosurgery.
New Delhi: National Book Trust: 1980;828,
2. Traquair HM. An Introduction to Clinical Perimetry. St. Louis:
CV Mosby Co, 1978.
3. O’Connel JE, Duboulay EP. Binasal hemianopia. J Neurol
Neurosurg Psychiatr 1973;6:697.
4. Newman SA, Miller NR. Optic tract syndrome: Neuro-
ophthalmologic considerations. Arch Ophthalmol 1983;
101:124.
5. Trobe JD, Lorber M, Schlezinger NS. Isolated homonymous
hemianopias: A review of 104 cases. Arch Ophthalmol
1973;89:377.
 Chapter 127
Optic Neuritis:
Optic Neuropathies
Demyelinating Diseases
LC Dutta
STRUCTURE OF THE OPTIC NERVE HEAD
On histological examination the optic nerve head can
be described in four portions: (a) surface layer, (b) pre-
laminar, (c) laminar, and (d) retrolaminar portions.1
The surface layer consists of nerve fibers entering the
optic nerve from the retina and is separated from the
overlying vitreous by the inner limiting membrane of
Elschnig which is composed of astrocytes and
continuous with the internal limiting membrane of the
retina. This surface layer is supplied by branches of
the central retinal artery. In the prelaminar region the
retinal nerve fibers are grouped into approximately
1000 fascicles. These fascicles are separated by
astroglias which provide support for their axons from
the retinal ganglion cells as they bend at a 90° angle
to enter the optic nerve. Astrocytes are also found in
the nerve fiber layer of the retina in the posterior pole.
The vascular supply of the prelaminar region arises
from the centripetal branches of peripapillary
choroidal vessels but some blood supply may come
directly from the short posterior ciliary arteries.2
The laminar portion known as lamina cribrosa, is
continuous with the surrounding sclera and consists
of fenestrated connective tissue through which the
nerve passes. The connective tissue is lined by
astrocytes, thereby preventing direct contact between
nerve fibers and connective tissue. This region is
supplied by centripetal vessels derived from the short
posterior ciliary arteries and the circle of Zinn-Haller.
This is an incomplete system, surrounding the
prelaminar nerve, which itself is supplied by the short
posterior ciliary arteries.3
The retrolaminar portion of the optic nerve actually
is not a part of the optic nerve head. The collagenous
septae of the lamina cribrosa continue posteriorly
within it while the axons here have a myelin sheath
derived from oligodendrocytes. The nerve approxi-
mately doubles its thickness at this point. Blood supply
of the retrolaminar portion of the optic nerve is from
the centrifugal branches from the central retinal artery
and centripetal pial branches derived from the
vascular pial plexus surrounding the nerve.
On anatomical basis, inflammation of the optic
nerve may be divided clinically into (a) papillitis
(inflammation of the intraocular part) and
(b) retrobulbar neuritis (inflammation of the nerve
between the eyeball and the chiasm). So far as the
structure of the nerve is concerned the inflammation
may be: (a) perineuritis or peripheral optic neuritis
and (b) inflammation of the substance of the nerve or
the nerve fibers which is the actual optic neuritis.
Papillitis or Anterior Optic Neuritis
The optic nerve head or the papilla, ophthalmo-
scopically marked as the optic disk, is a transitional
zone between the retinal nerve fibers and fibers of the
optic nerve. Inflammation of this part is known as
papillitis.
There may be numerous etiological factors of
papillitis, but in most of the cases especially in the age
group of 15 to 45 years the condition is idiopathic;
however 90 percent of cases of demyelinating diseases
develop optic neuritis and between 20 and 40 percent
974 Section 8: Neuroophthalmology
cases of optic neuritis develop signs and symptoms
of multiple sclerosis.
Systemic diseases like diabetes, endocrine distur-
bance, malignant diseases, viral or bacterial encepha-
litis, toxic agents, etc. can produce optic neuritis.
Endogenous toxins from septic foci like tonsillitis,
sinusitis, septic teeth, etc. are also included in the list
of etiological agents of optic neuritis. Ischemic
papillitis may develop in giant cell arteritis, collagen
disorder, herpes zoster ophthalmicus, and embolic
arterial occlusive condition in vascular diseases.
Clinical features of papillitis mainly consist of
visual defect and typical ophthalmoscopical picture
of the optic disk and the adjacent retina. The visual
loss is of almost sudden onset and rapidly deepens
sometimes even to loss of perception of light.4 Mild
form of visual loss may be dense centrocecal scotoma.
Sluggish direct pupillary light reaction with normal
consensual and accommodation reaction is a typical
sign. In early stage of optic neuritis especially in
retrobulbar neuritis pupillary contraction to direct
light cannot be retained and there is exaggeration of
the normal alternate constriction and dilatation of the
pupil known as hippus. In retrobulbar optic neuritis
the patient complains of pain on movement of the eyes
specially on looking up.
Ophthalmoscopic picture in papillitis consists of
blurred disk margin, filling up of the physiological
cup, hyperemia of the disk, neuroretinal edema, flame-
shaped hemorrhage and dilatation of the retinal veins.
Occasionally there may be clouding of the posterior
vitreous. Swelling of the nerve head is minimal. The
exudate and edema spread from the disk up to the
retina producing neuroretinitis and in the macular
area the exudates arrange in a fan shaped or star
shaped manner known as macular star. This appea-
rance is due to accumulation of the exudated fluid in
the vitreoretinal interface or loosely speaking under
the posterior hyaloid membrane.
In management of optic neuritis two factors to be
considered are: (a) drugs to reduce the exudative
process so that pressure effect upon the nerve fibers
is reduced, for this purpose systemic steroid in proper
therapeutic dose should be started, and (b) to
supplement enough vitamin B1, B6, B12 to enable the
nerve fibers to tide over the crisis. Though routine
investigations are done the results come out negative
almost in all the cases. However a course of broad-
spectrum antibiotic may be started for the benefit of
doubt.
Visual prognosis of papillitis is very good provided
diagnosis is made early and proper treatment
instituted. Some amount of paleness of the disk with
blurred margin and perivascular gliosis of the retinal
vessels on the surface of the disk may persist as a
legacy to the inflammatory process. This appearance
of the disk is clinically known as postneuritic optic
atrophy.
Retrobulbar Neuritis
The etiology of retrobulbar neuritis can be almost the
same as those of papillitis. The typical signs of optic
nerve dysfunction are afferent pupillary defect, loss
of color vision and central scotoma. There is no change
in the optic disk. Pupillary sign typically called retro-
bulbar pupil is inability to maintain pupillary
contraction to direct light. Pain in the orbit or in the
affected side of the frontal region or in the eyeball itself
is an additional diagnostic symptom.
The vision loss is dramatic. Fogginess of vision
starts suddenly like a cloud coming in front of field of
vision and within a few days vision comes down to
lowest level. Sometimes patients may indicate that
vision is better in dim light than in bright light. Central
scotoma is a typical sign of retrobulbar neuritis. This
is due to the fact that the papillomacular fibers which
lie in the central part of the optic nerve are compressed
by the inflammatory exudates inside the meningeal
coverings.
DEMYELINATING DISEASES AS
ETIOLOGY OF OPTIC NEURITIS
There are four demyelinating diseases which may
cause optic neuritis:
a. Multiple sclerosis/disseminated sclerosis
b. Acute disseminated encephalomyelitis
c. Neuromyelitis optica (Devic’s disease) and
d. Diffuse periaxial encephalitis (Schilder’s disease).
The etiology of the demyelinating diseases is not
known although multiple factors appear contributory.
Recent works suggest that a viral infection early in
life precipitates an autoimmune process which affects
the myelin. The measles (Rubella) virus is implicated
by recent immunologic studies.5 Acute demyelinating
disease was produced in chimpanzee three years after
inoculation of brain cells from a patient with multiple
sclerosis.6
Basic pathology consists of destruction of the
myelin sheath followed by development of acute
 Chapter 127: Optic Neuritis: Optic Neuropathies
inflammatory lesions including a perivascular infiltra-
tion of inflammatory cells. This stage is followed by
removal of the disintegrated myelin by the phagocytic
microgial cells accompanied by degeneration of the
axis cylinders with proliferative gliosis. This pathology
may occur in the optic nerve, chiasm and tracts. As
myelin sheath of the optic nerve normally terminates
at the lamina cribrosa, demyelination is possible in
the retrobulbar portion of the optic nerve causing
retrobulbar neuritis. Extension of the disease process
along the axis cylinder may cause papillitis and
neuroretinitis. In multiple (disseminated) sclerosis,
retrobulbar neuritis is unilateral in about 95 percent
of cases. In periaxialis diffusa the pathology is
extensive, progressive and may be fatal.
Multiple Sclerosis (Disseminated Sclerosis)
Multiple sclerosis, also called disseminated sclerosis
(DS), is a chronic relapsing and remitting disease in
which discrete foci of myelin covering the axonal
processes of the neurons are disintegrated in the brain,
spinal cord and the optic nerve.
Multiple sclerosis is the most common demye-
linating disease of the nervous system. Its incidence
varies considerably in different parts of the world. The
prevalence of multiple sclerosis increases with
increasing latitude both north and south of the
equator. Multiple sclerosis is rare in Asia and Africa.
Women are more affected than men in the ratio of
about 2:1. The disease is extremely rare among black
people and more common in Jewish population.
Peculiarly, it affects people with a high socioeconomic
background. Children under the age group of ten
years are not commonly affected. The highest inci-
dence is in the young adults between 25 and 40 years
of age and it seldom appears for the first time after 50
years of age.7
As in other demyelinating diseases, the causes of
multiple sclerosis remain obscure. Experimental
evidence and laboratory tests suggest that it may be
an autoimmune disease in which the brain tissue is
sensitized by past viral infection probably coming
from the mucosal surfaces. The IgG concentration of
tear fluid is increased in multiple sclerosis. Along with
the improvement of symptoms the quality of tear also
improves.8
The disease has special affinity for the optic nerve.
About 80 percent cases of optic neuritis develop
multiple sclerosis within a period of 10 to 20 years.
Optic neuritis is probably a forme fraste variant of
975
multiple sclerosis and individuals with optic neuritis
have subclinical dissemination or represent an end of
a continuum with fully developed clinical multiple
sclerosis at the other end.9
The course of the disease is variable. It may
progress rapidly or slowly. In majority of cases irres-
pective of the severity and mode of onset, spontaneous
remission occurs and 90 percent of cases have a
relapsing and remitting course. Relapse at an interval
of months or years is common. Subsequent recurrent
episodes are usually more marked than the preceding
ones each of which may result in additional permanent
disability due to accumulated incomplete recovery
from preceding lesions. A slow apparently continuous
deterioration of the neurological status is observed in
the late course of the disease. There is great variation
of prognosis of the disease. When the disease involves
the cerebral hemisphere, cerebellum and the spinal
tracts there may be total disability and even on rare
occasions death results within one to two years of onset
of the disease. In some patients the subsequent
episodes may be even milder or may appear to recover
completely after few years. About one-third of the
patients run a benign course. On rare occasions
plaques of multiple sclerosis are found at autopsy in
the brains of individuals who were not known to have
suffered from the disease prior to death. In general,
longer the interval between the first and the subse-
quent episode, the better is the prognosis. Young
patients develop more fulminating symptoms from
the very onset of the disease than middle-aged
patients.
Ocular Features of Multiple Sclerosis
There may be widespread anatomic distribution of
lesions of multiple sclerosis and hence, its clinical
picture is also greatly variable. Ocular manifestations
will depend upon the site of the lesions in the nervous
system concerned with ocular functions. Multiple
sclerosis is the most common cause of retrobulbar
neuritis and papillitis; conversely the most common
manifestation of multiple sclerosis is optic neuritis.
Recurrent attacks of optic neuritis usually does not
occur in the same eye in subsequent episodes of
multiple sclerosis.
Optic Atrophy
Temporal pallor of the optic disk is a recognized
neuro-ophthalmological sign of multiple sclerosis.
976 Section 8: Neuroophthalmology
This is probably due to involvement of the papillo-
macular bundles which occupy the central position
of the optic nerve and are compressed by the
inflammatory exudates in retrobulbar neuritis.
However, this has got to be differentiated from the
physiological temporal pallor. Complete primary
looking optic atrophy with papery with appearance
and clear cut margin is a terminal sign of recurrent
episodes of retrobulbar neuritis. Postneuritic or
postedematous optic atrophy characterized by waxy
looking disk with indistinct margin is a sign of past
papillitis.
Ocular Motor Paralysis
Multiple sclerosis is a common cause of ocular palsies.
Diplopia develops in 25 to 30 percent of cases as an
initial symptom. Several attacks of transient diplopia
often occurs before an obvious muscle paresis deve-
lops. Usually diplopia is accompanied by strabismus
or by demonstrable weakness of the affected muscle.
All varieties of diplopia may occur but it is most
common on lateral deviation of the eyes. An episode
of diplopia in a young person lasting days or weeks
in the absence of any other abnormal physical sign is
very suggestive of disseminated sclerosis. Sometimes
the muscle weakness is obvious clinically. If a single
muscle is affected it is likely to be the lateral rectus.
Paralysis of the third nerve or complete ophthalmo-
plegia is rare. There may be abnormality in conjugate
deviation of the eyes due to plaques of demyelination
in the pons or midbrain which cause interference with
the commissural fibers. Similar pathology may occur
adjacent to the nuclei of the ocular motor nerves.
Internuclear ophthalmoplegia is almost characteristic
of multiple sclerosis.10 Incidence of paralysis of lateral
conjugate movement is more frequent than that of
other types of conjugate movements.
Nystagmus of various types It is a common neuro-oph-
thalmological sign in DS. It may be fine, coarse or
medium and usually horizontal. Vertical and rotatory
nystagmus is rare. Jelly nystagmus can be detected
only under ophthalmoscopic examination. Ataxic
nystagmus occurs on extreme lateral gaze. Nystagmus
may be one of the signs of Charcot’s triad which
consists of nystagmus, intention tremor and slurring
speech.
Pupillary reactions in multiple sclerosis It is sluggish due
to retrobulbar neuritis; the sluggish reaction is only
to light with normal accommodation reaction similar
to Argyll Robertson pupil (ARP); but typical features
of ARP is not present. On the other hand reverse of
ARP may be rather common. The site of lesion is
probably near the nucleus of Perlia.
Lid retraction in multiple sclerosis It is more common
than ptosis. It is due to irritation of the descending
sympathetic fibers at the region of midbrain. There
may be unilateral or bilateral ptosis. Horner’s
syndrome may develop due to lesions in the brain
stem or cervical cord.
Diagnosis
Diagnosis is mainly made on clinical findings. There
is no single test which unequivocally establishes the
diagnosis of multiple sclerosis. Following are some of
the tests which may give some indications about the
disease:
Visual evoked response (VER) or visual evoked potential
(VEP) In optic neuritis due to demyelinating disease
the amplitude of VER may be normal but the latency
is prolonged. A prolonged latency also may be
obtained in the asymptomatic eyes of patients with
optic neuritis. Compressive and ischemic optic neuro-
pathies also demonstrate abnormalities of the VER but
in these disorders there is alteration of the amplitudes
and not of the latency. The change may be caused by
focal demyelination and conduction slowing. Thus
most fibers may be functioning showing normal
amplitude but at a slower conduction velocity which
means an increase in the latent period.11
Cerebrospinal fluid Abnormal immunoglobulins in the
form of an oligoclonal electrophoretic pattern have
been reported in about one quarter of the patients with
optic neuritis due to multiple sclerosis.12 Moreover
there is overall elevation of immunoglobulin G
thereby causing elevation of IgG albumin index.
Computerized tomography (CT) scan CT scan of the brain
may be helpful in diagnosing acute multiple sclerosis
and in follow up of the course of white matter lesion:
CT scan often demonstrates perivascular and deep
white matter lesions although such lesions are more
likely to be present in patients with advanced disease
rather than early disease.13
Nuclear magnetic resonance imaging (NMRI) NMRI is a
remarkably sensitive investigation for detecting
cerebral lesions in multiple sclerosis. In many of the
cases of optic neuritis lesions of multiple sclerosis is
detected with MRI.
 Chapter 127: Optic Neuritis: Optic Neuropathies 977
Acute Disseminated Encephalomyelitis spinal fluid is usually normal but in some cases there
is an increase in protein and cells. Due to its wide-
This usually affects the young adults but children may
spread lesion, the visual impairment is commonly
also suffer. The ailment starts with fever, headache,
preceded by some amount of psychotic features,
vomiting, drowsiness and convulsions. If the patient
deafness, aphasia, upper motor neuron type of para-
recovers from the initial attack, after few weeks or days
lysis, sensory changes and ataxia.
fresh symptoms may develop showing involvement
The prominent ophthalmological feature of
of various parts of the central nervous system. Visual
Schilder’s disease is loss of vision due to occipital lobe
system is involved due to the lesion in the optic nerves,
lesion. In the early stage of the disease field defects
tracts or chiasm. There may be retrobulbar optic
occur but as the demyelination process progresses
neuritis or papillitis leading to optic atrophy; ocular
complete blindness sets in. Optic nerve, chiasm and
involvement is bilateral but may not be always
the tracts may also be involved in the demyelination
simultaneous.
process to a variable extent; therefore, optic atrophy
Similar pathology may develop following some
with visual loss is common. Brain stem lesions
specific infection particularly of viral origin, vacci-
involving the oculomotor pathways, cause nystagmus,
nation or other inoculations. Measles and mumps are
ocular palsies and pupillary abnormalities. But these
some of the viral infections which may cause
changes are insignificant in comparison to the other
demyelination of the nervous system. Blindness due
more severe features of the disease.14
to optic neuritis or papillitis, field defects due to
involvement of the chiasm and the tracts are common
Leber’s Hereditary Optic Atrophy
manifestations. Visual prognosis is usually very poor.
In 1871 T. Leber first described this condition and is
Neuromyelitis Optica (Devic’s Disease) named after him. It is a relatively rare disease of
unknown etiology affecting predominantly the males
This disease is characterized by involvement of the
between the age group of 11 to 53 years with a mean
optic nerve, spinal cord and the ocular sympathetic
of 25 years. Symptomless female carries and the
system. Bilateral retrobulbar neuritis precedes myelitis
diseased ones transmit the disease to their sons as well
or sometimes it follows the latter. The difference
as the carrier state to most of their daughters. About
between Devic’s disease and multiple sclerosis is that
10 to 20 percent of female carriers manifest the disease.
in the former the pathology is more extensive, less
In the female members of the family having Leber’s
sharply defined and results in greater destruction of
disease some peripapillary vascular changes like
the axis cylinders. Retrobulbar neuritis is frequently
telengiectetic microangiopathy can be demonstrated
accompanied by some degree of papillitis with severe
in fundus fluorescein angiographic studies. This may
visual loss generally down to perception of light. The
be an asymptomatic stage of the disease.
prognosis of neuromyelitis optica is more severe than
Leber’s disease manifests itself soon after puberty.
disseminated sclerosis. Fifty percent of cases presen-
To start with, there is acute or subacute painless visual
ting with bilateral optic neuritis is preceded or
failure which deteriorates over days, weeks or months
followed by paraplegia or monoplegia. The prognosis
with occasional significant improvement; complete
is fatal. If the acute illness does not prove fatal then
blindness is rare. Though the disease is bilateral, both
some amount of recovery takes place.
eyes are seldom affected simultaneously or to the same
extent. Ophthalmoscopically there may be some signs
Encephalitis Periaxialis diffusa: Diffuse Cerebral
of papillitis in the form of hyperemia of the optic disk
Sclerosis: Diffuse Periaxial Encephalitis:
with blurring of the disk margin but without
Schilder’s Disease
hemorrhage and exudate as seen in other cases of
This rare disease of infancy and childhood is charac- papillitis. After the acute stage has passed off, in mild
terized by massive demyelination in the cerebral and cases, the appearance of secondary optic atrophy sets
cerebellar hemispheres followed by a process of in causing pallor of the temporal part of the optic disk
gliosis. The demyelination process starts first in the due to involvement of the papillomacular bundle; in
occipital cortex and then spreads forward. There may severe cases the color of the disk becomes completely
be some additional small scattered areas of demyeli- bluish gray. Pupillary reactions are usually normal.
nation in the brain stem and spinal cord. The cerebro- Field defects include central or centrocecal scotoma
978 Section 8: Neuroophthalmology
sometimes with peripheral constriction of field of
vision.
It is not rare to detect some associated neurological
abnormalities like paresthesia, ataxia, etc. When these
signs are present then differentiation from multiple
sclerosis may pose a problem. Uhtoff’s phenomenon
(lowering of conductivity of nerve impulse after pro-
longed physical exercise) may also be present. Electro-
physiological tests like ERG, EOG and VER may be
normal but reduction of amplitude; increased latency
or even extinction of pattern evoked response may
result. In cases with advanced visual impairment the
VER is bilaterally absent while in those less severe
involvement, responses are delayed, desynchronized
and much smaller than normal.15
Pathology
Pathology of Leber’s disease consists of demyelination
of the axial optic nerve with atrophy of the ganglion
cells and nerve fiber layer of the retina. As in tobacco
amblyopia, demyelination is thought to be due to
defective cyanide metabolism. Probably the diseased
process is due to failure to detoxify cyanide as a result
of some genetic disorder.16 Exogenous cyanide from
diet and tobacco smoke is conjugated with sulfur of
sulfur containing amino acids like cystine to form
nontoxic thiocyanite mainly in the liver. In Leber’s
hereditary optic atrophy there is a hepatic deficiency
of the enzyme rhodanase which is involved in
detoxification of cyanide. Another important aspect
to consider is the role of zinc which acts as a coenzyme
in many systems. In many optic neuropathies as in
ethambutol and penicillamine toxicity, hereditary
optic atrophy and tobacco-alcohol amblyopia, the zinc
concentration is lowered.
Treatment
Treatment of Leber’s hereditary optic atrophy is
difficult. Opening of the optic nerve sheath to release
the pressure upon the optic nerve fibers during the
early inflammatory process is a theoretical propo-
sition. 4 to 8 gm daily oral dose of cystine and
intramuscular injection of hydroxycobalamin 1000
microgram on alternate days may help conversion of
cyanide mixed with cystine to nontoxic thiocyanate.
On the same basis cyanide intake specially from
smokes of tobacco should be minimized. Supple-
mentation of zinc is also essential.
Alzheimer’s Syndrome: Ophthalmic
Manifestations of Alzheimer’s Disease:
Alzheimer’s Type of Dementia
Some degree of dementia in persons above the age of
65 years due to shrinkage in size and reduction of
weight of the brain is common; this is called senile
dementia. Alzheimer’s syndrome (described by Alois
Alzheimer in 1906) is a condition which occurs at an
early age and clinical as well as pathological
manifestations are more widespread and severe.
Pathologically it is characterized by diffuse atrophy
of the convolutions and symmetrical enlargement of
the lateral and third ventricles which can be demons-
trated by CT scan. Microscopically widespread loss
of nerve cells in the cerebral cortex and basal ganglia
occurs. The main pathological process is selective
degeneration of the acetylcholine releasing neuron
with cell bodies in the basal ganglia.17 The brain tissue
of the patients contain 60 to 90 percent less accetyl
choline transferase.18 Dementia is associated with
emotional disturbances like depression, anxiety and
unpredictable knack of behavior. The progressive
deterioration of cognitive function is clinically
indistinguishable from senile dementia.
The patients usually complain of poor vision,
specially problems with reading and of bumping into
objects but central visual acuity remains normal.
Pupillary reactions, color vision, and ocular motility
are not affected; there may be poor initiation of eye
movements. Visual evoked potentials are found to be
delayed and this is thought to be due to reduction in
cortical cholinergic activity. Some amount of color
vision abnormality may be present. Histopathological
study reveals 30 to 60 percent reduction of the
ganglion cells and hence of the optic nerve fibers.19
The optic disk may appear perfectly normal or there
may be some amount of temporal pallor; deep cupping
of the optic disk having normal intraocular pressure
is also reported. There is tendency to believe that
heredity also plays some role.
Classification of Optic Atrophy
Optic atrophy may broadly be divided into primary
and secondary or consecutive. Classically primary
optic atrophy is due to neurosyphilis. Primary optic
atrophy results from degeneration of the nerve fibers
without any complicating process. The typical picture
of primary optic atrophy consists of papery white disk
 Chapter 127: Optic Neuritis: Optic Neuropathies
with clear-cut margin and minute dark dot like
appearance in the floor of the disk. These dots
represent the holes in the lamina cribrosa. Optic
atrophy following retrobulbar neuritis, toxic neuro-
pathy, quinine amblyopia and due to pressure in the
optic nerve or chiasm may produce similar picture to
primary optic atrophy and hence, this type of atrophy
is called ‘primary looking’ optic atrophy. Secondary
or consecutive optic atrophy is characterized by some
evidences of past neuritis or papilledema. Ophthalmo-
scopic types of optic atrophy are as follows:
Consecutive optic atrophy This follows diseases of the
posterior segment of the eye as in late stage of retinitis
pigmentosa or diffuse chorioretinitis. Here the color
of the disk becomes waxy and the arteries grossly
attenuated.
Glaucomatous optic atrophy The optic cup becomes very
prominent, sometimes extending to the extreme
periphery of the disk.
Vascular atrophy After attenuation of the vessels as
occurs in central retinal arterial occlusion in malignant
hypertension, temporal arteritis and aneurysm of the
carotid artery.
Postneuritic or postedematous optic atrophy It is due to
papillitis or papilledema.
Cavernous (lacunar) optic atrophy (Schnabel optic
atrophy) In this condition atrophy of the nerve fibers
is not associated with proliferation of the neuroglial
cells. Therefore, empty spaces are formed in between
the nerve fibers which can be seen on histopathological
sections. This pathological process is due to insuffi-
cient blood circulation in the tissue. Clinically, asso-
ciated with the atrophy there is development of field
defect.
Traumatic optic atrophy Mechanical trauma may cause
optic atrophy and consequent blindness due to several
causes:
a. Avulsion of the optic nerve—in concussion injury
when the eyeball is suddenly pushed away from
the normal position, optic nerve is stretched and
is torn either at its attachment to the orbital end of
the optic foramen or to the sclera behind the lamina
cribrosa. When the optic nerve is severed anterior
to the site of entrance of the central retinal artery
into the optic nerve then there may be hemorrhage
over the optic disk. In avulsion of the optic nerve
in its posterior part, the disk may appear normal
soon after the injury but later on optic atrophy sets
979
in. Sudden complete loss of vision after concussion
injury of the eyeball with loss of direct pupillary
reaction is the diagnostic feature of avulsion of the
optic nerve.
b. In some cases there may not be any neuro-
radiological sign of avulsion or even on explora-
tion, the optic nerve may be seen to be intact. These
cases of loss of vision following concussion injury
are due to reflex spasm of the central retinal artery.
Ophthalmoscopic appearance of traumatic optic
atrophy is of primary looking type.
REFERENCES
1. Anderson DR. Ultrastructure of the optic nerve head. Arch
Ophthalmol 1970;83:63.
2. Henkind P, Levitsky M. Angio-architecture of the optic nerve:
The papilla. Am J Ophthalmol 1970;68:979.
3. Idem II. Lamina cribrosa. Am J Ophthalmol 1969;68:986.
4. Duane TD (ed). Clinical Ophthalmology. Hagerstown, MD
Harper and Row 2: 1981.
5. Adams JM, Imagawa B. Measles antibodies in multiple
sclerosis; P. Soc, UK Exp Bol Med 1962;3:562.
6. Rorke LB, Iwaski Y, Kiprowski H. Acute demyelinating
disease in a chimpanzee three years after inoculation of brain
cells from a patient with multiple sclerosis. Am J Neurol
1979;5:89.
7. McAlpine D. Multiple sclerosis: A review. Br Med J 1973;2:292.
8. Coyle PK, Sibony PA. Tear analysis in multiple sclerosis.
Neurology 1986;36:547.
9. Ebers GC. Optic neuritis and multiple sclerosis. Arch Neurol
1985;42:702.
10. Baker RS. Internuclear ophthalmoplegia following head
injury. J Neuro Surg 1979;5:552.
11. Wilson WB. Visual response differentiation of ischaemic optic
neuritis from the optic neuritis of multiple sclerosis. Am J
Ophthalmol 1978;86:530.
12. McDonald WI. The significance of optic neuritis. Trans
Ophthalmol Soc UK 1983;103:230.
13. Harding AE, Radue EW, Whitely AM. Contrast enchanced
lesions on computerised tomography in multiple sclerosis. J
Neurol Neurosurg Psychiatry 1978;41:754.
14. Nevin S, Kiloh LG. Organic affections. In Sorsby A (ed):
Modern Ophthalmology. London: Butterworths, 1972;2.
15. Carroll WM, Mastoglia FL. Leber’s optic neuropathy: A
clinical and visual evoked potential study of the affected and
asymptomatic members of a six generation family. Brain
1979;102,559.
16. Syme JG, Stewart JB, Foulds WS et al. Clinical and bio-
chemical finding of Leber’s Hereditary optic atrophy. Trans
Ophthalmol Soc UK 1983;103:556.
17. Cocyle JT, Price DL, Long MP. Alzheirner’s disease: A dis-
order of cortical cholinergic innervation. Science 1982;219:
1184.
18. Kolata G. Clues to Alzheimer’s disease emerge. Science
1983;219:941.
19. Sadun AA, Borchert M, Devito E et al. Assessment of visual
impairment in patients with Alzheirmer’s disease. Am J
Ophthalmol 1987;104:113.
 Chapter 128

Ocular Motor Palsies

G Natchiar, Subhuram

The third, fourth and sixth cranial nerves supply the
extraocular muscles. In addition, the third cranial
nerve provides parasympathetic input to the iris
sphincter and ciliary muscles, and motor input to the
levator palpebrae superioris muscles.
The oculomotor paralysis may be congenital or
acquired and the paralysis may be partial (paresis) or
complete. The paralysis may be due to thrombotic
occlusion of small perforating vessels coming off from
the basilar artery or emboli or thrombotic occlusive
disease of the bigger vessels (Table 128.1).
OCULOMOTOR NERVE
Nucleus
The nucleus of the oculomotor nerve is a complex mass
of cells located in the periaqueductal gray matter of
the rostral midbrain at the level of the superior
colliculi. The inferior rectus and inferior oblique
subnuclei have uncrossed projections, as does the
medial rectus subnucleus. The superior rectus
subnucleus has a crossed projection. The visceral
nucleus mediating parasympathetic innervation to the
pupil and the subnucleus of the levator palpebrae
superioris are midline and have bilateral projections.
Isolated lesions of the third nerve nucleus are rarely
caused by vascular disease or congenital hypoplasia.
Ptosis and pupillary involvement must either be
bilateral or absent. Also, the contralateral superior
rectus may be involved with possible ipsilateral
sparing.
Fasciculus
The oculomotor neurons leave the nuclear complex
and pass ventrally through the red nucleus, leaving
the brainstem through the medial portion of each
cerebral peduncle to emerge in the interpeduncular
space (Fig. 128.1). Vascular disease or tumor may
involve this region. Weber’s syndrome involves the
cerebral peduncle as well as the fasciculus and
produces ipsilateral third nerve palsy with contra-
lateral hemiplegia or tremor. If there is damage to the
medial lemniscus and red nucleus, a contralateral
“rubral” tremor is also present, producing Benedikt’s
syndrome.

Table 128.1: Causes of 3rd nerve palsies

Location Signs and symptoms Common cause
No clear lesion Complete 3rd nerve with contralateral ptosis with Vascular occlusion
contralateral superior rectus weakness Hemorrhage
Fasciculus Contralateral hemiparesis (Weber’s) Metastatic tumor, vascular occlusion,
Contralateral tremor (Benedikt’s) hemorrhage, neoplasm, demyelination
Ipsilateral ataxia
Cavernus sinus 4th, 6th, V1, V2, ocular sympathetic dysfunction, Neoplasm, inflammation, aneurysm,
pain prominent, proptosis visual loss microvascular occlusion, thrombosis, A/V fistula
Orbit Proptosis, visual loss Trauma, neoplasm, inflammation
 Chapter 128: Ocular Motor Palsies
Fig. 128.1: Arrangement of the nuclei of the
3rd cranial nerve and the course of the nerve
Peripheral Nerve
Subarachnoid Space
The third nerve leaves the brainstem and passes
between the posterior cerebral and superior cerebellar
arteries to travel lateral to, but parallel with the poste-
rior communicating artery. It pierces the dura just
lateral to the posterior clinoid process. Within the
subarachnoid space, the nerve may be pressed by
aneurysm of the posterior communicating artery, by
extra-axial tumor, or in meningitis. The posterior
communicating artery aneurysms, which typically
arise at the junction of the internal carotid artery, are
the most common cause of spontaneous acute third
nerve palsy with pupil involvement. Injury to the third
nerve is produced by aneurysmal distention coupled
with intraneural hemorrhage. Pupillary involvement
is seen in 95 percent of cases, and pain is always
present. As the third nerve passes under the tentorial
edge, it is susceptible to uncal herniation and trauma.
Pupillary involvement is an early sign in uncal
herniation, probably because of the superficial, dorsal-
medial location of the pupillomotor fibers at this level.
Intracavernosus Space
Once the third nerve enters the cavernosus sinus, it
runs dorsal to the fourth nerve in the lateral wall of
the sinus (Fig. 128.2). Within the sinus it is susceptible
to damage from carotid-cavernosus fistula, aneurysm,
tumor, pituitary apoplexy as well as infectious and
granulomatous processes such as herpes zoster and
Tolosa-Hunt syndrome. Within the cavernosus sinus,
981
Fig. 128.2: (A) Structure related to the cavernosus sinus,
(B) Relation of the circle of Willis with the chiasm
the third nerve palsy is often accompanied by
involvement of the fourth, sixth and trigeminal nerves.
An important exception is the nerve infarction
associated with diabetes. This pupil-sparing palsy
(usually seen in older patients) is often accompanied
by intense periorbital pain. The incidence of significant
pupillary involvement is less than 10 percent. Ischemic
third nerve palsies spontaneously recover within 8-
12 weeks, but may recur.
Orbital Space
As the third nerve enters the orbit through the superior
orbital fissure, it divides into superior and inferior
branches. The superior division supplies fibers to the
superior rectus and levator palpebrae superioris
muscles; the inferior division carriers fibers inner-
vating the medial rectus, inferior oblique, and inferior
rectus muscles, as well as the parasympathetic fibers
to the ciliary ganglion, which will eventually innervate
the iris sphincter and ciliary muscle. The most
common cause of intraorbital involvement of the third
nerve is trauma, with occasional involvement by viral
infections and mechanical pressure by orbital mass.
Special Syndromes Related to the Third Nerve
Aberrant Regeneration
It occurs during the repair phase which follows injury
to the third nerve from trauma, aneurysm, or
tumor. Sprouting axons are misdirected so that they
reinnervate the wrong extraocular muscle. Thus,
several different patterns of movement can result.
982 Section 8: Neuroophthalmology
The upper lid may elevate on attempted adduction or
depression, producing the so-called pseudo-Graefe’s
phenomenon. Similarly, segmental pupil constriction
may occur with attempted adduction, elevation, or
depression. Actual retraction of the globe may occur
with attempted vertical gaze. This misdirection
process never occurs with diabetic oculomotor
neuropathy. Aberrant regeneration of the oculomotor
nerve without a preceding acute third nerve palsy,
so-called primary aberrant regeneration, is diagnostic
of intracavernosus meningioma or aneurysm.
Ophthalmoplegic Migraine
It is a rare entity. It usually occurs in children who
have a family history of migraine. Ocular pain, nausea,
and vomiting usually precede the onset of ophthal-
moplegia and abate when the paresis occurs.
Cyclic Oculomotor Palsy
It is an exceedingly rare syndrome of intermittent
spasms in a paretic eye. During the spastic interval,
the paretic eye turns from its exotropic position toward
midline, the ptotic eye lid elevates, and the dilated
pupil constricts.
CLINICAL APPROACH TO
ISOLATED OCULOMOTOR PALSY
Sudden onset of painful or painless oculomotor palsy
with spared pupil in the middle-aged or elderly
patient having diabetes, hypertension, or both is
almost always suggestive of a microvascular etiology.
Estimation of blood sugar and ESR may be indicated
in the initial evaluation. Complete resolution of the
palsy is expected 2-3 months after onset. Pupil sparing
oculomotor palsy in younger patients without obvious
etiology should be fully evaluated.
Sudden onset of painful third nerve palsy with
pupillary involvement at any age is an indication for
carotid angiography to exclude posterior communi-
cating artery aneurysm.
Chronic third nerve palsies regardless of pupil
involvement suggest the need for imaging studies to
exclude a mass along the course of the peripheral
nerve. Aberrant reinnervation may be present. Forced
ductions help to exclude restricted etiologies.
TROCHLEAR (FOURTH CRANIAL) NERVE
The trochlear nerve arises in cells located in the
periaqueductal gray matter beneath the aqueduct of
Sylvius, caudal to and continuous with the oculomotor
nucleus. The medial longitudinal fasciculus passes
inferolateral to the trochlear nucleus. Isolated trochlear
palsy at the nuclear level is unusual, most often
occurring with vascular disease, trauma or demyeli-
nation.
Fasciculus
The axons of the fourth nerve curve dorsocaudally
around the aqueduct decussating completely
(Fig. 128.3) in the anterior medullary velum and
leaving the brainstem on its dorsal surface just caudal
to the inferior colliculus. The lesions that affect the
fasciculus are usually vascular and demyelination.
Peripheral
The trochlear nerve curves forward around the
brainstem, running beneath the free edge of the
tentorium to pass between the posterior-cerebral and
superior-cerebellar arteries. It then pierces the dura
behind the cavernosus sinus below the third nerve and
enters the orbit through the superior orbital fissure,
to innervate the superior oblique muscle. It is the
longest of the cranial nerves and the only to exit on
the dorsal surface of the brainstem.
Because of its long course within the subarachnoid
space, the peripheral trochlear nerve is especially
subjected to damage from closed head trauma due to
contercoup forces, which then transmitted to the
brainstem by the free tentorial edge. Bilateral
traumatic fourth nerve palsy occurs in the anterior
medullary velum, where the nerves emerge together.
Ischemic injury, often associated with diabetes
Fig. 128.3: Trochlear nerve nucleus and course
of the nerve
 Chapter 128: Ocular Motor Palsies
mellitus, is the second most common cause of fourth
nerve palsy. Pressure on the fourth nerve may be
caused by hydrocephalus, vascular loops, or tumor.
Aneurysm is an extremely rare cause of isolated
trochlear palsy.
Congenital fourth nerve paralysis is not un-
common. A long-standing head tilt used to maintain
binocular vision may be unrecognized until decom-
pensation occurs years later. Large amplitudes of
vertical fusion are usually present in congenital, but
not in acquired fourth nerve palsies.
Superior Oblique Myokymia
it is an arrhythmic twitching of the superior oblique
muscle. Symptoms include blurred vision due to
tremor, as well as torsional and vertical diplopia due
to the action of the muscle.
Clinical Approach to Isolated
Trochlear Nerve Palsy
The three-step test is useful in the diagnosis of
trochlear nerve palsy. The first step is to identify the
side of the hyperdeviation. The second step is to
observe an increase in the hyperdeviation with gaze
to the opposite side. The third step is to document an
increase in the hyperdeviation with head tilt to the
same side. Patients with bilateral fourth nerve palsies
classically demonstrate an acquired V esotropia, right
hypertropia on left gaze left hypertropia on right gaze,
and torsional diplopia on down gaze.
Onset of vertical diplopia in the absence of lid
involvement is most commonly due to trochlear palsy.
Traumatic, vascular and demyelinating etiologies are
common. Compressive causes are rare.
Chronic trochlear palsy may be due to decompen-
sation of a congenital lesion. Congenital lesions are
relatively more common than acquired ones. Special
syndromes and myasthenia need to be excluded by
forced duction and/or Tensilon test.
ABDUCENS (SIXTH CRANIAL) NERVE
The sixth nerve nucleus is situated in the floor of the
fourth ventricle beneath the facial colliculus in the
caudal pontine paramedian tegmentum. The facial
nerve fasciculus loops over the top of the abducens
nucleus, forming the genu of the facial nerve, and the
medial longitudinal fasciculus passes medial to it. The
nucleus contains both motor neurons and “surrogate”
interneurons which project to the contralateral medial
983
rectus subnucleus to mediate conjugate gaze.
Therefore, damage to the abducens nucleus always
results in a gaze palsy and not in an abducens palsy.
Pontine infarction, pontine gliomas, cerebellar tumors,
and Wernicke-Korsakoff syndrome (alcoholic ence-
phalopathy) are common lesions involving the
abducens nucleus.
Fasciculus
The emerging fibers of the abducens nerve leave the
ventromedial aspect of the nucleus and pass ventrally
to exit the brainstem at the pontomedullary junction
just lateral to the pyramidal prominence. If the damage
to the fasciculus occurs in the dorsal pons (Foville’s
syndrome) an ipsilateral abduction weakness occurs
in association with ipsilateral facial weakness,
ipsilateral facial analgesia, ipsilateral Horner’s
syndrome, and ipsilateral deafness. If the damage to
fasciculus occurs in the ventral pons (Millard-Gubler’s
syndrome), the pyramidal tract is involved, causing
an ipsilateral weakness and a contralateral hemiplegia.
These syndromes almost always are the result of
brainstem vascular disease in the elderly. Demyeli-
nating disease and tumor are occasionally encountered
as causes of fascicular damage to the abducens nerve.
Peripheral Nerve (Subarachnoid)
After leaving the brainstem, the sixth nerve courses
upward along the clivus, passing between the pons
and the anterior cerebellar artery before penetrating
the dura. Within the prepontine basal cistern, the nerve
is vulnerable to compression or invasion by basilar
tumors, such as nasopharyngeal carcinoma. Many cra-
nial nerves can be affected in patients with naso-
pharyngeal carcinoma, but the sixth nerve is second
only to the fifth nerve in frequency. Often these
patients will have hearing problems and abnormalities
of tear function due to vidian nerve involvement.
Chordoma, which arises from notochordal remnants,
is another rare basilar tumor; it arises from the clivus
between the sixth nerves. Meningiomas also occur in
this location presenting with similar signs. Increased
intracranial pressure can cause downward displace-
ment of the brainstem to produce a sixth nerve palsy
(false localizing sign) by stretching the subarachnoid
segment between its point of exit from the brainstem
and its dural attachment on the clivus. Along with
headache, vomiting and papilledema, sixth nerve
paralysis is frequent finding in any condition (inclu-
ding pseudotumor cerebri) causing increased
intracranial pressure.
984 Section 8: Neuroophthalmology

Peripheral Nerve (Petrous)

The sixth nerve enters the dura on the clivus at a
variable distance below the posterior clinoid processes
about 1 cm below the crest of the petrous bone. It then
passes around the inferior petrosal sinus beneath the
petroclinoid ligament. At this level, the nerve is
susceptible to trauma associated with fractures of the
temporal bone and to infections from the underlying
mastoid. Petrositis or septic thrombosis of the inferior
petrosal sinus may result in facial pain in association
with sixth nerve palsy (Gradenigo’s syndrome).

Peripheral Nerve
(Cavernosus Sinus and Orbit) Fig. 128.4: Structures directly related to the cavernosus
sinus
In the cavernosus sinus the sixth nerve runs forward Duane’s Retraction Syndrome
with the third and fourth cranial nerves to enter the
it is characterized by limited abduction with narrow-
orbit through the superior orbital fissure (Fig. 128.4).
ing of the palpebral fissure on adduction. Duane’s
Whereas the third and fourth nerves are relatively
retraction syndrome is seen in three forms but is
protected within the wall of the cavernosus sinus, the
always associated with a narrowed palpebral fissure
abducens nerve runs within the middle of the sinus
on adduction. Type one is most common and has
and is more prone to damage. Within the cavernosus
limited abduction with full adduction. In type two,
sinus the sixth nerve is joined briefly by sympathetic
abduction is normal, but adduction is limited. Type
branches from the paracarotid plexus; these subse-
three is characterized by limitation of both adduction
quently pass via branches of the first division of the
and abduction. Although the syndrome may be caused
trigeminal nerve to the iris dilator. This finding may
by various orbital pathological processes, the
account for the occasional association of a post-
congenital abnormality is likely to be due to hypo-
ganglionic Horner’s syndrome with a sixth nerve palsy
plasia or aplasia of the abducens nucleus with
due to an intracavernosus lesion. The sixth nerve
innervation of the lateral rectus muscle by branches
terminates by innervating the lateral rectus muscle.
of the third nerve.

Special Syndromes of the Sixth Nerve Clinical Approach to Isolated

Abducens Palsy of Childhood
It may be a benign postviral condition if additional
signs do not develop within 12 weeks. Coexistent gaze
palsy suggests pontine glioma. Associated cerebeller
signs indicate astrocytoma, ependymoma or medullo-
blastoma.
Mobius’ Syndrome
It is a congenital disturbance of horizontal eye move-
ments associated with facial diplegia. Gaze palsy,
instead of or in addition to abduction paresis, suggests
a possible failure of development of the abducens
nuclei. Patients with Mobius’ syndrome may utilize
vergence movements and cross-fixation to compensate
for their loss of conjugate gaze; head movements may
also be substituted for eye movements.
Sixth Nerve Palsies
Weakness of abduction is characteristic of sixth nerve
palsy.
Esotropia It is present in primary gaze and becomes
more prominent with versions to the side of the
affected eye. Head turn to the side opposite the paresis
is often present to reduce diplopia. Sudden onset of
painful or painless sixth nerve palsy in the middle-
aged or elderly patient having diabetes, hypertension
or both is almost always suggestive of a microvascular
etiology. Testing of glucose tolerance and sedimen-
tation rate may be indicated in the initial evaluation.
Gradual complete resolution is expected 2-3 months
after onset.
Chronic sixth nerve paresis not due to a special syndrome
It is highly suggestive of compressive etiology.
 Chapter 128: Ocular Motor Palsies
Neurodiagnostic imaging studies are indicated.
Tensilon testing and forced ductions are indicated to
exclude myasthenia and restrictive etiologies.
Multiple Ocular Motor Nerve Palsies
Brainstem
The nuclei and fascicles of all the ocular motor nerves
lie between midbrain and pons, a relatively compact
anatomic space. Therefore, vascular lesions and
tumors may easily result in involvement of multiple
nerves.
Subarachnoid Space
Lesions such as infectious or neoplastic, meningitis,
head trauma, midline tumor or aneurysm may affect
multiple ocular motor nerves.
985
Cavernosus Sinus
Lesions within the cavernosus sinus affect more than
one ocular motor nerve. Because the three branches
of the trigeminal nerve exit at different levels of the
cavernosus sinus, the presence or lack of their
involvement may aid significantly in localization of
the process. The mandibular branch (V3) exits almost
immediately from the posterior cavernosus sinus; the
maxillary branch (V2) exits from midcavernosus sinus.
Only the ophthalmic branch (V1) passes through the
anterior cavernosus sinus and superior orbital fissure.
Intracavernosus aneurysm, arterialvenous fistula,
meningioma, pituitary adenoma (with apoplexy or
lateral invasion), granuloma (Tolosa-Hunt syndrome),
and metastatic tumors are commonly encountered
lesions.
 Chapter 129
Supranuclear Disorders of the
Eye Movements and
Visual Integration
G Natchiar, Subhuram
SUPRANUCLEAR DISORDERS
OF EYE MOVEMENTS
Accurate binocular vision is achieved by the associated
action of the ocular muscles, which allow sa visual
stimulus to fall on exactly corresponding points of the
two retinae. The symmetrical and synchronous
movement of the eyes is termed conjugate movement
or gaze (conjugate = yoked or joined together).
Area 8 in the frontal lobe (the frontal eyefield)
initiates the voluntary conjugate movements of the
eyes to the opposite side. They can be elicited by
instructing the patient to look to the right or left; hence
are referred to also as movements on command. These
movements are characteristically rapid and jerky or
saccadic and their purpose is to quickly change ocular
fixation, i.e. to bring new images of objects of interest
on to the fovea. The neuronal firing pattern that
produces a saccade has been characterized as “pulse-
step” in type.1 This refers to the sudden increase in
neuronal firing (the pulse) that is necessary to move
the eyes into their new position, followed by a return
to a new baseline firing level (the step) which
maintains the eyes in their new position.
Pursuit or following movement’s are slower and
smoother and are largely involuntary; the major
stimulus is a moving target upon which the eyes are
fixated. The function of pursuit movements is to
stabilize the image of moving object on the fovea as a
fixated object is tracked by the eyes (smooth tracking)
and thus to maintain continuous clear vision of objects
moving within the environment. Pursuit movements
to each side are generated in the ipsilateral parieto-
occipital cortex; the ipsilateral vestibulocerebellum
(flocculus and nodulus) also is involved.
Slow, smooth pursuit, movements are initiated
when one attempts to follow a moving target. As the
visual image slips off the fovea, the motor neuron
firing rate increases in proposition to the speed of the
moving target, so that normally eye velocity matches
target velocity. If another visual target enters the field,
as when watching a series of stripes on a rotating drum
a quick saccade refocuses the eyes centrally and
optokinetic nystagmus (OKN) results. If the ratio of
the eye and target velocity is less than unity, i.e. if the
eyes fall behind the target, supplementary catch-up
saccades are required for refixation. The pursuit
movement is then not smooth but jerky (cog-wheel).
A lesion of one cerebral hemisphere causes pursuit
movements to that side to break into saccades.2 This
is often associated with but not dependent upon a
homonymous hemianopia. If the parietal lobe is
involved OKN toward the involved hemisphere is lost
or impaired.
Vestibular influences are of particular importance
in establishing images on the retina. By means of the
vestibulo-ocular reflex (VOR), a movement of the eye
is produced that is equal and opposite to movement
of the head. The VOR is a response to rapid transient
head movements. During sustained rotation of the
 Chapter 129: Supranuclear Disorders of the Eye Movements and Visual Integration 987
head the VOR is supplemented by the optokinetic Congenital Ocular Motor Apraxia3
system which enables one to maintain compensatory (Cogan’s Syndrome)
eye movements for a prolonged period. If the VOR is
This is a disorder3 characterized by abnormal eye and
lost, as occurs with disease of the vestibular apparatus
head movements during attempts to change the
(e.g. streptomycin toxicity), the slightest movements
position of the eyes. Patients are unable to make
of the head, even those produced by transmitted
normal voluntary horizontal saccades when their
cardiac pulsations, cause a movement of images across
heads are stationary. If the head is free to move and
the retina, large enough to impair vision.
they are asked to look at an object to either side, they
Ultimately, all the pathways mediating impulses
turn their head in thrusting movement and their eyes
for saccadic and pursuit movements converge onto
turn in the opposite direction. The head overshoots,
the pontine centres for horizontal gaze. These
and the eyes as they return to the central position fixate
comprise of the paramedian pontine reticular
on the target. Both voluntary saccades and the quick
formation (PPRF), the sixth nerve nuclei and pathways
phase of vestibular nystagmus are defective. The
in the pontine and mesencephalic tegmentum
pathologic anatomy has not been studied. This pheno-
connecting the ocular motor nuclei. For many years it
menon is also seen in ataxia- telangiectasia and in
was thought that the abducens nucleus contained only
association with agenesis of the corpus callosum.
the neurons that activated the ipsilateral lateral rectus
muscle; but now it is known that it has two groups of
Frontal Gaze Palsy
neurons each with distinctive morphologic and
pharmacologic properties: (1) the abducens motor This usually follows acute injury to one frontal lobe.
neurons, which project to the ipsilateral lateral rectus There is a gaze preference toward the side of the lesion
muscle; and (2) the abducens interneurons, which and the paucity of saccades contralateral to the side
project via the contralateral MLF to the medial rectus of the lesion. The gaze palsy is usually temporary.
neurons of the third nerve nucleus. Conjugate lateral
gaze is accomplished by the simultaneous innervation Clinical Disorders Affecting the
of the ipsilateral lateral rectus and the contralateral Calibration of Saccadic Eye Movements4
medial rectus, the latter through fibers that run in the
When saccadic eye movements are unable to bring a
medial portion of the MLF. It is the interruption of
target to the fovea, they are dysmetric.
these fibers that accounts for the discrete impairment
or loss of abduction of the ipsilateral eye, a pheno-
Ocular Motor Dysmetria
menon called unilateral internuclear ophthalmoplegia.
It consists of overshooting of a saccade beyond the
CLINICAL DISORDERS AFFECTING THE intended fixation point followed by several to- and
INITIATION OF EYE MOVEMENTS fro oscillations about the endpoint before fixation is
established.
Oculomotor Apraxia
This disorder is characterized by inability to initiate Ocular Flutter
normal voluntary horizontal saccades. The acquired
It consists of bursts of to- and fro saccades occurring
type results from bilateral lesions of the supranuclear
without any intersaccadic interval. Flutter may be seen
gaze pathways, usually localized to the frontoparietal
in the same patients who have dysmetria.
areas. A defect in bidirectional saccadic initiation
occurs without affecting smooth pursuit of moving
Opsoclonus
targets or responses to oculocephalic stimulation,
although the fast phases of vestibular (caloric) It consists of continuous chaotic, irregular unpre-
nystagmus are impaired. Patients with acquired dictable, multidirectional saccades. It is a sign of
oculomotor apraxia must utilize blinks to break the cerebellar or brainstem disease and is most commonly
fixation reflex, moving their heads toward the new encountered as a postviral encephalopathic syndrome
fixation point while the fixation reflex is disrupted. in which postural tremulousness is a major accompa-
988 Section 8: Neuroophthalmology
nying feature. Occult neuroblastoma may present with
opsoclonus and cerebellar ataxia, a fact which must
be kept in mind in the pediatric age group.
Clinical Disorders Affecting the
Size and Velocity of Saccades
Progressive Supranuclear Palsy
This is a degenerative neurologic disorder charac-
terized by axial rigidity, dementia, dysarthria, and a
progressive defect of voluntary eye movement. 5
Downward gaze is frequently affected first, with
horizontal and upward movements being affected
later. Terminally, all movements, even caloric and
oculocephalic, may disappear. The condition inevita-
bly leads to death over a course of several years.
Olivopontocerebellar Atrophy
It may occur on a hereditary or sporadic basis. Its onset
is in early adulthood with unsteadiness of station and
gait. Speech becomes slurred, and there may be
dementia. Optic atrophy and pigmentary degene-
ration of the retina may occur. Eye movements become
progressively slowed in all directions, finally resulting
in complete external ophthalmoplegia.
Other Degenerative Conditions of CNS
Other degenerative conditions of the central nervous
system which have been associated with slowed or
paretic conjugate saccades are Huntington’s chorea,
Wilson’s disease, ataxia-telangiectasia, Whipple’s
disease, the lipid storage diseases, and multifocal
leukoencephalopathy.
GAZE PARESIS
When the paramedian pontine reticular formation
(PPRF) is injured, the pulse-step of innervation to the
ocular motor nuclei is diminished, resulting in gaze
paresis. A similar syndrome results from a nuclear
lesion of the sixth nerve. Mixed in with abducens
motor neurons are cells that are abducens interneurons
(Highstein). The axons from these interneurons cross
at the level of the abducens nuclei and ascend to the
contralateral medial longitudinal fasciculus to synapse
with cells in the medial rectus subnucleus of the third
nerve nucleus. Thus, a sixth nerve nuclear lesion
destroys not only ipsilateral abducens motor neurons
but also the neurons connecting to the contralateral
third nerve nucleus via the medial longitudinal
fasciculus causing a gaze palsy.6
Clinical Disorders Affecting
the Conjugacy of Gaze
Internuclear Ophthalmoplegia
Interconnecting the ocular motor nuclei in the pons
and midbrain is a prominent group of fibers called
the medial longitudinal fasciculus (MLF), located
dorsally on either side of the brain stem midline. It
passes between the abducens nuclei, below and lateral
to the trochlear and oculomotor nuclei.7 This group
of fibers integrates the oculomotor nuclei and has
major connections with the vestibular nuclei. An intact
MLF is essential for the production of conjugate eye
movements of all kinds. Injury to the MLF results in a
typical pattern of disconjugate eye movement called
internuclear ophthalmoplegia.
The ipsilateral eye adducts slowly and incom-
pletely or not at all, while the abducting eye exhibits
a characteristic horizontal nystagmus. Bilateral inter-
nuclear ophthalmoplegia is a commonly seen
oculomotor abnormality in patients with demyeli-
nating disease, but may also occur in patients with
vascular accidents and tumors.
One and a Half Syndrome (Fisher’s)
Injury to the PPRF or the sixth nerve nucleus results
in an ipsilateral paralysis of gaze (the one). If the lesion
extends into the adjacent MLF, then an ipsilateral
internuclear ophthalmoplegia with paralysis of the
ipsilateral medial rectus also occurs (the one-half). Eye
movement would then be limited only to abduction
of the contralateral eye via the intact contralateral sixth
nerve nucleus, a so-called paralytic pontine exotropia.
CLINICAL DISORDERS OF
VERTICAL EYE MOVEMENTS
Paralysis of Upgaze
This is most commonly associated with compressive
lesions at the level of the posterior commissure. Pineal
region tumors, hydrocephalus, and hemorrhage are
the most commonly encountered lesions which affect
the structures of the periaqueductal gray matter,
leading to Parinaud’s syndrome. Lid retraction, often
present in primary gaze and exaggerated with
attempted upgaze, is referred to as Collier’s sign.
 Chapter 129: Supranuclear Disorders of the Eye Movements and Visual Integration
Other features of Parinaud’s syndrome include light-
near dissociation of the pupils, papilledema, and
convergence-retraction nystagmus. Downgaze may
also be paralyzed as part of Parinaud’s syndrome. Of
course, any of the diffuse ocular motor disorders
which lead to paresis of horizontal eye movements
may also affect vertical movements. Progressive
supranuclear palsy (PSP) often begins with paralysis
of vertical gaze.
Skew Deviation
This is a non-localizing vertical misalignment of the
eyes. When seen in conjunction with a unilateral
internuclear ophthalmoplegia, the hypertropic eye is
usually ipsilateral to the medial rectus weakness.
Alternating skew has been attributed to lesions near
the interstitial nucleus of Cajal in the mesencephalon.
NYSTAGMUS AND OTHER
OCULAR MOTOR OSCILLATIONS
Nystagmus is a rhythmic oscillation of the eyes in
which each phase is of equal amplitude. Jerk
nystagmus consists of an initial slow phase followed
by a fast phase and is named by the direction of the
fast phase. Pendular nystagmus consists of two phases,
opposite in direction, but equal in velocity. Arrhy-
thmic, repetitive eye movements also occur, which are
grouped under terminology of ocular motor oscilla-
tions.
Physiologic Nystagmus
Endpoint Nystagmus
This is a jerk nystagmus of fine amplitude and
moderate frequency commonly found in extreme gaze
positions. The fast phase of end point nystagmus is
the direction of gaze. The rhythm and amplitude are
often irregular, and the amplitude is often greater in
the abducting eye.
Optokinetic Nystagmus (OKN)
This is a jerk nystagmus elicited by moving repetitive
visual stimuli through the visual field. The slow phase
is a pursuit movement in which the eyes follow the
moving target; the fast phase is a saccadic movement
in the opposite direction as the eyes return to fixate
on the next target in the series. If the OKN type moves
from right to left, the left parieto-occipital region
989
controls slow phase pursuit movements to the left, and
the left frontal lobe controls the recovery fast phase to
the right. Lesions of the occipitomesencephalic or
frontomesencephalic pathway may cause defects in
OKN. The optokinetic response is difficult to inhibit,
and it can be helpful in detecting functional blindness.
Vestibular Jerk Nystagmus
This is a result of altered input from nuclei to the
horizontal or vertical gaze centers. The slow phase is
initiated by the vestibular nuclei, and the fast phase
by the brain stem and frontomesencephalic pathway.
Vestibular nystagmus can be horizontal, rotatory or
vertical. Rotatory nystagmus is usually due to a
pathologic vestibular condition.
Sensory Deprivation Nystagmus
It occurs when afferent visual defects result in loss of
central vision. The ability of the micromovement
system to keep target precisely on the fovea is lost. It
being pendular, is often dampened by convergence,
and may be accompanied by head oscillation if it
occurs within the first few months of life, the severity
depends on the severity of the visual loss. Latent
nystagmus is similar to deprivation nystagmus, but
occurs in each eye when a “seeing” eye is occluded.
Congenital Motor Nystagmus
In primary position of gaze the movement may be
primarily pendular or jerky in type. With eccentric
gaze, the nystagmus is almost always of the jerk type.
The null point is an eye position where the nystagmus
is minimized. Some patients develop significant head
turns to maintain their eyes at the null point.
Convergence may also decrease the amplitude of the
nystagmus. Despite the rapid, continual movements,
patients do not complain of oscillopsia; nor do they
have severe reduction in visual acuity.
Monocular Forms of Nystagmus
Acquired Monocular Nystagmus
It has also been reported in patients with chiasmal
gliomas and multiple sclerosis.
Blind Eye
Occasionally, blind eyes may exhibit nystagmoid
movements.
990 Section 8: Neuroophthalmology

Acquired Forms of Horizontal Nystagmus
Gaze-evoked Nystagmus
This is a jerky nystagmus of slow frequency, which is
similar to endpoint nystagmus, except that it begins
with the eye in less extreme position of gaze and is of
greater amplitude. It is probably the result of an
inadequate tonic “step” innervation to the extraocular
muscles. This defect in calibration is often associated
with cerebellar disease, but may also occur with
hemispheric or brain stem lesions which affect
conjugate gaze mechanisms (gaze-paretic nystagmus).
Rebound Nystagmus
It consists of a horizontal jerk-type nystagmus with
rapid phase initially directed toward the position of
gaze, but it reverses direction after several seconds of
eccentric gaze. Similarly, if gaze is returned to primary
position, a spontaneous nystagmus opposite in
direction to the previous eccentric eye position is seen.
Rebound nystagmus may occur on gaze to one or both
sides. This type of nystagmus is a feature of cerebellar
parenchymal disease, but may occur in other lesions
of the posterior fossa also.
Periodic Alternating Nystagmus
It consists of a periodic reversal in the direction of the
nystagmus. It may occur congenitally or in patients
with craniovertebral junction anomalies, multiple
sclerosis, in blind patients, and as a toxic response to
anticonvulsant therapy.
ACQUIRED FORMS OF VERTICAL NYSTAGMUS
Upbeat Nystagmus
It occurs in the primary position of gaze and is
associated with impaired upward pursuit. It is caused
by lesions of the anterior vermis and lower brain stem.
Drug intoxication and Wernicke’s encephalopathy are
frequent causes of upbeat nystagmus.
Downbeat Nystagmus
It occurs in the primary position of gaze and is
associated with impaired downward pursuit. It is
caused by lesions of the craniovertebral junction. The
conditions that cause downbeat nystagmus are
Arnold-Chiari malformation, basilar invagination,
multiple sclerosis, cerebellar atrophy, hydrocephalus,
metabolic disorders, familial periodic ataxia, and drug
intoxication.
See-Saw Nystagmus
It is characterized by one eye rising with an intorting
movement, while the other eye falls with an extorting
movement. If acquired, bitemporal hemianopia and
third ventricle tumors are usually present. The other
causes are brain stem vascular disease and trauma. A
disturbance of connections to the internuncial nucleus
of Cajal has been postulated as the etiology.
VERGENCE SYSTEM
The vergence system keeps the image of the target on
corresponding elements of the two retinae by
controlling the visual axes of the eyes. There are two
primary stimuli to vergence eye movements—blur
(accommodative vergence) and diplopia (disparity
vergence). Vergence is a component of the “near-
triad”, which also includes accommodation (change
in lens shape) and pupillary constriction. Unlike
conjugate movements which utilize the gaze centers
of the PPRF, vergence movements seem to have an
independent pathway to the oculomotor nuclei. The
cortical substrate for vergence movements is probably
derived from cells in the visual cortex maximally
simulated by binocular inputs, retinal disparity, and
depth clues. The exact efferent pathway mediating
vergence eye movements is unknown.
High accommodative convergence to accommodation (AC:
A ratio) It is a congenital abnormality of the near triad
responsible for some types of childhood strabismus.
Spasm of the near reflex It is frequently encountered
functional problem. These patients may appear to
have sixth nerve paresis. Rarely, it may also occur in
generalized seizures and following head injury. The
hallmark of such spasms is miosis during the attack
of induced esotropia.
Convergence paralysis This condition in which accom-
modation and miosis are preserved while convergence
is lost can result from a variety of insults to the dorsal
midbrain, including trauma, demyelinating disease,
and brain stem occlusive vascular disease. However,
senescence and lack of effort are the most common
causes of reduced convergence.
Convergence-retraction nystagmus It is associated with
abnormalities of vertical gaze, often as part of the
 Chapter 129: Supranuclear Disorders of the Eye Movements and Visual Integration
Parinaud’s periaqueductal syndrome due to lesions
of the posterior third ventricle.
DISORDERS OF VISUAL INTEGRATION
Visual information received by both occipital lobes is
ultimately analyzed in the dominant parietal lobe,
usually in the left hemisphere. Visual information
from the right homonymous hemifields of vision is
transmitted to the left occipital cortex. From there it
may be transmitted directly to the adjacent parietal
lobe for processing. Visual information from the left
homonymous hemifields of vision arrives at the right
occipital cortex and must be transmitted to the left
parietal lobe. This transmission occurs through the
splenium of the corpus callosum, a group of neural
fibers that transmits information from one cerebral
hemisphere to the other.
Alexia is the inability to read despite relatively
normal vision. Alexia with agraphia (inability to write)
occurs with left parietal lesions involving the angular
gyrus. Alexia without agraphia occurs when a left
occipital lesion is large enough to involve fibers in the
splenium of the corpus callosum that are crossing to
the left angular gyrus from the right occipital cortex.
The patient has a right hemianopia and visual
information from the left visual field cannot gain
access to the left parietal lobe. Reading ability should
be checked in any patient with a left occipital lesion.
Visual neglect occurs when the patient ignores one
side of visual space. Visual extinction occurs when the
patient ignores one side of visual space when pres-
ented with double simultaneous stimuli to both visual
fields. These syndromes are usually associated with
some degree of hemianopia, and they occur more often
with right parietal lesions.
There are a variety of syndromes that result from
lesions of the inferior occipitotemporal area. Visual
agnosia occurs with bilateral lesions and is defined as
the inability to recognize them by touch, in the
presence of intact visual sensory processing, language,
and intellect. This should be distinguished from
anomia (the inability to name objects). Prosopagnosia
also occurs with bilateral lesions; this is the inability
to recognize or distinguish faces.
The inferior occipitotemporal area subserves color
sensation for the entire opposite visual field. A lesion
here causes loss of color sensation in the opposite
hemifield; the visual world appears in shades of gray.
991
This cerebral achromatopsia may be unilateral or
bilateral; if bilateral, it is frequently associated with
prosopagnosia. Superior homonymous visual field
defects may also occur.
Visual hallucinations consist of two types.8 Release
hallucinations are formed (e.g. faces) or unformed (e.g.
flashes of light) and occur in an area of blindness. They
tend to be continuous and variable and can occur with
lesions anywhere in the visual pathway. Ictal halluci-
nations (hallucinations occurring in association with
seizures) are stereotyped and paroxysmal. Formed
ictal hallucinations occur with temporal lobe disease.
Unformed ictal hallucinations occur with occipital lobe
disease.
Palinopsia is an abnormal persistence of visual
images. It is only an isolated symptom and tends to
occur with evolving lesions, more often in the right
hemisphere.
Phosphenes might be confused with uniformed
visual hallucinations. These sensations occur normally
with pressure on the eye, in the dark, etc. Phosphenes
in the temporal periphery occur with retinal traction
at the vitreous base (Moore lightning streaks).9 Eye
movement-induced phosphenes occur in optic
neuritis, and sound-induced phosphenes occur in
optic neuritis and ischemic optic neuropathy.
REFERENCES
1. Troost BT, Dell’Osso LF. Fast eye movements (saccades): Basic
science and clinical correlation. In Thompson HS (Ed): Topics
in Neuro-ophthalmology Baltimore: William and Wilkins Co,
1979;246.
2. Cogan DG. Ophthalmic manifestations of bilateral non-
occipital cerebral lesions. Br J Ophthalmol 1965;49:281.
3. Cogan DG. A type of congenital ocular motor apraxia
presenting jerky head movements. Trans Am Acad Ophthal-
mol Otolaryngol 1952;56:853.
4. Leigh J, Zee DS. The Saccadic system: The Neurology of Eye
Movements. Philadelphia: FA Davis Co, 1983.
5. Steele JC, Richardson JC, Olszewski J. Progressive supra-
nuclear palsy. Arch Neurol 1968;10:333.
6. Fisher CM. Some neuro-ophthalmological observations. J
Neurol Neurosurg Psychiatr 1968;30:383.
7. Sharpe JA, Rosenberg MA, Hoyt WG. Parlytic pontine
exotropia: A sign of acute unilateral pontine gaze palsy and
internuclear ophthalmoplegia. Neurology 1974;24:1076.
8. Brust JCM, Behrens MM. Release hallucinations as the major
symptom of posterior cerebral artery occlusion: A report of 2
cases. Ann Neurol 1977;2:432.
9. Lessel S. Higher disorders of visual function. In Neuro-
ophthalmology St. Louis: CV Mosby Co, 1975;8.
 Chapter 130
Papilledema
LC Dutta
Papilledema also called plerocephalic edema is an
ophthalmoscopic sign of swelling of the optic nerve
head without any inflammatory element whatsoever.
On the other hand edema of the optic disk occurs in
inflammation of the optic nerve head (papillitis) or of
the chorioretina adjacent to the optic disk. The most
common cause of papilledema is raised intracranial
pressure; 80 to 85 percent of intracranial tumors
produce papilledema. It most commonly develops in
tumors of the cerebellum, the fourth ventricle and the
temporosphenoidal lobe of the cerebral hemisphere.
In precentral and postcentral tumors it is not a constant
sign and may develop in the late stage of the lesion.
Tumors of the midbrain are always associated with
papilledema but it may be absent in pontine tumors.
Papilledema is common in children in the age group
between one and five years. It may be argued that as
sutures between the cranial bones are not closed in
early childhood, sutural separation may help expand
the cranial cavity thereby lessening the possibility of
development of papilledema. But the relative
frequency of chocked disk in children can be explained
by the special character of childhood cerebral tumors
which grow rapidly and they are mostly infratentorial
hence blockage of cerebrospinal fluid circulation
develops early.
Papilledema is usually bilateral but does not
always develop simultaneously and symmetrically in
both the eyes. Unilateral papilledema in intracranial
space occupying lesions occurs if the other eye has
got optic atrophy (Foster-Kennedy syndrome);
otherwise unilateral papilledema is due to ocular or
orbital cause. In highly myopic eyes papilledema may
not develop inspite of prolonged intracranial pressure;
though the actual cause is not known, the anatomic
peculiarities of the myopic disk and the area
surrounding it may prevent development of papill-
edema. Orbital causes of unilateral papilledema are
tumors, aneurysms, inflammatory conditions,
abscesses or edema of the orbit. Papilledema due to
ocular cause is very rare; it may develop due to very
low intraocular pressure in cases of over-drainage after
filtration operation.
PATHOGENESIS OF PAPILLEDEMA
Various concepts of pathogenesis of papilledema have
been described; however none of them is conculsive.
It was suggested that the cerebrospinal fluid is forced
under increased pressure from the subarachoidal
space into the corresponding intravaginal space of the
optic nerve or its perivascular lymph spaces. It is also
possible that an edematous process in the brain
spreads forward to the disk.
Experimental work of Hayreh1 is important in
understanding the pathogenesis of papilledema. He
gradually inflated intracranial balloons in monkeys
and demonstrated that papilledema is usually evident
ipsilaterally before becoming bilateral. It was also
demonstrated that when one optic nerve sheath is
fenestrated before increasing the intracranial pressure
the ipsilateral optic disk does not develop papill-
edema. Development of papilledema seems to depend
on the intact and patent subarachnoid space. In
unilateral optic atrophy, myopia and glaucoma,
papilledema does not develop in the affected side due
to obliteration of this path.
Another theory of development papilledema is due
to interference with the axoplasm transport mecha-
nism of the optic nerve fibers. Distal or orthograde
movement of proteins and cellular organelles in the
axons of normal peripheral nerves is an established
 Chapter 130: Papilledema
neurophysiological phenomenon; this has been
confirmed by various workers by isotope labeled
experiments. The orthograde axoplasmic transport
probably occurs at various rates, i.e. a rapid compo-
nent 200 to 1000 mm per day and a slow component
0.5 to 3 mm per day. Both rapid and slow components
of axoplasmic transport operate in nonmyelinated and
myelinated nerves. Optic nerve axoplasmic transport
transmits material from the retinal ganglion cells to
the entire axons and to its termination in the lateral
geniculate body where some of the material is
degraded and is returned to the cell body via the
retrograde transport system. Both the slow and fast
components of axonplasmic transport systems work.
The cessation of axoplasmic transport particularly of
the rapid component at the lamina cribrosa is a
consistent finding in optic disk swelling.2 When the
raised intracranial pressure exerts pressure upon the
optic nerve fibers at the level of the lamina cribrosa
there is interference with the axoplasmic flow which
interferes with nutrition of the nerve fiber; the
accumulated toxic elements may cause further
damage leading to swelling of the nerve head.
Whatever may be the mode of action the main
cause of papilledema is mechanical. The increased
pressure is transmitted along the subarachnoid space
around the nerve leading to dilatation of the space
near the optic disk; the central retinal vein as it crosses
the space is compressed by increased pressure of the
albuminous fluid.
PATHOLOGY OF PAPILLEDEMA
Papilledema is a simple edema of the nerve head with
edematous swelling of the nerve fibers. The interstitial
tissue also becomes edematous leading to anterior
convex displacement of the glial fibers of the lamina
cribrosa. The physiological cup becomes filled up with
fluid. As the entire disk mushrooms into the vitreous,
the adjacent retina also becomes edematous and
displaced away from the disk margin. There is
accumulation of fluid between the sensory retina and
pigment epithelium which is a contributory factor of
enlargement of the blind spot. The veins and
capillaries of the optic disk are dilated. Hemorrhage
over the disk or in the adjacent nerve fiber layer of the
retina shows ophthalmoscopic appearance of flame
shaped hemorrhage. The peripheral nerve fibers show
edematous changes in the early stage of the condition.
The non-medullated fibers upon the disk, particularly
those near the disk margin swell up and shows
993
varicosities. After a variable time degenerative
changes start; the neurofibrils in the varicosities
disappear forming homogenous granular structure
filling the fusiform enlargements. This gives rise to
formation of cytoid bodies. Finally centripetal
Wallerian degeration starts in the nerve fibers with
axonal chromatolysis in the retinal ganglion cells along
with proliferation of the astrocytes and neuroglial
cells. Ophthalmoscopically this corresponds to the
grayish white discoloration of the disk which is
accompanied by visual loss.
OPHTHALMOSCOPIC APPEARANCE
OF PAPILLEDEMA
Frequently the ophthalmologists are confronted with
some neurological cases referred for opinion whether
papilledema is present or not. In fairly late stage of
raised intracranial pressure when full blown papill-
edema sets in there is no problem in ophthalmoscopic
diagnosis. Problem arises at the very early stage. It is
difficult to label which is the earliest ophthalmoscopic
sign of papilledema; absence of venous pulsation at
the disk margin is found to be a reliable sign. In cases
where spontaneous venous pulsation is not seen in
about 20 percent of the normal individuals, it can be
induced by light pressure over the eyeball; but in early
cases of papilledema venous pulsation cannot be
induced even by pressure upon the globe when
spontaneous pulsation is absent. Filling up of the
physiological cup and blurring of the disk margin are
fairly late signs. Moreover normal physiological cup
also is not a constant finding in the disk. Another early
sign is reddish coloration of the optic disk due to
capillary stasis. Gradually slight haziness of disk
margin sets in always first at the upper and lower
margin usually at the upper nasal quadrant. Then it
spreads to the nasal margin and lastly in the temporal
margin. This order of development is due to the
anatomical arrangement of the nerve fibers at the
margin of the optic disk; as the papillomacular bundle
occupies the temporal margin of the disk the fibers
from the rest of the temporal retina have got to be
crowded at the upper and lower margins of the disk.
Fully developed papilledema is a positive sign of
raised intracranial pressure. This shows mushrooming
of the nerve head into the vitreous drawing the
tortuous and dilated veins with it. The disk diameter
is increased.
The enlargement of the disk is due to swelling of
the nerve head as well as spreading of the edematous
994 Section 8: Neuroophthalmology

fluid into the surrounding retina. In the early stage complains of headache and vomiting but funduscopy
the swelling can be easily appreciated by indirect shows optic atrophy with fullness of the optic disk
ophthalmoscopy or by stereophotography. Though without peripapillary edema. This stage is known as
not very accurate, the swelling of the disk can be “vintage papilledema”.
measured with an ophthalmoscope in the following
way: The ophthalmoscope is first focused on the most SYMPTOMATOLOGY OF PAPILLEDEMA
prominent vessel over the optic disk and the strongest
Symptomatology of papilledema is basically the same
plus lens or weakest minus lens is put in the sighthole
as that of raised intracranial pressure. Amblyopic
to have a clear view of the vessels. The next step is to
attacks and obscuration of vision lasting for 20 to 30
select a vessel, parallel to the one first observed near
seconds are quite frequent symptoms.
the disk margin in the retinal plane and again to find
Visual loss is due to atrophy of the optic disk in
out the strongest plus lens or weakest minus lens which
late stage of papilledema. Enlargement of the blind
gives a clear picture of the vessel. The difference of
spot has been the visual field hallmark of papilledema.
power of these two lenses gives the prominence of the
The normal blind spot lies in a zone between 13 and
disk in diopters. The conventional conversion rate is
18.5 degree temporal to the point of fixation and has
3 diopters for one mm of prominence. It is immaterial
dimension of 5.5 degrees in (horizontal) width and
whether the observer is emmetropic or ametropic or
7.5 degrees in (vertical) height. This is the area of
whether the corrective spectacles are worn during
absolute scotoma and does not change in size or shape
ophthalmoscopy or not.
with higher stimulus intensity or color. Surrounding
The reddish coloration of the disk is due to venous
the absolute scotoma there is a narrow amblyopic zone
congestion; the capillaries become dilated simulating
of relative scotoma. Enlargement of the blind spot in
small vessels and sometimes the color of the optic disk
papilledema may affect both the absolute and relative
becomes almost the same with that of the retina. This
scotomatous area. Enlargement of the absolute blind
factor, coupled with blurring of the optic disk makes
spot is due to detachment of the sensory retina from
it difficult to differentiate the optic disk from the rest
the pigment epithelium by the edematous fluid.3 The
of the fundus. Arteriovenous ratio changes due to
sloping relative scotoma is due to compression and
dilatation of the veins rather than narrowing of the
displacement of the retinal percipient elements by the
arterial caliber; the ratio of vein to artery becomes
edematous optic nerve fibers and the Stiles Crawford
about 4:2 or 5:3 in place of normal ratio of 3:2. The
effect. This phenomenon proposes that the wrinkles
veins appear to climb at the neck of the papilla to the
and folds in the peripapillary retina cause light to fall
surface of the optic disk and traverse the sloping of
obliquely on the photoreceptors, thus making the light
the disk periphery up to the plane of the retina.
a less effective stimulus. Along with this, production
Hemorrhage over the disk in the adjacent retinal nerve
of peripapillary hypermetropia due to elevation of the
fiber layer is a result of venous stasis.
retina by the edematous fluid also plays some part in
Pathogenesis of cytoid bodies has already been
modifying the size of the relative scotoma.4 Concentric
indicated before. The white patches seen over and
contraction of the visual field in later stage of the
adjacent to the disk margin are not soft exudates or
condition is due to pressure atrophy of the optic nerve
cotton-wool patches but they are cytoid bodies. If the
fibers situated in the peripheral part of the nerve.
edema increases it may extend into the adjacent retina
and even into the macular area. Droplets of fluid
FLUORESCEIN ANGIOGRAPHY IN PAPILLEDEMA
occasionally accumulate underneath the internal
limiting membrane and become visible as brilliant Normally after the injection of the dye, within fraction
dots in a radial arrangement giving the appearance of of a second before the retinal artery is filled, the optic
macular hemi-star or macular fan. disk begins to fluoresce due to circulation of the dye
Lack of timely surgical intervention leads to optic through the anastomotic plexus of Zinn supplying the
atrophy; it takes about one year for development of optic disk. The capillary branches of the central retinal
complete optic atrophy. As the atrophic optic nerve artery are filled together with the main vessels a little
cannot imbibe edematous fluid, papilledema dis- later. The disk is covered by a network of fine vessels.
appears even though the causative factor is not In papilledema the first sign appears during the
removed. This is a critical stage. The patient still arterial and early venous phase. During this phase a
 Chapter 130: Papilledema
network of dilated tortuous capillaries become visible
on the surface of the disk. The tortuous capillaries
appear to come from the depth of the physiological
cup. The margin between the vascular net on the
elevated disk and the surrounding retina becomes
conspicuous. The second sign is a diffuse fluorescence
of the entire disk tissue. This starts in the late venous
phase and may last several hours. It is also well demar-
cated and is confined to the disk itself. Fluorescein
angiography helps in differentiating papilledema
from pseudopapilledema.5 Capillary dilatation, dye
leakage, microaneuaysm and excess disk vascularity
are present in papilledema but not in pseudo-
papilledema.
DIFFERENTIAL DIAGNOSIS OF
UNILATERAL OPTIC DISK EDEMA
Following four conditions deserve consideration in
differential diagnosis of unilateral optic disk edema:
1. Congenital
2. Local condition of the disk and orbit
3. Orbitocranial disease
4. Papilledema.
Congenital Abnormalities
Some congenital abnormalities may simulate edema
of the optic disk. Congenital abnormalities of the disk
constitute about 14 percent of cases of pseudopapill-
edema. The common conditions in this group are as
follows:
a. Very small disk with tortuous vessels seen in high
degree of hypermetropia.
b. Drusen of the optic disk. Drusen or hyaline
(colloid) bodies are deposits of degenerative
hyaline like materials on the surface of the optic
disk or in the optic nerve. To a certain extent they
are comparable to the hyaline deposits occurring
in Descemet’s and Bruch’s membrane. Drusens are
common in elderly persons. It may be associated
with acquired diseases of the eyeball or of the optic
nerve, viz hypertensive retinopathy, vascular
occlusion, chorioretinopathies, papillitis, long-
standing glaucoma, etc. However, diseases like
tapetoretinal degeneration also lead to formation
of drusen. Drusen may be exposed or buried.
Drusen of the optic disk shows autofluorescence
and fluorescein angiograms show irregular
fluorescence in the late stage which does not spread
995
to the retina. Buried drusen of the disk causes
benign disk swelling in children.
Local Condition of the Orbit and the Disk
Orbital diseases Chronic orbital space occupying lesion
may give rise to unilateral optic disk edema. Tense
orbit or orbit with granulomatous or infiltrating lesion
may show disk edema. Patient with unilateral disk
edema should be carefully evaluated for signs of
orbital disease. Ocular movements, intraocular
pressure on upgaze position, biochemical tests for
thyroid disease, CT scan, etc. should be done.
Local condition of the optic disk The common local
conditions are as follows:
1. Inflammatory—which include:
i. Papillitis
ii. Juxtapapillary choroiditis.
2. Vascular:
i. Arterial (anterior ischemic optic neuropathy)
ii. Venous (central retinal vein occlusion).
3. Primary or secondary tumor of optic nerve or
sheath.
4. Infiltration e.g. Sarcoid, lymphoma, leukemia,
carcinoma.
5. Ocular hypotony.
The differentiating point from papillitis and papill-
edema is mainly vision which is grossly defective in
papillitis; in papilledema good vision is maintained
for quite a long time. In peripapillary choroiditis
(Jensen’s choroiditis) measurable papilledema and
vascular changes are not present.
Orbitocranial Diseases
Concomitant involvement of both the orbital and
intracranial compartments may rarely be seen and this
usually occurs with infiltrative conditions which may
be either neoplastic or inflammatory. Granulomatous
inflammations may spread from the orbit through the
optic canal or orbital fissure to involve the cavernous
sinus, pituitary fossa and anterior or middle cranial
fossa.
Meningioma arising from the region of the optic
canal or sphenoid ridge spreads either into the orbit
or into the cranial cavity. Disk edema of chronic in
nature and with opticociliary shunt vessels and
peripapillary choroidal striae may indicate an optic
nerve sheath meningioma which can be confirmed
with CT scan or MRI.
996 Section 8: Neuroophthalmology
Unilateral papilledema
Raised intracranial pressure usually produces bilateral
and symmetrical papilledema but unilateral disk
edema may be seen in tumors of particular sites or
when congenital or acquired factors may alter the
patency of the space under the optic nerve sheaths.
REFERENCES
1. Hayreh SS. Pathogenesis of oedema of the optic disk (Papill-
oedema): A preliminary report: Br J Ophthalmol 1964;43:522.
2. Minekler DS, Tso MIM, Zimmerman LE. A light microscopic
autoradiographic study of exoplasmic transport in the optic
nerve head during ocular hypotony, increased intraocular
pressure and papilloedema. Am J Ophthalmol 1976;82:741.
3. Duke-Eider S, Scott GI. Neuro-ophthalmology. In Duke-Elder,
S (Ed). System of Ophthalmology 12: St. Louis, CV Mosby,
1971.
4. Corbet JJ, Jacobson DM, Mauer RC et al. Enlargement of the
blind spot caused by papilloedema. Am J Ophthalmol
1988;105:26.
5. Cartlidge NEF, Ng RCY, Tilley PJB. Dilemma of the swollen
optic disc: A fluorescein retinal angiography study. Br J
Ophthalmol 1977;61:385.
 Chapter 131
Idiopathic Intracranial
Hypertension
(Pseudotumor Cerebri)
LC Dutta, NK Dutta
SYNONYMS
Pseudotumor cerebri, Benign intracranial hyper-
tension, Serous meningitis, Meningeal hydrops, Otitic
hydrocephalus.
DEFINITION
Idiopathic intracranial hypertension (IIH) is a clinical
syndrome characterized by increased intracranial
pressure, cytologically and biochemically normal
cerebrospinal fluid (CSF), optic nerve head edema and
headache in the absence of intracranial mass lesion
(granuloma or neoplasm) and hydrocephalus with
normal sized ventricles and without neurological
finding of intracranial space occupying lesion or
hypertensive encephalopathy.
CIRCULATION OF CSF
The CSF is secreted from the choroid plexus in the
lateral, third and 4th ventricles of brain. It leaves the
ventricles through the apertures in the roof of the
fourth ventricle and flows through the cerebral and
venous sinuses to be absorbed by the arachnoid villi.
Increased CSF pressure is caused by increased volume
of the CSF which in turn may be due to decreased
absorption by the cauliflower like arachnoid granu-
lations of superior sagittal venous sinus. High CSF
pressure in case of intracranial space occupying lesion
is due to blockage of the internal circulatory process
of CSF.
ETIOLOGY OF IIH
Although it is not known what are the causes of IIH,
there are several clues for the causative factor. The
condition occurs mostly in fat women of child-bearing
age but not in thinly built persons. Role of hormone is
also not ruled out. Hameed et al1 reported that patients
treated with danazol for gynecological disorders like
endometriosis and benign cystic breast diseases
develop IIH and after discontinuation of the drug, the
condition regressed. Danazol is also used in the
treatment of some diseases of the hemopoietic system
like thrombocytopenic purpura and immune hemo-
poietic anemia.2
A recent report2 of pediatric pseudotumor cerebri
implicated several diseases of endocrine origin as
possible cause of IIH. This condition is reported to be
associated with Addison’s disease3,4 and Cushing’s
disease5 in childhood. Its association with reduction
in dosage of prolonged corticosteroid therapy in
children of renal, dermatological or respiratory
disorders have been described.2 Liu and coworkers6
reported two adults and one adolescent with
inflammatory bowel disease who developed classical
pseudotumor cerebri during corticosteroid with-
drawal. IIH has been reported after administration of
high dose of vitamin A, tetracycline, cyclosporine, use
of oral contraceptive and bodybuilding drugs. Borruat
and Regli have reported IIH occurring after use of
amiodarone for treatment of auricular fibrillation; the
998 Section 8: Neuroophthalmology
disk edema regressed after discontinuing the drug.7
IIH may also occur along with infectious systemic
disorders like Lyme disease. 8 In patients with
inflammatory bowel disorders like ulcerative colitis
and Crohn’s disease, ocular inflammatory disturbance
are reported but not papilledema.9,10 But papilledema
is also reported in iron deficiency anemia.11,12
PATHOLOGY
Basically any disproportion between the rate of
formation and reabsorption of CSF causes increased
volume of the fluid and subsequently increased
intracranial pressure. Normal intracranial pressure (of
CSF) is 5-15 cm of water as measured by lumbar
puncture in lying on side position. In IIH it may go
up to 100 cm of water. The blockage in the flow of
CSF between the brain and its route to the blood, the
jugular vein, can cause raised pressure. Scarring of
the cells next to the brain that absorb the CSF, i.e. the
arachnoid villi of the lateral and third ventricles can
cause raised pressure.
When the intracranial pressure remains high, the
optic nerve fibers are atrophied. The pressure may
cause damage to the abducens nerve in its long
intracranial course. Optic disk drusen is also a
common finding in longstanding cases of IIH.13
SYMPTOMS OF IIH
More often than not, IIH is a disease of children or
obese women. Headache is a common presenting
symptom. The headaches are usually severe and occur
daily. Often they are throbbing in character and may
awaken the patient at night. The headaches last for
several hours. Nausea is common though vomiting is
less common. Sometimes there may be pain behind
the eyeball which worsens on eye movements.
Pulsatile intracranial noise or pulse synchronous with
tinnitus is common. The sound is often unilateral.
Compression on the jugular vein abolishes the sound.
Transient obscurations of vision which are episodes
of blurred vision that usually lasts less than 30 seconds
are followed by full recovery of vision. This symptom
occurs in about 3/4th of IIH patients. The attacks may
involve one or both eyes. They are not correlated with
the degree of intracranial hypertension or with the
extent of optic nerve swelling. Visual obscuration do
not seem to be associated with poor visual outcome.
The most serious problem of the patients is loss of
vision. About 5 percent of patients go blind in at least
one eye. These are usually patients who don’t turn up
for regular follow-up evaluation. Vague dizziness,
diplopia due to slight abducens weakness (a false
localizing sign), paresthesia of some parts of the body
are also not uncommon but signs of gross neurological
deficit are absent.
Visual field defects Except in very late stage patients do
not complain of any symptom suggestive of defective
field of vision. However, visual field should be
analyzed with appropriate methods to detect early
field defect because this indicates damage to the optic
nerve fibers by the high intracranial pressure.
DIAGNOSIS
Final diagnosis of IIH is made by exclusion of other
causes of papilledema and intracranial hypertension,
like intracranial space occupying lesions, hydro-
cephalus, hypertensive encephalopathy and throm-
bosis of the sagittal sinus. However the characteristic
presenting symptoms of the disease should suggest
the possibility of IIH, and this is confirmed by spinal
tap.
By fundus examination it is not possible to differen-
tiate whether the papilledema is due to IIH or due to
intracranial space occupying lesion. However
extensive disk edema may elevate the peripapillary
retina or cause macular chorioretinal folds.14 Detach-
ment of the neurosensory retina may be caused by
subretinal accumulation of fluid extending from the
optic disk into the macula and formation of exudative
lipid macular star due to increased capillary permea-
bility.15 Other fundus abnormalities include pigment
epithelial mottling and hemorrhage into the vitreous,
choroid and nerve fiber layers.16 Branch retinal arterial
occlusion may develop presumably as a result of
vascular compression.17,18
Lumbar puncture for diagnosis of IIH is important.
The CSF pressure is very high. CSF is crystal clear, no
cells on microscopic study and normal biochemical
examinations.
Neuroimaging procedures such as CT scan or MRI
scan several no abnormality. The size of the ventricles
are normal or even smaller but never enlarged.
Arteriography shows patency of venous sinuses and
veins.
TREATMENT
The main target of treatment of IIH is to protect the
optic nerve. Prolonged raised intracranial pressure
 Chapter 131: Idiopathic Intracranial Hypertension (Pseudotumor Cerebri)
with papilledema will lead to optic nerve atrophy due
to degeneration of the nerve fibers. The best way to
prevent visual loss is to test the central vision and
visual fields once or twice a year or whenever new
symptoms appear. The disease tends to occur or recur
during periods of weight gain.
The management of patients with IIH can be
divided into medical and surgical treatment. The
cornerstone of medical therapy is weight loss. In
practice the weight loss is correlated to loss of water
from the body tissue. As in the etiology of IIH
treatment for weight gaining is a risk factor, on the
same ground quantitative weight loss will cause
improvement in the symptoms of IIH.
Loss of fluid from the body can be achieved by
using diuretics. Diamox is the most commonly used
medication for this purpose. It is safe and effective
but nearly all patients complain of tingling or ‘pins
and needles’ sensation over the extremities. Rarely,
kidney stones and blood disorders may develop as
complications of diamox therapy. Lasix (frusemide)
is another diuretic which is stronger than diamox. Liu
and associates18 treated four patients of IIH, who
developed acute and severe visual loss with methyl
prednisolone and acetazolamide. They used combi-
nation therapy with intravenous methyl prednisolone
250 mg 4 times a day, acetazolamide 500 mg twice
per day and ranitidine (for possible gastritis) for 5 days
followed by prednisolone 80 mg per day tapered over
six weeks. If this treatment fails to improve visual
function, they recommend surgical treatment. Most
of the patients recover after medical therapy over a
period of weeks or months. If satisfactory result is not
obtained after medical therapy, surgical treatment
should be instituted without further delay. Increased
intracranial pressure causes visual dysfunction by
compressing the optic nerve fibers in the sub-
arachonoid space of the retrobulbar portion of the
optic nerve with obstruction of intra-axonal fluid
mechanics. After weeks or months, nerve fibers
attrition causes progressive loss of visual field.
Therefore, if the CSF pressure remains extremely high,
episodes of cloudy vision may herald the onset of
blindness. Such cases require early surgical treatment.
Surgical Treatment
Surgical treatment consists of the followings:
a. Repeated lumbar puncture
b. Optic nerve sheath decompression
c. Shunt operation.
999
Lumbar Puncture
It is not a permanent measure for lowering the
intracranial pressure. After few days the pressure will
go up again demanding repeated lumbar puncture.
This procedure is inconvenient to the patient and also
is not without risk of infection and other procedural
complications. Therefore repeated lumbar puncture
is poorly tolerated and not recommended.
Optic Nerve Sheath Decompression
Optic nerve sheath decompression is safe and effective
form of treatment for patients with papilledema and
visual loss secondary to IIH. Initial description of optic
nerve sheath decompression is attributed to DeWecker
in 1872 who described resolution of neuroretinitis by
blindly incising the retrobulbar nerve sheath. SS
Hayreh showed in primates that artificially induced
papilledema reduced when the optic nerve sheath was
incised.23 Thereafter the procedure showed favorable
results in treatment of IIH.
This procedure can be done under local anesthesia
through a transconjunctival medial orbitotomy. The
medial rectus muscle is temporarily disinserted to get
a better view and working space over the sheath of
the retrobulbar portion of the optic nerve. The sheath
is incised or fenestrated by making one or two snips
or a large hole on the optic nerve sheath and fluid
drains out taking the pressure off the optic nerve. The
operation may have to be repeated—a secondary or
tertiary procedure may have to be done.13,19-21 Optic
nerve decompression should be performed at the
appearance of first objective sign of progressive optic
nerve compression.
Operative complications of the procedure is
minimum if done with adequate magnification and
proper illumination using an operating microscope.
Otherwise common complication is late failure. Late
failure requires early detection and demands
secondary operation. Failure can be detected by B-scan
ultrasonography (vertical transverse echogram),
which reveals increased subarachnoid fluid. In
successful optic nerve sheath surgery, B-scan would
show cavitation or cystic appearance in the immediate
retorbulbar portion of the optic nerve. Or else
echoluscent fluid track emanating from the area of the
incision on the nerve sheath can be seen.22
Failure of the optic nerve sheath operation may be
due to the following causes:
1000 Section 8: Neuroophthalmology
i. Inadequate fenestration or incision into the nerve
sheath. This can be avoided by multiple fenestra-
tions or incisions on the optic nerve sheath.
ii. Marked thickening of the arachnoid of the optic
nerve sheath.
iii. Late failure due to extensive scarring and fibrosis
of the orbital fat throughout the retrobulbar
intraconal space. Repeat optic nerve decompres-
sion is difficult in such cases.
Intraoperative application of antifibrotic drugs like
mitomycin C at the site of fenestration has been used
to ensure that the site of the fenestration is not blocked
by fibrosis.
Lumbar-Peritoneal Shunt
The lumbar-peritoneal shunting is done when the
optic nerve sheath decompression operation fails.
Tubing is placed in the spinal fluid space. The space
is entered during a lumbar puncture or spinal tap and
the tubing is then run into the abdomen. This lowers
the pressure around the brain and optic nerve, thereby
eliminating the symptoms of raised intracranial
pressure. However these procedures are complicated
by various problems; the most severe one is periodic
clogging of the tubing causing recurrence of symptoms
and sometimes visual loss. A repeat operation is then
needed.
REFERENCES
1. Hameed LM, Gluser JS, Schatz NJ et al. Pseudotumor cerebri
induced by Danazol. Am J Ophthalmol 1989;107:105.
2. Lessal S. Pediatric pseudotumor cerebri (idiopathic
intracranial hypertension). Surv Ophthalmol 1992;37:155.
3. Alexandrekis G, Filatov V, Walsh T. Pseudotumor cerebri in
a 12-year old boy with Addison’s disease. Am J Ophthalmol
1992;116:650.
4. Walsh FB. Papilledema associated with increased intracranial
tension in Addison’s disease. Arch Ophthalmol 47:86, 195.
5. Weissman MN, Page LK, Bejar RL. Cushing’s disease in
childhood: Benign intracranial hypertension with trans-
sphenoidal adenectomy. Neurosurgery 1983;13:195.
6. Liu GT, Kay MD, Bienftang DC. Pseudotumor cerebri
associated with corticosteroid withdrawl in inflammatory
bowel disease. Am J Ophthalmol 1994;117:352.
7. Borruat F, Regli F. Pseudotumor cerebri as a complication of
amiadarone therapy. Am J Ophthalmol 1993;116:776.
8. Jacobson DM, Frene DB. Pseudotumor cerebri syndrome
associated with Lyme disease. Am J Ophthalmol 1989;107:981.
9. Reifer DM, Kaufman DI. Optic disc drusen and pseudotumor
cerebri. Am J Ophthalmol 1988;106:94.
10. Know DI, Schachat AP, Mustonen E. Primary secondary and
coincidental ocular complications of Crohn’s disease.
Ophthalmology 1984;91:163.
11. Lubeck MJ. Papilloedema caused by iron deficiency anaemia.
Trans Am Acad Ophthalmol 1959;63:303.
12. Capricks LF. Intracranial hypertension and iron deficiency
anemia: Report of four cases. Arch Neurol 1963;9:142.
13. Spoor TC, Ramosky JM, Madion MP et al. Treatment of
pseudotumor cerebri by primary and secondary optic nerve
sheath decompression. Am J Ophthalmol 1991;112:177.
14. Gittinger JW, Asdourian GK. Macular abnormalities in
papilledema from pseudotumor cerebri. Ophthalmology
1989;96:192.
15. Pollock SL. Acute papilledema and visual loss in a patient
with pseudotumor cerebri. Arch Ophthalmol 1987;105:752.
16. Morris AT, Saunders MD. Macular changes resulting from
papilledema. Br J Ophthalmol 1980;64:211.
17. Lam BL, Siatkowski RM, Fox GM et al. Visual loss in pseudo-
tumor cerebri from branch retinal arterial occlusion. Am J
Ophthalmol 1992;113:334.
18. Liu GT, Glaster JS, Schatz NJ. High dose methyl prednisolone
and acetazolamide for visual loss in pseudotumor cerebri.
Am J Ophthalmol 1994;118:88.
19. Kertna JL, Hart WH, Bude RM. Optic nerve sheath decom-
pression. How does it work? Has its time come? Arch
Ophthalmol 1988;106:1365.
20. Bourman ND, Sproon TC, Ramokki JM. Optic nerve sheath
decompression for pseudotumor cerebri. Arch Ophthalmol
1988;106:1372.
21. Sergot RC, Savino PJ, Basley TM. Modified optic nerve
decompression for pseudotumor cerebri. Arch Ophthalmol
1988;106:1372.
22. Byrne SF, Green RL. Ultrasound of the Eye and Orbit. Mosby
Year Book. 01968, 0-8016-1968-8,421.
23. Hayreh SS. Pathogenesis of edema of the optic disc
(Papilledema). A preliminary report. Br J Ophthalmol.
 Chapter 132
Abnormalities of
Optic Disk and Optic Nerve
G Natchiar, Subhuram
OPTIC NERVE DRUSEN
These degenerative chunks of hyaline-like material
occur within the substance of the optic nerve anterior
to the lamina cribrosa. Their incidence is 0.3 to 1
percent. They are bilateral in 75 to 80 percent of cases.
It is an autosomal dominant condition. Superficial
drusens appear as irregular, glistening, yellow
globules that may be isolated or clustered. Deep
drusens are not directly visible, thus causing
pseudopapilledema. Buried drusen often becomes
visible with advancing age. Histopathologically,
drusens appear as concentric hyaline-like laminations
with calcification. They stain positively for amino
acids, acid mucopolysaccharides, calcium, and
hemosiderin, and negatively for amyloid. The etiology
of drusen is unknown.
Drusen are generally asymptomatic. Visual loss
may occur from compression of nerve fibers, sub-
retinal hemorrhage, or subretinal neovascularization.
Visual field defects are common and include enlarge-
ment of blind spot, nerve fiber bundle defects and
occasionally irregular constriction of peripheral field.
Severe visual field loss is possible. Loss of visual acuity
from optic drusen is so rare that patients with drusen
and visual impairment should be evaluated for a
compressive lesion.
The ophthalmoscopic features of drusen (pseudo-
papilledema) include the followings:1,2
1. Central cup absent but spontaneous venous pulsa-
tions often present.
2. Vessels arise from central apex of disk.
3. Anomalous branching of vessels on disk and
increased number of major disk vessels.
4. Disk transillumination may show drusen.
5. Disk margins show irregular outline with derange-
ment of peripapillary pigment epithelium.
6. Absence of superficial capillary telangiectasia,
hemorrhages, exudates, and cotton-wool spots.
7. Absence of peripapillary retinal folds.
8. Lack of fluorescein leakage from disk vessels.
9. Drusen may show autofluorescence prior to fluore-
scein dye injection and may stain in the late stages
of the angiogram.
It should also be remembered that disk with
pseudopapilledema can also develop true papill-
edema.
TILTED OPTIC DISK
The main features of this anomaly are: (i) an oval disk
with a depression on one side, usually inferiorly, and
elevation of the other side, usually superiorly, (ii) a
crescent on the side of the disk depression, and (iii) an
oblique direction of retinal vessels.3 There may be an
associated high myopia or moderate oblique myopic
astigmatism. Bitemporal field defects that do not
respect the vertical midline may occur.
OPTIC NERVE DYSPLASIA
Aplasia
True aplasia is rare. Typically it occurs uniocularly in
an otherwise healthy person but may be seen with
anencephaly or major cerebral maldevelopment.
Aplasia is not hereditary.
1002 Section 8: Neuroophthalmology
Coloboma
It results from incomplete closure of fetal fissure and
is often associated with decreased visual acuity and
superior visual field defect.
Pit
Usually in inferior temporal portion of disk, it may be
associated with serous macular detachment with a
corresponding visual field defect. Fluid probably
comes from vitreous through the pit to subretinal area.
Morning Glory Disk
Funnel-shaped, enlarged, excavated disk with white
tissue at center, surrounded by a raised annulus of
pigmented chorioretinal tissue. Disk appearance
resembles the morning glory flower. Usually unila-
teral, and more common in females (2:1). Visual acuity
usually 20/100 or worse. It may be associated with
nonrhegmatogenous retinal detachment around the
disk. It is not hereditary.
Hypoplasia
It may be unilateral or bilateral. The disk is small with
normal vessels, and there is a “double ring” sign
caused by concentric choroidal-retinal pigment
changes. The cause is often not identified but this
condition has been reported with increased incidence
in children of diabetic mothers and in children whose
mothers have taken antiepileptic drugs, quinine or
LSD during pregnancy. More importantly, hypoplasia
may be a sign of congenital intracranial tumors such
as craniopharyngioma, or optic glioma. 4 Many
patients with optic nerve hypoplasia also have
endocrine abnormalities and may develop hypo-
glycemic seizures or growth retardation if untreated.
Septo-optic dysplasia (de Morsier syndrome) consists
of optic nerve hypoplasia and absence of the septum
pellucidum with endocrine deficiencies. Any of the
above dysplasias may be associated with a basal
encephalocele. The work-up includes a CT head scan
and, in children with hypoplasia, a pediatric endo-
crinology evaluation.
INFILTRATIVE OPTIC NEUROPATHY
Infiltration of the optic disk by tumor (glioma, leuke-
mia, lymphoma, plasmacytoma, metastasis) or
inflammatory conditions (sarcoidosis, tuberculosis,
cryptococcosis, toxoplasmosis, cytomegalovirus infec-
tion) may cause disk swelling and visual loss. The disk
has an unusual appearance. It may appear grayish-
white with associated hemorrhages, or a mass may
be visible. Retrobulbar infiltration may occur in
lymphoreticular disease or meningeal carcinomatosis.
The latter condition represents metastasis to the
meninges by cancer, usually originating in the breast
or lung.
TOXIC/NUTRITIONAL OPTIC NEUROPATHY
Bilateral visual loss may occur from nutritional
deficiency, tobacco-alcohol amblyopia, drugs, toxins,
or hereditary optic neuropathies. Specific causes
include chloramphenicol, ethambutol, and lead
toxicity as well as thiamine and vitamin B12 deficiency.
Whether or not tobacco-alcohol amblyopia is a definite
entity or whether it represents a nutritional optic
neuropathy, is controversial. Generally the visual loss
is gradually progressive and symmetrical in both the
eyes in all of these conditions. The classic field defect
is a bilateral cecocentral scotoma. The optic disk may
show atrophy or appear normal. If the cause is
corrected, vision may recover.
DOMINANT BEHR OPTIC NEUROPATHY
Visual function in this condition is minimally to
moderately abnormal in both eyes. Onset is insidious,
usually between ages of 5 and 10 years. Progression
may occur for several years, but visual loss generally
is stable after the midteens. Often a tritanopic color
defect is present. Central or cecocentral scotomas are
the rule, but those may not be easy to find with routine
testing. Temporal optic disk pallor is common, often
with focal excavation of the temporal disk.
OPTIC NERVE TRAUMA
Damage to the optic nerve may occur in head injuries.
Injury is usually due to a frontal blow to the head and
loss of consciousness is common. Visual loss occurs
generally at the time of impact due to shearing forces
within the optic nerve. Prognosis for recovery of vision
is poor. Treatment with high dose intravenous cortico-
steroids has been advocated (although only a small
percentage of patients will show a major response).
Surgical decompression of the optic canal may be
considered in cases with delayed or progressive visual
loss.5-8
OPTIC DISK VASCULITIS (PAPILLOPHLEBITIS)
This condition is characterized by unilateral disk
swelling in young, otherwise healthy patients who
generally have normal or near normal visual acuity,
 Chapter 132: Abnormalities of Optic Disk and Optic Nerve
full visual field, and normal pupillary responses. There
may be nerve fiber layer hemorrhages in the peri-
pheral retina. The etiology is unclear; it may merely
represent partial central retinal vein occlusion. The
condition is self-limited. All patients should have a
complete medical evaluation with careful attention to
serum proteins and blood clotting abnormalities.
Optic disk edema usually resolves without visual loss.
COMPRESSIVE OPTIC NEUROPATHY
Compressive optic neuropathy is characterized by
progressive visual loss associated with a central visual
field defect and an afferent pupillary defect. Occasio-
nally, sudden expansion of a tumor by hemorrhage
can cause acute nerve compression, or the patient may
report with acute visual loss when he accidentally
notices decreased vision in one eye. The optic nerve
may appear swollen if there is an orbital mass lesion
or Graves’ ophthalmopathy, but usually the nerve
appears normal or pale. All patients with evidence of
optic nerve dysfunction and progressive visual loss
should be presumed to have a compressive lesion until
proven otherwise. Likewise, all patients with inci-
dentally discovered optic atrophy or cupping of the
disk with normal intraocular pressure should be
evaluated for compressive etiology.
OPTIC NERVE GLIOMA
Seventy-five percent of optic nerve gliomas present
in the first decade of life, 90 percent in the first two
decades. About 30 percent of patients with glioma
have neurofibromatosis. Progressive painless visual
loss precedes proptosis. Strabismus and nystagmus
result from loss of vision. The optic nerve may appear
swollen or pale. Pathologically the tumor is a pilocytic
astrocytoma of juvenile type with a benign cytologic
appearance.9
Surgical resection of the tumor along with the
affected optic nerve is indicated when visual loss is
associated with cosmetically unacceptable proptosis.10
When chiasm is involved surgery is not indicated;
radiotherapy is given.
1003
OPTIC NERVE MENINGIOMA
Patients with optic nerve meningiomas present with
progressive visual impairment. Females are affected
more commonly than males. Proptosis and disk edema
are common. Orbital scanning may either reveal a
mass or diffuse thickening of the optic nerve.
Compressive disk edema from meningioma may
resolve into optic atrophy, leaving optociliary shunt
veins—vessels that shunt blood from retinal to
choroidal venous circulations.11 The triad of optic
atrophy, blindness, and optociliary shunt veins is
highly suggestive of spheno-orbital meningiomas.
Meningiomas of the optic nerve sheath12 usually
cannot be removed without sacrificing vision. Since
they are slow growing, many feel that the lesions
should merely be followed up unless there is
radiological evidence of intracranial involvement.
REFERENCES
1. Rosenberg MA, Savino PJ, Glaser JS. A clinical analysis of
pseudopapilloedema I population, laterality, acuity,
refractive error, ophthalmoscopic characteristics and
coincident diseases. Arch Ophthalmol 1979;97:65.
2. Savino PJ, Glaser JS, Rosenberg MA. A clinical analysis of
pseudopapilloedema II visual field defects. Arch Ophthalmol
1979;97:71.
3. Brown GC, Tasman WS. Congenital Anomalies of the Optic
Disc. New York: Grune and Strautton: 1983.
4. Taylor D. Congenital tumours of the anterior visual system
with dysplasia of the optic discs. Br J Ophthalmol 1982;66:455.
5. Anderson RL, Panje WR, Gross CE. Optic nerve blindness
following blunt forehead trauma. Ophthalmology 1982;
89:445.
6. Kline LB, Moraweta RB, Swaid SN. Indirect injury of the optic
nerve. Neurosurgery 1984;14:756.
7. Lessell S. Indirect optic nerve trauma. Arch Ophthalmol
1989;107:382.
8. Worlin MJ, Lavin PJM. Spontaneous visual recovery from
traumatic optic neuropathy after blunt head injury. Ophthal-
mology 1990;109:430.
9. Kennerdell JS, Kazin M. Tumours of the optic nerve. In Lessell
S, von Dalen JTW (Eds): Current Neuro-ophthalmology, St
Louis: Mosby Year Book, 1991;3.
10. Wright JE, McDonald WI, Call NB. Mangement of optic nerve
gliomas. Br J Ophthalmol 1980;4:545.
11. Frisen L, Hoyt WF, Tengroth B. Optociliary veins disc pallor
and visual loss. Acta Ophthalmol 1973;51:241.
12. Sibony PA, Krauss HR, Kennerdell JS. Optic nerve sheath
meningiomas: Clinical manifestations. Ophthalmology
1984;91:1313.
 Chapter 133

Intracranial Space Occupying

Lesions of Ophthalmic
Importance
LC Dutta

ANEURYSMS Fusiform aneurysm It occurs in arteriosclerosis due to

degeneration of the elastic lamina, fibrous replacement
Intracranial aneurysms may arise from the arteries
of the muscular media and fatty deposits in the intima.
participating in formation of circle of Willis (Fig. 133.1)
As the aneurysms develop in the trunk of the arteries,
or any other major intracranial arteries. Basically the
fusiform dilatation takes place.
circle of Willis is an anastomosis between the two
internal carotids and the basilar arteries; the basilar Micotic aneurysm It is very rare; it is due to lodgement
artery divides into two posterior cerebral arteries; of infected emboli and subsequent necrosis of the
these two are connected with the internal carotids by arterial wall.
the posterior communicating arteries. The anterior
cerebral arteries are from the internal carotids and the
anterior communicating artery joins the two anterior
cerebrals. The circle of Willis lies in the subarachnoid
space and surrounds the structures of interpeduncular
fossa.
Pathologically aneurysms are due to local dila-
tation of arterial walls consequent to some patho-
logical changes. Aneurysms are of three types:
a. Saccular or berry aneurysms,
b. Micotic aneurysm and
c. Fusiform aneurysm
Saccular or berry aneurysm Sprouting out as blisters
from the wall of the blood vessels forming the circle
of Willis, Saccular or berry aneurysm, is the most
common type of intracranial aneurysm. This comm-
only occurs as a congenital anomaly due to localized Fig. 133.1: Formation of circle of Willis. (1) Middle cerebral
absence of the elastic membrane between the tunica artery, (2) Posterior cerebral artery, (3) Posterior communicating
intima and media of the arterial wall causing local artery, (4) Anterior communicating artery, (5) Anterior cerebral
dilatation in these sites. artery, (6) Internal carotid artery
 Chapter 133: Intracranial Space Occupying Lesions of Ophthalmic Importance
Ophthalmic manifestations of aneurysms may be
due to pressure effects (paralytic type) or due to
leakage of the aneurysm producing subarachnoid
hemorrhage (apoplectic type).
Aneurysm of Internal Carotid Artery
within the Cavernous Sinus
Aneurysm of this part of carotid artery, also called
intracavernous carotid aneurysm, produces the
clinical features of so-called cavernous sinus syndrome
which are almost similar to features produced by
lesions in the most medial part of superior orbital
fissure. The characteristic feature is more or less
simultaneous involvement of the third, fourth, fifth
and sixth cranial nerves. Only difference is that in
medial one-third superior orbital fissure syndrome the
first division of the trigeminal nerve is involved
whereas in cavernous sinus syndrome (as in intra-
cavernous carotid aneurysm) all the three divisions
of the trigeminal nerve are involved. This sympto-
matology results from close relationship of these
structures within the cavernous sinus and their
proximity to the internal carotid artery. It may also
be possible to differentiate between the anterior and
posterior cavernous sinus syndrome from impaired
function of these nerves: in anterior cavernous, sinus
syndrome only the first division of the trigeminal
nerve is involved associated with paresis of third,
fourth and sixth cranial nerve and in posterior
cavernous sinus syndrome all the three divisions of
trigeminal nerve are involved associated with paresis
of sixth nerve only.
Intrasellar Aneurysm of the Internal Carotid Artery
The intracavernous aneurysms of the internal carotid
artery encroaching through the medial wall of
cavernous sinus may cause chiasmal syndrome but
unlike pituitary lesion the field defect is asymmetrical.
Visual loss is sudden with headache and paresis or
paralysis of extraocular muscles. Absence of enlarge-
ment of pituitary fossa is the diagnostic point to
differentiate intrasellar aneurysm from pituitary
tumor.
Aneurysm of Intracranial
Portion of Ophthalmic Artery
These aneurysms originate from the junction of the
ophthalmic artery and the intracranial part of internal
carotid artery and hence called “carotico-ophthalmic
aneurysms”. Due to the immediate neighborhood of
1005
the optic nerve, these aneurysms produce signs of
optic nerve compression that may mimic the symp-
toms of retrobulbar neuritis like central scotoma and
abnormal pupillary reaction. Later on, pattern of field
changes may show upper temporal depression of the
contralateral field and ipsilateral blindness associated
with optic atrophy of varying degree.
Aneurysm of the Circle of Willis
Approximately 90 to 95 percent of intracranial
aneurysms are from the anterior part of circle of Willis.
The common sites are:
a. Anterior communicating artery.
b. Origin of the posterior communicating artery from
the internal carotid.
c. At the site of bifurcation of middle cerebral artery,
and
d. At the site of bifurcation of internal carotid into
middle and anterior cerebral arteries.
Saccular aneurysm of circle of Willis is usually
asymptomatic prior to its rupture. Occasionally large
aneurysms immediately distal to cavernous sinus may
compress the optic nerve, optic chiasm, third nerve,
hypothalamus or pituitary gland and produce neuro-
ophthalmological features. The mortality rate from
ruptured intracranial aneurysm is about 50 percent;
therefore early recognition is vital for successful
treatment.
The most common nonhemorrhagic indication of
treatment of an intracranial aneurysm is a third-nerve
palsy usually accompanied with pain.1
Third nerve palsy is usually caused by an aneu-
rysm originating from the intracranial portion of
internal carotid artery near the origin of the posterior
communicating artery. It may also be due to aneurysm
of distal part of basilar artery. Characteristic features
of third nerve palsy are blepharoptosis, mydriasis and
extraocular muscle weakness. Cerebral angiography
is an important definitive diagnostic procedure
whereas CT scan may miss one-third of the cases.
Incomplete third nerve paresis associated with recent
onset of ipsilateral headache suggests an enlarging
internal carotid or distal basilar artery aneurysm and
indicates the need for cerebral angiography. The
symptomatology of rupture of (apoplectic type)
aneurysm may be of three types:
a. Sudden generalized headache and vomiting imme-
diately followed by unconsciousness.
b. There may be headache but the patient remains
relatively lucid.
1006 Section 8: Neuroophthalmology

c. The patient may become unconscious without any
preceding complaint.
In addition to the meningeal symptoms due to
subarachroid hemorrhage there are usually bilateral
pyramidal signs. Lumbar puncture shows hemorr-
hagic cerebrospinal fluid. Rupture of aneurysms may
also lead to intracerebral hemorrhage. Though full
blown papilledema is relatively rare intraocular
hemorrhage with considerable reduction of visual
acuity is fairly common. The hemorrhage may be
retinal or preretinal (subhyaloid) with a typical
horizontal fluid level. The preretinal hemorrhage,
usually bilateral, may spill over the vitreous after
breaking through the hyaloid membrane. The
pathogenesis of retinal and preretinal hemorrhage is
not clearly known. In raised intracranial pressure the
hemorrhage is due to impediment of venous drainage
but definitely cannot be due to seepage of blood from
intracranial subarachnoid space through the sub-
arachnoid space of the optic nerve to the retina because
the intervaginal space of the nerve forms a cul-de-sac
like termination near the eyeball (Table 133.1).

Table 133.1: Symptomatology of intracranial aneurysms

Locations Ocular symptoms
A. Infraclinoid aneurysms
1. Aneurysm of Unilateral ophthalmoplegia,
internal carotid especially of third nerve
artery within the (rarely optic atrophy with
cavernous sinus loss of vision and field
defects)
a. Posterior Mostly only paresis of sixth
syndrome nerve
b. Middle Complete ophthalmoplegia
syndrome
c. Anterior Paresis of third nerve or
syndrome complete ophthalmoplegia
2. Intraseller aneurysm Chiasmal syndrome with
of internal carotid asymmetrical bitemporal
artery within hemianopia; sudden onset;
cavernous sinus flunctuations of visual field
defects; occasionally
ophthalmolplegia
B. Supraclinoid aneusyms
3. Aneurysm of ante- More or less atypical
rior cerebral and chiasmal syndrome
anterior communi- (bitemporal inferior
cating arteries quadrantanopia); uni-
lateral or bilateral loss of
vision, subject to fluctuations;
possible optic atrophy
4. Aneurysm of Partial or complete
carotid-posterior oculomotor palsy with
communicating mydriasis and disturbance
artery junction of accommodation
5. Aneurysm of Possible homonymous
posterior cerebral hemianopia (optic tract or
artery (very rare) radiation)
6. Aneurysm of Possible bilateral abducent
basilar and vertebral or oculomotor paresis
artery (rare)
Trigeminal signs
Intense pain in area of
first, second and third
branches of trigeminal
nerve; hyposthesia and
hypoalgesia in same
area (sensation of numbness)
Involvement of all
sensory and motor fibers of
trigeminal nerve
Involvement of first and
second branch
Involvement of first
branch
Negative
Negative
Negative except pain in
forehead and eye;
neuralgic pain of
ophthalmic branch
Negative
Negative
Other signs
Violent headache (generally
sudden onset); destructions in
region of lesser wing of sphenoid
and clinoid processes; enlarge-
ment of superior orbital fissure
More or less pronounced
headache; no roentgenologic
evidence of enlargement of sella
With exception of olfactory
nerve, cranial nerves remain
intact; aneurysm frequently
apoplectic in type
Sudden onset of unilateral
headache, pain in forehead or
eye (ophthalmoplegic migraine);
with severe pain in neck,
aneurysm located in posterior
communicating artery
Possible Weber’s syndrome
Frequently no symptom
whatsoever; occasionally bulbar,
pyramidal or cerebellar signs;
this aneurysm frequently belongs
to apoplectic type
 Chapter 133: Intracranial Space Occupying Lesions of Ophthalmic Importance
Anteriovenous Aneurysms:
Caroticocavernous Fistula
Anteriovenous aneurysms within the cavernous sinus
may be due to spontaneous rupture of an aneurysm,
penetrating orbitocranial injuries, blunt head injuries,
artherosclerosis, trans-sphenoidal surgical procedures,
small dural arteriovenous shunts and rarely due to a
congenital fistula. The most important sign is exoph-
thalmos on the side of the fistula but in some case
exophthalmos may be bilateral. Exophthalmos may
be pulsating synchronizing with the arterial pulse. A
characteristic bruit can be heard, synchronous with
the pulse, with the stethoscope placed directly over
the eye or in the frontotemporal region. The bruit
disappears on compression of the carotid artery in the
neck. Very often the noise is noted by the patient
himself. Sixth nerve paresis or oculomotor paresis may
lead to restricted ocular movement and mydriasis.
Defective venous return due to increased pressure
inside the cavernous sinus may show congested
conjunctival and retinal vessels even with papill-
edema; venous stasis in the orbital tissue may further
contribute to exophthalmos, chemosis of the conjunc-
tiva and swelling of the eyelids.
Diagnosis of caroticocavernous fistula is confirmed
by carotid angiography. Retrograde filling of the
superior ophthalmic vein during arterial phase and
opacification of the cavernous sinus are the charac-
teristic radiological sinus.
The treatment of caroticocavernous fistula is ligation
of the internal carotid artery inside or outside the
cranial cavity in an attempt to close the fistula.
Embolization of the cavernous sinus has been
attempted by various procedures through different
approaches viz through the artery or through a vein.
The most common route is endoarterial, either by a
direct puncture of the carotid artery or via the femoral
artery. The cavernous sinus may also be approached
through the ophthalmic vein; by antegrade catheteri-
zation a wire may be passed through the vein into the
cavernous sinus to produce electrothrombosis of the
caroticocavernous fistula.2
SUBDURAL HEMATOMA
It almost always follows more or less a pronounced
trauma to the head, the history of which may not be
revealed spontaneously. Concussion injury to the head
due to fall on the floor, hitting a door, kicking by horse
or knocking by horn of cow, etc. are common history
1007
which may be linked to subdural hematoma. In chil-
dren severe birth trauma is a common cause of
subdural hematoma. Other causes are spontaneous
idiopathic or infective hemorrhagic pachymeningitis.
The most common site of subdural hematoma is
frontoparietal region. Hemorrhage is the result of
rupture of cerebral veins as they cross the subdural
space to enter the superior longitudinal sinus. In
adults, symptoms include gradually increasing
headache associated with psychic disturbance and
personality changes. Memory disturbance, lassitude,
apathy, loss of energy, sensory disturbance and
disorientation leading to coma. In children the condi-
tion is suspected when generalized epileptic attacks,
vomiting, irritability, restlessness leading to stupor
and unconsciousness develop in the postnatal period.
Papilledema is one of the common neuro-ophthal-
mological signs of subdural hematoma. Disk edema
varies from filling up of the physiological cup with
blurring of the disk margin to measurable choked disk.
Sometimes ipsilateral choked disk is more pronounced
than the one of the opposite sides. Hematoma in
frontal, frontotemporal and parieto-occipital region
may give rise to field defects; contralateral homony-
mous hemianopia may be due to disturbance of
circulation of posterior cerebral artery resulting from
herniation of hippocampal gyrus through the tentorial
notch.
CLIVUS RIDGE SYNDROME
Due to generalized increase in the intracranial pressure
as a result of increasing size of the hematoma there is
downward displacement of the brain substance which
presses the oculomotor nerve at the site of its
emergence from the brainstem either against the clivus
ridge of the tentorial notch or against the superior
cerebellar artery thus causing its damage. The pressure
exerted upon the nerve causes interference with
intraneural or perineural blood circulation, therefore,
the signs of oculomotor paresis may be transitory;
especially the pupillary signs may completely disap-
pear following medical or surgical decompression.
Involvement of the oculomotor nerve in increased
intracranial pressure is sometimes called “Clivus
Ridge syndrome”. The clinical picture of Clivus Ridge
syndrome is described in four stages:
Stage-I Constriction of the ipsilateral pupil which is
considered to be due to irritation of the oculomotor
nerve preceding the lesion. This stage is very transient
and may be easily overlooked.
1008 Section 8: Neuroophthalmology
Stage-II The pupil is dilated but still reacts to light and
in convergence. Occasionally slight ptosis is seen. The
patient’s sensorium is completely free.
Stage-III Increasingly sluggishness of the dilated pupil
and the shape of the pupil also may be changed. With
increasing intracranial pressure, the somnolence and
apathy of the patient becomes more severe and even
may deepen to coma. The pupil becomes dilated, fixed
and irregular in shape. At this stage along with the
pupillary fibers, the fibers destined to supply the
muscles are also pressed and the eye remains in a
divergent position with ptosis. Along with the
oculomotor nerve, the 4th and 6th nerves also show
signs of paresis.
Stage-IV This is the terminal stage; the contralateral
pupil becomes dilated and fixed.
TUMORS OF CEREBELLOPONTINE ANGLE
The most common tumor of cerebellopontine angle is
acoustic neuroma or neurofibroma of the neurilemma
sheath of the vestibular nerve; it may present as a
solitary lesion or in association with von Reckling-
hausen’s disease. The other tumors which may
develop in this area are meningioma, ependymoma,
cholesteotoma, osteoma, etc. The tumor occupies the
space between the cerebellum, pons and medulla
posteriorly, the petrous pyramid anteriorly and the
tentorium above. These tumors produce symptoms
and signs which are characteristic of lesions of 5th,
6th, 7th and 8th cranial nerves with features of
cerebellar involvement. In addition to these, glosso-
pharyngeal and vagus nerves may also be stretched.
Clinical features of the tumor may be divided into
ocular and nonocular. Nonocular symptoms are
deafness, tinnitus and vertigo. Headache associated
with vomiting is due to raised intracranial pressure.
The most important and early sign is horizontal
nystagmus with occasional rotatory element due to
involvement of the cerebellum. Visual symptoms like
amaurosis fugax and blurring or loss of vision are due
to raised intracranial pressure. Horizontal diplopia is
due to paralysis of the 6th nerve. Facial nerve
involvement causes myokymia of orbicularis oculi
muscle, blepharospastic twitching and blepharospasm
in early stage and paralysis of orbicularis oculi muscle
in late stage.3 Paralysis of the orbicularis oculi muscle
may lead to exposure keratitis. Diminution or loss of
sensation of the cornea and skin supplied by the
ophthalmic division of the trigeminal nerve are
manifestations of 5th nerve involvement. Decreased
corneal sensation is an important sign for diagnosis
of acoustic neuroma. In late stage of the disease in
addition to facial weakness there may be dysphagia
and dysphonia with ipsilateral cerebellar ataxia of the
arms and legs.
X-ray shows widening of the internal auditory
meatus and CT scan may reveal deformed, displaced
and narrowed fourth ventricle with hydrocephalic
enlargement of the aqueduct and third and lateral
ventricles. Protein content of CSF is raised. Special
otological investigations may show abnormal
audiogram, impaired vestibular function and abnor-
mal brainstem auditory evoked response.3
TUMORS OF IIIRD VENTRICLE AND
INTERNAL HYDROCEPHALUS
Colloid cysts, astrocytoma, glioma, and apendymoma
are some of the tumors which may arise within the
third ventricle. Out of these, colloid cyst is the most
common tumor. This papillomatous tumor is situated
in the anterior extremity of the third ventricle between
the interventricular foramina. The cyst is about one
to two centimeter in diameter and contains colloid
material which is probably secreted from the epithelial
cells lining the inner surface of the fibrous covering.
The tumor causes impediment to circulation of
cerebrospinal fluid by obliteration of either the
foramina of Monro or the anterior opening of the
aqeuduct leading to formation of internal hydro-
cephalus which leads to symptoms of raised intra-
cranial pressure. The tumors may also invade the
thalamus, internal capsule and basal ganglia. Main
neurological symptoms of internal hydrocephalus are
headache and vomiting; in early stage headache is
characteristic in the sense that it decreases in intensity
or disappears when the patient resumes prone position
possibly due to ball valve mechanism of the peduncu-
lated tumor which obstructs or allows the cere-
brospinal fluid to pass depending upon the head
posture. Internal hydrocephalus may also be caused
by extraventricular tumors arising from the pons,
pineal body or particularly from the vermis of the
cerebellum. These lesions block the aqueduct of
Sylvius or invade the ventricle. An eighth nerve tumor
also may produce internal hydrocephalus.
It is quite characteristic that tumors of third
ventricle predominantly produce pronounced
papilledema; sometimes disk swelling may be to the
tune of 5-6 diopters. Atrophic changes in the disk may
 Chapter 133: Intracranial Space Occupying Lesions of Ophthalmic Importance
lead either to field defects or even complete loss of
vision. In the early stage intermittent attacks of blurred
vision or even transient amaurosis may be combined
with paroxysmal headache. Like the headache,
transient loss of vision is related to the position of the
head; when the head is bent to the side of the lesion
the vision may be suddenly lost and with the head in
an erect to backward position vision comes back
gradually. This peculiar visual phenomenon is
probably due to intermittent pressure of the dilated
third ventricle upon the chiasm and optic nerve.
Pressure upon or involvement of the chiasm
produces bitemporal field defect. Bitemporal hemi-
anopia accompanied with papilledema is commonly
due to third ventricle tumor; pituitary adenoma rarely
obstructs the third ventricle to produce papilledema.
A lateral extension of the tumor toward the thalamus
or the optic tract produces homonymous hemianopia.
Pressure on the pituitary body may produce symp-
toms of hypopituitarism and hypothalamic symptoms
of somnolence, polyuria, hypoglycemia and glyco-
suria.
TUMORS OF PINEAL BODY AND MIDBRAIN
The pineal body is about 8 mm in diameter and lies
below the splenium of corpus callosum and forms the
posterior wall of the third ventricle; it lies in the
depression between the superior colliculi. Actual
function of the pineal body is not known. The pineal
body consists of some photoreceptor cells like those
of the retina; in lower animals there is a structure called
pineal eye. It is also suggested that it functions as a
neuroendocrine transducer; hence pinealomas in boys
often produce precocious puberty with premature
development of the sex organs, appearance of axillary
and pubic hairs and breaking of voice.
Table 133.2: Brainstem syndrome of neuro-ophthalmologic interest
Syndromes Sites Cranial nerves
involved
Weber’s Midbrain III and VII
Benedikt’s Tegmentum of III
midbrain
1009
Tumor of the pineal body may be true pineal
tumors like benign pineocytoma and malignant
pinealoblastoma. Teratoma, glioma and cystic
swellings may also occur.
Pinealoblastoma in children may be associated
with retinoblastoma gene and the histological
structure of pinealoblastoma may have some simi-
larity with retinoblastoma including even Flexner
Winter Steiner rosette. According to some authors4 the
concept of multicentric orgin of retinoblastoma is
confirmed by the so-called trilateral retinoblastoma,
i.e. pinealoblastoma and bilateral retinoblastoma. This
intracranial lesion does not seem to be secondary
metastasis because blood vessels carrying the tumor
cells are not found, neither there is extension of ocular
retinoblastoma through the optic pathways.5
Symptoms of tumors of the midbrain are practi-
cally identical with those of the pineal body specially
if they develop in the roof of the midbrain in the region
of corpora quadrigemina. In diagnosis of tumors of
the pineal body and midbrain, ocular signs are of most
diagnostic importance. Parinaud’s syndrome which
consists of disturbance of conjugate movements of the
eyes in the form of vertical gaze palsy due to
supranuclear lesion in addition to Argyll Robertson
type of pupillary disturbance along with signs of
oculomotor paresis, is a clinical entity of midbrain
lesion. There may be symptoms of unidentified
sensation or blurred vision followed by actual
diplopia. Benedikt’s syndrome, due to affection of the
red nucleus and ipsilateral oculomotor nerve is
characterized by rhythmic tremor of the arm on the
contralateral side and oculomotor paresis on the side
of the lesion. If the tumor is of more ventral position
then it causes Weber’s syndrome consisting of
ipsilateral oculomotor paresis with hemiplegia on the
opposite side (Table 133.2).
Tracts and nuclei Signs
involved
Corticospinal tract Ipsilateral oculomotor palsy
with contralateral facial palsy
and hemiplegia.
Red nucleus and Oculomotor palsy
corticospinal tract with contralateral cerebellar
ataxia, tremor and corticospinal
signs.
Contd...
1010 Section 8: Neuroophthalmology

Contd...

Syndromes Sites Cranial nerves Tracts and nuclei Signs

involved involved

Claude’s Tegmentum of III Red nucleus Oculomotor palsy

midbrain with contralateral ataxia, and
tremor.
Parinaud’s Tectum of Supranuclear Nuclei and fibers Paralysis of upward
midbrain control of posterior and sometimes
mechanism commissure and downward gaze;
for vertical periaqueductal grey fixed or light-near
gaze and supranuclear dissociated pupils.
pupillomotor fibers
Millard-Gubler Bulbopontine VI and VII Corticospinal tract Ipsilateral lower motor neuron
type of facial palsy and abducens
palsy with contralateral
hemiplegia.
Foville’s Dorsolateral V, VI, VII Descending Ipsilateral abducens
tegmentum of sometimes sympathetic fibers, and facial palsy;
pons VIII sensory tract of facial hyposthesia
trigeminal nerve ipsilateral Horner’s syndrome
and deafness.
Wallenberg’s Tegmentum of V, IX, X and Lateral spinothalamic Ipsilateral IX, X and
medulla XI tract, descending XI palsy; Horner’s
sympathetic fibers, syndrome and
olivocerebellar tracts, cerebellar ataxia;
and descending contralateral loss of
tract of fifth nerve. pain and temperature sense in
extremities and ipsilateral facial
hyposthesia

REFERENCES 3. Huber A. Eye Symptoms in Brain Tumour. CV Mosby

1. Trautman JC, Sundt TM. Minimal oculomotor nerve paresis
secondary to unruptured intracranial aneurysm. Arch Neurol
1986;43:1015.
2. Utlacker R, Lima S, Ribas GC et al. Carotico-cavernous fistula:
Embolization through superior ophthalmic vein approach.
Radiology 1986;159:175.
Company: Saint Louis, 1971.
4. Rodrigues MM, Bardenstein DS, Donoso, LA et al. An
immuno-histopathologic study of trilateral retinoblastima.
Am J Ophthalmol 1987;103:776.
5. Dudgeon J, Lee WXA. The trilateral retinoblastoma
syndrome. Trans Ophthalmol Soc UK 1983;103:523.
 SECTION 9: MISCELLANEOUS TOPICS

Chapter 134

Applied Anatomy of the

Eye and Adnexa
AS Mehrotra

The two eyeballs are well-protected in two orbital COMMUNICATIONS WITH THE ORBIT
cavities placed in a cushion of fat on either side of the
Through the following fissures and canals the orbital
sagittal plane of the skull between the cranium and
cavity communicates with the adjacent regions.
the skeleton of the face. The immediate relations of
the orbital cavities are the anterior cranial fossae Superior orbital fissure Between the roof and lateral wall
above, nasal cavity and ethmoidal sinuses medially of the orbit formed by the gap between greater and
and the maxillary sinus inferiorly. Laterally it is related lesser wing of sphenoid the retort shaped fissure is
to the middle cranial fossa and temporal fossa. The divided into a posteroinferior wider and antero-
bones taking part in formation of orbital cavity are superolateral narrower part. The wider part transmits
(Fig. 134.1): Frontal bone and lesser wing of sphenoid all the important vessels and nerves into the orbit. The
form the roof of orbit. The medial wall is formed by tendinous U-shaped origin of the lateral rectus muscle
four bones from anterior to posterior part, viz. maxilla, forms the annulus of Zinn through which upper
lacrimal bone, the ethmoid and a part of sphenoid. division of 3rd nerve, nasociliary nerve, sympathetic
Bones forming the floor of the orbit are maxilla, roof of the ciliary ganglion, inferior division of 3rd
zygomatic and palatine bones and the lateral wall is nerve and the 6th nerve pass in that order from above
formed by zygomatic and sphenoid bones. Thus
sphenoid bone takes part in formation of roof, medial
and lateral walls of the orbit.
The dimension of the orbit, which is roughly of
the shape of quadrilateral pyramid in an average
normal adult are as follows:
Height — 35 mm
Width — 39 mm
Depth — 40 mm
Volume — 30 ml
(Volume of eye is about 7.00 ml).

CONTENTS OF ORBIT
The bulk of contents are eyeball, muscles and orbital
fat. Besides this it also has nerves and vessels Fig. 134.1: Bones of orbital cavity.
(Fig. 134.2). View into right orbital cavity
1012 Section 9: Miscellaneous Topics
Fig. 134.2: Contents of orbit: A sagittal section through the
orbit to show the distribution of connective tissues and their
relation to other orbital structures
downward. 4th frontal and lacrimal nerve, the
superior ophthalmic vein and the recurrent lacrimal
artery pass through the space above the annulus of
Zinn.
Inferior orbital fissure This is formed by the maxilla and
the orbital process of palatine bone anteriorly and
whole of the lower margin of the orbital surface of the
greater wing of the sphenoid. Through this fissure the
infratemporal and pterygopalatine fossae communi-
cate with the orbit. The main structures passing
through this fissure are maxillary division of trige-
minal nerve, zygomatic nerve and branches from
sphenopalatine ganglion to the orbital periosteum.
Optic foramen This is formed by the two roofs of orbital
plate nerve with the meninges and the ophthalmic
artery with its sympathetic plexus.
Supraorbital foramen This foramen (notch) is situated
about 2.5 cm lateral to the midline in the superior
orbital margin; sometimes converted into a foramen
it transmits the supraorbital vessels and nerves.
Ethmoidal foramen—anterior and posterior These are the
orbital openings of the canals of the same name
situated at the line of junction of roof and medial wall
of the orbit. These canals open into the cranial cavity.
Zygomatic foramen (Grooves) transmits the zygomatico-
temporal and zygomaticofacial nerves.
Infraorbital canal This starts from the infraorbital
groove to exit 4 mm below the inferior orbital margin
and transmit the vessels and nerves.
OCULAR APPENDAGES
The ocular adnexa or ocular appendages comprise
eyelids, eyebrows, the conjunctiva and the lacrimal
apparatus.
Eyelids
The two eyelids are the shutters protecting the eye
from injury and they control the entry of light. Not
only this, the lids also help in spreading the tears over
to cornea, thereby keeping it wet and the excessive
tears are pumped on to the lacrimal sac, through
puncta and canaliculi.
The upper eyelid is more mobile and on looking
straight ahead it just covers the upper part of cornea,
a millimeter or two, whereas the lower lid margin just
grazes the lower limbus at 6 o’clock position. The
opening between the two lids, the palpebral fissure,
in its widest part, is 13-15 mm in an average adult,
and the length from medial to lateral canthus is 28-30
mm.
The two lids join medially and laterally to form
the canthus, medial and lateral canthus respectively.
The former which is more or less round in shape is
separated from the eyeball by a small bay-lacus
lacrimalis whereas the lateral angle is placed directly
on the globe. The caruncle is a prominent round
yellowish elevation which stands as an island in the
lacus lacrimalis. The structure of the caruncle is just
like that of the skin with hair follicles and sebaceous
glands. Sometimes long hairs grown over the caruncle
may be a constant source of irritation which may
demand their epilation. A small reddish fold lateral
to the caruncle called plica semilunaris, represents the
third eyelid or nictitating membrane of the lower
animals.
Lid Margins
The free margin of lid has two borders, anterior and
posterior, and is about 2 mm broad. The anterior
border is rounded and eyelashes project out from this.
The posterior border is sharp and is placed against
the globe. Just in front of this border are small orifices
of the tarsal glands (Fig. 134.3). Between these orifices
and the row of lashes is a thin gray line. This line is of
importance for surgeons as lid can be split up easily
into an anterior and posterior portion at this line. On
the medical end of this palpebral margin, is a small
elevation, lacrimal papilla, having a hole in its center
known as punctum lacrimalis or simply puncta. This
 Chapter 134: Applied Anatomy of the Eye and Adnexa
Fig. 134.3: Sagittal section of the upper eyelid. 1. Orbicularis
muscle; 2. Sweat gland; 3. Gland of Zeis; 4. Cilium; 5. Gland of
Moll; 6. Pars marginalis of orbicularis muscle; 7. Inferior arterial
arcade; 8. Meibomian gland; 9. Gland of Krause; 10. Müller’s
muscle; 11. Levator palpebrae superioris; 12. Fat
puncta divides the lid margin into ciliary portion on
temporal side and lacrimal portion on medial side.
This lacrimal part is, as a rule, devoid of cilia and
glands, and is rounded because it carries of the canali-
culus in it, which connects puncta to the lacrimal sac.
Gross Structure of Lids
From anatomical point of view and to understand
various common diseases affecting the lids, structure
of the lid can be described into following layers, from
skin (anterior) to conjunctiva (posterior) surface.
Skin It is thinnest in the body, having thickness of
about 1.0 mm. The skin of upper lid has folds and is
easily wrinkled to give free movement to lids.
Subcutaneous-areolar tissue A layer of the loose connec-
tive tissue without fat.
Striate muscle layer The palpebral part of orbicularis
palpebrarum forms a thin layer around the orbit,
underneath the skin, in a concentric manner. This is
supplied by facial nerve.
Submuscular areolar tissue This areolar tissue lies
between the orbicularis muscle fibers and tarsal plate.
It communicates above with the subaponeurotic
stratum of scalp also known as “dangerous area.” The
pus or blood from dangerous area can make its way
to lid through this plane in the upper lid. The main
nerves to eyelids also lie in this space, therefore, while
1013
giving local anesthesia, for the lid, the anesthetic agent
is infiltrated in this layer, deep to muscular layer.
Fibrous layer It forms the framework of the lid. Its
central part is thicker and known as tarsal plate,
whereas peripheral part is thin, and forms the
palpebral fascia or orbital septum. The tarsal plates
are roughly ‘D’ shaped and the tarsal glands or
meibomian glands are embedded in it. In other words
the wall of the unicellular meibomian glands form the
tarsal plates. The upper lid tarsal plate is about 11 mm
high at its middle 28-30 mm long and 1 mm thick.
The free border forms the lid margin. The meibomian
glands, in the tarsal plate, are multilobulated
sebaceous glands, placed vertically and are about 25
in upper and 20 in lower lid. As described earlier, they
open on intermarginal strip each with a separate
orifice.
Conjunctiva It is thin and translucent membrane,
running between inner surface of lid to eyeball. For
descriptive purpose it is divided into three portions.
a. Palpebral part: This is the one lining the lid, from
lid margin to whole under surface of lid.
b. Fornix The tarsal part of palpebral conjunctiva
continues to cover the anterior one-fourth of the
eyeball. The fornix is the cul-de-sac where the tarsal
conjunctiva is reflected to form the bulbar
conjunctiva. The lower fornix is shallow and can
be easily examined by pulling the lower lid down.
c. Bulbar conjunctiva The fornix part of conjunctiva
after covering the tendons of recti muscles
continues over eyeball up to a point close to cornea
and finally its epithelium becomes continuous with
epithelium of cornea.
The conjunctiva has important glands, the glands
of Krause which are also known as accessory lacrimal
glands. They have the structures similar to main
lacrimal gland, and are placed deeply in the sub-
conjunctival connective tissue. Another type of
important glands, also known as accessory lacrimal
glands, are the glands of Wolfring. They are lesser in
number as compared to glands of Krause. The
unicellular goblet cells secrete mucus which keeps the
ocular surface hydrophilic.
The arterial supply of conjunctiva is from anterior
ciliary arteries and peripheral marginal arterial
arcades. The corresponding venous drainage is into
palpebral veins, ophthalmic vein and into muscular
veins.
The nerve supply is mainly derived from long
ciliary nerves, lacrimal and infratrochlear nerves.
1014 Section 9: Miscellaneous Topics

Lacrimal Apparatus
It comprises the lacrimal glands and lacrimal excretory
system starting from puncta to opening of naso-
lacrimal duct in the inferior meatus of nose. It is
described in detail in the Chapter of Lacrimal System
along with the diseases of lacrimal system.

Eyeball
The eyeball, little smaller than a table tennis ball, is
well protected in the cage of orbit and covered by the Fig. 134.4: The poles, axes meridians and
eyelids. It is placed in the anterior part of the orbit, in equator of the ocular globe
a way that it is nearer to roof than the floor and close
to the lateral wall than medial (Fig. 134.2). Each eyeball
is suspended by extraocular muscles and their sheaths
in the bony orbit. There is a pad of fat behind the
eyeball which provides a protective cushion.

Size of Eyeball
The normal size of the eyeball measures antero-
posteriorly about 17.5 mm at birth and it reaches to
24 mm in an adult. The horizontal diameter is little
more than vertical, measuring 23.5 mm and 23.0 mm
respectively. These diameters are little less in
hypermetropes and more in myopes.
The two poles, anterior and posterior, are the
central points on maximum convexities of anterior and
posterior (Fig. 134.4) curvatures of eyeball. Equator is
the line dividing the eyeball into anterior and posterior
parts and is about 14.5 mm from the limbus. The
vertical axis is the longest at the equator. The optic
nerve leaves the eyeball 3 mm medial to the posterior
pole. Fig. 134.5: Section of eyeball

c. Surgical limbus. This is almost triangular in

Structure of the Eyeball
It is composed of three concentric tunics. Each one is
modified as per its special function (Fig. 134.5).
1. The outer tunic is protective hence tough. The
anterior one-sixth known as cornea has to perform
special function of vision; hence transparent so as
to permit the rays of light to enter into the eye as
well as to converge the rays. The posterior five-
sixths is opaque and tough called sclera. Besides
protection it has a special function for attachment
of extraocular muscles controlling the movements
of eyeball. The junction of cornea and sclera is
called as limbus. The limbus may be:
a. Corneoconjunctival Corneoconjunctival
limbus limbus over sides
b. Corneoscleral The corneoscleral
limbus limbus
section. This is the area between the two lines
through the substance of the cornea one passing
from corneoconjunctival limbus and the other
from the corneoscleral junction to the peripheral
end of the Descemet’s line.
2. The middle one is vascular tunic. For performing
different functions, it is divided into three parts:
a. Iris-controlling the size of pupil.
b. Ciliary body-giving attachment of lens and
formation of aqueous humor.
c. Choroid highly vascular layer primarily for
nutrition of rods and cones.
3. The inner most layer is the retina. The primary pur-
pose of this layer is photoreception.
The cavity of eyeball is divided into two main seg-
ments, i.e. anterior and posterior. The anterior segment
consists of the portions behind the cornea, anterior
 Chapter 134: Applied Anatomy of the Eye and Adnexa
chamber, iris, posterior chamber, lens and ciliary body.
The posterior segment is the cavity posterior to lens
and consists of vitreous cavity filled by vitreous
humor, retina and choroid covered by sclera externally
(Fig. 134.6).
The anterior chamber is the space bounded ante-
riorly by posterior surface of cornea and posteriorly
by posterior surface of iris and lens, the peripheral
boundary is formed by angle of anterior chamber,
through which the aqueous humor is drained. The
posterior chamber is lined by posterior surface of iris
(anteriorly) and ciliary body and zonules posteriorly.
Aqueous humor fills both these chambers.
OUTER TUNIC
Cornea
The cornea, along with aqueous, lens and vitreous
form the optical media. It has a refractive effect of
about 40 diopters and therefore forms a major optical
surface of the dioptric system of the eye.
The cornea and sclera are basically composed of
fibrous tissue, both of which are modified for different
functions they have to perform. Corneal fibers are
arranged in such a way that they are of optical advan-
tages as well as they are adopted to resist intraocular
pressure to which cornea and sclera are equally
exposed.
The horizontal diameter of cornea is slightly more
than vertical diameter measuring 12 mm and 11 mm
respectively. The radius of curvature of anterior sur-
face is 7.8 mm and that of posterior is 7.0 mm, central
part is thinner, 0.6 mm as compared to peripheral,
which is 1.0 mm. Microscopically it has five layers:
1. Epithelium
2. Bowman’s membrane
3. Substantia propria
4. Descemet’s membrane and
5. Endothelium.
The corneal epithelium is in continuation with con-
junctival epithelium, the substantia propria with
scleral and corneal endothelium with that of iris. That
is why diseases of these tissues affect the cornea as
well.
The epithelium has five layers, similar to skin
epithelium, except that keratinized layer is missing
here. It can regenerate. The Bownman’s membrane is
formed by compact and condensed fibers of substantia
propria; it is thin and formed of collagen fibers and
does not regenerate once damaged. The third layer,
substantia propria, is thickest layer of cornea and
constitutes 90 percent of its thickness. It has lamellae
1015
Fig. 134.6: The region of the angle of the anterior chamber
of ribbon like bands of fibers arranged in a very regular
way running parallel to each other. The Descemet’s
membrane is a structureless, elastic and strong layer.
It is peculiar in a way that it can regenerate. The
innermost layer, endothelium, consists of single layer
of flat hexagonal cells. Their count per cubic mm is an
important guide of its health and are of great
importance before planning intraocular lens implant.
Cornea is avascular; this is one of the factors
responsible for its transparency. It derives its nourish-
ment from superficial vascular plexus, around limbus,
formed by episcleral branches of anterior ciliary
arteries. It is richly supplied by branches of trigeminal
nerves through ciliary nerves.
Sclera
The sclera forms posterior five-sixth of outer tunic. It
is white, dull and tough coat, protecting the inner
tissues of eyeball. The anterior surface is covered with
conjunctiva. It also gives attachment to external ocular
muscles viz. the rectii and oblique muscles. Posteriorly
the optic nerve leaves the globe 3.0 mm medial to and
little above posterior pole. Also posteriorly, around
lamina cribrosa there are small orifices transmitting
the long and short posterior ciliary nerves and arteries.
Little behind equator four venae vorticosae pierce the
sclera near or under cover of rectii muscles. The outer
surface of sclera is adhered to the Tenon’s capsule, by
fine strands. The sclera is largely avascular. Regarding
nerve supply it is described to be supplied by sensory
and vasomotor fibers from ciliary nerves. But this view
is not accepted by all.
Uveal Tract
The middle layer is a vascular tunic between the outer
fibrous and inner neural coat. The vascular layer
provides nutrition to the vital structures of the eye.
1016 Section 9: Miscellaneous Topics
The whole uveal tract is divided into choroid, ciliary
body and iris; the structure and functions of these three
parts of the uveal tract are somewhat different from
each other.
Choroid
The choroid extends from the optic nerve head to the
ora serrata. In between the choroid and the sclera there
is a potential space known as suprachoroid which is
traversed by delicate lamellae having an endothelial
coat. Elastic fibers, some smooth muscle fibers, wande-
ring cells, occasional ganglion cells and melanoblasts
are present in this space.
Structure of the Choroid
Histologically the choroid consists of the following
three layers.
Vascular layer Though there is no clear cut demar-
cation, the two layers can be seen:
i. Haller’s layer—composed of large vessels.
ii. Sattler’s layer—composed to medium sized
vessels.
The arteries are deeper posteriorly and become
superficial anteriorly. The veins are larger in size near
the posterior pole and near the opening of the venae
vorticosae. Each terminal arteriole ends in a lobule of
capillaries. The stroma between the vessels contain
wandering cells, pigment cells, collagen fibers, smooth
muscle fibers and fine nerves.
Layer of choriocapillaries It is meant for nutrition of the
visual receptor cells—the rods and cones. The
capillaries are endothelial and their interspaces
contain elastic and collagenous fibers but no pigments
or chromatophores.
Bruch’s membrane It is also called lamina vitrea. It con-
sists of an outer elastic and inner cuticular lamellae.
The elastic lamella is derived from mesoderm and the
cuticular lamella is formed by pigment epithelium and
hence is of neural ectodermal origin.
Ciliary Body
This is ring like structure at the junction of choroid
and iris. The beginning of the ciliary body is the ora
serrata which can be seen as zigzag margin with
indirect ophthalmoscope using scleral depressor. The
width of ciliary body is 6-7 mm on temporal side and
5.9 on nasal side. It consists of two parts—pars plana
or orbicularis ciliaris and pars plicata or corona ciliaris.
Pars plana zone extends up to 7 to 8 mm from the
limbus; this surface anatomy is very important for
planning the incision for pars plana surgery. Pars
plicata or corona ciliaris, situated anterior to pars
plana, is composed of about 70 meridional ciliary
processes of 2 mm length and 0.8 mm raised above
the surface forming deep interspaces. Ciliary body is
triangular in cross section, the apex of which is conti-
nuous posteriorly with the choroid, the base is situated
anteriorly and bears the iris, outer surface is in contact
with the sclera and the inner surface with the vitreous.
Structure of Ciliary Body
Ciliary muscles These have unstriped smooth muscle
fibers arranged in three layers:
i. Outer meridional fibers arise from suprachoroid
and attached to scleral spur.
ii. Radial fibers deep to the meridional fibers and
inserted to the circular fibers.
iii. The circular fibers are continuous with the radial
fibers and just behind the root of the iris and forms
a sphincter.
Layer of vessels and ciliary processes This is the conti-
nuation of forwards of the vascular layer of the choroid
except the choreocapillaris and the ciliary process. The
penetrating branches of ciliary artery pass through
perichoroidal space to the major arterial circle at the
root of the iris from which the branches pass to enter
the anterior ends of the ciliary processes.
Epithelium The lamina vitrea at the ciliary body which
is the continuation of the lamina vitrea of the choroid,
is lined by two layers of epithelial cells. Anteriorly
they are continuous with two pigmented layers of iris
and posteriorly continuous with the retinal pigment
epithelial layers. Inner surface of this epithelial layer
is covered by internal limiting membrane which is
continuous with that of the retina.
The blood supply of the ciliary body is mainly from
anterior ciliary arteries but long posterior ciliary
arteries also take part. The vessels consist largely of
veins which drain to venae vorticosae.
Retina
It is highly sensitive tissue and inner most tunic of
eyeball. It consists largely of end organs rods and
cones and nerve elements. Except the pigment
epithelium retina itself is transparent and its color is
due to the underlying pigment epithelium, retinal
capillaries and the visual purple of the rods.
 Chapter 134: Applied Anatomy of the Eye and Adnexa
Structure of Retina
From choroid toward vitreous, the retina is divided
into following layers (Fig. 134.7).
Pigment epithelium A thin brown layer from ora serrata
to the optic disk. The cells of the retinal pigment
epithelium (RPE) are hexagonal in cross-section. This
layer expands from the ora serrata to the optic disk
and beyond the ora serrata this layer merges with the
pigment epithelium of the ciliary body. The apices of
the cells have multiple villous processes which
interpose in between the outer segments of rods and
cones. The cell membranes of adjacent RPE cells are
attached by a lateral intercellular adhesions known
as zonula occludentes and zonula adherentes. This
tight junction forms the blood-retinal barrier.
Rods and cones These are photoreceptive elements of
retina. The rods are responsible for dim light vision
and cones for bright light and fine vision. The former
are about 125 million and latter about 7 million in
number. Cone population is highest at the fovea;
toward the periphery number of cones decreases and
that of rods increases so much so that near the ora
serrata there are no cones but only rods.
The external limiting membrane It is fine reticulum,
punctuated by large and small orifices containing cone
processes and rod fibers.
Outer nuclear layer It consists of nuclei of rods and
cones cells. This is also called outer granular layer.
Outer plexiform layer It is zone of synapses between the
photoreceptors and their sensory neurons, the bipolar
cells. This layer also contains the fibers of horizontal
cells and neuroglial element, Muller’s cells. In the
macular region the outer plexiform layer is thicker
because the axon of the rods and cones become more
oblique and longer as they deviate from the fovea. This
layer is known as Henle’s layer.
Inner nuclear layers It contains nerve cells as well as
axons of certain association neurons. The nuclei of
fibers of Muller also appear in this zone. Capillaries
of retinal system are also present in the inner nuclear
layer. They do not penetrate into layers external to it.
Inner plexiform layer It is largely composed of synapses
between axons of bipolar cells with dendrites of
ganglion cells as well as neuroglial cells.
Ganglion cell layer The cell bodies and nuclei of secon-
dary sensory neurons of visual pathways are promi-
nently seen in this layer. It also contains neuroglia and
branches of retinal artery and vein.
1017
Fig. 134.7: Structure of the retina
Stratum opticum The axons of ganglion cells are mainly
present in this layer. They converge toward optic disk
as optic nerve fibers to go out of the eyeball.
Internal limiting membrane It is a fine membrane on
vitreous side of the retina.
The macula lutea is a special region of the retina. It
is about 3-4 mm lateral to and below level of optic
disk. Its diameter varies from 1 to 3 mm. The central
depressed part of macula is called fovea. It has a high
concentration of cones and has the best discrimination
of vision.
All the fibers from nerve fiber layers of retina pass
to optic nerve at optic disk. The retinal layers other
than nerve fiber layer, stop short abruptly at the edge
of the optic disk. The fibers are nonmedullated up to
lamina cribrosa, passing which posteriorly the optic
nerve fibers become surrounded by medullary sheath.
The diameter of optic nerve head is 1.5 mm and just
outside the eyeball it become 3.0 mm thick because
now the fibers get medullated. Since the neurilemma
is absent, the nerve fibers of optic nerve do not
regenerate after section.
The optic nerve starts at the lamina cribrosa, runs
a slightly wavy course to permit free movements to
the eyeball and passes through optic foramen.
Reaching cranial cavity it joins with fellow optic nerve
from other eye at the optic chiasm.
The length of optic nerve is about 5.0 cm and its
course is divided into four parts:
a. Intraocular part—about 0.7 mm in length.
b. Intraorbital—longest and wavy part, measuring
25 to 30 mm.
c. Intracanalicular part—measuring about 6.0 to
10.0 mm and travels in the optic canal.
1018 Section 9: Miscellaneous Topics
d. Intracranial part—is about 10.0 mm and ends
at optic chiasm.
The optic nerve essentially has afferent fibers
largely sensory (corticopetal), but some fibers termi-
nate in midbrain (pupillary fibers) to take part in mid-
brain reflex arc. It is said to contain efferent fibers also
which are believed to be retinomotor and trophic
fibers.
Blood Supply of the Retina
The retina is supplied by the blood vessels arising from
the central retinal artery. Cilioretinal artery and retino-
cilial vein are present in 50 percent of eyes. The
capillaries of the retinal vessels contain a single layer
of nonfenestrated endothelial cells with tight junctions
which form the blood-retinal barrier. A basal lamina
covers the outer surface of the vessels; within this there
is an interrupted layer of pericytes or mural cells.
The Lens
The human crystalline lens is a transparent biconvex
structure measuring about 9-10 mm in horizontal
diameter and nearly 5.0 mm anteroposteriorly along
its optic axis. The posterior surface is more convex and
rests on anterior face of vitreous. The diameters are
altered considerably during accommodation which
become weaker with advancing age. The lens is held
in place by suspensory ligaments or zonule of Zinn.
The bundle of fibers pass from ciliary body to equator
of lens. With the lens the zonular fibers form the
septum between the aqueous and vitreous humor (see
Figs 134.5 and 134.6).
1. Central part—the nucleus: The innermost part is
embryonic nuclei and as the lens grows older,
successive zone of nucleus are laid down.
2. Cortex: Surrounding the nucleus.
3. Capsule: For the cataract surgeons proper know-
ledge of the anatomy of the lens capsule is of
utmost importance. The capsule of the lens is a
transparent envelope; the inner surface of the
anterior capsule up to the equator is lined by a
single layer of cuboidal germinal epithelial cells;
lens fibers are formed from these cells. Like the
Bruch’s membrane and the Descemet’s membrane,
the lens capsule is derived from the surface
ectoderm; when the lens vesicle is separated from
the surface ectoderm at 12 mm stage, the lens
capsule becomes visible. The capsule is said to be
independent of metabolism but it is seen that the
capsule thickens progressively until senescence. In
morgagnian cataract the capsule becomes very thin
and may even rupture spontaneously.
Thickness of the lens capsule varies in different
meridians and this controls the changes of the shape
of the lens during accommodation. The anterior
capsule, specially equatorial and midperipheral region
is thicker than the posterior capsule. This is of practical
importance to the extracapsular surgeons.
The capsule is composed of a collagen framework
the interspaces of which are filled with a mucopoly-
saccharide substance. Substances of low molecular
weight can pass through it but albumin and globulin
cannot. The suspensory ligaments extend to the
peripheral part of the anterior capsule and the
germinal layer of the subcapsular epithelium extends
up to the equatorial zone: this fact has got to be remem-
bered in extracapsular extraction because a liberal
anterior capsulectomy might damage the suspensory
ligaments and a conservative one leaves a greater
chance of formation of after cataract (unless the
epithelial cells from the equatorial part are not
completely removed).
Even after complete disappearance of the hyaloid
artery a small dot known as Mittendorf’s dot remains
in the posterior capsule. The circular Wieger’s
ligament (hyaloidocapsular attachment) persists in
young persons. This causes high rate of rupture of
anterior vitreous face in attempting intracapsular
extraction in persons below the age of 30 years. The
circular retrolental space (of Berger) formed by
attachment of Wieger’s ligament may remain even
after implantation of intraocular lens after ECCE.
When posterior primary capsulotomy is done after
IOLI, it should be done within the boundary of the
Berger’s space. In YAG laser posterior capsulotomy,
just after the first shot the space collapses, then it is
difficult to make optimum capsulotomy opening
without rupturing the anterior vitreous face.
The tensile strength of the anterior capsule allows
it to mould itself for the catch between the two blades
of the intracapsular forceps and into the bell of the
erysiphake as well as the pull by the cryoprobe. The
chemical composition of the lens capsule is different
from that of the zonules as the former is not digested
by alpha chymotrypsin.
Vitreous Humor
The vitreous is transparent and gelatinous material
filling the posterior four-fifth of the globe. Its
consistency is like uncooked white of egg. It is directly
in touch with posterior surface of lens, zonules, ora
serrata, retina and optic disk. The vitreous body is
more adherent at optic disk, macula, the ora serrata
 Chapter 134: Applied Anatomy of the Eye and Adnexa
Figs 134.8A to F: Development of eye: Solid black line-neural ectoderm,
hatched line—surface ectoderm, dotted area—mesoderm
and to the posterior aspect of the lens, near its equator.
It can easily be separated from retina. During
development phase, it is traversed by hyaloid artery
from the center of optic disk to the back of lens, which
may sometimes persist even at birth, or later life, fully
or in part. Usually it disappears at birth leaving a
canal, called the hyaloid canal. The vitreous body has
loose fibrous framework of collagenous fibers whereas
its cortex is made up of collagen like fibers together
with protein (see Fig. 134.5).
EMBRYOLOGY OF EYEBALL
The development of eyeball takes place from the
neural groove, as a part of central nervous system.
The neural groove invaginates to form the neural tube.
On either side of the cephalic end of this tube (Figs
134.8A and B) appear two vesicles, called primary
optic vesicles; each one developing into eye. This
process starts at the 4 mm stage of the embryo. The
vesicles (neuroectoderm) come in contact with surface
ectoderm and by its invagination the optic cup forms
(Fig. 134.8C). The surface ectoderm thickens to form
lens plate which invaginates to form lens cup (Fig
134.8D). With the time and development of embryo,
this lens cup detaches from the surface ectoderm and
sinks into the cavity of optic cup to develop into future
crystalline lens. The mesenchymal tissue also enters
in the optic cup through optic fissure. With the
development of embryo the inner layer of optic cup
1019
gives rise to future retina, epithelium of ciliary body
and iris, sphincter and dilator pupillae. The outer layer
of cup gives rise to pigment epithelium layer of retina.
The paraxial mesodermal layer forms the ciliary body
and iris. Vitreous later fills up the eyeball cavity,
presumably it is secreted by the surrounding
neuroectoderm. Optic nerve develops by the axons of
ganglion cells of retina. The outer coats of eyeball,
choroid and retina (Figs 134.8E and F), are formed by
condensation of mesoderm around optic cup; similarly
other structures of orbit including eye muscles
develop from the surrounding mesoderm. From the
mesodermal condensation also develops the stroma
of the cornea, anterior layer of the iris and the angle
of anterior chamber. The epithelium of the cornea and
the conjunctiva develops from the surface ectoderm
(Figs 134.8E and F). The lids develop from the surface
ectoderm and mesoderm. The extraocular muscles
develop from the preoptic myotomes and are
innervated by the oculomotor, trochlear and abducent
nerves.
The lacrimal gland develops from superolateral
part of the conjunctiva whereas lacrimal sac from a
solid column of cells from surface ectoderm. The
canaliculi and the nasolacrimal duct also develop from
surface ectoderm.
The canalization of the cellular column starts at
about third month and mostly completed by the
seventh month of intrauterine life. In some cases
failure of this process leads to epiphora in infancy.
 Chapter 135

Introduction to Computed
Tomography and Magnetic
Resonance Imaging in
Ophthalmic Practice
N Medhi, SK Handique

Since the discovery of X-rays by WC Roentgen in 1895,
various other sophisticated imaging modalities have
been introduced. These imaging modalities have
revolutionized the diagnosis and management of
various orbital diseases. A major role in this regard is
played by computerized tomography (CT) and MR
(magnetic resonance) imaging and to a lesser extent
by ultrasound and plain X-rays.
COMPUTERIZED TOMOGRAPHY (CT)
The invention of the CT scanner has revolutionized
the diagnosis and management of orbital disease. CT
was the end product of years of work by numerous
investigators. Though various scientists like J. Radon
(1917), Bracewell (1956), Oldendroff (1961) and
Cormack (1963) contributed to its development, it was
GN Hounsfield senior research scientist at EMI
laboratory in Middlesex, England in 1972 who first
announced the invention of the CT scanner.1 Initially
it was known as EMI scan (Electrical and Musical
Industries). The first CT scanner was specifically
designed for head. This was later termed as the first
generation CT scanner. This scanner was very slow
compared to the present day CT scanners. There has
been continuous development of the original EMI
scanner and a few more generations came during the
next 5 years. The present day CT scanners are much
faster, have very good spatial resolution and their use
has been extended to scan the whole body, hence the
name whole body CT scanner. The basic principle of
CT is very simple. Here, a thin cross section of the
human body (tomographic slice) is examined by a thin
pencil like beam of X-rays from different angles. The
transmitted radiation falls on a detector which
receives, records and transmits the signals to a
computer which ultimately analyzes the data. The
reconstructed tomographic images are displayed in
the monitor for viewing and subsequent hard copying.
Translating the X-ray tube makes transmission
measurements of adjacent tissues and produces a
complete scan projection (Fig. 135.1). By measuring
many additional projections at different angles,
enough information is obtained for the computer to
produce an image by a variation of the back-projection
process.2,3
Spiral CT
Introduction of the spiral CT scanners in the 1980s
greatly improved on the applications of CT scanning.
In spiral CT scanners the patient table moves
continuously during data acquisition and data are
therefore acquired in a spiral fashion (Fig. 135.2). Here
 Chapter 135: Introduction to CT and MRI in Ophthalmic Practice
Fig. 135.1: Basic components of a CT scan machine. The tube
and the detector row rotate 360 degree, the patient being
stationary. Transmitted radiation through the patient is received
by the detectors. From the detector data the image is
reconstructed
Fig. 135.2: Mechanism of the spiral CT scan. The patient table
moves in a continuous fashion while the tube moves in a
continuous circular fashion around it. These motions effectively
sample data from the body in a spiral fashion as shown
scan time is determined by scan volume (total distance
traveled by the table) divided by the table speed. The
radiation dose is drastically reduced in spiral CT.
Improved resolution results due to volume data
acquisition and reduction of various movement
artifacts. There is greater patient comfort due to redu-
ced scan time. Less intravenous contrast volume is
used due to the reduced scan times. Also fast imaging
is achieved in uncooperative and acutely injured
patients.
Multislice (Multidetector) CT
Multislice or multidetector CT scanners use multiple
rows of detectors unlike the single row in spiral CT
scanners. Therefore, multiple slices are acquired in one
rotation in contrast to conventional spiral CT scanners.
The advantages of multislice CT scanners include
1021
larger and faster anatomical coverage. Large volumes
of data can be acquired in a single breath hold. Near
isotropic scanning allows true 3-D data acquisition.
This opens up a totally new dimension in CT scanning
allowing orthogonal reconstructions in any plane
without actually scanning the patient a second time
in another plane. Routine scanning of any body part
is therefore more efficiently done on a multislice CT
scanner as it allows thinner slices, longer scan ranges
and shorter scan duration. In the orbit, it is possible
to acquire in the axial plane with the patient
recumbent, and reconstruct the data for coronal and
sagittal planes. This benefits difficult patients such as
trauma and pediatric patients who may find it difficult
to maintain the prone position for coronal scanning
as in conventional scanners. A single breath Valsalva
maneuver scan is possible which may be useful to
confirm orbital venous malformations. Vascular
lesions are better imaged due to excellent capability
of CT angiography.
Scanning Protocols
Orbital CT scans are to be routinely taken in axial and
coronal planes. Wherever possible it should be
supplemented by sagittal and oblique reconstructed
images. Axial planning is the most comfortable
position for the patient and is done by taking 2 to 3
mm sections. The scanning angle is between the
cantho-meatal line and Reid’s base line 4 (Fig. 135.3A).
Scanning area should be covered from the floor to the
roof of the orbits. The coronal sections are done with
2 to 3 mm slice thickness extending from the level of
anterior globe wall to the sella turcica and planning is
done perpendicular to the Reid’s base line
(Fig. 135.3B). Slice thickness selection depends upon
the clinical condition and the size of the lesion to be
assessed. In diseases of the optic nerves, 2 mm slice
thickness should be selected. The optic canal forms
an angle of –30 degrees with the Reid’s base line with
the patient looking up.
Use of intravenous iodinated contrast media
should be judged according to the clinical situation.
The basic aims of injecting intravenous contrast are
three. Firstly, lesions not detected in the plain scans
may be visualized after contrast injection; secondly,
contrast may help in lesion characterization and lastly,
contrast may help visualize the full extent of the
disease specially for surgical evaluation and planning.
As there is associated cost involvement and risk of
contrast reaction, every patient should be judged
1022 Section 9: Miscellaneous Topics
Fig. 135.3A and B: (A) Planning for axial CT of the orbits. 2
mm cuts are taken extending from the floor to the roof of the
orbit, (B) Planning for coronal CT sections. 2 mm slices are
obtained from the anterior globe wall to the sella turcica
before administering contrast. Ocular space occupying
lesion, retrobulbar masses, orbital infections and
vascular lesions are some of the conditions where
intravenous contrast is mandatory. Contrast infusion
helps in defining the extraocular spread of the disease
process. Contrast is generally not required in evalu-
ation of bony orbital injury and congenital conditions.
MAGNETIC RESONANCE (MR) IMAGING
Magnetic Resonance Imaging (MRI) is another
imaging modality increasingly used for the diagnosis
of orbital pathologies. Its superiority over CT is due
its multiplanar capability, high contrast resolution and
lack of ionizing radiation. Nuclear magnetic resonance
(NMR) is a phenomenon that was first mentioned in
scientific literature more than 50 years ago. Various
scientists separately worked on the magnetic pro-
perties of nucleii at different times. It was seen that
when these nuclei were placed in a magnetic field,
they absorb energy in a specific radiofrequency range
and re-emit this energy during transition to their
original orientation. This is the basis of the NMR
signal. Though many scientists worked on this pheno-
menon, it was Paul Lauterbur in 1973 who first
indicated that the phenomenon of NMR could be
employed for image formation.5
The Basics of MRI
The human body is composed of atoms which consist
of protons, electrons and neutrons. Protons and
neutrons comprise the nucleus. The protons are
positively charged. The electrons surround the nucleus
and are negatively charged. The neutrons do not have
charge. The nucleus has an inherent spinning property
around its own axis and produces a small magnetic
field around it. The atoms having even number of
protons have no charge due its interaction with one
another. Hence the nuclei having odd numbers of
protons are utilized in the production of magnetic
resonance signal. Most commonly utilized nuclei are
H, C, F, Na and O. Out of these, H (hydrogen) is most
commonly used atom in magnetic resonance imaging
because it is abundantly found in the human body.
Hydrogen has just one positively charged proton in
its nucleus. These positively charged nuclei act like
small magnets and are arranged randomly in the
human body. When the human body is put into a very
strong magnetic field, these positively charged nuclei
try to align themselves either in a parallel or anti-
parallel orientation to the external magnetic field.
These nuclei at this stage have two types of move-
ments. Firstly, they move around their own axes and
secondly, they ‘precess’ (a spinning top like move-
ment) around the external magnetic field in a specific
frequency called the Larmor frequency (Figs 135.4A
and B). This precession frequency is directly propor-
tional to the strength of the external magnetic field,
stronger the magnetic field higher will be the
precession frequency. The nuclei which precess in the
direction of the external magnetic field are in lower
energy level and those precessing in the opposite
direction will be at a higher energy state. The excess
precessing nuclei in the lower energy state is termed
as net nuclear magnetization (NNM) (Fig. 135.5). Since
the energy difference between these two states is very
 Chapter 135: Introduction to CT and MRI in Ophthalmic Practice
Fig. 135.4A and B: (A) Protons in the body have a spin which
creates a small magnetic moment µ. (B) When an external
magnetic field M is applied, the moment precesses in the
direction of the external magnetic field, a motion rather like a
spinning top
weak the resulting signal is very low. To detect this
NNM it is necessary to tip it away from the main
magnetic field. This is done by applying an electro-
magnetic radiofrequency (RF) pulse at the resonance
frequency. The resonance frequency is defined as the
frequency at which the lower energy nuclei will be
transferred to higher energy states. In this process the
net nuclear magnetization is tipped by 90 degree RF
pulse which shifts the NNM from the X-axis to the Z-
axis (Fig. 135.6). When this excitation pulse is switched
off, the spins (NNM) start returning to equilibrium
state and emit signals. These signals are called the MR
signals. These signals contain spatial information and
are received and processed by the computer to form
an MR image.
The process of returning to the equilibrium from
an unstable state is called spin lattice relaxation or
1023
Fig. 135.5: Positively charged protons possess magnetic fields
which can be described as magnetic dipoles. These magnetic
dipoles are abundant in the body and arranged randomly in
the body. When an external magnetic field (vector M in the
figure) is applied, these dipoles align themselves parallel or
antiparallel to the external magnetic field. More protons align
in the parallel than antiparallel direction resulting in a net nuclear
magnetization (NNM) shown above with the vector B
longitudinal relaxation. The T1 relaxation time of a
tissue is the time required to recover to 63% of its
equilibrium value after it has been exposed to 90
degree pulse. Again after the spin has been excited by
an RF pulse all protons precess in phase (all together)
around the direction of the external magnetic field.
However as time passes the observed signal starts to
decrease as the spins start to dephase. The decay of
signal in the XY plane is called spin-spin or transverse
relaxation or T2 relaxation. Images in MR depend on
three fundamental parameters: proton density,
longitudinal relaxation-T1 and transverse relaxation-
T2. The brightness of the MR images depend on the
strength of the signal intensity. Stronger the signal
intensity brighter will be the image and is referred to
as hyperintense. Weaker the signal, darker the images
and is referred as hypointense. Various parameters
influence the intensity of the MR signals. Strong
signals are obtained from the tissues having a short
T1 and long T2 relaxation time ( high concentration of
hydrogen ion) and low signal intensity is obtained
from the tissues having long T1 and short T2 relaxation
time (low hydrogen concentration). By applying a
desired frequency of RF pulse the T1 and T2 charac-
teristic image contrast can be obtained. T1 and T2
weighted images are the images whose picture
elements represent pure T1 and T2 values respectively
but in practice these images have only a certain
amount of T1 and T2 dependence.
1024 Section 9: Miscellaneous Topics
Fig. 135.6: (Top) The net nuclear magnetization (NNM) after
the protons in the body are exposed to an external magnetic
field M is shown as vector B along the Z-axis, (middle) After
the NNM is exposed to a 90 degree pulse of appropriate
frequency, it is tipped from its equilibrium (from Z-axis to X-
axis). (bottom) If the RF pulse lasts twice as long a 180 degree
pulse results which inverts the magnetization
MR Protocols for Orbits
In routine practice orbital MR is done by obtaining
transverse, coronal and oblique sagittal images. T1-
weighted axial sections are preferably taken in axial
and coronal planes. T2-weighted images are also
obtained in axial and coronal planes. Whenever
necessary oblique sagittal images should be obtained,
specially for the optic nerves. Additional T2-weighted
fat suppressed sequence should be taken which causes
the pathologies to stand out prominently against the
dark background of suppressed fat signal. 4 mm slice
thickness with 1 mm interslice gap is normally
obtained. Gadolinium compounds injected intra-
venously are used as MR contrast. Postcontrast study
is done by T1-weighted axial and coronal images with
fat suppression. Decision to infuse contrast is guided
by the clinical situation and after assessment by the
radiologist. The MR contrast is expensive, though
relatively safer than CT contrast. The purpose of using
MR contrast is the same as that of CT.
NORMAL ANATOMY
The normal CT and MR anatomy of the orbit is shown
in Figures 135.7 through 135.15.
Bony orbits are paired pyramidal cavities situated
on either side of the nose and consist of multiple bones.
The roof of the orbit is formed by the orbital plate of
the frontal bone. The medial wall is formed by lamina
papyracea which is perforated by many small fora-
minae for vascular communication. The floor of the
orbit is formed by the roof of the maxillary sinus.
The orbits are connected to the intracranial cavities
by two foraminae. They are superior orbital fissure
and optic canals which transmit important structures
from the intracranial cavities to the orbits. The superior
orbital fissures (one on either side) are formed by the
lesser and greater wing of the sphenoid bones and
transmit the III ,IV ,VI and V-2 cranial nerves along
with the ophthalmic veins.
The optic canals are formed within the lesser wing
of the sphenoid and they are directed anteriorly,
inferiorly and laterally. The canal is 8 to 10 mm long
and 4.5 to 6 mm in diameter. The optic canal transmits
the optic nerve and ophthalmic artery.6,7
Fig. 135.7: Axial CT section through the inferior part of orbits.
Note how the fat appears hypodense, the soft tissues and
muscles appear of intermediate density and the bones
hyperdense. 1. Orbicularis oculi muscle. 2. Orbital septum. 3.
Globe. 4. Lateral orbital wall. 5. Inferior rectus muscle. 6. Inferior
orbital fissure. 7. Retrobulbar fat. 8. Sphenoid sinus
 Chapter 135: Introduction to CT and MRI in Ophthalmic Practice 1025
The inferior orbital fissures connect the orbit with
the infra temporal and pterygopalatine fossae.

Globe
The globes or the eyeballs are the paired structures
situated one on each side within the bony orbits. The
globe measures 23 to 26 mm in the equatorial
diameters. It is filled up with aqueous humor anterior
to the lens (within the anterior and posterior
chambers) and vitreous humor (within the vitreous
cavity) posterior to the lens. The aqueous and vitreous
are both water rich while the lens is the least hydrated
organ in the body. This allows good contrast of the
eyeball structures both in CT and MR (Figs 135.7, 135.8,
135.12 and 135.13). The globe wall consists of three Fig. 135.9: Axial CT section through the superior part of orbits.
layers: outer sclera, inner retina and the uvea in the 1. Globe. 2. Lacrimal gland. 3. Superior ophthalmic vein. 4.
middle. The retina is composed of rods and cones Superior oblique tendon. 5. Levator palpebrae superioris muscle
which are stimulated by incident light. The light complex
energy is converted into electrical energy which is
transmitted by the bipolar cells to the ganglion cells.
The axons of these ganglia meet and form the optic
disc from which the optic nerve begins. Tenon’s
capsule is a thin fibrous membrane that surrounds the
posterior portion of the globe from the margin of
cornea to the optic nerve. There is a potential space
between the sclera and the Tenon’s capsule.

Retrobulbar Space
The retrobulbar space extends from the orbital septa
and eyeball to the orbital apex. For convenience of

Fig. 135.10: Coronal CT section through the mid part of

retrobulbar space. 1. Bony roof of orbit. 2. Levator palpebrae
superioris/superior rectus muscle complex. 3. Superior
ophthalmic vein. 4. Lateral rectus muscle. 5. Optic nerve. 6.
Medial rectus muscle. 7. Superior oblique muscle. 8. Inferior
rectus muscle. 9. Retrobulbar fat

description the retrobulbar space is divided into extra-

Fig. 135.8: Axial CT section through the mid part of orbits. Note
the normal hyperdense appearance of the lens. 1. Lens. 2.
Globe. 3. Lacrimal gland (palpebral part). 4. Lateral rectus
muscle. 5. Medial rectus muscle. 6. Lamina papyracea. 7. Optic
nerve. 8. Superior orbital fissure. 9. Sphenoid sinus
conal and intraconal compartments by the extraocular
muscles along with the intermuscular membranes.
These spaces are filled with fatty tissue which contrasts
well with the orbital muscles, optic nerve and vessels,
both on CT and MRI. The fat appears hypodense on
CT images and hyperintense both on T1 and T2-
weighted images (Figs 135.12 through 135.15). Fat
suppression techniques may be used to suppress the
1026 Section 9: Miscellaneous Topics
Fig. 135.11: Coronal CT section through the orbital apex.
1. Muscle cone. 2. Optic nerve. 3. Inferior orbital fissure.
4. Maxillary antrum. 5. Nasal septum
Fig. 135.12: Axial T2-weighted MR image through the lower
part of orbits. 1. lens. 2. Globe (vitreous) 3. Inferior rectus
muscle. 4. Sphenoid sinus.5. Retrobulbar fat. 6. Lacrimal gland.
7. Orbital septum. Note the contents of the eyeballs appear
hyperintense in this image with the lens being hypointense.
Also note the dark appearance of bone due to lack of MR signal
from dense bone. The orbital fat appears hyperintense, but less
than that of the vitreous
signal from fat on MR to show non-fatty pathology
within the fat, or to highlight contrast enhancement.
There are six extraocular retrobulbar muscles, four
rectii and two obliques. The four rectus muscles
Fig. 135.13: Axial T2-weighted MR image through the mid part
of orbits. 1. Lens. 2. Lateral rectus muscle. 3. Medial rectus
muscle. 4. Optic nerve. 5. Globe. 6. Retrobulbar fat. 7. Superior
orbital fissures. 8. Sphenoid sinus. 9. Cavernous sinus. 10. Lack
of signal in the internal carotid artery due to which it appears
dark
Fig. 135.14: Axial T1-weighted MR image through the mid part
of orbits. The nature of contrast of the different orbital structures
are altered in comparision to the T2 -weighted images in Figures
135.12 and 135.13. Note the eye balls which are hypointense
and the lens which is hyperintense in these sets of images.
The orbital fat is still hyperintense. 1. Lens. 2. Extraconal space.
3. Lateral rectus. 4. Globe. 5. Optic nerve head. 6. Optic nerve.
8. Medial rectus muscle. 9. Superior orbital fissure. 10.
Cavernous sinus. 11. Basilar artery
originate in the annulus of Zinn and courses anteriorly
to be inserted in the sclera. The superior oblique
 Chapter 135: Introduction to CT and MRI in Ophthalmic Practice 1027
muscle arises from the superomedial part of the optic
foramen and inferior oblique muscle originates from
the orbital plate of maxilla and inserts into the orbital
globe. The extraocular muscles are isodense on plain
CT scan and uniformly enhance after infusion of
intravenous contrast (Fig. 15.8 and Fig. 135.10). On
MR they have signal intensity similar to other muscles
of the body. On T1-weighted images these extraocular
muscles are iso to hypointense and hypointense on
T2-weighted images. Due to multiplanar capability of
MRI these muscles are better seen with MR along its
entire course.
The optic nerve is formed by the axons of the
ganglion cells of the retina. Like the white matter tracts
of the central nervous system the optic nerve fibers
also contain myelinated sheath. The optic nerve
extends from the optic disk through the muscle cone
and the optic canal to meet its counterpart in the optic
chiasm. The optic nerve is divided into four segments
for convenience of description. The intraocular portion
Fig. 135.15: Axial T1-weighted MR image through the superior
measures approximately 1mm in length and re- part of orbits. 1. Intracanalicular part of optic nerve. 2. Lateral
presents the part within the optic disk. The orbital rectus. 3. Globe. 4. Lateral wall of orbit. 5. Ethmoid sinuses.
portion measures 20 to 30 mm in length and is embed-
ded in the retrobulbar fat. The canalicular part
measures approximately 9 mm in length and lies nerve along with the sheath measures approximately
within the optic canal along with the ophthalmic 4.5 mm in diameter.8
artery.
The last part of the optic nerve is the intracranial REFERENCES
part, the length of which is variable and ranges from 1. Hounsfield GN. Computerized transverse axial scanning
4 to 16 mm. The intracranial part of the optic nerve (tomography). Br J Radiology 1973;46:1016.
lies in close contact with the sphenoid sinus and there 2. Brooks RA, DiChiro G. Theory of image reconstruction in
are four types of arrangements which can be seen in computed tomography. Radiology 1975;117:561.
3. Gordon R, Herman GT, Johnson SA. Image reconstruction
relation to the sphenoid sinus. In type I the optic nerve
from projections. Sci Am 1975;233:56.
traverses along the side wall of the sphenoid sinus, 4. Hesselink JR, Karampekios S. Normal computed tomography
no indentation is noted on the side wall. In type II the and magnetic resonance imaging anatomy of the globe, orbit
optic nerve indents the sinus wall. In type III the optic and visual pathways. Neuroimaging Clin North Am
nerve traverses within the sphenoid sinus and in type 1996;6:15.
IV, the optic nerve is in contact with the posterior 5. Rink PA. Magnetic Resonance in Medicine: The Basic textbook
of the European Magnetic Resonance Forum. 5th edition.
ethmoid sinus. The optic nerve sheath is the continu- ABW Wissenschaftsverlag, Austria, 2003;p.1-3.
ation of the pial, arachnoid and dural intracranial 6. Burt AM. Textbook of Neuroanatomy. Philadelphia, WB
membranes. The subarachnoid space also extends into Saunders, 1993; p. 403-66.
the optic nerve sheath along with these perineural 7. Hammerschlag SB, Hesselink JR, Weber AL. Computed
structures. The subarachnoid space is better seen in Tomography of the Eye and Orbit. Norwalk, CT, Appleton-
Century-Crofts, 1983;p.1-29.
the T2-weighted MR scans as a hyperintense space 8. Grossman RI, Youssem DM. Orbit. In Grossman RI, Youssem
around the optic nerve. This perioptic space becomes DM (Eds): Neuroradiology: The requisites. St Louis: CV
prominent in raised intracranial tension. The optic Mosby Co, 1994;1277-304.
 Chapter 136
Computed Tomography and
Magnetic Resonance Imaging of
the Eye and Orbit
SK Handique, N Medhi, B Saharia
The introduction of computerized tomography (CT)
and magnetic resonance imaging (MR) have changed
the approach to orbital imaging by providing a
comprehensive means of evaluation of the soft tissue
and bony structures of the orbit and the surrounding
anatomy. The general principles and indications of CT
and MR have been discussed in the previous chapter.
This chapter deals with the different orbital soft tissue
and bony lesions, and visual pathways with their
appearance on CT and MR. The relevant anatomy,
pathology and clinical features are discussed briefly
with each condition, as the imaging interpretation
depends on these.
OCULAR LESIONS IN CHILDREN
Retinoblastoma and its Mimics
One of the most common reasons for ordering an
imaging study of the orbits is leukocoria or cat’s eye
reflex, caused by intraocular pathology that reflects
incident light through the pupils to the observer. The
common causes of leukocoria are retinoblastoma,
persistent primary hyperplastic vitreous (PHPV),
retinopathy of prematurity, congenital cataract, Coats’
disease, toxocariasis, retinal detachment and many
others.1
Retinoblastoma
Retinoblastoma is the most common intraocular
malignant tumor of childhood with a worldwide
incidence of 1 in 18,000 to 30,000 live births.2 Patients
usually present in the first decade. However presen-
tation may be late when the disease is far advanced.3
When the disease extends beyond the eye, mortality
approaches 100%.4 With early diagnosis, the 5-year
survival rate is 92%.5 Retinoblastoma may be inheri-
ted, non-inherited, unilateral (65%), bilateral (35%) or
associated with intracranial primitive neuroecto-
dermal tumor in the pineal or suprasellar region
(trilateral retinoblastoma). 6,7 Hereditary retino-
blastoma may be associated with a second malignant
tumor, especially osteogenic sarcoma at the site of
radiation.8
The diagnosis of retinoblastoma may be difficult
clinically due to its various other mimics. Three forms
of growth patterns are recognized; (i) endophytic: the
tumor extends anteriorly, breaks through the internal
limiting membrane of the retina, and grows into the
vitreous; (ii) exophytic: the tumor arises intraretinally
and subsequently grows into the subretinal space,
causing elevation of the retina, subretinal exudation
or hemorrhage and retinal detachment. Exophytic
tumors can mimic traumatic retinal detachment
ophthalmoscopically;3 (iii) diffuse: characterized by
diffuse infiltration along the various layers of the retina
without a definite tumor mass. This form is misleading
both to the ophthalmologist and the radiologist, as
calcification, the major sign of typical retinoblastomas
may or may not be present; it may simulate inflam-
matory or hemorrhagic conditions and presents
outside the typical age group.9
 Chapter 136: Computed Tomography and Magnetic Resonance Imaging of the Eye and Orbit 1029

Fig. 136.1: (A) Plain axial CT of retinoblastoma. Note intraocular mass (arrow) with calcification (open arrow). (B) Contrast
enhanced axial CT scan. After contrast infusion there is mild enhancement of the mass. (C) Axial T2-weighted MR of the same
case shows slightly hypointense intraocular mass (arrow). The calcified areas appear dark but are not as well seen as on CT. (D)
Axial T1-weighted MR of the same patient as above shows the mass to be slightly hyperintense to the vitreous (arrow). Calcification
cannot be differentiated. Note subretinal exudates, (double arrows) better picked up than on the CT. (E) Axial post gadolinium
MR shows moderate enhacement of the lesion

Even if retinoblastomas are apparent clinically,
diagnostic imaging is required to assess retrobulbar
extension, intracranial spread, metastases, subtle
contralateral tumor and differentiation from its
mimics. CT and MR are the most useful techniques.2,10
Trilateral retinoblastomas have a distinctly poor
prognosis. Meta-analytic data have shown that
screening by imaging of all patients with bilateral
retinoblastoma may be helpful in picking up the
intracranial tumor before these patients are sympto-
matic, as asymptomatic patients had better overall
survival after treatment.7,11
On computed tomography (CT) the tumor appears
slightly hyperdense to vitreous on the plain scans.
After intravenous (I.V.) contrast infusion there is
usually mild to moderate enhancement of the lesion.
CT is very sensitive to calcifications and picks up the
tumor calcifications well (Figs 136.1A and B). 80-90%
of retinoblastomas show calcification and can be
picked up on CT scan.12,13 Associated retinal detach-
ment can be seen well and exophytic lesions picked
up. Diffuse lesions may appear as a plaque and pose
a diagnostic problem, as calcifications are less
common.9 Gross extraocular extension and extension
1030 Section 9: Miscellaneous Topics

along the optic nerve can also be seen. Intracranial Color Doppler examination of the eye may help in
spread along the optic nerves can be seen as thickening diagnosing PHPV in the experience of the author and
of the nerve sheaths. This usually shows enhancement others.20 A band-shaped arterial blood flow represen-
after IV contrast.14 ting the persistent hyaloid vessels coursing from the
The lack of sensitivity of magnetic resonance optic disk to the posterior aspect of the lens may be
imaging (MR) to calcifications makes it less specific seen (Fig 136.3).
to detection of these lesions.3 MR shows the lesions as
slightly hyperintense than vitreous on T1-weighted
and slightly hypointense to the same on T2-weighted
images (Figs 136.1C and D). There is mild to moderate
enhancement after IV gadolinium (Fig. 136.1E).
Though CT is more sensitive in the diagnosis of retino-
blastoma, MR may be more sensitive in detecting early
extension along the optic nerve, second malignant
tumors and intracranial involvement.3,15

Persistent Hyperplastic Primary Vitreous (PHPV)

PHPV is a congenital condition that presents as uni-
lateral or bilateral leuokocoria and results when the
Fig. 136.2: PHPV: Axial contrast enhanced fat-suppressed T1-
embryonic hyaloid vascular system fails to regress
weighted MR image. The left eye is microphthalmic. A contrast
completely. The hypervascular embryonic vitreous enhancing mass behind the lens and Cloquet’s canal with
called the primary vitreous remains as a small linear remnants of the hyaloid system extending from the optic disk
vascular space in the central vitreous by the 8th month to the posterior aspect of an altered lens are shown. (From
of gestation, called the canal of Cloquet, which Galuzzi P, Hadijstillianou T, Venturi C: Leukocoria: Clinical and
connects the lens and the optic nerve. In PHPV, the neuroradiological findings. Revista di Neuroradiologia
primary vitreous fails to regress leaving the retrolental 17:61,2004. With permission from the authors and Dr Marco
Leonardi, ed, Revista di Neuroradiologia)
space with highly vascular embryonic tissue. The
condition may be associated with various other
congenital defects and neurological abnormalities.16
CT shows the persistent retrolental soft tissue along
the Cloquet’s canal, which may enhance after contrast
infusion. The vitreous may appear diffusely hyper-
dense although minimally-involved cases may show
normal vitreous density. Calcification is absent. The
globe may be normal or microphthalmic. In early
stages however, the globe may be large due to buph-
thalmos resulting from glaucoma due to anterior
displacement of the lens by the vascular mass.
Decubitus positioning may show a fluid level within
the vitreous representing the subretinal or subhyaloid
serosanguinous fluid. The lens may be small and the
anterior chamber shallow. The retrobulbar soft tissues
are normal, the optic nerve may be normal or
atrophied.6,17
MR may show microphthalmos, funnel-shaped
retinal detachment with the subretinal fluid appearing
hyperintense on both T1 and T2-weighted images, a
tubular lesion representing the Cloquet’s canal, Fig 136.3: Persistent hyperplastic primary vitreous. Color
retrolental mass or fluid-fluid levels in the vitreous Doppler ultrasound shows the persistent hyaloid vessels
chamber. Contrast enhancement is inconsistent coursing from the optic disc to the posterior aspect of the
(Fig. 136. 2).18,19 abnormal lens within the Cloquet’s canal
 Chapter 136: Computed Tomography and Magnetic Resonance Imaging of the Eye and Orbit
Coats’ Disease
Coats’ disease is a congenital condition characterized
by idiopathic retinal telengiectasis with intraretinal
or subretinal exudation. The condition is more
common in juvenile males and mostly unilateral,
though bilateral disease has been reported.3,21 There
is breakdown of the blood-retinal barrier by the retinal
telengiectasis, with lipoproteinaceous exudates
leading to the pathological changes seen in Coats’
disease. Even though the condition is congenital,
symptoms are not caused until the retina detaches and
central vision is lost.22
CT findings depend on the progression of the
disease. Advanced disease reveals retinal detachment
with denser substance posterior to the vitreous. There
may be linear contrast enhancement at the boundary
between the vitreous and the exudation.23 It may not
be possible to differentiate Coats’ disease from a
diffuse or unilateral non-calcifying retinoblastoma.22
The globe volume may be small in Coats’ disease. This
may help in differentiating from retinoblastoma,
which is not associated with microphthalmia.24
On MR, subretinal exudates may show hyper-
intense signal on T1 and PD-weighted images and
hyper to slightly hypointense signal on T2-weighted
images. After gadolinium infusion there is usually
linear enhancement of the detached retinal layers and
the telengiectatic vessels in the retinal periphery.23,25
The contrast enhancement is usually more apparent
than on CT and the lack of an underlying mass (seen
in retinoblastoma) more confidently demonstrable.
Ocular Toxocariasis (Sclerosing Endophthalmitis)
Human toxocariasis is a helminthozoonosis due to the
infestation of ascarid larvae of the genus Toxocara. Two
species, namely Toxocara canis and Toxocara cati are
pathogenic in humans. The adult form of both the
species live in the upper digestive tracts of their
definitive hosts, canids (dogs) and felids (cats) respec-
tively. Eggs of the worms are passed in feces and
contaminate soil. Humans are accidentally infected
either due to direct ingestion of contaminated soil (pica
in children) or infected vegetables or meat.26
The ingested eggs in the embryonated form hatch
in the small intestine to form larvae, which perforate
the walls of the intestine and invade the blood vessels
to migrate to the lungs, liver, heart, eye and brain.
They are associated with migratory tracks charac-
terized by hemorrhage, necrosis and inflammation
1031
with eosinophils predominating. In the eye, the
inflammatory response can lead to retinal detachment
with visual loss.27
Ocular toxocariasis typically occurs unilaterally in
children and young adults and fundoscopic and
biomicroscopic examination may reveal uveitis,
endophthalmitis, papillitis, retinal granulomatous
lesions or inflammatory masses in the peripheral
vitreous.26
CT may demonstrate diffuse increased density in
the vitreous that corresponds to detached retina, orga-
nized vitreous and inflammatory subretinal exudates.
This finding simulates diffuse retinoblastoma or Coats’
disease.28 The granulomas may be seen as localized
or diffuse ill-defined masses of the sclerouveal coat
which may show no or slight enhancement. 2 MR
shows the proteinaceous subretinal exudates as varia-
bly hyperintense on T1 and T2-weighted sequences.
The granulomas may be seen as enhancing lesions.3
Retinopathy of Prematurity (ROP)
ROP occurs in premature infants exposed to high
oxygen tension over a prolonged period for the
treatment of respiratory distress syndrome. The
occurrence of ROP is in inverse proportion to the
gestational age and birth weight.29 It is estimated that
ROP causes visual loss in 1,300 children and severe
visual impairment in 500 children born every year in
the USA.30 With increased survival of smaller and
more premature babies, there has been an increase in
the incidence of ROP.31
During the normal development of the retina,
vascularization of the retina occurs from the optic disk
to the ora serrata from the 16th week onwards. The
nasal part of the retina is vascularized upto the ora
serrata by 36 weeks and the temporal part by full term.
Prematurity and oxygen therapy arrest this normal
angiogenesis and the peripheral retina remains
avascular. Cessation of oxygen therapy may then
trigger an abnormal angiogenesis. These abnormal
vessels may proliferate inwards into the vitreous, can
cause retinal traction and detachment.31 The disease
is classified into five stages of which stages 4 and 5
have partial or total retinal detachment respectively.
This clinically presents with leukocoria and therefore
may need imaging to exclude retinoblastoma.
ROP is usually bilateral and asymmetrical. In the
early stages, there may be microphthalmia. CT and
MR reveal retinal detachment in advanced cases.
1032 Section 9: Miscellaneous Topics

Subretinal exudates may be hyperdense on CT and CONGENITAL LESIONS OF THE EYEBALL

may show hyperintense signal on T1 and T2-weighted
images. The presence of chronic blood degradation
products like hemosiderin, suggesting old hemorr-
hage, may produce hypointense T2 signal (Figs 136.4A
and B). Calcification is not common but may be present
in advanced disease. Advanced ROP usually presents
with bilateral microphthalmia and shallow anterior
chambers. With the presence of calcification in a
microphthalmic eye, retinoblastoma is less likely as
retinoblastomas with microphthalmia is rare. 3 A
careful history and imaging findings are usually
sufficient to establish the diagnosis.
Medulloepithelioma
Medulloepithelioma is a rare embryonic tumor of the
primitive medullary epithelium, typically occurring
in children in the first decade of life.32,33 Though adult
tumors have been reported.34 They usually arise from
the ciliary body or less commonly from the iris, retina
or optic nerve. From its point of origin in the ciliary
body, the tumor may spread forward along the surface
of the iris or backwards along the surface of the retina.3
In children the tumor has to be differentiated from
retinoblastoma and in adults from uveal melanoma;
conditions which may be simulated in imaging studies
as well. CT and MRI do not help in establishing a
diagnosis, but help in locating the full extent of tumor
and in monitoring tumor recurrence.35
Coloboma
Coloboma is a congenital ocular abnormality due to
the failure of closure of the embryonic choroid fissure.
It may affect any part of the eye. Typically the defect
is inferonasal and may involve the optic nerve, retina
and choroid. Less commonly the iris and lens may be
affected. The “morning glory” anomaly is a coloboma
that involves the optic nerve disk, so called because
of the fundoscopic resemblance to that particular
flower.36,37
CT findings are related to the extent of the ocular
and optic nerve defect. The globe may be mis-shaped
and the optic nerve head widened. The latter is of
water density and is continuous with the vitreous
humor, appearing as a funnel shaped defect. There
may be thinning and eversion of the sclera at the
margin of the defect. 37 Fat and smooth muscle
heterotopia has been reported within the disk and
should not be mistaken for tumor.38 Calcification may
be seen. Anomalies like microphthalmos, encephalo-
cele and agenesis of the corpus callosum and may also
be present.37 Coloboma in one eye may be associated
with microphthalmos with cyst in the other eye.39 CT
scanning is of value, especially where corneal,
lenticular, vitreal, or other opacities hamper clinical
evaluation of the optic disk MR reveals this defect well
and has the additional advantage of showing any
associated intracranial defects better.40

A B

Figs 136.4A and B: Retinopathy of prematurity. A) Axial T1-weighted MR image and (B) axial T2-weighted image. On the right
side, the retinal detachment (note the “V” configuration of the retinal detachment) appears mildly hyperintense on T1 and isointense
on the T2-weighted images with respect to the vitreous (arrows). On the left side the retinal detachment appears very hyperintense
on T1 and isointense on T2-weighted images (thick arrows); a fluid-fluid level (curved arrow) is also appreciable, consistent with
recent bleeding. (From Galuzzi P, Hadijstillianou T, Venturi C: Leukocoria: Clinical and neuroradiological findings. Revista di
Neuroradiologia 17:61,2004. With permission from the authors and Dr Marco Leonardi, ed, Revista di Neuroradiologia)
 Chapter 136: Computed Tomography and Magnetic Resonance Imaging of the Eye and Orbit
Two conditions that may be confused with colo-
boma on CT are staphyloma of the posterior pole of
the globe and microphthalmos with cyst. Staphyloma
is a degenerative condition in which there is localized
ectasia of the globe due to thinning and weakening of
the sclera ion high myopia. Microphthalmos with cyst
is a severe malformation due to non-closure of the fetal
cleft that results in a cystic structure beside the globe
that may be much larger than the globe itself. The
differentiating feature is that the neck of the cyst where
it connects with the globe is much smaller than the
actual cyst.41
Macrophthalmos/Buphthalmos
The eyeball may be large in patients with congenital
glaucoma (buphthalmos) that may result from intra-
uterine inflammation or maldevelopment. Macroph-
thalmos is unrelated to intraocular pressure and is
frequently associated with the phakomatoses (see Fig.
136.10). Upto 50% of patients with lid and facial
involvement with neurofibromatosis have glaucoma
on the affected side. Macrophthalmos may also be seen
associated with plexiform neurofibromatosis. Upto
30% of patients with Sturge-Weber syndrome have
glaucoma and nearly two-thirds of these develop
buphthalmos.42
Anophthalmos/Microphthalmos
Microphthalmia can occur as an isolated anomaly. It
can also accompany other craniofacial abnormalities
or be associated with cyst (see above). It can be seen
with phthisis bulbi, PHPV, ROP and congenital rubella
(see Fig. 136.2).
Anophthalmos or congenital complete absence of
the globe is rare and can accompany trisomy 13 to 15,
Klinefelter syndrome or other severe craniofacial
malformations.6
OCULAR LESIONS IN ADULTS
Ocular Detachment
Ocular detachment with collection of fluid can occur
in three potential spaces. The first is the posterior
hyaloid space where the collection occurs between the
base of hyaloid and the sensory retina. The second is
the subretinal space between the sensory and pigment
layers of the retina, collections in which are referred
to as retinal detachment. The third is the supra-
1033
choroidal space where the collection is between the
choroid and the sclera causing ciliochoroidal detach-
ment.
Posterior hyaloid detachment is seen on MR and
CT scans as an intravitreal curvilinear collection
unconnected to the optic disk. When the posterior
hyaloid membrane is not detached from the disk, it
may be difficult to differentiate it from retinal
detachment.3
Retinal detachment may be rhegmatogenous or
non-rhegmatogenous depending on whether the
detachment results from a tear (rhegma) or not. The
retina is attached to the optic disk posteriorly and the
ora serrata anteriorly. Collections in the subretinal
space therefore appear shaped like the letter V on CT
and MR with the inferior point of the V meeting the
optic disk and the arms of the V extending to the ora
serrata (see Fig. 136.4). The detached retina itself may
not be seen on CT or MR, but a different intensity or
density of the subretinal collection may render it
visible on MR or CT. Subretinal fluid in exudative
retinal detachment is rich in protein and tends to be
more hyperdense or hyperintense than rhegmato-
genous subretinal collections. Ingress of fluid vitreous
into rhegmatogenous collections may cause it to be
less hyperdense or hyperintense. As retinal detach-
ment is well seen on fundoscopic examination, the role
of imaging is to exclude underlying neoplasm. MR
may help in determining etiology of retinal detach-
ment.3,43
Choroidal detachments can be either due to serous
effusions or hemorrhagic collections. Choroidal
detachment appears on CT or MR as elevation of the
choroid that stops short anterior to the optic disk at
the level of the short posterior ciliary arteries and
nerves. Choroidal detachments frequently extend into
the ciliary body anteriorly whereas retinal detach-
ments stop at the ora serrata.44 Serous collections in
the suprachoroidal space can be hypodense on CT and
MR appearance is like that of an exudate. Subtle edema
of the choroid (choroidal effusion) may be seen on CT
or MRI as a more diffuse crescentic or ring-shaped
lesion unlike the lentiform appearance of a true
detachment.3,43
Malignant Uveal Melanoma
Malignant melanoma of the uvea is the most common
primary ocular malignancy; it occurs in five to seven
1034 Section 9: Miscellaneous Topics

of every 1,000,000 people. It is most often diagnosed
in the sixth decade and is more common in males and
whites.45,46
On CT the lesions are usually hyperdense, elevated
from the globe wall and show enhancement after IV
contrast (Figs 136.5A and B).47 Melanin, due to its para-
magnetic properties, characteristically appears
hyperintense on T1-weighted images and hypointense
on T2-weighted images. The lesions therefore appear
hyperintense to vitreous on the T1 and proton density-
weighted images and on T2-weighted images they
appear hypointense to the vitreous reflecting the
melanin content of these tumors (Figs 136.5C, D and
Fig. 136.6).48,49 IV gadolinium usually aids in the diag-
nosis of these lesions that show moderate enhance-
ment. Tumors with less melanin content and amel-
anotic melanomas may be iso or slightly hyperintense
on T1-weighted images and slightly hypointense on
T2-weighted images and may be confused with
metastases.50 MR can differentiate tumor from retinal
detachment better than CT especially after infusion
of IV gadolinium (Fig. 136.6).50 CT or MR scanning
can easily detect invasion of the sclera, extension of
the tumor to the optic disk, Tenon’s capsule and extra-
ocular extension with orbital invasion.
Choroidal Hemangioma
Choroidal hemangioma is a benign vascular tumor of
the choroid. They may occur sporadically or in
association with Sturge–Weber syndrome. 48 The
circumscribed variety is usually not associated with
any other abnormality whereas the diffuse type is
usually associated with Sturge-Weber syndrome.
Associated retinal detachment concealing the tumor
may make clinical diagnosis difficult.48
CT scans show the tumor as an ill-defined lesion,
that shows strong contrast enhancement on dynamic
CT scans. On MR the lesions may be seen as hyper-
intense, or rarely isointense to the vitreous on T2-
weighted images (Fig.136.7 B). This differentiates the
lesion from uveal melanoma, which is mostly
hypointense to the vitreous on T2-weighted images.
The T1 signal of the tumor is usually iso to slightly
hyperintense to the vitreous (Fig. 136.7A). After I.V.

A B

C D

Figs 136.5A to D: Uveal melanoma on CT and MR. (A) Plain and (B) post contrast axial CT. Note hyperdense mass in the globe
wall. Contrast enhancement is minimal unlike that of choroidal hemangioma, Compare with fig. 7. On T2-weighted axial MR
(C) the lesion appears hypointense and on T1-weighted axial MR (D) the lesion is hyperintense due to the presence of melanin
 Chapter 136: Computed Tomography and Magnetic Resonance Imaging of the Eye and Orbit 1035

A A

B
B
Figs 136.6A and B: Uveal melanoma on MR.T2-weighted (A)
and T1-weighted (B) axial images. Note the T2 hypointense
and T1 hyperintense mass (single arrow in A and B). Also note
retinal detachment (arrowheads in A and B) with T1
hyperintense subretinal exudates

gadolinium injection there is usually strong contrast

enhancement, that is usually more than that of uveal
melanoma (Fig. 136.7C). Dynamic contrast enhanced
MR may show characteristic centrifugal “fill-in” of
contrast.3,48
Optic Disk Drusen
Optic disk drusen are composed of small congregates
of mucopolysaccharides and proteinaceous material
in the nerve substance of the optic disks. These can
calcify with advancing age and are bilateral in 70%.
Most patients may have no symptoms at all. On the
other hand they can present with progressive visual
loss or pseudopapilledema. CT may reveal discrete
calcification in an otherwise normal optic disk.51
EXTRAOCULAR LESIONS OF THE ORBIT
Congenital and Developmental Conditions
Dermoid/Epidermoid
Dermoid is the most common congenital cyst of the
orbit followed by the epidermoid.52 They occur due
to developmental sequestration of ectoderm in the
C
Figs 136.7A to C: Choroidal hemangioma on MR. Axial T1-
weighted (A), axial T2-weighted (B), and post-gadolinium axial
(C) images. Note mild hyperintensity in relation to vitreous in
the T1-weighted image (arrow in A). In the T2-weighted image
the lesion is again mildly hyperintense to vitreous (arrow in B).
There is strong enhancement after I.V. gadolinium (arrow in C)
sutures of the orbital bones especially the fronto-
zygomatic suture or in the fronto-ethmoidal suture.
CT reveals well-defined cystic lesions with fat-like
density, possibly due to presence of sebum
(Fig. 136.8A). Epidermoids tend to be of fluid density.
Fat-fluid levels may be seen within the lesion. Bone
erosion and remodeling is frequent because of slow
growth. No enhancement is seen unless there is rup-
ture with inflammatory reaction. On MR the lesions
may show fat-like T1 and T2 hyperintensity
(Figs 136.8B to D).52,53
1036 Section 9: Miscellaneous Topics

Cephaloceles The cephaloceles that involve the orbit or optic

Cephaloceles represent herniation of intracranial
tissue through a congenital defect in the skull and
dura. Depending on the type of contents, cephaloceles
may be classified into (i) meningoencephalocele
(herniation of brain, meninges and CSF), (ii) meningo-
celes (herniation of meninges and CSF), (iii) ence-
phalocysto-meningocele (brain, meninges and a
portion of the ventricle),(iv) atretic cephaloceles
(formes frustes consisting of dura, fibrous tissue and
degenerated brain tissue) and (v) glioceles (glial lined
cyst containing CSF). Cephaloceles may be seen in
isolation, in conjunction with other anomalies or as
part of a syndrome.54,55
pathways include sphenoidal and fronto-ethmoidal
cephaloceles.52 In sphenoidal cephaloceles the defect
occurs in the floor of the sella in the midline. The
anterior third ventricle, optic chiasm and infundi-
bulum may extend through this defect to present as a
mass in the nasopharynx (spheno-pharyngeal) or
ethmoid complex (spheno-ethmoidal). Spheno-orbital
cephaloceles may occur with spheno-orbital dys-
plasias in neurofibromatosis (type 1). This is discussed
later in the text.
Fronto-ethmoidal cephaloceles result from a lack
of normal regression of a projection of dura that
extends through the foramen cecum, between the
developing cartilage and nasal bone. The various

A B

C D

Figs 136.8A to D: Two patients with dermoids: Axial CT scan (A) of a patient with bilateral dermoid tumors (arrows). Note the
density of the tumors resembling that of orbital fat. (Courtesy, Dr (Mrs.)K. Bhattacharjee). Axial T1-weighted (B), T2-weighted (C)
and fat-suppressed proton density (D) MR images in another patient with a right-sided dermoid tumor. The lesion (arrows in figs
A, B and C) is located in a temporal subconjunctival location, a common site for this condition, and appears hyperintense on both
T1 and T2-weighted, and dark on the fat-suppressed images suggesting presence of fat. Note similarity in signal with that of
orbital fat
 Chapter 136: Computed Tomography and Magnetic Resonance Imaging of the Eye and Orbit 1037
subtypes of fronto-ethmoidal cephaloceles include the
naso-ethmoidal, naso-orbital, naso-frontal and inter-
frontal. The naso-orbital cephalocele presents as a
medial orbital mass herniating through a defect
between the ethmoid and frontal process of the maxilla
(Figs 136.9A and B). The other subtypes do not directly
result in an orbital mass but may present with hyper-
telorism.52
CT reveals the bony defect well (Figs 136.9A and
B); this may of variable size. If there is ventricular
herniation, one sign that helps detection in axial cross A
sectional imaging is the tendency of the ventricles to
“point” to the defect. Where there is no ventricular
herniation, the brain tissue may appear distorted and
drawn towards the defect. MR, especially in the
sagittal or coronal plane, shows the full extent of herni-
ated structures especially in a sphenoidal cephalocele
where the herniated optic nerves and chiasm, pituitary
gland and infundibulum, third ventricle and hypo-
thalamus are well seen. Besides, other anomalies such
as callosal dysgenesis can also be evaluated.

Neurocutaneous Syndromes
with Ocular Manifestations
Many of the neurocutaneous syndromes are associated
with ocular manifestations. Spheno-orbital dysplasia,
optic nerve glioma, plexiform neurofibroma, solitary
neurofibroma and sometimes buphthalmos are asso-
ciated with neurofibromatosis. Choroidal heman-
gioma and buphthalmos are associated with Sturge-
Weber syndrome. Retinal neuroglial hamartoma is
associated with Tuberous sclerosis. Retinal heman-
gioblastoma with retinal detachment and hemorrhage
may also be associated with von Hippel-Lindau
disease.56
Spheno-orbital dysplasia is associated with
neurofibromatosis and involves the greater sphenoid
wing unilaterally, causing a defect in the anterior wall
of the middle cranial fossa. If the defect is large, there
may be herniation of the temporal lobe and lepto-
meninges into the orbit. Associated orbital plexiform
neurofibroma, optic nerve glioma or an enlarged globe
may be seen on imaging (Figs 136.10A and B).
Inflammatory Conditions
Orbital Pseudotumor
Oribital pseudotumor is an idiopathic non-granulo-
matous non-infective orbital inflammatory disease
characterized by a painful, red and swollen eye, which
B
Figs 136.9A and B: Left naso-orbital meningoencephalocele.
Axial CT scan (A) demonstrates the herniated brain (arrow)
that extends into the orbit through a large bony defect (double
arrows) in the supero-medial wall of the orbit. There is
associated left sided microphthalmos, Coronal CT scan (B)
demonstrates the bony defect (double arrows) and mass (arrow)
in a different perspective
responds to steroid. It commonly affects adults but
may also affect children. It is the third most common
orbital pathology after Graves’ disease and lympho-
proliferative disease of the orbit.3
CT reveals the various orbital structures that are
involved, and these may be (i) The lacrimal gland; (ii)
muscle; (iii) globe; (iv) orbital apex; (v) optic nerve
sheath; (vi) orbital fat involvement and diffuse
involvement of the orbital structures.53
Lacrimal gland is the most favored site of involve-
ment and is seen as diffuse enlargement of the gland
with poorly-defined margins.57 One or more of the
extraocular muscles may show enlargement and
enhancement. The enhancement of the involved
muscle is generally more intense than normal muscle.
Both the bellies and tendons of the muscle are usually
enlarged (Figs 136.11A to C). Scleritis is seen as
thickening and enhancement of the uveoscleral coat.
1038 Section 9: Miscellaneous Topics
Figs 136.10A and B: Neurofibromatosis 1. This 10-year old
girl was brought to the ophthalmologist because the father
noticed that the right eye was “popping out”. There was no
visual complaint. The axial CT (A) shows right sided spheno-
orbital dysplasia. Note the bony defect in the right anterior wall
of the middle cranial fossa (arrow). Note macrophthalmos on
the right side (thick white arrow) and a right optic nerve glioma
(double arrows).The optic nerve is thickened and tortuous. The
optic canal is widened (arrowhead). The enhancing lesion in
the globe wall on the temporal aspect could be a choroidal
hemangioma. Coronal T1-weighted MR (B) shows optic nerve
thickening due to glioma (arrow)
Ill-defined mass may be seen involving the Tenon’s
space (Figs 136.12A to C). The retro-orbital fat involve-
ment can be seen as diffuse infiltrative lesions similar
to lymphoproliferative disease (Figs 136.12A to C).
Occasionally they may present as masses, which may
be ill defined and heterogeneous and may invade the
C
Figs 136.11A to C : Inflammatory pseudotumor of the extra-
ocular muscles: Coronal CT scan (A) shows thickening of the
extraocular muscles on the left side, predominantly involving
the levator palpebrae-superior rectus complex (arrow), the other
muscles are also involved to a lesser extent. The medial rectus
is spared. Sagittal oblique T2-weighted MR scan of the left orbit
(B) of the same patient shows involvement of the tendon of the
superior muscle complex (arrow). Coronal fat-suppressed post
contrast MR study (C) of the same patient shows strong
enhancement of the involved muscles, especially the left
superior rectus (arrow). The enhancement is more intense than
that of the normal muscles of the opposite side. (Courtesy; Dr.
(Mrs.) K. Bhattacharjee)
 Chapter 136: Computed Tomography and Magnetic Resonance Imaging of the Eye and Orbit 1039
extraorbital structures or extend intracranially. These
may be difficult to differentiate from neoplastic
processes. The orbital apex lesion may be seen as a
mass that may compress or displace the optic nerve
(Figs 136.13A to C). The Tolosa-Hunt syndrome,
consisting of orbital pseudotumor involving the
orbital apex, superior orbital fissure and cavernous
sinus, presents with painful ophthalmoplegia and
hypoaesthesia of the periorbital skin. This is seen as
orbital apicitis with ipsilateral cavernous sinus A
enlargement. The optic nerve sheath complex can be
thickened due to perineuritis . There may be enhance-
ment of the optic sheath with the nerve appearing
hypodense due to relatively less enhancement (Figs
136.12A to C). Bone destruction is rare. On MR, the
infiltrates show low intensity on T1 and T2-weighted
images with enhancement after IV gadolinium.3,53
The differential diagnosis of orbital inflammatory
disease includes Graves’ disease, lymphoproliferative
disease, cancer, metastases and leukemia (see
B
Table 136.1). Besides the above conditions, an enlarged
lacrimal gland may be seen in Sjögren’s syndrome and
sarcoidosis as well. With an ambiguous clinical
picture, biopsy of the lesions may be indicated.53

Graves’ Disease
Graves’ disease (Thyroid ophthalmopathy, endocrine
exophthalmos, dysthyroid ophthalmopathy) is an
autoimmune process involving the thyroid gland and
orbital soft tissues. It is the most common orbital
pathology causing 15 to 28% of unilateral exoph-
thalmos and 80% of bilateral exophthalmos.58,59 It
occurs most commonly in the fourth to fifth decades.
Females are more commonly affected in a 4:1 ratio.3
The orbital involvement occurs during any time of the
course of the disease when the patient may be
hyperthyroid, hypothyroid or euthyroid.60
The disease is characterized by the swelling of the
extraocular muscles with increase in the bulk of retro-
orbital fat. This occurs due to inflammatory infiltration
and vascular congestion of the soft tissues with fibrosis
of the orbital fat. CT is used to assess the extent of
extraocular muscle enlargement, fat swelling and optic
nerve compression. Swelling of the extraocular
muscles generally involves the bellies with sparing of
the tendons unlike in pseudotumor where the tendons
may be involved (Figs 136.14A and B). The enlarged
extraocular muscle bellies may compress the optic
nerve in the orbital apex where they are more crow-
ded.61 There appears to be a quantitative relationship
C
Figs 136.12A to C: Pseudotumor: Axial contrast-enhanced CT
scan (A) shows perineural enhancement of the left optic nerve
(arrow). Note infiltrates in the left orbital fat. Axial contrast-
enhanced CT scan (B) of the same patient as A and at a slightly
lower level than A, shows thickening of the left medial rectus
belly and tendon (thin white arrow). There is Tenon’s space
involvement (thick white arrow). Another section at a higher
level (C) shows the enhancing thickened Tenon’s capsule (thick
arrow)
between the extraocular muscle enlargement and optic
neuropathy with orbital fat swelling probably playing
a less significant role.62 The most commonly involved
muscle is the inferior rectus with the medial rectus
and the levator palpebrae superioris rectus muscle
complex next commonly involved, in that order. The
lateral rectus is the least commonly involved muscle
and may be normal. The degree of muscle involvement
varies from mild to severe.3 Enlargement of the medial
rectus muscle may cause remodeling of the lamina
1040 Section 9: Miscellaneous Topics
A
C
Figs 136.13A to C: Orbital apex pseudotumor. This 13-year-
old girl presented with acute onset orbital apex syndrome. On
the axial contrast-enhanced CT (A) and coronal scans (not
shown) the lesion (arrow) could not be identified confidently
and the CT scan was called normal. The axial T1-weighted MR
image (B) shows the lesion (thin white arrow) better than CT as
an isointense mass in the orbital apex. Note compression and
displacement of the adjacent optic nerve (thick white arrow).
On the post contrast MR scan (C) there is strong enhancement
of the mass (arrow). The lesion resolved completely after
treatment with steroids
papyracea.61 The enlarged muscles may show focal
low-density areas within the bellies (Fig. 136.14A). The
second most common finding in Graves’ disease is
increase in the orbital fat, which may cause bulging
of the orbital septum with stretching and straightening
of the optic nerve (Fig.136.14B). This is difficult to
quantify and in the absence of significant muscle
enlargement and a clinical setting of exophthalmos
these signs may have to be consciously looked for.
MR reveals the muscle swelling and fat hyper-
trophy well. The muscles appear hypointense on T1-
weighted images and intermediate on T2-weighted
images.
Optic Neuritis
Optic neuritis may be the first symptom in 15 to 20%
of multiple sclerosis (MS) with 35 to 40% of MS
patients developing optic neuritis in the course of the
disease. It is usually seen in young adults and is rare
B
Figs 136.14A and B: Thyroid ophthalmopathy. Axial CT scan
(A) shows swelling of the extraocular muscles predominantly
involving the bellies (thin arrow) and sparing the tendons (thick
white arrow). There is bilateral increase in orbital fat causing
bulging of the orbital septae (curved arrows). Coronal scan of
the same patient (B) shows the thickened bellies well. Note
focal low density areas within the belly of right inferior rectus
(thin white arrow)
 Chapter 136: Computed Tomography and Magnetic Resonance Imaging of the Eye and Orbit
in children. The initial attack may be more commonly
unilateral than bilateral.
CT scanning may reveal thickening of the nerve
and enhancement in acute neuritis.63,64 MR is however
more sensitive and the investigation of choice. The
optic nerve may show increased T2 signal, swelling
and enhancement after IV contrast (Figs 136.15A and
B). Use of fat suppression techniques, STIR (Short tau
inversion recovery) sequences and surface coils give
better detectability of lesions.65
Neoplasms
Lymphoproliferative Disease of the Orbit
Lymphoma of the orbit is usually of the non-
Hodgkin’s type and varies in malignant potential. The
A
Figs 136.15A and B: Optic neuritis. 15-year-old girl,
complaining of sudden onset blindness of the right eye. Axial
T2-weighted fat-suppressed MR scan (A) shows mild
hyperintensity of the affected part of the nerve which is hardly
appreciable (arrow). Post-contrast, fat-suppressed MR study
(B) shows enhancement of the posterior intraorbital optic nerve
on the right (arrow)
1041
lymphoid hyperplasias are usually benign. A large
percentage of lymphomas of the orbit are usually
indeterminate or borderline histologically. They are
usually insidious in onset and present with painless
proptosis.3 About 30 to 35% of orbital lymphoid
lesions are associated with systemic disease. Age at
presentation vary between 50 and 70 years with a
female predominance. Lesions in children are rare.3,68
On CT lymphoid tumors are characterized by their
tendency to mould themselves into existing orbital
structures without eroding bone or enlarging the orbit.
Lesions are often well-defined and involve the
extraconal space. In some cases however, margins are
less well-defined due to linear infiltrates that extend
from the bulk of the mass into adjacent potential
spaces defined by fascial planes. These band-like
densities arise from the edges of the mass and infiltrate
the retrobulbar fat. Large tumors may extend into the
intraconal space. Tumors in proximity to the globe
may wrap around the globe walls causing no inden-
tation of the sclerouveal coat (Fig. 136.16). No specific
enhancement pattern is usually seen.69,70 It may be
difficult radiologically to differentiate between
lymphoma and lymphoid hyperplasia. Presence of
bone destruction, though rare, and a homogenous
enhancement pattern, when present are seen more
often in lymphomas than in lymphoid hyperplasia,
and this finding may help in differentiating the two
in a suggestive clinical setting.71 It is also not possible
Fig. 136.16: Lymphoma. Axial contrast-enhanced CT scan
reveals bilateral masses in both the lacrimal glands. The masses
have moulded themselves along the bony orbital walls (thin
black arrows) and the globes (thick white arrows)
1042 Section 9: Miscellaneous Topics

to differentiate between Hodgkin’s from non-

Hodgkin’s lymphomas radiologically.72 The definition
of extraocular muscles may be obliterated secondary
to involvement of the extraconal space. The muscle is
rarely infiltrated. The lacrimal gland may be involved
which is seen as a diffuse enlargement of the gland
(Fig. 136.16). Less frequently the lymphomatous depo-
sits may be scattered through the entire orbit
obliterating the intraorbital spaces.
MR depicts the lymphocytic infiltrates less cons- A
picuously than CT. Signal is usually low on the T1-
weighted images. Signal on the T2-weighted images
vary according to cellular composition. In one study
only 35% tumors were hyperintense on T2-weighted
images.72 The pattern is usually low to intermediate
(Figs 136.17A and B). Enhancement after IV gadoli-
nium is variable and can be mild or strong.
Leukemia, Burkitt’s lymphoma, granulocytic
sarcoma, plasmacytoma, multiple myeloma, are some
related lesions, which should be considered in the
differential diagnosis. Burkitt’s lymphoma presents
in the pediatric age group with soft tissue mass and B
bone destruction. Orbital involvement in leukemia is
seen in children with acute myelogenous leukemia as
granulocytic sarcoma (chloroma) and in adults with Figs 136.17A and B: Lymphoma. Coronal T2-weighted MR
(A) shows bilateral extraconal lesions (thin black arrows) which
chronic lymphocytic leukemia (Fig. 136.18). Diffuse
have plastered the bony walls of the orbit. The right sided lesion
thickening of the sclera or uvea, infiltration of the has extended into the intraconal space, displacing the muscles
retrobulbar fat, optic nerve or invasion of the extra- and optic nerve. The lesions are of intermediate intensity on
ocular muscles may be seen. Lytic bone destruction the T2-weighted images. On the left side, the medial rectus is
may also be seen. Granulocytic sarcoma (chloroma) displaced medially (arrowhead) and the inferior rectus encased
with similar invasion is seen in children with acute by the mass (thick white arrow). Coronal T1-weighted MR (B)
myelogenous leukemia. Bone destruction may be shows the lesions to be isointense to muscle (arrows)
obvious. Plasmacytoma and multiple myeloma are
tumors of the elderly and present with lytic bone
destruction and soft tissue mass in the roof and lateral
wall of the orbit with extension into the frontal sinus
and orbital cavity.73

Metastatic Lesions
Approximately 10% of all orbital neoplasms are meta-
static.74 Nearly all systemic malignancies metastasize
to the orbit. Common known primary sites include
breast, lung, prostate, and melanoma.75,76 19 to 42%
of patients may present with the orbital tumor as the
initial symptom of systemic malignancy.75,76,77 This is
usually the case with such primaries as gastrointes-
tinal, renal and lung.75 Because the orbits do not have Fig. 136.18: Metastases from leukemia in a 5-year-old child.
Axial contrast enhanced CT scan. Well-defined lesions are
lymphatics, it is believed that spread of metastases to
noted in extraconal spaces (arrow). Note involvement of Tenon’s
the orbits is hematogenous. Metastases may involve space and encasement of the globe on the right (thick white
the fat, bone, lacrimal gland, choroid or less arrow)
 Chapter 136: Computed Tomography and Magnetic Resonance Imaging of the Eye and Orbit 1043
commonly, the extraocular muscles. Bilateral involve-
ment is rare.76
Metastatic lesions appear as discrete or diffuse
lesions that are usually isodense to the extraocular
muscles on CT and may show enhancement after IV
contrast. There may be involvement of the extraconal
or intraconal space or both.78,79 Bone destruction is
commonly seen. A common site for metastases seems
to be the greater wing of sphenoid with contiguous
involvement of the lateral extraconal space and the
middle cranial fossa (Figs 136.19A and B).79 Bony
lesions may be either sclerotic or lytic. Lacrimal gland A
involvement may present with gland enlargement
similar to pseudotumors or lymphoma. Metastases to
muscle can cause muscle enlargement that is often
focal and may be associated with bony changes or
mass unlike the diffuse type of enlargement seen in
Graves’ disease. However when the enlargement is
diffuse, it may be difficult to differentiate it from other
causes of muscle enlargement (Table 136.1), and a
biopsy is indicated.
B
MR usually shows the metastatic lesions to be of
low signal intensity on T1-weighted images and mode-
rate to increased intensity on T2-weighted images.80
Intraocular metastases can involve the retina or the Figs 136.19A and B: Metastases: Contrast-enhanced axial
uvea with both eyes being involved in one-third cases. CT scan (A). This patient had undergone treatment for head
Uveal metastases can mimic uveal melanoma clini- and neck malignancy 3 years prior to this study. Note extensive
cally and in imaging.3 Uveal melanoma is however, enhancing lesions in the left orbit involving the orbital apex
rarely bilateral. Choroidal metastases are diffuse encasing the optic nerve and extraocular muscles (arrow).
infiltrating lesions associated with retinal detachment. There is extension of disease into the paranasal sinuses (double
MR has been shown to be superior to CT in differen- arrows) with intracranial extension to involve the cavernous
sinus (thick white arrow) and the dura of the middle cranial
tiating uveal metastases from melanomas.49
fossa (arrowhead). Bone destruction is noted in the medial wall
In children, the most common metastases are from of orbit (bent arrow).In the axial CT scan bone window image
neuroblastoma. Ophthalmic involvement is seen in (B), lateral wall bone erosion is better appreciated (arrow)
20% of neuroblastomas and 8% of patients may
present initially with orbital metastases. 81,82 Most majority under 4 years of age. Bilateral disease is
patients present between birth and late teens, with common and present in 50%.81,83 CT shows an orbital
mass with lytic bone erosions.
Table 136.1: Causes of enlargement of the
extraocular muscles66,67 Tumors of Neural Origin
• Graves’ disease Neurogenic tumors of the orbit include neuri-
• Pseudotumor orbit lemmomas (Schwannomas), neurofibroma and
• Carotid cavernous sinus fistula plexiform and diffuse neurofibromas. Most arise from
• Extradural arteriovenous fistula
the ophthalmic division of the Vth cranial nerve but
• Metastatic disease
• Lymphoproliferative disease
may arise from the other nerves of the orbit.
• Infections Neurilemmomas are benign slow growing tumors
• Acromegaly of adults usually presenting with slow painless
• Amyloidosis proptosis. They arise from the nerve sheath Schwann
• Cysticercosis cells and constitute 1 to 6% of all orbital tumors.84,85
• Trichinosis CT usually shows a well circumscribed ovoid or fusi-
1044 Section 9: Miscellaneous Topics

form mass, which may show intralesional low density

areas of cystic degeneration or hemorrhage
(Fig. 136.20). There is moderate to marked enhance-
ment. The optic nerve may be displaced or engulfed
by the mass. MR usually shows predominantly low
to intermediate signal on T1-weighted images and
high signal on T2-weighted images. A dark rim may
be seen around the mass on T1-weighted images
(Figs 136.21A to C). Heterogenous signal within the
mass is common due to the tendency for cystic
degeneration and hemorrhage.80
Neurofibromas unlike neurilemmomas consist of A
a mixture of Schwann cells, peripheral nerve axons,
perineural cells and endoneural fibroblasts. Localized
neurofibromas occur in the third through fifth decades
with a long history of proptosis, strabismus, and
sometimes, orbital discomfort.86 They form 0.6% of
all orbital tumors.80 They commonly occur in the lacri-
mal fossa. CT shows a well-defined ovoid or rounded
mass which appears isodense to muscle and shows
moderate contrast enhancement.53 Lacrimal fossa
masses may cause remodeling of the bone and may
resemble lacrimal gland tumor. On MR the masses
are isointense to muscle on T1-weighted images and
hyperintense on T2-weighted images.80
The plexiform neurofibroma is pathognomonic of B
neurofibromatosis whereas the diffuse variety shows
variable association with neurofibromatosis. They
usually present within the first two decades of life C
often between 2 to 5 years of age.87 Histologically, the
presence of a perineural sheath differentiates the

Figs 136.21A to C: Schwannoma . (A) T1-weighted axial MR

Fig. 136.20: Schwannoma. Axial contrast-enhanced CT scan
shows a multilobulated well defined mass in the left orbit. The
lesion has fairly homogenous density with moderate
enhancement. (Courtesy, Dr (Mrs) K Bhattacharjee)
shows a well-defined orbital tumor. The signal intensity is
predominantly isointense to muscle with partial hypointense
margins. (B) Coronal T2-weighted image of the tumor shows it
to be predominantly hyperintense with hypointense margins(C).
Contrast-enhanced axial MR showing fairly homogenous
enhancement of the centre of the tumor. Margins show less
enhancement in comparision. Note displacement of the optic
nerve in A and C
 Chapter 136: Computed Tomography and Magnetic Resonance Imaging of the Eye and Orbit 1045
plexiform from the diffuse variety. Both the lesions
are characterized by diffuse infiltration to involve the
orbital structures from which they cannot be easily
differentiated. On CT, plexiform neurofibromas show
a heterogenous density due to variable sized nerve
thickenings and tumor subunits.88 The nodularity is
usually located around the optic nerve within the
intraconal fat (Figs 136.22A to C). It may extend
intracranially through the superior orbital fissure.89
MR also reveals the nodular nature of the mass and
on T1-weighted images they are of low to moderate
signal intensity. Diffuse neurofibromas appear as
more homogenous masses both on CT and MR. Both
the lesions show moderate enhancement on contrast
CT and gadolinium enhanced MR.80 A

Neoplasms of the Optic Nerve

Optic nerve gliomas are commonly tumors of children B
occurring before age 10. 50% of them are associated
with neurofibromatosis type 1 (NF1). Bilateral tumors
are a hallmark of NF1. The tumor causes fusiform
enlargement of the optic nerve that is completely
invested by the dura. If they extend through the optic
canal, the tumor may have a dumbbell shape.
Intracranial extension to involve the intracranial optic
nerve and the chiasm is less common.90
CT shows the enlarged, fusiform and buckled
intraorbital portion of the nerve that is usually
isodense with the brain (see Figs 136.10). There may
be slight to moderate enhancement after IV contrast
injection. There may be enlargement of the optic canal
if the intracanalicular optic nerve is involved.
MR allows optimal assessment of the tumor. The
tumor is slightly hypointense on T1-weighted images,
whereas on T2-weighted images the tumor is slightly
hyperintense. Slight to marked enhancement may be
seen (Figs 136.23A to C) .65
Optic nerve sheath meningiomas are commoner
in women between the age of 35 to 50 years. They may
be associated with Neurofibromatosis type 2. Intra-
orbital optic nerve involvement is more common than
involvement of the intracanalicular portion. On CT
circumferential involvement of the nerve sheath
causes a tubular configuration of the nerve that C
appears embedded in the tumor. There is usually
strong enhancement of the tumor with the central Figs 136.22A to C: Plexiform neurofibroma: Axial CT scans
(A & B) show an irregular multinodular mass in the right orbit
nerve appearing hypodense , the so called “railroad causing mild proptosis (arrow in A). The optic nerve is encased
track” sign. Plaque-like, linear or globular calcifi- (arrow in B). The multinodularity is better appreciated on the
cations are common which make CT more appropriate coronal CT scan (C). (Courtesy Dr (Mrs) K Bhattacharjee)
1046 Section 9: Miscellaneous Topics
C
Figs 136.23A to C: Optic nerve glioma on MR, post-operative
status: (A) Axial T1-weighted MR scan shows residual tumor
involving the right intracanalicular and intracranial optic nerve.
The mass is isointense to brain. Note widening of the optic
canal (arrows). (B) Coronal T1-weighted MR shows the enlarged
intracranial optic nerve involvement on the right (arrow). Note
normal intracranial optic nerve on the left (thick arrow). (C) Post-
contrast fat-suppressed image shows moderate inhomogenous
enhancement
for their detection. When the intracanalicular nerve is
involved, the optic canal may be widened with or
without hyperosteosis of the margins of the canal.
Tumors causing focal and fusiform enlargement of the
nerve are also known. MR shows the tumor to be
slightly hypointense on T1-weighted images and
slightly hyperintense to brain on T2-weighted images
(Figs 136.24A to C). Small calcifications that may be
vital in establishing a diagnosis may be missed on MR.
Dense calcifications may cause the tumor to be
hypointense on both T1 and T2-weighted images.65
C
Figs 136.24A to C: Meningioma of the optic nerve on MR: (A)
T1-weighted coronal MR shows thickening of the left optic nerve
(arrow). (B) Coronal fat-suppressed contrast-enhanced T1-
weighted MR shows strong enhancement of the thickened optic
nerve (arrow). (C) Axial contrast-enhanced T1-weighted fat-
suppressed image shows the thickened and enhancing nerve
sheath (arrow). Note central non-enhancing nerve in the
posterior aspect of the tumor, the basis of the “railroad track”
sign
 Chapter 136: Computed Tomography and Magnetic Resonance Imaging of the Eye and Orbit
Rhabdomyosarcoma
Rhabdomyosarcoma represents a malignant tumor of
the skeletal muscle and is the most common primary
orbital malignant tumor of childhood. Mean age at
presentation is 7 to 8 years.80 In the head and neck,
rhabdomyosarcomas can affect the orbit, naso-
pharynx, oropharynx, paranasal sinuses and the
temporal bone. Four histological subtypes are seen
namely the embryonal, botyroid, alveolar and
pleomorphic. The embryonal type is the most common
accounting for 67 to 72 % of all types. The embryonal
type most commonly affects the orbital soft tissues
whereas the non-embryonal type affects the extra-
ocular muscles.91,92 Most lesions arise from behind the
globe (50%). The rest arise either above, in the
temporal or nasal aspect of the globe.80 Though CT
and MRI lack sensitivity, extent of tumor is assessed
well. On CT appearances may vary from a relatively
well-defined tumor to diffuse infiltrative forms.
Invasion to the surrounding structures, namely the
paranasal sinuses, intracranial spaces, infratemporal
fossa or nasopharynx may be seen in advanced cases.
The lesion is usually isodense to muscle and shows
homogenous contrast enhancement. Lytic bone
destruction is better visualized on CT than on MRI.
Intracranial extension may be associated with foramen
or fissure widening (Fig. 136.25). MR usually shows
the full extent of tumor better than CT and is the
preferred modality.93 Tumors have low signal on T1-
weighted images and intermediate to high signal on
T2-weighted images. There is homogenous enhance-
ment of the mass after IV gadolinium.94
INFECTIONS/INFESTATIONS OF THE ORBIT
Orbital and Periorbtial Cellulitis
Orbital and periorbital (preseptal) cellulitis most
commonly results from adjacent paranasal sinus
infection. Infection can spread directly across the bone
through dehiscences, especially from the ethmoid
sinuses through the lamina papyracea or through
associated retrograde thrombophlebitis. It can also
result from dental sepsis, trauma or primary infections
of the face and pharynx.
The orbital septum separates the soft tissues of the
eyelid from the orbital contents and is attached to the
orbital rim. It is a natural barrier to spread of disease.
When the infection is limited by the orbital septum it
is called a preseptal or periorbital cellulitis. Spread of
1047
Fig. 136.25: Rhabdomyosarcoma of the orbit in a 2-day-old
baby: Axial CT scan shows a mass of soft tissue density filling
most of the left orbit. There is pressure effect on the globe.
Note widening of the superior orbital fissure (arrows) due to
intracranial extension
infection posterior to the septum causes a postseptal
cellulitis or orbital cellulitis .95 This is a more dangerous
vision threatening development and the muscles,
retrobulbar fat and optic nerve may be involved.
Spread of infection under the periosteum may cause
a subperiosteal phlegmon or abscess. There may be
thrombosis of the ophthalmic vein and subsequently
the cavernous sinus. Intracranial spread can cause
epidural or subdural empyema from contiguous
spread of disease or may result in brain abscess from
spread through the draining valveless veins.
Extent of disease is delineated well on CT.
Differentiation of preseptal from post septal cellulitis
is possible on CT whereas this may be difficult to
differentiate on clinical grounds alone. CT can identify
abscesses and fluid collection, which may require
surgical intervention. Preseptal soft tissue swelling
with lid and conjunctival swelling is noted in peri-
orbital cellulitis (Fig. 136.39). Bulging of the medial
orbital wall or edema of the medial compartment
indicates post-septal involvement. Intraconal spread
of infection shows muscle thickening or fat streakiness
and dirtyness. Subperiosteal phlegmon presents as a
soft tissue mass in the extraconal space causing lateral
displacement of the medial rectus. Low-density areas
with peripheral enhancement may indicate a frank
abscess 53 (Fig 136.26). Because it demonstrates fluid,
soft tissue component of the inflammatory process and
bone involvement, CT remains the investigation of
choice for orbital and periorbital cellulitis.
1048 Section 9: Miscellaneous Topics

Fig. 136.26: Axial contrast-enhanced CT scan of ethmoid A

sinusitis with orbital spread of infection in a ten-year-old child.
Note extraconal abscess appearing hypodense (thin white
arrow). There is involvement of the medial rectus, which appears
swollen (thick white arrow). Note dehiscence of lamina
papyracea seen as discontinuity of the bone

Orbital Cysticercosis
Orbital cysticercosis results from infestation by the
larval form of the pork tapeworm, Taenia solium. It is
a commoner disease than thought earlier and can affect
any part of the orbit. Muscular or subconjunctival
involvement is common. The eyelid, subretinal space, B
optic nerve, intra or extraconal spaces or lacrimal Figs 136.27A and B: Two different patients with cysticercii:
gland may be involved.96,97 The lesion is usually visua- (A) Axial CT scan shows intraocular cysticercus (arrow) as a
lized on CT scan as a cystic lesion with hypodense subtle cystic lesion attached to the globe wall. (B) Axial CT of a
contents. The scolex may be identified as an eccentric different patient showing a cysticercus in the left lateral rectus
hyperdense nodule and when seen may identify this (arrow). Note the eccentric, hyperdense, nodular scolex and
condition obviating the need for further investigation. the swollen and enhancing lateral rectus which has indented
the globe
The cyst is most commonly seen in the extraocular
muscles (Figs 136.27A and B). A subconjunctival loca-
proptosis. The sphenoid sinus is less commonly
tion may also be seen on CT (Figs 136.27A and B).
involved, but when affected may cause blindness and
Occasionally they are identified within the globe. The
cranial nerve palsies due to orbital apex compression.
lesions may show peripheral enhancement.97 Some-
CT and MR are complimentary in the assessment of
times only the myositis may be picked up on CT that
mucocele. CT demonstrates the expanded sinus and
may pose a differential diagnosis problem
thinned out bony walls, which may eventually erode
(Table 136.1). MRI also shows the lesion well. 97
away (Fig. 136.28). Contents are often homogenous
Usually the cysts appear well defined and hyper-
with variable density. Contrast enhancement is absent.
intense on T2-weighted images and hypointense on
The walls may enhance in acutely infected muco-
T1-weighted images. Associated lesions can some-
celes.98 On MR the contents may show variable signal
times be seen in the brain that may also aid in differen-
intensity due to different protein concentration.
tial diagnosis.
VASCULAR LESIONS
Mucocele
Hemangioma
A mucocele results from trapped mucus secretions in
a paranasal sinus, causing expansion of the sinus in The angiomas represent a large group of hamarto-
the process. The expanded sinus can cause mass effect matous malformations. They include capillary heman-
on the orbital structures. Most commonly the frontal gioma, cavernous hemangioma, lymphangioma,
and ethmoid sinuses are involved, causing painless venous angioma and hemangiolymphangioma.
 Chapter 136: Computed Tomography and Magnetic Resonance Imaging of the Eye and Orbit 1049

Fig. 136.28: Axial CT scan of seven-year old boy with mucocele

of the ethmoid sinus. Note expansion of the bony walls (black
arrows) with encroachment of the orbital structures and resultant B
proptosis. There is erosion of the medial walls of the sinus (thick
white arrow)

Cavernous Hemangioma
Cavernous hemangioma is the most common retro-
bulbar mass lesion in the adult, excluding inflam-
matory pseudotumor and lymphoma. It consists of
large vascular channels lined by endothelial cells with
slow blood flow within it. Clinically, the commonest
presentation is slow onset painless proptosis. It’s most
common location is intraconal. Extraconal extension
is uncommon. On CT the mass is usually well defined,
isodense to muscle and intraconal. There is usually
strong, persistent enhancement due to the vascular
channels with slow flow (Figs 136.29A and B). Pre-
sence of phleboliths, which are seen as round calcified
bodies, is pathognomonic. The globe wall, even when
abutted is usually not deformed, as these lesions are
soft. Bone remodelling can occur with long standing
lesions. On MR, the lesions are well-defined and iso-
intense to muscle on T1-weighted images. They are
slightly to markedly hyperintense on T2-weighted
images. High signal on T1-weighted images may be
evident if there is thrombus within the lesion. As with
CT there is strong enhancement after intravenous
gadolinium contrast.43,99
Capillary Hemangioma
Capillary hemangiomas are seen in infants and are
apparent clinically as they involve the periorbital
tissues and eyelids. They grow rapidly in the first year
or two and subsequently involute. Unlike cavernous
hemangiomas they are infiltrative lesions and have
Figs 136.29A and B: Cavernous hemangioma: (A) Axial non-
contrast CT shows well defined intraconal mass which is
isodense to muscle (arrow). There is proptosis and though the
globe is abutted, it is not indented. (B) Axial contrast-enhanced
CT of the same patient shows strong homogenous enhance-
ment of the mass
high flow within them. CT reveals the infiltrating mass
with irregular lobulations that shows strong enhance-
ment after intravenous contrast. On MR the lesions
are ill-defined, infiltrating, lobulated and show
variable signal due to flow effects. Areas of signal void,
due to high-flow vascular channels are a key finding.
MR angiography or gradient echo sequences may
depict these flow effects better.43,99
Lymphangioma
Lymphangiomas occur in the pediatric age group.
They consist of clear fluid channels arising from
lymphoid follicles.100 Though they may present with
painless proptosis, the propensity to intermittent
1050 Section 9: Miscellaneous Topics

hemorrhage may lead to sudden proptosis. These are

A
infiltrating tumors that may involve the extraconal
spaces, or may extend into the intraconal space. CT
and MR show heterogenous density or signal intensity
due to the presence of clear fluid spaces and areas of
hemorrhage. MR shows the evidence of fresh or
chronic blood products. No flow voids are seen on
MR unlike in the capillary hemangioma. Enhancement
is not as strong and no enlarged vessels are usually
apparent. Phleboliths are absent in the pure form of
lymphangioma, but may be seen in the capillary
component of the mixed form known as hemangio-
lymphangioma.

Venous Varix
BA
The venous varix represents a postcapillary dilatation
of venous channels. These are usually small at rest
and can increase in size with increased venous
pressure.101 Intermittent exophthalmos usually preci-
pitated by activities that increase venous pressure, like
coughing, is the usual presentation. On imaging, this
increase in size can be demonstrated by asking the
patient to do a Valsalva maneuver or by jugular
compression. Sometimes simple hyperextension of the
head during coronal scanning may demonstrate this
increase. Presence of calcified phleboliths can
sometimes be seen on CT (Figs 136.30A and B). Figs 136.30A and B: Venous varix: Axial CT with the patient
Unclotted stagnant blood within the venous channels lying supine on the table (A) shows the irregular mass lesion in
is usually isointense to muscle on T1-weighted images the lateral aspect of the right orbit with a phlebolith of calcific
on MR. Orbital varices can also spontaneously density (arrow). Coronal CT (B) with the patient lying prone
thrombose, when they appear as constant masses shows increase in size of the lesion to more than three times
whose signal characteristics indicate clot.102 its size in (A)

called the dural arteriovenous malformation; the latter

Carotid Cavernous Fistula
The carotid cavernous fistula (CCF) is an abnormal
communication between the carotid arterial system
with the cavernous sinus. They are broadly classified
as direct or indirect.
The direct CCF results from a direct communi-
cation between the intracavernous part of the internal
carotid artery and the cavernous sinus. The usual
cause is trauma. It may also result from spontaneous
rupture of an intracavernous internal carotid artery
aneurysm or may be iatrogenic. Rarely, it may also
result from weakened arterial walls in connective
tissue disorders such as Ehlers-Danlos syndrome or
osteogenesis imperfecta.103,104 The indirect CCF results
from communication of the cavernous sinus with the
meningeal branches of the intracavernous internal
carotid artery, external carotid artery or both. Also
type is a lower flow lesion that tends to occur gradually
in middle-aged people.53
Although angiography remains the definitive
method to demonstrate these lesions (Fig. 136.31D),
non-invasive imaging is often the initial investigation
especially in clinically subtle cases. On CT the findings
tend to be non-specific. They are enlargement of the
ipsilateral cavernous sinus, enlargement and tortuo-
sity of the superior ophthalmic vein, enlargement of
the extraocular muscles and proptosis (Fig. 136.31A).53
These findings may be subtle and may be missed by
the casual observer if blinded to the history. It is also
worthwhile to remember that venous drainage of CCF
may vary and the superior ophthalmic vein dilatation
may not be seen.
In addition to the findings on CT, MR reveals flow
voids within the cavernous sinus and superior
 Chapter 136: Computed Tomography and Magnetic Resonance Imaging of the Eye and Orbit
ophthalmic vein due to arterialized flow (Fig. 136.31B).
The intercavernous venous channels can also dilate
and may be seen on MR images.105 The lateral wall of
the affected cavernous sinus may be convex. Indirect
CCFs may be more difficult to demonstrate on MR.
Additionally, MR angiography may show the fistula
and extension into the inferior petrosal sinuses (Fig.
136.31C).106
Radiological endovascular interventional tech-
niques are the treatment of choice at present.
Endovascular repair of the fistula involves the use of
1051
detachable balloons or coils which effectively close the
fistula.107
Orbital Trauma
The work-up of the orbital trauma patient may require
plain X-rays, CT or MRI. Several views of plain X-rays
may be required to assess the orbital trauma, espe-
cially in more complex orbito-facial injuries. Where
the fractures and soft tissue injuries are more complex,
CT scans are better in evaluating the same. Tradi-
tionally these are obtained in the coronal and axial

A B

C D

Figs 136.31A to D: Carotid-cavernous fistula. (A) Coronal CT scan reveals non-specific enlargement of the right extraocular
muscles (thin arrows).Note dilated superior ophthalmic vein (thick arrow). (B) Axial T2-weighted MR of the same patient as (A)
shows ‘flow voids’ within the cavernous sinus region (arrow). Note dilated superior ophthalmic vein (thick arrow). (C) MR angiogram
of the same patient. There is arterialized flow within the right cavernous sinus (arrow). Note arterialized flow within the superior
ophthalmic vein (double arrows) and inferior petrosal sinus (thick arrow). (D) Digital subtraction angiogram of the same patient
shows the fistulous communication and filling up of the cavernous sinus (arrow) with arterialized flow in the ophthalmic veins
(thick arrow)
1052 Section 9: Miscellaneous Topics

planes. Recent advances in CT technology allow

isotropic acquisition in axial planes and excellent
reconstructions in another plane. This is useful in
difficult trauma patients. MR may be required to
assess trauma to the globe and optic nerve.108

Orbital Fractures
Isolated orbital fractures may involve any part of the
orbit but the inferior orbital rim, superior orbital rim
and roof of the orbit are commonly involved. If the
sinuses are involved, there may be pneumocephalus
and/or surgical emphysema, subperiosteal hema-
toma, extradural or subdural bleed and cerebral
contusions. These are adequately picked up on CT
scans. Coronal scans in addition to axial scans help in Fig. 136.32: Blow-out fracture: Axial CT scan.There is a blow-
detection of these injuries.109 out fracture of the left orbit (arrow). Note herniation of the orbital
The blow-out fracture usually results from blunt fat and inferior rectus muscle
trauma to the orbit, possibly due to increased intra-
orbital pressure transmitted to the bony walls. It may
involve the floor of the orbit or the lamina papyracea
in the medial wall. Herniation of orbital fat or
extraocular muscles through the fracture site can give
rise to diplopia, enophthalmos or gaze limitations. CT
scans show the fracture adequately, especially those
subtle fractures which are missed on plain X-rays. It
also allows more detailed assessment of the fracture
for size, extent and nature of comminution. CT can
demonstrate herniation of the fat and extraocular
muscles and orbital emphysema (Fig. 136.32). It must
be remembered that clinical signs of entrapment may
be present even without CT evidence of muscle Fig. 136.33: Orbital apex fracture: Coronal CT scan shows the
bony fractured fragment encroaching the left optic canal (arrow)
herniation as few muscle fibers may be entrapped
within the fracture.
Fractures of the apex of the orbit and optic canal
may be isolated or associated with Le Fort type III
fractures. They may extend into the sphenoid sinus,
which may show a fluid level on CT or MR (Fig.
136.33). The optic nerve is invariably injured in these
types of fractures. CT reveals the fracture and may
show the optic nerve swelling or transaction (Fig.
136.34). MR better evaluates optic nerve injury along
with injury to the optic chiasm and tract. The nerve
edema and contusions show increased T2 signal.
Hemorrhagic changes can also be evaluated by MR
(Figs 136.35A and B).108,109 Fig. 136.34: Optic nerve avulsion injury on CT: Note the irregular
appearing optic nerve with heterogenous density (arrow). There
More complex fractures of the facio-maxillary
is a large Tenon’s capsule hematoma (thick arrow)
bones can involve the orbits. Fractures of the zygo-
maticomaxillary complex, Le Fort fractures and naso-
ethmoidal complex fractures all involve the orbit. CT of these fractures as they are usually associated with
is the modality of choice for the detailed assessment various degrees of comminution.108
 Chapter 136: Computed Tomography and Magnetic Resonance Imaging of the Eye and Orbit 1053

Figs 136.35A and B: MR of two patients with optic nerve injury.

(A) Coronal T2-weighted MR at the level of the optic canal shows
increased signal in the intracanalicular part of the right optic
nerve (arrow). Compare with the normal intracanalicular optic
nerve on the left (arrowhead). Note the fracture of the left optic
canal (thick arrow). It is difficult to visualize on this MR, but is
visible due to mucosal high signal in the sphenoid sinus. (B)
Fat-suppressed T1-weighted MR of a different patient who went
blind after a road traffic accident sustained a month before,
shows a hyperintense lesion in the intraorbital (R) optic nerve
(arrow) suggesting a hemorrhagic contusion
Figs 136.36A and B: Intraocular foreign body with globe rupture
in a patient with road traffic accident: (A) Axial CT scan shows
irregular globe walls due to rupture. Hyperdense foreign body
(glass pieces) noted (arrow). Note retinal detachment
(arrowhead) with hyperdense vitreous hemorrhage.(B) Axial CT
at a slightly higher level than (A) shows more intraocular foreign
bodies (arrows)

Soft Tissue Injuries X-rays may determine the presence of foreign bodies,
only MR or CT can assess the precise location of the
Injuries to the globe can be in the form of hemorrhage,
foreign body in relation to the soft tissues of the orbit
foreign body, lens subluxation or dislocation, retinal
(Figs 136.36A and B). Besides, other associated soft
and choroidal detachment and eyeball rupture.
tissue injuries can also be assessed. CT is the initial
Hemorrhage can occur in the anterior or vitreous
investigation of choice as it can clearly delineate
chambers causing increased density due to the
fractures and document the presence of small or
presence of blood. A subluxed or dislocated lens is
retained opaque foreign bodies. Metallic foreign
easily picked up on CT as the lens is normally hyper-
bodies can be identified on CT by the “spray artifacts”
dense in relation to the vitreous. Decubitus positioning
that are associated with the same (Figs 136.37A to C).
may help in certain cases where the diagnosis is
Organic foreign bodies may include wood, dirt or
doubtful. Globe rupture causes it to lose its normal
vegetable matter. It is important to remember that
shape giving a crumpled appearance and it appears
wood may appear of varied density and may even be
small (Figs 136.36A and B).
hypodense enough to resemble air.110 MR should be
done only after CT or X-ray has excluded metallic
Foreign Bodies
foreign body. It may aid in the diagnosis of wood or
Foreign bodies in the orbit can be assessed by plain other foreign bodies and help in optic nerve or globe
X-rays, ultrasound, CT or MR. Even though plain injury.109
1054 Section 9: Miscellaneous Topics

LACRIMAL GLAND PATHOLOGY

Lacrimal gland masses occupy the anterior superior
lateral aspect of the orbit as they arise from the lacrimal
fossa. Most are clinically palpable and displace the
globe inferomedially.
Approximately half of all lacrimal gland tumors
are epithelial proliferations, with the other half being
inflammatory or lymphoproliferative lesions. Out of
the epithelial proliferations half are pleomorphic
adenomas (also known as benign mixed tumor). The
rest are malignant tumors such as adenoid cystic carci-
noma, mucoepidermoid carcinoma, squamous cell
carcinoma and anaplastic carcinoma.80
A No specific feature in CT or MR helps in discerning
the etiological diagnosis of lacrimal gland lesions, or
benign from malignant, even if intravenous contrast
is used.102,111 Some features may help in narrowing
down the differential diagnosis. The status of the adja-
cent bone is to be carefully evaluated, which means
that CT is the investigation of choice to do this. Bony
remodeling is usually a feature of benign lesions such
as pleomorphic adnenoma (Fig. 136.38). Lytic bone
destruction is seen with malignant lesions. Bone
erosion (as opposed to destruction) suggests either
benign epithelial tumor or lymphoproliferative
B lesions.43,80 Lymphoproliferative lesions mold them-
selves along the bony orbital wall and globe (see
Fig. 136.16). The globe wall is usually indented by
tumors. Well-defined tumors may be benign or early
malignant lesions. Infiltrative lesions are more likely

Figs 137.37A to C: Metallic foreign body with multiple orbital

injuries. This unfortunate young man fell from a tree on a piece
of farm equipment, the handle of which was dislodged into the
right orbital region. (A) Digital radiograph of the skull shows the
metallic handle lodged in the head overlying the orbit, looking
as if it may have penetrated it. (B) Axial bone window CT scans
show the foreign body to be actually lodged outside the orbit in
the infratemporal fossa. The object had penetrated the middle
cranial fossa to cause injury to the temporal lobe. There are
fractures of the lateral wall of the orbit. Note “spray” artifacts
from the metallic foreign body (arrows). (C) Coronal CT scan of Fig. 136.38: Pleomorphic adenoma: Axial contrast enhanced
the same patient shows extensive orbital injury with multiple CT scan shows well defined mass lesion involving the right
fractures (arrows), orbital hematomas (thick arrow) and fat lacrimal gland (arrow). No bone erosion or remodeling is noted
lacerations causing “dirtyness” of the fat (Courtesy: Dr (Mrs) K Bhattacharjee)
 Chapter 136: Computed Tomography and Magnetic Resonance Imaging of the Eye and Orbit 1055
to represent malignant pathology. Encasement and
invasion of the extraocular muscles, extension into the
cavernous sinus or intracranial spaces usually are
features of malignant tumors. MR features of most of
the lacrimal lesions have markedly varied intensity
patterns. It appears that MR does not add any speci-
ficity to the non-specific CT patterns in evaluating
lacrimal lesions.43 Bilateral masses suggest inflam-
matory conditions (such as sarcoidosis, Graves’
disease, Sjögren’s syndrome) or lymphoproliferative
disorders and occasionally pseudotumor.
Despite the non-specificity of imaging, CT or MR
helps in delineating the full extent of the tumor and
involvement of adjacent structures. CT helps in identi-
fying bony changes and can provide a clue to the Fig. 136.39: Acute dacryocystitis. Axial contrast enhanced CT
etiological diagnosis. scan shows swelling of the left lacrimal sac (arrow). The walls
show regular enhancement and the contents are hypodense.
Lesions of the Lacrimal Sac and Duct Note preseptal soft tissue swelling due to periorbital cellulitis
The lacrimal drainage system consists of the upper
and lower canaliculus, common canaliculus, lacrimal
chronic dacryocystitis that irrigates freely, blood
sac and lacrimal duct. The lacrimal sac is located in
stained tears or epistaxis, all of which should raise the
the lacrimal fossa of the lacrimal bone and the naso-
possibility of malignancy.117 CT shows a mass in the
lacrimal duct courses through the bony nasolacrimal
medial canthus. A tumor should be suspected on CT
canal.112
if the lesion is isodense to muscle. Irregular margins
Acute or subacute dacryocystitis results from
and large lesions with bone destruction usually
bacterial, viral or fungal infection of the lacrimal sac
indicate malignancy. MR imaging usually adds no
and duct. On CT, it can be seen as enlargement of the
information to narrow the etiological diagnosis. It is
lacrimal sac as a well-defined cystic mass with central
useful however to differentiate fluid collections from
hypodense contents and enhancing walls. There may
solid masses. Fluid appears hyperintense on T2-
be inflammatory swelling in the soft tissues of the lid
weighted images while solid masses appear inter-
and face (Fig. 136.39). On MRI the mass shows low
mediate in signal intensity. It may also be of help to
intensity on T1-weighted images and high signal on
delineate tumor extension into the duct and surroun-
T2-weighted images.112
ding anatomy. IV gadolinium may help in differen-
Chronic infection may lead to stricture at the
tiating solid tumor and cyst.112
junction of the duct and sac and a dacryocele may
result. This can be seen on CT as a dilated sac with
LESIONS OF THE BONY ORBIT
smooth walls and hypodense contents without any
surrounding soft tissue changes.113 Dacryoliths may CT best assesses the Bony orbit as it detects bony
be seen in patients with dacryocystitis especially with pathology better than MR. The most common bone
actinomycosis or fungal infection.114,115 CT shows lesions in adults are metastases. This has been
hyperdense lesions within the hypodense fluid of the discussed in the section on orbital metastases. Primary
sac. bone tumors are rare, but hemangioma, aneurysmal
Tumors of the lacrimal sac and duct are un- bone cyst, giant cell tumor, osteoblastoma, osteo-
common. Malignant tumors are more common with sarcoma, chondrosarcoma and Ewing’s sarcoma are
one large series reporting 90% malignant tumors.116 known to occur.118
Benign tumors include polyps, fibromas, papillomas Langerhans’ cell histiocytosis (Histiocytosis-X)
or granulomatous disease that may simulate tumor. may involve the bony orbit. The frontal bone of the
Malignant tumors include squamous cell carcinoma, orbit and the lateral wall are the most favored sites of
muco-epidermoid carcinoma, adenocarcinoma, orbital involvement. Well-circumscribed bone
adenoid cystic carcinoma and lymphoma. 112,117 destruction with replacement by disease of soft tissue
Imaging is indicated if there is a mass in the lacrimal density without new bone formation is typical119
sac area in a patient with epiphora. Patients may have (Fig. 136.40).
1056 Section 9: Miscellaneous Topics

hyperintensity on T2-weighted images. Contrast

enhancement may or may not be present (Figs 136.41A
and B).122,123 Other rare lesions of the optic chiasm
include glioblastoma multiforme, gliomatosis cerebri,
cavernous hemangioma, hamartoma, lymphoma,
arteriovenous malformation,infection and demyeli-
nation (Figs 136.42A and B). The multiplanar capa-

Fig. 136.40: Langerhan’s cell histiocytosis: Axial CT scan of

the orbits show a mass of soft tissue density involving the lateral
wall of the left orbit, a site favored by this condition, causing
well defined bone destruction (arrow)

Fibrous dysplasia of bone can involve any part of

the craniofacial skeleton. It frequently involves the
bones around the orbit causing bone expansion,
proptosis and foraminal narrowing. The orbit may be
secondarily involved by a mucocele, which may result
from fibrous dysplasia.120,121 CT appearance is typical
with ground glass appearance of the expanded bone.
Foraminal narrowing and the full extent of disease can
be assessed.

IMAGING EVALUATION OF THE

INTRACRANIAL VISUAL PATHWAY B

The intracranial visual pathway consists of the

intracranial part of the optic nerves, optic chiasm, optic
tracts, radiations and visual cortex. CT or MR images
lesions of these areas and recent technical advances
have increased the sensitivity of detecting and deter-
mining the location and full extent of these lesions.
Lesions of the optic chiasm can be primary or
secondary. The most common primary lesion is the
chiasmatic/hypothalamic glioma. They are childhood
tumors and 75% occur in the first decade of life. Due
to the anatomical proximity of the hypothalamus and
the chiasm, it is often not possible to determine the
site of origin and therefore they are called chiasmatic/
hypothalamic gliomas. They are slow growing tumors Figs 136.41A and B: Chiasmatic/hypothalamic glioma: (A).
and frequently large on presentation. They are iso to Axial T1-weighted MR shows a suprasellar extension of the
hypothalamic mass (arrow) with optic chiasm involvement (thick
hypodense on CT with mild to moderate contrast
arrow).There is hydrocephalus (arrowhead) due to extension
enhancement. Cyst formation may be seen in larger of the mass into the anterior third ventricle, with resultant
tumors. Calcification is rare. On MR, it is easier to foramen of Monro obstruction (Not shown) (B). A slightly inferior
appreciate the full extent of these tumors. T1-weighted section shows the intracanalicular and intracranial optic nerve
images reveal an iso to hypointense lesion with slight involvement (arrows)
 Chapter 136: Computed Tomography and Magnetic Resonance Imaging of the Eye and Orbit 1057

B
Figs 136.42A and B: Sudden onset loss of vision: (A) Coronal
T2-weighted MR image of the optic chiasm shows increased
signal within it (arrows). (B) Axial T2-weighted MR shows the
same within the optic chiasm (arrows). Suspected demyelination

bility, superior contrast resolution and lack of beam

hardening artefacts make MR the modality of choice
in the assessment of the optic chiasm.
Many different lesions arising from the sella,
suprasellar and parasellar regions may secondarily B
affect the optic chiasm. Some of the more common
lesions include suprasellar extension of pituitary
macroadenoma, meningioma, craniopharyngioma
and aneurysm. Other common lesions are optico-
chiasmatic tuberculosis and tuberculoma (Figs
136.43A and B), metastases, chordoma, sarcoidosis,
pituitary abscess, tumor like conditions such as
Langerhan’s cell histiocytosis and hamartoma. Cystic Figs136.43A and B: Tuberculoma. This 30-year-old female
lesions include Rathke’s cleft cyst, arachnoid cyst, patient was treated for tubercular meningitis and arachnoiditis
8 months ago. The CT scan (not shown) done at that time was
epidermoid, dermoid and teratomas.65 Though CT
normal. (A) Contrast-enhanced coronal T1-weighted MR shows
picks up most of these lesions, MR is the investigation enhancing tuberculoma involving the optic chiasm (arrow). (B)
modality of choice. Contrast-enhanced sagittal T1-weighted MR scan showing the
Lesions involving the optic tract are inflammation, tuberculoma involving the optic chiasm and tract (arrow). Note
demyelination and primary tumors such as glioma. other enhancing tuberculomas in the suprasellar and ambient
Lesions in the temporal lobes, cerebral peduncles and cisterns
1058 Section 9: Miscellaneous Topics
suprasellar areas may secondarily involve the optic
tracts. Anterior or posterior choroidal artery infarcts
involve the optic tracts. Vascular lesions such as caver-
nous hemangiomas and infestations such as cysticercii
may also involve the optic tracts (Figs 136.44A and
B). Post-traumatic hemorrhage may rarely be
strategically located in the optic tract to cause visual
symptoms.
Lesions in the geniculate body are rare. Contiguous
spread from tumor can occur from adjacent structures
such as the thalamus. Infarcts and demyelination may
also involve the geniculate bodies.
A A
Figs 136.44A and B: Cysticercii of the right optic tract: Sudden
onset difficulty in vision. (A) Axial T2-weighted MR shows
hyperintense cyst in the right optic tract with mild hyperintense
perifocal edema (arrow). (B) Coronal T1-weighted MR shows
the hypointense cysts which show a conglomerate appearance
(arrowhead). There is an eccentric mural nodule (arrow), the
scolex
Tumors, infarcts, demyelination, trauma and
infection can involve the optic radiations and the
visual cortex in the occipital lobes (Figs 136.45A
and B). MR is the investigation of choice as it is not
prone to beam hardening artifacts and lesions in the
temporal lobe can be assessed as well. Demyelinating
lesions such as plaques of multiple sclerosis may be
missed on CT scanning. Vascular lesions such as
B
Figs 136.45A and B: Infarct in the visual cortex. Sudden onset
homonymous hemianopia in a 34 year-old lady. Axial T2-
weighted MR (A) shows a hyperintense lesion (arrow) in the
left occipital posterior cerebral artery (PCA) territory. (B) MR
angiography maximum intensity projection image shows
occlusion of the distal left PCA (arrow). Suspected arteritis
 Chapter 136: Computed Tomography and Magnetic Resonance Imaging of the Eye and Orbit
arterio-venous malformations are diagnosed better on
MR and MR angiography. However recent advances
in CT and CT angiography have made detection of
vascular lesions by CT easier.
Today, CT and MR are the preferred imaging
modalities for evaluation of various orbital soft tissue
and bony lesions. CT is the preferred modality for the
evaluation of the bony orbit and calcification in tumors
such as retinoblastoma. Many intraconal and extra-
conal lesions show up well on CT due to inherent
contrast with the orbital fat. MR with its superior
contrast is complimentary to CT scans on most
occasions and is the preferred modality for evaluation
of the eye, optic nerve and the intracranial visual path-
way. It is important that the ophthalmologist provides
the relevant clinical details to the radiologist, which
will help in the choice and focus of the investigation.
REFERENCES
1. Howard GM, Ellsworth RM. Differential diagnosis of
retinoblastoma. A statistical survey of 500 children.I. Relative
frequency of the lesions which simulate retinoblastoma. Am
J Ophthalmol 1965;60:610.
2. Mafee MF, Goldberg MF, Greenwald MJ, Schulman J et al.
Retinoblastoma and simulating lesions: Role of CT and MR
imaging. Radiol Clin North Am 1987;25:667.
3. Mafee MF, Ainbinder D, Afshani E, Mafee RF. The eye.
Neuroimaging Clin North Am 1996;6:29.
4. Kodilyne HC. Retinoblastoma in Nigeria: Problems in
treatment. Am J Ophthalmol 1967;63:467.
5. Abramson DH, Ellsworth RM, Tretter P et al. Treatment of
bilateral groups I through III retinoblastoma with bilateral
radiation. Arch Ophthalmol 1981;99:1761.
6. Kirkwood RJ. The Cranial Nerves, Orbit, and Temporal bone.
In Kirkwood RJ, editors. Essentials of Neuroimaging, 2nd ed.
Churchill Livingstone,1995.
7. Paulino AC. Trilateral retinoblastoma: is the location of the
intracranial tumor important? Cancer 1999;86:136.
8. Abramson DH, Ellsworth RM, Zimmerman LE. Nonocular
cancer in retinoblastoma survivors. Trans Am Acad
Opthalmol Otolaryngol 1976;81:454.
9. Brisse HJ, Lumbroso L, Fréneaux PC et al. Sonographic, CT,
and MR imaging findings in diffuse infiltrative retino-
blastoma: report of two Cases with histologic comparison.
AJNR 2001;22:499.
10. Mafee MF, Goldberg MF, Cohen SB et al. Magnetic resonance
imaging versus computed tomography of Leukokoric eyes
and use of in vitro proton magnetic resonance spectroscopy
of retinoblastoma. Ophthalmology 1989;96:965.
11. Kivela T. Trilateral retinoblastoma: a meta-analysis of
hereditary retinoblastoma associated with primary ectopic
intracranial retinoblastoma. J Clin Oncol 1999;17:1829.
12. Capper SA, Leopold IH. Mechanism of serous choroidal
detachment. Am J Ophthalmol 1956;55:101.
13. Char DH, Hedges TR 3rd, Norman D. Retinoblastoma. CT
diagnosis. Ophthalmology 1984;91:1347.
14. John-Mikolajewski V, Messmer E, Sauerwein W, Freundlieb
O. Orbital computed tomography. Does it help in diagnosing
1059
the infiltration of choroid, sclera and/or optic nerve in
retinoblastoma? Ophthalmic Paediatr Genet 1987;8:101.
15. Ainbinder DJ, Haik BG, Frei DF et al. Gadolinium enhance-
ment: improved MRI detection of retinoblastoma extension
into the optic nerve. Neuroradiology 1996;38:778.
16. Marshman WE, Jan JE, Lyons CJ. Neurologic abnormalities
associated with persistent hyperplastic primary vitreous. Can
J Ophthalmol 1999;34:17.
17. Goldberg MF, Mafee MF. Computed tomography for diag-
nosis of persistent primary hyperplastic vitreous (PHPV).
Ophthalmology 1983;90:442.
18. Kuker W, Ramaekers V. Persistent hyperplastic primary
vitreous: MRI. Neuroradiology 1999;41:520.
19. Sun MH, Kao LY, Kuo YH. Persistent hyperplastic primary
vitreous: magnetic resonance imaging and clinical findings.
Chang Gung Med J 2003;26:269.
20. Yang H, Wu Z. Color Doppler imaging of persistent
heperplastic primary vitreous. Yan Ke Xue Bao1997;13:56.
21. Alexandridou A, Stavrou P. Bilateral Coats’ disease: long-
term follow up. Acta Opthalmol Scand 2002;80:98.
22. Sherman JL, McLean IW, Brallier DR. Coat’s disease. CT
pathologic correlation in 2 cases. Radiology 1983;146:77.
23. Edward DP, Mafee MF, Garcia-Valenzuela E, Weiss RA.
Coats’ disease and persistent hyperplastic primary vitreous.
Role of MR imaging and CT. Radiol Clin North Am
1998;36:1119.
24. Galluzzi P, Venturi C, Cerase A et al. Coats disease: smaller
volume of the affected globe. Radiology 2001;221:64.
25. Lai WW, Edward DP, Weiss RA et al. Magnetic resonance
imaging findings in a case of advanced Coats’ disease.
Ophthalmic Surg Lasers 1996;27:234.
26. Magnaval JF, Glickman LT, Dorchies P, Morassin B.
Highlights of human toxocariasis. Korean J Parasitol
2001;39:1.
27. Neafie RC and Connor DH. Visceral larva migrans. In
pathology of Tropical and extraordinary diseases. In: Blinford
CH, Connor DH (Eds). Armed Forces Institute of Pathology:
Washington DC, USA. 1976;433-36.
28. Margo CE, Zimmerman LE. Retinoblastoma: the accuracy of
clinical diagnosis in children treated by enucleation. J Pediatr
Ophthalmol Strabismus 1983;20:180.
29. Palmer EA, Flynn JT, Hardy RJ. Incidence and early course
of retinopathy of prematurity. The Cryotherapy for
Retinopathy of Prematurity Cooperative Group. Ophthalmo-
logy 1991;98:1628.
30. Phelps DL. Retinopathy of prematurity the United States—
1979. Pediatrics 1981;67:924.
31. Sears J, Capone A. Retinopathy of Prematurity. In: Opthalmo-
logy.Yanoff M, Duker JS (Eds).pp 8.19.1-8 Mosby 1999.
32. Broughton WL, Zimmerman LE. A clinicopathologic study
of 56 cases of intraocular medulloepitheliomas. Am J
Ophthalmol 1978;85;407.
33. Shields JA. Shields CL. Tumors of the nonpigmented ciliary
epithelium. In: Shields JA, Shields CL (Eds): Intraocular
Tumors. A Text and Atlas. Philadelphia: Saunders 1996;461-
87.
34. Floyd BB, Minckler DS, Valentin L. Intraocular medullo-
epitheliomas in a 79-year-old man. Ophthalmology 1982;89:
1088.
35. Al Torbak A, Abboud EB, Al-Sharif A, El-Okda MO.
Medulloepithelioma of the Ciliary Body. Indian J Ophthalmol
2002;50:138.
36. Pyhtinen J, Lindholm EL. Imaging in optic nerve coloboma.
Neuroradiology 1996;38:171.
1060 Section 9: Miscellaneous Topics
37. Murphy BL, Griffin JF. Optic nerve coloboma (morning glory
syndrome): CT findings. Radiology 1994;191:59.
38. Willis R, Zimmerman LE, et al. Heterotopic adipose tissue
and smooth muscle in the optic disc. Arch Ophthalmol 1972;
88:139.
39. Mafee MF, Jampol LM, Langer BG, Tso M. Computed
tomography of optic nerve colobomas, morning glory
anomaly, and colobomatous cyst. Radiol Clin North Amer
1987;25:693.
40. Auber AE, O’Hara M. Morning Glory syndrome. MR
imaging. Clin. Imaging. 1999;23:152.
41. Weiss A, Martinez C, Greenwald M. Micropthalmos with cyst:
clinical presentations and computed tomographic findings. J
Pediatr Ophthalmol Stabismus 1985;22:6.
42. Zion VM. Phakomatosis. In Duanne’s Clinical Opthalmology,
Vol 5.Philadelphia, JB Lippincott,1990;1-12.
43. Mafee MF, Atlas SW, Galetta SL. Eye, orbit and visual system.
In Atlas SW (ed): Magnetic Resonance Imaging of the brain
and Spine, third ed. Lippincott Williams & Wilkins,
Philadelphia 2002;1433-1524.
44. Mafee MF, Linder B, Peyman GA et al. Choroidal hematoma
and effusion: evaluation with MR imaging. Radiology
1988;168:781.
45. Egan KM, Seddon JM, Glynn RJ et al. Epidemiologic aspects
of uveal melanoma. Surv Ophthalmol 1988;32:239.
46. Mahoney MC, Burnett WS. The epidemiology of ophthalmic
malignancies in New York State. Ophthalmology 1990;97:
1143.
47. Mafee MF, Peyman GA, McKusick MA. Malignant uveal
melanoma and similar lesions studied by computed
tomography. Radiology 1985;156:403.
48. Stroszczynski C, Hosten N, Bornfeld N et al. Choroidal
hemangioma: MR findings and differentiation from uveal
melanoma. Am J Neuroradiol 1998;19:1441.
49. Mafee MF, Peyman GA, Grisolano JE et al. Malignant uveal
melanoma and simulating lesions: MR imaging evaluation.
Radiology 1986;160:773.
50. Lemke AJ, Hosten N, Bornfeld N et al. Uveal melanoma:
correlation of histopathologic and radiologic findings by
using thin-section MR Imaging with a surface coil. Radiology
210:775,1999.
51. Ramirez H, Blatt ES, Hibri NS. Computed tomographic
identification of calcified optic nerve drusen. Radiology
1983;148:137.
52. Barnes PD, Robson CD, Robertson RL, Poussaint TY. Pediatric
orbital and visual pathway lesions. Neuroimag Clin North
Am 1996;6:179.
53. Maya MM, Heier LA: Orbital CT. Current use in the MR era.
Neuroimag Clin North Am 1998;8:651.
54. Freide R. Uncommon syndromes of cerebellar vermis aplasia.
II. Tecto-cerebellar dysraphia with occipital cephalocele . Dev
Med Child Neurol 1978;20:764.
55. Cohen M, Lemire R. Syndromes with cephaloceles. Teratology
1982;25:161.
56. Barnes PD. Clinical principles of pediatric neuroradiology.
In MRI in Pediatric Neuroradiology. St. Louis, Mosby-Year
Book, 1992;41-82.
57. Nugent RA, Rootman J, Robertson WD et al. Acute orbital
pseudotumors: classification and CT features. Am J
Roentgenol 1981;137:957.
58. Dallow RL. Evaluation of unilateral exopthalmos with
ultrasonography: Analysis of 258 consecutive cases.
Laryngoscope 85:1905,1975.
59. Grove AS Jr. Evaluation of exopthalmos. N Engl J Med
1975;292:1005.
60. Gorman CA. Temporal relationship between the onset of
Graves’ opthalmopathy and diagnosis of thyrotoxicosis.
Mayo Clin Proc 1983;58:515.
61. Trokel SL, Jakobiec FA. Correlation of CT scanning and patho-
logic features of ophthalmic Graves’ disease. Ophthalmology
1981;88:553.
62. Feldon SE, Lee CP, Muramatsu SK, Weiner JM. Quantitative
computed tomography of Graves’ ophthalmopathy. Extra-
ocular muscle and orbital fat in development of optic
neuropathy. Arch Ophthalmol 1985;103:213.
63. Bee YS, Lin MC, Wang CC, Sheu SJ. Optic neuritis: clinical
analysis of 27 cases. Kaohsiung J Med Sci 2003;19:105.
64. Howard CW, Osher RH, Tomsak RL. Computed tomographic
features in optic neuritis. Am J Ophthalmol 1980;89:699.
65. Weber AL, Klufas R, Pless M. Imaging Evaluation of the optic
nerve and visual pathway. Neuroimag Clin North Am
1996;6:143.
66. Patrinely JR, Osborn AG, Anderson RL, Whiting AS. Compu-
ted tomographic features of nonthyroid extraocular muscle
enlargement. Ophthalmology 1989;96:1038.
67. Trokel SL, Hilal SK. Recognition and differential diagnosis
of enlarged extraocular muscles in computed tomography.
Am J Ophthalmol 1979;87:503.
68. Knowles DM, Jacobiec FA, McNally L, Burke JS. Lymphoid
hyperplasia and malignant lymphoma occurring in the ocular
adnexa (orbit conjunctiva and eyelids). A prospective
multiparametric analysis of 108 cases during 1977 to 1987.
Hum Pathol 1990;21:959.
69. Yeo JH, Jakobiec FA, Abbott GF, Trokel SL. Combined clinical
and computed tomographic diagnosis of orbital lymphoid
tumors. Am J Ophthalmol 1982;94:235.
70. Weber AL, Dallow RL, Oot RF. Computed tomography of
lymphoproliferative disease of the orbit. Report of 50 patients.
Acta Radiol Suppl 1986;369:333.
71. Westacott S, Garner A, Moseley IF, Wright JE. Orbital
lymphoma versus reactive lymphoid hyperplasia: an analysis
of the use of computed tomography in differential diagnosis.
Br J Ophthalmol 1991;75:722.
72. Polito E, Galieni P, Leccisotti A. Clinical and radiological
presentation of 95 orbital lymphoid tumors. Graefes Arch Clin
Exp Ophthalmol 1996;234:504.
73. Nikoskelainen E, Dellaporta A, Rice T et al. Orbital involve-
ment by plasmacytoma. Report of two cases. Acta
Ophthalmol (Copenh) 1976;54:755.
74. Henderson JW, Farrow GM. Metastatic carcinoma. In
Henderson JW: Orbital tumors, ed 2. New York, BC Decker,
1980.
75. Goldberg RA, Rootman J, Cline RA. Tumors metastatic to
the orbit: a changing picture. Surv Ophthalmol 1990;35:1.
76. Shields JA, Shields CL, Brotman HK, et al. Cancer metastatic
to the orbit: the 2000 Robert M. Curts Lecture. Ophthal Plast
Reconstr Surg 2001;17:346.
77. Goldberg RA, Rootman J. Clinical characteristics of metastatic
orbital tumors. Ophthalmology 1990;97:620.
78. Healy JF. Computed tomographic evaluation of metatases to
the orbit. Ann Ophthalmol 1983;15:1026.
79. Hesselink JR, Davis KR, Weber AL, Davis JM, Taveras JM.
Radiological evaluation of orbital metastases, with emphasis
on computed tomography. Radiology 1980;137:363.
80. Warner MA, Weber AL, Jakobiec FA. Benign and malignant
tumors of the orbital cavity including the lacrimal gland.
Neuroimag Clin North Am 1996;6:123.
 Chapter 136: Computed Tomography and Magnetic Resonance Imaging of the Eye and Orbit
81. Musarella MA, Chan HS, DeBoer G, Gallie BL. Ocular
involvement in neuroblastoma: prognostic implications.
Ophthalmology 1984;91:936.
82. Albert DM, Rubenstein RA, Scheie HG. Tumor metastasis to
the eye. II. Clinical study in infants and children. Am J
Ophthalmol 1967;63:727.
83. Alfano JE. Ophthalmological aspects of neuroblastomatosis:
a study of 53 verified cases. Trans Am Acad Ophthalmol
Otolaryngol 1968;72:830.
84. Rootman J, Goldberg C, Robertson W. Primary orbital
schwannomas. Br J Ophthalmol 1982;66:194.
85. Jacobiec FA, Jones IS. Neurogenic tumors. In Duanne TS(ed):
Clinical Ophthalmology, vol 2. Philadelphia, JB Lippincott,
1976.
86. Krohel GB, Rosenberg PN, Wright JE, Smith RS. Localized
orbital neurofibromas. Am J Ophthalmol 1985;100:458.
87. Francois J: Ocular aspects of phakomatoses. In Vinken PJ,
Bruyn GW (eds): Handbook of Clinical Neurology. New York,
Elsevier, 1972.
88. Levin LA , Jakobiec FA. Peripheral nerve sheath tumors of
the orbit. In Albert DM, Jakobiec FA (Eds) Principles and
Practice of Ophthalmology. Philadelphia, WB Saunders, 1994.
1978.
89. Tada M, Sawamura Y, Ishii N et al. Massive plexiform
neurofibroma in the orbit in a child with von Recklin-
ghausen’s disease. Childs Nerv Syst 1998;14:210.
90. Yanoff M, Davis RL, Zimmerman LE. Juvenile pilocytic
astrocytoma (“glioma”) of the optic nerve: Clinicopathologic
study of sixty three cases. In Jacobiec FA (Ed): Ocular and
Adnexal Tumors. Birminhgham, Aesculapius, 1978;685-707.
91. Jones IS, Reese AB, Krout J. Orbital rhabdomysarcoma: An
analysis of sixty-two cases. Trans Am Ophthalmol Soc
1965;63:223.
92. Porterfield JT, Zimmerman LE. Rabdomyosarcoma of the
orbit: A clinicopathological study of 55 cases. Virchows Arch
[Pathol Anat] 1962;335:329.
93. Barkovich AJ. Brain tumors of childhood. In Barkovich AJ
(ed). Pediatric Neuroimaging, 2nd ed. New-York, Raven
Press, 1995;321-437.
94. Yousem DM, Lexa FJ, Bilaniuk LT, Zimmerman RI.
Rhabdomyosarcomas in the head and neck: MR imaging
evaluation. Radiology 1990;177:683.
95. Jackson K, Baker SR. Periorbital cellulitis. Head Neck Surg
1987;9:227.
96. Pushker N, Bajaj MS, Betharia SM. Orbital and adnexal
cysticercosis. Clin Experiment Ophthalmol 2002;30:322.
97. Gadkari SS, Bhabha SK, Jehangir RP, et al. Orbital cysticer-
cosis. J Postgrad Med 1992;38:200.
98. Hesselink JR, Weber AL, New PF et al. Evaluation of
mucoceles of the paranasal sinuses with computed tomo-
graphy. Radiology. 1979;133:397.
99. Forbes G. Vascular lesions of the orbit. Neuroimag Clin N
Amer 1996;6:113.
100. Jones JS. Lymphangioma of the ocular adnexa. Trans Am
Ophthalmol Soc 1959;57:602.
101. Lloyd G, Wright JE, Morgan G. Venous malformations in the
orbit. Br. J Ophthalmol 1971;55:505.
102. Atlas SW, Bilaniuk LT, Zimmerman RA et al. Orbit; initial
experience with surface coil spin-echo MR imaging at 1.5T.
Radiology 1987;164:501.
1061
103. Graf CJ. Spontaneous carotid-cavernous fistula: Ehler-Danlos
syndrome and related conditions. Arch Neurol 1965;13:662.
104. de Campos JM, Ferro MO, Burzaco JA, Boixados JR.
Spontaneous carotid-cavernous fistula in osteogenesis
imperfecta. J Neurosurg 1982;56:590-93.
105. Elster AD, Chen MY, Richardson DN, Yeatts PR. Dilated
intercavernous sinuses: an MR sign of carotid-cavernous and
carotid-dural fistulas. Am J Neuroradiol 1991;12:641.
106. Uehara T, Tabuchi M, Kawaguchi T, Mori E. Spontaneous
dural carotid cavernous sinus fistula presenting isolated
ophthalmoplegia: evaluation with MR angiography.
Neurology 1998;50:814.
107. Wadlington VR, Terry JB. Endovascular therapy of traumatic
carotid-cavernous fistulas. Crit Care Clin 1999;15:831.
108. Weber AL. Radiologic evaluation of facial and orbital trauma.
In Taveras JM, Ferucci JT. Radiology. Diagnosis—Imaging-
Intervention. Lippincott Williams Wilkins, 1999.
109. Lustrin ES, Brown JH, Novelline R, Weber AL. Radiologic
assessment of trauma and foreign bodies of the eye and orbit.
Neuroimag. Clin N Amer 1996;6:219.
110. Roberts CF, Leehy PJ. Intraorbital wood foreign body
mimicking air at CT. Radiology 1992;185:507.
111. Balchunas WR, Quencer RM, Byrne SF. Lacrimal gland and
fossa masses: evaluation by computed tomography and A-
mode echography. Radiology 1983;149:751.
112. Weber AL, Rodriguez-De Velasquez A, Lucarelli MJ, Cheng
HM. Normal anatomy and lesions of the lacrimal sac and
duct evaluated by dacryocystography, computed tomo-
graphy, and MR imaging. Neuroimaging Clin of North Am
1996;6:199.
113. Hornblass A, Gabry JB. Diagnosis and treatment of lacrimal
sac cysts. Ophthalmology 1980;86:1655.
114. Berlin AJ, Rath R, Rich L. Lacrimal system dacryoliths.
Ophthalmic Surg 1980;11:435.
115. Blanksma LJ, Slijper J. Actinomycotic dacryocystitis.
Ophthalmologia 1978;176:145.
116. Ni C, D’ Amico D, Fan CQ et al. Tumors of the lacrimal sac.
A clinicopathological analysis of 82 cases. Int Ophthalmol
Clin 1981;121.
117. Rahangdale SRN, Castillo M, Shockley W. MR in squamous
cell carcinoma of the lacrimal sac. Am J Neuroradiol
1995;16:1262.
118. Resnick D, Kyriakos M, Greeway GD. Tumors and tumor-
like lesions of the bone: Radiographic principles. In Resnick
D (Ed): Bone and joint imaging. Philadelphia, WB Saunders,
1989; p. 1110.
119. Feldman RB, Moore DM, Hood CI et al. Solitary eosinophilic
granuloma of the lateral orbital wall. Am J Ophthalmol
1985;100:318.
120. Liakos GM, Walker CB, Carruth JA. Ocular complications in
craniofacial fibrous dysplasia. Br J Ophthalmol 1979;63:611.
121. Hirabayashi S, Kagawa K, Ohkubo E, et al. Craniofacial
fibrous dysplasia with rapidly increasing proptosis due to a
mucocele behind the globe. Ann Plast Surg. 1998;40:182.
122. Lum C, Kucharczyk W, Montanera WJ, Becker LE. The Sella
turcica and parasellar region. In Atlas SW (Ed): Magnetic
Resonance Imaging of the brain and Spine, third ed.
Lippincott Williams & Wilkins, Philadelphia 2002;1283-1362.
123. Osborn AG. Astrocytomas and other glial neoplasms. In
Osborn AG (Ed): Diagnostic Neuroradiology. Mosby, 1994;
pp 529-78.
 Chapter 137
Applications of
Ultrasound Biomicroscopy
M Baskaran, Muna Bhende
ULTRASOUND BIOMICROSCOPY (UBM):
INTRODUCTION
The development of high frequency, high resolution
ultrasound imaging has given researchers and
clinicians a new tool for understanding and diagno-
sing disease of the anterior aspect of the eye and ocular
adnexa. Ultrasound Biomicroscopy (UBM) has
provided the opportunity for the clinicians to visualize
at near microscopic resolution, the areas not easily seen
by other methods thereby paving the way for
diagnoses and reorienting therapeutic interventions
in various anterior segment eye disorders. Pavlin,1
who worked on the instrument, has opened new areas
of research in various fields of ophthalmology. It has
been proven to give useful results in physiology of
accommodation, etiopathology of certain glaucomas
and in various other clinical conditions. With the vast
information possible, there is a lot of scope for further
advances in the instrumentation and technique of this
tool.
Principle
Achieving the goal of real-time B-mode imaging at
higher frequencies has been facilitated by the
development of newer technology in three important
areas: (i) transducers, (ii) high frequency signal
processing and (iii) precise motion control.
The single most important component in an
ultrasound imaging system is the transducer. The
Humphrey 840 system uses polyvinylidene diflouride
(PVDF) as the piezoelectric polymer and poly-
vinylidene diflouride/triflouroethylene as the
copolymer. This 40 to 100 MHz transducer is moved
linearly over the imaging field up to 4 mm, collecting
radiofrequency ultrasound data, which is processed
and imaged on the monitor.
Instrumentation
There are at present two UBM machines commercially
available viz; Humphrey UBM model 840 (Paradigm,
USA) and Rion UBM model UX-02). Kobayashi and
colleagues have examined the correlation between
these two instruments and found them to agree to
almost 90%, even though Humphrey 840 has better
reproducibility.2 The routine A and B scans utilize a
frequency between 8 and 10 MHz, while the UBM
transducer utilizes frequencies from 50 MHz to even
100 MHz. The tissue resolution is about 50 microns,
which could be roughly compared to the light
microscopy with low power. The penalty paid for
higher resolution is lower penetration and the UBM
at present can penetrate up to a depth of 5 mm.3
Technique
The equipment consists of a special ultrasound probe
which is bigger in dimension than the routine probe
for B-scan. It is suspended from an articulated arm
and scanning is usually performed in the supine
position. PMMA scleral cups are inserted into the eye
under topical anesthesia. Methylcellulose is usually
used as a coupling medium; however, normal saline
 Chapter 137: Applications of Ultrasound Biomicroscopy
can also be used. Scans are performed in radial and
transverse meridians and a real-time two-dimensional
image is obtained which can be visualized on a display
monitor. Perpendicular orientation of the transducers
gives greater image resolution and quality. Adequate
patient cooperation is essential to prevent corneal
damage, since the probe is in constant motion and
works very close to the ocular surface. A bandage
contact lens may be used to protect the cornea.
Standard disinfective measures need to be followed
to clean the probe and cups after every use (70%
alcohol for the probe tip and 2% hydrogen peroxide
for the PMMA scleral shells is the routine practice).
CLINICAL APPLICATIONS (Table 137.1)
A brief summary of the current uses is given below.
Fig. 137.1 shows various structures of anterior segment
of the eye with UBM.
Cornea and Ocular Surface Disorders
1. Assessment of depth of conjunctival mass lesions—
conjunctival and corneal neoplasms are assessed
in terms of the lateral extent as well as depth of
involvement for proper surgical planning (Figs
137.2A and B). The reflectivity and pattern of
tumors can give an idea as to the diagnosis of the
condition also.
2. Evaluation of anterior segment anatomy in cases
of corneal opacity prior to penetrating kerato-
plasty.4 In patients with raised IOP it gives an idea
of the angle status and indirectly may give a clue
to the prognosis with the graft.
Fig. 137.1: Image of the normal eye anterior segment (C–
Cornea; S–Sclera, I–Iris, L–Lens, CB–Ciliary body; Arrow
indicates zonules)
1063
Table 137.1: UBM—Important clinical applications
Cornea
a. Conjunctival mass lesions
b. Pre-PK evaluation of anterior segment
c. Corneal thickness
Glaucoma
a. Evaluation of postoperative shallow AC
b. Malignant glaucoma
c. Plateau iris
d. PDS— iridozonular contact
e. Bleb evaluation
f. Cyclodialysis clefts
Lens
a. Zonular integrity
b. PC integrity in aphakia and pseudophakia
c. Haptic position in subluxated IOLs.
d. Haptic position in scleral fixated IOLs
Uvea
a. Parsplanitis in media opacity
b. Scleral and episcleral changes in scleritis—staging
Vitreoretinal diseases
a. Sclerotomy site evaluation for proliferation
b. Pars plana foreign body.
c. Peripheral VR disorders
Mass lesions
a. Iris and ciliary body cysts
b. Iris and ciliary body tumors
c. Lid lesions
3. Estimation of corneal thickness—this may be useful
when the ultrasound pachymeter is unreliable and
for research purposes as in keratoconus staging.4
Glaucoma
1. Estimation of anterior chamber depth.4
2. Estimation of angle measurements: It has been
found that normal eyes and eyes with primary
open angle glaucoma have similar parameters,
while eyes with angle closure glaucoma have
decreased parameters in terms of angle and
anterior chamber depth with relatively increased
lens thickness by using UBM.4 The angle recess
area has been measured recently and has been
found to decrease with age. Detailed angle
measurements have been possible by quantitative
UBM (Table 137.2).
3. Evaluation of anterior segment in congenital
glaucoma with corneal pathology—in infants
with cloudy cornea; it has been found to be useful
1064 Section 9: Miscellaneous Topics

Figs 137.2A and E: (A) Slit lamp photo shows a conjunctival papilloma, (B) UBM shows finger-like projections of the papilloma
and confirms the integrity of the deeper layers, (C) Slit lamp photograph shows iris root mass lesion, (D) UBM shows extension
on to the iris, angle and ciliary body, (E) Iris cyst on UBM

Table 137.2: Quantitative measurements (Fig. 137.9)

Measurement
Angle Opening Distance (AOD)
Trabecular – iris angle (TIA q1)
Iris thickness 1 (ID1)
Iris thickness 2 (ID 2)
Iris thickness 3 (ID 3)
Trabecular ciliary process distance (TCPD)
Iris-ciliary process distance (ICPD)
Iris-zonule distance (IZD)
Iris-lens contact distance (ILCD)
Iris-lens angle (q2)
Angle recess area (ARA)
Description
Distance between the trabecular meshwork (TM) and the iris at 500 mm
anterior to scleral spur
Angle of the angle recess
Iris thickness at 500 mm anterior to the scleral spur
Iris thickness at 2 mm from the iris root
Maximum iris thickness near the pupillary edge
Distance between the trabecular meshwork (TM) and the ciliary process at
500 mm anterior to scleral spur
Distance between the iris and the ciliary process along the line of TCPD
Distance between the iris and the zonules along the line of TCPD
Contact distance between the iris and the lens
Angle between the iris and the lens near the pupillary edge
A triangular area bordered by iris, cornea and a line drawn perpendicular
to the cornea from a point 750 mm anterior to the scleral spur

in differentiating true congenital glaucoma from 5. Diagnosis of malignant glaucoma: Schroender et

those due to associated aniridia, angle anomalies,
Peter’s anomaly and lens changes.5
4. Evaluation of postoperative shallow anterior
chamber and hypotony-related problems, espe-
cially after trabeculectomy.6
al 9 in their observation have reinforced the
theoretical mechanism proposed for malignant
glaucoma, i.e. ciliary block. Some have noted the
clear spaces suggestive of aqueous lakes. The
universal anterior rotation of ciliary processes is
 Chapter 137: Applications of Ultrasound Biomicroscopy 1065

Figs 137.3A to C: In-set shows slit lamp photograph of shallow

AC in a patient with malignant glaucoma. UBM picture shows
anterior rotation of ciliary body and shallow anterior chamber
before medical treatment (A and B). Reversal of anterior rotation
and deepening of AC seen (C and D) after 48 hours of starting
medical treatment

considered to be the hallmark of malignant glau-

coma.7 Reversal of this rotation after 48 hours of
medical treatment has been documented
(Figs 137.3A to C).
6. Diagnosis of plateau iris: The presence of
anteriorly placed thick iris processes on UBM with
reduced distance between the trabecular mesh-
work and ciliary processes (TCPD) has been
considered diagnostic of plateau iris (Fig 137.5B).4
7. Assessment of iridozonular contact in pigment
dispersion syndrome: The presence of irido-
Figs 137.4A and B: (A) Iridozonular contact before YAG
zonular contact in patients with pigmentary
peripheral iridotomy, (B) Absence of iridozonular contact after
glaucoma is related to the efficacy of laser YAG peripheral iridotomy
iridotomy and control of IOP.10 The change in iris
configuration in such eyes after a peripheral
iridotomy is dramatically seen on UBM11 10. Imaging of filtering bleb and confirming patency
(Figs 137.4A and B). The IZD and ILCD are used of the fistula (Figs 137.5C and D).4
to quantitatively measure this phenomenon. 11. As an adjunct in the evaluation of new anterior
8. Diagnosis of cyclodialysis clefts: In patients with segment surgical procedures (e.g. viscocanulo-
severe hypotony, small clefts and corneal stomy), the mechanism of action of this procedure
cloudiness, UBM serves as a confirmatory tool could be confirmed by UBM.
and in certain situations may supercede gonio- 12. Assessment of tubes in valve implants.4
scopy in diagnosis (Fig 137.5A).8 13. Diagnosis of epithelial downgrowth: The extent
9. Diagnosis and confirmation of angle recession in of epithelial downgrowth can be assessed,
media opacity.4 especially the involvement of the ciliary body.
1066 Section 9: Miscellaneous Topics

Figs 137.5A to D: (A) Cyclodialysis cleft—arrows show presence of cyclo dialysis cleft.
(B) Plateau iris—thickened anteriorly placed ciliary process. (C) Functioning bleb. (D) Nonfunctioning bleb

Lens 4. The IOL haptic and optic position in postoperative

1. Assessment of zonular and lenticular abnormalities
in developmental and traumatic disorders:
Zonular status in traumatized eyes in develop-
mental anomalies, microspherophakic eyes can be
assessed. In such cases, zonules will not be imaged
in UBM with squaring of the edges of the lens,
laxity of zonules will be seen as varying distances
between the lens edge and the ciliary processes and
the length of the zonules may be increased on
UBM.9 The assessment of the extent of zonular
dehiscence or laxity can help in planning a proper
surgical approach sometimes may prompt referral
to a vitreoretinal surgeon for a posterior approach
for removal of the lens (Figs 137.6A to C).
2. Assessment of PC integrity in aphakia and pseudo-
phakia prior to secondary IOL or IOL repo-
sitioning: Often, these eyes have extensive poste-
rior synechiae and poor dilation. Posterior capsule
and zonular integrity can be assessed with UBM
for accurate planning for IOL implantation in such
patients.
3. Surgical planning prior to penetrating kerato-
plasty, anterior segment reconstruction, IOL
removal and repositioning.
patients (e.g. in IOL-induced uveitis): Abnormal
positions of the IOL haptics can cause recurrent
uveitis prompting removal of the IOL. Assessment
of the location of the haptics on UBM can give a
clue to the possible cause of inflammation and a
decision on further management (Fig. 137.6B).13
The haptics are seen as high reflective elements in
UBM and can be assessed for position at various
locations to know the entire positioning of the
haptics.
5. The IOL and haptic positions in scleral fixated IOLs
and in phakic IOLs—scleral fixated IOLs are fast
becoming a popular option. The UBM has helped
refine the technique by studying the postoperative
haptic position in relation to the ciliary sulcus,
thereby helping one to decide the position of suture
placement from the external side. In phakic IOLs,
it is possible to assess the distance between the
crystalline lens and the IOL on UBM.11
Uvea
1. Pars planitis in media opacity or small pupil:
Diagnosis of active disease has management
implications in such patients, with special use in
 Chapter 137: Applications of Ultrasound Biomicroscopy
Figs 137.6A to C: UBM shows: (A) Normal
zonules (B) Lax zonules (C) Absence of zonules
timing of cataract surgery. Active disease presents
with dot-like echoes over the pars plana and in the
anterior vitreous cavity with clumps of exudates
over the inferior ciliary body and pars plana.
Membranes causing peripheral traction in resolved
cases can also be demonstrated (Fig. 137.7C).
2. Evaluation of scleral and episcleral lesions: The
clear demarcation possible in vivo with UBM with
respect to various layers of the eye enables one to
differentiate episcleral and scleral lesions in inflam-
matory conditions. The varying reflectivity can
help stage the disease and support the clinical
assessment to modulate therapy (Figs 137.7A
and B).
1067
Vitreoretinal Disorders
1. Shallow peripheral ciliochoroidal detachment: Can
be demonstrated both postoperatively or as part
of a disease entity such as Vogt-Koyanagi-Harada
syndrome.6
2. Diagnosis of fibrovascular proliferation at scleroto-
my sites: Recurrent vitreous hemorrhage can be
caused by fibrovascular proliferation at sclerotomy
sites and can be easily assessed with preoperative
UBM. The changes at the sclerotomy sites can be
categorized into: well healed, gape, plaque,
vitreous incarceration, fibrovascular proliferation
and anterior hyaloidal fibrovascular proliferation
(Fig. 137.8A to F). Cases with rebleed and no fibro-
vascular proliferation on UBM did better with fluid
gas exchange, while those with fibrovascular
proliferation required more extensive surgery.12
3. Visualization of angle and pars plana foreign
bodies.4
4. Evaluation of peripheral vitreoretinal disorders:
Cases of toxocariasis were reported to demonstrate
pseudocystic transformation of the peripheral
vitreous.17
Mass Lesions of Anterior Segment
1. Evaluation of iris and ciliary body cysts: Fine et al
have analyzed 210 iridociliary cysts with UBM and
found that 80% were found to be benign and the
rest were associated with tumors. Anterior segment
tumors sometimes can be associated with cysts and
can give a wrong impression of safety (Fig. 137.2).18
The cysts are seen as clear, well- demarcated spaces
with high reflective capsules and can be followed
up with UBM quantitatively.
2. Evaluation of iris and ciliary body tumors: The
posterior extent of ciliary body tumors and the
involvement of ciliary body in case of iris tumors
can be made with UBM which will help in the
surgical approach (Figs 137.2B and C).15
3. Lid tumors can be assessed before a surgical
procedure.
Research Aspects
1. Physiology of accommodation, effect of drugs: The
changes in the ciliary body contour with accommo-
dation and the changes in lens have been demons-
trated with UBM. The effect of drugs such as
pilocarpine and cycloplegics have been demons-
trated in various studies.4,16
1068 Section 9: Miscellaneous Topics

Figs 137.7A to C: (A) Slit lamp photograph shows a scleral nodule and the corresponding
UBM picture shows low reflective areas suggestive of scleral edema. (B) IOL haptics in the
ciliary sulcus and iris chafing in IOL-related uvetis. (C) Pars planitis shows clump-like echoes
in pars plana suggestive of active pars planitis

2. Development of eye and angle in infants: The angle
in infants is believed to be narrow and grows as
age progresses as per studies conducted with UBM.
Further studies which include embryos may enable
us to demonstrate causative factors for anomalies
of the anterior segment ocular structures and
possible therapeutic intervention.17,18
3. Staging of keratoconus: Use of UBM in staging
keratoconus by evolving corneal thickness at
various points in the cornea to derive a keratoconus
index has been part of a study by Avitable et al.19
4. Provocative tests in narrow angles.
5. Mechanism of malignant and pigmentary glau-
coma (theories supported).
6. Many types of angle configurations can be defined
using angle recess area and other quantitative data.
Iris volume and Iris speed with video UBM can be
assessed now with the new software available.
7. Doppler UBM.20
Future
Hitherto it was possible to perform UBM only in the
supine position. Esaki and colleagues3 have devised
 Chapter 137: Applications of Ultrasound Biomicroscopy 1069

Figs 137.8A to F: Sclerostomy sites in UBM: Patterns of healing in vitrectomized eyes for diabetic retinopathy. (A) Well healed
(B) Gape (C) Plaque (D) Vitreous incarceration (E) Fibrovascular proliferation (F) Anterior hyaloid fibrovascular proliferation

Fig. 137.9: Quantitative parameters on UBM depicted diagrammatically.

Refer to Table 137.2 for definitions (sketches are adopted from Ref 5)
1070 Section 9: Miscellaneous Topics
a simple technique in both sitting and prone positions.
With this, it may become possible to evaluate lesions
dynamically for changes in posture. The development
of linear array devices can vastly increase the flexibility
by increasing the frame rates, widening the field of
view and eliminate the hazard of corneal abrasion by
the moving probe. Video UBM is already available
with which dynamic images and measurements are
possible even though their clinical applications are yet
to be fully explored. Acquisition of three-dimensional
images and software for quantitative analysis can help
looking into the details of complex ocular structures.
It is also interesting to note that Doppler ultrasound
is being developed by Pavlin et al to map and quantify
the blood flow in normal and abnormal ciliary circu-
lation. The possibility of adding a therapeutic inter-
vention (e.g. a laser probe) may permit effective opti-
mization and verification of the results in case of tumor
related to this area. Ishikawa et al predict that the
inputs from advanced software with automated diag-
nostic capabilities in future can provide a useful tool
for the purposes of telemedicine.4
REFERENCES
1. Pavlin CJ, Sherar MD, Foster FS. Sub-surface ultrasound
microscopic imaging of the intact eye. Ophthalmology
1990;97;244.
2. Kobayashi H, Kobayashi K. Quantitative comparison of
Zeiss—Humphrey model 840 and Rion UX – 02 systems of
ultrasound biomicroscopy. Graefe’s Arch Clin Exp Ophthal-
mology 1999;237(S):381.
3. Esaki k , Ishikauz H, Liebmann JM et al. A technique for
performing ultrasound biomicroscopy in the sitting and prone
position. Ophthalmic Surg Lasers 2000;31;166.
4. Pavlin CJ, Foster FS. Ultrasound biomicroscopy of the eye,
1st edn. Springer-Verlag New York Inc 1995.
5. Erigels BF, Dietlein TS, Jacobi PC et al. Ultrasound
biomicroscopy diagnosis of congenital glaucoma. Klin
Monatsbe Augenheilkd 1999;215;338.
6. Bhende MP, Lekha T, Vijaya L et al. Ultrasound biomicro-
scopy in the diagnosis and management of cyclodialysis clefts.
Indian J of Ophthalmol 1999;47:19.
7. Schroeden W, Fischer K, Erdman I et al. Ultrasound
biomicroscopy and therapy of malignant glaucoma. Klin
Monatsbe Surgenheilted 1999;215;19.
8. Pillunat LE, Bohn A, Fristing B et al. Ultrasound bio-
microscopy in pigmentary glaucoma. Ophthalmology
2000;97;268.
9. Luring K, Wegscheiler E, Hoops JP et al. In vivo imaging of
the zonular apparatus with high-resolution ultrasound
biomicroscopy. Graefe’s Arch Clin Exp Ophthalmol 1999;
237;361.
10. Raizada S, Biswas J, Bhende MP. Ultrasound biomicroscopy
in IOL related uveitis AlOC Proceedings 1999;227-31.
11. Pop M, Man Fourth, Payette Y. Ultrasound biomicroscopy
of the iris-claw phakic intraocular lens for high myopia. J
Refract Surg 1999;15;632.
12. Bhende MP, Agraharam SG, Gopal L et al. Ultrasound
biomicroscopy of sclerotomy sites after pars plana vitrectomy
for diabetic vitreous hemorrhage. Ophthalmology 2000;
107:1729.
13. Tran VT, Lunsbroso L, Le Hoang P et al. Ultrasound biomicro-
scopy in peripheral retinovitreal toxocariasis. Am J
Ophthalmol 1999;127;607.
14. Fine N, Pavlin CJ. Primary cysts in the iridociliary sulcus:
Ultrasound biomicroscopic features of 210 cases. Can J
Ophthalmology; 1999;34;325.
15. Biswas J, Bhende MP, Kumar FK et al. Leiomyoma of the
ciliary body extending to the anterior chamber; clinico-
pathologic and ultrasound biomicroscopic correlation. Surv
Ophthalmol 2000;44;336.
16. Arakarva A, Tamai M. Ultrasound biomicroscopic analysis
of the human ciliary body after 1% and 2% pilocarpine
instillation [In process citation]. Ophthalmologica 2000;
214;253.
17. Kingu J, Park M, Kobayasnitt et al. Ultrasound biomicroscopy
of the anterior segment of the eyes of infants. J Pediatr
Ophthalmol Strabismus 1998;35;320.
18. Kobayashi H, Ono H, Kingu J et al. Ultrasound biomicro-
scopic measurement of development of anterior chamber
angle. Br J Ophthalmol 1999;83;559.
19. Avitabile T, Marano F, Castiglione F et al. Keratoconus staging
with ultrasound biomicroscopy. Ophthalmologica
1998;212:10.
20. Foster FS, Pavlin CJ, Harasiewicz KA et al. Advances in
ultrasound biomicroscopy. Ultrasound Med Biol 1998;26;1.
 Chapter 138
Laboratory Techniques in
Ophthalmic Pathology
Geeta K Vemuganti
INTRODUCTION
Ophthalmic pathology, like all branches of pathology,
encompasses the essential nature of disease process,
especially of the structural and functional changes in
tissues that cause or are caused by disease. The under-
standing of any disease process includes etiology,
pathogenesis, morphology of the lesion, effects of
the lesion on course and prognosis, complications,
treatment and the undesirable effects of treatment.
The tissues removed during any surgical procedure
are obviously a storehouse of information. It is,
therefore, important for the ophthalmologist to
communicate with the pathologists before, during and
after surgical procedure so that a good
clinicopathologic correlation is established and the
pathologist is able to provide the most accurate inter-
pretation of the tissue submitted. Most of the aspects
of the diseases are covered in various chapters of
this book, and it is beyond the scope of this chapter
to include pathology details of individual diseases.
This chapter gives a brief and simple description of
the routine and special techniques adopted by most
of the ophthalmic pathology laboratories. This covers
the techniques of fixation, gross examination, tissue
processing, embedding, cutting and staining. It also
covers the techniques adopted by the pathologist in
providing a rapid intraoperative diagnosis of the
lesion. The aim of this chapter is to provide practical
tips and solutions to the ophthalmologists and
students on how to examine the tissues removed,
interpret the histologic findings of different types of
tissues and also meaningfully interpret and under-
stand the report provided by the pathologist. The
tissues routinely submitted to any ophthalmic
pathology lab include those removed from the eye
and orbit for diagnostic or therapeutic purposes, e.g.
cornea, conjunctiva, lid, orbit, intraocular structures;
and fluid samples like aqueous and vitreous taps and
aspiration from cystic lesions.
HISTOLOPATHOLOGY
This is a study of disease process based on the
histologic interpretation of the tissues removed. The
tissues removed from the body are finally cut into
thin sections, stained appropriately so that they can
be interpreted by the pathologist so as to arrive at a
morphologic diagnosis of the lesion. To facilitate this,
the tissues are subjected to a series of procedures
that include: fixation, processing, embedding, cutting,
staining, and mounting which are discussed in brief
in the following sections.
Tissue Fixation
Fixation is a complex series of chemical events that
aims at preventing the tissues from autolysis and
bacterial attack, at the same time maintaining them
in a state as close to their living state as possible with
no loss of molecules. Different tissues require
different fixatives. The practical approach is to fix
the proteins in the tissues, which is the most common
substance in tissues. The aldehyde fixatives used in
the laboratory produces cross links between proteins
thereby forming a gel, keeping everything to their in
vitro relations to each other. Thus, soluble proteins
1072 Section 9: Miscellaneous Topics

are fixed to “structural proteins” so that it can Table 138.1: Types of fixatives used for different
withstand subsequent steps of processing. These procedures
reactions are largely reversible by washing in excess
Type of fixative Indications
of water. Some of the common fixatives are given in
Table 138.1. Formaldehyde (10%) Routine processing
The most common fixative used in histopathology Glutaraldehyde EM
is 10% buffered formalin (the commercially available Formal/gluataraldehye EM
40% Formaldehyde solution is considered as 100%) 95% ethyl alcohol Smears
which stabilizes the protein, oil and the carbohy- Tissue culture media/RPM Karyotyping,
drate.1-4 For electron microscopy (EM), 2% glutaral- Tissue cultures
dehye or a 4% formaldehyde-gluataraldehyde Fresh Frozen sections
mixture is preferred.4 Penetration of fixatives into IO cytology
the tissues is variable and depends on the size of the
tissue, e.g. small biopsies can be fixed within a few
The full thickness lid biopsy is examined for the lesion,
hours, but the eyeball requires 24 hours’ fixation
It is preferable to process the surgical margins and
before it can be cut open for further fixation.
the main lesion in separate blocks after noting down
Nowadays, microwave energy is being used to hasten
the details of the specimen. All fresh specimens could
various procedures involved in histopathology,
be painted with Indian ink preparation before fixing,
including the process of fixation. Use of microwave
so that the surgical margin involvement can be
energy interacts with dipolar molecules causing their
commented upon on all sections. The recommended
oscillation thus increasing the thermal energy of
method of grossing is given in Figure 138.1
water molecules and polar chain of proteins in the
tissues thus resulting in denaturation of the proteins.5 Grossing an Eye
Corneal buttons could also be fixed in a fixative
Examination of the eyeball is one of the important
called Perenyi’s fluid (100 ml prepared by mixing of
aspects in ophthalmic pathology. Identify the side of
40 ml of 10% nitric acid, 30 ml each of absolute alcohol
the eyeball (Fig. 138.2) A thorough and systemic
and 0.5% chromic acid).
examination of the eyeball at various stages is very
important to the pathologist and the clinician.7-9 It
Grossing
involves the following steps:
Macroscopic examination of ocular tissue before 1. Fix the intact ocular globe in formalin for 24 hours
submitting the tissues for processing is very impor- before sectioning. Do not open the globe, cut
tant.6 A brief description of the techniques are given windows in sclera or inject fixative into the
below. vitreous. Wash in running water for one or more
hours, and place the eyeball in 60% ethyl alcohol
Corneal Button for a few more hours.
Gross examination of the corneal button includes: its 2. Review the summary of the clinical history and
size, thickness, surface and margins for irregularities,
translucency, perforation, vascularization, 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 thera-
peutic keratoplasty, half of the corneal button is
submitted for microbiologic studies and the rest of
the tissue is processed for histopathologic studies. Fig. 138.1: Schematic picture of the lid showing a lesion at the
mucocutaneous junction (black fill). The surgical margins A &
Lid Biopsy B and the main lesion C should be proceeded as different blocks
 Chapter 138: Laboratory Techniques in Ophthalmic Pathology
Fig. 138.2: The schematic diagram of the posterior surface of
the eyeball showing the prominent landmarks which help in
identifying the side of the eyeball
the results of the ophthalmic examination prior to
opening of the globe.
3. Measure the dimensions of the eye following
order: AP x horizontal x vertical dimensions of
the eyeball and corneal horizontal x vertical
diameter; length of the optic nerve attached to
the globe (Fig. 138.3). Identify the significant
external markings like scars; corneal leukomas;
staphylomas; areas of unusual pigmentation;
distinct and abnormal shadows on
Fig. 138.3: Shows an enucleated eyeball along the optic nerve
stump. Measurements of the eyeball should be taken in antero-
posterior, horizontal and vertical planes. The length of the optic
nerve and the diameter without sheath should be measured
separately
1073
transillumination, etc.
a. Transillumination: Before an eye is opened, it
should be transilluminated. The normal eye
transmits light well except at the ciliary body/
iris and at any optic nerve of significant
length. Abnormal shadows should be
described (Fig. 138.4).
b. If a choroidal melanoma is suspected, sample
at least one of the vortex veins from each of
the four quadrants.
c. Opening the eye in a “P-O” (pupil-optic nerve)
line, choosing any meridian that gives most
possible additional information to the P-O
section. With the eye held in one hand, cornea
down on a moistened towel, and holding the
razor knife between thumb and finger or in
the blade handle. Use a sawing motion to make
the first cut and then the second.
Examine the intraocular structures without any
manipulation and take a gross photograph whenever
indicated (Figs 138.5 to 138.7).
Ideally, the gross description should include each
and every eye7,8 mentioning the following structures,
in this order.
Corneal thickness, depth and configuration of
anterior chamber and angle.
• Condition of iris, ciliary body, lens
• Condition of choroid, retina, vitreous body,
Fig. 138.4: The picture shows transillumination of the globe
showing a shadow in the region of the tumor while the
surrounding area shows illumination suggestive of thinning of
the sclera. It was a case of retinoblastoma with choroidal
coloboma
1074
Fig. 138.5: The cut section of the eyeball showing a soft gray
white fluffy tumor filling the entire vitreous cavity
Fig. 138.6: (A) The picture shows a central calotte of an eyeball
with a mushroom-shaped melanoma. The whole mount
preparation fo the section taken from the same block shows
the tumor and the eyeball (B)
Section 9: Miscellaneous Topics
Fig. 138.7: The picture shows one of the slices of the exentera-
ted specimen with a large tumor covering the ocular surface
and involving the palpebral conjunctiva. The entire slice should
be submitted for processing so as to examine the entire tumor
and the eyeball in their location
sclera, optic disk and optic nerve. Further
detail, such as particular reference to the iris
pigment epithelium, the lens capsule, etc.
• If a tumor is present: Its location, size, color,
edges, consistency, presence of hemorrhage or
necrosis, involvement of other ocular
structures and extension into optic nerve.
4. Sections for histologic examination should include
the entire eyeball, abnormal area, cross section of
optic nerve in case of retinoblastoma and sample
of at least one of the vortex veins from each of
the four quadrant.
Exenterated Specimen
Fix the specimen over night. Take surgical margins
A separately from cutaneous, soft tissues, and optic
nerve. Measure the specimen and the adjacent skin.
Cut the specimen through skin, soft tissues and ocular
globe.
Examine and describe the specimen in the follow-
ing manner:
a. Skin: Shape and length, appearance of lesions
present— their size, shape, depth of invasion, color
etc.
b. Soft tissues of the tumor— size, shape and
contour.
c. Ocular globe: Same as done for enucleated eyeball.
B Sections for histology should include tumor,
cutaneous and soft tissue surgical margins, globe with
tumor, orbital soft tissues adjacent to the tumor and
surgical margin of optic nerve
Tissue Processing
 Chapter 138: Laboratory Techniques in Ophthalmic Pathology 1075
The term tissue processing refers to the treatment of
tissues necessary to impregnate them with a solid
medium to facilitate the preparation of sections for
microscopy.10,11 The other method to cut tissues is to
freeze them and then cut them in a freezing
microtome or a cryostat. 12 The most satisfactory
embedding material for routine histology is paraffin
wax. The fixed tissues which are in an aqueous state,
before being embedded in paraffin wax, must be
subjected to the following: (i) Completion of fixation;
(ii) Gentle and gradual, but complete dehydration;
(iii) Clearing with substance which is totally miscible
with both the dehydration agent which precedes it
and the embedding agent which follows it. The tissue
processing is done by an automated tissue processor; A
the process includes gradual dehydration through
graded alcohol, two bath of clearing agents to remove
all traces of alcohol, two baths of melted paraffin at
56°C in this order.

Tissue Embedding and Cutting

The tissues infiltrated with wax are then embedded
in molds in an appropriate orientation depending on
the type of specimen and then made into blocks that
are properly labeled9 (Fig. 138.8A). Paraffin embed-
ded tissues are cut on a rotary microtome. The
sections are usually 3 to 6 microns thick. Serial
sections of small tissues can be studied for further
details. Care should be taken to ensure that the
complete section of the tissue embedded is seen on
the glass slides (Fig. 138.8B). If sections thinner than
this are required, then the tissues are embedded in
plastic resins and then cut up to 1 micron for semithin B
sections and 2 microns for ultrathin sections that are
to be studied using an electron microscope.
Figs 138.8A and B: (A) The picture shows a block of the
exenterated specimen embedded in paraffin wax. (B) The whole
Staining mount picture of the same block shows a tumor covering the
Routinely, a combination of two stains— basic and ocular surface as well as infiltrating the ocular coats with an
acidic dyes are used to stain the nucleus and the intraocular extension
cytoplasm.13 Hematoxylin (blue or violet) being a It is to be used on the section to identify or confirm
basic dye stains the nucleus, while the eosin stain the presence of various types of deposits, micro-
(pink or lilac) stains the cytoplasm (Table 138.2). In organisms (Table 138.4) and other abnormal chan-
addition, perioidic acid- Schiff’s (PAS) stain (Table ges.13,14 The common special stains include those done
138.3) is done to stain the basement membranes, for orbital and lid tumors and corneal dystrophies.
glycogen, mucins, fungal filaments and other The different stains done on corneas to distinguish
substances that are not well distinguished with the various types of infections and corneal dystrophies
H & E staining. are given in Tables 138.5A and B.

Special Stains Electron Microscopy

1076 Section 9: Miscellaneous Topics

Table 138.2 Procedure of routine hematoxylin Table 138.4: Special stains for identification
and Eosin staining of microorganisms in ocular tissues
Hematoxylin and eosin staining procedure Microorganism Stain
Xylene 3 changes 2 minutes each Bacteria Grams
100% alcohol 10 dips Fungus PAS, GMS, CFW
Acanthamoeba Acridine O, PAS, GMS, CFW,
95% alcohol 10 dips Masson’s trichrome
Waterwash Acid-fast bacilli Ziehl-Neelsen stain, Fite’s stain,
(hot and cold stains)
Hematoxylin 10 minutes Microsporidia AFB, Grams,
Modified trichrome stain
Waterwash 2-5 minutes
1% acid alcohol 3 dips
Table 138.5A: Special stains for diagnosis
Waterwash 1 minute of corneal dystrophies
Eosin 5 dips Stromal dystrophy Special stain
80% alcohol 10 dips Granular Masson’s trichrome,
95% alcohol 10 dips Wilder’s reticulin
Avellino Congo red* stain
100% alcohol 10 dips
Lattice dystrophy type I Congo red*
Xylene 2 changes
Lattice dystrophy type II Congo red*
mounting
Macular dystrophy Alcian blue, Colloidal Iron
Fleck dystrophy Alcian blue, colloidal iron,
Table 138.3: Periodic acid-Schiff’s (PAS) staining and lipid stains

Xylene 3 changes 2 minutes each * Confirmation of amyloid deposits is by the congophilic

nature, diachorism and apple green birefringence when
100% alcohol 10 dips observed under polarized filters
95% alcohol 10 dips
Waterwash
Table 138.5B: Immunohistochemical pattern of
Periodic acid 5 minutes
small cell undifferentiated tumors
Rinse in distilled water 1 min
Neoplasm LCA Keratin NSE NF Desmin
Place in Schiff reagent 15 minutes
Lymphoma + — — — —
Wash in tap water 10 minutes
Counter staining in hematoxylin 15 minutes Leukemia + — — — —
Wash in tap water 5 minutes Neuroblastoma — — + + —
80% alcohol 10 dips Retinoblastoma — — + + —
95% alcohol 10 dips Rhabdomyosarcoma — — — — +
100% alcohol 10 dips Ewing’s sarcoma — — — — —
Xylene 2 changes Wilms’ tumor — + — — +/—
mounting
Small cell carcinoma — +/— +/— +/— —

Transmission electron microscopy is used selectively;
it has been supplanted by immunohistochemistry that
is cheaper, faster and less laborious. It is used to
identify the basic ultrastructural features of the cells.15
It is specifically employed to confirm the nature of
the lesion based on the presence of structures within
the cell that are identified only by ultrastructure, e.g.
the neurosecretory granules of neuroendocrine
tumors, the tennis racket-shaped body in
Langerhan’s cell histiocytosis, etc. In tumor
pathology, it is useful in determining the histogenesis
 Chapter 138: Laboratory Techniques in Ophthalmic Pathology
of various tumors.
Other utilities of the electron microscope include
differential diagnosis between a carcinoma, mela-
noma, and sarcoma; between adenocarcinoma and
squamous cell carcinoma; round cell tumors—Ewing’s
sarcoma, rhabdomyosarcoma, malignant lymphoma,
neuroendocrine tumors and spindle cell tumors of
orbit. Electron microscopy is used to characterize the
native cells as well confirm the nature of tumors.16
Immunologic and Molecular Techniques
Diagnosis of lesion is usually made on the basis of
morphology. However, in many instances, it has to
be aided by immunodiagnosis where the diagnosis
is made based on the property of the given tissue/
cell to express specific antigens. These antigens are
detected by using a set of antibodies that bind to
specific antigens and are labeled either directly or
indirectly with the help of secondary antibodies that
are attached to a chromogen.17-19 Some of the comm-
only used antibodies for diagnosing orbital tumors
are given in Table 138.6. The procedure of immuno-
histochemistry using peroxidase-antiperoxidase
method for paraffin sections is described in brief.
i. Prewarm all slides including the positive and
negative control for 10 minutes in 60°C oven.
ii. Dewax slides (3 × 5 minutes in Xylene, 1 × 5
minutes in absolute alcohol, 1 × 5 minutes 80%
alcohol, 1 × 5 minutes in 75% alcohol)
iii. Rinse in distilled water.
iv. Wash sections for 5 minute in wash buffer.
1077
v. Block endogenous peroxidase for 30 minutes
in methanol/ H2 O2 Solution.
vi. Wash slides in wash buffer for 15 minutes.
vii. Incubate sections in enzyme solution for 10 to
15 minutes (pepsin, trypsin, pronase)
viii. Wipe around each section separately. Drain off
as much buffer as possible but do now allow
sections to dry out at any stage after this. Place
slides in humidity chamber.
ix. Apply 100 Microliter of non-immune serum
(horse, goat, swine in 1: 50 dilutions) for 30
minutes.
x. Drain off the drop of serum, wipe around the
section carefully without touching the section.
Apply 100 Mic of diluted primary antibody and
incubate overnight at 4°C.
xi. Wash with wash buffer for 10 minutes × 2
changes.
xii. Wipe around sections again, apply 100M second
antibody for 30 minutes (anti mouse/anti
rabbit, anti swine in 1in 100 dilutions).
xiii. Wash for 15 minutes in wash buffer.
xiv. Wipe around sections. Apply 100 M of PAP
complex for 45 to 60 minutes in 1: 50 dilutions.
xv. Wash for 15 minutes in wash buffer.
xvi. Color determination step: Incubate in freshly
prepared DAB/ H2 O2 solution at room tempe-
rature for 5 to 10 minutes.
xvii. Wash for 5 minutes gently in running tap water.
xviii. Counterstain with Harris hematoxylin.
xix. Wash till blue and dehydrate, clear and mount.
In addition to academic interest, the common

Table 138.6: Immunohistochemistry for spindle cell tumors

Neoplasm Vimentin M actin SM actin Desmin S-100 FVII Ag Keratin Myoglobin
F. histio + ± ± — — — — —
RMS + + — + — — — ±
Leiomyo + + + — — — — —
Liposa + — — — ± — — —
HPC + — — — — — — —
Angio sa + — — — — + — —
Sch/NF + — — — + — — —
Chondro + — — — ± — — —
Spin C Ca ± — — — — — + —

M actin = muscle actin; SM actin = smooth muscle actin; FVIII Ag = factor VIII antigen; HPC = hemangiopericytoma;
Chondro = chondrosarcoma; Spin C Ca = spindle cell carcinoma
1078 Section 9: Miscellaneous Topics

A B
Figs 138.9A and B: Section of an orbital lymphoma showing monomorphic sheets of round cells with scant
rim of cytoplasm and a hyperchromatic nucleus with inconspicuous nucleoli, which is highly suggestive of
lymphoma (hematoxylin & eosin, x 400). The clonal nature of the tumor cells is confirmed in this case by
immunopositivity to B cell markers (DAB, x 200)

A B
Figs 138.10A and B: The section from a non-pigmented conjunctival tumor showing large epitheloid cells with
vesicular nucleus and prominent nucleoli, highly suggestive of amelanotic melanoma (hematoxylin & eosin, x
400). Immunohistochemistry using S-100 shows positive staining, confirming the diagnosis of a melanoma
and ruling out a large cell lymphoma (DAB, x 400)

A B
Figs 138.11A and B: (A) The spindle cell tumor of the optic nerve shows elongated spindle cells with ill-
defined cell margins and fibrillary background (hematoxylin & eosin, 200). (B) The tumor cells show
immunoreactivity to glial fibrillary acidic protein, thus confirming a glioma of the optic nerve (DAB, x 200)
 Chapter 138: Laboratory Techniques in Ophthalmic Pathology
indication for IHC is in diagnosing different types of
round cell tumors, e.g. differentiating lymphoma from
rhabdomyosarcoma (Fig. 138.9), amelanotic mela-
noma from carcinoma (Fig. 138.10), and glioma from
other spindle cell tumors (Fig. 138.11).
Molecular Diagnostic Tools
1. With the advancing techniques, it is now possible
to determine the actual presence or absence of a
segment of a gene by using appropriate molecular
tools and primers. A commonly employed tech-
nique is the polymerase chain reaction (PCR) which
amplifies a single strand of nucleic acid a thousand
times enabling the pathologic diagnosis.20,21 PCR
can thus be employed on DNA extracted from
formalin-fixed and paraffin embedded tissues
making it more feasible to use archived tissues.22,23
The in situ hybridization technique24,25 employs
nucleic acid probes whose sequences are comple-
mentary to the DNA of the organism or the gene
sought, e.g. detection of human papilloma virus
in conjunctival tumors.26,27 The labeling of probes
is usually done by either radioactive substances
or biotin and bromodeoxyuridine. The advantage
of in situ hybridization is that it allows the
visualization of cellular DNA or RNA in the tissue
sections, single cells or chromosome preparation.
In situ hybridization28 can be with an isotope or
non-isotope method. In brief, it involves choosing
the appropriate probes specific to detect the test
DNA, labeled probes, detection system (strept-
avidin-alk phosphatase or anti-digoxygenin conju-
gates), incubating the enzyme-treated sections
with test probes and then heated to denature both
the tissue and probe DNA. Hybridization is done
in the optimum temperature and medium and the
end product is stained for visualization. The main
use of this technique is in the detection of microbes
(mycobacteria, viruses) and oncogenes.
Principle of Polymerase Chain Reaction
The polymerase chain reaction, invented by Kary B
Mullis, is a technique to exponentially amplify in vitro
a small quantity of a specific nucleotide sequence in
the presence of template sequence, two oligonucleo-
tide primers that hybridize to opposite strands and
flank the region of interest in the target DNA, a
thermostable (taq) DNA polymerase. The reaction is
1079
cycled involving template denaturation, primer
annealing, and the extension of the annealed primers
by DNA polymerase until enough copies are made
for further analysis.
In order to accomplish this, it is necessary to know
at least some of the DNA sequence flanking the region
to be assayed before amplification can be carried out.
The brief protocol involves addition of a buffer,
forward and reverse primer, appropriate template
DNA, and subjecting it into thermocycler with
addition of enzyme (Taq, Tli, Pfu, etc.) and a few drops
of mineral oil. The PCR cycles are run for 29 cycle,
each containing steps of denaturation, annealing and
extension. The final product is then run on a gel for
confirmation. This protocol can be modified based
on the nature of the primers and test sample. In
ophthalmic practice, it has been applied to diagnose
various infections from ocular samples, to detect the
presence of virus in corneal tissues and in
tumors.22,23,26,27 For paraffin sections, the sections will
be deparaffinized in xylene, tissue will be subjected
to proteinase K digestion. DNA is isolated by phenol-
chloroform extraction and ethanol precipitation and
amplified using primers specific for different DNA
sequences of the test sample.
Flow Cytometry
Flow cytometry is used for simultaneous measure-
ment of several parameters while a suspension of cells
flows through a beam of light past stationary
detectors.29-31 The instrument allows analysis of 5,000
to 10,000 cells per second of information on
parameters like cell size, cytoplasmic granules, cell
viability, cell cycle time, DNA content, surface marker
phenotype and enzyme content. One of the main
limitations is that the cells should be in single cell
suspension. This requirement can be achieved in
blood, fluids, fresh tissues, needle aspirates and now
nuclear suspension recovered from thick sections of
routine formalin-fixed, paraffin-embedded tissues.
The current clinical uses include:
1. Support a diagnosis when the morphological
changes are equivocal
2. Subclassification of lesions of borderline malig-
nancy
3. Prognostic markers, independent of stage and
grade
4. Monitor response to therapy
5. Establish development of tumor relapse. In ocular
1080 Section 9: Miscellaneous Topics

tissues, it has been used to diagnose lympho- Preoperative Diagnosis

proliferative lesions of orbit and conjunctiva.32,33
Fine-Needle Aspiration/Sampling Technique
Tissue Culture and Karyotyping The procedure for FNAC at any site in the body is
the same and can be performed either by the
Though tissue cultures have been performed in non-
pathologist or a clinician, directly under vision or
ocular tumors,34 a few studies have been done of
under guidance of CT.43 Usually, there is no need
cultures of retinoblastoma tumors, melanoma and
for any local anesthetic injection in this technique
lacrimal gland tumor. 35-37 The rationale of tissue
except in children where a general anesthesia may
culture is to demonstrate the differentiation of the
be preferred. The technique of obtaining the material
tumor cells in ex vivo conditions, undertake karyo-
could be a “sampling technique” wherein a 23/24-
typing, immunocytochemistry or ultrastructural
gauge needle is introduced into the lesion and pushed
studies. The culture conditions could be modified
in various directions within the lesion and gently
based on the objectives of the study. The diagnostic
withdrawn (Fig. 138.12).44,45 By the capillary action,
utility of tissue cultures is, however, practically non-
the cells are drawn into the needle. The advantage
existent expect; but it has, however, contributed
of this technique is that it is easy, simple, less
extensively as a research tool, including pharmaco-
traumatic and causes less apprehension to the patient.
kinetic studies on drug resistance and may possibly
It is performed by using a syringe attached to the
pave way for development of treatment protocols
needle so as to create a negative pressure. To obtain
and vaccines.38,39
the greater possible yield, the needle could be moved
back and forth within the lesion along the same track
SPECIAL PROCEDURES IN with negative pressure maintained. Negative pressure
OPHTHALMIC PATHOLOGY should be released when the needle is being removed
from the lesion. Two different methods of fixation
Eye and orbital lesions with its diverse etiology
and staining are used in FNA cytology: air drying
remain an enigma and pose a challenge even to the
followed by staining with a hematologic stain such
most experienced ophthalmologist. In this section a
as MGG, Jenner-Giemsa, Wright’s stain, or Diff-Quik;
simple strategy to the cytologic and histologic
and alcohol fixation and staining with Pap or H &
diagnosis of the eye and orbital lesions is provided.
E.13-14 Both techniques are complementary to each
The tissue diagnosis in most instances is the final
other.
diagnosis. After coming to a presumptive clinical
The main advantage of this procedure is obtaining
diagnosis of orbital lesions based on the clinical and
an early cytological diagnosis of the lesion. It may be
radiologic features, a decision needs to be made
done as an outpatient procedure. A few
regarding the procedure to be adopted to confirm
disadvantages include inadequate material,
the nature of the lesion. The methods of tissue
diagnosis which include pre-operative fine-needle
aspiration cytology (FNAC) or biopsy (FNAB) or a
routine tissue diagnosis after a surgical biopsy,40 has
been well established in ophthalmology for orbital
lesions.41-43 A preoperative diagnosis is indicated if
the suspected tumor is planned to be treated without
surgical intervention. Rhabdomyosarcoma,
sarcoidosis, metastatic tumors, reactive lymphoid
hyperplasia, lymphoma, sclerosing and infectious
orbititis are the clinical conditions of this group. The Fig. 138.12: The figure shows a schematic diagram of the lesion
decision for the type of biopsy whether surgical in the orbit and lid. The first inset shows the method in which
the needle should be introduced into the lesion. The second
biopsy or FNAB would depend on the size, site,
inset shows the aspiration technique wherein a syringe is
shape, circumscription, encapsulation, consistency, attached to the needle. This can be done without the help of a
approximation to the neighboring structures and the syringe (fine needle sampling technique). The aspirated material
accessibility of the lesion from surgical point of view. is smeared on a slide and sent to the laboratory for cytologic
diagnosis
 Chapter 138: Laboratory Techniques in Ophthalmic Pathology 1081
hemorrhagic aspirate and bleeding at the site of
FNAC. 46-47 At our center, FNAC has yielded
diagnostic yield in more than 90% of cases, while Tijl
et al report the diagnostic yield of orbital FNAB
combined with clinical and radiological features as
80%.48 Very rare potential complications include are
globe penetration, retrobulbar hemorrhage, diplopia
and ptosis.

Intraoperative Diagnosis
There is often a need for a reliable intraoperative
diagnosis, specifically in situations where a definitive
preoperative tissue diagnosis is lacking and where
the tissue diagnosis is likely to influence the immediate
surgical management.49 It should be remembered that
it is not indicated merely to satisfy the curiosity of
the surgeon. The established methods of
intraoperative diagnosis include frozen section
diagnosis and intraoperative cytologic diagnosis, each
of which has its own merits and demerits. In general,
a complete excision of the mass (excisional biopsy) is
indicated for all cystic, well-circumscribed and
encapsulated lesions, easily accessible lesions and all
suspected benign lesions.50 For the lesions that are
suspected to be malignant, with infiltrative margins,
solid consistency and have a complex surgical
approach, an incisional biopsy may be indicated.
In an incisional biopsy only a portion of the lesion
is removed to provide a sample for diagnosis. The
best place to sample the tissue is at the periphery,
always including normal tissue for easier
interpretation. The center of the tissue should not be
biopsied, especially if there is central ulceration.
Frozen Sections
Frozen section is one of the most important
procedures that requires experience, knowledge of
clinical medicine, pathology, good judgment, capacity
conservative approach and a capacity to make quick
decision under pressure. It is generally indicated to
determine the nature of the lesion, if the resection
margins are free from tumor or if the surgeon has
biopsied representative material. 51,52 The fresh
unfixed tissue is embedded in a freezing media using
a block holder (Fig. 138.13). The sections are then cut
with the help of a cryostat and are stained with a
rapid hematoxylin and eosin technique. Interpretation
can be done within 6 to 10 minutes per block. The
advantages of this technique is that it gives good
architectural details and is extremely useful to
Fig. 138.13: The picture of a cryomicrotome that is
used for cutting frozen sections
comment on nature of the lesion, surgical margins of
malignant lid tumors and to differentiate between
in situ or invasive lesions. The disadvantages,
however, include the frozen section artifacts
produced in the sections which most of the
pathologists are familiar with. This technique requires
a special cryomicrotome, a technician and a patho-
logist trained for frozen section reporting. It is not
very useful for small tissue, fatty tissues or bony
lesions.
Squash or Imprint Cytology
The utility of imprint cytology in eye lesions was first
described by Fuchs for uveal melanoma in 1988.53
Imprint cytology of fresh unfixed tissue specimens
and squash cytology of central nervous system lesions
have been extensively used in the last few decades,
but has recently been introduced to ophthalmic
pathology practice.54,55 It can be utilized for the
following indications:
1. Infiltrative lesions, suspected malignant lesions or
deeply located lesions where a preoperative tissue
diagnosis was not available
2. Discrepancy between a preoperative clinical
diagnosis and the intraoperative findings
3. Unusual clinical presentations with diagnostic
dilemma.
Method Fresh unfixed tissue obtained at the time of
diagnostic or excision biopsy can be used for making
1082 Section 9: Miscellaneous Topics
Fig. 138.14: The picture shows the technique of doing imprint
cytology on a fresh specimen. Clean glass slides are touched
to the freshly cut surface of the tumor and gently pressed to as
to get the cells onto the glass slide
Fig. 138.15: The picture shows the technique of doing imprint
cytology wherein a small bit of fresh tissue is kept on the center
of a glass slide and then with the help of another glass slide
placed perpendicular to it, the tissue is firmly spread across
the glass slide
squash preparation and impressions on glass slides.
The procedure for making squash or imprint smears
is usually based on the size, shape, consistency and
crushability of the tissue submitted. For soft, easy-
to-spread tissues, tiny bit of the fresh tissue is placed
between two clean glass slides and gently drawn
apart (Fig. 138.14). For large firm specimens, the
imprint smears are prepared by touching the freshly
cut surface of the lesion with clean slides, avoiding
smearing to retain cell morphology (Fig. 138.15). If
the surface was covered with blood or exudates, more
number of smears are made, after gently wiping the
surface clean. It is preferable to make a minimum of
three slides for each case. It is advisable to preserve
extra unstained smears for further tests like immuno-
cytochemistry or for any molecular studies in future.
These smears are either alcohol fixed for rapid
hematoxylin and eosin staining, or fixed by air-drying
for Diff-quick staining. A provisional cytologic
diagnosis can be made by the pathologist based on
the cellular and architectural features seen on smears
prepared from either or both techniques. After
reporting on the cytology slides, the remaining tissue
should be fixed in 10% buffered formalin and
processed for permanent sections, and stained by
hematoxylin and eosin, and periodic acid-Schiff’s
stain (Table 138.3). Special and immunohistochemical
stains can be done. Though the accuracy of combined
frozen section and cytology is the ideal method of
intraoperative diagnosis, imprint and squash cytology
alone gives 96% accuracy.56
FLUID (VITREOUS, AQUEOUS OR
OTHER FLUIDS) CYTOLOGY
The most common fluid sample from ophthalmic
surgeries is vitreous fluid. The vitreous sample is
Fig. 138.16: The picture shows the cytospin machine which is
used to centrifuge a small amount of fluid in a manner that the
cells are spread across a small area on the glass slide and
show good yield and preservation of cytologic features. Rest
of the fluid in the sample is absorbed by the filter paper that is
kept between the slide and the holder
 Chapter 138: Laboratory Techniques in Ophthalmic Pathology 1083
obtained as a vitreous biopsy (undiluted) or from
vitrectomy procedures (diluted). The fluid obtained
is, therefore, unfixed and, therefore, requires urgent
attention in the laboratory. The samples can be
processed in different ways: celloidin bag techniques,
cytocentrifugation (Fig. 138.16), direct smears and
by Millipore filtration devices.57,58 Most commonly
used technique is cytospin, which gives good cellular
recovery and excellent cytologic details. Here, the
sample is fed into the plastic tube, and arranged in a
holder which contains a filter paper, glass slide and
the plastic tube. The cytospin is usually set for
10 minutes at 1000 revolutions per minute, which
concentrates the cells into a focal area on the glass
slide. The slides are then fixed either in alcohol or by Fig. 138.17: The picture of the conjunctival impression cytology
rapid air-drying. Depending on the indication of the using nitrocellulose paper shows sheets of epithelial cells on
the filter paper along with large PAS positive goblet cells (PAS-
vitreous biopsy, the sample is then submitted for
hematoxylin stain, 400)
routine cytology, electron microscopy,
immunocytochemistry, special stains and flow
cytometry.

CONJUNCTIVAL IMPRESSION CYTOLOGY

One of the tests that is frequently done in diagnosing
squamous metaplasia of the ocular surface is
Impression cytology of the ocular surface using a
nitrocellulose paper.59-64 This is based on the principle
that by capillary action, the superficial cells of ocular
surface are transferred to the filter paper, which can
be stained and interpreted for the type of cells lining
the ocular surface.65 This was initially and frequently
used for diagnosing squamous metaplasia due to
Vitamin A deficiency wherein there was loss of goblet
cells with gradual change of columnar cells to
squamous cells with keratinization.66

Method
1. Fix the filter paper in 70% ethanol for 2 minutes
2. Wash in tap water X 10 dips.
3. Apply periodic acid-Schiff reagent 0.5% for 2
minutes.
4. Wash in tap water X 10 dips
5. Immerse in 5% Sodium metabisufite for 2 minutes
6. Stain with hematoxylin for 2 minutes
7. Dehydrate in 95% ethyl alcohol X 10 dips
8. Stain with eosin for 2 minutes
9. Dehydrate in absolute alcohol for 2 minutes Fig. 138.18: The picture shows a steromicroscope under which
10. Transfer into xylene a specimen can be examined in detail and a gross photograph
11. Mount with glycerin mount or paramount of the specimen can be taken at appropriate magnification. It is
advisable to immerse the specimen in alcohol for restoration of
The filter paper becomes transparent in the organic
natural color and to avoid the glare
1084 Section 9: Miscellaneous Topics
solvents. Under the microscope, observe for the
presence of goblet cells which appear as magenta pink
cells (Fig. 138.17).
OPHTHALMIC PHOTOGRAPHY
Documentation of the cases is important not only for
academic interest or teaching purposes but also are
considered as a legal document. Hence gross and
microphotography is extensively used in this
specialty. It could be done with the help of a digital
camera or a well-equipped photographic system
(Fig. 138.18). 67 Ideally, the photograph of the
specimen is taken when it is submerged in 60% of
ethanol which restores the color of the specimen even
after initial fixation in 10% formaldehyde. Use of
appropriate lighting, good quality camera roll,
appropriate use of close up and macro lenses, clean
background free of artifacts are essential for good
microphotographs.67,68 The pictures can be taken with
a digital camera in-built or external or with traditional
film. The pictures should be taken at appropriate
magnification so as to highlight the relevant features
of the case. Even though the new photo editing
software can manipulate the picture, it is ideal to take
good pictures in the first instance which require
minimal modification.
REFERENCES
1. Pearse AGE. Histochemistry theoretical and applied (4th edn),
Vol 1. Edinburgh: Churchill Livingstone 1975.
2. Hopwood D. Fixation and fixatives. In Bancroft JD, Stevens A
(Eds): Theory and Practise of Histological Techniques (3rd
edn). Churchill Livingstone 1990;21-34.
3. Hopwood D. Theoretical and practical aspects of glutaral-
dehyde fixation. Histochemical Journal 1972;4:267.
4. Prophet EB, Mills B, Arrinton JB, Sobin LH. AFIP Laboratory
Methods in Histotechnology, American Registry of Pathology,
Washington DC, 1992;25.
5. Margo CE, Saxe S, Grossniklaus HE. Microwave-stimulated
chemical fixation of whole eyes. Ophthalmology 1992;99:1117.
6. Torczynski E. Preparation of ocular specimens for histopatho-
logic examination. Ophthalmology 1981;88:1367.
7. Spencer WH, Folberg R. Gross examination of the eye (Chap
2). In Spencer WH (Ed): Ophthalmic Pathology (4th edn),
Spencer WH, Philadelphia: WB Saunders Co, 1996.
8. Rosai J. Gross techniques in surgical pathology. Ackerman’s
Surgical Pathology. 7th edn. St Loius: CV Mosby Co, 1989;13-
29.
9. Gravanis MB, Rietz CW. The problem-oriented postmortem
examination and record: an educational challenge. Am J Clin
Pathol 1973;60:522.
10. Hall J. In Embedding. In Laboratory Methods in Histochemistry.
Prophet EB, Mills B (Eds): Armed Forces Institute of Pathology,
American Registry of Pathology. Washingtion DC 1992;39-44.
11. Emanuele PV. Ocular Histotechnology. In Prophet EB, Mills B
(Eds): Laboratory Methods in Histochemistry. Armed Forces
Institute of Pathology, American Registry of Pathology.
Washingtion DC 1992;109.
12. Bancroft. JD. Frozen and related section. In Theory and Practice
of Histological Techniques (ed). Edinburg, London: Churchill
Livingstone 1990;81-92.
13. Horobin RW. An overview of the theory of staining. In Theory
and Practice of Histological Techniques (ed). Edinburg,
London: Churchill Livingstone 1990;81-92.
14. White VA. Advanced diagnostic techniques—diagnostic
immunohistochemistry. In Albert DM, Jokobiec FA (Eds):
Principles and Practise of Ophthalmology. Philadelphia: WB
Saunders, 1994;2372-86.
15. Erfandson RA, Erlandson RA. Application of transmission
electron microscopy to human tumor diagnosis: An historical
perspective. Cancer Invest 1987;5:487.
16. Fine BS, Ts’o MO, Font RL, Zimmerman LE. Electron
microscopy of pathologic ocular tissue. Int Ophthalmol Clin
1971;11:57.
17. Mukai K, Rosai J. Immunocytochemistry in diagnostic
histopathology: Its contributions and limitations. Basic Appl
Histochem 1981;25:153.
18. Eagle RC Jr. Immunohistochemistry in ophthalmic pathology.
In Liabson PR (Ed): The year book of Ophthalmology, 1990. St
Louis: Mosby Year Book 1990;133.
19. Eagle RC Jr. Specimen handling in the ophthalmic pathology
laboratory. Ophthalmol Clin North Am 1995;8:1.
20. Mullis K, Faloona F, Scharf S, Saiki R, Hom G, Erlich H. Specific
enzymatic amplification of DNA in vitro: The polymerase chain
reaction. Cold Spring Harb Symo Quant Biol 1986;51:263.
21. Erlich HA. Basic methodology in PCR technology: Principles
and application for DNA amplification. W H Freeman and
Co, New York, 1992.
22. Madhavan HN, Therese KL, Gunisha P, Jayanthi U, Biswas J.
Polymerase chain reaction for detection of Mycobacterium
tuberculosis in epiretinal membrane in Eales’ disease. Invest
Ophthalmol Vis Sci 2000;41:822.
23. Chichili GR, Athmanathan S, Farhatullah S, Gangopadhyay
N, Jalali S, Pasricha G, Sharma S. Multiplex polymerase chain
reaction for the detection of herpes simplex virus, varicella-
zoster virus and cytomegalovirus in ocular specimens. Curr
Eye Res 2003;27:85.
24. Grody WW, Cheng L, Lewin KJ. Application of in situ DNA
hybridization in diagnostic surgical pathology. Pathol Annu
1987;151.
25. Sklar J. DNA hybridization in diagnostic pathology. Hum
Pathol 1985;16:654.
26. Nakamura Y, Mashima Y, Kameyama K, Mukai M, Oguchi Y.
Detection of human papillomavirus infection in squamous
tumours of the conjunctiva and lacrimal sac by immuno-
histochemistry, in situ hybridisation, and polymerase chain
reaction. Br J Ophthalmol 1997;81:308.
27. Saegusa M, Takano Y, Hashimura M, Okayasu I, Shiga J. HPV
type 16 in conjunctival and junctional papilloma, dysplasia,
and squamous cell carcinoma. J Clin Pathol 1995;48:1106.
28. De Gaetani C, Ferrari G, Righi E, Bettelli S, Migaldi M, Ferrari
P, Trentini GP. Detection of human papillomavirus DNA in
 Chapter 138: Laboratory Techniques in Ophthalmic Pathology
urinary bladder carcinoma by in situ hybridisation. J Clin Pathol
1999;52:103.
29. Braylum RC. Flow Cytometry. Arch Pathol Lab Med 1983;
107:1.
30. Coon JS, Landay AL, Weinstein RS. Biology of disease.
Advances in flow cytometry for diagnostic pathology. Lab
Invest 1987;57:453.
31. Frierson HF Jr. Flow cytometric analysis of ploidy in solid
neoplasm. Comparison of fresh tissue with formalin-fixed
paraffin-embedded specimen. Hum Pathol 1988;19:290.
32. Wolska-Szmidt E, Masiuk M, Krzystolik K, Chosia M. Flow
cytometry in the diagnosis of lymphoproliferative lesions of
the orbit and eye adnexa in fine needle aspiration biopsy. Pol J
Pathol 2003;54:253.
33. Laucirica R, Font RL. Cytologic evaluation of lymphoprolife-
rative lesions of the orbit/ocular adnexa: An analysis of 46
cases. Diagn Cytopathol 1996;15:241.
34. Murray MR, Stout AP. The classification and diagnosis of
human tumors by tissue culture methods. Tex Rep Biol Med
1954;12:898.
35. Char DH, Wood IS, Huhta K, Rand N, Morita CT, Howes EL
Jr. Retinoblastoma: Tissue culture lines and monoclonal
antibody studies. Invest Ophthalmol Vis Sci 1984;25:30-40.
36. Albert DM, Rabson AS, Dalton AJ. Tissue culture study of
human retinoblastoma. Invest Ophthalmol 1970;9:64.
37. Lauer SA, Levin RJ, Bradley MK, Rosenbaum PS, Rameau R.
An immortalized cell culture from a malignant mixed tumor
of the lacrimal gland. Ophthal Plast Reconstr Surg 1997; 13:168.
38. McNamara M, Clynes M, Dunne B, NicAmhlaoibh R, Lee WR,
Barnes C, Kennedy SM. Multidrug resistance in ocular
melanoma. Br J Ophthalmol 1996;80:1009.
39. Dillman RO, Nayak SK, Barth NM, DeLeon C, Schwartzberg
LS, Spitler LE, Church C, O’Connor AA, Beutel LD. Clinical
experience with autologous tumor cell lines for patient-specific
vaccine therapy in metastatic melanoma. Cancer Biother
Radiopharm 1998;13:165.
40. Koss LG. Aspiration biopsy: A tool in surgical pathology. Am
J Surg Pathol 1988;12:43.
41. Schyberg E. Fine needle biopsy of orbital tumors. Acta
Ophthalmol 1988;125:11.
42. Kennerdell JS, Slamovits TL, Dekker A, Johnson BL. Orbital
fine-needle aspiration biopsy. Am J Ophthalmol 1985;99:547.
43. Czerniak B, Woyke S, Danieal B, Krzysztolik Z, Koss LG.
Diagnosis of orbital tumors by aspiration biopsy guided by
computerized tomography. Cancer 1984;54:2385.
44. Santos JE, Leiman G. Nonaspiration fine needle cytology:
Application of a new technique to nodular thyroid disease.
Acta Cytol 1988;32:353.
45. Zajdela A, de Maublanc MA, Schlienger P, Haye C. Cytologic
diagnosis of orbital and periorbital palpable tumors using fine
needle sampling without aspiration. Diagn Cytopathol
1986;2:17.
46. Krohel GB, Tobin D, Chavis RM. Inaccuracy of orbital fine
needle aspiration biopsy. Ophthalmology 1984;91:83.
47. Liu D. Complications of fine needle aspiration biopsy of the
orbit. Ophthalmology 1985;92:1768.
48. Tijl JW, Koornneef L. Fine needle aspiration biopsy in orbital
tumours. Br J Ophthalmol 1991;75:491.
1085
49. Ackerman LV, Ramirez GA. Indication for and limitation of
frozen section diagnosis: A review of 1269 consecutive frozen
section diagnosis. Br J Surg 1959;46:336.
50. Dallow RL, Pratt SG. Approach to orbital disorders and
frequency of disease occurrence. In Albert DM, Jokobiec FA
(Eds): Principles and Practise of Ophthalmology. Philadelphia:
WB Saunders 1994;1881-1889.
51. Young I. Use of the cryostat: An aid to frozen section diagnosis
in surgical pathology. J Albert Einstein Med Cent (Phila).
1963;11:82.
52. Older JJ, Quickert MH, Beard C. Surgical removal of basal cell
carcinoma of the eyelids utilizing frozen section control. Trans
Am Acad Ophthalmol Otolaryngol 1975;79:658.
53. Fuchs U. Smear and imprint technique in malignant lesions of
the eye. Acta Ophthalmol (Copenh) 1988;66:445.
54. Font RL, Laucirica R, Ramzy I. Cytologic evaluation of tumors
of the orbit and ocular adnexa: An analysis of 84 cases studied
by the “squash technique”. Diagn Cytopathol 1994;10:135.
55. Vemuganti GK, Naik M, Honavar SG, GC Shekar. Rapid
Intraoperative diagnosis of tumors of the eye and orbit by
squash and imprint cytology. Ophthalmology
2004;111(5):1009-1015.
56. Mair S, Lash RH, Suskin D, Mendelsohn G. Intraoperative
surgical specimen evaluation: frozen section analysis,
cytological examination, or both? A comparative study of 206
cases. Am J Clin Pathol 1991;96:8.
57. Engel H, ZC de l Cruz, Jimenez- Abalahin LD, Green WR et al.
Cytopreparatory techniques for eye fluid specimens obtained
by vitrectomy. Acta Cytol 1982;26:551.
58. Chess J, Sebeg J, Tolentino FI, Schepens L, Calderone JP et al.
Pathologic processing of vitrectomy specimensl; a comparison
of pathologic findings with celloidin bag and cytocentrifugation
preparation of 102 vitrecomy specimens. Ophthalmology
1983;90:1560.
59. Egbert PR, Lauber S, Maurice DM. A simple conjunctival biopsy.
Am J Ophthalmol 1977;84:798.
60. Tseng SC. Staging of conjunctival squamous metaplasia by
impression cytology. Ophthalmology 1985;92:728.
61. Nelson JD. Impression cytology. Cornea 1988;7:71.
62. Nolan GR, Hirst LW, Bancroft BJ. Impression cytology for
detection of vitamin A deficiency. Arch Ophthalmol
1987;105:1224.
63. Puangsricharern V, Tseng SC. Cytologic evidence of corneal
diseases with limbal stem cell deficiency. Ophthalmology
1995;102:1476.
64. Sridhar MS, Vemuganti GK, Bansal AK, Rao GN. Impression
cytology-proven corneal stem cell deficiency in patients after
surgeries involving the limbus. Cornea 2001;20:145.
65. Spinak M, Friedman AH. Squamous cell carcinoma of the
conjunctiva: Value of exfoliative cytology in diagnosis. Surv
Ophthalmol 1977;21:351.
66. Nolan GR, Hirst LW, Bancroft BJ. Efficacy of a training
programme designed to teach cervical smear screeners to
identify ocular surface squamous neoplasia using conjunc-
tival impression cytology. Cytopathology 1997;8:388.
67. Eagle RC. Photographic tips for the ophthalmic pathology
laboratory. In Wilson R (Ed): The Year Book of Ophthalmology
1997. St Louis: Mosby 1997;341-54.
68. Biswas J, Babu K, Krishnakumar S, Vanitha K, Vaijayanthi P.
Gross photography of ophthalmic pathology specimens. Indian
J Ophthalmol 2001;49:273.
 Chapter 139
Viscoelastic Substances
in Ophthalmology
Anita Panda
Modern microsurgery involves manipulations and
micromanipulations involving a risk of involuntary
tissue damage. Therefore, microsurgical strategy
should not only be offensive, i.e. the desired action on
the tissue, but also defensive, i.e. the prevention of
undesired side effects on surrounding tissue.
Defensive tactics scan be surface tactics, whereby the
surface is protected against touch by instruments,
implants or other tissues, with a covering action of
similar to protecting agents, e.g. plastic sheets and
viscous layers. It also acts as space tactics by which
sufficient space is provided for manipulations within
the eye, e.g. by hydrodynamic flow systems, gas, oil
or viscoelastic substances.1-3
CRITERIA FOR SELECTION OF MATERIAL
Each commercial preparation varies in physical,
chemical and rheologic properties. The various
physical properties affect the clinical behavior of a
material.
Physical Properties
Optical As transparency is the main requisite, visibility
should not be impaired. Similarly, refractive index
should not deviate much from that of aqueous, and
for easier distinction it should be slightly different in
color from aqueous.
Coatability The coating ability of the substance can be
characterized by measuring the surface tension and
the contact angle. Lower surface tension and lower
contact angle indicate a better ability to coat.
Viscosity Viscous or viscoelastic substances are ideal
surface tactical tools. As space tactical tools, they are
useful in walling off of cavities with small orifices (e.g.
anterior chamber).
Elasticity Elasticity of a substance is defined as, any
substance after being forced through a fine needle its
molecules should regain their shape without altering
the physical characteristics. Elastic material does not
spread, into covering layers, and is easily wiped off.
Viscoelasticity Viscoelastic response to a mechanical
force depends on the velocity of the impact. When
slow velocity rearrangement of molecular confi-
guration occurs, viscous flow results. Similarly, when
high velocity deformation of molecular chains occur,
the energy is stored as elasticity.
Cohesiveness Most of the viscoelastic substances
maintain space and thus remain in place for a consi-
derable period because of their cohesive nature.
However, the more cohesive the substance the more
likely it will plug the trabecular meshwork and this
can explain the postoperative rise in intraocular
pressure.
Chemical Properties
It should be inert, iso-osmotic, free of particulate
matter, sterile, nonpyrogenic, nonantigenic, nontoxic,
nonallergenic, reabsorbable without inflammation,
hydrophilic, dilutable and having no interference with
wound healing. It has some properties of fluids and
some of solids but in general they are intermediate.
Each substance has a unique combination of physio-
 Chapter 139: Viscoelastic Substances in Ophthalmology
chemical properties that determine its clinical
applications.4
Preparations
Sodium Hyaluronate
Balaz in 1965 first introduced sodium hyaluronate
having a large polysaccharide molecule that is present
nearly in all connective tissues of vertebrates. In eye
it is found in the vitreous, in aqueous, in the iris, and
possibly in the corneal epithelium. It has been
extracted from a number of sources including the
dermis of rooster combs, umbilical cords and culture
of streptococci. In buffered physiological sodium
chloride solution without any preservative, the visco-
sity is 1000,000 to 3000,000 centipoise. The colloid
osmotic pressure is 5.9 ± 0.2 mm of mercury (0.29
MOS), the pH is 7.2 ± 0.1 mm, the density is 1.004, the
chain length is approximately 10,000 nm and
molecular weight of 1.1 to 1.8 × 106. Its transition from
viscous to elastic behavior occurs at low concentration
and low velocities. It can easily be injected through a
30 gauge cannula but retains its original shape in
aqueous. It is at least 400,000 times more viscous than
aqueous.
It is synthesized within the plasma membrane
without involvement of any protein template, and the
very long linear polysaccharide chain is extruded
directly into the extracellular matrix. It is the natural
biologic lubricating and shock-absorbing molecule of
the musculoskeletal system and also of the eye. It
stabilizes cells and tissues and plays an important role
during embryonic development and growth. At the
cellular level, it implicated in cell to cell interactions,
cell matrix adhesion, cell morbidity, and extracellular
organization. It exerts a facilitating influence on
wound repair.5,6
It has two fractions, one which can cause inflamma-
tion (IF–NaHa) and the other noninflammatory
fraction (NIF–NaHa). Healon is made up of the NIF–
NaHa fraction. This material is viscoelastic, which
means that it is as viscous as honey and as elastic as
rubber. At low frequency vibration (< 0.1 cycles per
second) it is mainly viscous, whereas at high frequency
vibration (< 20 cycles per second) it is predominantly
elastic. The molecules are capable of elongating to
assume a long parallel position during the passage
through a small opening and returning to their original
configuration when pressure is discontinued. Because
of these properties healon can be pushed through a
1087
very small bore, 30 gauge needle without altering its
physical or chemical properties.
Unlike hydroxypropylmethyl cellulose (HPMC) all
sodium hyaluronate products require refrigeration
and it remains unaltered even after 3-5 years at 2-8°C.
Prior to use it requires acclimation to room tempe-
rature. The main advantage of sodium hyaluronate
products is that it being a biological product it creates
and maintains space in anterior chamber, ease of
insertion and removal through a 30-gauge cannula
because of pseudoplasticity. A comparative study7 of
viscoelastic substances 2% HPMC, viscoat, 1% sodium
hyaluronate (healon), 1.4% sodium hyaluronate
(healon GV) used in phacoemulsification was done.
Postoperative intraocular pressure and visual acuity
were comparable among the four groups. Viscoat
tended to trap nuclear fragments and air bubbles
leading to decrease visibility during the surgery. The
high molecular weight viscoelastic substances, i.e.
healon and healon GV, performed better as visco-
surgical tool during surgery. Another prospective,
randomized study8 revealed that viscoat and healon
GV are effective in minimizing functional damage to
the endothelial structure in the early medium term
postoperative period.
The disadvantages of sodium hyaluronate are the
elevation in intraocular pressure postoperatively, poor
coatability and the necessity of refrigeration. Healon
is the most viscous, most elastic and most pseudo-
plastic of the viscoelastic substances. Prompt removal
of sodium hyaluronate at the end of the surgery is a
must, especially in glaucoma patients without filtering
bleb and ischemic optic neuropathy. Healon GV has
been reported to cause visually significant crystalline
deposits on the intraocular lenses. The deposits could
last for long time (at least 6 months) if sequestered by
the posterior capsule, and they are believed to be
visually significant (Snellen’s visual acuity 20/40 or
worse).
AMVISC It is nothing but diluted sodium hyaluro-
nate whose molecular weight is 2 × 106 and viscosity
40,000 cps. Its pH is 6.5-7.2 and osmolarity 318. Its
chamber maintaining property in an open system is
very poor and the tissue separating capability is hardly
more than that of BSS. However, it coats IOL, produces
no inflammation, no corneal striation, no increased
corneal thickness and no elevated intraocular pressure.
AMVISC plus This is a 1.6 percent sodium hyaluronate
product with a viscosity of 55,000 cps. The higher
1088 Section 9: Miscellaneous Topics
viscosity is obtained by increasing the total concen-
tration and using a sodium hyaluronate molecule of
lower molecular weight.
Chondroitin Sulfate
It is a polysaccharide similar to sodium hyaluronate
and is harvested from shark fin cartilage. It is also a
part of the extracellular matrix in human and is the
main polysaccharide component of harder connective
tissue such as cartilage. Within the ocular tissues, the
greatest concentration of it is in the cornea. During
biosynthesis of chondroitin sulfate, the sugar units are
added to a protein template.8
In the native state chondroitin sulfate does not exist
as a free polysacchride molecule (proteoglycan). It is
different from sodium hyaluronate by being sulfated
and this extranegative charge per repeating unit may
allow chondroitin sulfate to coat the positively
charged tissue or implant surface and thus decreases
the electrostatic interaction between the implant and
the endothelium. The molecular weight of chondroitin
sulfate is only about 20,000 and the chain length and
conformation are quite small. Its pH is 7.3 and the
chain length is 50 nm, CDS-1 (20% chondroitin sulfate)
is useful in coating tissue but poor in maintaining
space and separating tissue because of its low
viscosity.8-10 When the concentration and viscosity are
increased as in CDS-2 (50% chondroitin sulfate), it
becomes hyperosmotic and causes endothelial
dehydration and cell damage. Its osmolarity is 700 for
20 percent and 1050 for 50 percent.
Viscoat It is a 1:3 mixture of 4 percent chondroitin
sulfate and 3 percent sodium hyaluronate. The sodium
hyaluronate fraction is produced by bacterial
fermentation through genetic engineering technique
and the chondroitin sulfate is obtained from shark fin
cartilage.
Hydroxy Propyl Methyl Cellulose
It was introduced in 1976 by Fechner. The active
ingredient is a highly purified hydroxypropylmethyl
cellulose (HPMC).
It is obtained from wood pulp and cotton. It
consists of long chains of glucose molecules with
replacement of the hydrogen of hydroxyl groups by
methoxypropyl (up to 29%) and hydroxypropyl (up
to 8.5%) side chain.
Methyl cellulose is a viscous, but not elastic. It is a
highly purified brand of hydroxypropylmethyl
cellulose. The hydroxypropyl and methyl group
replacing the hydrogen groups increase the hydro-
philicity of the compound. The cellulose polymer is
widely found in nature forming the skeleton of most
plants. The solubility of HPMC changes with
temperature.
Advantages It is more popular because of its low cost,
easy to prepare and can be autoclaved. As it is highly
hydrophilic and easily diluted, it can easily be
irrigated from the eye. It is used mainly as a surface
tactical tool.
Preparation To prepare 1000 ml of a 2% solution 20 g
of methylcellulose powder to be dissolved in 280 ml
of boiling solvent (balanced salt solution/Ringer’s
lactate solution/Ringer’s solution) and will be allowed
to cool. Then 700 ml of cold or icy solvent will be
added. The solvent should contain 6 mg of sulphan
blue per 1000 ml (0.0006%). Thereafter, it will be stored
in a refrigerator overnight at 10 to 0°C.
Ocugel
It is a combination of HPMC and chondroitin sulfate
which offers better viscosity and coating. As the
viscoelasticity of ocugel is much less it requires a large
bore cannula for insertion and aspiration ability.
Collagen
Human placental collagen (type IV) has been found,
to be an useful viscoelastic substance.14 A 2 percent
solution is obtained as supernatant after centrifugation
for removal of fibrillar material. Collagen is a protein
whereas the other viscoelastic substances are poly-
saccharides. Various preparations of collagen can be
produced that become gel when conditions such as
temperature, pH, and ionic strength are changed.8
Cellugel
It is a synthetic polymer of modified carbohydrate
with a molecular weight of about 100,000 and viscosity
between 12,000 and 15,000 cps at 25°C.
Advantages It can be autoclaved, does not require
refrigeration, and may be stored at room temperature
for two years. It can be injected with a 25 gauge
cannula.
Newer Viscoelastics
New polymers, like poly TEGMA 40 percent (tri-
ethylenglycol monomethacrylate) and poly GLYMA
(glycerol monomethacrylate).
 Chapter 139: Viscoelastic Substances in Ophthalmology
CLINICAL USE OF VISCOELASTIC SUBSTANCES16
Cataract Surgery
Protection of Corneal Epithelium
A small drop of viscoelastic substance placed on the
cornea offers prolonged protection of the epithelium
without altering visibility to any significant degree.
Control of Capillary Oozing
When placed over an area of capillary oozing it
controls the oozing by mechanical action. The oozing
area can be deepened with viscoelastic. The blood-
contaminated substances, however, must be removed
from time to time with cellulose sponges rather than
a stream of fluid, which may open up the capillaries
again.
Anterior Chamber Maintenance
During Incision Making
Injection into the anterior chamber prevents the
collapse of the chamber and damage to the iris with
knives and scissors during wound making.
ECCE
Viscoelastic substance protects intraocular structures
in many ways in extracapsular surgery. (Detailed
description in Chapter 62).
ICCE
Viscoelastic substance in the anterior chamber protects
the corneal endothelium against the trauma by capsule
forceps and erisiphake application. Also, it facilitates
lens delivery as in modified Smith Indian technique
and wire vectis delivery of subluxated or anteriorly
dislocated lens; the substance should be washed off
before cryoextraction or else there will be fair chance
of capsule rupture.
Miscellaneous
Selective tissue separation is also possible with visco-
elastic substance. For instance, when placed between
iris and cornea, vitreous and iris, anterior capsule and
iris, anterior and posterior capsule, it creates and
maintains adequate space to place the haptics of
intraocular lenses without endangering the walls of
such spaces. It may be used to tamponade planned or
unplanned openings inside the eye through which
vitreous could be lost.
1089
Glaucoma
The major glaucoma procedure where use of visco-
elastic substances plays a great role include: (1)
Goniotomy, (2) Filtering operations such as trabe-
culectomy, subscleral trephine, subscleral Scheie’s
operation, etc. and (3) Cyclodialysis.
In goniotomy, they help maintain the chamber,
protecting the crystalline lens while cutting the
angular membrane.
In scleral filtration operation, small amount (0.1
mm) of the substance is injected into the superior
chamber angle which helps in sealing the iris colo-
boma already made and pushes the iris away from
the cleft to be created. If a small cyclodialysis is
desired, the substance can be injected between sclera
and ciliary body around the edge of the cleft.
The abandoned cyclodialysis operation could be
reintroduced in aphakic and pseudophakic eyes, using
the tissue separating and space maintaining properties
of viscoelastic substance.
Keratoplasty17
Donor Eye
Injection of viscoelastic into the anterior chamber of
the donor eye permits the trephination of the corneal
button over a cushion that protects the endothelium
from being rubbed against the iris and the crystalline
lens. It also permits an even and circular cut, rather
than an uneven oval disk. It can also detach the iris
roots from the periphery of the button making the
peeling off of the iris. A drop of viscoelastic over
prepared corneal disk/button prevents atmospheric
and other trauma.
Recipient Eye
Injection of viscoelastic substance into the recipient
eye serves several purposes.
i. It pushes the iris and the other tissues away from
the cornea.
ii. It separates some of the synechiae, if present.
iii. It raises the intraocular pressure to a level that
allows the trephine cut to be made round and
even with vertical wound edges.
This elevation of the intraocular pressure is
accomplished without raising the intraorbital
pressure and the vitreous is displaced posteriorly
instead of toward the anterior segment.
iv. It protects the intraocular tissues against the sharp
trephine edges.
1090 Section 9: Miscellaneous Topics
v. It prevents sudden loss of anterior chamber during
trephination.
If any other synechiae are present, most of them
can be separated gently without hemorrhage and
tissue loss. The chamber angle may be opened up with
the gentle message of the substance, preventing
widespread damage.
Once the recipient eye is ready for the donor disk,
the entire chamber is filled with viscoelastic substance.
The prepared donor corneal button is placed upon this
cushion, which prevents the graft from tilting.
In lamellar keratoplasty, intrastromal injection of
viscoelastic substance (2% methylecellulose or healon)
facilitates the separation of deep stroma during
dissection of recipient stroma. This procedure is
known as viscodelamination of the cornea.
Retinal Surgery
Viscoelastic substance can be effectively used to
replace diseased vitreous and to help in pushing the
detached retina closer to the choroid. Unlike air, it
allows visibility. It can be used to raise and regulate
the intraocular pressure during the formation of scleral
trap doors and during the placement of sutures.
However, postoperative pressure can rise to high
levels, which demands immediate control. Occa-
sionally, viscoelastic substance might need to be
drained from the vitreous cavity. Injection of
viscoelastic substance should be directed away from
the tear. On the other hand, if injected from the sides
of the edges of the tear it helps to iron out the
detachment. It may also drain through this hole behind
the retina, which is an undesirable occurrence.
On occasions when a large amount of substance is
injected, inflammatory changes develop. Therefore,
the use of steroid therapy, sub-Tenon injection at the
end of surgery, or even administration of systemic
steroid is indicated.
Trauma
During care of the anterior segment in primary trauma
viscoelastic substances permit the sorting out of the
traumatized tissues and their separation from each
other while the hopelessly crushed tissues are
removed and the salvageable ones are reposited and
sutured. Thus a deliberate and orderly reconstruction
is possible, making secondary procedures less
frequent and simple.
In posterior segment injury, the collapsed globe can
be restored to a near normal shape and the intraocular
pressure can be raised to a level where a careful evalu-
ation of the situation and restoration of the wall of the
eye is possible.
Membrane Surgery
Secondary or inflammatory membrane can be
dissected in a relatively atraumatic way with the use
of viscoelastic substance. Under the protection of this
a stab incision is made into the anterior chamber and
a very small amount of viscoelastic substance is
injected under the membrane to separate it from the
underlying tissue usually the vitreous. When the
membrane is secured between the jaws of a viscoelastic
substance, the incision is to be enlarged with Vannas
scissors. Again, a small amount of the substance is
pushed behind the membrane in the direction of the
planned cut.
Vitreous Loss
If there is vitreous loss during surgery, after
completing vitreous toilette, viscoelastic can be used
to restore the integrity of the globe. Prevention
includes thorough wash of the intraocular tissue with
balanced salt solution at the end of the surgery and
prophylactic use of topical and systemic antiglaucoma
therapy.
Extraocular Surgery
Tear duct The obstruction of the nasolacrimal duct is
not rare among the elderly. During repeated probing
and irrigation of the lacrimal drainage system, if the
passage is filled with viscoelastic substance the
patency can be expected to be maintained from one
month to six months.
Extraocular muscle surgery Coating of extraocular
muscles during surgery with viscoelastic cushion
seemed to indicate a significant decrease of scarring
of the epimuscular tissue.
Postoperative Period
Main problem being the increase in intraocular
pressure. This rise is rapid in onset and dependent on
dilution.
Cause It is due to mechanical obstruction of trabecular
outflow channels, magnitude of pressure increase and
 Chapter 139: Viscoelastic Substances in Ophthalmology
duration depends on quantity of material left behind
and viscosity of the material (molecular size and
entanglement).
Diagnosis Clear residual substance cannot be visua-
lized directly.
• It can be presumed by immobility of particles
suspended in a cavity
• There may be coalescene of blood into small
droplets
• Delayed disappearance of viscoelastic from the
chamber is an important early warning sign of
abnormal inflammatory reaction.
In general, ocular inflammation can be prevented
by its complete wash following surgery. If still occurs
it could be managed either with topical or systemic
corticosteroid therapy depending upon the severity.
CONCLUSION
In conclusion though viscoelastic substances tremen-
dously increase the efficiency of modern ophthalmolo-
gists who are more akin to ophthalmic microsurgeries
one has to be aware of about the pros and cons of visco-
elastic substances:
• Viscous material spreads slowly, so to speed up
surgical action inject as near as possible to the target
• Viscoelastic material stays where it is put and must
be applied directly at the target and removed after
the work is completed
• Viscoelastic material is capable of producing
postoperative inflammation and rise of intraocular
pressure, so it must be washed off after surgery
• Use best, do best and achieve best.
1091
REFERENCES
1. Arshinoff SA. Physical properties of ophthalmic viscous
materials. Curr Can Ophthalmol Proc 1989;7:1-4.
2. Arshinoff SA. Viscoelastic substances. Curr Can Ophthalmic
Proc 1986;4:64-65, 72-74.
3. Vijaya Sekharan S, Chirila TV, Hong Y et al. Polyhydrogel as
vitreous substitutes J Biomater Sci Polym 1996;7:685-96.
4. Alpar J John. Fechner’s IOL New Delhi: Jaypee Brothers, 1988.
5. Anatangelo G, Martelli M, Vecchia P. Healing of hyaluronic
acid enriched wounds. J Surg Research 1983;35:410-16.
6. Balazs FA. Viscosurgery treatment of anterior segment ocular
trauma. Medicopea 1986;121-28.
7. Ferreira RC, Lamberts M, Moreira JB et al. HPMC and sodium
hyaluronate in adjustable strabismus surgery. J Paed
Ophthalmol Strabismus 1995;32:39-42.
8. Harrison SF, Soli DB, Shaygan M et al. Chondroitin sulphate.
Ophthalmology 1982;89:1254-60.
9. Bothner H. Wik O’Rheology of intraocular solutions: Basic
science and clinical application. New York, 1989;3-22.
10. Harrison SE, Soli DB, Arturi FC et al. Evaluation and
protection of corneal endothelium. Am J Intraocular Impl Soc
1982;6:239-42.
11. Drews RC. Use of millipore filters in ophthalmic surgery. Am
J Ophthalmol 1960;59:159.
12. Meltzer DW. Gamma-ray sterilization and its effect on intra-
ocular lenses. J Am Intraocular implant Soc 1981;7:126-29.
13. Ray-Chaudhuri N, Jayamanne DGR, Strong NP. New
generation HPMC-ophthal H for intraocular surgery: A
confocal laser scanning microscopy study. Eye 1998;12:723-
24.
14. Charleux J, Dupont D, Charleux Metal. Human placental
collagen type IV proceeding of XXV International congress
of ophthalmol, 1066-067, Rome 1986, Amsterdam 1987.
15. Thim K, Krag S, Corydon L. Hydroexpression and visco-
expression of the nucleus through a circular capsulorrhexis.
J Cat Refractive Surg 1993;19:209-12.
16. Thomas JL. Viscoelastic substances in ophthalmology. Surv
Ophthalmol 1990;34:268-93.
17. Jeremy E Levenson, Paul S. Imperia viscoelastic materials. In
Frederick Bright bill, (Ed): Corneal Surgery, second edition.
St Louis: Baltimore: Mosby, 1993;212-20.
 Chapter 140
Principles of Biostatistics
S Krishnaiah, N Rishita, BR Shamanna
Statistics in its plural sense may be defined as the
numerically stated facts or facts expressed in figures
and in its singular sense, as science dealing with the
methods of collection, compilation, tabulation and
analysis of data so as to enable us to interpret the
results meaningfully and validly with a scientific basis.
It’s a method of dealing with quantitative or quali-
tative information. It has applications in health,
medicine, nutrition, agriculture, genetics, biology,
biochemistry, demography, epidemiology, anthro-
pology, and many others.
Biostatistics may be defined as the application of
statistical methods to the solution of medical,
biological and public health problems. It is the branch
of applied statistics that concerns the application of
statistical methods to medical and biological prob-
lems. The main theory of statistics lies in the term
‘Variation’. No two things in the universe are alike,
e.g. a physician taking the pulse rate reading of a
patient. They are different at different times of
recording. The term Biostatistics can still be under-
stood by looking at the points of
i. Statistics arising out of biological sciences,
particularly from the fields of medicine, biology
and public health
ii. The methods used in dealing with statistics in the
field of medicine, biology and public health, and
in planning, conducting and analyzing the data,
which arise in investigations in these branches.
It is an obvious fact that drawing results of an
experiment, either in a laboratory or in the field of
epidemiological investigation from the whole
population is rather difficult or not advisable. The
reason for this may be manifold. The important ones
among them are the increased cost, labour and time
involved in covering the whole population. The
necessity of drawing a representative sample from the
whole lot adopting suitable sampling methods arises
in such situations. Basic tools for collecting data using
sampling procedures and presenting numerical data
in tabular and pictorial forms and expressing the
nature of the characteristics under study in terms of
frequency distributions, average (mean, median or
mode), variation (range and standard deviation),
correlation, prediction equation etc. are called
descriptive statistics. Methods for drawing inferences
of the whole lot based on the sample studies are called
statistical inference.
Although the primary objective of medical sciences
is to improve the health or cure the diseases of the
‘individual’, the relevant knowledge usually has to
be accumulated slowly by the observation of groups
of individuals. Once the data has been collected and
analysed in any medical research, interpretation of the
data results is an important factor in the statistical
evaluation of the results. The figures obtained might
be influenced by numerous correlated factors. Proper
care should be taken in evaluating them. Comparison
of a group consisting of young patients with another
group consisting of elderly patients will not be valid
to find the efficacy of a new drug administered to the
younger group while the standard drug administered
to the elderly group. Knowledge of the logical basis
of the statistical approach and the rationale of the
commonly used statistical techniques will be an
essential prerequisite.
WHAT ARE VARIABLES
The items or characteristics on which observations are
made are known as variables. Variables are things that
we measure, control, or manipulate in research. They
 Chapter 140: Principles of Biostatistics
differ in many respects, most notably in the role they
are given in our research and in the type of measures
that can be applied to them. Before planning for any
study it is more important to discuss about the data
collection methods and is also more essential to discuss
as to what types of variables are used for various
characteristics on which the data items are measured.
The observations can be broadly classified under
two headings—Qualitative and Quantitative.
Qualitative Variables
• Characteristics such as sex, consanguinity,
Occupation, Religion.
• In case of sex, the observed individual can be either
male or female.
Quantitative Variables
Continuous Variable
A characteristic whose observation can take any value
over a particular range, e.g. age, VA (log mar), IOP
and Duration of follow up
Discrete Variable or Discontinuous
A characteristic whose observation can have only
intermittent values over a range, e.g. number of people
attending the eye clinic per day.
SCALE OF MEASUREMENT
The weakest level of measurement is nominal scale. In
this scale, the observations are placed in broad
categories, which may be denoted by symbols or labels
or names, e.g. classifying patients according to
diagnostic groups or type of residence (rural, urban),
sex (male, female), eye (right, left) constitute a nominal
scale.
The next higher level of measurement is the ordinal
scale. This consists of ranking all categories of a
variable according to some criterion such as ranking
of socio-economic status (high, middle, low), academic
performance (excellent, fair, poor) and VA (> 20/60,
20/60 – 20/400, < 20/400). In this scale each category
is in a unique position in relation to other categories,
but the distance between categories are not known.
In interval scale the distance between any two
numbers (values for the variable) is fixed and equal.
For an interval-scale variable, the ratio of different
values may not have a clear interpretation, e.g.
temperature, when measured in centigrade scale, i.e.
1093
an interval-scale variable since a difference of two
temperatures is defined in measured degree units;
however, the ratio of two temperatures (e.g., 40° and
20°C) does not imply that 40°C is twice as hot as 20°C.
Since 0°C does not correspond to the absence of
temperature, the ratio of temperatures lacks a clear
meaning.
Ratio scale In contrast to temperature, 0 lb. of body
weight implies no body weight. Accordingly, the ratio
of two body weights, 200 to 100 lb., has the inter-
pretation that one person is twice as heavy as the other.
Such variables are termed ratio-scale variables.
MEASURES OF CENTRAL TENDENCY
In many biological characteristics, the values of all
observations are not equal. But we notice a general
tendency of such observations to cluster around a
particular value, which is called the central tendency
of that group. This single value serves as represen-
tative of that group. Several measures of central
tendency can be calculated for a group of observations.
Three important measures of central measures are as
follows.
ARITHMETIC MEAN OR AVERAGE
This measure is calculated by dividing the total of all
the observations by the total number of observations.
In case of grouped data (frequency distribution),
arithmetic mean is calculated assuming that each
observation in a class interval is equal to the midpoint
of that class interval, e.g. albumin Levels (g%) of 10
pre-school children are given below.
2.90, 3.57, 3.73, 3.55, 2.90, 3.45, 3.71, 3.84, 2.90 and 3.30
The computation arithmetic mean or average as
follows:
The total of all these values = 33.85 and the total
number of observations (n) = 10
Therefore, the arithmetic mean = 33.85/10 = 3.38
MEDIAN
The median is the magnitude of the observation that
occupies the middle position when all the observations
are arranged in order of their magnitude.
When there are an even number of observation in
the group, the median is the average of the magnitudes
of the middle pair of these observations, all the
observations having arranged in order. In case of
grouped data, the median is calculated assuming that
1094 Section 9: Miscellaneous Topics
the observations in each class interval are uniformly
distributed over that class interval, e.g. calculation of
the median for the data given above.
In first step arrange all the values either in
ascending or descending order:
i.e., 2.90, 2.90, 2.90, 3.30, 3.45, 3.55,3.57, 3.71, 3.73, 3.84
Median = the average of the middle two obser-
vations i.e., (3.45+3.55)/2 = 3.50
MODE
Mode is the most frequently occurring value. In other
words, the mode of a group of observations is the
value around which the observations tend to be most
heavily concentrated, e.g. calculation of mode for the
data given above.
For the data given above, the observation 2.90 is
most commonly occurring and hence, the mode is 2.90.
MEASURES OF DISPERSION
The measures of dispersion are designed to provide
information; that indicates if the different values of
the variable are close to a measure of location or away
from it. These are used to describe the amount of
scatter around the centre of the distribution. A
measure of dispersion about the mean will tell us
whether the observations are close to the mean value
or not. Similarly, a measure of dispersion about the
median will tell us about the degree of scatter of the
observations.
These measures are also called measures of
variation. The most commonly used measures of
variation are range, standard deviation and coefficient of
variation.
Range
The range is the difference between largest and
smallest observations of the distribution. If ‘A’ and
‘B’ are the largest and smallest observations in a
distribution respectively, then its range is A-B., e.g.
IOP values (g%) of the 10 normal children are given
as follows:
16.8, 15.4, 13.6, 13.2, 15.2, 14.3, 13.8, 15.9, 16.7, 12.5
Therefore, Range = 16.8 – 12.5 = 4.3
Standard Deviation
Standard Deviation (SD) is the most important
measure of dispersion or variation, which is most
commonly used in statistical analysis, which provides
an average distance for each element from its mean.
It is denoted by ‘σ’, and is given by (for ungrouped data)
n
Standard Deviation (SD) =
 (xi  x )
i 1
2
n
For grouped data (for frequency distribution)
n
 fi(xi  x ) 2
Standard Deviation (SD) = i 1
N
A large standard deviation explains that the values
of the frequency distribution are widely spread out
from the central value mean, i.e. larger the SD value
larger the variation exist in the given distribution. A
low SD value indicates that, there exists homogeneity
among the given distribution.
Applications of Standard Deviation
1. It summarizes the deviations of a large distribution
from mean in one figure used as a unit of variation.
2. It indicates whether the deviation of difference of
an individual from mean is by chance or due to
some other reasons.
3. It helps in finding standard error, which deter-
mines whether the difference between means of
two similar samples is by chance or real.
4. It also helps in determining the suitable sample size
for valid conclusions.
Coefficient of Variation (CV)
To compare the variability of two series which differ
widely in their averages or which are measured in
different units, a relative measure of dispersion is used
which is known as coefficient of variation. It is
calculated from SD and mean of the characteristic.
When the variability of two series is compared the
series having greater CV is expected to have more
variation. The series, which is having lower CV, is said
to be more consistent or homogeneous than the other.
The coefficient of variation is given by:

 100
Coefficient of variation (CV) = 
x
CORRELATION
Sometimes we have to study the relationship between
two continuous variables, which are measured from
 Chapter 140: Principles of Biostatistics
the same individual such as hemoglobin and choles-
terol or height and weight or age and blood pressure
etc. The relation between two quantitatively measured
or continuous variables is called correlation. In other
words, if the change in one variable affects the change
in other variable then the variables are said to be
correlated or related.
Importance of Studying the
Relationship between two Variables
Generally speaking, the ultimate goal of every research
or scientific analysis is finding relations between
variables. There is no other way of representing
“meaning” except in terms of relations between some
quantities or qualities; either way involves relations
between variables. Thus, in any research the new
insights of science would always involve finding new
relations between variables. Correlation analysis
involves measuring such relations in the most
straightforward manner.
In order to understand the relationship between
two variables the following various methods are used.
Scatter Diagram
We can understand the relationship between two
variables by the diagrammatic representation of the
data in a scatter diagram. From the scatter diagram
we can form a fairly good or vague idea whether the
variables are correlated or not. i.e. if the points are
very widely scattered a poor correlation is expected.
Correlation Coefficient
To measure the degree or strength of the relationship
between two continuous variables, correlation
coefficient is used.
Correlation coefficient determines the association
between two variables, but it does not prove that one
particular variable alone causes the change in the
other. The cause of change may be due to other factors.
The correlation coefficient ranges between –1 and +1.
Assumptions
1. Subjects are chosen with a random sampling
procedure.
2. Data units collected on the characteristics (varia-
bles) of the subjects are continuous
3. The variables assumed to follow normal distri-
bution.
1095
Interpretation of the Values of Correlation
Convenient and useful way of interpreting the value
of coefficient of correlation between two variables is
to use the square of the coefficient of correlation, which
is called coefficient of determination. The correlation
coefficient represents the linear relationship between
two variables and coefficient of determination
represents the proportion of common variation in the
two variables. If the value of correlation coefficient,
say r = 0.9, then the coefficient of determination r2 will
be 0.81 (or 81%) and this would mean that, 81% of the
variation existing in the dependent variable has been
explained by the other variable.
Regression Analysis
Regression is used more broadly to describe relation-
ships between variables. Regression analysis is a
mathematical measure of the average relationship
between two or more variables in terms of the original
units of the data.
In regression analysis there are two types of
variables. The variable whose value is influenced or
is to be predicted is called “dependent variable” and the
variable, which influences the values or is used for
prediction is called “independent variable”. In regression
analysis independent variable is also known as
“predictor or explanatory variable” while the depen-
dent variable is also known as “explained variable”.
In medical research regression analysis is mostly
used for prediction. If there exists a perfect linear
relationship between two quantitative continuous
variables then there exists a best possible prediction
on dependent variable based on independent
variables. Regression analysis will help us to estimate
the regression coefficient that gives the idea about for
each change in independent variable the corres-
ponding units of change in the response variable. The
regression coefficient is also called the slope of the
regression equation.
Example: Let us suppose that an investigator wishes
to fit the regression model for the data collected on
preoperative IOP and postoperative IOP from a
tertiary eye care center. The model gives the best
prediction if there exists a linear relationship between
these two variables. That is, for each unit of change in
preoperative IOP the corresponding unit of change
on postoperative IOP will be predicted from the
regression model. The regression model for the above
data would be as follows.
Postoperative IOP = a + b Preoperative IOP
1096 Section 9: Miscellaneous Topics
Simple Regression
It is a problem of only one independent variable is
used for the prediction on the dependent variable.
Example: If the preoperative IOP is used for the
prediction on postoperative IOP then it is a problem
of simple regression analysis.
Multiple Regression Analysis
If more than one independent variable is used for
prediction on dependent variable then it is problem
of multiple regression analysis.
Example: If age and preoperative IOP is used for
prediction on postoperative IOP then it is a problem
of multiple regression analysis (i.e.)
Post IOP = a + b1´age + b2´ Pre IOP
(‘a’ is a constant, b1, b2 are regression coefficients)
Difference between Correlation
and Regression Analysis
Correlation coefficient gives us the degree or strength
of relationship between two variables, where as the
regression analysis enable us to predict the values of
one variable on the basis of other variable. Thereby
the cause and effect relationship between two
variables is understood precisely.
STATISTICAL AND CLINICAL SIGNIFICANCE
Inferential Statistics
It determines how likely a given result has occurred
by chance alone. Since we can rarely study an entire
population, we study a sample of the population and
by inference apply that result to the entire population.
Before going into details of statistical significance it is
of most important to understand about “sampling
distribution”.
Sampling Distribution
Very rarely do sample values (statistic) coincide with
the population value (parameter). The discrepancy
between the sample value and that of population
parameter is known as “sampling error”, when this
discrepancy is the result of random sampling. For
instance, imagine that the IOP (mm Hg) values of 500
individuals were collected and these individuals
constitute the population. Let the mean IOP level of
the entire group is 16.32 mm Hg. Take a random
sample of size 10 and calculate its mean. For example,
let the sample consist of the following values: 12.51,
18.02, 16.75, 11.42, 14.83, 19.6, 12.96, 13.92, 15.88 and
16.38; the mean of these values is 15.23 mm Hg. Take
another sample of the same size 10 and calculate its
mean; let us assume it is 16.99 mm Hg. Let us repeat
the same procedure and get 400 samples of the same
size and calculate their means. We shall have 400 such
sample-estimated means in such a sample experiment.
This distribution is called the sampling distribution
of means.
It is found that, most of the sample means cluster
around the population mean (i.e., 16.32 mm Hg). Very
few sample values deviate seriously from the
population mean. The standard deviation of the
sampling distribution is known as “standard error”.
This standard error will give us the idea about the
variability of the sample estimates around the true
population estimate. If we have taken samples of
larger size than 10 as in this case, we will find a smaller
scatter (standard error) of the sample means.
In medical research, most of the times the
researcher would come across making use of the
following two most important aspects of statistical
analysis in inferential statistics.
Estimation
Estimation is done to know the magnitude of the
disease in the population. The estimate may be a single
statistic such as the mean, which is called the point
estimate or a range with attached probability, called
confidence interval.
For example, prevalence of blindness in India,
mean IOP in normal population, etc.
Testing of Hypothesis
Testing of the null hypothesis is fundamental in all
tests of significance. This involves making an assump-
tion about the parameter and checking the plausibility
of that assumption using sample data. We can also
identify two types of research procedures with refe-
rence to hypothesis testing:
1. Comparison of two or more populations, e.g.
patients with disease A and disease B.
2. Relationships between two or more factors in a
population, e.g. smoking and cataract disease, intra
operative complications and success, smoking and
lung cancer, etc.
 Chapter 140: Principles of Biostatistics
Null Hypothesis
It is a tentative statement against which it is tested.
The proposal that “no difference” exists between
groups or that there is no association between risk
indicator and outcome variables. If the null hypothesis
is true then the findings from the study are the result
of chance or random factors.
Statistical Significance
Usually, medical research examines the difference
between two groups to determine if it is statistically
significant. The difference between two groups is
statistically significant, if it cannot be explained by
chance alone. Usually, statistical significance is
determined by calculating the probability of error (p-
value) by appropriate statistical analysis. The diffe-
rence between two groups (such as an experiment vs.
control group) is judged to be statistically significant
when p < 0.05. That is, the difference between two
groups has only a 5% of probability of occurring by
chance alone. And if the “p-value” is less than 0.01
then the difference between two groups has only a
1% of probability of occurring by chance alone.
CLINICAL SIGNIFICANCE
The problem with the p value approach is that two
groups could differ significantly (with p= 0.05 or less),
yet the actual difference between the two groups could
be so small that it is not clinically significant. This
problem usually occurs when:
• The group sizes are very large.
• Scores within the groups are very similar (i.e., the
groups have small standard deviations).
• The experimental design uses repeated measures
(e.g., scoring an individual’s progress repeatedly
over time).
Clinical vs Statistical Significance
Statistical significance means the likelihood that the
difference found between groups could have occurred
by chance alone. In most research studies, a result is
statistically significant if the difference between
groups could have occurred by chance alone in less
than 1 time in 20. This is expressed as a “p-value”
< 0.05 or < 0.01. Clinical significance has little to do
with statistics and is a matter of judgment. It answers
the question “Is the difference between groups large
enough to be worth achieving?” Studies can be
statistically significant yet clinically insignificant and
1097
vice versa. There are ways of determining if the
difference between two groups is both statistically and
clinically significant. The most commonly used
method of determining the clinical significance of the
difference between two groups is to calculate the effect
size.
Level of Significance
The probability of incorrectly rejecting the null hypo-
thesis, i.e. saying that there is a difference between
two groups when actually there is none. Otherwise
known as the probability of Type I error. Type 1 error
or level of significance is considered to be serious error
in medical research. By convention, the level of
significance is often set to a p value of 0.05 or 0.01.
Power
The probability of detecting an effect in the treatment
vs. control group if a difference actually exists. Must
also specify the size of the difference. For example, a
paper describing a clinical trial with a new hyper-
tension medication may contain the following
statement. “The study had a power of 80% to detect a
difference of 5 mm Hg in diastolic blood pressure
between the treatment and control groups.” Typical
power probabilities are 80%, 85% and 90%. Power = 1
- β (see Type II Error, below)
Type II Error
Mistakenly accepting (not rejecting) the null hypo-
thesis when it is false. The probability of making a
Type II error is called beta. Power = 1 - β. For trials the
probability of a type II error is usually set at 0.20 or
20%, 0.10 or 10% probability. A 20% or 10% chance of
missing a true difference. It is well described as
follows:
Testing the null hypothesis to assess efficacy of two
treatments (e.g. drug vs placebo).
In reality
Decision Null hypothesis Null hypothesis
is true is false
Rejected NH Type I error (α) Correct decision
Accepted NH Correct decision Type II error (β)
Tests of Significance
Tests of significance are mathematical methods by
which the probability (p) of an observed difference
occurring by chance is found. Common tests in use
1098 Section 9: Miscellaneous Topics
are ‘Z’ test, ‘t’ test and ‘χ2’ test. There are various types
of problems for which the tests of significance are used
for drawing conclusions. Different types of problems
need different tests but the basis of all tests and the
steps involved in the procedure are the same.
The usual procedure for making inference about
population parameter is as follows:
1. Find the type of research question to be answered
2. State the Null Hypothesis (NH). It is denoted by
Ho and usually set it as no difference between
groups.
3. Utilization of the appropriate statistical test and
calculation of test statistic based on the type of
procedure.
4. The test statistics is given by
Difference between the statistics
______________________________________
=
Standard error of the difference
5. Fixation of the level of significance (α). Usually
levels of 5% (0.05) or 1% (0.01) or 0.1% (0.001) are
chosen. Minimum fixation is 5% level
6. Comparison of the calculated test criterion value
with that of the theoretical value at 5%, 1% or any
prefixed level of significance
7. If the calculated test criterion value is lower than
the theoretical value, null hypothesis is accepted.
If the calculated value is higher than the theoretical
value, null hypothesis is rejected
8. Drawing of the conclusion or inference on the basis
of level of significance is deciding whether the
difference observed is due to chance alone or is it
due to the true effect
Large Sample Tests
Samples with number exceeding 30 in size or above
are called large and such samples follow normal
distribution. Normal curve test (‘Z’ test) is utilized for
differences in mean values or proportions based on
large samples. When Z-test is applied to the sampling
variability, the difference observed between a sample
estimate and that of population estimate is expressed
in terms of standard error (SE). The score of value of
the ratio between the observed difference and SE is
called critical ratio ‘Z’.
Small Sample Tests
Small samples do not follow normal distribution as
the large ones do. In case of small samples, the test is
known as student’s t-test. If sample sizes are large,
student’s t-test and normal curve test provide similar
results. When samples are small and population
variance is not known, t-test is utilized.
Student’s ‘t’-test
Student’s t-test or simply t-test can be useful for testing
differences between:
i. Two means of small independent samples
ii. Paired data observations from one sample only
iii. Sample mean and population mean
The ‘t’-test gives the probability that the difference
between the two means is caused by chance. It is
customary to say that if this difference is if this
probability is less than 0.05, that the difference is
‘significant’, the difference is not caused by chance.
Paired ‘t’ test
‘t’ test is applied to paired data of observations from
one sample only when each individual gives a pair of
observations say pre and post treatment. It is used to
determine the if the difference between paired
observations is significant. For example, to study the
change in IOP following surgery. Another example is
comparison of the measurements of skinfold thickness
or height of individuals before and after some
experiment.
χ2 - test
Often, in medical research, we are interested in
studying the correlation or association between two
or more variables. The relationship between two or
more continuous variables can be studied by the
method of correlation and regression. Frequently we
come across occasions to study the association
between two discrete variables like smoking and
cancer. Sometimes, we may be interested to know the
association between a continuous variable grouped
into categories, (e.g., anemia (Hb) – mild, moderate
and severe) and a discontinuous variable, (e.g.,
economic status—lower, middle and upper) or
between two continuous variables grouped into
categories. Under such conditions, to study the asso-
ciation or otherwise, we turn to ‘χ2test’ of association.
The test χ2 is defined as,
(observed frequency – expected frequency)2
χ2 = ________________________________________________________
expected frequency
(Oij  Eij )2
2  
ij Eij
where Oij–Observed frequency of ith row, jth column cell
Eij–expected frequency of ith row and jth column cell
 Chapter 140: Principles of Biostatistics
The values of chi-square are compared with chi-
square table values at 5% or 1% levels of significance.
These table values are available for various degrees
of freedom.
If the value of χ2 Cal is greater than χ2 table at 5%
level it is said to be significant at 5% level i.e., we reject
the null hypothesis.
If the value of χ2 Cal is less than χ2 table at 5% level
it is said to be insignificant at 5% level, i.e. we accept
the null hypothesis.
Analysis of Variance (ANOVA)
Many biological and medical experiments are
performed for the purpose of comparing the effects
of two or more treatments. In a case of only two
treatment groups, a commonly used significance
testing procedure for the comparison of means is
student’s ‘t’ test. In case of more than two treatments
groups, the analysis of variance (ANOVA)-F test is
utilized. However, the ANOVA-F test rarely provides
an adequate basis for drawing inferences. If the F test
shows significance (a minimum probability level of
0.05), further analysis of the data using post hoc tests
is necessary to determine which of the treatment
groups differ.
Non-parametric Tests
The t-tests for equal means and F-test for equal
variances assume an underlying normal distribution
1099
for the data. There are alternative test procedures that
do not require such an assumption and that are still
valid if the data are normal. Testing and estimation
procedures that do not require, or are free, from, the
normality assumption are called distribution-free
procedures. In addition to being called distribution-
free tests, these tests are also called nonparametric tests.
Rank tests are distribution-free test procedures that
utilize the rank order of the observations in the place
of the observations; thus the ranks constitute a
transformation of the data. Historically, the study of
the normal distribution and t-tests preceded the study
of rank tests. Today, parametric and nonparametric
test procedures are each commonly applied to the
problems of data analysis. If normality assumptions
are not met, nonparametric tests are typically in
preference to the parametric tests.
Statistical Methods and Computer Programs
There are simple spreadsheet programs like Microsoft
Excel can do a surprisingly wide range of statistical
methods. Further statistical packages and computer
programs are available with the various Analysis Tool
kits or Add-ons. If we have a large data set or data
which requires a lot of description SPSS (Statistical
Package for Social Sciences) is the better statistical
tool for analysis. Some other licenses are available for
Statgraphics, Epi-Info for Windows, which are user
friendly and offers a range of tests, analysis and
displays.
 Chapter 141

Genetics in Ophthalmology
Chitra Kannabiran

INTRODUCTION on sequences of disease genes, concomitant studies

on gene function and expression in normal and
Genetics deals with the study of hereditary trans-
diseased tissue in experimental systems will even-
mission and variation. Traditionally, genetics as of
tually provide insights into disease mechanisms. The
inherited characteristics as well as medical genetics
knowledge about gene mutations in ocular diseases
have dealt with traits or disorders that are determined
and about disease processes at the subcellular level
by a single gene and therefore transmitted according
has paved way for explorations into novel approaches
to Mendel’s laws. Single-gene or “Mendelian”
to therapy.
disorders as they are called are usually very rare in a
Table 141.1 lists several genetic ocular disorders
population. They are caused by extremely rare altera-
and the number of genes mapped or identified for
tions in a gene, referred to as mutations. These muta-
each.1,2 It is not possible here to cover basic molecular
tions sufficiently modify or impair the function of the
biologic concepts3 or to go into the details of the gene-
protein product encoded by the gene so as to cause
tics of specific eye diseases [information on genetics
disease. The concept of genetic diseases has been
of various diseases can be found in publicly available
expanded in the recent past to include those diseases
databases;1,2 for the current state of knowledge in the
that have a partial genetic component to their etiology
genetics of various ocular disease, which is an evolving
and are multifactorial or complex diseases. Unlike
field, see reviews in refs.4-9 A brief overview of the
single gene disorders, these diseases have contri-
general concepts of genetics is provided here,
butions to their etiology from several genes and
highlighting the potential uses of genetic knowledge
possibly, from the interactions of genes with the
for patients with the idea that this will be useful in
environment. Most common diseases belong to this
the understanding of ophthalmic genetic diseases and
category, including among ocular diseases like age-
in applying these concepts in practice.
related cataract, adult-onset glaucoma, and age-
related macular degeneration. With the advent of
TYPES OF VARIATION IN DNA
molecular genetics, genes responsible for most
Mendelian ocular disorders have been identified and Variations in the DNA sequence of the genome of any
advances are being made in unraveling the genetic organism are generally of two types. Extremely rare
components of complex diseases as well. variations are termed as mutations and the corres-
The explosion of molecular genetic knowledge ponding altered phenotype is mutant as opposed to the
mainly in the last two decades, has been catapulted normal or wild type form. Medical genetics deals with
by the technological advances in molecular biology rare diseases that arise due to mutations in a specific
including recombinant DNA techniques, DNA sequen- gene. Mutations can involve one base in the gene
cing and polymerase chain reaction (PCR). The genes sequence (point mutation) or involve a few bases or
responsible for many ocular genetic diseases and the large segments of the gene (deletions, insertions, etc).
exact gene defect underlying each phenotype are now More drastic alterations involve deletion or rearrange-
known. Along with the vast amount of information ment of chromosomal segments so that one or more
 Chapter 141: Genetics in Ophthalmology 1101
Table 141.1: Ocular genetic disorders. Modes of inheri- genes are affected. Small mutations involving one or
tance and no. of genes known are indicated for various a few bases occur most often in the coding sequences
disorders1,2 of genes and thereby affect structure and function of
No. of
the protein encoded.
genes mapped/
Disease Inheritance identified
Common variations in the genome, in which the
least frequent variant occurs in 1% or more of the
Hereditary AD 20 population, are termed as polymorphisms which can
cataracts AR 3
occur in non-coding regions in the genome as well as
X-linked 1
in genes. Intragenic polymorphisms may in some cases
Retinitis pigmentosa AD 13 alter the coding sequence of the gene but mostly are
AR 21
found in introns or are silent changes in the exons and
X-linked 5
mitochondrial 3
do not affect the coding sequence. Polymorphisms are
useful in human genetic studies for mapping (tracking)
Usher syndrome AR 11 a disease gene when they are in close proximity to it.
Macular degeneration AD 12
AR 1 DNA Testing
mitochondrial 1
Polymorphisms
Cone-rod dystrophy AD 8
AR 4 There are different types of polymorphisms that are
X-linked 3 detectable by different methods. Listed below are
Familial exudative AD 2 polymorphisms from the oldest known to the most
vitreoretinopathy AR 1 recently characterized. The last two categories are
X-linked 1 currently the most widely used. They are used in
diagnostics in order to identify individuals who are
Retinoschisis X-linked 1
carriers of the disease gene in a family and in forensic
Retinoblastoma AD 1 and paternity testing.
Optic atrophy AD 2 1. Restriction fragment length polymorphisms:
AR 1 Sequence variations in DNA that alter the recog-
X-linked 1 nition site of restriction endonucleases are known as
mitochondrial 1 restriction site polymorphisms. A recognition site
PCG AR 2 in the DNA for a restriction enzyme is either
created or abolished by the sequence variation. This
POAG AD 6
in turn generates DNA fragments of different sizes
Rieger syndrome AD 2 upon digestion of DNA with the relevant enzyme,
Axenfeld-Rieger anomaly AD 2 known as restriction fragment length polymor-
phisms (RFLPs). Thus, different individuals will
Peters anomaly AD 4
have different patterns of restriction-enzyme-cut
Macular corneal dystrophy AR 1 DNA if they differ in these polymorphisms. Some-
Lattice & granular corneal AD 1 times, disease-causing mutations result in restric-
dystrophies tion site polymorphisms and RFLPs can be directly
used to track the presence of the mutation. In most
Congenital hereditary AD 1
cases, sequence variations in non-coding regions
endothelial dystrophy AR 1
of the genome give rise to RFLPs (Fig. 141.1).
Fuchs endothelial dystrophy AD 1 2. Variable number of Tandem Repeats (VNTRs):
Posterior polymorphous AD 2 These are repetitive sequences in the genome that
dystrophy consist of repeat units of 5-64 base-pairs (also
Ocular coloboma (isolated) AD 2
known as minisatellie DNA). They are poly-
morphic due to variation in the number of basic
Microphthalmia AR 1 repeat units. Alleles for VNTRs can be identified
AD = Autosomal Dominant; AR = Autosomal Recessive by their sizes.
1102 Section 9: Miscellaneous Topics
Fig. 141.1: RFLP analysis showing presence or absence of
disease-causing mutation in a family with primary congenital
glaucoma. PCR products obtained from amplification of the
CYP1B1 (cytochrome P4501B1) gene were digested with
restriction enzyme Eco1301. The presence of a mutation in the
amplified fragment results in loss of recognition site for Eco
1301 and is not digested by it, while normal control DNA is
digested to produce 2 smaller fragments of 384 and 158 base-
pairs. Affected individuals (lanes 4 & 5) represented by shaded
symbols are homozygous for the mutation, indicated by absence
of digestion (Size of uncut DNA-542 base-pairs). Carriers of
the disease, lanes 1, 2 & 3, marked by dots, are heterozygous
for the mutation and show the normal allele (2 fragments of
384 and 158 bp) and the mutant allele (542 bp fragment). The
normal control DNA (lane C), shows complete digestion
producing 2 smaller fragments. M-DNA size marker. [Data
courtesy of Dr. S.G. Panicker and ABM Reddy, LV Prasad Eye
Institute, Hyderabad]
3. Short Tandem Repeat Polymorphisms (STRPs):
These are another class of repetitive sequences, also
known as microsatellites, consisting of repeat units
of 1-4 base-pairs. There are at least 6000 micro-
satellie markers known so far in the human
genome. They are used commonly for mapping
disease genes since they are easily amenable to
analysis on a large scale.
4. Single nucleotide polymorphisms (SNPs) are the
most common type of variation in the human
genome and consist of two alternative bases at a
position. They are less polymorphic than the other
markers listed above since they have only 2 alleles,
but have the advantage of being very abundant.
There is one SNP every 1000 base-pairs in the
human genome.
MENDELIAN INHERITANCE
All disorders that are due to a single gene follow
Mendelian inheritance.10,11 There are three traditional
modes of Mendelian inheritance: autosomal domi-
nant, autosomal recessive and sex-linked. In the
autosomal dominant mode, one allele of the disease gene
is sufficient for disease to occur and affected
individuals are heterozygous for the disease gene. In
such families, one finds vertical transmission of
disease with affected individuals usually in every
generation. In the recessive mode, two alleles of the
disease gene are required for disease to occur and
affected individuals are homozygous for the disease
gene. The parents of a child with recessive disease are
carriers since they will each have one allele of the
disease gene. In families with recessive disease,
affected individuals may be found only in one
generation with all previous generations having no
affected members. In X-linked inheritance, there are
two types; X-linked recessive and X-linked dominant.
In the former, more males are generally affected than
females. Affected males inherit the gene from their
mother and females as heterozygous carriers inherit
the gene from either parent. In X-linked dominant
diseases, females as well as males are affected. Most
X-linked diseases are recessive. X-linked pedigrees are
characterized by an absence of male-to-male trans-
mission of disease. X-linked recessive diseases often
show manifesting female heterozygotes and this
makes it difficult to distinguish this transmission from
an X-linked dominant one. This occurs because in
females, one X chromosome is inactivated and the
process occurs at random in all cells. Thus, if one of
the X chromosomes has a mutation, the mutant one
may be inactive in some cells of the body while the
normal one may be inactive in other cells thus giving
a mosaic pattern for the X chromosome in an indi-
vidual. Depending on the status of the tissues in which
the disease phenotype occurs, carrier females often
show variable extents of disease.
In most cases, single-gene disorders have high or
full penetrance, i.e. the effect of the mutant gene is
strong enough to express the disease and usually, most
or all individuals with the disease-causing gene do
have the disease phenotype. In some cases, the disease
has low penetrance and hence the presence of the
disease-causing gene does not always result in the
phenotype. Thus, not all individuals carrying the
mutant gene are affected. Penetrance is the probability
 Chapter 141: Genetics in Ophthalmology
Table 141.2: Standard risks for Mendelian disorders
Mode of First degree Risk
inheritance relatives at risk
Autosomal dominant Sibs, parents, children 50%
Autosomal recessive Sibs 25%
Children Negligible (in the
absence of
consanguinity)
X-linked recessive Brothers 50%
Sisters as carriers
that an individual with a susceptible genotype will
actually manifest the disease. Low or incomplete
penetrance of a gene can give rise to deviations from
the classic Mendelian patterns in a pedigree. For
example, in an autosomal dominant disease, one may
find an apparent skipping of generations.
NON-TRADITIONAL MODES OF INHERITANCE
Mitochondrial Inheritance
Mitochondrial diseases arise due to mutations in the
mitochondrial genome. Since only the cytoplasm of
the oocyte is retained in the fertilized embryo all
mitochondria are derived from the mother. The
mitochondrial genome consists of 16,569 bp of DNA
and there are 2-10 copies of the genome in each
mitochondrion. Mutations in mitochondrial DNA are
therefore transmitted through the maternal line. All
offspring (male and female) of affected females inherit
the mutation and will therefore be affected. Affected
males, however, cannot transmit the disease to their
offspring. Note that this can appear like autosomal
dominance in the absence of sufficient numbers of
offspring of affected males. The phenomenon of
heteroplasmy (copies of mutant and normal mito-
chondrial genomes in the cells of an individual) gives
rise to very variable phenotypes for mitochondrially
transmitted disorders. The severity of disease depends
on the number of mitochondria carrying copies of
mutant genomes in a given organ or tissue. Thus one
can have a wide range of manifestations among
siblings carrying a mitochondrial mutation. The ocular
disease that is inherited through the mitochondrion
is Leber’s hereditary optic neuropathy. Kearns-Sayre
syndrome is another example of mitochondrial
inheritance although it is a disorder involving multiple
organs with ocular involvement.
1103
Other relatives
at risk Risk
Uncles, aunts, nephews, nieces 25%
First cousins 12.5%
Uncles, aunts, nephews, nieces Negligible
first cousins
Maternal uncle 50%
Maternal aunt as carrier
USES OF GENETIC INFORMATION
Genetic Counseling
Family History and Pedigree Analysis
The essential knowledge that one requires in order to
make a genetic diagnosis is a detailed family history
of the disease in question as well as relevant general
medical history. This is done for all first-degree
relatives of the patient and the grand-parental gene-
ration as well. Detailed questioning of patients about
the status of all relevant family members and possibly,
direct clinical examinations are required in order to
assign each individual in the family as normal or
affected. This information is then recorded in the form
of a pedigree drawing which is a family tree showing
all relevant relations in the family and disease status
of the individuals. Details of symbols used in pedi-
grees are shown in Figure 141.2. The most immediate
application of this knowledge is in prediction of risks
of recurrence of disease and in counseling of families.
The purpose of counseling is generally to inform
the patient and family about the nature and conse-
quences of the disease, and the options available to
them so that they can make the required decisions.
The general procedure involved is as follows.
i. Construct a family history or pedigree with entry of
all medical problems. Construct a pedigree and
enter information regarding affection with the
disease in question and other medical and
ophthalmic history in the family. Information on
causes of death in the family as well as stillbirths
should be noted. Details of family history with
regard to consanguinity in patient and previous
generations should be sought and recorded. If
consanguineous, determine the exact relationship
between spouses and indicate in the pedigree
drawing.
1104 Section 9: Miscellaneous Topics
Fig. 141.2: Standard symbols used in drawing pedigrees. This
figure depicts various symbols used in pedigree drawing and
their explanations
ii. Analyze the family history for genetic risk. Examine
the pedigree to determine mode of inheritance.
AR inheritance is very often seen in association
with consanguinity. One can have pseudo-
dominance in recessive disease, if one of the
parents of the proband is affected. This should
be distinguished from true dominance. If there is
consanguinity in the family, or the disease is
known to be of recessive inheritance, it should be
taken as recessive.
iii. Determine the risk for occurrence (or recurrence) of
genetic conditions in the family Risk of recurrence
is the risk of siblings, offspring and other relatives
of the proband for developing the disease. This
is predicted on the basis of the mode of inheri-
tance in Mendelian disorders and can be modified
by penetrance or by the presence of mosaicism.
The recurrence risks in different types of
inheritance are as summarized below, if full
penetrance is assumed.
iv. Discuss the nature of the condition (s), including the
contribution of heredity. The features of the disease
including the normal course, effect on vision,
morbidity, treatment options, impact on patient’s
lifestyle, and contribution of heredity should be
explained to the patient.
v. Discuss the options available to reduce recurrence
risk(s), including testing, if available. Since testing
is not a reality at present for ocular diseases in
India, options to reduce occurrence of disease in
future generations including prenatal testing are
not generally available. Since recessive disease is
seen most often in consanguineous families,
patients from such families can be informed of
the increased risk to future offspring in the event
of a consanguineous union. For treatable disease
(such as retinoblastoma, glaucoma) the family can
be advised to seek medical surveillance of
members at risk and if required, early inter-
vention so that effective treatment is possible. In
the event that a genetic test is available for the
disease in question, patients should be explained
about the usefulness of the genetic information.
i.e., is it likely to have an impact on clinical
management? What are the risks of having this
information? Knowing that one is genetically
predisposed to a disease can create a psycho-
logical burden on an individual and can poten-
tially lead to discrimination in the community and
by employers and insurance agencies. These
considerations have to be taken into account in
recommending any available genetic tests.
vi. Communicate risks and benefits of each option
available in a manner that is comprehensible to
the patient and assist in selecting the option
appropriate for an individual or family.
vii. Provide supportive counseling and/or referral to
community resources when appropriate. In the event
that a patient requires other support services such
as special aids, counseling on schools or employ-
ment for the visually handicapped, he/she should
be referred to such services.
Genetic Testing
Genetic testing involves the detection of the disease
gene in an individual. It is often a complex and
involved procedure due to the high degree of genetic
heterogeneity that is characteristic of most hereditary
ocular disorders (see Table 141.1) with many different
mutations in a given gene or even many different
genes being possible causes of a disease. Depending
on the types and range of mutations underlying the
disease in question, one or more of a number of
molecular or cytogenetic methods are employed to
identify the pathogenic mutation.
The potential uses of genetic testing are:
a. As an aid in diagnosis of a disease in cases where
clinical findings are ambiguous or due to variable
expressivity of the disease or when the manifes-
tations are atypical.
b. Pre-symptomatic diagnosis—detection of the
disease gene in an individual would imply that he/
 Chapter 141: Genetics in Ophthalmology
she is likely to develop the disease and may be used
as an indication to frequently monitor such
individuals and initiate early intervention. Siblings
and offspring of affected individuals are screened
for the mutation to determine whether they are
predisposed to develop the disease. The benefit of
genetic testing has been recognized in retino-
blastoma where early intervention is critical for
effective management.12,13 Testing and mutation
identification in the affected proband of the family
will enable the testing of all at risk family members
so that one can unambiguously identify mutation
carriers. The individuals predisposed to the disease
by virtue of having the mutation can be subjected
to monitoring while those who are negative for the
mutation can be exempt from unnecessary
surveillance, which involves frequent exami-
nations under anesthesia.
There are many caveats that have to be taken into
account in regard to presymptomatic diagnosis in
general. Knowledge that one is genetically predis-
posed to a disease can place an enormous psycho-
logical burden on the individual since it involves the
entire family and future generations as well. Secondly,
presymptomatic diagnosis does not always have
proven benefits. For example, it is questionable
whether testing a child for a gene causing an adult-
onset disease is warranted when no action can be taken
until signs and symptoms of the disease appear.
Another consideration would be that in diseases that
are not fully penetrant, the presence of a susceptible
genotype in an individual does not always imply that
disease will actually occur (for example, in adult-onset
glaucoma). In these instances, the benefits of testing
may be doubtful while there is the possible risk of
causing undue anxiety to the patient.14
Other considerations involved in the use of genetic
tests are:
i. The cost of testing, and affordability to the patient.
ii. The potential of the test to be informative-this
would depend on the efficiency of detection of
mutations (the sensitivity of the methods used)
and the implications of both positive and negative
results. As mentioned above, a positive result in
a disease with incomplete penetrance does not
necessarily indicate that the person tested is
predisposed to develop disease. Similarly,
absence of a disease-causing mutation in a gene
could indicate that it has been missed by the
techniques used or that the disease is linked to
other genes not covered by the test.
1105
iii. Patient assessment of risks and benefits-the risks
are essentially psychosocial and the impact of
genetic information and the perception of risks
could be culture-specific.
PROBLEMS WITH DIAGNOSIS
OF DISORDERS AS HEREDITARY
Variable Penetrance and Expressivity
As mentioned in the previous section, incomplete
penetrance of a disease gene can result in the absence
of phenotype in mutation carriers. Since the trans-
mission of the disease does not coincide with the
transmission of the disease gene, it can lead to
misspecification of the inheritance model. For
example, in a disease with an autosomal dominant
mode of inheritance, the transmitting parent may be
unaffected due to low penetrance, although the
offspring are affected. Another term that is often used
synonymously with penetrance is expressivity, which
refers to the extent and range phenotypic expression
for a disease gene. Many inherited eye disorders have
variable expressivity. This implies that individuals
with the same genotype (such as members of a family)
can have very different manifestations and degree of
severity of disease. Thus, age of onset and progression
of the disease can be different among affected indi-
viduals in a family and one may find individuals who
are very mildly affected so that the disease is not
evident except upon clinical examination. Diseases
that often show variable expressivity are congenital
cataracts, retinitis pigmentosa and the phakomatoses.
Sporadic Cases
These are isolate cases where only one member is
affected in a family. About one-third or more of
patients with many hereditary eye diseases may
present as sporadic cases. It may not be possible to
determine the recurrence risks in these cases since the
mode of inheritance is not evident. Sporadic cases may
be due to:
a. Small family size
b. Non-genetic cause of disease, also known as
phenocopies (e.g. congenital cataract can be due to
other non-genetic causes)
c. Chromosomal aberrations: these occur as sporadic
events and the recurrence risk is negligible.
d. New mutations: the mutation was not transmitted
from previous generations, but occurred de novo
either during germ cell division in the parent (see
1106 Section 9: Miscellaneous Topics
mosaicism, below) or during embryonic develop-
ment. In such cases, the siblings of the proband
may not be at risk, but the proband’s offspring may
be at risk. This would depend on whether the
mutation is constitutional (present in all cells of
the body) in the proband.
e. Autosomal recessive inheritance: since the pre-
vious generations are not affected in recessive
disorders, it may be possible that the parents are
carriers and only one child is affected. This should
be suspected in sporadic cases where the proband’s
parents are consanguineous.
f. X-linked recessive inheritance: can also lead to
sporadic cases, as in autosomal recessive inheri-
tance.
Mosaicism
Post-zygotic mutations can give rise to mosaicism.
This is defined as the presence of two or more
genotypes in an individual. The mutation is present
in some cells of the body but not in others. Mutations
that occur during division of germ cells result in a
population of germ cells having the mutation and
others that are not derived from the mutant cell,
normal. In such a situation, an unaffected person can
have multiple affected offspring. Mosaicism is
common in some diseases, particularly in retino-
blastoma. Retinoblastoma is of autosomal dominant
inheritance but if germ cell mosaicism is present in
one of the parents, he/she may be unaffected and have
more than one affected child. The pedigree pattern
thus appears like recessive inheritance since both
parents would be unaffected. Recurrence risks are not
easy to predict when mosaicism is present in a family
and have to be derived empirically from observations
on populations.
SUMMARY AND FUTURE PROSPECTS
The genetics of ocular diseases is a rapidly growing
field with recent molecular genetic studies revealing
a great degree of genetic heterogeneity in several
diseases. Knowledge of the mode of inheritance of the
disease and family history can aid in risk prediction
and counseling of families. Extensive genetic hetero-
geneity poses a challenge to the detection of the
underlying disease gene in patients and renders
genetic testing more complicated than desirable for
routine use. The increase in our knowledge of gene
mutations, along with an understanding of functions
of these genes in ocular tissues and the effect of
mutations on their function will open up new appro-
aches to therapy. This is being attempted, through the
introduction of genes (gene therapy) in the relevant
tissue, or by novel therapeutic strategies such as
catalytic RNA and antisense oligonucleotides that are
designed to target specific mutations especially for
dominant diseases.15,16 Knowledge about the path-
ways involved in pathological processes may also
enable the development of newer conventional drugs.
GLOSSARY
Allele One of the alternative forms of a gene/locus.
An individual can have 2 alleles at any locus, one
derived from each parent (see genotype).
Antisense oligonucleotides The sense strand of DNA
refers to the strand that contains the coding sequence
and is identical in sequence to the messenger RNA.
‘Antisense’ is the complementary sequence that can
base pair with the sense-strand. Antisense oligo-
nucleotides are short fragments of nucleic acid that
are synthetic and contain the sequence of the antisense
strand for a particular gene. They can form thus
complementary base-pairs with a portion of the
messenger RNA. When introduced into cells, they can
bind to the corresponding mRNA by base-pairing and
block its function. Their potential for therapy lies in
blocking the function of a specific gene (such as a
mutant gene) against which they are designed.
Catalytic RNA RNA molecules having the ability to
bring about the cleavage of RNA substrates (i.e, they
function as ribonucleases). These are also known as
RNA enzymes or ‘ribozymes’. They hybridize to
complementary sequences of a particular target
mRNA transcript through complementary base
pairing and, under appropriate conditions, cataly-
tically cleave a sequence-specific target. Ribozymes
can be synthetically designed to cleave any mRNA
including mutant mRNAs bearing specific mutations.
They have potential therapeutic use since they can
target and destroy an ‘unwanted’ mRNA in a diseased
tissue.
Cytogenetic Pertaining to chromosomes. Cytogenetic
techniques involve the preparation, staining and
analysis of chromosomes in order to detect structural
or numerical abnormalities in any of the chromo-
somes.
 Chapter 141: Genetics in Ophthalmology
Exons The coding segments of a gene. Exons are joined
(spliced) together to form the mRNA.
Genetic heterogeneity A disorder is genetically
heterogeneous when there are several genes/loci
(locus heterogeneity) or several mutations of a
particular gene (allelic or mutational heterogeneity)
causing it in different families.
Genotype The combination of alleles at a specific locus.
Introns The non-coding regions of a gene that occur
between the exons or the coding regions. Introns are
removed during formation of the mRNA.
Mapping The process of localizing a gene in the
genome and ascertaining its physical position on a
chromosome.
Phenocopies The occurrence of the same phenotype in
a family with a genetic disorder but due to other non-
genetic causes.
Phenotype The total observable characteristics of an
organism.
Polymerase chain reaction (PCR) The process by which
a specific segment of DNA can be amplified in the
laboratory from total genomic DNA of any organism
by repeated cycles of DNA synthesis using a thermo-
stable DNA polymerase.
Point mutations Mutations involving single base
changes. These may be nonsense mutations (the base
change converts the codon for an amino acid into a
stop codon) or missense mutations (the base change
substitutes one codon for another so that there would
be a change of amino acid at this position in the
protein).
Proband The index patient or the first patient in a
family through whom the family was ascertained.
Recombinant DNA technology The technique of gene-
rating a hybrid DNA molecule by combining DNA
from two different sources for the purposes of
obtaining multiple copies of a specific gene (cloning)
or for entry and expression into selected cells.
1107
Restriction endonucleases Enzymes that cut DNA at
specific sequences. The recognition sequences for
restriction enzymes are often palindromes or inverted
repeats.
Silent changes Base changes that do not change the
codon specificity-i.e., the amino acid encoded remains
the same and thus has no effect on the protein. Usually,
codon specificity is not altered by a change at the third
base position of the triplet codon, known as the
‘wobble’ phenomenon.
REFERENCES
1. Website for Online Mendelian inheritance in Man. Available
at- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db =
OMIM
2. Website for RetNet-Retinal Information Network. Available
at- http://www.sph.uth.tmc.edu/Retnet/
3. Website for NCBI- A Science Primer. Available at- http://
www.ncbi.nlm.nih.gov/About/primer/
genetics_molecular.html.
4. Young TL. Ophthalmic genetics/inherited eye disease. Curr
Opin Ophthalmol 2003;14:296.
5. Bessant DA, Ali RR, Bhattacharya SS. Molecular genetics and
prospects for therapy of the inherited retinal dystrophies. Curr
Opin Genet Dev 2001;11:307.
6. Hims MM, Diager SP, Inglehearn CF. Retinitis pigmentosa:
genes, proteins and prospects. Dev Ophthalmol. 2003;37:109.
7. Michaelides M, Hunt DM, Moore AT. The genetics of
inherited macular dystrophies. J Med Genet 2003;40:641.
8. Francis PJ, Berry V, Bhattacharya SS, Moore AT. The genetics
of childhood cataract. J Med Genet 2000;37:481.
9. Klintworth GK. The molecular genetics of the corneal
dystrophies—current status. Front Biosci 2003;8:687-7.
10. Griffiths AJF, Miller JH, Suzuki DT, Lewontin RC, Gelbart
W. Introduction to Genetic Analysis (7th edn). WH Freeman
& Co., New York, c1999.
11. Strachan T, Read AT. Human Molecular Genetics 2 (2nd edn).
Bios Scientific Publishers Ltd., Oxford, UK, 1999.
12. Noorani HZ, Khan HN, Gallie BL, Detsky AS. Cost
comparison of molecular versus conventional screening of
relatives at risk for retinoblastoma. Am J Hum Genet
1996;59:301.
13. Gallie BL. Predictive testing for retinoblastoma comes of age.
Am J Hum Genet 1997;61:279.
14. ASHG/ACMG Report. Available at: http://
genetics.faseb.org/genetics/acmg/pol-13.htm
15. Borras T. Recent developments in ocular gene therapy. Exp
Eye Res 2003;76:643.
16. Chaum E, Hatton MP. Gene therapy for genetic and acquired
retinal diseases. Surv Ophthalmol 2002;47:449.
 Chapter 142

Molecular Genetics in Clinical

Ophthalmology*
B Jay, M Jay

INTRODUCTION synthesis.
The structure of mRNA is very similar to that of
Recent advances in molecular genetics are producing
DNA but it differs in two respects. mRNA is single
fundamental changes in our understanding and
stranded; it is complementary to one strand of DNA
practice of medicine which are both exciting and
but the base uracil (U) is subsituted for thymine (T).
important. In order to help ophthalmologists under-
It differs also from DNA in that there are intervening
stand these advances, we are describing here some
sequences of DNA known as introns which are spliced
of the techniques that are applied in molecular
out when RNA is transcribed, and the remaining
biology, and are illustrating the use of these
sequences known as exons from the basis of mRNA
techniques in
(Fig. 142.1).
X-linked ophthalmic disorders, Leber’s hereditary
Much of DNA consist of highly repetitive sequ-
optic neuropathy and retinoblastoma.
ences which, like introns, are thought not to have
any function, so that only a certain proportion of DNA
TECHNIQUES OF MOLECULAR BIOLOGY
can be considered to consist of genes. It is estimated
Basic Concepts that the human genome, the total amount of DNA in
the nucleus of each cell, consists of about 3 × 109 base
DNA has been called the molecule of life, and it
pairs and that there may be about 10,000 genes.
constitutes the template which governs cellular repli-
Much of the manipulation of DNA in the
cation. DNA molecules consist of two strands of
laboratory depends on two of its properties. The first
nucleotide bases joined by hydrogen bonds to form
is that DNA can be cleaved in a reproducible manner
a double helix. Each strand is formed by a sequence
by the use of certain enzymes known as restriction
of anyone of four bases, i.e. adenine (A), guanine
(G), cytosine (C) and thymine (T), joined to a sugar
(deoxyribose) and a phosphate. The bonding between
bases links the two strands in such a way that A
always pairs with T, and G always pairs with C and
reciprocally. If the sequence of bases along one strand
is known, then the sequence along the complementary
strand can be inferred. The sequence of bases along
one strand forms the genetic code, since each triplet
determines an amino acid. DNA is transcribed into a
ribonucleic acid called messenger RNA (mRNA),
and it is mRNA which moves from the nucleus to the Fig. 142.1: Showing loss of introns (I) when DNA is transcribed
into mRNA, the mRNA consisting largely of exons (E)
cytoplasm, where it acts as the blueprint for protein
*Reproduced with permission from Recent Advances in Ophthalmology, No. 8, 1992, published by Churchill Livingstone, Edinburgh, UK
 Chapter 142: Molecular Genetics in Clinical Ophthalmology
enzymes.1 These enzymes are endonucleases, for the
most part derived from bacterial organisms, which
recognize a specific sequence of DNA, usually of the
order of four to ten base pairs and which cleave DNA
at some point in that sequence. Each restriction
enzyme has its own specific recognition sequence or
cleavage site and will always cleave DNA in the same
way, generating fragments of various lengths (Fig.
142.2). The second property of DNA which is used
in the laboratory is its ability to form hybrids in
certain conditions. DNA from one individual can be
separated into its constituent strands by a process of
denaturing, either by heating to 95°C or by treatment
with alkali. If single-stranded DNA from another
source is then introduced, the two DNAs from
different origins will form a hybrid, provided their
sequences of base pairs are complementary. These
two properties form the basis of a technique used to
analyze genes, a technique called Southern blotting.2
Southern Blotting
DNA is isolated from a blood sample and cleaved
with a restriction enzyme. This generates hundreds
of thousands of fragments of DNA which are then
separated according to size by gel electrophoresis.
The smaller fragments travel faster through the gel,
the larger fragments remaining nearer the top. The
whole gel is then blotted on to a nitrocellulose filter
and the strands are denatured. The filter thereby
retains the pattern of single-stranded fragments of
DNA according to their size. At this point cloned
DNA, which has been radioactively labeled and which
is known as a probe, is now applied. A probe is so
Fig. 142.2: The restriction enzyme EcoRI recognizes the
sequence of bases GAATTC, and cleaves this sequence
between G and A. The loss of a cleavage site in B results in
larger fragments of DNA than in A
1109
named because it is a short sequence of single-
stranded DNA which will select any sequence
complementary to it among the fragments on the
filter, and will hybridize with such sequences. The
excess of probe which has not hybridized is washed
off, and autoradiography on X-ray film will reveal
any hybrids as bands (or Southern blots). It is the
analysis of the patterns of these blots which form the
basis of much of gene mapping, and many of the
methods used depend on the choice of probes.
Probes
There are three main types of probe. These are gene-
specific probes, oligonucleotide probes and probes
recognizing variation.
Gene-specific probes are used where the gene
product is known, as for example factor VIII in
classical hemophilia.3 It is possible to work from the
protein sequence in the gene product, to the amino
acid sequence, and to construct the corresponding
mRNA. Under the action of an enzyme known as
reverse transcriptase, the mRNA is copied to single-
stranded DNA, which in turn, and with the use of
the enzyme DNA polymerase, acts as a primer for
the synthesis of a complementary strand; the result
is a molecule known as cDNA (DNA complementary
to the mRNA). This cDNA can be cloned, labeled
radioactively and used in Southern blotting. The
pattern of the blots obtained is shown to be different
in normal and affected individuals, and is due to the
presence, or the absence, of an abnormality of the
gene product.
Another group of probes are the oligonucleotide
probes and, as the name implies, these are short
sequences of DNA usually of the order of 15-30 bases
and which correspond to a sequence which is known
to occur in the gene. Oligonucleotide probes
recognize point mutations which involve the
substitution of one base for another within these
particular sequences.4
The third group of probes are those which
recognize variation in the form of DNA polymor-
phisms. In addition to much of DNA containing non-
coding sequences, much of DNA containing non-
coding sequences, much of DNA is also polymorphic,
that is to say that alternative forms exist. It is
estimated that about one base in 150 is polymorphic,
that is, it can exist as anyone of the four bases A, T,
G or C. As a consequence, some of these polymorphic
sites occur within a cleavage site of a restriction
enzyme and result in the loss of a cleavage site. It
1110 Section 9: Miscellaneous Topics
follows that these polymorphisms affect the size of
fragments generated by cleavage, and they are
therefore termed as restriction fragment length
polymorphisms or RFLPs. Due to an RLFP, two given
fragments from a pair of homologous chromosomes
will be either of the same length, or of different
lengths (Fig. 142.3). Individuals are therefore
homozygous or heterozygous for and RFLP which
can be considered as a two-allele system and which
is transmitted in a mendelian fashion. Probes which
detect an RFLP are usually sequences of DNA taken
from a known source or chromosome and which are
near a polymorphic site. There are other probes
detecting variation known as variable number of
tandem repeats (VNTR).5 These tandem repeats are
very short sequences of DNA, usually between two
and 80 base pairs in length, which are repeated either
in a head-to-tail or in a back-to-back fashion. The
distance between two cleavage sites containing
VNTRs varies according to the number of repeats,
and probes may be selected which detect this
variation. VNTR probes are also known as
minisatellite probes, and they have the advantage
that they are highly polymorphic, so that there is great
variation among individuals, and the proportion of
people in the population who are heterozygous for
this multi-allele system is far higher than those
heterozygous for RFLPs.
Preparation of Probes
The construction of gene-specific probes has already
been described, but other probes are constructed on
the principle that they must be sequences of DNA
from a known source, and each sequence must be
present in a large quantity. Sequences of DNA from
Fig. 142.3: Showing two homologous chromosomes with the
locus of the gene of interest upstream (black box). The arrows
indicate cleavage sites and illustrate an RFLP. This RFLP is
detected by a probe which is shown as a short line in the region
of the polymorphism
a known source may be selected either from somatic
cell hybrids,6 or by chromosome isolation using a
fluorscence-activated cell sorter (FACS).
Somatic cell hybrids have been used in gene
mapping since 1967, when it was found that under
certain laboratory conditions it is possible to fuse
nuclei of cells of two species, usually human and
rodent cells. In subsequent cell culture, these hybrid
cells lose human chromosomes, and finally retain only
one human chromosome. The presence of a human
protein in the hybrid cell is then correlated with the
presence of a particular human chromosome. Hybrid
cell lines containing a given chromosome can therefore
be used as a source of material for probes.
Another method of isolating chromosomes is the
use of a fluorescence-activated cell sorter (FACS), a
machine which uses a laser to sort chromosomes
according to their fluorescence.7 Chromosomes are
stained with ethidium bromide which makes them
fluoresce, and each chromosome has its own fluores-
cence profile which depends on its DNA content.
The next step in the process of producing probes
is to amplify the amount of DNA obtained from a
given chromosome. This is done by molecular cloning
using a vector, which is a vehicle for cloning. DNA
from a chosen chromosome is cleaved with a
restriction enzyme and inserted into vectors, usually
plasmids, cosmids or phage. Plasmids are circular
DNA which will accept an insert of foreign DNA and
which can be cloned in bacteria. Cosmids and phage
are similar to plasmids and are selected according to
the size of the insert of foreign DNA which is
required. A collection of clones with at least one copy
of every DNA sequence in a chromosome is known
as a chromosome library, and similarly there are
genomic libraries. Probes are selected at random from
clones, and are tested against a panel of DNAs from
a number of normals. Those probes which detect
variation are those which are finally chosen, and these
probes are used in linkage.8
Linkage
Two genes are linked if their locus, or chromosome
location, is on the same chromosome. The first step
in gene mapping is to find a chromosome location,
or marker, which is physically close to the disease
locus so that the presence of the marker implies the
presence of the disease locus. RFLPs constitute a
marker system which is of value providing the
polymorphism is sufficiently close to the gene of
 Chapter 142: Molecular Genetics in Clinical Ophthalmology
Fig. 142.4: Crossing over or recombination. The maternally
and paternally derived chromosomes exchange segments at
meiosis
interest. At meiosis, homologous chromosomes
exchange segments in a process called recombination
(Fig. 142.4). The order of genes is altered and genes
which are close together will tend to remain
undisturbed on the same chromosome, but genes
which are further apart may become separated from
each other and end on separate chromosomes. The
frequency of recombination between two genes, or
between one gene and a marker, is a measure of the
distance between them. By convention, one percent
of recombination is equal to a unit called the
centimorgan (cM), and the centimorgan is equivalent
approximately to the megabase (Mb) (1 Mb is equal
to 1000 kilobases (kb) or 1000,000 base pairs (bp)).
The other parameter used in linkage is the lod score,
which is a logarithm of the odds (or probability) of
linkage. A lod score is calculated for each pedigree
and for a given recombination fraction. Linkage is
significant if the lod score, represented by the letter
z, is equal to or greater than 3. This corresponds to
odds of 1000:1 in favor of linkage. Linkage is excluded
for values of z less than 2. The advantage of using
logarithms is that these are additive when calculating
probabilities of linkage using data pooled from
several pedigrees. It is often the case in gene mapping
that data are pooled from several studies, since the
disorder studied may be rare and there is only a finite
number of suitable families for DNA linkage. In
practice, linkage is first found to one marker or RFLP
identifying a chromosomal locus. The notation which
is used for probes is somewhat haphazard the based
on laboratory bench numbers or even the initials of
1111
researchers. A probe, however, identifies an RFLP
whose locus is designated by a precise combination
of letters and numbers: ‘D’ for DNA, followed by
the chromosome number or the letter X or Y for a
sex chromosome, ‘S’ or ‘Z’ for single or repeat
sequence, and finally a number which corresponds
to the chronological order in which the loci on the
relevant chromosome have been mapped. Linkage
to one marker is found first, and followed by linkage
to several markers in the same region. The order of
these markers relative to the disease locus is
calculated by a process called multi-point linkage and
which requires the use of a computer program. The
result is a map which gives the genetic distance
between markers and the disease locus. The actual
physical distance between markers may not be the
same as the genetic distance, and this is due to the
fact that the frequency of recombination is not
constant along a chromosome. Physical distance are
determined using other methods, one of which is
pulsed field gel electrophoresis.
Pulsed Field Gel Electrophoresis (PFGE)
Conventional electrophoresis is a process in which
an electrical field is used to move DNA fragments
through an agarose gel. The rate at which the
fragments move depends on their size, and this
method is used for fragments which do not exceed
20-30 kb. A development of this method is PFGE,
which can separate fragments which are between 50
kb and 10,000 kb in size. 9 DNA is cleaved with
restriction fragments which are chosen for having
rare cutting sites, and this generates fragments of
large size. These fragments are separated by gel
electrophoresis in which the electrical pulse is applied
in two perpendicular directions, and in which the
duration of the pulse is varied. The gel can now be
used for Southern blotting in the same way as in
conventional electrophoresis.
This technique is one way of constructing a long-
range restriction map of a region of interest. If DNA
from a specific region is subjected to successive
cleavage by different restriction enzymes, and
fragments separated by gel electrophoresis, the
relative order of the cleavage sites can be inferred.
These sites are arranged in order and represent a
map which covers a chromosome region. PFGE is
used to construct such a map by identifying any two
probes which hybridize to the same fragment, since
the probes will therefore be separated by a distance
1112 Section 9: Miscellaneous Topics
which is no greater than the length of the fragment.
A map of probes and the physical distance between
them can be constructed. The aim is to find markers
flanking the gene which are separated by no more
than 1 Mb and identified by a particular fragment on
a PFGE gel. It is then possible to cut that fragment
out of the gel and use the DNA to create a library of
clones of the region of interest. It is also possible to
amplify a PFGE fragment by molecular cloning using
an appropriate vector, in this case yeast artificial
chromosomes which are capable of accepting large
inserts. Amplification of much shorter sequences of
DNA, of the order of 1 kb, is achieved by the use of
the polymerase chain reaction technique.
Polymerase Chain Reaction (PCR)
The PCR requires two flanking sequences to the
sequence which is being implied.10 Short sequences
of about 20 bp are constructed from these flanking
sequences and act as primers which are mixed with
the target DNA. A heatstable enzyme, Taq poly-
merase, is used, and the ingredients mixed with the
four nucleotides (A, C, T, G). Heating separates the
target DNA into its two strands, the primers then
anneal to each end and the target sequence is
synthesized. This constitutes one cycle during which
the amount of target DNA is doubled (Fig. 142.5).
Repeated cycles double the quantity at each cycle,
and the reaction is usually run 30 times, which
amplifies the target DNA by 105 to 106 fold. Much of
this process is now automated and allows rapid
results in many different types of DNA analysis
including prenatal diagnosis.
Chromosome Walking and Jumping
In gene mapping, a situation will arise when a more
precise characterization of a DNA sequence of about
80 kb or more is needed. The principle is to construct
a library of clones by cleaving the entire genome and
cloning the fragments, and then to identify a clone
taken from the library which contains a known
marker such as an RFLP. That clone will act as the
start of a walk into the unknown contiguous
fragments. The clone at the start of the walk is cleaved
into smaller fragments which are then subcloned. One
of the subcloned fragments is then used as a probe
to screen the library, and this will select the adjacent
clone. Using this technique, the DNA sequence of
interest can be characterized in terms of overlapping
Fig. 142.5: The polymerase chain reaction. The short sequence
of DNA (shown on the far left) is denatured, primers (small black
boxes) are annealed and initiate the synthesis of the
complementary sequence of DNA. The figure shows how four
copies of one sequence are obtained in the first two steps of a
PCR
clones of a size of the order of 15 kb. There are
drawbacks to this strategy and these are due to the
fact that (a) the ‘walk’ has to be in both directions,
and (b) the ‘walk’ may come to a halt if a highly
repetitive sequence of DNA is reached. This latter
drawback may be overcome by using chromosome
jumping, which is an extension of the same principle
as chromosome walking. In chromosome jumping,
libraries are generated using restriction enzymes
which cleave at rare cutting sites, thus generating
larger fragments, one of which may hopefully
contains the gene of interest. These larger fragments
are cloned and are used in chromosome jumping in
the same way as smaller clones are used in
chromosome walking.
The potentials for the application of molecular
biology to all branches of clinical medicine are
enormous, and hopefully will lead to exciting advances
in many aspects of ophthalmology.
THE X CHROMOSOME AND THE EYE
Many of the earliest applications of molecular genetics
were in the study of X-linked disorders, partly
because the very characteristic mode of inheritance
identified the X chromosome as being the site of the
gene locus, thus obviating a search throughout the
22 autosomes, and partly because the X chromosome
contained a large number of polymorphic sites which
could be used for linkage studies. We will look at a
number of X-linked conditions of interest to
ophthalmologists and the advances that have occurred
in understanding their genetic bases.11-13
 Chapter 142: Molecular Genetics in Clinical Ophthalmology 1113
X-linked Retinitis Pigmentosa (XLRP)
XLRP is one of the most severe forms of these hetero-
geneous group of disorders, occurring in 15-20
percent of index patients in Britain.14,15 In affected
(hemizygous) males it produces symptoms of night
blindness from childhood, considerable constriction
of the visual fields by early adult life, and blindness
usually by the age of 40 years. Occasional families
appear to have a milder form of the disease; it is not
yet known whether these patients have a mutation
allelic with one of the two already identified (see
below) or a mutation at a third locus.
In 1984 the gene responsible for XLRP was
mapped to the short arm of the X chromosome. The
initial report16 was of close linkage of XLRP to the
polymorphism DXS7, identified with the probe L1.28,
which maps to band 11.3 on the short arm of the X
chromosome (Xp 11.3). Several subsequent reports
suggested, however, that there may be a more distal
Fig. 142.6: X chromosome showing sites of the two retinitis
site for XLRP at Xp21,17-19 and that families with a pigmentosa genes, RP2, and RP3 on the short arm ‘p’. The
scintillating golden-metallic sheen (tapetal reflex) in sites of the genes for congenital stationary night blindness
the fundi of carriers had a form of XLRP that mapped (CSNB), choroideremia and blue cone monochromatism, the
distal to DXS7. last two loci being on the long arm ‘q’, are also shown, as are
Support for this more distal site resulted from the sites of most of the probes and loci mentioned in the text
studying two boys with deletion syndromes. In one
boy with Duchenne muscular dystrophy, chronic associates17 was studied further when the carrier
granulomatous disease (CGD), McLeod phenotype females were found to have a metallic sheet in their
and retinitis pigmentosa, an interstitial deletion of fundi. The XLRP locus showed close linkage with
part of Xp21 was identified (Francke et al 1985), a Xp21 marker loci OTC and DXS206.22 In one family
deletion at an appreciable distance from Xp11.3, the from Northern Ireland, the RP gene appeared to be
site of the originally described locus for XLRP. In the located between XJ1.1 and M27b,23 but unlike other
second boy CGD, McLeod phenotype and retinitis reports of families with RP3,19,24 none of the females
pigmentosa20 could be explained by the occurrence in this Irish family exhibited a tapetal reflex.
of a microdeletion involving these loci. His mother The evidence at present available suggests that in
displayed mild abnormalities in her fundii, consistent families where a tapetal reflex is seen in carrier
with the diagnosis of the carrier state of X-linked females this indicates the RP3 gene; its absence is
retinitis pigmentosa. In the affected boy, markers unhelpful in distinguishing between the RP2 and RP3
close to Xp11.3 (754, L1.28, 2bA3 and OTC) were all genes.
present, but the CGD gene in the Xp21 region was At the present time about one half of families are
deleted. Unless the gene deletion in this patient is informative for a probe linked to one or other locus,
part of a more complex rearrangement, the and this information has been used for genetic
occurrence of CGD. McLeod phenotype and XLRP counseling and prenatal diagnosis.
would support localization of these genes to Xp21.18
These findings argue for there being two loci for Congenital Stationary
XLRP, and this heterogeneity was accepted at the Night Blindness (CSNB)
9th Human Gene Mapping Workshop21 when the
The complete form of CSNB is characterized by
proximal locus in band Xp11.3-p11.2 was designated
nonprogressive night blindness from birth,
RP2 and the distal locus in band Xp21.1-p21.4 was
subnormal visual acuity, myopia and normal fundii.
designated RP3 (Fig. 142.6).
Children may present with nystagmus and subnormal
The family previously reported by Nussbaum and
1114 Section 9: Miscellaneous Topics
vision and the importance of making the correct
diagnosis is that this is a stationary condition, not a
progressive retinal dystrophy. These patients have a
Schubert-Bornschein or negative type
electroretinogram (ERG), with no demonstrable
scotopic rod-mediated ERG b-wave, and the
oscillatory potentials are markedly reduced.25
Seven out of eight families with CSNB
demonstrate close linkage with DXS7 and looser
linkage with tissue inhibitor of metalloproteinase
(TIMP) and DXS255, all of which are in Xp11,26 as is
the RP2 gene. In three other families with CSNB
similar close linkage to DXS7 was observed27 and it
remains to be seen whether the genes for the complete
form of CSNB and RP2 are allelic.
Norrie’s Disease
Affected males with Norrie’s disease are blind from
birth; one-third have an appreciable hearing loss and
one-quarter are psychotic and appear mentally
retarded. Histological examination of the eye shows
retinal dysplasia, abundant vascular proliferation and
hemorrhages. Carrier females have normal fundii.
Close linkage has been demonstrated between
Norrie’s disease and the locus DXS7 as defined by
the Taql RFLP detected with the probe L1.28.28-31
Recombination between the gene for Norrie’s disease
and L1.28 has been described,32,33 and it has been
suggested that there may be about a 4 percent error
rate introduced by meiotic crossovers in carriers on
prenatal diagnosis based on linkage between Norrie’s
disease and DXS7.32
Both the Norrie’s disease and DXS7 loci are
included in small submicrosocpic interstitial deletions
of the X chromosome in three independent fami-
lies,28,34-36 and the exclusion of Norrie’s disease was
confirmed by demonstrating the DXS7 DNA sequence
in a fetus. 35 The DXS7 locus, together with the
monoamine oxidase A and B genes, was deleted in
another patient with Norrie’s disease, adding further
confirmation that these loci are close together, the
deletion involving band Xp11.3.37
Using human ornithine aminotransferase (OAT)
cDNA which recognizes OAT-related sequences in
the same region of the X chromosome as the L1.28
probe,38 an RFLP of 4.8 kb in size was found. In the
family reported by Ngo and associates, 33 this
fragment was not expressed in affected males but
was in obligate heterozygotes and normal males. This
finding suggests linkage between this locus and the
Norrie’s disease locus,39,40 thus making the OAT-like
gene sequences a good candidate for a DNA marker
for the disease.
Choroideremia
Choroideremia, like X-linked retinitis pigmentosa,
presents in childhood with night blindness, but
thereafter the course of choroideremia is slower, with
field defects becoming apparent in young adults, and
useful central vision usually being preserved into the
sixth decade of life. Carrier females tend to have a
characteristic fundus appearance, with deep retinal
pigmentation often in a linear distribution in the mid-
periphery, associated with spotty pigment epithelial
atrophy. Choroideremia may be difficult to distin-
guish from XLRP, but the presence of a carrier female
with characteristic fundus changes makes the
distinction easier.
The gene locus for choroideremia has been
assigned to the proximal long arm of the X chromo-
some through demonstration of tight linkage with
various RFLPs located in the Xq13-q21 region.41-44
Recombinations between choroideremia and DXYS1
and DXS3, two of the loci in this part of the long arm
of the X chromosome, have been reported and this
suggests that linkage is not as close as had previously
been suggested.45
Deletions spanning part of Xq21 are associated
with choroideremia and mental retardation deafness
being another common feature.42,46-48 In two patients
a deletion of the DXS165 locus and (part of) the
choroideremia gene were demonstrated,49 while more
extensive studies have assigned the choroideremia
locus to Xq21, spanning the loci DXS95, DXS165 and
DXS233.50 In two patients with choroderemia and X-
linked deafness with stapes fixation and
perilymphatic gushing (DFN3), the overlapping
deletions included DXS233 and DXS95.51
These recent studies have resulted in the majority
of families with choroideremia being informative, and
confirmation of the carrier state, more accurate
genetic counseling and prenatal diagnosis are now
all possible in this condition.
Color Vision and its Defects
Advances in molecular genetics have increased our
understanding of the genes encoding visual pigments.
This in turn has given us new insight into the
mechanisms of normal and abnormal color vision.
Visual pigments consist of an apoprotein, opsin,
linked to 11-cis-retinal, the apoprotein in each of the
visual pigments being encoded by a different gene.
 Chapter 142: Molecular Genetics in Clinical Ophthalmology
The absorption of a photon by a visual pigment results
in the isomerization of retinal from the 11-cis to the
all transconfiguration and this ultimately results in
the production of a neural signal.
Recent work started with the assumption that the
rod pigment rhodopsin and the cone pigments all
evolved from a common ancestor and, as a result,
would contain similar sequences of nucleotides.52,53
Using a bovine rhodopsin gene as a probe, they found
that it bound strongly to one segment of human DNA
and less strongly to three other DNA segments. The
segment to which the bovine rhodopsin gene bound
strongly was shown to be the gene encoding human
rhodopsin which resides on chromosome 3.54,55 The
three segments to which it bound less strongly were
shown to be the genes encoding the color vision
pigments, two (the red and the green color vision
genes) being on the X chromosome and one (the blue
color vision gene) on chromosome 7.53 Bovine and
human rhodopsin are approximately 90 percent
identical in DNA sequence,56,57 human rhodopsin and
color pigments are approximately 40 percent iden-
tical,57 while the red and green pigments show only
43 percent identity with the blue pigment but 96
percent mutual identity.52 The fact that the genes
encoding the red and green pigments are 96 identical
and are located at the end of the long arm of the X
chromosome suggests that they arose by a duplication
event that occurred recently (in evolutionary terms).
One unexpected finding was that while males with
normal color vision have one red pigment gene on
each X chromosome, the number of green pigment
genes varied from one to three,52 while occasionally
there can even be four or more green pigment
genes.58
Nathans and his colleagues then studied indi-
viduals with the four classes of red and green color
blindness. Individuals with deuteranopia were found
to have a normal red pigment gene but no green
pigment gene(s). Those with protanopia lacked a
normal red pigment gene which was replaced by a
hybrid red-green pigment gene, and had no green
pigment gene or a variable number of them. Deuter-
anomalous trichromats had a normal red pigment
gene, a hybrid red-green gene, with or without
normal gene pigment genes. Protanomalous
trichromats had no normal red pigment gene, a
hybrid red-green pigment gene and a variable
number of green pigment genes. These findings were
explained by unequal crossovers that resulted in the
1115
deletion of a pigment gene or the production of
different fusion genes consisting of varying portions
of the red and green pigment genes.53,59 Individuals
with protanopia and protanomaly appear to have the
same genotype (one red-green fusion gene and one
intact green gene). Their phenotypic differences could
be due to slight differences in the crossover points
between the red and green pigment genes, resulting
in protein pigments with different in vivo light
sensitivity, causing different color perception. 60
Similarly, differences in crossover points could
explain the variations that have been described in
the degree of impairment in individuals with
anomalous trichromacy (protanomaly and deuterano-
maly). The molecular methods used up to the pre-
sent are unable to distinguish between small
differences in the position of crossover points.
Blue Cone Monochromatism
Affected males with this uncommon condition
typically present with poor vision from infancy,
nystagmus that tends to reduce in amplitude with
age, apparently complete or almost complete color
blindness, variable degrees of myopia and astig-
matism ‘with the rule’.61-64
In three kindreds, tight linkage was found
between blue cone monochromatism and two RFLP
loci, DXS52 and DXS15, both at Xq28,65 a band on
which the red and green color genes are known to
be located. 52,53 Abnormalities have been
demonstrated in the red and green visual pigment
gene cluster, either an unequal homologous
recombination and point mutation or a deletion of a
579-bp region upstream of the red pigment gene,
which appears to be essential for the activity of both
pigment genes.66 Further studies of this rare form of
monochromatism may throw additional light on the
mechanism of color vision in man.
LEBER’S HEREDITARY
OPTIC NEUROPATHY (LHON)
LHON is an uncommon hereditary disorder presen-
ting most commonly in young adult males, but
occurring in both sexes and at almost any age, and
characterized by the rapid onset of visual failure
affecting both eyes within a few weeks of each other.
In the acute stage the optic disks are swollen and
hyperemic; in the end stage they are flat and pale.
The disorder has been a puzzle and a fascination to
1116 Section 9: Miscellaneous Topics
ophthalmologists and geneticists for many years. Its
hereditary nature has been in no doubt since the
original description by Leber in 1871,67 although the
pattern of inheritance, which does not follow
mendelian principles, has until recently been difficult
to explain. Our understanding of the disease
increased when it became apparent that LHON was
transmitted through females mainly to their sons, the
sons themselves never passing the disease to their
offspring. Another advance occurred when it was
shown that most of the offspring of carrier females
had a characteristic fundus abnormality, peripapillary
microangiopathy.68 This abnormality is present in
most daughters and sons of a female carrier, thus
satisfying the criteria for a maternally inherited
disorder.69
One possible explanation for maternal inheritance
is the occurrence of a mutant gene on the mito-
chondrial chromosome. Mitochondria contain several
copies of a small circular DNA molecule, which in
humans consists of 16 569 bp. Mitochondrial DNA
differs from DNA in the cell nucleus in being
transmitted exclusively by mothers. The most
important function of mitochondrial DNA is that it
helps to code for a number of enzyme complexes
involved in the process of oxidative phosphorylation.
It was inevitable, therefore, that a search was made
for a mutation in mitochondrial DNA in patients with
LHON, and it was exciting when a mutation was
found.
A specific alteration in mitochondrial DNA
resulting in a single amino acid substitution has been
described as being unique to nine out of 11 families
with Leber’s optic neuropathy. 70 This mutation
converts a highly conserved arginine residue, at
position 11 778, to a histidine in the gene for part of
complex I of the respiratory chain. In another series,
this mutation was found in only four out of eight
families, and was associated with 11 778 mutation
regained useful vision.71 All but one of the subjects
had a variable mixture of mutant and normal
mitochondrial DNA, the relative proportions appear-
ing to be correlated with the risk of developing or
transmitting LHON. In another study, the results
suggested that different mutations in the genes
coding for subunits of complex I may be the cause of
the neuropathy, 72 a suggestion supported by the
finding of a reduction in mitochondrial electron
transport activity in four affected patient.73 It seems
likely that more than one mutation in the mitochon-
drial DNA may result in LHON.
The substitution of histidine for arginine in a gene
coding for a subunit of complex I is relatively conser-
vative and may result in only a partial reduction in
the mitochondrial production of energy. This would
result in an energy deficit similar to that caused by
potassium cyanide, a known inhibitor of complex I
activity, and it is possible that this energy deficit could
be exacerbated by cyanide.
The strong male bias in LHON cannot be explained
by a single mitochondrial gene defect alone. The
suggestion of an interaction between a mitochondrial
gene defect and X-linked gene coding for an optic
nerve isozyme74 has not, however, been supported
by multipoint linkage analysis.75 The difficulties in
diagnosing LHON in females with no apparent family
history have recently been emphasized76 and may
go some way toward explaining the apparent male
preponderance in Leber’s optic neuropathy. This is,
however, just one of the questions still to be answered
in this fascinating disorder.
RETINOBLASTOMA
One of the most exciting and fundamentally important
advances in ophthalmic genetics has been our increa–
sing understanding of the genetics of cancer as
demonstrated by the story of retinoblastoma, the
retinoblastoma gene (Rb) now being regarded as the
prototype of a class of tumor-suppressor genes (anti-
oncogenes) whose presence in normal cells is required
to prevent the occurrence of a tumor. It has been
known for a number of years that retinoblastoma is
most commonly a unilateral tumor and, when unila-
teral, is usually sporadic (without a family history).
Less commonly, retinoblastoma is bilateral and then
there is often a family history of other affected mem-
bers, the mode of transmission being autosomal
dominant.
That retinoblastoma has a genetic basis was
supported by the observation that a small percentage
of tumors were associated with a deletion of part of
a chromosome belonging to the D group
(chromosomes 13-15). 77 This observation was
confirmed by many others and, with improved
banding techniques, it became apparent that the
deletion involved the long arm of chromosome 13. It
is now known that about 4 percent of Rb patients
carry this deletion.78 The extent of the deletion varies
between cases and, when large, is associated with
other congenital anomalies, including mental
 Chapter 142: Molecular Genetics in Clinical Ophthalmology
retardation, cranial and facial abnormalities,
anomalies of the fingers and male genital malfor-
mations. In each of these cases the deleted band
common to all was 13q14.79 In addition, similar dele-
tions have been found in the cells of some tumors
from patients with a normal karyotype.
Additional confirmation of the retinoblastoma
predisposition gene being located in band 13q14 came
from studies of the enzyme esterase-D (ESD), the
locus of which is also one chromosome 13.80 Patients
with retinoblastoma associated with a deletion,
however small, of chromosome 13 usually have an
ESD level about 50 percent of normal and this
indicates that the loci for Rb and ESD are closely
linked on band 13q14 ESD is a polymorphism with
two common variants, ESD1 and ESD2, although
ESD1 is much more common than ESD2 in Britain.
Because ESD and Rb are so closely linked, the ESD
polymorphism can be used to track the inheritance
of the Rb gene in informative families and thus make
the prenatal diagnosis or retinoblastoma (Fig. 142.7).
However, because of the low incidence of the ESD2
allele, only about 10 percent of families in Britain are
at present informative for this polymorphism.
Although the predisposition to retinoblastoma is
transmitted as an autosomal dominant trait, it is now
known that tumor formation results from a recessive
mechanism involving the occurrence of two mutant
tumor-suppressor genes. The observation that
hereditary cases are usually bilateral, multifocal and
have an earlier age of onset than unilateral cases,
which are usually sporadic and unifocal, led
Knudson81 to propose that only two mutational events
were necessary for tumor formation. In this ‘two hit’
hypothesis it was postulated that in hereditary
retinoblastoma the first mutational event would be
inherited through the germ line and be present in
every retinal cell, while in sporadic retinoblastoma it
would be a somatic mutation in one of the retinal
cells. In both types of retinoblastoma the second
mutational event would occur somatically and the
tumor would develop in any doubly mutant retinal
cell. It has now been shown that loss of the second
allele in tumor cells often involves loss of a large piece
of chromosome 13 resulting either from non-
disjunction or from mitotic recombination.82
After the Rb locus was mapped to band 13q14 it
was then necessary to isolate the gene. A chromosome
13 lambda phage library was constructed, the source
of the chromosome 13 DNA sequences being either a
1117
Fig. 142.7: Pedigrees of two families with hereditary
retinoblastoma, showing linkage between the retinoblastoma
and ESD genes. In family A the retinoblastoma gene is closely
linked to ESD2, while in family B it is linked to ESD1
fluorescence-activated cell sorter83 or rodent/human
somatic cell hybrids.84 Having found one sequence
which could detect deletions involving 13q14, chromo-
some walking techniques were then used to map the
surrounding genomic DNA. One of the single copy
fragments generated during the chromosome walk
recognized a DNA sequence in the mouse genome
and in human chromosome 13, suggesting that this
fragment contains a coding exon of a gene. This
fragment was then used to isolate a cDNA sequence
4.7 kb in length that was present in all normal cells
but structurally altered in 30 percent of retino-
blastomas. 84 This work has been confirmed by
others,85,86 and it is now accepted that 4.7R represents
the retinoblastoma predisposition gene. It is a complex
gene and consists of 27 exons scattered over a region
of about 200 kb.87,88
Patients who survive the heritable form of retino-
blastoma are at greatly increased risk of developing
osteosarcoma and interestingly, the Rb gene has been
found to be deleted in some osteosarcomas. It would
appear that homozygous loss of the Rb gene can
result in retinoblastoma if the loss of the second allele
occurs in the embryonic retina, and in osteosarcoma
if the second mutation occurs in bone tissue. Similar
changes have been found in a percentage of cell lines
from breast cancer89 and from small cell lung cancer.
The latter tumor does not appear to have a hereditary
component and it has been suggested that the Rb
gene may be particularly susceptible to carcinogens
in tobacco smoke.90 Continuing research in this area
will help us understand the development of second
primary tumors in patients who have had a retino-
blastoma, and the occurrence of some primary tumors
1118 Section 9: Miscellaneous Topics
in relatives of retinoblastoma patients.
CONCLUSIONS
Using several ophthalmic disorders as our examples,
we have indicated some of the advances that are
occurring in our understanding of the genetic basis
of disease. In XLRP, the gene locus was mapped to
the short arm of the X chromosome by linkage studies
involving restriction fragment length polymorphisms.
Shortly afterward a second locus on the short arm
was demonstrated by deletion mapping and further
linkage studies. In similar studies, the gene locus for
choroideremia was assigned to the proximal long arm
of the X chromosome by linkage to RFLPs, and by
studying patients with small deletions involving the
choroideremia locus. As a result of these advances,
more accurate genetic counseling and prenatal diag-
nosis are now possible in many families with these
two disorders.
Using the bovine rhodopsin gene as a probe, the
genes encoding human rhodopsin and the color vision
pigments have been isolated and sequenced. These
studies have confirmed the hypothesis that
rhodopsin and the cone pigments all evolved from a
common ancestor and, as a result, contain similar
sequences of nucleotides. These advances have
increased our understanding of the physiology of
color vision and of its defects.
The pattern of inheritance of Leber’s hereditary
optic neuropathy can now be explained by mutations
in mitochondrial DNA, mitochondria being trans-
mitted exclusively by mothers. The variation in
severity and the strong male basis in this disorder
have yet to be completely understood.
In retinoblastoma, Knudson’s ‘two hit’ hypothesis
has been confirmed by demonstrating deletions of
the retinoblastoma gene, or of ESD closely linked to
it, in many patients with the tumor, and loss of the
second allele in tumor cells indicated by loss of parts
of chromosome 13. The retinoblastoma predisposition
gene has been isolated by methods including deletion
studies and chromosome walking techniques. These
advances are of fundamental importance in our
understanding of the genetics of cancer and are being
applied to a number of other cancers in different
organs.
These advances have opened the way to believe
that, before long, therapies will become available for
many of these genetically determined disorders.
REFERENCES
1. Roberts RJ. Restriction enzymes. In Hames BD, Higgins SJ
(Eds): Nucleic Acid Hubridisation: A practical approach.
Oxford: IRL Press 1985; 203.
2. Southern EM. Detection of specific sequences among DNA
fragments separated by gel electrophoresis. J Mol Biol
1975;98:503.
3. Gitschier J, Drayna D, Tuddenhan EGD et al. Genetic mapping
and diagnosis of haemophilia: A achieved through a BdI
polymorphism in the factor VIII gene, Nature 1985;314:738.
4. Wallace RB, Schold M, Johnson MJ et al. Oligonucleotide
directed mutagenesis of the human beta-globin gene: A general
method for producing specific point mutations in cloned DNA.
Nucleic Acids Res 1981;9:364.
5. Jeffreys AJ, Wilson V, Thein SI. Hypervariable minisatellite
regions in human DNA. Nature 1985;314:67.
6. Ruddle FH. A new era in mammalian gene mapping: Somatic
cell genetics and recombinant DNA methodologies. Nature
1981;294:115.
7. Davies KE, Young BD, Elles RG et al. Cloning of a representative
library of the human X chromosome after sorting by flow
cytometry. Nature 1981;293:374.
8. Ott J. A short guide to linkage analysis. In Davies KE (Ed):
Human Genetic Diseases: A practical approach. Oxford: IRL
Press. 1986;19-32.
9. Barlow D. Pulsed field gel electrophoresis. Genome
1989;31:465.
10. Saiki RK, Gelfand DH, Stoffel S et al. Primer directed enzymatic
amplification of DNA with a thermostable DNA polymerase.
Science 1988;239:487.
11. Weatherall DJ. The New Genetic and Clinical Practice 2nd edn.
Oxford: Oxford university press 1985.
12. Davies KE (Ed). Genome Analysis: A practical approach.
Oxford: IRL Press, 1988.
13. Kingston HM. ABC of clinical genetics. British Medical
Association, London, 1989.
14. Jay M. On the heredity of retinitis pigmentosa. Br J Ophthalmol
1982;66:405.
15. Bundey S, Crews SJ. A study of retinitis pigmentosa in the city
of Birmingham. II. Clinical and genetic heterogeneity. J Med
Genet 1984;21:421.
16. Bhattacharya SS, Wright AF, Clayton JF et al. Close genetic
linkage between X-linked retinitis pigmentosa and a restriction
fragment length polymorphism identified by recombinant DNA
probe L1.28. Nature 1984;309:253.
17. Nussbaum RL, Lewis RA, Lesko JG et al. Mapping ophthal-
mological disease. II. Linkage of relationship of X-linked retinitis
pigmentosa to X chromosome short arm makers. Hum Genet
1985;70: 45-50.
18. Francke U, Ochs HD, de Martinville B et al. Minor Xp21
chromosome deletion in a male associated with expression of
Duchenne muscular dystrophy, chronic granulomatous disease,
retinitis pigmentosa, and McLeod syndrome. Am J Hum Genet
1985;37:250.
19. Denton MJ, Chen JD, Serravalle S et al. Analysis of linkage
relationships of X-linked retinitis pigmentosa with the following
Xp loci: L1.28, OTC. XJ-1.1, pERT87, and C7. Hum Genet
1988;78:60.
20. Saint-Basile G de, Bohler MC, Fishcer A et al. Xp21 DNA
 Chapter 142: Molecular Genetics in Clinical Ophthalmology
microdeletion in a patient with chronic granulomatous disease,
retinitis pigmentosa, and McLeod phenotype. Hum Genet
1988;80:85.
21. Human Gene Mapping 9 (HGM9). Cytogenet Cell Genet
1987;46:1-762.
22. Musarella MA, Anson-Cartwright L, Burghes A et al. Linkage
analysis of a large Latin American family with X-linked retinitis
pigmentosa and metallic sheen in the heterozygote carrier.
Genomics 1989;4:601.
23. Redmond RM, Graham CA, Craig IW et al. DNA analysis and
recombination in X-linked retinitis pigmentosa. Evy 1990;4:204.
24. Friedrich U, Warburg M, Wieacker P et al. X-linked retinitis
pigmentosa: Linkage with the centromere and a cloned DNA
sequence from the proximal, short arm of the X chromosome.
Hum Genet 1985;71:93.
25. Miyake Y, Yagasaki U, Horiguchi M et al. Congenital stationary
night blindness with negative electroretinogram: A new
classification. Arch Ophthalmol 1986;104:1013.
26. Musarella MA, Weleber RG, Murphey WH et al. Assignment
of the gene for complete X-linked congenital stationary night
blindness (CSNB1) to Xp11.3. Genomics 1989;5:727.
27. Gal A, Schinzel A, Orth U et al. Gene of X-chromosomal
congenital stationary night blindness is closely linked to DXS7
on Xp. Hum Genet 1989;81:315-18.
28. Gal A, Bleeker-Wagemakers L, Wienker TF et al. Localisation
of the gene for Norrie’s disease by linkage to the DXS7 locus.
Cytogenet Cell Genet 1985;40:633.
29. Gal A, Stolzenberger C, Wienker TF et al. Norrie’s disease:
Close linkage with genetic markers from the proximal short
arm of the X chromosome. Clin Genet 1985;27:282.
30. Bleeker-Wagemakers L, Friedrich U, Gal A et al. Close linkage
between Norrie’s disease, a cloned DNA sequence from the
proximal short arm, and the centromere of the X chromosome.
Hum Genet 1985;71:211.
31. Kivlin JD, Sanborn GE, Wright E et al. Further linkage data on
Norrie’s disease. Am J Med Genet 1987;26:733.
32. Katayama S, Wohlferd M, Golbus MS. First demonstration of
recombination between the gene for Norrie’s disease and probe
L1.28. Am J Med Genet 1988;30:967.
33. Ngo JT, Spence MA, Cortessis V et al. Recombinational event
between Norrie’s disease and DXS7 loci. Clin Genet 1988;34:43.
34. Gal A, Wieringa B, Smeets DFCM et al. Submicroscopic
interstitial deletion of the X chromosome explains a complex
syndrome dominated by Norrie’s disease. Cytogenet Cell Genet
1986;42:219.
35. de la Chapelle A, Sankila EM, Lindlof M et al. Norrie’s disease
caused by a gene deletion allowing carrier detection and
prenatal diagnosis. Clin Genet 1985;28:317.
36. Forrest SM, Smith TJ, Kenwrick SJ et al. Genetic and physical
mapping of markers localised Xp11.0-Xp22.3 on the human X
chromosome. Ninth International Workshop on Human Gene
Mapping (HGM9). Cytogenet Cell Genet 1987;46:615.
37. Lan NC, Heinzmann C, Gal A et al. Human monoamine oxidase
A and B genes map to Xp11.23 and are delated in a patient
with Norrie’s disease. Genomics 1989;4:552.
38. Barrett DJ, Bateman JB, Sparkes RS et al. Chromosomal
localisation of human ornithine aminotransferase gene
sequences to 10q26 and Xp11.2. Invest Ophthalmol Vis Sci
1987;28:1035.
1119
39. Ngo JT, Bateman JB, Cortessis V et al. Norrie’s disease linkage
analysis using the L1.28 and the human ornithine-aminotrans-
ferase (OAT) cDNA probes. In Piatigorsky J, Shinohara T,
Zelenka PS (Eds): Molecular Biology of the Eye: Genes, Vision,
and Ocular Disease. New York: Liss, 1987;329-38.
40. Ngo JT, Bateman JB, Cortessis V et al. Norrie’s disease: Linkage
analysis using a 4.2kb RFLP detected by a human ornithine
aminotransferase cDNA probe. Genomics 1989;4:539.
41. Nussbaum RL, Lewis RA, Lesko JG et al. Choroideremia is
linked to the restriction fragment length polymorphism DXYS1
at Xq13-21. Am J Hum Genet 1985;37:473-81.
42. Schwartz M, Rosenberg T, Niebuhr E et al. Choroideremia:
Further evidence for assignment of the locus to Xq13-Xq21.
Hum Genet 1986;74:449.
43. Sabjuka E-M, de La Chapelle A, Karna J et al. Choroideremia:
Close linkage to DXYS1 and DXYS12 demonstrated by
segregation analysis and historical-genealogical evidence. Clin
Genet 1987;31:315.
44. Lesko JG, Lewis RA, Nussbaum RL. Multipoint linkage
analysis of loci in the proximal long arm of the human X
chromosome: Application to mapping the choroideremia locus.
Am J Hum Genet 1987;40:303.
45. MacDonald IM, Sandre RM, Hunter AGW et al. Gene mapping
of X-linked choroideremia with restriction fragment-length
polymorphisms. Can J Ophthalmol 1987;22:310.
46. Nussbaum RL, Lesko JG, Lewis RA et al. Isolation of
anonymous DNA sequences from within a submicroscopic X
chromosomal deletion in a patient with choroideremia, deafness
and mental retardation. Proc Natl Acad Sci USA 1987;84:6521.
47. Hodgson S, Robertson ME, Fear CN et al. Prenatal diagnosis of
X-linked choroideremia with mental retardation, associated
with a cytologically detectable X-chromosome deletion. Hum
Genet 1987;75:286.
48. Cremers FPM, Sankila EM, Brunsmann F et al. Deletions in
patients with classical choroidermia vary in size from 45 kb to
several megabases. Am J Hum Genet 1990;47:622.
49. Cremers FPM, Brunsmann F, van de Pol TJR et al. Deletion of
the DXS165 locus in patients with clasical choroideremia. Clin
Genet 1987;32:421.
50. Cremers FPM, van de Pol TJR, Diergaarde PJ et al. Physical
fine mapping of the choroideremia locus using Xq21 deletions
associated with complex syndromes. Genomics 1989;4:41-46.
51. Merry DE, Lesko JG, Sosnoski DM et al. Choroideremia and
deafness with stapes fixation: A contiguous gene deletion
syndrome in Xp21. Am J Hum Genet 1989;45:530.
52. Nathans J, Thomas D, Hogness DS. Molecular genetics of
human color vision: The genes encoding blue, green, and red
pigments. Science 1986;232:193.
53. Nathans J, Piantanida TP, Eddy R1 et al. Molecular genetics of
inherited variation in human color vision. Science 1986;232:203.
54. Sparkes RS, Mohandas T, Newman SL et al. Assignment of the
rhodopsin gene to human chromosome 3. Invest Ophthalmol
Vis Sci 1986;27:1170.
55. Sparkes RS, Klisak I, Kaufman D et al. Assignment of the
rhodopsin gene to human chromosome three, region 3q21-
3q24 by in-situ hybridization studies. Curr Eye Res 1987;5:797.
56. Nathans J, Hogness DS. Isolation, sequence analysis and intron-
exon arrangement of the gene encoding bovine rhodopsin. Cell
1983;34:807.
1120 Section 9: Miscellaneous Topics
57. Nathans J, Hogness DS. Isolation and nucleotide sequence of
the gene encoding human rhodopsin. Proc Natl Acad Sci USA
1984;81:4851.
58. Drummond-Borg M, Deeb S, Motulsky AG. Molecular detection
of colour vision anomalies. Am J Hum Genet 1987;41:A96.
59. Vollrath D, Nathans J, Davis RW. Tandem array of human
visual pigment genes at Xq28. Science 1988;240:1669.
60. Drummond-Borg M, Deeb S, Motulsky AG. Molecular basis of
abnormal red-green color vision: A family with three types of
color vision defects. Am J Hum Genet 1988;43:675.
61. Blackwell HR, Blackwell OM. Rod and cone receptor
mechanisms in typical and atypical congenital achromatopsia.
Vision Res 1961;1:62.
62. Spivey BE. The X-linked recessive inheritance of atypical
monochromatism. Arch Ophthalmol 1965;74:327.
63. Alpern M, Lee GB, Maaseidvaag F. Colour vision in blue-cone
‘monochromacy’. J Physiol 1971;212:211.
64. Smith VC, Pokorny J, Delleman JW. X-linked incomplete
achromatopsia with more than one class of functional cones.
Invest Ophthalmol Vis Sci 1983;24:451.
65. Lewis RA, Holcomb JD, Bromley WC. Mapping X-linked
ophthalmic diseases. III. Provisional assignment of the locus
for blue cone monochromacy to Xq28. Arch Ophthalmol
1987;105:1055.
66. Nathans J, Davenport CM, Maumenee IH. Molecular genetics
of human blue cone monochromacy. Science 1989;25:831.
67. Leber T. Ueber hereditare, congenital angelegte. Schnerven-
leiden Graefes’ Arch Clin Exp Ophthalmol 1871;2:249.
68. Nikoskelainen E, Hoyt WF, Nummelin K. Ophthalmoscopic
findings in Leber’s hereditary optic neuropathy: 1. Fundus
findings in asymptomatic family members. Arch Ophthalmol
1982;100:1597.
69. Nikoskelainen EK, Savontaus ML, Wanne OP. Leber’s
hereditary optic neuro-retinopathy, a maternally inherited
disease: A genealogic study in four pedigrees. Arch Ophthalmol
1987;105:665.
70. Wallace DC, Singh G, Lott MT et al. Mitochondrial DNA
mutation associated with Leber’s hereditary optic neuropathy.
Science 1988;242:1427.
71. Holt IJ, Miller DH, Harding AE. Genetic heterogeneity and
mitochondrial DNA heteroplasmy in Leber’s hereditary optic
neuropathy. J Med Genet 1989;26:739.
72. Vilkki J, Savontaus ML, Kalimo H et al. Mitochondrial DNA
polymorphism in Finnish families with Leber’s hereditary optic
neuroretinopathy. Hum Genet 1989;82:208.
73. Parker WD Jr, Oley CA, Parks JK. A defect in mitochondrial
electron-transport activity (NADH-coenzyme Q oxido-
reductase) in Leber’s hereditary optic neuropathy. N Engl J
Med 1989;320:1331.
74. Wallace DC: Maternal genes. Mitochondrial disease. Birth
Defects 1987;23:137-90.
75. Chen JD, Cox I, Denton MJ. Preliminary exclusion of an X-
linked gene in Leber optic atrophy by linkage analysis. Hum
Genet 1989;82:203.
76. Franks WA, Sanders MD. Leber’s hereditary optic neuropathy
in women. Eye 1990;4:482.
77. Lele KP, Penrose LS, Stallard HB. Chromosome deletion in a
case of retinoblastoma. Ann Hum Genet 1963;27:171.
78. Cowell JK, Rutland P, Jay M et al. Deletions of the esterase-D
locus from a survey of 200 retinoblastoma patients. Hum
Genet 1986;72:164-67.
79. Yunis JJ, Ramsay N. Retinoblastoma and subband deletion of
chromosome 13. Am J Dis Child 1978;132:161.
80. van Heyningen V, Bobrow M, Bodmer WF et al. Chromosome
assignment of some human enzyme loci: Mitochondrial malate
dehydrogenase to 7, mannosphosphate isomerase and
pyruvate kinase to 15, and probably esterase-D to 13. Ann
Hum Genet 1975;38:295.
81. Knudson AG Jr. Mutation and cancer: Statistical study of
retinoblastoma. Proc Natl Acad Sci USA 1971;68:820.
82. Hansen MF, Cavanee WK. Retinoblastoma and the progression
of tumor genetics. Trends Genet 1988;4:125.
83. Lalande M, Dryia TP, Schreck RR et al. Isolation of human
chromosome 13-specific DNA sequences cloned from flow
sorted chromosomes and potentially linked to the retino-
blastoma locus. Cancer Genet Cytogenet 1984;13:283.
84. Friend SH, Bernards R, Rogelj S et al. A human DNA segment
with properties of the gene that predisposes to retinoblastoma
and osteosarcoma. Nature 1984;323:643.
85. Lee WH, Shew JY, Hong FD et al. The retinoblastoma
susceptibility gene encodes a nuclear phosphoprotein
associated with DNA binding activity. Nature 1987;329:642.
86. Fung Y-KT, Murphree AL, T’Ang A et al. Structural evidence
for the authenticity of the human retinoblastoma gene. Science
1987;236:1657.
87. Wiggs J, Nordenskjold M, Yandell D et al. Prediction of the risk
of hereditary retinoblastoma using DNA polymorphisms within
the retinoblastoma gene. N Engl J Med 1988;318:151.
88. Hong FD, Huang HJS, To H et al. Structure of the human
retinoblastoma gene. Proc Natl Acad Sci USA: 1989;86:5502.
89. Lee E Y-H P, To H, Shew J-Y et al. Inactivation of the
retinoblastoma suscepitbility gene in human breast cancer.
Science 1988;241:218.
90. Harbour JW, Lai SL, Whang PJ et al. Abnormalities in structure
and expression of the human retinoblastoma gene in SCLC.
Science 1988;241:353.
 Chapter 143
Infection Control Practices
for Ophthalmologists
Savitri Sharma
Asepsis or antisepsis is the cornerstone of clinical
practice across all medical disciplines, health care
settings and patient populations including ophthal-
mology. An increased risk of nosocomial (hospital
acquired) infection among patients has been epidemio-
logically associated with certain patient care proce-
dures. Bacterial and viral infections have been
reported to spread through contaminated ophthalmic
instruments.1-6 Demonstration of human immuno-
deficiency virus (HIV) and other viruses in tears7,8 has
been alarming, especially in an ophthalmology setting.
In ophthalmic practice, a great deal of screening
procedures are relegated to paramedical staff which
involves repeated use of instruments touching
patient’s eye thereby increasing the risk of cross-
infection. Clear guidelines must be in place to prevent
spread of infection by clinical procedures. Appropriate
education of all staff involved in patient care is the
only way to help stop the spread of infection. Most
essential components of such education programs
should make the personnel understand what causes
infection and how are they spread and teach them
special infection hazards and infection control
procedures pertaining to their job.
Besides ensuring safe patient examination and
screening methods, modern aseptic techniques are also
aimed at making surgical procedures safe for the
patient. Sources of cross-infection in operating rooms
are: (i) the surgeon, the patient and support staff;
(ii) contaminated instruments; (iii) contaminated
fluids; and (iv) air-borne contamination. Of these,
contaminated fluids and instruments have been the
cause of most devastating cross-infection in eye
surgery.9 Attempt has been made in this chapter to
emphasize on the infection control methods that are
essential to an ophthalmic practice as much as they
are so to other disciplines of medicine and surgery.
INFECTION CONTROL PRACTICES
IN PATIENT CARE AREAS
Handwashing
Handwashing is absolutely essential for prevention
and control of nosocomial infections. It must be
practiced faithfully by all hospital personnel in the
following situations:
a. When hands are obviously soiled.
b. After any direct patient contact.
c. After handling used dressings, soiled instruments
or any potentially contaminated articles.
d. Before handling sterile products.
e. During personal hygiene.
The agent used for handwashing is determined by
the type of patient care being administered in an area.
An approved surgical scrub is required before
performing any aseptic technique such as suture
removal, syringing, collecting corneal scrapings or any
clinical sample for microbiological investigations, etc.
A liquid soap product containing mild antiseptic will
be required in treatment rooms where staff members
handle potentially contaminated articles or equip-
ment. Liquid soap containing no antiseptic is sufficient
for handwashing in general patient care areas. Bar
soaps have been shown to harbor microorganisms and
should never be used by personnel engaged in patient
care activities.
1122 Section 9: Miscellaneous Topics
The quality of water used for handwashing may
be an issue where safe tap water supply is not a
routine. Reasonably clean (not sterile) water would
suffice under most circumstances except when an
aseptic procedure on the patient is being contemp-
lated. Filtered water (e.g. Aquaguard®) may serve as
a simple solution to this problem.
Universal Body Substance
Precautions (UBSP)
This system emphasizes that moist body substances
from all patients may be infectious and are to be
treated the same. It is designed to protect hospital
personnel from patients’ body substances (blood,
urine, oral secretions, tears, etc.) primarily by the use
of barriers (gloves or glove substitutes). By providing
the same standard of care for all patients, there are
fewer chances for spread from persons who are
unrecognized as reservoirs of potentially infectious
microorganisms.
UBSP includes the following:
a. Gloves or glove substitutes to be used for
contact with any patient’s blood or body secre-
tions. These barriers are not required for contact
with unsoiled articles or intact skin. Hand-
washing is required after all patient contacts.
b. Masks and protective eyewear are required for
situations in which splatter of blood or body
substances may occur.
c. Gowns and aprons are used to prevent soilage
of personal clothing by moist body substances.
d. Laboratory specimens are to be labeled for
specific diseases (HIV or hepatitis B) only if
these diseases have been diagnosed and patient
remains infectious. In any case, all specimens
are considered potentially infective and are
processed with standardized precautions.
e. Needles and other sharps are placed in a
“sharps container” without cutting, bending or
recapping.
Care of Instruments/Sterile Supplies/Drugs
Tonometers and Gonioscopes
A detailed account of care of various types of
tonometers and gonioscopes has been recently
described.10 The authors have recommended use of
1:1000 Merthiolate for the sterilization of Schiotz
tonometer. For the contact type applanation tono-
meters they recommend either wipe (70% isopropyl
alcohol) or soak (1:10 dilution of sodium hypochloride
or 70% isopropyl alcohol or 3% hydrogen peroxide)
method. When alcohol is used it can just be allowed
to evaporate. In case of other solutions, they need to
be rinsed off with sterile saline before use. Gonioscope
lens may be cleaned in running water and placed in 3
percent hydrogen peroxide or 1:10 sodium hypo-
chloride or 1 percent formaldehyde or 2 percent glutar-
aldehyde. It should be thoroughly rinsed off with
sterile saline before use. Noncontact tonometers do
not touch the cornea or tear fluid; however, the front
surface may be cleaned with soft tissue or cloth as it
may occasionally touch the eyelashes.
A-scan and Pachymetry Probes
The instruction manuals of most machines contain
policies for cleaning and disinfection of probes. It is
safest to use the recommended procedure. Hibitane
(0.5%) or 70 percent alcohol soaked cotton can be used
to disinfect the probes followed by thorough rinsing
with saline or water. The probe without the protection
cap can be sterilized in ethylene oxide gas sterilizer.
Ophthalmic Drops and Ointments
Most commercial eyedrops and ointments can be
stored at room temperature unless refrigeration is
recommended. Many fortified antibiotic drops are
prepared from injectable antibiotics. Aseptic proce-
dures (laminar flow hood) must be followed while
preparation and such drugs may need to be refrige-
rated after preparation. Ideally, each patient must use
individual bottles and the drops should never be
shared. Contamination of in-use ocular medications
is not uncommon and can lead to serious conse-
quences.11
Sterile Instruments and Other Accessories
Appropriate procedures must be followed for steriliza-
tion of all instruments used for patient care. A
description of the methods recommended is outlined
earlier.12 Cotton balls, eyepads, swabs, etc. should be
sterilized in small packs which will help avoid reuse
from an already opened container.
All sterile supplies should preferably be stored in
closed cabinets. Unopened sterile packages can be
stored for a week. All packages must be taped to
indicate they have undergone sterilization and the
date of sterilization must be visible on the tapes.
 Chapter 143: Infection Control Practices for Ophthalmologists 1123
Well-planned use of disinfectants and sterilization Table 143.1: Classification of items
procedures is important to avoid cross-contamination and disinfection process
and cross-infections. It is unnecessary to sterilize all Item classification Spaulding process classification
items in patient care areas; therefore, policies must be
formulated regarding indications for cleaning, Critical Sterilization
disinfection or sterilization on the basis of intended Enters sterile tissue or Sporocidal chemical, prolonged
vascular system contact
use of items. Table 143.1 (reproduced from Reference
12) shows the classification of devices with the Semicritical High level disinfection
corresponding process of disinfection. The types Touches mucous Sporocidal chemical, short
of disinfectants and recommended concentration membranes contact
are outlined in Table 143.2 (reproduced from Refer- Noncritical Intermediate or low level
ence 12). Touches intact skin Disinfection
Trial contact lenses used in the contact lens clinics
should be sterilized by standard methods between
patients. While solutions containing chlorhexidine are Table 143.2: Types of disinfectants and
recommended for the disinfection of gas permeable recommended concentration for use
lenses, multipurpose “Renu” solution is adequate for Disinfectants Recommended concentration
most types of soft lenses. High level
Moist heat (autoclaving) is the most effective Glutaraldehyde 2%
method of sterilization for all heat stable critical items. Formaldehyde 6%
Heat labile materials are best sterilized in gas Hydrogen peroxide 6%
sterilizers which use ethylene oxide. Regular servicing Demand-release chlorine dioxide MR
of sterilizers and regular check on efficacy (using Intermediate level
biological indicators) are crucial to obtaining satisfac- Chlorine 1000 ppm
tory results. Phenol MR
Iodophor MR
Disposal Lower level
Procedures for the disposal of different categories of Alcohols 70-90%
Sodium hypochlorite-100 ppm MR
items in patient care areas should be well-defined. All Phenolic germicidal detergent MR
concerned must strictly adhere to the rules laid down. Iodophor germicidal detergent MR
Sodium hypochloride is one of the best disinfectants Quaternary ammonium compounds MR
to decontaminate items in the clinic. Separate disposal
MR—Manufacturer’s recommendations
bins of reusable and disposable items is ideal with all
disposables preferably undergoing incineration. All
waste bins should contain plastic bags for the safety INFECTION CONTROL PRACTICES IN
of the cleaning staff. Sharps must be discarded in THE OPERATING ROOM (OR)
special bins meant for the purpose and unless reusable Design of the OR
should be incinerated.
Safe and efficient operating room patient care is
influenced by many factors, two of which are
Infection Control Manuals particularly important, i.e. design of the OR and staff
Every patient unit, department and clinic must possess of the OR. The most appropriate time to implement
its own tailor-made infection control manual. The infection control practices is therefore during
manual should contain hospital-wide infection control construction and recruitment. Design and equipment
policies which pertain to all employees in all areas of of a surgical suite can affect utilization patterns,
the hospital as well as specific to a particular area. The material movements and traffic in and around the OR
manuals (updated annually) can be divided into thereby influencing the effectiveness of the people as
sections dealing with policies pertaining to personnel, well as machines. This indirectly affects the incidence
precautions, sterilization, disinfection, the environ- of surgical infection in an OR. The design concept for
ment and patient care. an ideal, large OR complex has been described earlier
1124 Section 9: Miscellaneous Topics
in detail.12 Using the same concept smaller OR suites
can be designed (Fig. 143.1).
It is not advisable to have a separate room for septic
surgery (minor OR) since cases with obvious pus are
not the only ones infected. Every case is potentially
infective. Modern aseptic techniques have made
separate, low-usage facility unnecessary. Moreover,
a separate septic OR may meet with neglect in terms
of maintenance and cleanliness which may result in
postoperative infection by organisms other than the
one harbored by the patient. Presence of an infection
in a patient does not justify introduction of additional
infection. However, to be on the safe side, a septic case
may be scheduled at the end of the day rather than in
the beginning of the day.
Personnel of the OR
While hiring OR staff a ratio of 70:30 has been recom-
mended for registered nurse: technician because
registered nurses can fulfill both scrub and circulating
Fig. 143.1: Layout of a surgical suite for a small ophthalmic set-up
positions, while technicians are only appropriate for
circulating positions. Appropriate training of all staff
in the OR is of paramount importance. The dangers
associated with unskilled, poorly trained staff can
cripple an otherwise well-designed OR.
The environment of OR may be seriously abused
by irresponsible staff. Proper discipline which
ultimately protects the environment in the OR
includes not leaving the door open to the corridor
during surgery and covering hair, sideburns or beards
at all times in all areas of the OR. Particulate biologic
material shedding in the environment is directly
proportional to the number and movement of people
in the room and the amount of exposed hair and skin.
Unnecessary activities by people such as flapping of
drapes, towels or any other movement may blow
particles off horizontal surfaces.
Decontamination of OR Surfaces
The floor, walls, ceilings and other surfaces in the OR
need to be made of hard and nonporous materials.
 Chapter 143: Infection Control Practices for Ophthalmologists
Smooth ceramic, laminated polyester with epoxy
finish, hard vinyl, etc. are preferred building materials.
The floors are best cleaned by wet mopping with
phenolic solution between each patient. The OR table,
instrument stands, supply tables require to be wiped
down with detergent before the first patient of the day.
Any phenolic solution in appropriate concentration
is good for decontamination of the OR surfaces.
Recently introduced disinfectant “BacillocidR Special”
containing formaldehyde and glutaraldehyde is a very
effective antimicrobial agent that can be used for
mopping and wiping of all surfaces in the OR
including the microscopes.
The OR Environment
A variety of items that form the OR environment do
not come in direct contact with the patient and their
role in the causation of postoperative infection is
controversial. However, every effort is worthwhile to
keep the environment germ free. A contaminated
environment can easily find its way to the more critical
areas with devastating consequences. Though routine
culturing of the OR environment is not recom-
mended,13 microbiologic evaluation of all possible
samples to trace the possible source when an infection
occurs and to evaluate the efficacy of the cleaning
methods, is recommended. A periodic microbiologic
evaluation may also serve the purpose of maintaining
high level of awareness in the OR staff.
An ideal OR should be ventilated by high-
efficiency particulate air-filtered (HEPA) systems
which filter out particles greater than 0.3 μm in size.
Air handling system has been described in detail in
an earlier publication.12 All areas in the OR including
closets, storage areas, personnel areas and recovery
rooms, should be ventilated like the OR. The efficacy
of several other air systems such as “laminar flow” or
“curtain effect” are yet to be determined, especially
in the absence of efficient ventilation system in the
OR.
Though the formalin fogging of ORs is no more a
practice in the west, most hospitals in India continue
to use it routinely. Objections to formalin fogging are
related to its carcinogenic properties and the
availability of better alternatives.14 There is no denying
that formaldehyde is a high level disinfectant. High
standards of cleaning and disinfection with controlled
air supply should be in place in the OR before formalin
fumigation or fogging can be given up.
1125
Surgical Scrub and Skin Preparation
The hands and forearms of the chief surgeon, the
assistant surgeon and the scrub nurse, must be washed
before an operation. This wash or scrub must be for at
least 10 minutes and should consist of constant friction,
soaping and repeated rinsing. Scrubbing much longer
can result in raising bacteria from deep dermal layers
to the surface and lead to higher bacterial counts on
the surface. Scrubbing for less than 10 minutes have
also been shown to be as effective; nevertheless, a full
period of 10 minutes is still advocated at least for the
first scrub of the day. The scrub agent may be a
detergent that contains either iodophor (BetadineR) or
chlorhexidine gluconate (Microshield 4). Hands
should be free of infections or cuts and nails must be
kept short. Soft brush may be used initially with
special attention to nails. Between cases, the hands
must be washed again with an antimicrobial agent
albeit for a shorter time. Soap and detergent dispensers
have been shown to harbor gram-negative (Pseudo-
monas spp) bacteria therefore they should not be
refilled.
Scrub sinks should have either foot, knee or elbow
pedals to allow operation of the tap without using
one’s hands. The quality of water used for the surgical
scrub is important. It seems ideal but it may not be
feasible to use autoclaved water. Filtered (e.g.
AquaguardR) water, though not sterile, is a good alter-
native. Boiled and cooled water may be a substitute
where facilities are meager. It is important to get the
water storage tank cleaned and chlorinated frequently
to lower the microorganism load.
Besides being a good scrub agent BetadineR contai-
ning 5 percent w/v povidone-iodine is also an ideal
microbicidal for skin preparation prior to surgery. In
addition, 1-2 drops of the same can be safely instilled
in the conjunctiva of the patient few minutes prior to
surgery.15
Gowning and Gloving
Before scrubbed personnel can touch sterile equipment
or the sterile field, they must put on sterile gowns and
sterile surgical gloves to prevent microorganisms on
their hands and clothing from being transferred to the
patient’s wound during surgery. The sterile gowns
and gloves also protect the hands and clothing of
personnel from microorganisms present in the patient.
All patients must be considered potentially infective.
While donning gloves, care must be taken to prevent
1126 Section 9: Miscellaneous Topics
bare hands coming in contact with outside of the
gloves. Once mastered, both open and closed methods
of donning gloves are good.
Used gowns and gloves must be discarded in
laundry bags marked for the purpose and they should
never be kept near sterile items. Masks and caps
should be removed after leaving the operating area,
preferably, in the changing room and taking care not
to touch the inside. Hygienic and commonsense
storage and processing of clean and soiled linen is
recommended.
Record Keeping
Ideally there should be a separate committee on
surgical infections whose function would be to define,
monitor and investigate all infections. A standard
method should be formulated by the committee and
adopted by all concerned.
REFERENCES
1. Nardi M, Bartolonei MP, Falco L et al. Disposable film covers
for tips of Goldmann tonometers. Graefe’s Arch Exp
Ophthalmol 1989;223:109.
2. Noren NS. Ultraviolet disinfection of applanation tonometer
prism.Acta Ophthalmol 1973;51:687-91.
3. Carboy JM, Borchandt KA. Mechanical sterilization of
applanation tonometers: Bacterial study. Am J Ophthalmol
1971;71: 889-91.
4. Carboy JM, Gaveher GK, Parnes CA. Mechanical sterilization
of applanation tonometers: Viral study. Am J Ophthalmol
1971;71:891-93.
5. Buchler JW, Finton RJ, Goodman RA et al. Epidemic kerato-
conjunctivitis: Report of an outbreak in an ophthalmology
practice and recommendations for prevention. Inf Control
1984;5:390-94.
6. Keenlyside RA, Herbolzen JC, Angelo LJ. Keratoconjunctivitis
associate with adenovirus type 37: An extended outbreak in
an ophthalmologist’s office. J Inf Dis 1983;147:191-98.
7. Fujikawa GS, Palestine AG, Nussenblatt RB et al. Isolation of
lymphotrophic virus type III from tears of a patient with
AIDS. Lancet 1985;2:529-30.
8. Fujikawa LS, Salahudding SZ, Abhilashi D et al. HTLV-III in
tears in AIDS patients. Ophthalmology 1986;93:1479-81.
9. Samples JR, Binder PS. Contamination of irrigating solution
used for cataract surgery. Ophthalmic Surg 1984;15:66.
10. Sood D, Honavar SG. Sterilization of tonometers and gonio-
scopes. Ind J Ophthalmol 1998;46:113-16.
11. Schein OD, Hibberd PL, Starck T et al. Microbial contami-
nation of in-use ocular medications. Arch Ophthalmol
1992;110:82-85.
12. Sharma S, Bansal AK, Gyanchand R. Asepsis in ophthalmic
operating room. Ind J Ophthalmol 1996;44:173-77.
13. Laufman H. The operating room. In Bennett JV, Brachman
PS (Eds): Hospital Infections. Boston: Little Brown and Co,
1986;315-24.
14. Publication of hospital infections and microbiologic control
branches. Bacterial disease division, Bureau of epidemiology,
Center for Disease Control, Atlanta, 1980.
15. Speaker MG, Menikoff JA. Prophylaxis of endophthalmitis
with topical povidone-iodine. Ophthalmology 1991;98:
639-49.
 Chapter 144
Acquired Immunodeficiency
Syndrome and the Eye
J Biswas, A George
Acquired Immunodeficiency Syndrome (AIDS) was
first described in 1981, and within three years the
causative virus which is currently known as Human
Immunodeficiency Virus (HIV) was identified.1,2 Since
1981, AIDS has become a global pandemic with more
than 40 million people in the world being affected. In
India it is estimated that about 3.8-4.5 million people
have been affected by the end of the year 2000.3 The
Center for Disease Control in 1993 has revised its
classification of HIV infection and expanded the AIDS
surveillance definition to include those individuals
with severe immunosuppression (defined as CD4+ T-
lymphocyte count of less than 200 cells/μl).4 (Table
144.1). Since the first description of ocular lesions in
1982 there are several studies of ocular involvement
in AIDS from different parts of the world.5 The first
published report of ocular lesions in AIDS from India
Table 144.1: CD4 count in different
opportunities infections in AIDS
CD4 Count Disease
3
1000 cells/mm Normal level
3
< 500 cells/mm Kaposi’s sarcoma
Lymphoma
Tuberculosis
< 250 cells/mm3 Pneumocystosis
Toxoplasmosis
< 100 cells/mm3 Retinal/Conj. microvasculopathy
Keratoconjunctivitis sicca
Varicella zoster virus retinitis
CMV retinitis
was in 1995. 5 Since then several cases have been
reported from various centers in India.6-9
Ocular lesions in AIDS are varied and affect almost
all structures of the eye. They are usually seen in the
final stages of the disease when the immunity is
lowest. However they have been known to be the
initial manifestation in many cases and can help the
clinician to suspect underlying HIV infection.
Ocular lesions associated with AIDS can be broadly
categorized into four groups:
1. HIV retinopathy
2. Opportunistic infections caused by viruses,
bacteria, fungi and protozoa
3. Neuroophthalmic lesions
4. Unusual neoplasms, including Kaposi’s sarcoma
Ocular lesions can also be categorized by the ocular
structures affected.
• Ocular adnexal involvement
• Anterior segment involvement
• Posterior segment involvement
• Neuroophthalmic involvement
• Posterior segment involvement10 is relatively more
common.
HUMAN IMMUNODEFICIENCY VIRUSES (HIV)
HIV belongs to the Lentivirus sub-family of retro-
viruses and causes a chronic infection resulting in
progressive damage to the immune system of the
human host. Two major types, HIV type 1 and type 2,
cause infections in humans. HIV type 1 is the most
common type found throughout the world. Type 2 is
1128 Section 9: Miscellaneous Topics

primarily found in persons from West Africa although

it occurs in other parts of the world. HIV 1 shows a
large amount of genetic variation not only between
infected individuals but also within the same infected
person during the course of the disease. The analysis
of the nucleotides and the deduced amino acid
sequences show the existence of at least 8 “clades” or
“genotypes” of HIV 1.The phylogenetic tree of HIV 1
consists of a major group “M” and another group “O”
(outliers or out group).11 The subtypes of “M” are A–
H and those occurring in India are B, C and A.
Ocular lesions occur in 40 to 70 percent of AIDS pati-
ents. However autopsy findings suggest that as many
as 95 percent of AIDS patients have ocular lesions.12
Fig. 144.1: Fundus photograph showing multiple cotton-wool
spots in the posterior portion of the retina in a case of AIDS
POSTERIOR SEGMENT LESIONS
Posterior segment lesions are present in more than half retinopathy has reduced. 14 HIV retinopathy is a
the patients with ocular lesions. They can involve the noninfectious microvascular disorder characterized by
retina, choroid or optic nerve; sometimes more than cotton-wool spots, microaneurysms, retinal hemorr-
one structure may be involved (Table 144.2). Some of hages, telangiectatic vascular changes, and areas of
these lesions can be sight threatening. Patients may capillary nonperfusion. Cotton-wool spots occur in
be asymptomatic when the lesions do not involve the approximately 25-50 percent of patients with advan-
posterior pole. The common presenting symptoms ced HIV disease and are the earliest and most
include floaters, flashes of light, visual field defects consistent finding in HIV retinopathy.15 They may be
and dimness of vision. In India patients often present differentiated from the cotton-wool spots in diabetic
in advanced stages of the disease, as a routine ophthal- and hypertensive retinopathy by the absence of
mic check up is not done in many instances. Posterior microaneurysms and the lack of associated vascular
segment lesions are divided into following categories. changes like arteriolar narrowing. The average time
of disappearance of cotton-wool spots in HIV
Non-infectious Retinopathy (HIV Retinopathy) retinopathy is 6 to 12 weeks.16 They are not vision
threatening, although in advanced HIV disease they
HIV related retinal micro-angiopathy was the most
may cause small visual field defects corresponding to
common ocular lesion in patients with AIDS before
the cotton-wool spots. Hemorrhages, blot or flame-
the introduction of highly active antiretroviral therapy
shaped, are less commonly seen than cotton-wool
(HAART) therapy. Retinal microangiopathy was
spots and are estimated to occur in about 20 percent
detected in almost 50 percent of the cases during the
of patients with advanced HIV disease and in
latest phase of HIV infection (Fig. 144.1).13 Recently
approximately 3 percent of patients with mildly
due to early treatment the prevalence of HIV
symptomatic HIV disease.17 Telangiectatic vascular
Table 144.2: Common posterior segment
changes may be seen in patients with HIV disease and
lesions in AIDS patients are often associated with microaneurysms.
• HIV retinopathy Opportunistic Infections
• Cytomegalovirus retinitis
• Toxoplasmic retinochoroiditis An expanding list of infections of the retina and
• CMV optic neuritis choroid have been reported to affect individuals with
• Pneumocystis carinii choroidopathy advanced HIV disease. Although a number of these
• Acute retinal necrosis infections can also be seen in immunocompetent
• Herpes zoster retinopathy patients, it is important to remember that there may
• Progressive outer retinal necrosis be significant differences in the clinical presentation
• Endogenous endophthalmitis
in HIV-infected patients. Such individuals may
 Chapter 144: Acquired Immunodeficiency Syndrome and the Eye
present with less accompanying inflammation, take
longer time to respond to therapy, and have a greater
chance of recurrence after therapy. Multiple foci of
infection and bilateral infection as well as more than
one infection in the same eye are also more likely to
occur in HIV-infected patients. The introduction of
HAART has added several confounding features in
the presentation and course of previously described
diseases. Finally, new, as yet undescribed infections
of the retina and choroid are likely to be encountered
in the setting of HIV infection in the future. A strong
correlation exists between the level of immuno-
suppression (CD4 count) and the appearance of parti-
cular opportunistic infections18 (Table 144.1).
1129
brushfire border, with the active edge of whitening
spreading from the previously infected area. With
involvement limited to the peripheral retina, patients
either have no subjective complaints, or may complain
of floaters. If the retinitis begins in the posterior pole,
the patient may notice a central scotoma. The possible
mechanisms for visual loss are direct retinal necrosis
by infection, optic nerve involvement, and retinal
detachment.21 Rhegmatogenous retinal detachment
has been reported in 13.5-29 percent of patients with
CMV retinitis and may occur during the active or
healed phase of the disease.22 These detachments are

Cytomegalovirus (CMV) Retinitis

CMV retinitis is the most common retinal infection in
patients with HIV disease affecting 15 to 40 percent
of HIV infected patients in the pre-HAART era.19 It
occurs when the CD4 cell count is less than 100 cells
per mm3.20 It is bilateral in 30 to 50 percent of patients;
although the incidence may be lower as the disease
often presents unilaterally and the administration of
anti-CMV medication almost always prevents the
onset of retinitis in the fellow eye. CMV is a species-
specific DNA virus classified in the herpes group of
viruses. CMV disease affecting the eye, however, tends
to occur only in the developing fetus or in immuno-
compromised patients. CMV infection of the retina Fig. 144.2: Fundus photograph showing typical cyto-
leads to viral invasion of retinal cells with resultant megalovirus retinitis with white necrotic retina associated with
retinal necrosis. The classic description of CMV reti- retinal hemorrhages
nitis is one of scattered yellow-white areas of
necrotizing retinitis with variable degree of hemorr-
hage and mild vitreous inflammation. Some authors
have described this appearance as “cottage cheese
with catsup” or “pizza pie” retinopathy. Initially
presenting as small white, granular patches, these
areas continue to enlarge if left untreated. Active
lesions show white areas of retinal necrosis usually
associated with hemorrhages (Fig. 144.2). The retinitis
often follows a perivascular distribution. The
advancing edge of these lesions is usually very sharp
and spreads contiguously. Typically, over several
weeks untreated lesions progress to full-thickness
retinal necrosis with resultant retinal gliosis and
pigment epithelial atrophy (Fig. 144.3). The pathway
of expanding lesions can be predicted by the
appearance of venous sheathing or white dots distal
to the leading edge, indicative of direct cell-to-cell Fig. 144.3: Fundus photograph showing
spread of infection. Expanding lesions often take on a end-stage untreated cytomegalovirus retinitis
1130 Section 9: Miscellaneous Topics
particularly difficult to repair using standard retinal
detachment surgery. Other findings associated with
CMV retinitis include perivasculitis, vascular attenu-
ation, and vessel closure, as well as vitritis, anterior
uveitis, and papillitis.
Retinal Detachment in CMV Retinitis
Risk factors for development of retinal detachment are
peripheral involvement > 25%, presence of active
retinitis, higher patient age and lower CD4 counts. As
the results of traditional surgeries are often dis-
appointing, laser photocoagulation for selected
nonmacular detachments may delay the need of
vitrectomy with silicone oil tamponade. Surgery for
CMV related rhegmatogenous retinal detachment can
be done under local or general anesthesia. Three-port
pars plana vitrectomy and silicone oil tamponade is
often recommended.23 Some surgeons add Ganciclovir
30mg/ml in the infusion bottle. 24 Dissection of
posterior cortical gel is quite crucial but can be difficult
in areas of thin atrophic retina. One can use a
disposable soft tipped extrusion cannula for that
purpose along with membrane picks and intraocular
scissors. In most of the cases with CMV related retinal
detachment silicone oil removal has not been
performed due to the short life expectancy of the
patients with advanced AIDS disease. However due
to the advent of HAART, removal of silicone oil is now
required increasingly. Good anatomical success rates
with a final reattachment rate of 64-82%25 and a
macular reattachment rate of 86-92%26 have been
described. A mean best postoperative visual acuity of
6/18 was reported in a series of 65 eyes of 51 patients.25
However the vision drops after 1-2 months due to
CMV optic neuritis, progressive smoldering retinitis,
retinal detachment, complicated cataract and anterior
segment complications of silicone oil.
VARICELLA ZOSTER VIRUS DISEASE
Acute Retinal Necrosis (ARN)
ARN has typically been described in otherwise healthy
adults of either sex and any age, but recent reports
have described it in immunocompromised patients as
well, including patients with AIDS.27 In the vast majo-
rity of patients the acute retinal necrosis syndrome
appears to be caused by herpes zoster. However,
herpes simplex has also been implicated as a causative
agent.
The presentation of ARN is similar to that seen in
immunocompetent patients with mild to severe
anterior uveitis, vitritis and necrotizing peripheral reti-
nitis. The retinitis may progress within a matter of
days to weeks to dramatic whitening of the peripheral
retina in multifocal and coalescent patches. Vasculitis
involving both arteries and veins is a prominent
feature. Optic nerve head and macular edema are often
present during the active phase of the disease. If the
second eye becomes involved, the clinical course is
similar.
Regression begins at the outer margin of the lesions
and moves centrally, this may be quite rapid, taking
only 2-3 weeks. Multiple tiny sieve like retinal holes
are present following resolution of the infection.
Vitreoretinal traction leads to rhegmatogenous
detachment. Clinical differentiation between the
various HSV types and VZV is still not possible,
however, there are indications that retinitis due to
HSV-2 begins at the posterior pole. The American
Uveitis Society has laid down some standard
diagnostic criteria for ARN in 199428 (Table 144.3).
Table 144.3: Diagnostic criteria of ARN
1. One or more foci of retinal necrosis with discrete
borders located in the peripheral retina.
2. Rapid progression of the disease without antiviral
therapy.
3. Circumferential spread of disease.
4. Evidence of occlusive vasculopathy with arteriolar
involvement.
5. Prominent inflammatory reaction in the vitreous and
anterior chamber
6. Not required characteristics: optic neuropathy/
atrophy, scleritis, pain.
7. If not all of these criteria are seen, the term ‘Necrotizing
herpetic retinopathy ‘ should be used.
Staging
Stage 1 Necrotizing retinitis
Stage 1a Discrete areas of peripheral retinitis
Stage 1b Confluent areas of peripheral retinitis, papillitis,
macular edema
Stage 2 Vitreous opacification or organization
Stage 3 Regression of retinal necrosis, secondary
pigmentation of the lesion with condensation of
the vitreous base
Stage 4 Retinal detachment
Stage 4a Acute retinal tears or detachment with traction
or proliferative vitreoretinopathy
Stage 4b Chronic retinal detachment
 Chapter 144: Acquired Immunodeficiency Syndrome and the Eye 1131
Progressive Outer Retinal Necrosis (PORN)
PORN, is a recently recognized variant of necrotizing
herpetic retinopathy representing a distinct form of
ARN, developing in patients with AIDS or conditions
causing an immune compromised status. 29 It is
characterized by early macular retinitis in the presence
of little or no intraocular inflammation. There is rapid
progression with the development of lesions in the
mid and peripheral retina with no consistent direction
of disease spread unlike what is seen in cases of ARN.
Fig. 144.4: Montage fundus photograph showing progressive
Unlike ARN and typical CMV retinitis, which involve outer retinal necrosis. Note sparing of retinal vessels
full thickness of the retina, PORN is characterized by
deep retinal opacification without granular borders, of retina become necrotic, large retinal breaks occur
giving the impression of an “outer retinitis”. With leading to rhegmatogenous retinal detachment in the
progression there is clearing of areas around retinal majority of affected eyes, contributing to overall poor
vessels, which have been described as a “cracked prognosis. The diagnosis of PORN is always clinical,
mud” appearance (Fig. 144.4). These areas are regions based on its characteristic appearance as described.
of perivascular retinal sparing which is due to early However it closely mimics ARN and CMV retinitis.
removal of necrotic debris and edema from retinal The differentiating features between ARN, PORN and
tissue adjacent to the blood vessels. As infected areas CMV retinitis are given in the Table 144.4.

Table 144.4: Differentiating features of three types of viral retinitis in AIDS

ARN PORN CMV retinitis
Immune status Healthy/rarely Immunosuppressed Usually immunosuppressed
immunosuppressed
Laterality Bilateral 30-80% Bilateral 71% Bilateral 30-50%
Visual loss Initial mild,later gross Early loss of central vision Variable, depending on site of
involvement
Anterior segment Mild to moderate anterior Mild NGU Mild NGU
uveitis
IOP Raised Normal Normal
Vitreous reaction Significant vitritis Minimum/no Minimum/no vitritis
vitritis
Retinal involvement Full thickness Deep retinal involvement Full thickness involvement with
without granular border granular border
Pattern of Multifocal, predominantly Multifocal, early macular Usually unifocal , fovea
involvement peripheral involvement relatively spared
Classic appearance Late swiss-cheese Cracked mud Cottage cheese with cats up or
pizza-pie
Vasculitis Common Uncommon Seen but not common
Retinal hemorrhage Common Uncommon Common in active lesion
Retinal detachment Common Common Less common
Optic nerve Common Uncommon Seen but not common
involvement
Progression Rapid Rapid Slow
1132 Section 9: Miscellaneous Topics

Frosted Branch Angiitis

Frosted branch angiitis is essentially a severe form of
vasculitis that affects the entire retina (Fig. 144.5). It can
be idiopathic or associated with ocular and systemic
diseases. CMV retinitis, HIV retinitis and Toxoplasmic
chorioretinitis are the most frequent ocular asso-
ciations, while systemic lupus erythematosus, Crohn’s
disease, large cell lymphoma and acute lymphoblastic
leukemia have been described as systemic disorders
associated with frosted branch angiitis. Approxi-
mately 6 percent of patients with CMV retinitis are
estimated to have frosted branch angiitis.30

TREATMENT OF VIRAL RETINITIS

The treatment of viral retinitis may be systemic, local,
or a combination of the two. The following are the
various treatment modalities that are available for use.
Ganciclovir
Ganciclovir is a nucleoside analog that acts as a
competitive inhibitor and faulty substrate for CMV
DNA polymerase. Ganciclovir inhibits all herpes
viruses, including CMV by preventing DNA elon-
gation. An induction dose of 5 mg/kg every 12 hours
for 14 to 21 days should be followed by maintenance
doses of 5 mg/kg/day, indefinitely, i.e. until there is
evidence of relapse or progression.31 Since treatment
may be life-long, usually a permanent or semi-
permanent indwelling venous catheter is required. It
takes 2-3 weeks before the clinical effect is apparent
and 3-6 weeks before complete healing is achieved.
Since ganciclovir is virostatic, recurrences often occur
within 10 to 21 days of discontinuation of the drug. A
major side effect is neutropenia (15-40%), which can
Fig. 144.5: Fundus photograph showing cytomegalovirus
retinitis with severe sheathing of the retinal vessels, resembling
frosted branches of a tree in frosted branch angiitis
be managed with G-CSF 300 mcg daily. Other adverse
effects include thrombocytopenia, anemia, nausea,
vomiting, and elevated liver enzymes. It is necessary
to monitor hematologic counts twice each week.
Resistance to the drug is known and hence sensitivity
should be checked after 3 months of therapy.
Ganciclovir is a better choice in patients with baseline
renal insufficiency or patients taking nephrotoxic
drugs (e.g., amphotericin B, amikacin) (Fig. 144.6).
Foscarnet
Foscarnet is a pyrophosphate analogue that inhibits
DNA polymerase of CMV and other herpes viruses
(HSV-1, HSV-2, VZV, and Epstein-Barr virus) and

Figs 144.6A and B: Resolution of cytomegalovirus retinitis following treatment with intravenous ganciclovir.
(A–Fundus photograph prior to injection, B–Fundus photograph following injection)
 Chapter 144: Acquired Immunodeficiency Syndrome and the Eye
reverse transcriptase by directly affecting the
pyrophosphate binding site. This agent is also
virustatic and it has an intrinsic anti-HIV effect that
may be beneficial for reducing HIV viral load in
combination with other antiretroviral agents.
Foscarnet also has been used successfully to treat
patients with acyclovir-resistant HSV and VZV
infections, in addition to ganciclovir-resistant CMV
retinitis. An induction dose of 90 mg/kg twice a day
for 14-21 days is followed by a maintenance dose of
90-120 mg/kg/day indefinitely, i.e. until evidence of
relapse or progression.32 Cessation of retinal lesion
advancement and resolution of the acute inflammation
are usually seen within 4 weeks. The major side effects
are nephrotoxicity and hypocalcemia, causing
arrhythmias and seizures. Electrolyte imbalance may
cause hypercalcemia and hyperphosphatemia or
hypophosphatemia. Practical guidelines for the use
of foscarnet include administration through a infusion
pump to avoid the potential consequences of overdose
or too rapid infusion, adequate hydration of patients
with saline loading to reduce the risk of nephro-
toxicity, avoidance of administration of other
potentially nephrotoxic agents, and monitoring of
renal function two or three times per week during
induction therapy.
Combinations of foscarnet and ganciclovir are
more effective in the treatment of recurrent or resistant
retinitis than is continued monotherapy.33 Unfortu-
nately, combination intravenous therapy necessitates
multiple intravenous infusions daily and has a marked
negative effect on patient’s lifestyle.34
Acyclovir
Acyclovir is a nucleoside analog that has potent
activity against HSV-1, HSV-2 and VZV. It selectively
targets infected cells only by a virally encoded
enzyme, thymidine kinase, to phosphorylate it into
an active form. The recommended intravenous dose
is 1500 mg/m2/day divided into three daily doses for
7 to 10 days. This should be followed by an oral
therapy of 800 mg five times daily for 14 weeks.
Complete regression occurs within 4 weeks and fellow
eye involvement is also reduced with this therapy.
Catheter-less Therapy
The use of intravenous ganciclovir or foscarnet
requires long-term indwelling catheters. The risk of
catheter-related sepsis is high, these lines are expen-
1133
sive to maintain and are associated with a substantial
negative impact on quality of life. There has been great
interest in developing therapies that do not require
an indwelling catheter. 35 The following are the
catheter-less treatment options:
1. Oral ganciclovir
2. Intravenous cidofovir
3. Ganciclovir intraocular implant
4. Intravitreal injections (ganciclovir, foscarnet,
cidofovir, fomivirsen).
Oral Ganciclovir
Oral ganciclovir (1g 3 times daily) can be used for
maintenance therapy of CMV retinitis after induction
and stabilization of disease with an intravenous agent.
It is however less effective than intravenous gan-
ciclovir.36 Currently, oral ganciclovir is not routinely
used as prophylaxis because of its high cost, difficulties
with compliance of the dosing schedule, lack of
demonstrated survival benefit and toxicities. As of
today, the most common use of oral ganciclovir is in
patients being treated with intravitreal ganciclovir in
whom it is desired to prevent extraocular and fellow-
eye CMV disease.
Intravenous Cidofovir
Cidofovir is a nucleotide analog which does not
require phosphorylation by viral encoded enzymes.
It is active in uninfected cells, can act pre-emptively,
and may retain activity against ganciclovir-resistant
strains. An induction dose of 5 mg/kg intravenously
every week for 2 weeks followed by a maintenance
dose of 5 mg/kg every 2 weeks indefinitely, is
recommended.37 Increased proteinuria and elevations
in serum creatinine are the major dose-limiting
toxicities.38 To reduce renal toxicity, saline hydration,
concomitant administration of probenecid, dose
reduction or interruption for changes in renal function,
and extension of the dosing interval are indicated.
Probenecid competes with cidofovir at the proximal
renal tubule cells and is administered with cidofovir
in order to protect the tubule cells from taking up
cidofovir in toxic concentrations, thus decreasing the
systemic uptake of the drug. Ocular complications
include transient iritis (upto 40% cases) and ocular
hypotony (12% cases). 39 However, since decreased
intraocular pressure is common and usually clinically
insignificant in patients with advanced AIDS, the
clinical relevance of this finding is not clear.40 The iritis
1134 Section 9: Miscellaneous Topics

is easily treated with topical steroids and cycloplegics.

Ganciclovir Intraocular Implant

The ganciclovir implant is a sustained-release drug
delivery device that contains about 4.5-6 μg of
ganciclovir. The pellet of ganciclovir salt is first coated
with permeable layer of polyvinyl alcohol, followed
by an impervious coating of ethylene vinyl acetate,
and then by another coating of polyvinyl alcohol. It is
placed into the vitreous cavity through a 5-6 mm
incision in the pars plana and sutured to the sclera.
The drug diffuses into the vitreous cavity by passive
diffusion at the rate of 1 mcg/hour over a 6-8-month
period. After that, the device is usually surgically
removed and/or replaced with a new device. The
intravitreal levels attained by this drug are over twice
those after intravenous administration, and this
appears to be associated with a lower incidence of
resistance and progression of retinitis. Adverse events
include retinal detachments (12%), endophthalmitis
(1.7%), and transient vitreous hemorrhage (7.8%).
However, as with all local treatments, there is a risk
of CMV disease in the fellow eye (upto 40% cases) and
extraocular CMV disease (10.3%). 41

Intravitreal Medications
Fig. 144.7: Technique of administering
a. Ganciclovir. Ganciclovir was the first anti-CMV intravitreal ganciclovir
compound administered as an intravitreal injection
(Fig. 144.7). The dose varies from 200-2000 mcg/
can be controlled with topical steroids and
0.1 ml. These injections are given on a weekly basis.
cycloplegics.45 Probenecid prophylaxis is routinely
They are usually well-tolerated, highly effective,
advocated to prevent these side effects. Multiple
and relatively inexpensive. The main adverse
intravitreal cidofovir injections given every 5 to 6
effects include endophthalmitis, retinal detach-
weeks for the maintenance treatment of CMV
ment, and vitreous hemorrhage.42
retinitis is highly effective, with only rare episodes
b. Foscarnet. The dose recommended for intravenous
of reactivation and progression.
foscarnet is 2400 mcg per 0.1 ml; the undiluted
d. Fomivirsen. Fomivirsen is a 21-base phosphoro-
stock solution is used for the intravitreal adminis-
thioate antisense with potent antiviral activity.
tration. The half-life is shorter than ganciclovir and
Injections in the dose of 330 mcg are given on days
recommended dose indicate twice weekly injec-
1 and 15 and then monthly thereafter. The median
tions for induction and once a week for mainte-
time to progression of retinitis is around 90 days.
nance. Like ganciclovir, these injections are well-
The principal toxicity is intraocular inflammation
tolerated but are more expensive to administer.43
and elevation of intraocular pressure (10-20%).46
c. Cidofovir. Cidofovir, given intravitreally in doses
of 15 mcg to 20 mcg/0.1 ml, is safe and effective
INVESTIGATIONAL AGENTS
for the local treatment of CMV retinitis, providing
a long duration of antiviral effect. The median time Valganciclovir, is the valine ester of ganciclovir and
to retinitis progression after a single injection is is rapidly converted to ganciclovir in the intestinal
around 55 days.44 Transient iritis (upto 50%) and wall. When given orally, it achieves intravenous
mild asymptomatic reduction in intraocular ganciclovir levels with 2 pills twice daily. Valacyclovir,
pressure (20%) are the main adverse reactions, and is a prodrug of acyclovir that produces much higher
 Chapter 144: Acquired Immunodeficiency Syndrome and the Eye
serum levels of acyclovir when given orally. 47
Valacyclovir has been shown to suppress CMV viral
load in blood and urine; however, its ultimate role is
still not defined. Intravitreal injection of liposome-
encapsulated ganciclovir reduces the number of
intravitreal injections and stabilizes CMV retinitis.
Recently, human trials with systemic cytokine
immunotherapy with interleukin-2 have also shown
potential antiviral effects.
Ocular Toxoplasmosis
Toxoplasma gondii, a protozoa, affects about 10 percent
of AIDS patients. The healed lesions of past toxo-
plasmosis may become active or these may be de novo
lesions. However, toxoplasmic retinochoroiditis is
relatively rare and accounts for 1 percent of AIDS-
related retinal infections.48 It produces a necrotizing
retinitis similar to CMV retinitis (Table 144.5). Ocular
toxoplasmosis is much less common in HIV infected
patients than toxoplasmic encephalitis probably due
to the difference in parasite load in AIDS patients.
There can be single lesion, multifocal lesions in one or
both eyes and broad areas of retinal necrosis. The
retina appears to have a hard, “indurated” appearance
with sharply demarcated borders with little retinal
hemorrhage. Progression is generally slow. It is
usually caused by newly acquired infection. Central
nervous system lesions are seen in 29-50 percent of
HIV infected patients with ocular toxoplasmosis.48
Serologic diagnosis is often difficult due to a depressed
antibody response, in which IgM and IgG titers may
not be of much use.
Table 144.5: Difference between CMV retinitis and toxoplasma lesion in AIDS
CMV retinitis in AIDS
Immune status CD4 cells: <100 cells/mm3
Anterior segment Less inflammation
Vitreous Min. vit. inflammation
Retinal lesion Relatively flat
May be hemorrhagic
Dry granular borders
FFA Hyperfluorescence starts at center
of lesion and progresses to borders
Final hyperfluorescent area is smaller
than the lesion observed on green free photo
1135
Ocular Syphilis
A syphilitic lesion of the eye is the most common
intraocular bacterial infection. About 1-2 percent of
HIV positive patients are found to have ocular
syphilis.49 The most common ocular manifestation
of syphilis in HIV infected patient is uveitis.
Other ocular findings may include retinitis, optic
neuritis, papilledema and optic perineuritis.
An unusual manifestation of syphilis is acute
necrotizing retinopathy.50 This can mimic acute retinal
necrosis.
In HIV positive patients, ocular syphilis is more
closely associated with neurological abnormalities.
Such patients also often show abnormal CSF findings.
Diagnosis can be very challenging as upto 38 percent
of HIV positive individuals can be seronegative
despite active syphilitic disease.49
Mycobacterial Infection
Extrapulmonary and disseminated tuberculosis is seen
more commonly in HIV positive patients. However
choroidal tuberculosis has not been so commonly
reported. It is possible that many case of choroidal
tuberculosis remain asymptomatic and probably
regress with the anti-tubercular treatment for extra-
ocular tuberculosis. It usually presents as multifocal
choroiditis with discrete yellow choroidal lesions
mainly at posterior pole. It may be associated with an
exudative retinal detachment with variable vitreous
inflammation.
There are several reports of choroidal lesions due
to tuberculosis in HIV infected patients. These include
Toxoplasmosis in AIDS
CD4 cells: <250 cells/mm3
More inflammation
Marked vitritis
More fluffy and edematous
Non-hemorrhagic
Smooth borders
Hyperfluorescence starts from edges
of lesion and progresses to center
Final hyperfluorescent area is larger
than the lesion observed on green free photo
1136 Section 9: Miscellaneous Topics
non-reactive single or multiple choroidal nodules, soli-
tary nonreactive tuberculoma or chorioretinitis.51-53
While atypical mycobacteria like Mycobacterium
avium-intracellulare infection can occur around 15 –20%
of AIDS patients, such organisms have been demons-
trated in the choroids in 1-6% of eyes on autopsied in.
Pneumocystis carinii and M.avium-intercellulare were
found in the choroid of same patient.54
Fungal Infection
Candida and cryptococcus are the most common intra-
ocular fungal infections. Candidal endophthalmitis is
remarkably uncommon in contrast to systemic
candidal infection in HIV positive patients. The
majority of patients give a history of treatment with
indwelling venous catheters or abuse of intravenous
drugs. The eye could also be part of a disseminated
candida infection. Fluffy-white chorioretinal lesions
along with snowball like masses are seen usually.
Other lesions are creamy-white multiple chorioretinal
masses with overlying vitreous inflammation.
Cryptococcus neoformans is the most common
neurologic fungal infective agent in AIDS. It usually
causes chronic meningitis, which results in papill-
edema, optic neuropathy, and chiasmal involvement
(Fig. 144.8). It can involve any part of the eye, most
commonly causing chorioretinitis. Cranial nerve
palsies indicate a poor prognosis.55
Pneumocystis Carinii Choroidopathy
Pneumocystis carinii, a unicellular protozoon, is the
most common opportunistic infection in patients with
AIDS usually presenting as pneumonitis. P. carinii
spreads to the choroidal layers through the hemato-
genous route. Pneumocystis carinii choroidopathy is
often seen in the patients treated with aerosolized
pentamidine for PCP prophylaxis. Pneumocystis carinii
choroidopathy can be an initial sign of disseminated
life-threatening P. carinii infection.
Patients often do not have visual symptoms. The
fundus shows multiple yellowish white usually round
subretinal plaques distributed through the posterior
pole. The lesions can coalesce as they progress.
Typically there is no vitreous inflammation. Fundus
fluorescein angiography shows early hypofluore-
scence of the lesion with late staining. Histopathologic
study of the autopsy eyes revealed multiple eosino-
philic, acellular, frothy and vacuolated material.
Special stains can demonstrate mature cysts of
Pneumocystis carinii.56 Pneumocystis carinii choroido-
Fig. 144.8: Fundus photograph showing optic disk edema with
peripapillary flame-shaped retinal hemorrhages in the left eye
of a patient with cryptococcal meningitis
pathy indicates poor prognosis for life. Average
survival after diagnosis is noted to be four months.
Adnexal and Anterior Segment Lesions in AIDS
HIV infection affecting the ocular adnexa and anterior
segment are not uncommon, and have been reported
to occur in upto 50 percent of cases57(Tables 144.6
to 144.8). The structures involved include the eyelids,
conjunctiva, lacrimal drainage system, cornea, anterior
chamber and the iris. Anterior segment lesions may
often be the initial ocular presentation of AIDS.
Common manifestations include the following:
Table 144.6: Type of anterior uveitis
• Herpetic anterior uveitis (VZV, HZV )
• Cidofovir associated uveitis
• Rifabutin associated uveitis
Table 144.7: Common ocular adnexal lesions
in AIDS patients
• Herpes zoster ophthalmicus
• Kaposi’s sarcoma of eyelid, conjunctiva
• Molluscum contagiosum of the eyelid
• Conjunctival microvasculopathy
Table 144.8: Common anterior segment lesions
in AIDS patients
• Dry eye
• Infective keratitis
(varicella zoster, herpes simplex, microsporidia)
• Anterior uveitis
• Rifabutin induced
• Spill over from cytomegalovirus retinitis
• Herpes zoster ophthalmicus
 Chapter 144: Acquired Immunodeficiency Syndrome and the Eye 1137
HERPES ZOSTER OPHTHALMICUS (HZO)
Herpes zoster ophthalmicus is caused by the varicella-
zoster virus and involves the ophthalmic distribution
of the trigeminal nerve. Its occurrence in a person less
than 50 years of age should arouse suspicion of an
immunosuppressive condition. Its incidence in the
HIV population is reported to be 5-15 %.58 Concurrent
posterior segment involvement may also occur. Acute
panuveitis with hemorrhagic hypopyon associated
with HZO has been reported as the initial presenting Fig. 144.9: External photograph showing
feature of AIDS.59 Molluscum contagiosum lesions on face and lids
Treatment consists of intravenous acyclovir
(10 mg/kg body weight, three times a day for seven
days) followed by oral maintenance regimen (800 mg
three to five times daily). Famciclovir can be used in a
dosage of 500 mg three times daily. Intravenous
Foscarnet should be considered if poor response to
acyclovir or famciclovir is noted.

Molluscum Contagiosum
Molluscum contagiosum is a contagious dermatitis
caused by a poxvirus. Clinically seen as multiple,
small, painless, umbilicated lesions, these lesions are
more severe in HIV positive individuals (Fig. 144.9).60
Lid involvement may be seen in upto 5 percent of HIV
infected cases and can also be associated with lid
abscess as a result of secondary bacterial infection.61
Fig. 144.10: Ulcerated lesion in upper eyelid
Treatment options include cryotherapy, curettage,
with overhanging granulation tissue
incision and excision.62

Lid Infections Keratoconjunctivitis Sicca

Severe blepharitis, styes and lid ulceration may also
be the initial manifestation of ocular involvement in
AIDS (Fig. 144.10).63
Treatment with antibiotics along with lid hygiene
needs to be continued for a longer duration in these
cases than in normal individuals.
Conjunctival Squamous Cell Carcinoma
Conjunctival squamous cell dysplasia and neoplasia
have been associated with HIV infection and AIDS in
the sub-Saharan African population.64 Squamous cell
carcinoma was reported in an unsuspected healthy
young patient, who was diagnosed post-conjunctival
biopsy to be positive for HIV-2 infection.65
Any rapidly growing mass lesion of the conjunctiva
should arouse the suspicion of an immunosuppressed
condition.
Keratoconjunctivitis sicca occurs in 10 to 20 percent
of patient of HIV positive individuals. 66 This is
probably secondary to the destruction of the primary
and accessory lacrimal glands as a result of either HIV
mediated inflammation or an autoimmune pathology.
Treatment is basically directed towards providing
symptomatic relief using artificial tear substitutes and
lubricating ointments.
Infectious Keratitis
HIV infection is associated with a wide spectrum of
ocular infections. Viral keratitis is more common
compared to bacterial and fungal infections although
in certain geographic areas, fungal keratitis has been
reported to be an indirect indicator of HIV infection.67
Recurrence is more common both for varicella-zoster
virus keratitis and herpes simplex keratitis.
1138 Section 9: Miscellaneous Topics

Treatment is similar in both viral keratitis, with Table 144.9: Common orbital lesions in AIDS patients
oral acyclovir 400 mg five times daily or famciclovir
125-500 mg three times daily. • Burkitt’s lymphoma
• Orbital cellulitis (aspergillus)
Microsporidia are obligate intracellular parasites
known to cause gastroenteritis, sinusitis, and pneumo-
nitis in HIV infected patients. Ocular involvement is
lymphomas and squamous cell carcinoma in HIV
in the form of a diffuse superficial punctate kerato-
patients.
pathy associated with conjunctivitis.68 Diagnosis is
usually by characteristic staining of the intracellular
Ophthalmic Kaposi’s Sarcoma
organism.
Treatment is usually with topical fumagillin, Kaposi’s sarcoma is the most common lesion involving
popamidine isethionate, and oral itraconazole or the anterior segment of eye. Generally, ophthalmic
albendazole. Kaposi’s sarcoma is indolent. Ocular tumor growth
can result in severe damage to the ocular adnexa and
Anterior Uveitis ocular surface. Involvement of the eyelids can cause
significant disfigurement and lid dysfunction.
Anterior uveitis is less common than posterior or
Trichiasis can develop from mechanical ectropion or
panuveitis.69 Table 144.6 lists causes of anterior uveitis
entropion. Lagophthalmos and trichiasis can result in
in HIV positive patients. Drug induced anterior uveitis
profound irritation and dryness, infections and corneal
can be caused by cidofovir and rifabutin.
scarring.71
The lesions are purplish-red to bright red and
ORBITAL INFECTIONS (Table 144.9)
highly vascular with surrounding telangiectatic
Aspergillosis and mucormycosis are the orbital vessels. They may be macular, plaque-like or nodular.
infections seen in AIDS patients. Aspergillosis presents
as a nongranulomatous disease with abscess formation Lymphoma
and lack of fibrosis, in contrast to slow granulomatous
High-grade lymphoma is an AIDS defining disorder.
and fibrotic response in immunocompetent hosts. The
Orbital and intraocular involvement is uncommon and
classic presentation of orbital mucormycosis is unila-
is seen in less than 1 percent of patients of AIDS.72
teral severe headache, nasal stuffiness with granular
The clinical appearance of an intraocular lymphoma
or purulent discharge, facial or eyelid edema, fever
is multifocal, yellow-white, multiple chorioretinal
and leucocytosis.
lesions associated with vitritis. They may be associated
with primary CNS lymphoma.
NEUROOPHTHALMIC LESIONS
In the final stages of the HIV disease, the brain is MANAGEMENT
involved, either with direct infection by HIV or with
There are now 15 antiretroviral agents approved for
opportunistic infections. Neuroophthalmic compli-
the treatment of HIV infection. The use of these agents
cations such as papilledema, cranial nerve palsies,
in potent combination regimens has allowed HIV-
optic neuritis, optic atrophy and gaze palsies are
infected individuals to achieve both substantial control
known to occur in 10 to 15 percent of HIV infected
of viral replication and improvement in their host
patients.70 Blurred vision, problems with eye move-
defenses.73, 74 When initiating therapy in the patient
ment or double vision may result. Non-viral infections
naïve to antiretroviral therapy, one should begin with
are responsible for 50 percent of CNS abnormalities,
a regimen that is expected to achieve sustained
toxoplasmosis and cryptococcal involvement being
suppression of plasma HIV RNA, a sustained increase
the most common.
in CD4+ T cell count, and a favorable clinical outcome
(i.e., delayed progression to AIDS and death).
NEOPLASMS
Additional consideration should be given to the
Degradation of immune system predisposes to specific regimen’s pill burden, dosing frequency, food
malignancies like Kaposi’s sarcoma, non-Hodgkin’s requirements, convenience, toxicity, and drug
 Chapter 144: Acquired Immunodeficiency Syndrome and the Eye
interaction profile compared with other regimens.
HAART generally includes three or four drugs in two
distinct categories: nucleoside analog and protease
inhibitors.
The Impact of HAART on the Clinical Spectrum of
Ocular Lesions in AIDS
The advent of highly active antiretroviral therapy
(HAART) has changed the clinical spectrum and
management of ocular lesions in AIDS. HAART
consists of combination therapy with at least three
drugs, usually two nucleoside reverse transcriptase
inhibitors and either a protease inhibitor or a non-
nucleoside reverse transcriptase inhibitor. HAART
suppresses HIV replication markedly thus allowing
immune reconstitution. This in turn has resulted in
decreased opportunistic infections and improved
survival of HIV infected people.74
The most dramatic influence of HAART has
perhaps been on the incidence and management of
CMV retinitis. There has been a 55-95 percent reduc-
tion in the number of new cases of CMV retinitis with
the advent of highly active antiretroviral therapy
(HAART). 75 The restoration of specific anti-CMV
immunity has been demonstrated in studies of patients
with CMV retinitis and HAART induced immune
reconstitution.76 It is now possible to discontinue anti-
CMV maintenance therapy in patients with immune
reconstitution from HAART. CMV retinitis also does
not relapse as long as immune reconstitution is
maintained.77-79
GUIDELINES FOR DISCONTINUATION OF
ANTI-CMV THERAPY IN PATIENTS WITH IMMUNE
RECONSTITUTION FROM HAART
Level of CD4+ T Cell Count Prior to
Discontinuation of Anti-CMV Therapy
Persistent CD4+ T cell levels of at least 100 cells × 106/
l for at least 3 months in combination with CMV
retinitis that has been inactive for 3-4 months.78
HIV Viral Load Estimation
Plasma HIV RNA < 10,000 copies/ml. Ideally the goal
of HAART is to reduce HIV viral load to undetectable
levels. However, even low levels of HIV replication
are not associated with relapse, as long as the CD4+ T
cell count has increased. Long-term loss of immune
1139
reconstitution will probably occur in patients with low
levels of HIV replication.
When to reinstitute anti-CMV therapy: Consider
reinstitution of anti-CMV therapy when the CD4+ T
cell count falls to <50 cells × 106/l.78,80
Immune Recovery Uveitis (IRU)
Although HAART has resulted in substantial benefits
such as the increased survival rate and decrease in
the incidence of opportunistic infections, the recons-
tituted immune system has in many cases caused
intraocular inflammation—immune recovery uveitis
(IRU). This entity has been described in patients with
immune recovery whose CMV retinitis was in
remission.81-83
These patients have CMV retinitis that is initially
responsive to treatment. As immune reconstitution
occurs signs of inflammation appear: anterior uveitis,
vitritis, papillitis, and macular edema. Common ocular
complications of the inflammation include epiretinal
membrane and/or cataract formation. Extensive
retinal neovascularization84 and uveitic angle closure
glaucoma85 have also been reported as a late feature
in IRU.
The changes are only seen in the eye with CMV
infection, not in an uninvolved fellow eye. The exact
mechanism of immune recovery uveitis is unknown.
Since IRU does not occur in eyes without CMV
retinitis, the ocular inflammation appears to be related
to the CMV infection, which causes breakdown in the
blood-ocular barrier. This may allow CMV antigen to
leak out of the eye and give the antigen access to
lymphoid organs and stimulate an antigen-specific
immune response. Reconstitution of CMV specific T
cells may play a role in IRU. The extent of the retinitis
as well as the prior treatment may also relate to the
development of this condition. A recent study86 has
reported that the use of cidofovir is a primary risk
factor in the subsequent development of immune
recovery uveitis. Ongoing treatment of healed CMV
retinitis after immune recovery does not appear to
protect against the development of immune recovery
uveitis.86
The treatment of immune recovery uveitis is topical
and periocular steroids. Periocular steroids need to
be used with caution as there have been reports of
reactivation of CMV retinitis after treatment of IRU
with subtenon’s steroids.87
1140 Section 9: Miscellaneous Topics

Has HAART Resulted in Improved However, these advances have had little impact on
Visual Outcome in CMV Retinitis? patients in the developing world where the vast
majority of infected individuals have no access to these
In a study on the long-term visual outcome of patients
new therapies due to the high cost. The impact of the
with extramacular CMV retinitis treated with HAART
AIDS epidemic in the developing world continues to
Goldberg et al conclude these patients lose vision
increase at a rate of over 16000 new infections per day
while on HAART. This long-term decrease in vision
as estimated by UNAIDS this represents 90 percent of
has been attributed to the occurrence of IRU. The
all new infections worldwide. Provision of highly
highest incidence of epiretinal membrane, macular
active antiretroviral therapy (HAART) is well beyond
edema and cataract occurred in patients with immune
the available health resources of many of the
recovery and IRU and the lowest incidence in patients
developing world. Therefore, the approach to the
with immune recovery without IRU. The incidence of
management of the HIV-infected patients in develop-
retinal detachment was highest in the immune failure
ing countries should be based on a holistic, cost-
group, (because of the full thickness retinal necrosis
effective approach. This should take into account the
leading to retinal breaks and detachment) and the
number of infected people, the spectrum of HIV
second highest incidence was in the group with
disease and the available resources in each individual
immune recovery with IRU (due to the vitritis and
country.
resultant traction).88
Priorities for managing established HIV infection
HAART and the subsequent immune recovery
in an individual in a developing country include
have resulted in certain unusual clinical situations in
encouragement of early diagnosis and access to
AIDS patients. Disseminated Mycobacterium avium
medical care; the prevention, early diagnosis and
complex (MAC) infection is the third most common
treatment of the more prevalent opportunistic
opportunistic infection in AIDS (15 to 40% of AIDS
infections in that country; appropriate antiretroviral
patients in the US). Ocular infections are extremely
therapy; palliative care; and encouragement of a
rare. After initiation of HAART a new syndrome has
healthier lifestyle for those infected. Since AIDS
been reported in which sub-clinical, disseminated
remains a highly stigmatized disease in most
MAC infection may become clinically overt. In the eye
countries, the HIV-infected patient also needs
this may present as areas of chorioretinal inflam-
considerable psychosocial support. The integration of
mation, which may be mistaken for other more
services at all levels, including teaching hospitals,
common infections such as CMV retinitis. 89 The
community hospitals, day-care services, community-
inflammation can be devastating and can result in
based care services and home care is crucial to the
panophthalmitis. This is part of a systemic postinfe-
success of clinical management guidelines. This
ctious immune restoration syndrome against pre-
involves coordination between doctors and other
viously “quiet” antigens and has been reported in
health care community-based services and non-
systemic tuberculosis90 and MAC infections. It is attri-
governmental organizations.
buted to the large numbers of new, functionally
competent immune cells that become available to
ANTIRETROVIRAL THERAPY
respond to the preexisting microbial burden.
In summary, in the HAART era, significant benefits Antiretroviral drugs suppress the viral replication by
have been obtained for patients in terms of increased inhibiting either reverse transcriptase or protease.
survival and improved quality of life. However the
immune recovery syndrome also poses challenges for Indications for Antiretroviral Therapy
clinicians both from a diagnostic and management 1. Acute infection
aspect. 2. Symptomatic
3. Asymptomatic: CD4<350 cells or HIV RNA >30,000
Management of HIV Infections and copies RT PCR
Opportunistic Infections
Recent advances in management of the HIV-infected Investigations
patient in developed countries have led to an Baseline: CBC, LFT, S. amylase, lipid profile and blood
improved length and quality of life in these patients. sugar.
 Chapter 144: Acquired Immunodeficiency Syndrome and the Eye
Monitoring: viral load*: 0,1,3,6 and every 6 months
CD4: 0,3,6 and every 6 months.
* viral load should be done in the same laboratory
and by the same technique.
Factors that influence probability of prolonged
viral suppression using regimens that are strongly
recommended:
1. Adherence
2. Baseline CD4 count
3. Baseline viral load
4. Prior exposures to antiretroviral agents
5. Nadir of viral load
6. Rapidity of viral load response.
When to Change Therapy
The goal of therapy is to reduce the level of HIV RNA
to as low a level as possible for as long as possible,
preferably using antiretroviral regimens that preserve
future options, are relatively free of side effects and
are tailored to individual patient needs for adherence.
The probability of achieving the goal of < 50 copies/
ml can be crudely predicted by the slope of the decay
in plasma HIV RNA levels, which should show <500
copies/ml by 12 weeks and < 50 copies/ml at 16-24
weeks. Once the goal of therapy has been achieved,
therapy should be continued indefinitely with
monitoring of HIV RNA levels at 6-month intervals
and CD4 counts at 6-month intervals.
Antiretroviral therapy in Patients with
Tuberculosis
In HIV infected patients being treated for tuberculosis,
protease inhibitors increase the serum levels of
rifampicin. On the other hand, rifampicin decreases
the level of protease inhibitors. In consequence,
rifampicin cannot be given along with protease
inhibitors. Rifabutin can be used with protease
inhibitors if the dose of rifabutin is appropriately
decreased to 150 mg daily with nelfinavir or indinavir
or 150 mg three times a week with ritonavir.
REFERENCES
1. Barre-Sinoussi F, Chermann J-C, Rey F et al. Isolation of a T-
lymphotropic retrovirus from a patient at risk for acquired
immunodeficiency syndrome (AIDS). Science 1983;220:868.
2. Gallo RC, Salahuddin SZ, Popovic M et al. Frequent detection
and isolation of cytopathic retroviruses (HTLV-III) from
patients with AIDS and at risk for AIDS. Science 1984;224:500.
3. NACO (2003) ‘HIV/AIDS Surveillance in India’,
www.naco.nic.in/indianscene/esthiv.htm /.
4. CDC, Center for Disease Control and Preventive, MMWR,
1992;44.
1141
5. Biswas J, Madhavan HN, Badrinath SS. Ocular lesions in
AIDS: A report of first two cases in India. Indian Ophthalmol
1995;43:69.
6. Biswas J, Madhavan HN, George AE, Kumarasamy N,
Solomon S. Ocular lesions associated with HIV infection in
India: A series of 100 consecutive patients evaluated at a
referral center. Am J Ophthalmol 2000;129:1-9.
7. Kaur A, Babu PG, Jacob M et al. Clinical and laboratory profile
of AIDS in India. J Acquir Immune Defic Syndr Hum
Retrovirol 1992;5:883.
8. Jalali S, Rao UR, Laxmi V. Acute retinal necrosis syndrome
in an HIV positive case: The first case reported from India.
Ind J Ophthalmol 1996;44:95.
9. Sahu DK, Namperumalsamy P, Walimbe P, Rajalakshmi C.
Ocular manifestations of HIV infection/AIDS in South Indian
patients. Ind J Ophthalmol 1999;47:79.
10. Levy RM, Bredesen DE, Rosenblum MC et al. Neurologic
manifestations of the acquired immune deficiency syndrome.
Exercise of UCSF and review of literature. J Neurosurg
1985;62:475.
11. Hu DJ, Dondero TJ, Rayfield MA, George JR, Schochetman
G, Jaffe HW, Luo CC, Kalish ML, Weniger BG, Pau CP,
Schable CA, Curran JW. The emerging genetic diversity of
HIV. The importance of global surveillance for diagnostics,
research and prevention. JAMA 1996;275:210.
12. Jabs DA, Green WR, Fox R et al. Ocular manifestations of
acquired immune deficiency syndrome. Ophthalmology
1989;96:1092.
13. Glasgow BJ, Weisberger AK. A quantitative and cartographic
study of retinal microvasculopathy in acquired immuno-
deficiency syndrome. Am J Ophthalmol 1994;11:46.
14. Whitley RJ, Jacobson MA, Friedberg DN et al. Guidelines for
the treatment of cytomegalovirus diseases in patients with
aids in the era of potent antiretroviral therapy. Arch Intern
Med 1998;158:957.
15. Freeman WR, Lerner CW, Mines JA, Lash RS, Nadel AJ, Starr
MB, Tapper ML. A prospective study of the ophthalmologic
findings in the acquired immune deficiency syndrome. Am J
Ophthalmol 1984;97:133.
16. Mansour AM, Rodenko G, Dutt R. Half-line of cotton-wool
spots in the acquired immunodeficiency syndrome. Int J STD
AIDS 1990;1:132.
17. Holland GN, Pepose JS, Pettit TH, Gottlieb MS, Yee RD, Foos
RY. Acquired immune deficiency syndrome, ocular
manifestations. Ophthalmology 1983;90:859.
18. Tumer BJ, Hecht FM, Ismail RB. CD4+ T-lymphocyte
measures in the treatment of individuals infected with human
immunodeficiency virus type 1: A review for clinical practi-
tioners. Arch Intern Med 1994;154:1561.
19. Henderly DE, Freeman WR, Smith RE, Causey D, Rao NA.
Cytomegalovirus retinitis as the initial manifestation of the
acquired immune deficiency syndrome. Am J Ophthalmol
1987;103:316.
20. Henderly DE, Freeman SW, Causey DM, Rao NA.
Cytomegalovirus retinitis and response to therapy with
ganciclovir. Ophthalmology 1987;94:425.
21. Kupperman BD, Petty JG, Richman DD, Mathews WC,
Fullerton S, Richman ST et al. Correlation between CD4+
counts and prevalence of cytomegalovirus retinitis and
human deficiency. Am J Ophthalmol 1993;1125:575.
1142 Section 9: Miscellaneous Topics
22. Freeman WR, Quiceno JI, Crapotta JA, Listhaus A, Munguia
D, Aguilar MF. Surgical repair of rhegmatogenous retinal
detachment in immunosuppressed patients with cyto-
megalovirus retinitis. Ophthalmology 1992;99:466.
23. Irvine AR. Treatment of retinal detachment due to CMV
retinitis in patients with AIDS. Trans Am Ophthalmol Soc
1991;89349.
24. Kao GW, Peyman GA et al. Retinal toxicity of gancyclovir in
vitrectomy infusion bottles. Retina 1987;7:80.
25. Kuppermann BD, Flores AM et al. A masked prospective
evaluation of outcome parameters for CMV related RD
surgery in patients with AIDS. Ophthalmology 1994;101:46.
26. Lim JI, Enger C et al. Improved visual results after surgical
repair of CMV related RDs. Ophthalmology 1994;101:264.
27. Omerod LD, Larkin JA, Margo CA, Pavan PR, Menosky MM,
Haight DO et al. Rapidly progressive herpetic retinal necrosis:
blinding disease characteristic of advanced AIDS, (see
commentary by CL Lowder, pp 46-47). Clin Infect Dis
1998;26:34.
28. Holland GN et al. Standard diagnostic criteria for acute retinal
necrosis syndrome. Am J Ophthalmol 1994;117:663.
29. Foster DJ, Dugel PU, Frangieh GT, Liggett PE, Rao NA.
Rapidly progressive outer retinal necrosis in the acquired
immunodeficiency syndrome. Am J Ophthalmol 1990;
110:341.
30. Spaide RF, Vitale AT, Toth IR, Oliver JM. Frosted branch
angiitis associated with cytomegalovirus retinitis. Am J
Ophthalmol 1992;113:522.
31. Spector SA, Weingeist T, Pollard RB. A randomized,
controlled study of intravenous ganciclovir therapy for
cytomegalovirus peripheral retinitis in patients with AIDS. J
Infect Dis 1993;168:557.
32. Palestine AG, Polis MA, DeSmet MD et al. A randomized,
controlled study of foscarnet in the treatment of cyto-
megalovirus retinitis in patients with AIDS. Ann Intern Med
1991;115:665.
33. Studies of the Ocular Complications of AIDS Research Group,
in collaboration with the AIDS Clinical Trials Group.
Foscarnet-ganciclovir cytomegalovirus retinitis trial 4: Visual
outcomes. Ophthalmology 1994;101:1250.
34. Studies of Ocular Complications of AIDS Research Group in
collaboration with the AIDS Clinical Trials Group. Combi-
nation foscarnet and ganciclovir therapy vs monotherapy for
the treatment of relapsed cytomegalovirus retinitis in patients
with AIDS. Arch Ophthalmol 1996;114:23.
35. Stanley HD, Charlebois E, Harb G, Jacobson MA. Central
venous catheter infections in AIDS patients receiving
treatment for cytomegalovirus disease. J Acquir Immune
Defic Syndr 1994;7:272.
36. Brosgart CL, Louis TA, Hillman DW et al. A randomized,
placebo-controlled trial of the safety and efficacy of oral
ganciclovir for prophylaxis of cytomegalovirus disease in
HIV-infected individuals. AIDS 1998;12:269.
37. Lalezari JP, Stagg RJ, Kupperman BD et al. A randomized
controlled trial of intravenous cidofovir for peripheral CMV
retinitis in patients with AIDS patients. Ann Intern Med
1997;126:257.
38. Studies of Ocular Complications of AIDS Research Group in
collaboration with the AIDS Clinical Trials Group. Parenteral
cidofovir for cytomegalovirus retinitis in patients with AIDS:
The HPMPC peripheral cytomegalovirus retinitis trial. Ann
Intern Med 1997;126:264.
39. Davis JL, Taskintuna I, Freeman WR, Weinberg DV, Feuer
WJ, Leonard RE. Iritis and hypotony after treatment with
intravenous cidofovir for cytomegalovirus retinitis. Arch
Ophthalmol 1997;115:733.
40. Banker AS, Arevalo JF, Munguia D et al. Intraocular pressure
and aqueous humor dynamics in patients with AIDS treated
with intravitreal cidofovir(HPMPC) for cytomegalovirus
retinitis. Am J Ophthal 1997;124:168.
41. Martin DF, Parks DJ, Mellow SD et al. Treatment of
cytomegalovirus retinitis with an intraocular sustained-
release ganciclovir implant: A randomized controlled clinical
trial. Arch Ophthalmol 1994;112:1531.
42. Cantrill HL Jr, Henry K, Melroe NH et al. Treatment of
cytomegalovirus retinitis with intravitreal ganciclovir, long
term results. Ophthalmology 1989;96:367.
43. Diaz-Llopis M, Chipont E, Sanchez S et al. Intravitreal
foscarnet for cytomegalovirus retinitis in a patient with
acquired immune deficiency syndrome. Am J Ophthalmol
1992;114:742.
44. Kirsch LS, Arevalo JF, De Clercq E et al. Phase I/II study of
intravitreal cidofovir for the treatment of cytomegalovirus
retinitis in patients with the acquired immune deficiency
syndrome. Am J Ophthalmol 1995;119:466.
45. Taskintuna I, Rahhal FM, Rao NA et al. Adverse events and
autopsy findings after intravitreous cidofovir (HPMPC)
therapy in patients with acquired immune deficiency
syndrome. Ophthalmology 1997;104:1827.
46. Rickman LS, Freeman WR. Retinal disease in HIV-infected
patients. In Ryan SJ, Schachat AP (Eds). Retina. St. Louis:
Mosby, Inc; 2001;2:1576-1622.
47. Feinberg J, Hurwitz S, Cooper D et al. A randomized, double
blind trial of valaciclovir (VACV) prophylaxis for cyto-
megalovirus (CMV) end-organ disease in patients with AIDS.
J Infect Dis 1998;177:48.
48. Holland GN, Engstorm RE, Glasgow BJ, Berger BB, Daniels
SA, Sidikaro Y, Harmon JA, Fischer DH, Boyer DS, Rao NA.
Ocular toxoplasmosis in patients with acquired immuno-
deficiency syndrome. Am J Ophthalmol 1988;106:653.
49. McLeish VM, Pulido JS, Holland S, Culberston WW,
Winward K. The ocular manifestations of syphilis in the
human immunodeficiency virus type 1 infected host.
Ophthalmology 1990;97:196.
50. Stoumbos VD, Klein ML. Syphilitic retinitis in a patient with
acquired immunodeficiency syndrome related complex. Am
J Ophthalmol 1987;103:103.
51. Croxatto JO, Mestre C, Puvete S, Gonzalez G. Nonreactive
tuberculosis in a patient with acquired immune deficiency
syndrome. Am J Ophthalmol 1986;102:659.
52. Blodi BA, Johnson MW, Mcleigh WM, Gass JDM. Presumed
choroidal tuberculoma in a human immunodeficiency virus
infected host. Am J Ophthalmol 1989;108:605.
53. DiLoreto DA Jr., Rao NA. Solitary nonreactive tuberculosis
in a patient with acquired immune deficiency syndrome. Am
J Ophthalmol 2001;131:138.
54. Morinelli EN, Dugel PU, Riffenburgh R, Rao NA. Infectious
multi-focal choroiditis in patients with acquired immune
deficiency syndrome. Ophthalmology 1993;100:1014.
55. Battu RR, Biswas J, Jayakumar N, Madhavan HN,
Kumarasamy N, Solomon S. Papilloedema with peripapillary
retinal hemorrhage in an AIDS patient with cryptococcal
meningitis. Ind J Ophthalmol 2000;48:47.
 Chapter 144: Acquired Immunodeficiency Syndrome and the Eye
56. Rao NA, Zimmerman PL, Boyer D, Biswas J, Causey D, Beniz
J, Nichols PW. A clinical, histopathologic and electron
microscopic study of Pneumocystis carinii choroiditis. Am J
Ophthalmol 1989;107:218.
57. Akduman L, Pepose JS. Anterior segment manifestations of
acquired immunodeficiency syndrome. Semin Ophthalmol
1995;10:111.
58. Jabs DA, Quinn TC. Acquired immunodeficiency syndrome.
In: Pepose JS, Holland GN, Wilhemus KR (Eds): Ocular
Infection and Immunity. St Louis: Mosby-Year Book,
1996;289-310.
59. Biswas J, Samanta TK, Madhavan HN, Kumarasamy N,
Solomon S. Acute panuveitis with haemorrhagic hypopyon
as a presenting feature of acquired immunodeficiency
syndrome. Ind J Ophthalmol 2000;48:311.
60. Tschachler E, Bergstresser PR, Stingl G. HIV related skin
diseases. Lancet 1996;348:659.
61. Bardenstein DS, Elmets C. Hyperfocal cryotherapy of multiple
Molluscum Contagiosum lesions in patients with the acquired
immunodeficiency syndrome. Ophthalmology 1995;102:1031.
62. Biswas J, Therese L, Kumarasamy N, Solomon S, Yesudian
P. Lid abscess with extensive molluscum contagiosum in a
patient with acquired immunodeficiency syndrome. Ind J
Ophthalmol 1997;45:234.
63. Biswas J, Madhavan HN, Kumarasamy N, Solomon S.
Blepharitis and lid ulcer as initial ocular manifestation in
acquired immunodeficiency syndrome patients. Ind J
Ophthalmol 1997;45:233.
64. Lewallen S, Courtwright P. HIV and AIDs and the eye in
developing countries. Arch Ophthalmol 1997;115:1291.
65. Fogla R, Biswas J, Kumar SK, Madhavan HN, Kumarasamy
N, Solomon S. Squamous cell carcinoma as initial presenting
sign in a patient with acquired immunodeficiency syndrome
due to human immunodeficiency virus type-2. Eye 2000;
14:246.
66. Geier SA, Libera S, Klauss V, Goebel FD. Sicca syndrome in
patients infected with the human immunodeficiency virus.
Ophthalmology 1995;102:1319.
67. Mselle J. Fungal keratitis as an indicator of HIV infection in
Africa. Trop Doct 1999;29:133.
68. Lowder CY, McMahon JT, Meisler DM et al. Microsporidial
keratoconjunctivitis caused by Septata intestinalis in a patient
with acquired immunodeficiency syndrome. Am J Opht-
halmol 1996;121:715.
69. Cunningham ET (Jr). Uveitis in HIV positive patients. Am J
Ophthalmol (editorial), Br J Ophthalmol 2000;84:233.
70. Levy JA, Shimabukuro J, Hollander H, Mills J, Kaminsky L.
Isolation of AIDS associated retroviruses from cerebrospinal
fluid and brain of patients with neurological symptoms.
Lancet 1985;2:586.
71. Dugel PU, Gill PS, Frangieh GT, Rao NA. Ocular adnexal
Kaposi’s sarcoma in acquired immunodeficiency syndrome.
Am J Ophthalmol 1990;110:500.
72. Schnzer MC, Font RL, O’ Malley RE. Primary ocular
malignant lymphoma associated with the acquired immune
deficiency syndrome. Ophthalmology 1991;98:88.
73. Volberding PA. HIV/AIDS: Protease inhibitors vindicated.
Lancet 1997;350:10.
74. Palella FJ Jr, Delaney KM, Moorman AC et al. Declining
morbidity and mortality among patients with advanced
human immunodeficiency virus infection. N Engl J Med
1998;338:853.
1143
75. Jabs DA, Bartlett JG. AIDS and ophthalmology: A period of
transition. Am J Ophthalmol 1997.
76. Jabs DA. Discontinuing anticytomegalovirus therapy in
patients with cytomegalovirus retinitis and AIDS. Br J
Ophthalmol 2001;85:381.
77. Vrabec TR, Baldassano VF, Whitcup SM. Discontinuation of
maintenance therapy in patients with quiescent cyto-
megalovirus retinitis and elevated CD4+ counts. Ophthal-
mology 1998;105:1259.
78. Macdonald JC, Karavellas MP, Torriani FJ et al. Highly active
antiretroviral therapy-related immune recovery in AIDS
patients with cytomegalovirus retinitis. Ophthalmology
2000;107:877.
79. Jabs DA, Van Natta ML, Kempen JH, Reed Pavan P, Lim JI,
Murphy RL, Hubbard LD. Characteristics of patients with
cytomegalovirus retinitis in the era of highly active
antiretroviral therapy. Am J Ophthalmol 2002;133(1):48.
80. See RF, Rao NA.Cytomegalovirus retinitis in the era of
combined highly active antiretroviral therapy. Ophthalmol
Clin North Am 2002;15(4):529.
81. Karavellas M, Lowder C, Macdonald C, Avila C, Freeman
W. Immune recovery vitritis associated with inactive
cytomegalovirus retinitis. Arch Ophthalmol 1998;116:169.
82. Karavellas MP, Azen SP, Macdonald JC, Shufelt CL, Lowder
CY, Plummer DJ, Glasgow B, Torriani FJ, Freeman WR.
Immune recovery vitritis and uveitis in AIDS: Clinical
predictors, sequelae, and treatment outcomes. Retina
2001;21(1):1.
83. Biswas J, Choudhry S, Kumarasamy, Solomon S. Immune
recovery vitritis presenting as panuveitis following therapy
with protease inhibitors. Indian J Ophthalmol 2000;48(4):313.
84. Wright ME, Suzman DL, Csaky KG, Masur H, Polis MA,
Robinson MR. Extensive retinal neovascularization as a late
finding in human immunodeficiency virus-infected patients
with immune recovery uveitis. Clin Infect Dis 2003;
15;36(8):1063.
85. Goldberg DE, Freeman WR. Uveitic angle closure glaucoma
in a patient with inactive cytomegalovirus retinitis and
immune recovery uveitis. Ophthalmic Surg Lasers 2002;
33:421.
86. Song MK, Azen SP, Buley A, Torriani F, Cheng L,
Chaidhawangul S, Ozerdem U, Scholz B, Freeman WR. Effect
of anti-cytomegalovirus therapy on the incidence of immune
recovery uveitis in AIDS patients with healed cytomegalo-
virus retinitis. Am J Ophthalmol. 2003;136:696.
87. Dalessandro L, Bottaro E. Reactivation of CMV retinitis after
treatment with subtenon corticosteroids for immune recovery
uveitis in a patient with AIDS. Scand J Infect Dis. 2002;34:780.
88. Goldberg DE, Wang H, Azen SP, Freeman WR. Long-term
visual outcome of patients with cytomegalovirus retinitis
treated with highly active antiretroviral therapy. Br J
Ophthalmol 2003;87:853.
89. Zamir E, Hudson H, Ober RR, Kumar SK, Wang RC, Read
RW, Rao NA. Massive mycobacterial choroiditis during
highly active antiretroviral therapy: Another immune-
recovery uveitis? Ophthalmology 2002;109:2144.
90. Furrer H, Malinverni R. Severe inflammatory reaction (SIR)
after starting HAART in AIDS patients treated for disse-
minated tuberculosis: Role of corticosteroids. 12th
International AIDS Conference. Geneva, Switzerland; 1998.
 Chapter 145

Color Vision and

Color Blindness
YR Sharma, Nikhil Pal, Deependra V Singh

The spectral wavelengths of different colors are as Wavelength Discrimination

follows: violet 430 nm; blue 460 nm; green 520 nm;
The normal observer is able to detect a difference
yellow 575 nm; orange 600 nm and red 650 nm. The
between two spectral lights that differ by as little as 1
concept of white light is vague, most agreeable defini-
nm in wavelengths in the regions of 490 nm and 585
tion is, white surface is one which has spectral reflec-
nm. In the region of violet and red a difference of
tion factors Ph independent of wavelength (in the
greater than 4 nm is necessary.2
visible spectrum) and greater than 70 percent.
Hue, Saturation and Lightness
FACTORS AFFECTING COLOR VISION
Hue is the extent to which the object is red, green, blue
Lens
or yellow. Saturation is the extent to which a color is
The lens absorbs shorter wavelengths; in young wave strong or weak. Lightness is self explanatory attribute,
lengths of less than 40 nm and in old people up to 550 for example, yellow by color it is light.
or 600 nm are absorbed by the lens resulting in
defective color vision on shorter wavelength side. Illumination
It affects color vision of low illuminances, the errors
RETINAL DISTRIBUTION OF COLOR VISION
increase due to poorer discrimination for most of the
The center of the fovea (1/8 degree) is blue blind. hue range while testing color vision. An illuminance
Trichromatic vision extends 20-30° from the point of of 400 lux (± 100 lux) would be practical value for most
fixation. Peripheral to this red-green become indis- clinical applications.3
tinguishable up to 70-80° and in far peripheral retina
all color sense is lost although cones are still found in Bezold-Burcke Effect
this region. 1,2 In the central 5°, macula contains
von Bezold (1873) and Burcke (1878) discovered
carotenoid pigment, xanthophyll. The molecules of the
independently the phenomenon named after them,
pigment are arranged in such a way that they absorb
that variation of the luminance levels modifies hues.
blue light polarized in the radial direction. If one looks
at a white card through linear polarizer, one will see
Color Constancy:
two blue sectors separated by two yellow sectors, the
Aperture Colors and Surface Colors
figure is called Haidinger’s brushes. Macular pigment
may also be seen as in homogeneity in the field of blue Color constancy is phenomenon in which color of the
or white light called Maxwell’s spot. objects can be recognized unchanged in spite of
 Chapter 145: Color Vision and Color Blindness
possible differences in the illumination. Aperture
colors are colors that alter due to change in illumi-
nation. Surface colors do not vary with illumination.
Extrafoveal vision favors the appearance of aperture
colors and foveal vision that of surface colors.
Complementary Wavelengths
Complementary wavelengths are those which, when
mixed in appropriate proportions, give white.
Simultaneous Color Contrast
It is visually demonstrated by observing the color of
a spot in a surround. The general rule is that the color
of the spot toward the complementary of the color of
the surround.
Successive Color Contrast
More commonly described as colored after images,
when one stares at a red spot for several seconds and
then looks at a gray card, one sees a green spot on the
card. The after image tends toward the comple-
mentary of the primary image.
Stiles-Crawford Effect
The light entering near the edge of the pupil is less
effective than light entering at the center of the pupil
because of the shape of the receptors and the fact that
they are embedded in a medium of different refractive
index. This effect is wavelength-dependent.
Color Triangle
It can be drawn to describe the trichromacy of color
mixtures and is useful for deciding which bands of
wavelength are indistinguishable from each other.
Three reference wavelengths are chosen, i.e. 450 nm,
520 nm and 650 nm and are placed at vertices of X, Y
and Z of a triangle, the position of other wavelengths
is determined. A color triangle does not describe the
color of a band of wavelengths unless other circum-
stances are defined.
THEORIES OF COLOR VISION
This is a complex topic; no theory explains the pheno-
menon of color vision fully. Few important theories
are given below:
Young-Helmholtz Theory
Young’s (1802) guiding concept is that there are three
types of retinal receptors with different spectral
1145
sensitivities. Young’s principal colors are red, green
and violet. Young’s hypothesis was not followed up
until it was revived by Helmholtz (1852). The Young’s
theory4 may be summarized as follows:
a. At some stage of visual receptor mechanism there
are three different types of sensory apparatus G1,
G2, G3. These receptors must be same for everyone,
on the other hand they may not be same at the fovea
as at the periphery.
b. Each of these receptors is characterized from the
spectral point of view by particular function of
wavelengths which may be denoted by G and the
response G1 of a receptor for radiation with a
spectral energy distribution Eλ may be supposed
to have the form.
G1 = Sgi Eλ dλ
c. The sensation of color is a function of the relative
values of the three responses G1.
d. The sensation of light is a function of a linear
combination of the three responses.
Fundamental Sensations
By determining approximately the coordinate of the
confusion points of dichromats Arthur Konig5 (1893)
established a system of fundamental sensations and
identified red, green and violet as fundamental colors.
Blue was also identified as fundamental color in
addition to red and green by Gothelin.6
Granit’s Theory of Color Vision
Granit7 divides retina into receptor units, each unit
comprising groups of cones and rods which are
connected with a single ganglion cell or several
ganglion cells which synchronize their discharges.
These units are classified as “dominators” or
“modulators”. The dominators, which are numerous,
have a spectral sensitivity curve which indicates that
they are responsible for the sensations of luminosity.
Modulators show a selective sensitivity which often
causes them to be considered as responsible for color
discrimination.
Granit’s theory does not explain the fact of trichro-
matism.
Herring’s Theory of Color Vision
Herring8 assumed six distinct sensations arranged in
three opposing pairs: white-black; yellow-blue and
red-green; he explains three pairs as being due to
opposing actions of light on three substances of the
1146 Section 9: Miscellaneous Topics
retina, a catabolism producing warm sensation (white,
yellow, red) and an anabolism the cold ones. This
theory is clearly a psychological concept and aims at
explaining complex percepts than the intermediate
effect of the stimuli.
ANATOMY OF COLOR VISION
The understanding of visual pathways is complex and
not evident fully.
Cones
In the retina three types of cones responsible for the
red, green and blue sensations have been isolated. The
blue cones are absent in very center of the macula.
Trichomatic vision perception occurs in central 30°
field. The pigments responsible for red, green and blue
sensation of cone are erythrolabe, chlorolabe and
cyanolabe.
Color Coded Cells
Two types of color-coded cells are found at peripheral
levels (ganglion cells and lateral geniculate body) of
the visual system and they have been named opponent
color cells and double opponent color cells. More
complex types are found at more central levels (striate
cortex).
Opponent Color Cells
An opponent color cell is one that gives only polarity
of response for some wavelengths and opposite
polarity of response for other wavelengths. Opponent
color cells are concerned with successive color
contrast.
Double Opponent Color Cells
These are cells opponent for both color and space. The
response may be onto red light, off to green light in
the center of the receptive field and off to red light,
onto green light in the periphery of the receptive field.
Double opponent cells are concerned with simul-
taneous color contrast.
Simple, Complex and Hypercomplex Cells
In rhesus monkey striate cortex there are a variety of
cells that are specific for both color and orientation.
They have been categorized as color sensitive simple,9
complex and hypercomplex cells.11 Simple cells have
a bar-flank double opponent arrangement to their
receptive fields.9 Complex color-coded cells respond
to color boundaries of the appropriate orientation and
the response is independent of the part of the receptive
field being stimulated. For hypercomplex cells, the
edge must be short.
Opponent color cells are found among ganglion
cells of the retina12 and lateral geniculate body.13,14
Double opponent cells with center-surround or flank
receptive fields are present in the input layer IV of the
striate cortex.9 Complex and hypercomplex color-
coded cells are also found in the striate cortex,10,11 in
layers II, III, V and VI. Vaetichin (1953)15 recorded
negative slow potentials from fish retinae of grant
amplitudes, called “S-potential”. Two types of S-
potentials: L type (luminosity type) and C-type
(chromaticity type). Mitarai (1961) 16 regarded
horizontal cells as responsible for S-potentials of L-
type and Muller’s fibers for those of C-type. The
properties of S-potentials support the Herrings oppo-
nent color theory more than the trichromatic theory
of Young.
TESTING OF COLOR VISION
Lantern Tests
In marine, rail and airline transportation, and in the
military, it is often necessary to correctly identify
signals and navigational aids that make extensive use
of color. Lantern tests are performance-based and they
do not diagnose, classify, or grade the level of color
vision defect. Rather, they attempt to determine
whether the person is capable of performing the color
signal recognition tasks with adequate proficiency to
maintain safety standards. There are two types of
lantern tests—those that use actual signal light filters
and those that use simulations of signal lights. In the
United States, the Farnsworth Lantern (Falant) is the
standard lantern test and is pretty much the only test
in use. It simulates marine signal lights under a variety
of atmospheric conditions. Two lights are presented
in a vertical display in any of the nine possible
combinations of three colors—red, green and white—
in the two positions. A patient must average eight of
nine correct responses to pass the test. White lights
are particularly problematic, especially for milder
color defects. Patients report that the test is not
representative of actual field conditions.
 Chapter 145: Color Vision and Color Blindness 1147
Pseudoisochromatic Color Plates
Patterns of colored and gray dots that reveal one
pattern to the normal and another to the color
deficient, e.g. Ishibara plates and Hardy-Rand-Ritter
plates. The most common use of plate tests is to
identify persons with congenital color defects.
Pseudoisochromatic plates (for example, AO-HRR,
Ishihara, Dvorine, Tokyo Medical College, SPP-1)
provide efficient screening of congenital red-green
defects (efficiency, 90-95%). Other tests have been
designed to detect achromatopsia (Sloan Achro-
matopsia test), to differentiate incomplete achro-
matopsia from complete achromatopsia (Berson blue
cone monochromatism plates, to detect acquired
defects (SPP-2), or to detect color confusion (City
University Test). Plate tests have the advantages of
being relatively inexpensive, easily available, simple
to use, and appropriate with children and persons who
are illiterate. They are only suitable for screening
purposes, however, because they neither provide a
quantitative evaluation of color vision nor distinguish
the type and severity of the color vision defect. Plate
tests are designed to distinguish congenital color-
defective from color-normal observers, but they do
not evaluate the wide range of abilities and aptitudes
of observers with normal color vision to distinguish
colors. Given individual differences in prereceptoral
filters and normal photopigment polymorphisms, no Fig.145.1: FM 100-hue test results from four subjects
plate test can be 100 percent effective in screening. with congenital color defects. (A) Deutan defects
When used improperly (nonstandard illuminant,
binocular viewing, colored lenses not removed from City University Color Vision Test
observer), their efficiency can diminish dramatically.
Highly inaccurate test based on erroneous concepts The test is developed by Fletcher, it consists of 10 black
of color vision. charts each of which has 5 color dots. One of the dots
is located in the center being encircled with the 4 other
Farnsworth 100-hue Test dots, so that a subject has to match the central color
dot with one of the 4 other dots.
This simple and useful test consists of 85 colored chips
that are designed to approximate the minimum Anomaloscope
difference between the hues that a normal observer
Nagel (1970) constructed anomaloscope for studying
can distinguish (1-4 nm). Color deficient persons make
the color vision defects. In anomaloscope the observer
characteristic errors in arranging the chips. The results
is asked to match a mixture of red and green
are recorded on a circular graph. The greater the error
wavelengths to a yellow. One indication of the defect
in ordering the chips, the farther the score is plotted
is the relative amounts of red and green required.
from the center of the circle. Automated score for FM
Another defect is the range of settings found
100-hue test is also available (Fig. 145.1)
acceptable by the observer.
Farnsworth D-15 Electroretinography (ERG)
It consists of single box of 15 colored chips. The test Use of ERG in modern era is more useful for detection
can be carried out more rapidly than the 100-hue test. of color vision deficiencies for two reasons. New
1148 Section 9: Miscellaneous Topics
methods allow to separate and observe accurately the
photopic and scotopic components of ERG with the
possibility of better study of cone activity and with
the use of computer averaging, picking up of oscilla-
tory potentials are more easy.
Microspectrophotometry
In spectrophotometry, an individual cone of a
dissected retina is aligned under a small spot of light
and its absorption is measured at various wavelengths.
The most direct evidence of Young’s trichromatic
theory (3 classes of cones) comes from spectrophoto-
metry. The results of microspectrophotometry confirm
three groupings with peak sensitivities at 437-458 nm,
520-542 nm and 562-583 nm.17
ANOMALIES OF COLOR VISION
Deficiency of color vision first described by Dalton
(1794), the Founder of the atomic theory, who himself
was colorblind; hence the term is daltonism. In clinical
evaluation of color vision it is important to distinguish
between acquired and congenital defects. Congenital
color vision defects are stationary and usually affect
both eyes equally. Acquired color vision defects are
frequently progressive and may affect one eye more
than the other.
Congenital Color Vision Deficiency
The color vision anomalies commonly being X-linked
are relatively common (8%) in men and rare in women.
Color deficiency can be congenital or acquired. Nearly
all congenital color defects are due to absence or
alteration of one of the pigments in photoreceptors.
Congenital color deficits may be divided into classes
according to whether they are red deficient (protans),
green deficient (deutans) or blue deficient (tritans)
(absolute deficiency—anopia, relative deficiency—
anomaly) (Table 145.1).
Table 145.1: Classification of congenital
color deficiency
Red Green Blue
deficient deficient deficient
Anomalous Protano- Deuterano- Tritano-
Trichromats maly maly maly
Dichromats Protanope Deuteranope Tritanope
Monochromats Rod mono- Blue mono-
chromat chromats
Anomalous trichromats are people who generally
require three wavelengths to match another wave-
length but do not accept the color matches made by
normal people. Lord Raleigh (1881) discovered
trichromacy.
Anomalous trichromats have three classes of cones
but one is abnormal. Protanomalous people lack the
red receptors and instead they have two pigments
both peaking in the range of the normal green.18
Similarly the deuteranomalous people lack green
receptors.
Dichromats require only two wavelengths to match
another wavelength and will accept the color matches
made by normal people. The dichromats have two
classes of cone receptors with normal spectral sensi-
tivity, the third class being absent. Measurements of
their pigments can be made by reflection densi-
tometer19 and cone processes isolated by colored
backgrounds20 confirm the findings. Protanopes have
normal green and blue cones, red cones being absent.
Deuteranopes have normal red and blue cones, and
tritanopes normal red and green cones.
Protans color deficient subjects are easier to test
and classify than deuterans and tritans; because the
red cone pigment is quite sensitive to green wave-
lengths and both red and green cone pigment are quite
sensitive to blue wavelength covering the green and
blue range, in deuterons and tritans, according to
general rule the sensitivity of visual pigment does not
fall off sharply on the short wavelength side of the
peak.
Monochromatics can be blue cone monochromatics
and rod monochromatics. Blue cone monochromatics
have normal blue cone pigment but no red or green
cone pigment. In rod monochromatism only 500 nm
pigments are present in the retina and all three cones
pigments are absent.
DISORDERS OF COLOR VISION
Genetics of Congenital Color Deficiencies
The protans and deuterons are commonly sex-linked
recessive. In male population about 1 percent are
protanopes, 1 percent protanomalous, 1 percent
deuteranopes and 5 percent deuteranomalous. The
incidence of color vision deficiency in females is 0.4
percent for red-green deficiency. The gene for tritans
is autosomal incompletely dominant. Rod mono-
chromatism is very rare; occurs 1 in 30,000 autosomal
recessive and thus an increased incidence is seen in
consanguineous offspring.
 Chapter 145: Color Vision and Color Blindness
Acquired Deficiency of Color Vision
Koellner formulated that lesions in the outer layers of
the retina give rise to a blue-yellow defect, while
lesions in the inner layers of the retina and the optic
nerve gives rise to red green defect.21 However, the
correlation is not always true. Some patients with
lesions in the cerebral cortex may have color deficits.22
These may involve naming of the colors or perception
of colors.
Ocular Disease Causing Deficiency of Color Vision
Squint Amblyopia
Francois23 by means of clinical tests stated that color
vision deficiencies in squint amblyopia do not
correspond to the classical types of acquired defi-
ciencies but rather approximate the normal color sense
of eccentric retinal positions.
Glaucoma
Angle closure glaucoma causes a tritan defect. Open
angle glaucoma cases and cases of ocular hypertension
also cause tritan type of defect.
Diabetic Retinopathy
The type of color vision defect acquired in diabetic
retinopathy may vary from a mild loss of hue discri-
mination to moderate blue yellow color vision
deficiency. In severe cases of diabetic retinopathy the
defect may resemble tritanopia.
Retinal Disorders
Blue yellow deficits are found in senile macular
degeneration, myopia, retinitis pigmentosa, siderosis
bulbi and chorioretinitis of varied etiology.
Optic Nerve Disorders
In one study about 57 percent of the studied cases of
resolved optic neuritis were found to have color vision
defects.24 Red-green defects have been found in cases
of multiple sclerosis and optic atrophy. Tobacco
amblyopia causes blue-green defect.
Color Vision after Lasers
After argon-laser photocoagulation there may be
overall loss of hue discrimination or color deficiency,
mostly of blue-yellow deficiency.
1149
DRUGS CAUSING DEFICIENCY IN COLOR VISION25
Many drugs are known to cause deficiency of color
vision. Even though they can cause more than one type
of color deficiency we herein describe the most
common type of color deficiency caused by the
particular drug.
Blue-yellow deficiency occurs with chloroquine,
indomethacin, oral contraceptives, antihistaminics,
estrogens, digitalis and butazolidin.
Red-green deficiency occurs with ethyl alcohol and
in some cases of ethambutol.
Mixed type of color deficiency is seen with tri- and
bicyclic antidepressants.
SYSTEMIC DISORDERS CAUSING
DEFICIENCY IN COLOR VISION
Apart from diabetes which has already been descri-
bed, few systemic disorders are known to be asso-
ciated with defective color vision; most are caused by
involvement of the eye secondarily.
Cardiovascular Disease
Patients with heart diseases have been found to have
blue-yellow deficiency.
Turner’s Syndrome
Red-green color deficiency was usually encountered
in such cases.26
REFERENCES
1. Yves le Grand. Light Colour and Vision. London: Chapman
and Hall Ltd, 1957.
2. Nigel W Daw. Colour vision: Adler’s Physiology of the Eye,
Robert Moses, (Ed) St Louis: CV Mosby Co, 1981.
3. Vola JL, Leprince G. 100 Hue at mesopic level. Mod Probl
Ophthal 1978;19:67-70.
4. Young T. A course of lectures on natural physiology (1801-
07). Phil Trans 91, 43, 92, 12, 387.
5. Arthur Konig. Psy Phys Sinnes 1892;4:241.
6. Goth lin. Am J Psych 1943;61:537.
7. Granit. Am J Physiol 1930;94:41.
8. Herring. Pfugers Arch 1895;60:519.
9. Michael CR. Colour vision mechanisms in monkey striate
cortex: Simple cells with dual opponent colour receptive
fields. J Neurophysiol 1978;41:1233.
10. Michael CR. Colour sensitive complex cells in monkey striate
cortex. J Neurophysiol 1978;4:1250.
11. Michael CR. Colour sensitive hypercouplex cells in monkey
striate cortex. J Neurophysiol 1979;42:726.
12. Gouras P. Identification of cone mechanism in monkey
ganglion cells. J Physiol (London) 1968;199:533.
1150 Section 9: Miscellaneous Topics
13. De valois RL, Abramov I, Jacobs GH. Analysis of response
patterns of LGN cells. J Ophthalmol Soc Amer 1966;56:966.
14. Wiesel TN, Hubel DH. Spatial and chromatic interactions in
the lateral geniculate body of the rhesus monkey. J
Neurophysiol 1966;29:1115.
15. S Vaetichin G. The cone action potential. Acta Phys Scan
1953;29:565.
16. Mitarai G. Glia-neuron interactions and Adaptional
mechanisms of the retina. In R Jung, H Kormaluber (Ed): The
Visual System: Neurophysiology and Psychophysics 1961.
17. Brown PK, Wald G. Visual pigments in single rods and cones
of the human retina. Science 1964;144:45.
18. Alprey M, Mocller J. Red and green cone visual pigments of
deuternomalous trichromacy. J Ophysiol (London) 1977;
266:647.
19. Rushton WAH. A cone pigment in the protanope. J Physiol
(London) 1963;168:345.
20. Wald G. Defective colour vision and its inheritence. Proc Nat
Acad Sci USA 1966;55:1347.
21. Francois J, Verriest G. On aquired deficiency of colour vision.
Vision Res 1961;1:201.
22. Pearlman AL, Birch J, Meadows JC. Cerebral colour blindness:
An aquired defect in hue discrimination. Amer Neurol
1979;5:253.
23. Francois J. La discrimination chromatique dans amblyopie
strabique. Documents Ophthal 1967;23:318.
24. John A, Fleishman, Roy W Beck. Defects in visual function
after resolution of optic neuritis. Ophthalmology 1987;
94:1029.
25. Olof Lager Lof. Quantitative assessment of aquired colour
vision defeciency in maculopathy. Mod Probl Ophthalmology
1978;19:276.
26. Georgia Antonakon. Chrousos ocular findings in Turner’s
syndrome: A perspective study. Ophthalmology 1984;91:926.
 Chapter 146
Indocyanine Green Angiography
in Neovascular Age-related
Macular Degeneration
Sandeep Saxena, Tomohiro Lida
INTRODUCTION
Age-related macular degeneration (AMD) is the most
common cause of legal blindness in the United States
among persons 60 years of age and older. AMD has
been classified into non-neovascular (dry or atrophic)
and neovascular (wet or exudative) forms. The
majority of patients who experience severe visual loss
from AMD have the neovascular pattern. The visual
loss is secondary to choroidal neovascularization
(CNV) and related manifestations such as subretinal
hemorrhage, detachment of the RPE, and disciform
scarring.
Fluorescein angiography has been instrumental in
the imaging and early characterization of exudative
AMD. Patients with well-demarcated, actively
proliferating capillaries, that are seen early and leak
late, on fluorescein angiography are said to have
classic CNV.1 However, only a small percentage of
patients with exudative AMD present with classic
CNV.2 Most patients present with ill-defined areas of
CNV on fluorescein angiography, which are called
occult CNV.1 Fluorescein angiography is the only form
of angiography that has been linked to any proven
therapy for AMD via conventional laser or photod-
ynamic therapy.
Digital Indocyanine Green (ICG) angiography is a
diagnostic technique used to image the choroid and
its associated pathology. It has been found to
significantly improve the imaging of the occult
lesions.3-6 ICG angiography, although interesting, has
not been associated with any treatment that has been
proven statistically to work in AMD.
INDOCYANINE GREEN ANGIOGRAPHY
Properties of Indocyanine Green Dye
Indocyanine green is a tricarbocyanine dye that has
several special properties that give it certain advan-
tages over sodium fluorescein as a dye for ophthalmic
imaging. It is a water-soluble dye with a molecular
weight of 775 daltons. When administered intra-
venously, ICG rapidly and almost completely (98%)
binds to plasma proteins and is distributed within the
vascular compartments. Eighty percent of ICG is
bound to globulins, probably alpha-1 lipoproteins.7
This protein binding property of ICG is useful because
it causes the dye to remain within the choriocapillaris,
which allows imaging of the choroid and of any
associated abnormalities. This is in contrast to
fluorescein, which extravasates rapidly from the
choriocapillaris and fluoresces in the extracellular
space, thus preventing delineation of choroidal
anatomy.8 The ICG dye is active between 790 and 805
nm. Twenty-five mg of ICG dissolved in 2ml of
aqueous solvent provides high contrast images. For
patients with poorly dilated pupil or with a darkly
pigmented fundus, a higher concentration of 50 mg
of ICG dissolved in 3 ml of aqueous solvent is
necessary.9
1152 Section 9: Miscellaneous Topics

INDOCYANINE GREEN ANGIOGRAPHY IMAGING

Indocyanine green angiography is done with digital
imaging and can be performed using conventional
fundus cameras, and scanning laser ophthalmo-
scopes.10 Confocal scanning infrared laser ophthalmo-
scope provides better images of the retina in the early
phases of the angiogram. Conventional fundus
cameras provide better late-stages. Furthermore,
confocal laser scanning angiography allows for
quasisimultaneous fluorescein and ICG angiography.
Compared with consecutive angiographic investi-
gations using both dyes, simultaneous angiography
is less time consuming, requires only one injection,
and, because quasisimultaneous frames are obtained,
it may facilitate interpretation of the angiograms.11 An
advantage of digital ICG image processing is that it
allows image enhancement, which can provide a Fig. 146.1A: Fluorescein angiogram shows occult CNV
higher diagnostic yield as compared to non-enhanced,
images.12 Wide-angle ICG angiography also provides
visualization of the choroidal angioarchitecture, hemo-
dynamics and pathologic changes up to 160 degrees.13
In a study of 1000 consecutive eyes with occult
CNV, 14 three morphological types of CNV were
defined by ICG angiography:

Focal Spots
Focal spots (hot spots) are areas of clinical subretinal
exudation that appears as occult CNV on fluorescein
angiography. ICG angiography demonstrates a
hyperfluorescent lesion less than 1 disk area in size. It
is usually noted to be outside the foveal avascular zone
and is thus potentially treatable with thermal laser
photocoagulation. Focal spots are observed in 29
percent of occult CNV cases (Figs 146.1A and B)
Fig. 146.1B: Indocyanine green angiography
Plaques shows a hot spot
The most common pattern of occult CNV on ICG
angiography is a plaque. It is a hyperfluorescent lesion
greater than 1 disk area in size and is usually subtypes exist depending upon the relationship
subfoveal. Plaques are noted in 61 percent cases and between the focal spot and plaque.
can be well defined or poorly defined (Fig. 146.2). They
tend to become larger with time, the enlargement Marginal Spot
reaching about 40 percent growth over 1 year of A marginal spot is a focal spot at the edge or margin
follow-up. The resulting loss of visual acuity is not of a plaque of neovascularization. Such spots are noted
significant. Therefore, ICG-guided laser photo- in 3 percent of cases.
coagulation is not advisable.
Combination Spot
Combined Lesions A combination spot is a focal spot that overlies the
These are the least common types of occult CNV and plaque of neovascularization. Such a lesion is noted
consist of both a focal spot and a plaque. Three in approximately 4 percent of cases.
 Chapter 146: Indocyanine Green Angiography in Neovascular Age-related Macular Degeneration 1153

Fig. 146.2: Fluorescein angiogram shows occult CNV, whereas, indocyanine green angiography shows a plaque

Remote Spot defined in 49 percent of eyes. In the remaining 4

percent of eyes no CNV was detected. Classic CNV
A remote spot is a focal spot that is not contiguous
membranes are best characterized with fluorescein
with a plaque. It occurs in 1 percent cases.
angiography, however ICG angiography can provide
more information on the feeding vessels. ICG has also
IMAGING OF CHOROIDAL been more successful in demonstrating retinal
NEOVASCULARIZATION choroidal anastomoses in classic CNV.
Classic Choroidal Neovascularization
Occult Choroidal Neovascularization
Classic CNV presents as a discrete, grayish-green
The clinical appearance of occult CNV depends on the
elevation of the RPE commonly associated with
vascular growth pattern, the effect on the overlying
subretinal exudation, hemorrhage and lipid depo-
RPE, and the associated exudative and hemorrhagic
sition. Fluorescein angiography reveals a well-
manifestations. More than 85 percent of newly
demarcated area of early vascular hyperfluorescence
diagnosed patients with exudative AMD present with
with progressive leakage in the late stages. ICG
occult CNV.2 On fluorescein angiography, occult CNV
angiography has similar findings, however the
may present either as late leakage of undetermined
fluorescein imaging is usually more intense and better
source or as a fibrovascular pigment epithelial
delineated.14 Only 12 percent of newly diagnosed
detachment. However, occult CNV has been classified
patients with exudative AMD present with classic
in other ways.
CNV on fluorescein angiography.2 The ICG angio-
graphic findings of classic CNV have been documen-
Occult CNV without Serous
ted as: vessels architecture in 66 percent, feeding
Pigment Epithelial Detachment
vessels in 29 percent and late hyperfluorescence in 93
percent of eyes. The borders of classic CNV, on ICG, This type of occult CNV is caused by subpigment
were found to be well defined in 47 percent and ill epithelial choroidal vascular proliferation. The early
1154 Section 9: Miscellaneous Topics
stages of fluorescein angiography reveal minimal,
subretinal stippled hyperfluorescence of undeter-
mined source that slowly increases to produce an
irregular staining of the subpigment epithelial tissue.
The ICG angiography reveals early vascular hyper-
fluorescence and late staining of abnormal vessels. If
ICG angiographic imaging has reasonably distinct and
complete margins, it is considered to be well defined
area neovascularization. Two-thirds of newly
diagnosed cases with occult CNV present without an
associated serous pigment epithelial detachment
(PED).15
Occult CNV with Serous
Pigment Epithelial Detachment
This type of occult CNV is associated with a serous
PED of at least 1 disk diameter in size. Combined CNV
and PED are called as vascularized PED. This results
from subpigment epithelial neovascularization that
becomes associated with a serous detachment of the
RPE. The determination whether a serous PED is
present is best made on the basis of fluorescein
angiography, which may also demonstrate occult
vessels as late indistinct subretinal staining beneath
or at the margin of the serous PED. ICG angiography
reveals early vascular hyperfluorescence and late
staining of CNV. The serous PED is comparatively
hypofluorescent, because only minimal ICG leakage
occurs beneath the serous detachment. ICG angio-
graphy provides better differentiation between a
serous PED and a vascularized PED. It also permits
better identification of the vascularized and serous
components of vascularized PEDs. Fluorescein
staining is more intense in the serous portion of the
detachment than in the vascularized portion, diffe-
rences in intensity are often too minimal. However,
the ICG angiographic findings are infinitely more
reliable in making this differentiation. The serous
detachments are hypofluorescent and the vascularized
elevations are hyperfluorescent. One-third of newly
diagnosed cases of with occult CNV have an asso-
ciated serous PED.15
Combined Choroidal Neovascularization
Most patients with CNV and exudative manifestations
at presentations do not demonstrate classic-CNV on
fluorescein angiography. As many as 85 percent of
newly diagnosed patients demonstrate occult-CNV,
on initial examination.2 Combined classic-CNV and
occult-CNV can be observed in the majority of cases.
Polypoidal Choroidal Vasculopathy (PCV)
Polypoidal choroidal vasculopathy is generally
thought to be a primary abnormality of the choroid,
consisting of a network of vessels with two distinct
components: (1) a complex of branching vessels and
(2) multiple terminal, reddish-orange, aneurysmal or
polypoidal lesions16 (Figs 146.3A to 146.4B). Because
of its location within the inner choroid, the lesion is
generally masked on fluorescein angiography by the
overlying fluorescence of the choriocapillaris. ICG
imaging, however, penetrates through the RPE and
any overlying serosanguineous opacity providing a
more enhanced angiographic delineation of not only
the active lesion, but also of the entire vascular
component. Originally, PCV was thought to be present
predominantly as a bilateral disorder affecting the
peripapillary area with bullous serous and hemorr-
hagic detachments of RPE and neurosensory retina.
Some patients may even develop vitreous hemorr-
hage. However, solitary PCV lesions have been
described in the macula as well as in the peripheral
fundus.17 When PCV involves large caliber vessels
terminating in reddish-orange, aneurysmal or poly-
poidal dilatations, the vascular abnormality may be
seen clinically through atrophic RPE, even when the
vessels are dormant or quiescent, free of sero-
sanguineous complications.17 In such eyes, the fluore-
scein angiogram can sometimes confirm the diagnosis,
but the ICG angiogram is generally regarded as the
preferred method for imaging these choroidal vessels,
particularly when they are external to the chorio-
capillaries. The longer wavelengths used in ICG angio-
graphy penetrates the RPE and any associated
serosanguineous complications with higher levels of
sensitivity and specificity. Laser photocoagulation
treatment of active polypoidal lesions, accounting for
serosanguineous detachments of the macula, has been
used empirically to accelerate the resolution of
subfoveal blood and exudate. Such treatment is
presumptive, anecdotal and rational, yet unproven in
terms of its efficacy and safety.
Retinal Angiomatous Proliferation (RAP)
Retinal angiomatous proliferation (retinochoroidal
anastomosis) can present as a primary manifestation
of the exudative process in AMD.18 RAP is originally
intraretinal neovascularization. They may present
 Chapter 146: Indocyanine Green Angiography in Neovascular Age-related Macular Degeneration
Fig. 146.3A: Fluorescein angiogram shows occult CNV
Fig. 146.4A: Fluorescein angiogram shows
peripapillary occult CNV
with or without PED. Suggestive clinical and
photographic features are:19 Preretinal/intraretinal/
subretinal hemorrhage, dilated and tortuous retinal
vessel and cystoid macular edema. Fluorescein
angiography reveals serous PED in association with
1155
Fig. 146.3B: Indocyanine green angiography revealed
polypoidal choroidal vasculopathy in macula
Fig. 146.4B: Indocyanine green angiography revealed
peripapillary polypoidal choroidal vasculopathy
occult-CNV with a “hot spot” at or near the retinal
surface in the absence of pigment epithelial atrophy
(window defect). ICG angiography reveals focal hot
spot in association with a serous PED, intraretinal
leakage of ICG dye surrounding fading neovascula-
1156 Section 9: Miscellaneous Topics
rization in the later phases of angiogram and two-tier
angiographic complex with small plaques of neo-
vascularization originating from the retina overlying
a larger bed of vessels from the choroid. Combined
clinico-angiographic features include localized bulge
or elevation of the serous PED at the site of ICG
angiographic hot spot and identical hot spot on a
serous PED noted with both fluorescein and ICG
studies (Fig. 146.5). Presence of RAP represents a poor
prognostic sign for successful ICG-guided laser
treatment.
ADDITIONAL CONSIDERATIONS
ICG angiography added clinically useful information
to fluorescein angiography by demonstrating well-
demarcated areas of hyperfluorescence in 50 percent
of eyes with occult CNV and in 82 percent of eyes with
PED. Sensitivity of ICG angiography has been assessed
in patients with occult CNV. Occult CNV was detected
in 68 percent of eyes. ICG angiography increased the
number of patients eligible for thermal laser treatment.
Fluorescein and ICG angiography has been used to
study the features before and after retinal pigment
epithelial tear. At the pretear stage fluorescein
angiography showed all signs of occult CNV asso-
ciated with delayed, slow and uneven filling of the
pigment epithelium detachment. CNV was observed
on ICG angiography. At the tear stage fluorescein
angiography showed an area of marked hyper-
fluorescence with well-defined margins. The torn RPE
was markedly hypofluorescent during all angio-
graphic phases. The bare choroid was always hypo or
normofluorescent on ICG angiography. The torn RPE
Fig. 146.5: Fluorescein and Indocyanine green angiography shows Retinal Angiomatous Proliferation.
showed moderate hypofluorescence. ICG angio-
graphy did not add anything substantial but helped
in visualization of the seat and extension of the
associated CNV. Patients with occult CNV have been
evaluated with digital subtraction ICG angiography
(DS-ICGA) and it was found that DS-ICGA uses time
to dissect the choroidal circulation. With DS-ICGA,
occult CNV could be imaged more quickly and in
greater detail than with conventional imaging
techniques.13
IMAGING OF RECURRENT
CHOROIDAL NEOVASCULARIZATION
Treatment of recurrent CNV is critically dependent
on accurate identification of the CNV. Stereo
fluorescein angiography, in conjunction with slit-lamp
biomicroscopic examination is the accepted means of
identifying recurrent CNV. In some cases, the
fluorescein angiography fails to identify the exact
location and extent of the recurrence. In such cases
the recurrent CNV is considered to be ill-defined or
“occult”. Enhancement of recurrent CNV imaging
with ICG angiography results from an overall
reduction in permeability of the dye and an increase
in contrast. The photocoagulation site is hypo-
fluorescent along with areas of exudative detachment
and surviving choriocapillaries. These dark zones
generally highlight the only hyperfluorescent tissue,
which is the staining recurrent occult CNV. The
normal choriocapillaries at the edge of the photo-
coagulation site does not stain on ICG, unlike
fluorescein angiography where the staining mimics a
recurrence.20
 Chapter 146: Indocyanine Green Angiography in Neovascular Age-related Macular Degeneration
Recurrent Classic CNV
Classic recurrent CNV is still best imaged with
fluorescein angiography. The ICG molecule and the
more prevalent protein-bound biconjugate do not
penetrate or leak as extensively from the small
capillaries associated with most recurrences, which are
similar in morphological composition to the chorio-
capillaries.20
Recurrent Occult CNV
Recurrent Occult CNV is characterized on ICG
angiography as a localized area of hyperfluorescence
with well-defined margins at the edge of the
hypofluorescent photocoagulation scar. When the
occult CNV is associated with a PED, ICG angio-
graphy shows an area of relative hypofluorescence
compared to the surrounding choroidal background
fluorescence that corresponds to the serous PED. This
allows the area of hyperfluorescent recurrent
neovascularization to stand out. Since the laser treat-
ment site is hypofluorescent, the recurrent neovascula-
rization may appear as an intensely staining, well-
defined area of hyperfluorescence between the scar
and the exudative RPE elevation.
In a subgroup of patients there is often no detec-
table evidence of recurrent neovascularization on
fluorescein angiography. However, ICG angiography
demonstrates a focal area of staining (“hot spot”) at
the margin of the previous laser site, which is
presumed to represent the CNV accounting for the
exudative changes and visual symptoms. Photocoagu-
lation of this tiny spot may result in resolution of
associated complications and improvement in vision.20
In patients with recurrent occult CNV studied with
ICG angiography, in most instances, a large subfoveal
recurrence was observed. 44 percent of these patients
were identified with a well-defined area of recurrent
CNV that was classified as treatable. Following laser
photocoagulation, 62 percent had resolution of
exudative manifestations.21 Clinical utility of routinely
using ICG angiography and fluorescein angiography
in detecting persistent and recurrent CNV has also
been evaluated. Fluorescein angiography showed well
defined, ill defined and no CNV in 19 percent, 35
percent and 46 percent eyes, respectively. ICG
angiography had a high concordance rate at 70 percent
and 88 percent eyes when persistent or recurrent CNV
was well-defined and absent, respectively. When CNV
was ill-defined by fluorescein angiography, the
1157
corresponding ICG angiography showed well-defined
CNV in 47 percent eyes.
Indocyanine green angiography can increase the
resolution of the neovascular complex in occult or
poorly defined choroidal neovascularization. This
may allow for more patients to be treated with laser
photocoagulation. Hence, this diagnostic adjunct may
redefine the eligibility criteria for laser photo-
coagulation treatment.5 In ICG angiography-guided
laser photocoagulation studies on primary occult
CNV; ICG angiography was able to convert occult
lesions to well-delineated vessels that were treated
with laser photocoagulation with promising anatomic
and functional results.
ICG-GUIDED LASER PHOTOCOAGULATION
OF PRIMARY OCCULT CNV
ICG angiography, with its enhanced imaging of the
choroidal circulation, can increase the number of
patients eligible for laser photocoagulation. The ICG
angiogram is used to evaluate the total size of the CNV
and to determine the treatment area. An overlay map
is created by mapping the area of hyperfluorescence
in the ICG onto the digital red-free photograph, which
is viewed during laser photocoagulation treatment.22
Direct ICG-guided Laser Treatment
ICG-guided laser photocoagulation treatment has
been performed solely on ICG angiographic findings.
Successful treatment was achieved in 63 percent eyes,
with 6 months of follow-up. A strong correlation was
noted between post-treatment persistence and
recurrence of ICG hyperfluorescence and treatment
failure. Occult CNV was divided into two categories,
in another study.22 The patients were divided into
those who presented with occult CNV with a serous
PED (Group 1) and those without a significant serous
PED (Group 2). 43 percent of group 1 eyes and 66
percent of the group 2 eyes had complete resolution
of the clinical manifestations, following treatment. The
overall recurrence rate was 43 percent; 51 percent of
group 1 eyes and 35 percent of group 2 eyes demons-
trated recurrent CNV.
Dye-enhanced Laser Treatment
ICG-dye enhanced diode laser photocoagulation has
been advocated for treatment of subfoveal occult CNV,
which is deemed untreatable by the Macular Photoc-
oagulation Study Group. This technique involves
1158 Section 9: Miscellaneous Topics

enhancement of the photo thermal effect of laser lesions may also be treated with Transpupillary
treatment by a photochemical reaction using the ICG Thermotherapy (TTT).26 Angiographic criteria for TTT
dye. The ICG molecule has peak absorption at 805- are entirely based on fluorescein angiography at
810 nm. In the late phases of an ICG study, the present. Perhaps there may be a role for ICG in this
neovascular membrane is the only structure that treatment technique in future. High-speed ICG
appears to contain residual ICG dye. The infrared angiography looking for feeder vessels is a new
diode laser emits light in the 810 nm wavelength evolving technique that may be used for minimally
range, corresponding to the peak absorption of ICG. classic or occult lesions.
Application of diode laser to neovascular complexes Polypoidal CNV may masquerade as central serous
containing ICG dye might permit an enhancement of chorioretinopathy (CSC) with persistent or recurrent
the photocoagulation effect by adding a photo- detachment.17 ICG angiography is useful in establi-
chemical effect, resulting from an interaction of the shing a correct diagnosis. There is a greater chance of
exciting diode laser and the ICG molecule. As a result, imaging the precise nature, location and extent of the
less overall laser energy would need to be delivered polypoidal CNV and ICG angiography confirms its
to a particular treatment area.23 In another study, presence. Furthermore, the ICG angiogram is also of
stabilization of visual acuity was achieved in 9 out of value in recording the absence of multifocal areas of
the ten treated eyes. choroidal hyperpermeability (late ICG staining),
which have no clinical or fluorescein angiographic
ICG-guided Feeder Vessel Photocoagulation counterpart (Fig. 146.6). These zones of choroidal
leakage, known to be indicative of CSC are not seen
ICG angiography enhances the imaging of entire
in PCV.
vascular network, in particular the identification of
feeder vessels, associated with the recurrent CNV.
Localized photocoagulation of the feeder vessels may
be particularly useful in patients with advancing or
active edge of the neovascularization beneath fixation.
By treating the extrafoveal feeding vessels, the
subfoveal neovascular lesion may be eliminated. ICG
angiography with the confocal SLO can identify
choroidal feeder vessels. Laser treatment to such
extrafoveal feeder vessels, particularly in membranes
that are large or subfoveal may be effective in closing
the feeder vessel. More than one treatment may be
required. Rate of success was affected by the width
and number of feeder vessels.24

When to use Indocyanine Green Angiography

In cases of AMD, firstly fluorescein angiography is
performed to determine if the patient has classic or
occult choroidal neovascularization and to determine
the location of CNV. If the patient has classic CNV,
not under the fovea, he may be a candidate for laser
photocoagulation. With predominantly classic lesions
that are subfoveal the patient would then be a
candidate for photodynamic therapy (PDT).25 More
recently, it has been shown that cases that have purely
occult lesions may also benefit from PDT. It is these
cases that have minimally classic lesions that do not
seem to respond to PDT. None of these patients would
seem to benefit from ICG. The patients with occult
Fig. 146.6: Indocyanine green angiography shows multifocal
areas of choroidal hyperpermeability (late ICG staining) in
Central Serous Retinopathy
REFERENCES
1. Macular Photocoagulation Study Group. Argon laser
photocoagulation for age-related macular degeneration. Arch
Ophthalmol 1982;100:912.
2. Freund KB, Yannuzzi LA, Sorenson JA. Age-related macular
degeneration and choroidal neovascularization. Am J
Ophthalmol 1993;115:788.
3. Destro M, Puliafito CA. Indocyanine green videoangiography
 Chapter 146: Indocyanine Green Angiography in Neovascular Age-related Macular Degeneration
of choroidal neovascularization. Ophthalmology 1989;96:846.
4. Guyer DR, Puliafito CA, Mones JM, Friedman E, Chang W,
Verdooner SR. Digital indocyanine green angiography in
chorioretinal disorders. Ophthalmology 1992;99:287.
5. Yannuzzi LA, Slakter JS, Sorenson JA, Guyer DR, Orlock DA.
Digital indocyanine green angiography and choroidal
neovascularization. Retina 1992;12:191.
6. Hayashi K, Hasegawa Y, Tokoro T, Delaey JJ. Clinical
application of indocyanine green angiography to choroidal
neovascularization. Jpn J Ophthalmol 1988;42:827.
7. Baker KJ. Binding of sulfabromophtalein (BSP) sodium and
indocyanine green (ICG) by plasma alpha-1 lipoproteins. Proc
Soc Exptl Biol Med 1966;122:957-63.
8. Hope-Ross MW. ICG dye: Physical and pharmacological
properties. In: Yannuzzi LA, Flower RW, Slakter JS (eds).
Indocyanine Angiography. St. Louis, Mosby, 1997;46-49.
9. Guyer DR, Yannuzzi LA, Slakter JS, Chang A, Hanutsaha P,
Fenster A. Principles of Indocyanine-green angiography. In:
Guyer DR, Yannuzzi LA, Chang S, Shields JA, Green WR
(Eds) Retina Vitreous Macula Vol 1. Philadelphia, WB
Saunders Co. 1999;39-46.
10. Bartsch DU, Weinreb RN, Zinser G, Freeman WR. Confocal
scanning laser ophthalmoscopy for indocyanine green angio-
graphy: preliminary results. Am J Ophthalmol 1995;120:642.
11. Holz FG, Bellman C, Rohrschneider K, Burk RO, Volcker HE.
Simultaneous confocal scanning laser fluorescein and indo-
cyanine green angiography. Am J Ophthalmol 1998; 125:227.
12. Maberly DA, Cruess AF. Indocyanine green angiography: an
evaluation of image enhancement for the identification of
occult choroidal neovascular membranes. Retina 1999;19:37.
13. Spaide RF, Orlock DA, Herrmann-Delemazure B, Ciardella
AP,Yannuzzi LA, Freund KB, et al. Wide-angle indocyanine
green angiography. Retina 1998;18:44-49.
14. Guyer DR, Yannuzzi LA, Slakter JA, Sorenson JA, Hanutsaha
P, Spaide RF, et al. Classification of occult choroidal
neovascularization by ICG Ophthalmology 1996;103:2054.
15. Guyer DR, Yannuzzi LA. Occult choroidal neovascula-
rization. In: Yannuzzi LA, Flower RW, Slakter JS (eds).
Indocyanine Angiography. St. Louis, Mosby, 1997;157-80.
16. Yannuzzi LA, Sorenson J, Spaide RF, Lipson B. Idiopathic
polypoidal choroidal vasculopathy (IPCV). Retina 1990;10:1.
1159
17. Yannuzzi LA, Freund KB, Goldbaum M, Scassellatti-
Sforzolini B, Guyer DR, Spaide RF, et al. Polypoidal choroidal
vasculopathy masquerading as central serous chorio-
retinopathy. Ophthalmology 2000;107:767.
18. Yannuzzi LA, Negrao S, Iida T, Carvalho C, Rodriguez-
Coleman H, Slakter JS, et al. Retinal angiomatous proliferation
in age-related macular degeneration. Retina.
19. Slakter JS, Yannuzzi LA, Schneider U, Sorenson J, Ciardella
A, Guyer DR, et al. Retinochoroidal anastomoses and occult
choroidal neovascularization in age-related macular
degeneration. Ophthalmology 2000;107:742.
20. Sorenson JA, Yannuzzi LA. Recurrent occult choroidal
neovascularization. In: Yannuzzi LA, Flower RW, Slakter JS
(Eds). Indocyanine Angiography. St. Louis, Mosby, 1997;217-
30.
21. Sorenson JA, Yannuzzi LA, Slakter JS, et al. A pilot study of
digital indocyanine green videoangiography for recurrent
occult-choroidal neovascularization in age-related macular
degeneration. Arch Ophthalmol 1994;112:473.
23. Slakter JS, Yannuzzi LA, Sorenson JA, Guyer DR, Ho AC,
Orlock DA. A pilot study of indocyanine green video-
angiography-guided laser photocoagulation of occult
choroidal neovascularization in age-related macular
degeneration. Arch Ophthalmol 1994;112:465.
23. Slakter JS. ICG-guided laser photocoagulation of primary
occult choroidal neovascularization. In: Yannuzzi LA, Flower
RW, Slakter JS (eds). Indocyanine Angiography. St. Louis,
Mosby, 1997;p.181-16.
24. Straungehi G, Orzalesi N, LaCapria A, Aschero M. Laser
treatment of feeder vessel in subfoveal choroidal neovascular
membranes: a revisitation using dynamic indocyanine green
angiography. Ophthalmology 1998;105:2297.
25. Treatment of Age-related Macular Degeneration with
Photodynamic Therapy (TAP) Study Group. Photodynamic
therapy of subfoveal choroidal neovascularization in age-
related macular degeneration with verteporfin. One-year
results of 2 randomized clinical trials – TAP Report 1. Arch
Ophthalmol 1999;117:1329.
26. Reichel E, Berrocal AM, Ip M, Kroll AJ, Desai V, Duker JS, et
al. Transpupillary thermotherapy of occult subfoveal
choroidal neovascularization in patients with age-related
macular degeneration. Ophthalmology 1999;106:1908.
 Chapter 147

Low Vision Devices

Sarfaraz A Khan

INTRODUCTION loss due to all blindness.12 Surveys of schools for the

blind in India have shown that 50% of children
Worldwide, there are currently 45 million people and
enrolled are in fact not blind, but have low vision.13
an additional 135 million with significant visual
It has been reported that only 3% of all blind and
impairment or low vision, and 90% of the world’s
visually impaired children in developing countries
blind live in the developing world.1 The evidence
have access to basic low vision care.
suggests that these numbers are growing at an
A global initiative for the elimination of avoidable
alarming rate. Many reasons have been identified for
blindness under the title “VISION 2020: The Right to
the rising tide of blindness and low vision, prominent
Sight” launched in 1999 by the WHO in collaboration
among them being the increase of the world’s elderly
with a number of international non-governmental
population, particularly in developing countries.2-4 It
organisations15 with the objective to eliminate all
is estimated that by the year 2025 there will be about
causes of avoidable blindness worldwide by the year
1.2 billion older people, with almost three-quarters
2020.15-18 The provision of good quality low vision
of them living in developing countries.5 In India, the
care has been identified as a key element of “Compre-
current life expectancy at birth of 64.5 years is
hensive Eye Service” model development within
projected to increase to 73-77 years in the year 2020,
Vision 2020 programs.16
and the percentage of the elderly is expected to
increase from the present figure of 8-10 to 20%.5-7
Ironically, low vision is a condition that has not DEFINING LOW VISION
received its due share of attention since persons with
A person with low vision is one who has impairment
low vision have some vision, but the level of vision
of visual functioning even after treatment and/or
does not place them in the category of the normally
standard refractive correction, and who has a best
sighted. A recent population-based study has shown
corrected visual acuity (BCVA) of less than 6/18 (20/
the prevalence of low vision to be 1.05% in India.8 If
60) to light perception or a visual field of less than
the data are extrapolated to the estimated 1014
10° from the point of fixation, but who uses or is
million population of India in the year 2000,9 10.6
potentially able to use, vision for the planning and/
million people would have the need for low vision
or execution of tasks.19
services.8
Of the estimated 1.5 million blind children
worldwide, 1 million live in Asia.10 A population- FUNCTIONAL VISION
based study conducted in south India showed that Functional vision is defined as person’s ability to
there are 0.25 million blind children in India.11 When integrate the components of vision effectively to
the cumulative loss for childhood blindness in India accomplish a task. Functional visual impairment is a
was calculated for the life time of 0.25 million blind significant limitation of visual capability resulting
children with 33 working years of life lost, it was from disease, trauma or a congenital condition which
found that the losses amounted to Rs.801 billion (US cannot be fully ameliorated by standard refractive
$ 22.2 billion). This is 28.7% of the cumulative GNP correction, medication or surgery. It is manifested
 Chapter 147: Low Vision Devices
by one or more of the following:
1. Insufficient visual resolution (worse than 20/60
in the better eye with best correction of
ametropia)
2. Inadequate field of vision (worse than 20° along
the widest meridian in the eye with the more intact
central field; or homonymous hemianopia)
3. Reduced peak contrast sensitivity (< 1.7 log CS
binocularly) and
4. Insufficient visual resolution or peak contrast
sensitivity (see 1 and 3) at high or low luminances
within a range typically encountered in everyday
life.20
IMPACT OF OCULAR DISEASE ON THE PATIENT
• Visual Disorder refers to anatomical changes in
the visual organs caused by diseases of the eye.
• Visual Impairment refers to the functional loss
that results from a visual disorder.
• Visual Disability refers to vision-related changes
in the skills and abilities of an individual. It
describes the level of performance of the person
based on functional vision.
• Visual Handicap refers to the psychosocial and
economic consequences of visual loss, such as the
loss of independence or the inability to work.21
CAUSES OF LOW VISION
Diseases of the Optical Media
Keratoconus, microcornea/microphthalmos, conge-
nital glaucoma, cataract, vitreous opacities, dislocated
lens (Marfan’s syndrome), Aniridia
Diseases of the Macula
• Hereditary (dominant or recessive)- Best’s
disease, Stargardt’s, achromatopsia, albinism,
macular coloboma
• Pigment epithelium—choriocapillary diseases, age
related macular degeneration, myopic retinopathy
• Retinal vascular disease in diabetes and hyper-
tension
• Inflammation—chorioretinitis of macula (tuber-
culosis, histoplasmosis, toxoplasmosis)
• Trauma—macular hole
Diseases of the Peripheral
Retina and Visual Pathways
• Diabetes
1161
• Retinitis pigmentosa and LCA
• Glaucoma
• Optic atrophy
• Retinopathy of pre-maturity (ROP)
• Intra-cranial lesion (vascular, tumors, head injury)
ENHANCING IMPAIRED VISION
Impaired vision can be enhanced in a variety of ways.
Magnification is the most obvious and most common
method. Improving the lighting not only adds to the
effectiveness of magnification but also enhances
contrast.
Types of Magnification
1. Relative distance magnification: moving the object
closer to the eye (shortening the distance), causing
a proportional enlargement of the retinal image
such as optical reading devices.
2. Relative size magnification: enlarging the physical
size of an object, such as large print rather than
standard print.
3. Angular magnification: Improving resolution of
objects by enlarging the image, thus bringing the
object closer (angular magnification).
SYSTEMATIC SEQUENCE FOR
SELECTING LOW VISION DEVICE
1. Determination of the visual acuity and the
complete history of the visually impaired person.
2. Establishment of the cause of visual impairment
(diagnosis).
3. Complete (subjective) refraction to achieve the
best retinal image.
4. Assessment of the best spectacle corrected visual
acuity and the required magnification.
5. Testing the patient’s ability to comprehend
written material (use large print, if necessary), if
reading is required and check the sufficiency of
visual field.
6. Selection of low vision device by the practitioner
and trial by the visually impaired user whilst
observing for proper application.
7. Upon dispensing: Schedule a follow-up appoin-
tment.
Please Note
1. Use the lowest possible magnification to solve the
required visual task.
2. Select the design of the low vision device (i.e.,
1162 Section 9: Miscellaneous Topics

hand-held, stand, etc.) appropriate to the visual

task.
3. No single low vision device can offer a solution
for all eye conditions and all visual tasks.
4. Different low vision devices need to be used for
different visual tasks.

LOW VISION DEVICES

Following categories of devices are available.
1. Optical: Incorporating lenses or optical magnifi-
cation
2. Non-optical: Supplementary devices that do not
use optical lenses.
3. Video magnifiers
4. Computer magnification software
Fig. 147.1: Spectacle devices
Optical Devices for Near Vision Tasks
Predicted add A predicted number of diopters of
spectacle add required by a person with impaired The convex lens enlarges the image on the retina.
vision to read a desired print size; its calculation is The lenticular and aspheric designed lenses have less
based on a known corrected visual acuity. peripheral aberration and could be prescribed in high
Determining the predicted add To determine the powers. The common types of spectacle devices for
predicted add, it is essential to determine the reading tasks are listed below (Fig. 147.1).
corrected acuity, and the goal-size print (or other For binocular use
visual target, if not print). • Base-in prism spectacles (half-eye and full field):
Kestenbaum formula22 Using this formula, when the goal +4.00 to +12.00D, each with base-in prism OU
is 1M (newspaper-size print), the predicted add can • Bifocals: +4.00D to +10.00D of binocular add
be determined simply by inverting a corrected visual decentered 1 millimeter per diopter
acuity. • Single-vision spectacles (full field): to +10.00D

Corrected = test distance = new required reading

distance
Acuity letter size goal-size print

Example: 20 ft = d (“d” is in meters)

160 1M

In the above example, d = .125 meters, the distance

at which 1 M print should be held from the eye in
order for this patient to read it. The inverse of this
distance is the number of diopters of add or
accommodation needed to focus at this new required
reading distance, in this case eight diopters (8D).
Note It is important to realize that the predicted add
should be considered a starting point for testing near
low vision lenses. Other functional deficits, such as
poor contrast sensitivity or paracentral scotomas, may
necessitate a higher magnification for efficient reading
among some patients.
Fig. 147.2: Devices for monocular use
Spectacle Devices23-26
For monocular use (Fig. 147.2)
 Chapter 147: Low Vision Devices
• Single-vision reading glasses up to +10.00D
• Lenticular high-plus spectacles: to +24.00D
• Aspheric microscopic lenses: 24.00D to 48.00D
• Doublet lenses:8.00D to 80.00D
Powers available Upto +24.00D (lenticular lenses)
Uses
1. Long -term reading
2. Writing tasks
3. Needle work
4. Writing / reading invoices, receipts, etc.
Advantages
1. “Psychologically” acceptable
2. Hands are free for tasks requiring manual
manipulation
3. Provides widest field of view
4. Useful for prolonged reading
5. Portable - easy to carry
Disadvantages
1. Fixed reading distance
2. Closer working distance with high add lens, which
may obstruct illumination
3. Inconvenient for spot reading tasks, in which
information is gained from single words or short
phrases (for example, price tags)
4. Difficult to use for patients with eccentric viewing
with eye/head turns. (working distance is fixed,
optical center is fixed)
5. Make writing difficult if lens add is stronger than
+10.00 D
6. Posture is awkward unless a reading stand is used
Please note
• Make sure to present the reading material at
correct focal distance
• Introduce overhead reading lamp as needed
• Use actual reading material or task
• Instruct to move the material in front of the eye
to read continuous text.
• Cover the weaker eye if patient complain of double
vision.
Magnifiers24, 26-28
Magnifiers could be either hand held or stand
mounted and are designed to help low vision patients
with short-term spotting tasks. Both the hand held
and the stand-mounted magnifier could be self-
illuminated for better contrast.
Lens designs
1163
Magnifiers are available in various lens designs:
• Spherical (biconvex, equiconvex, planoconvex)—
low power and inexpensive
• Aspheric (bi-aspheric)—most commonly used and
made in full power range
• Aplanatic (doublet)—best image quality, higher
priced and low power
• Triplet-best image for very high powers
Image location
• All magnifiers produce an enlarged virtual image,
which is “suspended” in space behind the magni-
fier
• Held at its focal length from an object, the image
will be at optical infinity and the patient will use
distance correction
• Held closer than its focal length from an object,
the image will be closer than optical infinity and
the patient will use near add
Uses
The typical uses of magnifiers are:
1. Reading newspaper and books for short time
2. Checking labels and prices while shopping
3. Reading dials, gauges and measuring tapes in a
vocational setting
4. Checking mail, phone numbers and addresses
5. As a training device for patients who resist the
close working distance of a spectacle device
Fig. 147.3: Small pocket magnifiers
Hand-held Magnifiers
Hand-held magnifiers are convex lenses mounted on
a handle. The closer the lens is held to the eye the
larger the seeing area. Small pocket-magnifiers fit
easily into the pocket or purse, and are relatively
inexpensive. The reading speed is usually slower than
with spectacles and therefore they are generally used
for a shorter duration or for spot reading. Powers
range from 10-24 diopters (Fig. 147.3).
1164 Section 9: Miscellaneous Topics

5. Useful for patients with constricted visual field

Fig. 147.4: Binoculin magnifier
Advantages
1. Inexpensive and readily available in the market.
2. Can be used for reading.
3. Easily accepted by the patient.
Stand Magnifier
A fixed focus stand is a convex lens in a rigid
mounting that has been set by the manufacturer to
focus closer to the page than its focal distance to
reduce peripheral aberration. Most stand magnifiers
are designed for use with a standard bifocal add or
reading glasses (Fig. 147.5).
Advantages
1. Variable eye to lens distance
2. Handy optical device as the focal distance is stable
3. Are suitable for patients with hand tremors,
arthritis
4. This device is especially useful to persons who
find it difficult to judge or maintain the correct
distance when using spectacles/hand magnifiers
Disadvantages
1. Inconvenient to carry
2. Awkward to use on non-flat surfaces (requires
the use of a reading stand)
3. Have small field of view
4. Cause excess shading and reduce lighting onto
surface (unless self-illuminated)
5. Impossible to write with most designs
6. May result in poor posture after prolonged use,
unless a reading stand is used
7. Requires hand eye coordination
Optical Devices for
Distance Vision-Telescopes23-24,26
The distance vision telescope is the only optical device
that can assist low vision persons with distance tasks
if conventional glasses are unsuccessful. It can be
hand-held or mounted in spectacles (monocular or
binocular) (Fig. 147.4). It improves resolution of
objects by enlarging the image, thus bringing the
object closer (angular magnification). The user should
in addition wear the refractive correction. The field
of view will be larger when it is held close to the
eye. It is available as a hand held device for
monocular use in powers of 2X, 3X, and 4X
magnification.
Ratings
The ratings provided by all the manufacturers
included:
• Power
• Size of the objective lens
• Field of view
acuity Patient’s distance visual
Expected visual acuity = _________________________________________
Power of the telescope

Galilean telescopes Keplerian telescopes

Smaller field of view
at a given level of
magnification
Usual magnification
available: up to 4X
Smaller, more compact
Lighter weight
Image formed is erect
Fig. 147.5: Stand magnifiers Less expensive
Large field of view of at a given
level of magnification
Usual magnification available:
up to 10X
Longer, bulkier
Heavier weight
Image formed is inverted,
requiring an internal re-
inverting prism
More expensive
 Chapter 147: Low Vision Devices
Telescopes are Available in two Optical Designs
1. Galilean system (terrestrial)—the rays do not
cross, this means that the image is erect.
2. Keplerian system (astronomical)—the rays do
cross, this means that the image is inverted.
Uses
The telescope may be used for the following distance
vision tasks.
a. Specific tasks requiring magnification at variable
distances, like reading the chalkboard in school
and recognizing faces at some distance
b. Spot distance viewing such as reading bus numbers
and street signs to enable independent travel or
to watch television and sports and theatre events.
Disadvantages
Telescopic devices are not readily accepted because
of cosmetic reasons. Other disadvantages include a
reduced field of view, disruption of spatial judgment,
(as the object appears closer), and the need for instruc-
tion and training program (localization, fixation,
scanning and tracking).
Glare Control Devices
Glare is distracting scattered light which is a
significant problem for patients with low vision. Glare
can be controlled with devices such as sun wear/
absorptive lenses, tints and ultraviolet coatings, filters
and anti-reflective coatings. There is no specific test
to determine what sun wear is best. Allow the person
experiment with different lenses outdoors.
Points to be Stressed for
using High Plus Reading Glasses
1. Sit in a comfortable, upright position with your
reading material placed on a flat, inclined surface.
Many individuals find that using a clipboard or
reading stand helps to hold the materials in
position.
2. Additional lightning may be necessary. Position
the light source so that it is on the side of your
better eye at a 45° angle to the side and behind
your line of vision, and shines directly on the
reading material. You may need to make slight
adjustments to avoid glare.
3. Find the correct focal distance of your glasses by
bringing the reading material toward you until it
touches the tip of your nose, then “push” it away
1165
slowly until the words are as clear as possible.
Your reading distance will be significantly closer
than what you are used to.
4. Read for short periods of time (10-20 minutes)
and take a break. This will help relieve eye fatigue
and back and neck strain.
5. If diplopia develops while reading, try covering
the lens of one eye (usually the weaker one) with
translucent tape.
Points to be Noticed in using Hand Magnifier
1. Sit in a comfortable, upright position with your
reading material placed on a flat, inclined surface.
Many individuals find that a clipboard or reading
stand will help to hold the materials in the proper
position.
2. Additional lightning may be necessary. Position
the light source so that it is on the side of your
better eye, at a 45° angle to the side and behind
your line of vision, and shines directly on the
reading material. You may need to make slight
adjustments to avoid glare.
3. Find the correct focal distance by placing the
magnifier directly on the page and raising it until
the letters appear the largest without distortion.
Some individuals have better success if they wear
their distance spectacle correction while using the
hand magnifier.
4. Look directly through the center of the lens to
minimize distortion.
5. Bring the eyes as close to the magnifier as is
comfortable. Although this will not make the print
larger; it will enable you to see more letters at a
time.
6. To avoid frequently losing a line or when having
difficulty in locating the next line:
• Use a line marker (length of dark, study paper)
placed under the line of print
• Place a finger at the beginning of the next line
of the print so that to backtrack only the finger
has to be moved to the start of the line.
• Note the first letter or word of the line that
follows the one that is being read.
7. Keep the magnifier in a protective case and clean
with a soft cotton cloth.
When using Stand Magnifier one should
1. Sit in a comfortable, upright position with the read-
ing material placed on a flat, inclined surface.
1166 Section 9: Miscellaneous Topics
Many individuals find that using a clipboard or
reading stand helps to hold material in position.
2. Additional lighting on the reading material may
be necessary
3. The base of the magnifier positions the lens at the
correct focal distance from the printed material.
The base should be kept in contact with the
reading material at all times while moving the
magnifier across the page.
4. Look directly through the center of the lens to
minimize distortion of the letters.
5. Bring the eyes as close to the magnifier as is
comfortable. Although this will not increase the
size of the print, it will enable you to see more
letters at one time.
6. Many individuals find that it helps to wear their
spectacle correction while using the illuminated
magnifier.
7. Keep the magnifier in a protective case and clean
with a soft cotton cloth.
Using Monocular Telescope
1. The telescope can be focused by turning the eye
piece.
2. The following techniques may be used to stabilize
the aid and minimize the “movement” of the
viewed object:
• When sitting, rest both elbows on a table or
desk while holding the aid
• When standing, hold the aid with one hand
while using the other hand to grasp the bent
elbow of the hand holding the telescope.
• When standing, hold the aid with both hands,
bringing the arms in firmly close to the body.
3. To find a distant object with the telescope:
• First use unaided vision to determine the
general location of the object
• Then, keeping the eye and head still, raise
the telescope and look through it to locate the
object
• When the object has been located, focus the
telescope so that the image is clear and sharp.
4. Use a systematic search pattern. When looking
for a vertical object like a pole, slowly look back
and forth in a horizontal pattern. If you are
looking for a horizontal object like a sentence
written on a blackboard, slowly look up and down
in a vertical pattern.
5. When using the telescope be very careful not to
scratch your glasses, especially if they have plastic
lenses.
6. If glasses are worn while using the telescope, the
field of view will be smaller than usual. It may be
necessary to practice without the spectacle
correction at first.
7. When the telescope is not in use, store it in the
carrying case to prevent scratching the lenses. A
neck strap helps to keep the telescope safe and
accessible.
Nonoptical Devices (Supplementary Devices)
The non-optical devices enable the low vision patient
to function more independently and helps improve
their quality of life. The following instructions are
mandatory to the incumbents.
Writing Guide
1. Place the letter writer in the correct position (black
portion of the guide with the cuts facing upwards).
2. Open the letter writer like a book and put the
writing paper inside the guide. Make sure that
the corners of the writing paper fall within the
four corners of the guide and close the book.
3. Feel and find the empty cut out spaces in the letter
writer and start writing.
4. Identify the end of each line by feeling the
elevated mark on the guide
Signature Guide
A rectangular black card with a rectangular cut out
in the middle of the card
1. Ask a friend to make a mark ( ) on the place where
you need to sign
2. Place the signature guide next to the marked place
3. Hold the signature guide firmly in place by using
your thumb and index finger.
4. Find the empty cut out space in the signature guide
with your fingers and start writing in the cut out
portion
Reading Lamp
1. Visually impaired persons need more light (illumi-
nation) when reading, to improve the contrast of
the print
2. The contrast can be improved by bringing the light
closer to the printed material
 Chapter 147: Low Vision Devices
3. The light should be directed towards the printed
material and not towards the eye
4. The 60 W incandescent and 11 W. fluorescent bulbs
used in the reading lamp are easily available at all
electrical shops
5. Use a soft cloth to clean the lamp gently once a
week.
Notex: Money/Currency Identifying Strip
1. Feel the notex with your fingers, you will find
the single cut edge in the left hand lower corner
and seven serrated edges in the right hand top
corner.
2. Now place the particular currency note behind
the notex
3. Make sure the corners of the currency note are
properly aligned with the notex at the top edge
of the note
4. Commit to memory the corresponding currency
note and the respective cuts. The 1st cut indicates
500/-; 2nd-100/-; 3rd-50/-; 4th-10/-; 5th- 5/-; 6th-
2/-; 7th-1/-.
5. To find out the difference between a twenty-rupee
note and a fifty-rupee note, touch the side cut at
the bottom left hand corner of the notex. (The
twenty-rupee note is a narrower one and will not
cross the cut at the bottom of the notex. A fifty-
rupee note will cross beyond the cut as it is
broader and covers the full length of the notex).
Needle Threader
1. Hold the needle with left hand, the hole of the
needle facing upward
2. Hold the needle threader in the right hand
3. Insert the needle threader into the needle by
slightly pressing the needle threader in the middle
of the needle hold
4. Make the beginning point of the thread slightly
thicker by 2 or 3 folds
5. Insert the thread into the threader
• Hold the thread and needle threader together
with one hand
• Now pull the needle threader outward using
the free hand
Assistive and Adaptive Devices
Video Magnifiers—Closed-circuit
Television (CCTV) Fig. 147.6
CCTV utilizes a camera (zoom lens and built in illumi-
1167
Fig. 147.6: Video magnifier
nation) and a monitor. An enlarged image is electro-
nically projected on to the monitor. The magnification
is the ratio of object size to the image size. However,
extra magnification can be achieved by moving closer
to the monitor.
Magnification being displayed
Equivalent viewing power =
Dioptric demand of the working distance
Power range 5 x to 20 x
Computer Systems
Computer systems are becoming increasing popular
among the visually impaired, particularly for help
with reading tasks. Internet access is an additional
benefit of using computers. The computer system can
be modified by large print software or with hardware
for use by visually impaired persons. Speech synthesis
is available as a non-visual option. Patients may
combine visual and non-visual options for greater
flexibility (Zoom Text & Jaws for Windows).
Field Utilization Device
Field utilization devices are occasionally prescribed
for use by Retinitis pigmentosa patients.
1. Fresnel Prisms are wedges of prisms in powers
ranging from 10-30 σ Ds which could be attached
to the outer edge of the spectacles with base
towards the peripheral field defects. Patients with
field loss of < 10° are good candidates for this
device. However, no improvement is seen in
patients with visual acuity of < 20 to 200. Patients
using the device complain of blurred and double
1168 Section 9: Miscellaneous Topics
vision.
2. Reverse Telescope are useful in patients with good
central acuity. The images are minified so that
more and more information could be compressed
on to the small central functional area in the retina.
These are available as hand held or spectacle
mounted.
Night Vision Devices
Symptoms of night blindness in Retinitis pigmentosa
may be alleviated using night vision devices. The
small amount of light in dim photopic and scotopic
conditions could be intensified upto 750 times. It
provides one X magnification and 40° field of view.
Concluding Remark
Low vision care could be offered in a variety of
settings, including: hospital clinics, private practices,
vision rehabilitation organizations and teaching
institutions. Each setting has its own unique charac-
teristics and constraints.
As physicians, ophthalmologists can render care
to the whole person, not just the eye. Every effort
should be made to help patients achieve a positive
attitude about their capabilities to use residual vision
successfully and to live a full, enjoyable life as a
visually impaired person. A positive attitude, more
than any other factor, serves to minimize the handicap
caused by visual impairment.
Equipment Required for Low Vision Clinic
1. High and low contrast visual acuity charts for
distance and near vision
2. Retinoscope
3. Trial frame (both adult and children)
4. Trial lenses (preferably full diameter)
5. Ishihara test chart for color vision
6. Amsler grid
7. Titmus fly stereo test for binocular vision
8. Perimetry
REFERENCES
1. Thylefors B. A global initiative for the elimination of avoidable
blindness. Indian J Ophthalmol 1998;46:129.
2. World Health Organization. Blindness and Visual Disability.
Fact sheet No. 146. Geneva: World Health Organization 1997.
3. World Health Organization. The management of low vision
care for the elderly. Workshop of WHO/PBL. Madrid: World
Health Organization 1996;96:57.
4. Weale RA. Human biological decline and mortality rates. Mech
Ageing Denel 1997;907:55.
5. The World Bank. World Development Report. Knowledge for
Development. New York: Oxford University Press 1999;190.
6. Central Bureau of Health Intelligence, Ministry of Health and
Family Welfare. Health Information India. New Delhi:
Government of India 1991;56.
7. Anonymous. Human Development Report. United Nations
Development Program. New York: Oxford University Press
1999;164.
8. Dandona R, Dandona L, Srinivas M, Giridhar P, Nutheti R,
Prasad MN. Planning Low Vision Services in India: A
population-based prospective. Ophthalmology 2002;
109:1871.
9. Dandona L, Dandona R, Naduvilath JJ et al. Burden of
moderate visual impairment in an urban population in
southern India. Ophthalmology 1999;106:497.
10. Foster A, Gilbert CE. Epidemiology of childhood blindness.
Eye 1992;6:173.
11. Dandona L,William JD,Williams BC, Rao GN. Population-
based assessment of childhood blindness in southern India.
Arch Ophthalmol 1998;116:545.
12. Shamanna BR, Dandona L, Rao GN. Economic burden of
blindness in India. Indian Journal of Ophthalmology 1998;
46:169.
13. Rahi JS, Sripathi S, Gilbert CE, Foster A. Childhood blindness
in India: Causes in 1318 blind school students in nine states.
Eye 1995;9:545.
14. World Health Organization. Preventing blindness in children.
WHO/PBL/00. 1999;77.
15. Pararajasegaram R. VISION 2020: The Right to Sight: from
strategies to action (editorial). Am J Ophthalmol 1999;
128:359.
16. Programme for the prevention of blindness and deafness, World
Health Organization. Global Initiative for the elimination of
avoidable blindness. Geneva: WHO 1997.
17. Thylefors B. A global initiative for the elimination of avoidable
blindness. (editorial). Am J Ophthalmol 1998;125:90.
18. Foster A. VISION 2020: The Right to Sight, IAPB News. 25, p.
3, 2000.
19. World Health Organization. Management of Low Vision in
Children. WHO/PBL/93.27. Geneva: World Health Orga-
nization 1993.
20. Arditi A, Rosenthal B. Developing an Objective Definition of
Visual Impairment. New York: Arlene R. Gordon Research
Institute. The Lighthouse Inc., 1996.
21. Colenbrander A. International Classification of Impairments,
Disabilities and Handicaps. Geneva: World Health Orga-
nization 1980.
22. Kestenbaum A, Sturman RM. Reading glasses for patients
with very poor vision. Arch Ophthalmol 1956;56:451.
23. Eaglestin A, Rapaport S. Prediction of low vision aid usage. J
Visual Impair Blindness 1991;85:31.
24. Faye EE (Ed). Clinical Low Vision. 2nd edn. Boston: Little
Brown & Co; 1984.
25. Fonda GE. Designing half-eye binocular spectacle magnifier.
Surv Ophthalmol 1991;36:149.
26. Fonda GE. Optical treatment of impaired vision. J Visual
Impair Blindness 1992;86:86.
27. Koenig AJ, Layton CA, Ross DB. The relative effectiveness of
reading in large print and with low vision devices for students
with low vision. J Visual Impair Blindness 1992;86:48.
28. Moss GS. Considerations on dispensing low vision devices.
J Visual Impair Blindness 1992;86:88.
 Chapter 148

Amniotic Membrane
Transplantation in
Ophthalmic Disorders
Anita Panda, Hrishikesh Das

BACKGROUND pterygia.23 Lavery24 in 1946 and Sorsby in 1946 and

The use of amniotic membrane (AM) dates back to
1910, when Davis first reported the use of fetal
membrane as surgical material.1 Encouraged by his
work, Stern 2 and Sabella 3 reported the use of
“Amniotic Membrane” on burned ulcerated skin
surface. Greater symptomatic relief, faster re-epithe-
lialization and non-development of secondary wound
infection were the important observations.3,4 Despite
the unique and exciting observations no importance
was given to the subject till Brindeau (1935) and Burger
(1937) reported the use of “amnion” as graft in forming
an artificial vagina.5,6 Though there were technical
difficulties for performing the surgery, patients gained
both anatomically and functionally. Total dis-
appearance of AM cells and replacement with normal
epithelial cells from the introitus excited the authors
to proceed in their research further.3,4 De Rotth in 1940
implanted the AM experimentally in the peritoneum
of dogs but did not achieve favorable results7. Same
year, Chao and associates performed successful AM
transplantation to prevent meningocerebral adhesion
after head injury7 following which, it is being utilized
as a biological dressing material in burns,8 surgical
wounds, 8-11 chronic leg ulcers, 13,14 skin graft, 12
vaginoplasty,15,17 omphaloceles repair,18 abdominal,19
head, 6 pelvis, cardiac and otolaryngological
surgeries.20,21
de Rotth, is credited for using the AM first time in
ophthalmology to close conjunctival defects in
1947 described AM transplantation in caustic burns
of the eye.24-26 Although they found good results, it
was not widely accepted as a good treatment
modality. Thereafter, the subject of AM trans-
plantation was not given any attention for about 5
decades and has re-emerged in 1995 as a useful
transplant material. 27 Presently, the AM trans-
plantation has been widely accepted as a potential
treatment modality in diverse ocular disorders.28-41
While the routine clinical use as a biological membrane
is in progress, a number of simultaneous experimental
works have been carried out to strengthen its scientific
value and to establish the amnion bank.42-44
EMBRYOLOGY, ANATOMY, PHYSIOLOGY
AND HISTOPATHOLOGY OF AM
The human embryo lies in a fluid-filled sac that
originates from the extraembryonic tissues namely the
epiblast. The fetal membranes essentially have two
main layers, the amnion and the chorion. Amniotic
membrane (AM) is the innermost layer of the fetal
membranes first identified at 7th or 8th day of
embryonic development. It provides the tensile
strength to the fetal membranes. AM essentially
comprises of a stromal matrix, a collagen layer, and
an overlying basement membrane with a single layer
of epithelial cells making up a total of five distinct
layers. The inner surface, which lies in contact with
the amniotic fluid, is an uninterrupted single layer of
1170 Section 9: Miscellaneous Topics
cuboidal epithelium derived from the embryonic
ectoderm. The epithelial cells have numerous
microvilli over the surface and lateral aspect of the
cells. The cytoplasmic core of the microvilli has a fine
fibrillar structure, probably supportive in function.
The cells are united at the surface by desmosomes,
which are also present at intervals along the lateral
membranes of the cells. The ultrastructure of the
epithelium suggests that the amnion is metabolically-
active. The AM epithelium has been documented to
survive for up to 70 days with preservation and for
6 months at a temperature of –80 degrees centigrade.
The outermost layer of the amnion is contiguous with
the second fetal membrane, the chorion laeve. The AM
lacks nerves, lymphatics and blood vessels. The tensile
strength of the AM is due to the compact layer that is
composed of cross-linked interstitial collagen.
Collagen III is primarily responsible for its extensibi-
lity and tensile strength. The interstitial collagens also
provide resistance to proteolytic degradation. It does
not express HLA-A, B or DR antigens which accounts
for its non-immunogenicity.43-44
Fully-formed human AM is 0.2 to 0.5 mm thick.45
It consists of a single layer of ectodermally-derived
columnar epithelium firmly fixed to an underlying
layer of basement membrane (BM).46 The basement
membrane is a thick and continuous membrane and
is constituted by collagen type IV, V and laminin.47,48
Additionally, collagens I through III and V are also
present in human placental amnion.49 The epithelium
of AM produces various growth factors including
basic fibroblast growth factor, hepatocyte growth
factor and transforming growth factor ß.50-53 These
growth factors may modulate the differentiation and
proliferation of conjunctival and corneal epithelium.
FUNCTIONS OF AM
The two basic functions of AM are:
1. Promotion of epithelialization32,54
2. Inhibition of fibrosis50, 55
Following factors explain the function:
1. AM contains various matrix proteins, which faci-
litate the basal epithelial cell migration, adhesion,
and differentiation and prevents the apoptosis of
the epithelial cells.57 This characteristic has special
value in ocular surface disorders.
2. The AM is also capable of binding growth factors,
which may help to promote wound healing. These
growth factors are transferring growth factor TGF
ß 1 and 2, basic fibroblast growth factor (b FGF)
and hepatocyte growth factor (HGF).34,50 Thus, AM
acts as a storehouse of different growth factors like
basic fibroblast growth factor, hepatocytic growth
factor and transforming growth factor, which also
enhances epithelialization.50-52
3. The antifibroblastic properties of AM are because
of down regulation of the fibroblastic receptors.
4. It reduces inflammation by inhibiting chemokines
release by fibroblast and interleukin -1 secreation
by epithelial cells.57
5. It also contains anti-inflammatory proteins and
protease inhibitors like tissue inhibitor of metallo-
proteinase (TIMPs).54
6. It contains anti-angiogenic proteins, which inhibit
neovascularization by inhibiting vascular endo-
thelial cell growth.58
Besides, the AM also has few more properties
such as:
1. Antimicrobial effect59,60
2. Antiadhesive effect 61-63
3. Wound protection
4. Pain reduction
Kim et al in 1998 also showed that AMT reduces
the protease activity in chemical burns, which makes
it a transplant material of choice in such conditions.54
The transparency of AM allows an ambulatory vision
to the patient even when it is applied over the corneal
surface. More precisely, it becomes indistinguishable
from subconjunctival tissue once covered by the
conjunctiva. Because of these special properties, it is
considered to be an excellent transplantation material
for ocular surface. The immunological reactivity of
AM has been extensively studied. Since it does not
express the HLA A, B or DR antigens on their
surface43,44, the rejection reactions of the transplant are
not known. Because of Its antimicrobial properties it
is an accepted membrane for transplantation in corneal
ulcers.41,61 Its tough basement membrane acts as a
scaffold for growing epithelium thereby promoting
epithelialization.
TISSUE HARVESTING AND USE
Tissue procurement and processing must be under
totally sterile conditions and a strict quality control
over the entire asepsis should be maintained. The
human placenta is obtained shortly after an elective
caesarean section delivery from a mother who had
prior serological tests to rule out human Hepatitis type
A, B and C, syphilis, human immunodeficiency virus
(HIV) and human T cell leukemia virus. It is
mandatory to have a written consent for tissue
harvesting. Ideally the above tests, especially that for
 Chapter 148: Amniotic Membrane Transplantation in Ophthalmic Disorders
HIV are to be repeated 6 months post partum.
There are 3 methods to preserve the AM prior to
clinical use:
i. Freeze drying
ii. Freezing
iii. Hypothermic storage
PROCEDURE FOR OF HUMAN
AM PREPARATION AND PRESERVATION40
Procedure I
Under a laminar flow hood the placenta is cleaned of
blood clots with sterile Earle’s balanced saline solution
containing 50 mg/ml of streptomycin, 100 mg/ml of
neomycin and 3.5 mg/ml of amphotericin B. The
amnion is separated from the rest of the chorion by
blunt dissection through the potential spaces between
these two layers and flattened with the epithelial/
basement membrane surface up on to a nitrocellulose
paper having a pore size of 0.45 mm. The paper with
the adherent membrane is then cut into 4 × 4 cm disks
and stored before transplantation at minus 80°C in a
sterile vial containing Dulbecco modified Eagle
medium and glycerol at the ratio of 1:1. Prior to
surgery, the container with AM is thawed at room
temperature and the membrane is rinsed three times
in saline, followed by once more in saline containing
100 mg of dibekacin sulphate.
Procedure II
After washing the membrane either with physiological
saline or 0.01M phosphate buffered saline (PBS)
containing 100mg of dibekacin sulphate, the AM with
the chorion is separated from other tissue by blunt
dissection. The membrane is then cut into pieces
measuring 5 × 5 cm and rinsed three times in 0.01M
PBS. Each piece is rinsed in 0.5 M DMSO dissolved in
PBS, then in 1.9M and 1.5 M DMSO in PBS, for 5
minutes each. The membrane is placed in a plastic
container and preserved at –80°C until use. The
container with AM is rinsed three times in saline, then
once in saline containing 100mg of dibekacin sulphate.
At the time of surgery the AM is separated bluntly
from the underlying chorion with forceps..
The vials with membrane can be kept frozen upto
70 days. Upon use, the membrane is thawed for
10 minutes at room temperature and then soaked in
normal saline containing gentamicin (3 mg/ml) for at
least 3 minutes. The jelly-like materials (nitrose
cellulose paper) over the stromal side of the membrane
1171
is removed with meticulous care prior to placing over
recipient bed.
Procedure III
Alternatively, the fresh membrane can be used.58,64,65
The procedures from tissue harvesting till disk cutting
are similar to procedure I and II. Thereafter, the disks
are profusely irrigated and are aseptically stored in
vial with saline solution. No antibiotics or other rea-
gents are used for storage. It is kept in the refrigerator
at 4°C and is used before 24 hours.
Transmission of infectious agents is one of the
important risks associated with the transplantation of
AM and adequate care must be taken to prevent this.
The recipients of the AM graft must be assured that
the donors have been tested for infections but there
still exists a risk of transmission of certain agents
whose detection might not have been possible due to
the ‘window period’. Testing for cytomegalovirus and
Toxoplasma are not relevant for AM transplantation.40
Advantages of freezing /freeze drying of AM:
1. The ease of surgical manipulation of the tissue
2. Least chance of contamination.
3. Ready availability
CLINICAL USES OF AMT (Table 148.1)
Accordingly, AMT can be undertaken
alone 33,59,69,72,77,78,81,82 or may be combined with
other ocular surgeries like limbal stem cell trans-
plantation,28,34,35,70 Lamellar and penetrating kerato-
plasty.35,83 There are three basic components critical
to maintaining ocular surface integrity. They are:
1. The limbal stem cells or conjunctival epithelial cells,
which can differentiate into corneal epithelial cells
2. The basement membrane substrate and
3. Tear fluid.
Situation I
If the cell sources for epithelial regeneration and the
tear supply remain available, like in persistent
epithelial defect of different origins (e.g. Herpes
simplex virus keratitis)—then simple AM Trans-
plantation is indicated.
Situation II
Limbal stem cells deficient conditions with normal tear
secretion (e.g. chemical or thermal burns) require
limbal auto graft (for unilateral cases) or allograft (for
bilateral cases) in addition to AM transplantation.
1172 Section 9: Miscellaneous Topics
Situation III
In the most devastating situation, wherein basement
membrane, stem cells, and tear secretion are all
affected (e.g. Stevens Johnson Syndrome)—then
intensive dry-eye therapy, such as partial tarsorraphy
and serum eye drops are necessary along with limbal
cell and AM transplantation. Ocular surface conditions
with tissue destruction extending to deeper stroma
(e.g. Ocular Cicatricial pemphigoid) may need a
combined lamellar or penetrating keratoplasty along
with AM transplantation.28
INDICATIONS AND SURGICAL PROCEDURES
FOLLOWING ARE THE POSSIBLE SURGICAL
PROCEDURES
The indications are discussed under following
headings:
a. Simple AM transplantation
b. AM transplantation with limbal cell trans-
plantation (LT)
c. AM transplantation with lamellar /penetrating
keratoplasty (LK/PK
d. AMT with cyanoacrylate glue and human fibrin
glue84,85,86
e. Miscellaneous
SURGICAL TECHNIQUE
Surgical technique largely depends on the disorder
for which AMT is indicated. However, the basic
technique remains the same. Following peritomy at
the limbus, the perilimbal inflamed and scarred tissue
is removed to expose the bare sclera up to 5 to 7 mm
from the limbus. Abnormal vascularized corneal
epithelium and pannus are removed. The AM is then
removed from the storage media and brought under
room temperature. The membrane is peeled off from
nitrocellulose and fashioned into a size similar to the
defect found in the recipient eye. It is flattened over
the recipient bed the epithelial side facing up and is
then secured to the corneal edge of the defect by
interrupted 10-0 monofilament nylon. In cases of large
size defect (> 2 clock hours), AM is sutured to the
scleral side.
IDENTIFICATION OF EPITHELIAL SURFACE
The AM is sutured to the ocular surface where it acts
as a scaffold for epithelization to occur. It is of prime
importance to identify correctly the correct sides of
the membrane. This is easy when the tissue is fresh
but cumbersome in defrosted AM. Following methods
are described to achieve this identification correctly
• Mounting the membrane on the nitrocellulose
paper the right side up
• Putting a suture with its knot facing a particular
side,
• Marking with an indelible ink
• Scraping with a blunt forceps trying to lift up a
strand resembling the vitreous, which is only
possible from the mesenchymal side.
Simple AMT
Indications (Table 148.1)
• Persistent epithelial defect due to herpes simplex
keratitis (HSK)
• Entropion surgery
• Non-healing corneal ulcer (single or multilayer)
• Bullous keratopathy
• Following removal of band shaped keratopathy
• Corneal haze post photo therapeutic keratectomy
(PRK)
• Bare scleral area in the following conditions
a. Pterygium surgery
b. Excision of large limbal tumor
c. Symblepharon release
Table 148.1: AMT in ophthalmology
Ocular Surface Disorders
• Persistent epithelial defect33, 66,67
• Pterygium34, 68,69
• Post chemical surgery and thermal injury to cornea31,70-73
• Posttraumatic symblepharon34
• Following extensive tumor removal from conjunctiva and
cornea32, 58,70
• Deep corneal ulcers41, 74,75
• Neurotrophic cornel ulcers76
• Symptomatic Bullous keratopathy77
• Band shaped keratopathy78
Limbal Stem Cell Deficiency
• Stevens Johnson Syndrome28, 35,39,40,59, 72
• Toxic epidermal necrolysis (Pseudo pemphigoid)59,70,71
• Contact lens induced keratopathy71
• Aniridia71, 79
• Following multiple limbal surgeries71, 79
• Ocular cicatricial pemphigoid71
Glaucoma Surgery
• During trabeculectomy36
• Repair of over filtering and leaking bleb37, 80
Miscellaneous
• Entropion surgery
• Management of corneal haze following PRK29,30
 Chapter 148: Amniotic Membrane Transplantation in Ophthalmic Disorders
Persistent Epithelial Defect 33,66,67
The ulcerated area is debrided with a cellulose surgical
sponge. Then the AM is removed from its storage
medium, peeled off the nitrocellulose filter paper, and
is placed onto the recipient cornea to cover the debri-
ded area completely. The excess membrane is trimmed
off and is secured with multiple 10-0 Nylon or 9-0
polyglactin sutures.
If the defect is deep due to stromal ulceration then
more than one layer of AM can be used to fill the ulcer
crater.
Postoperatively bandage contact lens is applied
and topical antibiotic and topical corticosteroids are
administered until reepithelisation is completed.
Pterygium 34,68,69,83 After excising the pterygium, a
rectangular conjunctival defect of approximately 5 ×
7 to 6 × 8 mm, or even larger, is created. The bare
scleral area is then covered with preserved AM, which
is properly oriented. The AM is sutured through the
episcleral tissue to the edge of the conjunctiva along
the bare scleral border with 7 to 8 interrupted stitches
of 8-0 vicryl sutures.
For symblepharon34,83 The procedure is the same as in
pterygium surgery with the additional step of fornix
reformation and symblepharon ring application at the
end of the surgery.
For corneal ulcer 41,76 For single layer application the
procedure is same as that used in persistent epithelial
defect, the multilayer AMT has some special steps.
The base of the ulcer is to be debrided adequately,
following which the poorly attached epithelium at the
edge of the ulcer is removed as bluntly as possible.
After the apparently healthy area is visible a single
layer of the AM is placed over the exposed area.
Thereafter, small pieces of the membrane are cut and
stuffed into the depressed area caused by the ulcer.
The second layer of the membrane is placed over the
stuffed area with epithelial side facing up (This acts
as a basement membrane) and secured with 10-0 nylon
sutures. The third layer was put as a cover (AM patch)
up to the limbus with epithelial side up and sutured
with 10-0 nylon / 8-0 vicryl sutures.
LT + AMT 28,35,83
(LT = Limbal autograft transplantation)
Three sixty-degree peritomy is performed about two
mm posterior to the limbus and the limbal sub-
conjunctival scarred and inflamed tissue is removed
to the bare sclera up to 5-7 mm from the limbus. Then
1173
the corneal pannus is removed by blunt dissection (if
deep) or by cellulose sponge (Weck-cel and tissue
forceps) (if superficial). The exposed stromal surface
is made smooth by additional gentle scraping of the
entire limbal and the corneal surfaces. The bare area
is covered by the AM, which is sutured to the
conjunctiva and episclera, by 8/0 vicryl suture. A 360
cadaveric donor corneo limbal ring graft is obtained
by removing central 8 mm of corneal button. The
excess of scleral tissue is removed and it is flattened
in a petri dish with the epithelial surface facing down
on a viscoelastic cushion. The posterior layer of the
corneo limbal tissue (leaving the epithelium and 1/
3rd of the stroma is removed by a sharp vannas scissors
and forceps taking care to have this surface as smooth
as possible. The partial thickness corneo scleral ring
is then placed over the limbal area (can be modified
to two lenticules) and sutured to the conjunctiva with
episcleral anchorage by 8-0 vicryl sutures and to the
cornea by 10-0 monofilament nylon continuous
sutures.
LT + LK/PK + AMT 28,35,83
The peritomy and recipient preparation up to AMT is
same as that of LT + AMT. The central 7.5 mm LK/
PK is performed for optical purpose and eight
interrupted cardinal sutures with 10-0 monofilament
nylon are applied. The donor limbo-corneal ring is
prepared in similar manner to that of LT+AMT. Either
the whole doughnut shaped limbal tissue is placed at
the recipient limbus or cut at two ends to have two
lenticules. The limbo corneal tissue is placed over the
recipient limbal area to fit exactly with the outside
border of the central corneal button. Eight more
cardinal sutures are applied through the AM and
central corneal button and then the peripheral cornea
and donor ring graft/lenticule and the previous eight
cardinal sutures are removed. The limbal edge is
secured to conjunctiva with anchoring episcleral
sutures with 8-0 vicryl sutures. The AM covering the
central corneal button is cut and removed.
AMT with Glue Application84,85
This is indicated when there is corneal perforation.
The base of the ulcer is debrided gently and dried with
a cellulose sponge. A small drop of cyanoacrylate
tissue adhesive is applied to the perforation site with
the help of a 30-gauge needle fitted to a 1 ml glass
syringe. After polymerization of the cyanoacrylate
1174 Section 9: Miscellaneous Topics

glue, visco elastic is injected to the anterior chamber eye is patched till the next morning, after which steroid
through a side port incision to make the iris free from drops are administered four times a day, followed by
tissue adhesive and cornea. If there is incomplete tapering schedule. Antibiotic drops are given four
release, a thin iris repositor is inserted through the times per day for 1 week.
side port and the iris is made completely free from
adhesion. The AM is placed over the cyanoacrylate During Trabeculectomy36
glue and secured to the surrounding tissue with 10-0
The scleral flap is raised as in routine trabeculectomy.
monofilament nylon sutures.
An AM of 8 × 2 mm size with mesenchymal side facing
Alternatively, the AM 2 mm larger than the
the scleral bed is sutured in such a way that it does
perforation is placed on the perforated area over
not obstruct the proposed sclerosotomy site and a
viscoelastic cushion. The membrane is stretched
2 mm of membrane projects on either side of the scleral
completely and the cyanoacrylate glue is applied over
flap.The AM is sutured to the sclera at its corners with
the surface of the AM. A bandage contact lens is
10/0 monofilament nylon suture.The rest of the
applied. The glue falls within passage of time and the
procedure is continued as routine.
perforation is sealed.
During Entropion Surgery
Miscellaneous
AM is a useful alternative to mucous membrane
For Repair of Leaking Filtering Bleb37,80 for forming posterior lamina in case of cicatricial
entropion of the upper lid.
A conjunctival peritomy is performed, including
In all procedures, bandage contact lens application
2-3 mm of normal conjunctival adjacent to the existing
is recommended. For simple AMT the therapy
filtering bleb. The old filtering bleb is completely
includes tear substitute every hour and topical
excised and the conjunctiva adjacent to the previous
antibiotics and topical corticosteroids 4 times a day.
bleb is undermined 2-3 mm. Sutures are applied to
Postoperative management for the combined
the trabeculectomy flap if excessive flow of a shallow
surgery includes vigorous immunosuppression and
anterior chamber is noted. If excessive flow persists, a
tear supplements. Systemic cyclosporin is started 1
donor scleral patch graft can be used to limit excessive
day before surgery at a daily dose of 10 mg/kg. The
flow. The peripheral corneal epithelium is debrided
serum cyclosporin level is assessed weekly to achieve
in the area for a distance of 2-3 mm with a # 64 blade
a concentration of 100 to 150 ng/ml, and usual
or bipolar cautery to allow better adhesion of the
maintenance dose of cyclosporin is 2 to 4 mg/kg/day.
tissue. Preserved human AM prepared and cut into a
Kidney and liver functions are also monitored. Topical
rectangular or square shape of adequate length and
1% methyl predenisolone (preferably preservative
width to cover the defect in the conjunctive and extend
free) is initiated at every 2 hr and is tapered to about
at least 2 mm under the surrounding conjunctiva and
four times daily. A fluroqunolone is used for
onto the peripheral cornea. The membrane is inserted
antibacterial prophylaxis. If available, topical 0.05%
underneath healthy conjunctiva. The inferior corners
cyclosporin in alpha-cyclodextrine is also applied.
of the membrane are sutured to the peripheral cornea,
using interrupted 9-0 nylon sutures for fixation during
Ocular Surface Disorders58,67
suturing. 8-0 polyglactin suture on a vascular needle
is used to suture the AM to the underside of the Use of AM in ocular surface disorders like chemical
conjunctiva in the continuous running closure. The or thermal burns, decreasing scarring following
anterior edge of the membrane is sutured to the excimer laser photo ablation, advanced ocular
Bowman membrane using either 10-0 nylon mattress cicatricial pemphigoid and Stevens Johnson Syndrome
or 9-0-compression suture, which stretched across the is well established. AMT is a useful alternative
entire edge of the membrane-corneal interface. The substrate for conjunctival surface reconstruction
paracentesis tract is made to inject balanced salt during removal of large tumors, disfiguring scars or
solution into the anterior chamber to confirm flow into symblepheron, especially for those whose surroun-
the newly created filtering bleb and to check leaking ding conjunctiva, is relatively normal.32 Besides, its
with the Seidel test. All leaks are treated with role for management of PBK and BSK cannot be
additional suturing until Seidel testing is negative. The overemphasized.
 Chapter 148: Amniotic Membrane Transplantation in Ophthalmic Disorders
AM in Persistent Epithelial Defect (PED)
AM basement membrane facilitates migration of
epithelial32 cells reinforces adhesion of basal epithelial
cells, and promotes epithelial differentiation. It also
prevents apoptosis.56 These properties make AM a
useful treatment modality in treating PED. PEDs,
which are unresponsive to traditional management,
have shown adequate response to AMT. Lee and
Tseng33 demonstrated its efficacy in treatment of PED
with sterile ulceration in 11 patients. The patients had
non healing corneal ulceration for a mean of +SD of
17.5 + 13.9 weeks. After AMT, 10 patients healed
within 3.9 + 2.3 weeks without recurrence over a
follow up period of 9.0 + 5.9 months. The transplanted
AM became transparent or dissolved several months
later. On basis of results obtained commented that
AMT is an alternative method for treating PED and
sterile ulceration that are refractory to conventional
treatment They recommended AMT over conjunctival
flap or tarsorraphy as it provided better cosmesis and
visual acuity. Lekto et al in 2001 compared inlay and
overlay grafting in eyes with PED and did not find
any difference.69 However, there overall results were
sub optimal.
AMT in Corneal Ulcers
Role of AMT for the management of neurotrophic
ulcer is reported either alone or in combination with
limbal cell transplantation depending upon the
presence or absence of associated limbal cell defi-
ciency.76
AMT is a useful method for treatment of refractory
sterile corneal ulcers. A multilayer AM transplantation
(MAMT) has been recommended for deep corneal and
scleral ulcers.74 The study conducted by Kruse et al41
in 1999 proposed AMT for the treatment of deep
corneal ulcers by multilayer AM transplantation for
patients with deep corneal ulcers refractory to
conventional treatment. Multilayer AMT with cryo-
preserved human AM was done in all patients. It was
seen that AMT markedly reduced ocular inflammation
in all patients. Epithelium healed above all corneal
ulcers within 4 weeks and remained stable for 1 year.
Thus AMT allows corneal surface reconstruction in
patients with persistent corneal ulcers too. The
multilayer technique was found to be useful for
treating deep corneal ulcers and even descemetoceles.
Because the procedure results in stability of the ocular
surface over a period of more than 12 months in most
1175
patients, it was considered to be an alternative to
conventional surgical techniques for ocular surface
reconstruction.
Pterygium Surgery
Prabhasawat et al30 in 1997 compared the use of AMT
in pterygium surgery and compared it with primary
closure and autologous conjunctival transplantation.
They concluded that the relatively low recurrence rate
for primary pterygium operation allows one to use
AMT as an alternative first choice, especially for
advanced cases with bilateral heads or those who
might need glaucoma surgery later. Ma et al68 in 2000
compared the recurrence rate following AM graft for
primary pterygium with that of topical Mitomycin C
and found a comparable recurrence rates (3.8% for
AMT and 3.7% for Topical Mitomycin C). Schimazaki
et al34 studied the AMT and limbal auto grafts in
preventing recurrence in 4 patients with recurrent
pterygium with symblepharon followed up for of 59.8
weeks. There was marked improvement in ocular
mobility in 3 patients with significant suppression of
subconjunctival fibrosis.
Tekin et al in 2001 used non-preserved AM
following excision of primary pterygium and found
it quite effective.69
Pseudophakic Bullous Keratopathy (PBK)
AMT has been recommended as an alternative
procedure for painful PBK. Pires et al in 1999 tried
AMT in symptomatic bullous keratopathy with poor
visual potential.77,79 They observed decreased pain
and early epithelialization after AMT and recom-
mended it as an alternative to conjunctival flaps.
Following Management of
Band Shaped Keratopathy (BSK)
Anderson et al 2001 studied 16 eyes with BSK who
underwent surgical removal of calcific deposit, with
or without EDTA application with AMT suggested
AMT represents as a safe and effective method to
restore a stable corneal epithelium in these eyes.78
Acute Chemical Burns
AM though has been used in acute chemical burns by
various authors, its role however is debatable
especially in grade 3 and 4 burns. However, in chronic
stage it is very effective in mild chemical and thermal
1176 Section 9: Miscellaneous Topics
burns.31 In severe condition, it appears effective if it is
combined with autolimbal transplantation.
Su CY et al reported the combined use of AM and
cyanoacrylate glue.84 They applied AM and cyano-
acrylate glue in a perforated cornea following chemical
injury. The patient responded to this treatment and
after 6 months had a vision of 20/25.
Sridhar MS et al also studied the effect of AMT in
one case each of chemical and thermal burns with
more than 180 degrees of limbal ischemia87 within the
first weeks of injury. After 6 months of follow up, the
ocular surface was better in both the cases with
improvement of vision (20/25 in the alkali burn and
20/20 in the thermal injury).
In Stem Cell Deficiency
Anderson et al in 2001 studied 17 eyes with partial
stem cell deficiency and commented that the proce-
dure is alone sufficient for such eyes without any
limbal transplantation (LT). 72 therefore; it can be
performed as an alternative to LT also in early stage
of Stevens Johnson’s syndrome.
Total Limbal Stem Cell Deficiency
A number of studies have been carried out on the
subject of AMT with allo/auto LT with encouraging
results.28,35,39,40,59,72 It is also recommended the eyes
with total limbal stem cell deficiency and corneal
opacity requiring simultaneous lamellar/penetrating
keratoplasty depending upon the depth of the corneal
involvement. As these eyes are with severe dry eye,
use of auto serum drop (preservative free) along with
tarsorraphy has been recommended.28
Following Removal of OSSN
Mejfa et al in 2000 used non preserved AM for a
number of cases with ocular surface disorders inclu-
ding removal of extensive ocular surface squamous
neoplasia.88 They commented that AMT is a useful
technique for such eyes. They further added that non-
preserve AMT provides equal result as that of
preserved tissue. Considering the easy availability
they recommended the use of non-preserved AM
(NPAM).
Following Keratorefractive Surgery
Wang et al in 1997conducted an experimental study
in rabbits following PRK and found reduction of haze
after AMT. 29 Hong et al, on the basis of their
preliminary study has reported usefulness of AMT in
treating myopic regression with corneal haze after
photo refractive keratectomy (PRK) in high myopia.30
In Glaucoma Surgery
Because of its anti-adhesive property, which is
desirable after trabeculectomy or during repair leaking
bleb, AMT is advocated in closing leaking blebs and
to improve the success of trabeculectomy. As AM
epithelizes rapidly and integrates to surrounding
conjunctiva, has high hydraulic conductivity,
antifbrotic properties and a low immune response
potential, it is considered as an ideal tissue for the
repair of leaking filtering bleb.37 The AM reduces
subconjunctival fibrosis and promotes filtration when
placed under the scleral flap. Fujishima et al 36
reported a better outcome of trabeculectomy in a small
series of uncontrollable glaucoma where AMT was
supplemented with Mitomycin C. The mature AM
bleb is typically avascular and similar in appearance
to a bleb that has received antimetabolite; therefore,
it may be prone to late leakage in the same manner as
mitomycin blebs.
As Epithelial Cell Carrier
More recently, Koizumi N et al in 2000 examined the
viability of AMs as a culture material for procuring
corneal epithelial cells by transplanting them into
severely injured rabbit corneas.86 A confluent primary
culture of limbal corneal epithelial cells was esta-
blished on a cellular human AM after 14 days. Cells
were partially stratified and fairly well attached to the
underlying AM, although a fully formed basement
membrane was not evident. Thus they concluded that
autologous transplantation of cultivated corneal
epithelium is feasible by using acellular AM as a
carrier.86
To sum up, AM has brought a revolution for
ophthalmologists. It has become a panacea for treat-
ment of ocular surface disorders. Its easy availability
and storage, lack of immunogenicity, antimicrobial
and antifibrotic properties make it a biological tissue
of choice for ocular surface reconstruction. It is
predicted that AMT will remain a panacea to all the
ocular surface disorders. Thus, in the years to come,
AMT will become a major tool in the hands of the
corneal surgeon not only in these areas, but also in
many more disorders.
 Chapter 148: Amniotic Membrane Transplantation in Ophthalmic Disorders
REFERENCES
1. Davis JW. Skin transplantation with a review 550 cases at
The Johns Hopkins Hospital. John Hopkins Medical Jour
1910;15:307.
2. Stern M. The grafting of preserved AM to burned and
ulcerated surfaces. J. Am Med Assoc 973;1913;60.
3. Sabella N. Use of the fetal membranes in skin grafting. Med
Rec N Y 1913;83:478-80.
4. John D Trelford, Marilyn Trelfords The amnion in Surgery,
Past & Present, Am. J. Obstet. Gynecol 1979;134:833.
5. Brindeau A. Creation d’un vagina artificial a L’aide des
memb. Ovularies. Gynecol. Obstelet 1934;29:385.
6. Burger K. Experimental and clinical studies on transplantation
of the fetal membranes. Orv Hetil 1938;82:800.
7. Chao YC, Humphreys S, Penfield WA. new method of
preventing adhesions. The use of amnioplastin after
craniotomy. Br Med J 1940;1:517.
8. Douglas B. Homografts of fetal membranes as a covering for
large wounds especially in burns. Tenn State Med J
1952;45:230.
9. Colocho G, Graham WP, GreeneAE, Matheson DW, Lynch
D. Human AM as a physiologic wound dressing. Arch Surg
1974;109:370.
10. Chuntrasakal C. Clinical experiences with the use of AMs as
temporary dressing in treatment of burns and other surgical
wounds. Med Assoc. Thailand J 1977;60:66.
11. Talmi Yp, Kinckelstein Y. Zohar Y use of human AM is a
biological dressing. Eur J Plastic Surg 1990;13:160.
12. Subrahmanyam M. AM as a cover for micro skin grafts. Br J.
Plastic surg 1995;48:477
13. Ward DJ, Bennett JP. The long-term results of the use of
human amnion in the treatment of leg ulcers. Br J Plastic Surg
1984;37:191.
14. Ward DJ, Bennett JP, Burgos H, et al. The healing of chronic
venous leg ulcers with prepared human amnion. Br J Plastic
Surg 1989;42:463.
15. Dhall K. Amnion graft for treatment of congential absence of
the vagina. Br. J. Obstet Gynaecol 1984;91:279.
16. Nisolle M, Donnez J. Vaginoplasty using AM in cases of
vaginal agenesis or after vaginectomy. J Gynecol Surg
1992;8:25.
17. Georgy MS, Aziz NL. Vaginoplasty using amnion graft: new
surgical technique using the laparoscopic transillumination
light. J Obset Gyanaecol 1996;16:262.
18. Tokomori K, Ohkura M, Kitano Y, et al. Advantages and
pitfalls of AMT far large unruptured omphalocele. J Paed
Surg 1992;27:882.
19. Badway SZA, baggish MS, elbary MM, Baltoya unis P.
Evaluation of tissue healing and adhesion formation after an
intra abdominal AMT. J Reproductive Med 1989;34:198.
20. Gharib M, Ure BM, Klose M. Use of amniotic grafts in the
repair of gastroschisis. Pediatr Surg Int 1996;11:96.
21. Douglas B, Conway H, Stark RB, Joslin D, Nieto Cano G. The
fate of homologous & heterologous chorionic transplants.
Plast. Reconstru. Surg 1954;13:125.
22. Zohar Y, Talmi YP, Finckelstein Y et al. Use of human AM in
otolaryngologic practice. Larynygoscope 1987;97:978.
23. de Rotth A. Plastic repair of conjunctival defects with fetal
membrane. Arch Ophthalmol 1940;23:522.
24. Lavery FS. Lime burn of conjunctiva and cornea treated with
amnioplastin graft. Trans Ophthalmol Soc UK 1946;66:668.
1177
25. Sorsby A, Symmons HM. AM grafts in caustic burns of the
eye (burns of second degree). Br J Ophthalmol 1946;30:337.
26. Sorsby A, Heythorne J, Reed H. Further experiene with AM
grafts in caustic burns of the eye. Br J Ophthalmol 1947;31:409.
27. Tsubota K, Toda I, Saito H, et al. Reconstruction of the corneal
epithelium by limbal allograft transplantation for severe
ocular surface disorders. Ophthalmology 1995;102:1486.
28. Tsubota K, Satake Y, Ohyama M, et al. Surgical reconstruction
of the ocular surface in advanced ocular cicatricial
pemphigoid and Stevens-Johnson syndrome. Am J Ophthal-
mol 1996;122:38.
29. Wang M, Gray T, Prabhasawat P, et al. Corneal haze is
reduced by amniotic membreane metrix in excimer laser
photoablation in rabbits. Invest Ophthalmol Vis Sci
1997;38:S405.
30. Choi YS, Kim JY, Wee WR, et al. Application of AM on corneal
wound healing after excimer laser PRK. Invest Ophthalmol
Vis Sci 1997;38:S536.
31. Shimazaki J, Yang H-Y, Tsubota K. AM transplantation for
ocular surface reconstruction in patients with chemical and
thermal burns. Ophthalmology 1997;104:2068.
32. Tseng SCG, Prabhasawat P, Lee S-H. AMT for conjunctival
surface reconstruction. Am. Jour Ophthalmol 1997;124:765.
33. Lee SH, Tseng SCG. AM transplantation for persistent
epithelial defects with ulceration. Am J Ophthalmol
1997;123:303.
34. Shimazaki J, Shinozaki N, Tsubota K. Transplantation of AM
and limbal autograft for patients with recurrent pterygium
associated with symblepharon. Br J Ophthalmol 1998;82:235.
35. Tseng SCG, Prabhasawat P, Barton K, et al. AM trans-
plantation with or without limbal allografts for corneal
surface reconstruciton in patients with limbal stem cell
deficiency. Arch Ophthamol 1998;116:431.
36. Fujishima H, Shimazaki J, Shinozaki N, et al. Trabeculectomy
with the use of AM for uncontrollable glaucoma. Ophthalmic
Surg Lasers 1988;29:428.
37. Budenz DL, barton K, Tseng SCG. Repair of leaking glaucoma
filtering blebs using preserved human AM graft. Invest
Ophthalmol Vis Sci 1998;39:93.
38. Hong JW, Kang SM, Kim HJ, et al. The effect of photo-
therapeutic keratectomy (PTK) – AM transplantation (AMT)
on myopic regression with corneal opacity after PRK in high
myopia. Invest Ophthalmol Vis Sci 1998;39:S941.
39. Azuara-Blaco A, Pillai CT, Dua HS. AM transplantation for
ocular surface reconstruction. Br J Ophthalmol 1999;39:S90.
40. Harminder S Dua, Augusto Azuar-Blanco. AM trans-
plantation. Br J Ophthalmol 1999;83:748.
41. Kruse FE, Klaus R, Hans EV. Multilayer AMT for corneal
ulcers. Ophthalmology 1999;106:1504.
42. Dino BR, Eufemio GG, Devilla MS. Human amnion. The
establishment of an amnion bank and its practical application
in surg. J Philippine Med Assoc 1966;42:357.
43. Adinolfi M, Akle CA, McColl I et al. statement of HLA
antigens by amniotic membrane. Nature 1982;295:325.
44. Akle CA, Adinolfi M, Welsh Kl et a. Immunogenicity of
human amniotic membrane. Lancet 1981;2:1003.
45. Van Herendel BJ, Oberti C, Brosens I. Microanatomy of the
human amniotic membranes. Am J Obstet Gynecol 1978;
131:872.
46. Pollard SM, Aye NN, Simmonds EM. Scanning electron
microscopic appearance of normal human amnion and
umbilical cord at term. Br. J Obstet Gynaecol 1976;83:470.
1178 Section 9: Miscellaneous Topics
47. Modesti A, Scarpa S, D’Orazi G et al. Localization of type IV
& V collagens in the stroma of human amnion. Prog Clin Biol
Res 1989;296:459.
48. Fukuda K, Chikama T, Nakamura M, Nishida T. Differential
distribution of subchaines of the basement membrane
components type IV collagen and laminin among AM, Cornea
and Conjunctiva. Cornea 1999;18:73.
49. Polzin WJ, Lockrow EG, Morishige WK. A pilot study
identifying type V collagenolytic activity in human amniotic
fluid. Am J. Perinatol 1997;14:1-3.
50. Tseng SG, Li-D-Q, Ma X. Down regulation of TGBβ1, β2, β3,
and TGFβ receptor II expression in human corneal fibroblasts
by AM.Invest. Ophthalmol Vis Sci.1998;39:s428. J. Cell Physiol
1995;163:61.
51. Sato H, Shimazaki J, Shimazaki N et al. Role of growth factors
for os reconstruction after AMT. Invest Ophthalmol Vis Sci
1998;39:5428.
52. Tseng SCG, Lee SB, Li DG et al. Suppression of TGFβ
signaling. Invest Ophthalmol Vis Sci 1999;40 S 579.
53. Tseng SCG, Li DG, Ma X. Supression of transforming growth
factors. J. Cell Physiol 1999;179:325.
54. Kim JS, Park Sw, Kim JH et al. Temporary AM graft promotes
healing and inhibits protease activity in corneal wound. Invest
Ophthalmol Vis Sci 1998;39:590.
55. Li DW, Tseng SCG. Three patterns of cytokine expression
potentially involved in epithelial fibroblast interaction of
human ocular surface. J Cell Physiol 1998;163:61.
56. Bourdreau N, Sympson CJ, Werb Z, Bissell MJ. Suppression
of ICE and apoptosis in mammary epithelial cells by extra
cellular matrix. Science 1995;267:891.
57. Shimmura S, Shimazaki J, Ohasi Y, Tsubota K. Anti-
inflammatory effects of AM transplantation in ocular surface
disorders. Cornea 2001;20:408.
58. Mejia LF, Acosta C, Santamaria JP. Use of non-preserved
human amniotic membrane for reconstruction of the ocular
surface. Corneal 2000;19:288.
59. Trelford JD, Trelford-Sauder M. The amnion in surgery past
and present. Am J Obstet Gynaecol 1979;134:833.
60. Talmi UP,Sigler L,Inge E.Antibacterial property of human
AM.Placenta 1991;12:285.
61. Tayyar M, Turan R, Ajaza D. The use of AM plus heparin to
prevent postoperative adhesions in the rabbit. Tokai J Exp
Clin Med 1993;18:57.
62. Rennekampff HO, Dohrmann P, Fory R, Fandrich F.
Evaluation of AM as adhesion prophylaxis in a novel surgical
model. J Invest Surg 1994;7:187.
63. Vander Linden PJQ, Edrkers HWH, de Goeij AFPM et al. Cell
adhesion in an in vivo model using intact AM. Feril Steril
1996;65:76.
64. Panda A. Preserved vs Fresh AM transplantation. Am J
Ophthalmol 1999;83:1410.
65. Philip JA, Charles J. Hund, John KG Dart. AMT, fresh or
frozen. Br J Ophthalmol 2001;85:905.
66. Prabhasawat P, Teasavibul N, Kamolsuradej W. Single and
multilayered AM transplantation for persistent epithelial
defect with and without stromal thinning and perforation.
Br J Ophthalmol 2001;85:1455.
67. Letko E, Stechschulte US,Kenyon KR, Sadeq N, Romero RT,
Samson MC et al.AM inlay and overlay grafting for corneal
epithelial defects and stromal ulcers.Arch. Ophthalmol
2001;119:659.
68. Ma DHK, See LC, Liau SB, Tsai RJF. AMT for primary
pterygium. Br J Ophthalmol 2000;84:973.
69. Tekin NF, Kaynak S, Saatci AO, Cingil G.Preserved human
AM transplantation in the treatment of primary ptery-
gium.Ophthal. Surg.Lasers 2001;32:464.
70. Tsai RJF, Li ml, Chen JK.Reconstruction of damaged corneas
by transplantation of autologous limbal epithelial cells. N Eng
J Med 2000;343:86.
71. Prabhasawat P, Tseng SCG. Impression cytology study of
epithelial phenotype. Arch Ophthalmol 1997;115:1360.
72. Anderson DF, Ellies P, Pires RTF, Tseng SCG. Amniotic
memebrane transplantation for partial limbal defiency. Br J
Ophthalmol 2001;85:567.
73. Stoiber J, Muss WH, Gubo PG, Ruckhofer J, Grabner G.
Histopathology of human corneas after AM and limbal stem
cell transplantation for severe chemical burn.Cornea.
2002;21:482.
74. Hanada K, Schimazki J, Shimura S, Tsubota K.Multilayered
AM transplantation for severe ulceration of the cornea and
sclera. Am J Ophthalmol 2001;131:324.
75. Ma DHK, Wang SF, Su WY, Tsai RJF. AM graft for
management of scleral melting and corneal perforation in
recalcitrant infectious scleral and corneo scleral ulcers. Cornea
2002;21:275.
76. Hong J, Chen, Pires TF, Tseng SCG. AMT in neurotrophic
ulcer. Br J Ophthalmol 2000;84:826.
77. Mejfa LF, Santamaria JP, Acosta C. Symptomatic management
of postoperative bullous keratopathy with non-preserved
human AM. Cornea 2002;21:342.
78. Anderson DF, Prabhasawat P, Alfonso E, Tseng SCG. AM
transplantation after primary surgical management of band
keratopathy.Cornea 2001;20:354.
79. Pires RTF, Pires JL, Tseng SCG. Transplante de membrana.
Arq. Bras. Oftalmol 1999;62:340.
80. Azuara-Blanco A, Katz LJ. Dysfunctional filtering blebs.
Survey Ophthalmol 1998;43:93.
81. Shimura S, Shimazki J, Ohashi Y, Tsubota K. Antii-
nflammatory effects of AM transplantation in ocular surface
disorders. Cornea 2001;20:408.
82. Adds PJ, Hunt CJ, Dart JKG.Amnioticmembrane grafts,”
fresh” or frozen? A clinical and in vitro comparison. Br J
Ophthalmol 2001;85:905.
83. Kenyon KR, Tseng SCG,. Limbal autograft transplantation
for ocular surface disorders. Ophthalmology 1989;96:709.
84. Su CY, Lin CP.Combined use of an AM and tissue adhesive
in treating corneal perforation: A case report.Ophthalmic Surg
Lasers 2000;31:151.
85. Duchesne B, Tahi H, Galand A.Use of human fibrin glue and
AM transplantation in corneal perforation. Cornea 2002;
20:230.
86. Cohen EJ.Use of autologous limbal epithelial cells cultured
on AMs for unilateral stem cell deficiency.Arch. Ophthalmol
2001;119:123.
87. Sridhar MS, Bansal AK, Sangwan VS, Rao GN. AM
transplantation in acute chemical and thermal injury. Am J
Ophthalmol 2000;130:134.
88. Shield J, Shield CL, de Potter P. Surgical management of
conjunctival Tumor. The 1994 Lynn B Mc Mohan Lecture.
Arch Ophthalmol 1997;115:808.
 Chapter 149

Limbal Stem Cells of Corneal

Epithelium: Concepts, Disease
and Management
Himanshu P Malik, Virender S Sangwan

OCULAR SURFACE Table 149.1: Ocular surface functional unit

The ocular surface is the mucosal lining between upper 1. Corneal epithelium
2. Limbal epithelium
and lower eyelids, which is an interface between the
3. Conjunctival epithelium
eye and the outer world. The main function of the 4. Mucocutaneous junction of lids
ocular surface is to provide a quality refractive surface 5. Meibomian glands
for sharpest vision along with the protection to the 6. Lacrimal glands
eye from external stimuli. The components of ocular 7. Tear film
surface (Table 149.1) work as a functional unit. They
share a feed back mechanism and are in dynamic the corneal epithelium is devoid of goblet cells. The
equilibrium, constantly rejuvenating the ocular sur- other unique feature of corneal epithelium is its
face. The dynamic nature of ocular surface is mainly expression of specific cytokeratins (cytokeratins are
the responsibility of limbal and conjunctival stem cells, the cytoskeletal proteins) K3 and K12, which are
which are the source of newly generating epithelia.1 expressed by only the central corneal epithelium and
are not significantly found in limbal and conjunctival
Ocular Surface Epithelia epithelium.2
Corneal epithelium is a stratified squamous epithelium. Limbal epithelium is a stratified squamous epithelium
It has 5-6 layers of cells comprised of basal columnar comprising of 10-12 layers. The basal layer is thrown
cells, intermediate “wing cells” and the superficial into folds. The limbal epithelial stem cells are located
squamous cell. The superficial squamous cells shed in this region. It also has melanocytes and Langerhan’s
off and are replaced by new cells from beneath. The cells. The folds in basal layer help to accommodate
whole corneal epithelium is replaced by new cells large number of cells by increasing surface area and
within 7-10 days. The source of the basal corneal also help to supply nutrition by the blood vessels in
epithelial cells, which replace the superficial cells is this region.
the limbal stem cells (vide infra). The complete
epithelial turn over from limbal stem cells to shedding WHAT IS A STEM CELL?
off superficial squamous cells, takes nearly 9 months.
Definition
Characteristically, the corneal epithelium has got
desmosomes or tight junctions, which do not allow Stem cells are a small subpopulation of specialized
fluorescein to permeate through it. Unlike conjunctiva undifferentiated, self-renewing cells, which are
1180 Section 9: Miscellaneous Topics
capable of indefinite proliferation to large number of
differentiated progeny, responsible for the cellular
replacement and regeneration in all the self-renewing
tissues.2
Characteristics of Stem Cells
Stem cells are poorly differentiated cells with primitive
cytoplasm and very few differentiation products. They
have long cell cycle time (slow mitotic activity) and
long lifespan under steady state conditions. The stem
cells have unique property of self-renewal, as after the
cell division within stem cells one of the daughter cells
becomes parent and replenish the population of stem
cells. The other daughter cell divides and differentiates
into the specific cell type of that tissue. Based on cell
kinetics, all the cells in a self-renewing tissue can be
placed into either of the two compartments—
proliferative or non-proliferative. The cells in
proliferative compartment are capable of DNA
synthesis and cell division whereas cells in the non-
proliferative compartment differentiate and become
mature under the effect of surrounding tissue
environment. The serial steps of ‘clonogenic’ division
are summarized in (Fig. 149.1). The cells in the
proliferative compartment are stem cells (SC) and
transiently amplifying cells (TAC) that are derived
from mitotic division of stem cells and amplify by
undergoing a few rounds of cell division. Cells in non-
proliferative compartment are post-mitotic cells
(PMC) which are in different stages of maturation by
differentiation into the terminally differentiated cells
Fig. 149.1: Ocular surface epithelia covering the cornea, limbus and conjunctiva
(TDC). Thus, the cellular hierarchy of these self-
renewing tissues is comprised of different cell
population in the order of SC-TAC-PMC-TDC. SC
being the source and hence at the highest rank.1
CORNEAL EPITHELIAL STEM CELLS
The corneal epithelium has a dynamic equilibrium
with a constant replacement of dead and revitalized
cell by new cells from the peripheral basal layers.
Devanger and Evensen (Nature 1971) conceptualized
the corneal epithelial stem cells and suggested their
presence in the limbal area in palisades of Vogt. The
corneal epithelial stem cells are hypothesized to be
located at the limbus, however the methods to identify
these limbal stem cells are indirect.2,3
1. Corneal epithelium specific keratin pairs (cyto-
skeleton) K3/K12 are present in all over the cornea
but only in the superficial layers of epithelium at
limbus. Whereas the cells of the conjunctiva shows
presence of another keratin K19, which is absent
in limbal cells as well as corneal epithelial cells.
All these are suggestive of undifferentiated nature
of basal limbal epithelium.
2. Limbal basal epithelial cells have more prolife-
rative potential and slower cell cycle than central
corneal epithelial cells, suggestive of reservoir of
the epithelial cells.
3. Experimental removal of limbal epithelium results
in defective central corneal epithelium. In normal
eyes limbal epithelial defects heal faster than
central corneal epithelial defects.
 Chapter 149: Limbal Stem Cells of Corneal Epithelium: Concepts, Disease and Management
4. Ex-vivo cultivation of limbal epithelial cells and
encouraging results of its transplantation.
5. Relatively higher prevalence of limbal neoplasm
to central corneal neoplasm suggesting of more
undifferentiated cells at limbal than at the central
cornea.
6. Vortex pattern of corneal epithelium in toxic
keratopathy, melanokeratosis and superficial iron
lines suggest centripetal growth of the corneal
epithelial cells.
7. Mathematical model, suggestive of maintenance
of corneal epithelium by limbal stem cells, without
any help from conjunctival epithelial cells.
LIMBAL STEM CELLS DEFICIENCY (LSCD)
Introduction
Limbal stem cells being the source of newly generated
corneal epithelial cells, any injury to them can cause
severe derangement of ocular surface. The injury can
be an exogenous insult or a change in their micro-
environment (niche). The condition resulted from this
is called limbal stem cell deficiency. The concept of
limbal stem cells, as reported by Tseng,3 not only
helped us to understand the physiology of the limbal
stem cells but also helped us to understand its
pathology including its management.
Classification and Etiology
• Partial/focal LSCD-Total LSCD Limbal stem cell
deficiency can be classified depending upon the
extent of deficiency into partial/focal LSCD and
total LSCD (Fig. 149.5). Partial/focal LSCD is
characterized by partial/focal loss of stem cell
function with rest of the limbus being normal (e.g.
following multiple surgeries at limbus, cryo-
therapy, pterygium, less severe chemical/thermal
burns etc.). More severe condition where there is
total loss of limbal stem cells without any normal
area spared, is called as total LSCD (e.g. severe
chemical/thermal burns, Stevens-Johnson syn-
drome (SJS), advanced cicatricial pemphigoid,
contact lens wear etc.).
• Limbal stem cells—dysfunction versus destruction
Limbal stem cells dysfunction is usually primary
or hereditary and can be a part of other ocular or
systemic anomalies. Due to abnormal micro-
environment of the limbal tissues, the stem cells
never achieve their normal function. The condition
is usually bilateral and less severe as the rest of the
1181
ocular surface may be normal (e.g. aniridia,
keratitis associated with multiple endocrinal
deficiency). Limbal stem cells destruction is an
acquired loss of functioning stem cells. The condi-
tion can be unilateral or bilateral and associated
with severe ocular surface damage (e.g. chemical/
thermal burns, Stevens-Johnson syndrome, ocular
cicatricial pemphigoid, multiple surgeries or
cryotherapy to limbus, contact lens wear etc.).
• Etiological classification of LSCD The etiology of
LSCD is important for the assessment of extent and
severity of the damage, to prognosticate the case,
to plan other supportive surgical treatment and to
treat the cause, if possible. Table 149.2 shows
various causes of LSCD.
Clinical Features of LSCD
The clinical symptoms of LSCD are decreased vision,
redness, watering, photophobia and recurrent attacks
of pain due to repeated epithelial breakdown. The
hallmark of LSCD is a triad of conjunctivalization,
neovascularization and chronic inflammation. The
other features include loss of limbal palisades of Vogt,
fibrovascular pannus, persistent epithelial defect,
destruction of basement membrane and scarring.
Other manifestations of the etiology of LSCD may
further complicate the condition (e.g. extensive
symblephara, dry eye, lid anomalies, corneal melting,
etc.).
Table 149.2. Etiological classification of
limbal stem cells deficiency
1. Trauma
a. Chemical (acid, alkali, traditional medicines, un-
known)
b. Thermal
c. Radiational
d. Surgical (multiple surgeries at limbus, cyclocryo-
therapies, anti-glaucoma surgeries with anti-metabo-
lites, donor site: limbal transplant, multiple PKPs
2. Local (ocular) conditions
a. Post-infectious keratitis, neurotrophic keratitis
b. Tumour/malignancy at limbus
c. Aniridia
d. Contact lens use
e. Vernal kerato-conjunctivitis
3. Systemic conditions
a. Stevens-Johnson syndrome, ocular cicatricial pem-
phigoid
b. Multiple endocrine disorders
c. Systemic chemotherapy
4. Idiopathic
1182 Section 9: Miscellaneous Topics

Diagnosis of LSCD
The diagnosis of LSCD is mainly based on the history
and clinical signs, which can be confirmed by
laboratory tests like impression cytology, and
histopathology of the pannus. Impression cytology
performed with nitrocellulose acetate paper strips can
detect presence of goblet cells on the cornea; it can
also be used to perform immunohistochemistry for
different markers.

Management of Limbal Stem Cell Deficiency

The limbal stem cells are limited in number and they

do not regenerate. Due to this property of limbal stem
cells it is impossible to treat their deficiency by any
pharmacological agent. Apart from the definitive
treatment of LSCD, it is also important, if possible, to
take care of the cause responsible for the disease. The
management of LSCD requires a complex and step-
wise approach as recommended below.1,4
• The initial treatment is for non-specific or immune
mediated inflammation: Any surgical treatment in
an inflamed eye may not give desired results. The
active inflammation can also be detrimental to the
transplanted stem cells.
• Treatment of associated adnexal conditions: Most
of the time LSCD is associated with adnexal
abnormalities, especially in the conditions like
chemical burns, which is the most common cause
of LSCD in our series. It is very important to
manage the adnexal deformities before planning
any definitive surgical treatment.
• Management of dry eye: The conditions like SJS,
chemical burns, etc. can have LSCD and very
severe dry eye with poor quantity and as quality
of tear film. Normal ocular surface health requires
stable and normal tear film. Hence, it is mandatory
to treat the dry eye and its components before
limbal transplantation.
• Limbal stem cells transplantation
• ± Penetrating keratoplasty
Limbal Stem Cells Transplantation
Fig. 149.2: Algorithm of management of LSCD
SURGICAL TECHNIQUES OF
LIMBAL TRANSPLANTATION
Management of Partial LSCD
Non-progressive unilateral/partial LSCD left alone
but is to be observed. Progressive partial LSCD in a
small area can be dealt with repeated mechanical
debridement [sequential sector conjunctival epitheliec-
tomy (SSCE)]. More severe cases of partial LSCD can
be successfully treated by amniotic membrane
transplantation or ipsilateral conjunctiva limbal
autograft (CLAG).
Preparation of the Bed
Under peribulbar anesthesia, conjunctival peritomy
is performed 3-4 mm away from the limbus. The
pannus tissue is then “peeled off” or dissected with
No. 15 knife on Bard-Parker handle. The symblephara,
if present can be severed. A superficial keratectomy
is reserved for the cases where pannus cannot be
separated from the stroma. A drop of undiluted
(1:1000) adrenaline in conjunctival preoperatively will
help to control bleeding during the surgery. The
bleeding points can be cauterized with bi-polar wet
field cautery.

After first limbal transplant in human by Kenyon and AMNIOTIC MEMBRANE

Tseng in1989,11 the methods of limbal stem cells
transplant have under-gone remarkable changes in the
last decade. The management of LSCD varies with the
extent and bilaterality of the condition. Figure 149.2
shows algorithm of management of LSCD.
TRANSPLANTATION (AMT)
Introduction
Amniotic membrane (AM) has been used to restore
ocular surface, which not only decreases infla-
 Chapter 149: Limbal Stem Cells of Corneal Epithelium: Concepts, Disease and Management 1183
mmation, scarring and vascularization but also
provides a new basement membrane for the expansion
of surviving epithelial stem cells. The stroma of AM
can also prevent inflammatory cells, produces various
growth factors and several forms of protease inhibitors
(Figs 149.3 and 149.4).
Partial LSCD, as an adjuvant to CLAG, KLAL or Lr-
CLAL. It is used for cultivation of limbal epithelial stem
cells and is used as a carrier for the cultivated limbal
cell transplantation (Fig. 149.5).

Surgical Procedure
Fig. 149.3: Amniotic membrane transplantation (AMT)
Following preparation of the bed, a processed and
preserved amniotic membrane in Dulbeco’s modified
Eagles medium and glycerol at –80°C is spread over
the ocular surface with the epithelial side up. The
amniotic membrane is sutured in place with
6 circumferencial sutures with 10-0 nylon, monofila-
ment. The peripheral edge is sutured to conjunctiva
with 8-0 polyglactin sutures.

Current Status
It is a simple procedure and works in partial LSCD
and does not require immunosuppression also.
Anderson et al and our group have reported successful
reconstruction of ocular surface in partial LSCD of as Fig. 149.4: Live-related conjunctivolimbal allograft (Lr-CLAL).
much as 300°. However, in severe cases with Showing two lenticules from two donors each
symblephara it may not work. The availability of
preserved AM can also be a limiting factor. (ipsilateral CLAG) or from the other eye (contralateral
CLAG). A non-continuous 6 clock hours (3 superiorly
CONJUNCTIVAL LIMBAL AUTOGRAFT (CLAG) + 3 inferiorly) can be safely harvested from the donor
site. Each lenticule comprises of 4 × 4 mm size of
It is one of the earliest reported surgery for LSCD.
conjunctiva (without Tennon’s) with the limbus
Kenyon and Tseng were the first to report this surgery
including 1 mm of superficial clear corneal stroma.
especially for ocular surface reconstruction. As it does
According to the extent of LSCD, one/two lenticules
not need any allogenic tissue, it does not require
can be dissected from the donor site. These lenticules
immunosuppression. Unlike AMT, availability is not
are secured at donor site keeping their orientation
a limiting factor however, potential donor site LSCD
proper (i.e. epithelial side up and limbal area of the
may limit the size of donor tissue. Other than LSCD,
donor near the limbus). The limbal area is secured with
CLAG is widely performed along with the pterygium
2 circumferential sutures 10-0 nylon monofilament
excision.
and conjunctival part with 8-0 polyglactin.
Indication Immunosuppression Does not require immuno-
Partial LSCD/unilateral LSCD with or without suppression.
symblephara, pterygium excision, following excision
of a large tumour over the ocular surface. Current Status
CLAG is a useful procedure in partial LSCD with/
Surgical Procedure
without symblepheron specially when availability of
Following preparation of the bed, the donor tissue can AM is a problem. Donor site LSCD have been reported
be obtained from uninvolved areas of the same eye earlier, however, we believe it could be due to very
1184 Section 9: Miscellaneous Topics

A B

C D

E F

Figs 149.5A to F: Etiology of limbal stem cell deficiency: (A) Partial limbal stem cell deficiency following chemical burns, (B)
Total limbal stem cell deficiency with symblephara following chemical burns, (C) Total limbal stem cell deficiency following
severe active vernal keratoconjunctivitis (limbal form), (D) Total limbal stem cell deficiency following burnt-out vernal
keratoconjunctivitis (limbal form), (E) Total limbal stem cell deficiency following Mooren’s ulcer, (F) Total limbal stem cell deficiency
following ocular cicatricial pemphigoid
 Chapter 149: Limbal Stem Cells of Corneal Epithelium: Concepts, Disease and Management
deep dissection into the cornea. The surgery should
be performed in a relatively quiet eye for better results.
It can also be combined with AMT.
KERATOLIMBAL ALLOGRAFT (KLAL)
Introduction
KLAL is one of the most widely reported procedure
out of all the limbal transplantation. It involves use of
cadaveric tissue for the limbal transplantation. Being
an allogenic tissue it is mandatory to use immuno-
suppresants in these cases to avoid immunological
rejection.5 The advantage of KLAL is easy availability
of the donor tissue and repeatability of the procedure.
The limbal transplant surgery can also be combined
with Penetrating Keratoplasty (PKP) from the same
tissue, which would theoretically decrease the number
of alloantigens transplanted. However, viability of the
stem cells, its growth potential and long-term survival
following KLAL still remains questionable.
Indication
Bilateral LSCD, one-eyed patient with total LSCD, total
LSCD without availability of donor or culturing
technique (Fig. 149.6).
Surgical Procedure
Donor Tissue
Cadaveric donor tissue, the whole globe or
corneoscleral rim including limbus of a young donor
(< 50 mm), within 72 hrs of the death.
Donor Tissue Preparation
Donor tissue can be either dissected into multiple
limbal lenticules of partial thickness, which are
sutured on the recipient bed. Alternatively an annular
rim of peripheral cornea and limbus of 1/3 to 1/2
thickness can be dissected. The dissection can be
carried out either manually or using vacuum trephine
or microkeratome.
Donor Tissue Transplantation
Following preparation of the bed the lenticules are
secured to the limbus at its proper anatomical position
with 10-0 nylon monofilament. The procedure can be
combined with the AMT, which can be performed
before placing the lenticules. Simultaneous PKP from
the same donor can also be performed after KLAL,
which would theoretically decrease the number of
1185
alloantigen. Postoperative indefinite immuno-
supression following KLAL is mandatory to prevent
the rejection.
Current Status
Reported long-term survival of KLAL in different
study is not very encouraging. Soloman et al6 reported
success in 23.7 ± 13.4% at 5 years and Ilari et al7
reported success in 21.2% at 5 years. Results of
simultaneous PKP and KLAL are also very poor. In a
study by Ilari et al the failure rate was 93%.
LIVE RELATED DIRECT CONJUNCTIVAL
LIMBAL ALLOGRAFT (Lr-CLAL)
Introduction
The use of live related tissues for the transplantation
has definite edge over the use of cadaveric tissues. Not
only the growth potential of the tissues from live-
related donor is more, it also has better histo-
compatibility as it is from a first degree relative.8
However, the only concern in these cases would be
the availability of tissues, especially in cases of need
for the repeat surgery. The donor site LSCD is also a
possibility.
Indications
Bilateral total LSCD, one-eyed patient with total LSCD,
extensive symblephara and severe ocular surface
disorders. Very severe chemical burns, Stevens-
Johnson syndrome and oculocicatricial pemphegoid
are most common indications (Fig. 149.6).
Surgical Procedure
The procedure includes conjunctivo-limbal tissue
excision from the live-related donor (first-degree
relative). In case of total LSCD, tissue from 2 donors
can be harvested, which would cover the entire
recipient limbus. The surgical method is similar to the
CLAG and not more than 6 clock hours (3 clock hours
from superior limbus and 3 clock hours from inferior
limbus) of tissue should be harvested from one donor.
An AMT can be performed before suturing the donor
lenticules, which would help to reduce inflammation
and vascularization. The conjunctivo-limbal lenticules
are secured at the limbus with circumference sutures
with monofilament 10-0 nylon and to the conjunctiva
with 8-0 polyglactin.
Immunosuppression Indefinite immunosuppression is
required irrespective of HLA matching.
1186 Section 9: Miscellaneous Topics

A B

C D

E F

Figs 149.6A to F: Outcome of different surgical procedures to treat limbal stem cell deficiency: (A) Preoperative, and
(B) Postoperative-followup: Amniotic membrane transplantation for partial limbal stem cell deficiency, (C) Preoperative and
(D) Postoperative-followup: Caderveric keratolimbal allograft with penetrating keratoplasty for total limbal stem cell deficiency,
(E ) Preoperative and (F) Postoperative-followup: Live related direct conjunctivolimbal allograft followed by penetrating keratoplasty
for total limbal stem cell deficiency with severe ocular surface damage
 Chapter 149: Limbal Stem Cells of Corneal Epithelium: Concepts, Disease and Management 1187
Current Status ipsilateral: from uninvolved area of the same eye) or
live-related allograft depending upon the donor tissue.
Bilateral total LSCD especially in centers with no cell
As the technique involves culturing of the limbal
culture facility or with extensive symblephara, Lr-
epithelial cells by taking a very small donor tissue, it
CLAL is more effective than KLAL as it is a live tissue,
does not produce any donor site abnormalities.
it has more viable stem cells with better growth
Pellegrini et al 12 were the first to successfully
potential. Although HLA matching is not mandatory,
transplant cultivated autologous limbal epithelium
live related tissues are usually more histocompatible
into the patients. Later, Swab et al and Tsai et al also
than cadaveric tissues. However, live-related tissue
reported similar results in their small series.
being a precious tissue, it should not be used for initial
anatomical reconstruction in those cases where multi-
staged approach involving more than one limbal Indications
transplantation procedure is planned. The long-term Autograft: Unilateral LSCD, bilateral LSCD with partial
results of Lr-CLAL are not yet available. LSCD in one eye.

CULTIVATED LIMBAL Allograft: Bilateral total LSCD or one-eyed patient with

EPITHELIUM TRANSPLANTATION total LSCD (Figs 149.7A to D).

Introduction Surgical Procedure

It is most recent and most promising technique of Limbal graft is taken from the healthy contralateral eye
limbal stem cell transplantation.9 It can be an autograft or a healthy area of the same (ipsilateral) eye, in cases
(contralateral: from the same person’s uninvolved eye, of autologous transplantation and from the donor eye

A B

C D
Figs 149.7A to D: Cultivated limbal epithelium transplantation: (A) Preoperative, and (B) Postoperative-followup: Cultivated
contralateral autologous limbal epithelial transplantation for limbal stem cell deficiency following alkali burns, showing stable
ocular surface, (C) Preoperative and (D) Postoperative-followup: Cultivated live related allogenic limbal epithelial transplantation
for bilateral limbal stem cell deficiency following vernal keratoconjunctivitis, showing stable ocular surface
1188 Section 9: Miscellaneous Topics
in cases of allogenic transplantation (allograft). The
procedure includes careful dissection of a 2 × 2 mm
limbal tissue with 1 mm into clear corneal stromal
tissue at the limbus. The conjunctiva is excised just
behind the pigmented line (palisades of Vogt) and the
limbal tissue that contained epithelial cells and a part
of the corneal stroma is excised. The tissue is
transported in human corneal epithelium medium to
the tissue culture laboratory.
Cultivation of Epithelia
In tissue culture laboratory, the limbal tissue is
shredded into small pieces. The limbal tissue bits are
explanted over the central 10 mm of a 3 × 4 cm, de-
epithelialized, preserved human amniotic membrane
(HAM). HAM is the most commonly used substrate
for cultivation of limbal epithelial cells as it not only
maintains the stemness of the cells but it also acts as a
carrier for cultivated limbal epithelial cells. Anti-
inflammatory and anit-apoptotic action of HAM also
may help. The cells are cultured using human corneal
epithelial cell medium with 10% fetal bovine serum
or autologous serum. The growth is monitored daily
and the medium is changed every two days. The
culture is maintained for 10-15 days, by which time a
confluent monolayer of the presumed limbal epithelial
cells around the explanted tissues was achieved.
Although the other groups maintain culture for longer
time and wait for the stratification (multilayering) in
the culture plate by using T3T, we do not wait for the
startification.10
Transplantation
At the time of transplantation, after preparing the bed,
the HAM with the monolayer of cultivated limbal
epithelial cells is transplanted on the recipient cornea.
HAM is anchored as described above, without
damaging the monolayer of cultivated cells.
Immunosuppression
The autologous transplants do not require immuno-
suppression but the allogenic transplants do require
indefinite systemic immunosuppression.
Current status
It is the best technique for the unilateral LSCD as it
does not require an immunosuppression being
autologous procedure. This does not involve any risk
to the donor site, hence can be repeated. Presumably,
the allogenic cultivated limbal epithelial cells are
devoid of major antigen presenting cells like
Langerhan’s cells, theoretically decreasing the chances
of immunological rejection. However, severe ocular
surface disorders with LSCD like SJS may not show
good outcome in these cases, which may require a
direct live-related conjunctivo-limbal transplantation.
CORNEAL TRANSPLANTATION FOLLOWING
LIMBAL TRANSPLANTATION
Severe ocular surface disorders with limbal stem cell
deficiency (LSCD) require a complex approach of
multiple surgeries such as limbal transplantation and
penetrating keratoplasty (PK) for final visual
rehabilitation. Visual acuity in some of the patients
may improve following the limbal transplantation,
some of the cases still require a penetrating corneal
transplantation for the corneal scarring (Figs 149.8A
to D). The timing of PK may vary depending upon
the technique of limbal transplantation. However,
results of simultaneous PK with KLAL are not very
encouraging. Therefore, we prefer a two-staged
approach. The first stage is ocular surface recons-
truction by cultivated limbal epithelial transplantation
followed by the second stage of visual rehabilitation
by performing a PK with an interval of at least 3
months. Certain issues related to PK following limbal
transplantation must be highlighted. Most of these
patients have undergone pannus resection with or
without superficial keratectomy, the recipient bed is
usually thin and irregular, which could create
significant graft-host disparity with its attendant
problems. In rare cases with a thin recipient bed can
be considered for a lamellar keratoplasty along with
the limbal transplantation. Associated conditions like
lid abnormalities, glaucoma, dry eye, etc. may affect
the final outcome, and hence must be treated before
PK. Cases with allogenic limbal epithelium transplan-
tation need to be immunosuppressed even after the
PK. Some of the cases of LSCD may have normal
endothelium, these cases can be considered for deep
lamellar keratoplasty (DLK).
Immunosuppression
The limbal tissue being vascularized and populated
with various antigen presenting cells, has more chance
of rejection. All the limbal allograft patients require
an indefinite systemic immunosuppressant to avoid
 Chapter 149: Limbal Stem Cells of Corneal Epithelium: Concepts, Disease and Management 1189

A B

C D
Figs 149.8A to D: Penetrating keratoplasty following limbal transplantation: (A) Preoperative: Total limbal stem cell deficiency
following chemical burns, (B) Post-limbal transplantation: Stable ocular surface with leucomatous corneal opacity following
cultivated limbal epithelial transplantation, (C) and (D) Post-penetrating keratoplasty: Clear corneal grafts with a stable ocular
surface following penetrating keratoplasty after cultivated limbal epithelial transplantation

failure due to graft rejection. The regimen followed
by most authors comprises of oral cyclosporine
(5-7 mg/kg body weight/day in divided dosage)
gradually tapered to ensure serum levels between
50-150 ng/ml. Our routine immunosuppression
protocol is to start cyclosporine systemically in a
dosage of 5-7 mg/kg 48 hours prior to surgery, along
with methyl prednisolone 1 gm intravenous for first
three consecutive postoperative days. During the post-
operative period cyclosporine is tapered to the
maintenance dosage of 1.5-2 mg/kg with diltiazem
90 mg added as an adjunct to cyclosporine to reduce
the cost and to increase serum levels of cyclosporine.
Diltiazem also decreases the dosage required to
achieve immunosuppression and thus decreases the
possible systemic adverse effect of cyclosporine.4 Since
the onset of action of cyclosporine is 3 weeks, it should
be coupled with oral steroids (1 mg/kg/day) in
tapering dosage. Regular monitoring of blood and
renal parameters is essential. In addition to cyclos-
porine, azathioprine (1 mg/kg body weight/day) or
Tacrolimus (FK506) can also be considered. The role
of HLA matching before allogenic limbal trans-
plantation is debatable. However, despite HLA
matching, adequate immunosuppression is menda-
tory in all the allogenic limbal transplantation cases.
COMPLICATIONS
Immunological Rejection
Similar to any other solid organ transplantation,
allograft rejection still remains a major cause of failure
1190 Section 9: Miscellaneous Topics
following allogenic limbal transplantation, i.e. KLAL
or live-related (direct or cultivated) limbal trans-
plantation. Though HLA matching has been advised
by some of the groups, all the allografts irrespective
of their HLA matching, requires indefinite immuno-
suppression. However, various studies have proved
that immunological rejection can still occur in spite of
immunosuppression but the long-term survival of
limbal allografts is better in immunosuppressed
patients. It is very important to diagnose and treat the
limbal allograft rejection as promptly as possible to
avoid the death of surviving stem cells. The clinical
feature of limbal allograft rejection may defer
following different types of limbal allografts, but the
management remains the same. Daya et al have
reported the features of KLAL rejection and its
management. Rao et al and Daya et al reported the
features of rejection following Lr-CLAL. Similarly, we
have described the clinical features of rejection
following cultivated limbal allograft.
KLAL Rejection
It is divided into acute and low-grade rejection (Table
149.3). Apart from the features mentioned, patients
present with subjective discomfort, redness, photo-
phobia and mild pain of recent origin. In absence of
immunosuppression the outcome of treatment is very
poor. However, the use of immunosuppressants does
not prevent the rejection but has better long-term
survival.
Lr-CLAL Rejection
The clinical features and symptoms of presentation
are the same as KLAL except the congestion and
edema would include the conjunctival surface also and
would be limited to the area of lenticule only.
Interestingly, in case of more than one donor, rejection
can occur independently in the lenticules of that
Table 149.3: Clinical features of KLAL rejection
Acute
• Intense sectoral congestion with engorged blood vessels
• Edema and infiltration of the lenticules
• Epithelial rejection line
• Punctate epithelial keratopathy
• Epithelial defect in the periphery near rejected lenticule
particular donor without involving the lenticules from
the other donor.
Cultivated Limbal Transplant Rejection
In this condition the symptoms are less severe than
other types of limbal transplants. The clinical features
include epithelial rejection line, superficial punctate
keratopathy, epithelial irregularity and epithelial
defect.
Management Early intensive therapy can save the
transplanted allogenic cells. The cases, which do not
respond, may show features of LSCD in that particular
area of transplantation. Table 149.4 shows the
management protocol followed by us.
Glaucoma
Glaucoma is more common with LSCD, specially
following the chemical injury or it may be steroid
induced glaucoma. It is one of the important causes
of failure in these cases as it is not only refractory to
the routine medical treatment but the corneal
condition makes it impossible to detect and followup.
Some of these severe cases can be considered for anti-
glaucoma surgery first before limbal transplantation.
Use of tonopen is recommended in these cases to
monitor intraocular pressures.
Infection
Microbial keratitis is one of the most dreadful compli-
cations. Any eyes with severe ocular surface abnorma-
lities would have higher chances of microbial keratitis
than normal. The abnormal tear film plays a major
role followed by loss of goblet cells responsible for
the production of mucin, which prevents microbial
attachment to the ocular surface. Early detection of
the infection is important rather than keeping the
patients on indefinite antibiotics.
Low-grade
• Mild, diffuse perilimbal congestion
• Elevated perilimbal area
• Punctate epithelial keratopathy
• Epithelial irregularity
 Chapter 149: Limbal Stem Cells of Corneal Epithelium: Concepts, Disease and Management
Table 149.4: Protocol of management
of limbal allograft rejection
• Patient is hospitalized and baseline investigations are
performed
• Complete blood count, renal profile, examination by a
physician
• Topical
• Prednisolone acetate eye drops every hourly
• Lubricants-preservative free continue as required
• Systemic
• Methyl prednisolone 1 gm intravenously daily for 3 days
• Oral corticosteroids 1 mg/kg/day in tapering dosage
• Oral cyclosporine along with tab. Diltiazem continue
RECENT ADVANCES
Co-cultivated Limbal and Conjunctival Epithelium
Severe ocular surface disorders involving conjunctiva
with LSCD can be a difficult situation to manage. Our
group has developed a new technique of co-cultivation
of conjunctival and limbal epithelium, wherein the
central area of HAM has limbal epithelial cells and
peripheral part carries conjunctival epithelial cells.10
Hence the total ocular surface can be reconstructed
simultaneously.
Cultivated Oral Mucosal
Epithelium Transplantation
Kinoshita et al have successfully reformed the ocular
surface using autologous oral mucosa. If successful,
this may all together obviate the use of allogenic tissue
and hence use of immunosuppression, which has its
own potential complications. However, long-term
studies are still awaited.
Stem Cell Plasticity
The stem cells are known for its plasticity, which is
changing its phenotype according to the niche
1191
(surrounding microenvironment). Using this charac-
teristic of stem cells many groups including our
group are working on developing limbal stem cells
from other autologous sources like hemopoetic stem
cells, etc. to achieve an autologous tissue with better
long-term survival with any need of immuno-
suppression.
REFERENCES
1. Sangwan VS, Tseng SCG. New perspectives in ocular surface
disorders. An integrated approach for diangnosis and
management. Ind J Ophthalmol 2001;49:153.
2. Dua HS, Azuara-Blanco A. Limbal stem cells of the corneal
epithelium. Surv Ophthalmol 2000;44:415.
3. Tseng SC. Concept and application of limbal stem cells. Eye
1989;3:141.
4. Fernandes M, Sangwan VS, Rao SK, Basti S, Sridhar MS,
Bansal AK, Dua HS. Limbal stem cell transplantation. Indian
J Ophthalmol 2004;52:5.
5. Tsubota K, Satake Y, Kaido M, Shinozaki N, Shimmura S,
Bissen-Miyajima H, Shimazaki J. Treatment of severe ocular-
surface disorders with corneal epithelial stem-cell trans-
plantation. N Engl J Med 1999;340:1697.
6. Solomon A, Ellies P, Anderson DF, Touhami A, Grueterich
M, Espana EM, et al. Long-term outcome of keratolimbal
allograft with or without penetrating keratoplasty for total
limbal stem cell deficiency. Ophthalmology 2002;109:1159.
7. Ilari L, Daya SM. Long-term outcomes of keratolimbal
allograft for the treatment of severe ocular surface disorders.
Ophthalmology 2002;109:1278.
8. Daya SM, Ilari FA. Living related conjunctival limbal allograft
for the treatment of stem cell deficiency. Ophthalmology
2001;108:126.
9. Tsai RJF, Li L-M, Chen J-K. Reconstruction of damaged
corneas by transplantation of autologous limbal epithelial
cells. N Engl J Med 2000;343:86.
10. Sangwan VS, Vemuganti GK, Iftekhar G, Bansal AK, Rao GN.
Use of autologous cultivated limbal and conjunctival
epithelium in a patient with sever bilateral ocular surface
disease induced by acid injury. Cornea 2003;22:478.
 Chapter 150
Miscellaneous Aspects
of Conjunctiva
LC Dutta, Nitin Dutta
FLOPPY EYELID SYNDROME
This is a syndrome consisting of chronic papillary
conjunctivitis with a rubbery and easily everted floppy
upper eyelid. It was first described by Culbertson
and Ostler in 1981.1 Although reported in obese men,
this syndrome may occur in women also.2 The charac-
teristic features consist of a triad of: (a) diffuse
papillary conjunctivitis; (b) a loose upper lid that
readily everts while pulling it downward; and (c)
soft rubbery tarsus that can be folded on. An external
upward force applied to the upper eyelid causes the
tarsus to evert in a gradual rolling motion instead of
the usual all or nothing popping out. Large papilla
covers the upper palpebral conjunctiva with mucus
or mucous strands over the surface of the papilla.
Bulbar conjunctiva is mildly hyperemic. The upper
lid is pliant with lash ptosis and an abnormal type of
blepharoptosis. There may be thinning of the ptotic
eyelid above the tarsus. Levator function is not
diminished. It was initially postulated that eyelid
eversion during sleep, with cornea-pillow contact as
the cause of keratoconjunctivitis. Patients who tend
to sleep on one side may have more serious changes
on that side, whereas patients who sleep face down
may have bilateral problem. Parvinovic3 doubted this
etiology and some workers 4 suggested that the
mechanism of injury might be related to a poor
interface between the loose eyelid and the bulbar
conjunctiva. An association of floppy eyelid
syndrome with keratoconus also has suggested that
rubbing or mechanical pressure may be a contributing
factor.5 Similarly, association of the condition with
blepharochalasis has suggested that chronic inflamma-
tion may lead to many of the findings seen in
advanced floppy eyelid syndrome.6 The condition is
usually found in obese persons.
Pathology
The pathologic basis of the tarsal laxity is not known.
Chronic mechanical injury and irritation may have a
role in progression of the condition, but the exact
cause of initiation of the process has not been so far
identified. Standard histopathologic studies have
found no abnormalities in the tarsus except some
amount of meibomian dysfunction. Most studies
focused on the tarsal collagen which has been found
to be normal in appearance by light and electron
microscopic studies. However, immunohisto-
chemistry shows decrease in quantity of elastic fibers
in the tarsus. Elastic fibers were nearly absent except
for a few clumps of positive staining material around
the meibomian gland acini and in the perimysium
and endomysium of the pretarsal orbicularis muscle.7
The meibomian glands show cystic degeneration
and metaplasia as well as abnormal keratinization
and granuloma formation. These abnormalities of the
meibomian glands may result in qualitative abnor-
mality of the tear film, which may in turn contribute
to keratoconjunctivitis seen in the syndrome. Some
workers have found abnormal EEG due to apnea or
hypopnea.8 This may be due to a common underlying
connective tissue disorder with abnormalities in the
 Chapter 150: Miscellaneous Aspects of Conjunctiva
pharynx as in the tarsus. Though reports are
available9 in literature that hyperglycemia was found
in floppy eyelid syndrome, there is no explanation
about the mechanism in causation of this lid
abnormality.
The eyelash ptosis is due to matting or deformation
of the cilia by chronic mechanical injury.
Alternatively, the changes in tarsal laxity may have
affected the stability of the tissue into which the cilia
are anchored, causing changes in the direction of the
cilia. The quantitative change in the elastin in the
pretarsal orbicularis muscle may also contribute to
eyelash ptosis.
Management
As the exact cause of floppy eyelid syndrome is not
known, therapy is aimed at preventing the probable
nocturnal eyelid eversion. An eyelid shield while
asleep may give relief to some symptoms and prevent
lid rubbing. Topical lubricant and antibiotics may give
some relief of symptoms. Surgical treatment consists
mainly of shortening of the eyelids.10 Full thickness
shortening by full thickness excision of 10 to 15 mm of
the lateral part of the upper eyelid 11 and lateral
tarsorrhaphy12 gives immediate relief of symptoms.
Shortening may be achieved by tarsal strip procedure
also.
GIANT PAPILLARY CONJUNCTIVITIS (GPC)
The syndrome of giant papillary conjunctivitis,
first described by Allansmith and his coworkers in
1977 13-15 exists in wearers of both hard and soft
contact lenses. The syndrome consists of increased
mucus, mild itching, decreased lens tolerance, and
development of giant papillae (more than 1 mm in
diameter) in the upper tarsal conjunctiva. Excepting
contact lens wearers, wearing of other types of
PMMA prostheses has also been reported to cause
GPC.16,17 The sutures of postoperative penetrating
keratoplasty also might cause GPC.18
Symptoms of GPC occur before its signs. Itching
of eye when lenses are removed, accumulation of
mucus in the nasal corner of the eye, and slight
blurring of vision caused by coating on the lens are
common early symptoms of GPC. These symptoms
are so common and so minor that many patients
neglect to bring them to notice of the lens fitter. But
the later phases are usually severe enough to demand
attention. In advanced stages of GPC, the patient may
complain of foreign body sensation when wearing
the contact lenses and strings or sheets of mucus may
1193
glue the eye during sleep.
Mild hyperemia of the upper tarsal conjunctiva is
the early sign of GPC. There may be small strands of
mucus. Initially, the conjunctiva may look
transparent; but due to accumulation of cells, during
the process of inflammation cause the conjunctiva to
become opaque. Later, in the process of development
of the disease, wearing of contact lenses causes
significant discomfort and pain.
Pathology of GPC
Coatings on worn contact lenses are normal. These
coatings present both on the anterior and posterior
surfaces of the worn lens. Such coating may be
necessary for proper wetting and essential for the
wearers’ comfort. However, the amount of coating
required for comfort and the amount that might cause
discomfort is difficult to predict. Although a normal
amount of coating may be physiologically advan-
tageous, it does provide a sticky base that may act as
an attachment site for bacteria and other particulate
matter from the environment.
Contact lens coatings appear to consist of mucus-
like material, which may be derived from secretory
cells of the conjunctiva and the lacrimal gland.
Material found on the upper tarsal conjunctiva that
is believed to be mucus, is morphologically similar
to lens coating, and could be rubbed onto the surface
of the upper tarsal conjunctiva during blinking. Mucus
coating increases the hydrophility of a polymer
substance by facilitating the spreading of watery
fluid. Mucus has also been found to play an essential
role in wetting the corneal surface. In the absence of
mucus, the cornea becomes less hydrophilic.
Increased accumulation of plaque-like material,
along with mucus-like material, is seen as the lens is
worn over a time. Of course, contact lenses are
incapable of desquamation. Once materials accumu-
late, they remain as deposits. There are two types of
structures on and in the lens deposits, i.e. (a) bacteria19
and (b) structures that resemble cells or their
membranes alone.20 The cell type of structures are
similar to those seen on the surface of used IOL.
The abrasive effect of the contact lens upon the
conjunctival mucosal surface allows immunogenic
recognition of antigen (bacterial residue) on the
surface of the lens. The chronic inflammation caused
by the resulting immunogenic response leads to tissue
hyperplasia in the form of giant papilla. On the other
hand, the result of the mechanical trauma repeated
1194 Section 9: Miscellaneous Topics

with each excursion of the upper eyelids over the
deposits on the worn contact lens is coupled with
antigen-antibody reaction in formation of the papillae.
It is unlikely that the lesions of GPC are caused by
reaction to contact lens material itself. Though both
the hard and soft contact lens wearers may develop
GPC, the later is more implicated.21
Histopathology shows lymphocytes, plasma cells,
basophils, mast cells, and eosinophils in the papillae.
In the cytoplasm of the plasma cells and mast cells,
acidophillic hyaline PAS positive electron-dense
intracytoplasmic granular inclusion bodies are found.
These are called Russell bodies. They are thought to
represent inspissated immunologulins.22 They are
prominent in quiescent stage of GPC. It is presumed
that degranulation of the cells containing Russell
bodies act as chemotactic effect for cellular infiltration.
Scanning electron microscopy of the surface of the
giant papillae shows distortion of the cells with
increased number of microvilli. This cellular morpho-
logy may be secondary to stretching and elongation
of cells and enormous growth of tissue.13-19
D/D from Vernal Conjunctivitis
Clinically, GPC closely resembles to vernal kerato-
conjunctivitis (VKC). Both the conditions are charac-
terized by ocular irritation, and production of mucus.
Limbal and corneal lesions may appear in both the
conditions. Tranta’s dots are discrete, while dots that
appear in the apices of the limbal papillae. They are
focal collections of inflammatory cells and degene-
rating epithelium. Eosinophils are also noticed in the
dots.23 The simplest test to differentiate GPC from
VKC is that in the former, the symptoms disappear
immediately after removal of the worn lens, but there
is no immediate relief in VKC after treatment. Table
150.1 shows the differentiating points of VKC and
GPC.24
Management
It is a recognized fact that an increased coating of
the worn contact lens exacerbates the signs and
symptoms of existing GPC and also may contribute
to the onset of the disease. The following factors that
increase the patient’s exposure to lens coating may
enhance the clinical course. Therefore, for treatment,
the following should be taken into consideration:
a. Wearing the lens for a long time during the day.
b. Wearing the same lens for more than three
months.
c. Wearing larger lenses that present a greater area
to the conjunctival epithelium.
d. Inadequate cleaning of the lens.
The fluid for cleaning the lens should be free of
preservative because even in its lowest effective
concentration, it is notorious for causing keratitis.
Sterilization by hydrogen peroxide has been found
to be the latest method tolerated by the compromised
conjunctiva. Sterilization by boiling may bake the
coatings, and further traumatize the compromised
conjunctiva when the lenses are reinserted. Enzymatic
cleaning of the lens is essential to minimize the
accumulation of lens coatings and to remove accumu-
lated environmental antigens. Papain (solution of
2/1000th of 1% of the dry powder of any enzyme)
preparations are more effective and better tolerated

Table 150.1: Differentiating points of VKC and GPC

A. Clinical VKC GPC
Age Common in children Common in adults
Sex Common in males than in females No sex difference
Incidence Rare Common
Major atopic disease Usually associated Rarely associated
Season Common in spring Not seasonal
Mucus Characteristically severe Mild to moderate
Itching Common feature Variable
Corneal lesion Common Rare
B. Histological Mast cell in epithelium 100%25 78%
Eosinophil in epithelium 100% 4% (about 2 per 25x field)
Eosinophil in substantia propria 100% 38%
Basophils in epithelium 60% 5%
Basophil in substantia propria 100% 27%
C. Tear fluid Histamine content is 4 times Histamine content is equal
more than normal26 to or lower than normal
 Chapter 150: Miscellaneous Aspects of Conjunctiva
by the compromised conjunctiva than other enzymatic
preparations for lens cleaning.
OCULAR CICATRICIAL PEMPHIGOID
Ocular cicatricial pemphigoid (OCP) also called benign
mucous membrane pemphigoid is a systemic
autoimmune disease having both ocular and non-
ocular systemic manifestations. There is another
systemic autoimmune disease called bullous pemphi-
goid which does not produce cicatrization. Etiology
of OCP may be idiopathic or may be due to some
topical medications like betablocker (timolol) and
pilocarpine used for lowering the intraocular pressure
in glaucoma.27 The condition is relatively rare.
Usually, the disease develops in the age group of
60 to 70 years and females are more affected than
males. The ocular manifestations of the disease are
described in four stages.28
Stage 1 Characterized by chronic conjunctivitis with
mild conjunctival or corneal epitheliopathy or both
and early subepithelial fibrosis of the conjunctiva. The
fibrosis is best seen under the epithelium of the upper
or lower tarsal conjunctiva. About 25% or less
shrinkage of conjunctiva develops.
Stage 2 Progression of the cicatrizing process with
contraction of newly formed collagen which fore-
shortens the inferior fornix. About 25 to 50%
shrinkage of conjunctiva develops.
Stage 3 Characterized by formation of first visible
appearance of symblepharon. In this stage 75%
conjunctival shrinkage occurs.
Stage 4 or the end stage of the disease is characterized
by totally dry eye with symblepharon formation and
keratinization of the cornea. Pathologically, this stage
is associated with keratopathy with epitheliopathy
and progression to corneal scarring and vascula-
rization.
The final diagnosis is confirmed by immuno-
histopathological stains by biopsy of the conjunctiva
unaffected by symblepharon. The key sign deposition
of linear deposits of antibodies at the level of the
epithelial basement membrane shown by immuno-
fluorescence study.
Differential Diagnosis
Cicatricial conjunctival pemphigoid should be
differentiated from severe conjunctival inflammation
1195
caused in the following conditions:
a. Erythema multiforme (major and minor),
b. Toxic epidermal necrosis,
c. Alkali burn,
d. Infections: Trachoma, adenovirus Types 8 and
19 keratoconjunctivitis,
e. Application of drops and ointments containing epi-
nephrine, iodoxuridine aminoglycosides28,29 and
sometimes betablockers.
However, these pseudopemphigoids cannot be
differentiated from the pemphigoids clinically.
Correct diagnosis can only be done by direct
immunological studies.30 A biopsy taken from the
uninvolved tissue immediately adjacent to a lesion
shows linear deposits of IgG along the basement
membrane zone in cicatricial pemphigoid but not in
pseudopemphigoid.31
Pathology
Cicatricial pemphigoid is a systemic autoimmune
disease in which the autoantibodies directed against
the conjunctival epithelial cell basement membrane
initiate a Type II hypersensitivity reaction. The initial
pathology is vesicle formation which may be any-
where in the conjunctiva. The size of the vesicle may
vary from a few mm to one cm. The fluid inside the
vesicle is sterile; but when it ruptures, secondary
infection may set in which causes infiltration of
inflammatory cells. In the meantime, perivascular
thickening and subepithelial proliferation of fibrous
tissue lead to formation of macroscopic fibrous bands
in both bulbar and palebral conjunctiva.
Treatment
Symptomatic Treatment
a. Ocular discomfort in the early stage is due to
irritation and foreign body sensation caused by
the misdirected eyelashes. Epilation of the
eyelashes is a purely temporary procedure; a few
days later new eyelashes grow and the newly
formed eyelashes cause more severe symptoms.
Destruction of the eyelash root can be done by
electrolysis or cryo application to the lid margin.
Lubricating solutions may render some relief.
b. Systemic therapy to control the active pathology
is a difficult exercise for the ophthalmologist
alone. Guidance from oncologist is essential. The
systemic drugs currently in use are
i. Dapsone 25 mg twice daily
1196 Section 9: Miscellaneous Topics
ii. If response is unsatisfactory, methotrexate 7.5
mg once weekly or azathioprine 2 mg/kg/day
is added to dapsone therapy.
iii. If dapsone is ineffective, then a combination of
methotrexate and azathioprine is continued
Patients who fail to respond to the above
therapy are treated with high dose of steroid.
c. Surgical treatment to improve the vision: Kerato-
plasty is not indicated. The only surgical procedure
available is keratoprosthesis.
LABORATORY DIAGNOSIS OF
OCULAR INFECTIVE ORGANISMS
The detection of organisms or finding out the cause
of the infection is based on the two sets of tests, i.e.
(a) Standard methods, and (b) Tests for rapid
identification of organisms.
Standard Methods
There are four laboratory tests.
Cytological Tests
In these tests the cause of the disease is inferred from
the type of the inflammatory cells present in the
conjunctiva.33 The conjunctival cells are spread in a
slide by scraping and the smear is stained with
cytological stains like Giemsa. The results are,
however, not confirmative because polymorpho-
nuclear leukocytes predominate in acute stage of
inflammation and mononuclear leukocytes predo-
minate in chronic infections. The polymorphonuclear
leukocytes found in acute stage of trachoma may
contain the inclusion bodies.
Direct Detection Tests
In these tests specimens from the patients are tested
directly either for presence of relevant
microorganisms or of the antigen specific of that
microorganism. The microorganisms do not need to
be viable, but they may be present in small quantity
just to make the least sensitive. Chlamydia trachomatis
was first detected in Giemsa stained conjunctival
smear and later from the eye of an orangutan which
had been experimentally inoculated with materials
from the eyes of trachoma patients and later seen in
the smears from patients by Halberstaedter and von
Prowazek in 1907.
Immunochemical methods like immunofluore-
scent and immunoperoxidase staining are more
sensitive than standard Giemsa’s stain. Immuno-
peroxidase has the advantage of possibility of making
permanent preparations, and normal light field
microscopy can be used for the examination. The
development of antichlamydial monoclonal anti-
bodies and their use in immunochemical staining
allows chlamydial elementary bodies to be identified
reliably in such specimen. Commercially, available
fluorescein-labeled monoclonal antibodies to herpes
simplex virus have been used to detect virus infected
cells in smears from skin vesicles. Enzyme immuno-
assay is another method to detect microbial elements
in clinical specimens. Enzyme-labeled antibodies and
substrates are used to produce a color which can be
read spectrophotometrically.34
Culture and Isolation Test
In this test the specimen is cultured to grow the
organism. It is important that the specimens collected
contain sufficient epithelial cells and they must be
transported to the laboratory in a manner designed
to preserve the viability of the organism. It was
difficult to get cell culture of C trachomatis but egg
culture was easy. Special preparation of the cells is
necessary to make them suitable for culture of
C. trachomatis.35
Serological Tests
In these tests the patient’s sera or local secretions are
tested for antibodies to the microorganisms. The
presence of specific antibodies indicates the patient’s
exposure to a particular infection in the past or
present. The presence of specific IgM antibodies or a
high titer of IgG antibodies in blood is suggestive of
the present infection. In some cases, the presence of
antibodies in local secretions has been seen to
correlate active disease. The absence of antibodies
to a particular organism argues against it being the
cause of the infection unless the specimen has been
taken so soon after the onset that there has not been
enough time for antibody production. A definite
diagnosis can be obtained if a second sample is tested
at least two weeks after the first.36
Test for Rapid Identification of Organisms
The main laboratory techniques for ocular microbial
agents are the following: (a) Culture of organisms,
(b) Chemical assays, and (c) Direct examination of
 Chapter 150: Miscellaneous Aspects of Conjunctiva 1197
clinical specimen. a wavelength of 420 nm. 37,38 Blankophor and
Depending upon the type of organisms, it takes unitex are two other nonspecific chemicals used
about 48 hours to 14 days to get the culture result. for fluorescein stain for rapid diagnosis of mycotic
Direct examination of the specimen can be done by infections in tissue section and cytopathological
conventional methods like Gram, Giemsa or by newer preparation. The chitin present in the fungal cell
technique like fluorescent antibody staining lectins, wall absorbs the nonspecific fluorescein stains.
etc.
In case of smears from corneal ulcers or conjunc- Fluorescein Conjugated Lectin
tival discharge, one can have a gross impression of
Lectin is a type of protein found in plant seeds; it has
the causative organism by studying the nature of
the property of binding specifically to carbohydrate
inflammatory cell by Gram’s and Giemsa’s stain. For
group. Most of the cell wall macromolecules of fungi
example, preponderance of polymorphonuclear
consist of oligosaccharides, and fluorescein
leukocytes in bacterial and fungal infection, mono-
conjugated lectin can easily bind with these particles.39
nuclear cell in viral diseases and macrophages and
Using epifluorescein microscope, mycotic organisms
plasma cells in chlamydial infections. Bacteria, fungi,
are easily detected in smears and tissue section which
and cysts of acanthameba can be identified rapidly
have been treated with brief exposure with
by a good Gram’s stain. Giemsa’s stain is also helpful
fluorescein conjugated lectin.
in the detection of mycotic organisms in about 75%
of cases.
Affinity Membrane Test for
Superficial Corneal Herpes
Fungus Identification
A protein-binding affinity membrane is gently
Accurate diagnosis of mycotic infection can be made
touched to the corneal lesion. The membrane is
only by examination of scrapings or biopsy specimens
allowed to dry for five minutes and is immersed in a
from the affected parts. Culture of fungus requires a
0.5% casein-blocking buffer containing 1:1000 dilution
minimum of 48 to 72 hours for diagnosis. Current
horseradish peroxidase conjugated antiherpes
staining methods are either insensitive (Gram and
simplex virus antibody for 15 minutes at room
Giemsa) or tedious to perform and difficult to
temperature. The membrane is washed in three
interpret without some experience (Gomori’s
changes of 0.1% solution of Triton 100 detergent in
methenamine silver and PAS). The following two
phosphate buffer saline and two changes of deionized
methods are relatively quick and simple to perform
water, and then immersed in a substrate solution
and easier to interpret:37
made as follows: 100 mg of tetramethyl benzidine
a. Ink-potassium hydroxide preparation A mixture of
dissolved in 10 ml of dimethyl sulfoxide and one ml
10% potassium hydroxide and ink (Parker blue-
of tetramethyl benzidine solution diluted in 100 ml
black super) is prepared in 9 : 1 ratio. The specimen
of 0.1 M sodium acetate/citrate buffered at pH 6.0,
is placed in the glass slide; a drop of the mixture
and 0.1 ml of 30% hydrogen peroxide.39
is added and coverslip is placed on the top. The
Membranes which adsorbed herpes virus antigen
slide is stored in moist chamber and examined by
from contact with an infected cornea develop a
light microscopy one, two, and 18 to 24 hours later.
pattern of intense deep blue staining almost
b. Calcofluor Calcofluor is a stilbene derived fluore-
immediately upon contact with the tetramethyl
scent dye that stains cellulose and chitin. 1%
benzidine solution. The reaction is complete in 3 to 5
calcofluor and 0.1% Evans Blue (to decrease
minutes. Membrane without antigen and those
nonspecific fluorescence) in distilled water is used.
blotted on nonherpetic corneal lesions remain
Specimen is placed on a glass slide. After one
colorless. The total time needed to obtain the result
minute, the slide is rinsed in distilled water; and
of this test is about 30 minutes.
putting a nonfluorescent mounting medium, the
specimen is covered with a glass coverslip. The
Limulus Amebocyte Lysate Assay
slide is examined with an epifluorescence micro-
scope using an exciter filter that transmits a wave- By this, new test rapid diagnosis of ulcerative corneal
length of 365 nm and a barrier filter that transmits and intraocular lesions caused by gram-negative
1198 Section 9: Miscellaneous Topics

organisms like Pseudomonas and Proteus can be Use of Monoclonal Antibody

made.40,41 The principle of this test is based on the
Monoclonal antibody also can be used in diagnosis
fact that the endotoxin of the gram-negative bacteria
of viral, bacterial, and chlamydial infections.
activates clotting of proteins extracted from amebo-
Monoclonal antibodies are highly specific and are
cytes of the horseshoe crab limulus polyphemus. This
produced by hybridoma cell lines. This procedure
test is more sensitive than Gram stain smears of the
consists of immunizing a mouse to a particular antigen
specimens obtained from the lesion. Moreover, the
of a pathogenic organism and fusing spleen cells of
test is positive even after initiation of antibiotic
the immunized animal with myeloma cells to produce
therapy because the endotoxin remains at the site of
hybrid cells. These hybridoma cells have the capacity
the lesion even after starting of treatment. The result
to produce antibody specific to the antigenic deter-
of the test may be obtained within one hour.42
minant of the pathogen.
Some newly developed tests are very costly and
difficult to perform. As test kits for these tests are
Nucelic Acid Hybridization Reactions
becoming increasingly available in well-equipped
laboratories in developed countries, ophthalmologists Hybrid means offspring of parents of two species.
should know about their applications (Table 150.2).43 The principle of the test is that the structure of the
double stranded DNA is to be denatured by exposing
the test material at extreme temperature. When such
denatured single stranded DNA of the specimen

Table 150.2: The rapid laboratory methods for identification of ocular microbial infections
and their clinical application and reliability (Rao NA, 1989)
Methods Time required Infectious Practical Reliability
to perform agent application
the test
Conventional Techniques
Gram’s stain 15 min ½ hr Bacteria Simple technique, low cost Positive in 60% to 70% of cases.
Giemsa’s stain 15 min ½ hr Chlamydia, fungi Simple technique, low cost Useful in chlamydial infections,
reliable in identification of fungi
in 75 to 90% of cases.
KOH 10-15 min Fungi Simple technique, low cost Less reliable, yields positive
result in 33% of cases.
Gomori’s 2-3 hr Fungi Special technique, low cost Yields positive result in 85% of
cases.

Newer Methods
Endotoxin assay 1 hr Gram-negative Special technique, requires More sensitive than Gram’s stain,
Limoids bacteria aseptic precautions, strict can be used in treated cases,
amoebocyte adherence to time/ some compounds can induce false-
lysate test temperature needed positive or false-negative results.
Fluorescein stains 30 min Fungi, acanthameba Simple technique, Reliable techniques, species
Conjugated lectins microscope differentiation when a panel of
lectins is used.
Nonspecific 30 min Fungi, acanthameba Simple technique Reliable, claimed to be better than
fluorescein stains requires special Gomori’s methenamine silver stain.
Calcofluor white microscope
Blankophor Uvitex
2B
Eectron 1 hr Major groups of Special technique, Organisms need to be present at
microscopy with viruses needs sophisticated concentrations of 1 × 106
negative staining equipment and skilled particles/ml.
observer.
 Chapter 150: Miscellaneous Aspects of Conjunctiva
comes in contact with single stranded DNA probe, a
double stranded molecule is formed consisting of one
strand from the infectious agent and one strand from
testing DNA probe. This is the hybridization of
nucleic acid.
With specific kits detection of infectious agents
like human immunodeficiency virus, adenovirus,
cytomegalovirus, Epstein Barr virus, herpes simplex
virus, Mycobacterium tuberculosis, and Chlamydia can
be done within a few hours.
Fluorescent-antibody staining is more sensitive
than the traditional method of Giemsa’s staining for
detection of chlamydial inclusions in conjunctival
staining. Culture in irradiated McCoy cells is more
sensitive than the direct demonstration of chlamydial
inclusions in Giemsa’s stained smears.34
Electron Microscopy
For detection of virus of vesicular lesions, the inclusion
bodies in the cells may be detected by light micro-
scopy. Special preparations like Papanicolaou smear
or Tzanck tests are methods for rapidly detecting
some viral infections but are of limited use because
of their low sensitivity in detecting the agent.
Electron microscopy with negative staining is
particularly useful in rapid detection of viruses in
vesicular lesions. This technique needs 15 minutes to
one hour to prepare the specimen and half an hour
to identify the major group of viruses. By this
method, the morphology of the infectious agent can
be directly identified and the concentration of the
agent must be about 1 × 106 or more particles per ml
of the specimen.
Immunofluorescent Staining
This method is used in diagnosis of viral infections
caused by herpes simplex,44 herpes zoster, aden-
ovirus,45 enterovirus, and cytomegalovirus.46,47 The
principle of the method is demonstration of
fluorescein isothiocyanate conjugated antibody
complex with viral antigen in specimen using
ultraviolet illumination. Such antigen-antibody
complexes can be visualized by the following: (a)
direct, (b) indirect, and (c) anticomplement immuno-
fluorescent methods:
a. Direct method This method consists of examination
of the specimen after application of fluorescein
conjugated antibody to the fresh or preserved
specimen.48 This method is more specific than the
indirect one (described below), but it requires high
1199
titerd antisera for conjugation.
b. Indirect method In this method, the specimens are
treated first with unlabeled antisera after which
the fluorescein-labeled immunoglobulins are
added. This secondary antibody is directed
against the animal species in which primary
antisera are prepared. However, the indirect
method is less specific because additional reagents
are introduced into the reaction system.
c. Anticomplement immunofluorescence method In this
method, addition of primary antibody is followed
by addition of complement and then addition of
fluorescein tagged antibodies.
REFERENCES
1. Culbertson WW, Ostler HB. The floppy eyelid syndrome. Am
J Ophthalmol 1981;92:568.
2. Paciue M, Mier ME. A woman with floppy eyelid syndrome
(Letter). Am J Ophthalmol 1982;93:255.
3. Parunavic A. Floppy eyelid syndrome. Br J Ophthalmol
1983;330(67):264.
4. Schwartz LK, Gelender H, Forster RK. Chronic conjunctivitis
associated with floopy eyelid. Arch Ophthalmol 1983; 101:1884.
5. Parunovic A, Illie B. Floppy eyelid syndrome associated with
keratoconus. Br J Ophthalmol 1998;72:634.
6. Goldberg R, Seiff S, Mc Farland J et al. Floppy eyelid syndrome
in blepharochalasis. Am J Ophthalmol 1986; 102:376.
7. Netland PA, Sugrue SP, Albert DM et al. Histological feature
of the floppy eyelid syndrome. Ophthalmology 1994;101:174.
8. Woog JJ. Obstructive sleep apnea and floppy eyelid syndrome.
Am J Ophthalmol 1990;110:314.
9. Gerner EW, Hughes SM. Floppy eyelid syndrome with
hyperglycinemia. Am J Ophthalmol 1984;98:614.
10. Dutton JJ. Surgical management of floppy eyelid syndrome.
Am J Ophthalmol 1985;99:557.
11. Moore MB, Harrington J, Mc Cullen JP. Floppy eyelid syndrome
management including surgery. Ophthalmology 1986;93:184.
12. Bouchard CS. Lateral tarsorrhaphy for noncompliant patient
with floppy eyelid syndrome. Am J Ophthalmol 1992;114:367.
13. Allansmith MB, Korl DB, Greiner JV et al. Giant papillary
conjunctivitis in contact lens weares. Am J Ophthalmol
1977;83:697.
14. Greiner JV, Convinction HL, Allansmith MR. Surface
morphology of giant papillary conjunctivitis in contrast to
normal contact lens wearers. Am J Ophthalmol 1978;85:242.
15. Korm DR, Allansmith MR, Greiner JV et al. Prevalance of
conjunctival changes in wearers of hard contact lens. Am J
Ophthalmol 1980;90:336.
16. Srinivas RD, Jocobiec FA, Iwanamoto R et al. Giant papillary
conjunctivitis with ocular prosthesis. Arch Ophthalmol
1974;97:892.
17. Meister DM, Krashma JH, Clockson JA. Immunologic study
of giant papillar conjunctivitis associated with an ocular
prosthesis. Am J Ophthalmol 1981;92:368.
18. Sugar A, Meyer RF. Giant papillary conjunctivitis after karato-
plasty. Am J Ophthalmol 1981;91:239.
19. Fowler SA, Greiner JV, Allansmith MR. Attachment of bacteria
to soft contact lens. Arch Ophthalmol 1979;97:659.
1200 Section 9: Miscellaneous Topics
20. Fowler SA, Greiner JV, Alansmith MR. Soft contact lens from
patients with giant conjunctivitis. Am J Ophthalmol
1979;88:1056.
21. Kafmann HE, Katz JI. Endothelial damage from intraocular
lens insertion. Invest Ophthalmol 1974;15:996.
22. Henriques AS, Allansmith MR. Russell bodies in contact lens
associated giant papillary conjunctivitis. Arch Ophthalmol
1979;94:473.
23. Meisler DM, Zaret CR, Stock EL. Tranta’s dots and limbal
inflammation associated with soft contact lens wear. Am J
Ophthalmol 1980;89:66.
24. Allansmith MR, Baird RS, Greiner JV. Vernal conjunctivitis
and contact lens associated with giant papillary conjunctivitis
compared and contrasted. Am J Ophthalmol 1979;87:544.
25. Allansmith MR, Baird RS. Percentage of degranulated mast
cells in vernal conjunctivitis and giant papillary conjunctivitis.
Am J Ophthalmol 1979;91:71.
26. Abalson MB, Soter NA, Simon MA et al. Histamine in human
tear. Am J Ophthalmol 1977;83:417.
27. Duke Elder S. System of Ophthalmology. London:Henry
Kimpton, 1965;8(Part 1):139.
28. Davidson CR, Tuff SL, Dart JKG. Conjunctival necrosis after
administration of topical fortified aminoglycosides. Am J
Ophthalmol 1991;11:690.
29. Jacob IH, Goldberg DB, Flore PA. Drug induced pemphigoid:
A spectrum of disease. Arch Ophthalmol 1987;105:1660.
30. Foster CS, Shaw CD, Wells PA. Scanning electron microscopy
on conjunctival surface in patients with ocular cicatrizing
pemphigoid. Am J Ophthalmol 1986;102:554.
31. Power WJ, Naves RA, Rodriguez A et al. Increasing the
diagnostic yield of conjunctival biopsy with suspected
cicartricial pemphigoid. Ophthalmology 1995;105:1158.
32. Morrison LH, Swan KC. In Fraunfelder, Roy, Saunders (Eds):
Cicatricial Pemphigoid in Current Ocular Therapy. 1990; 3:403.
33. Thygeson P. The cytology of conjunctival exudates. Am J
Ophthalmol 1946;29:1449.
34. Darougar S, Woodlands RM, Jones BR et al. Comparative
sensivity of fluorescent antibody staining the conjunctival
scraping and irradiated McCoy cell culture for the diagnosis of
hyperendemic trachoma. Br J Ophthalmol 1980;64:276.
35. Darougar S, Woodlands RM, Walpita P. Value and cost
effectiveness of double culture for diagnosis of viral chlamydial
infection. Br J Ophthalmol 1987;71:673.
36. Woodland RM. Laboratory diagnosis of chlamydial and viral
disease. Eye 1988;(2 Suppl) 5:70.
37. Arffa RC, Avni I, Robin J et al. Am J Ophthalmol 1985;100:719.
38. Day DM, Akrabawl PI, Head WS et al. Laboratory isolation
techniques in human and experimental fungus infection. Am J
Ophthalmol 1979;87:688.
39. Robin JB, Arffa RC, Avni I, Rao NA. Rapid visualization of
three common fungi using fluorescein conjugated lactins. Invest
Ophthalmol Vis Sci 1986;27:500.
40. Wolters RW, Jogresson JH, Calzada E et al. Limulus lysate
assay for early detection of certain gram negative corneal
infections. Arch Ophthalmol 1979;97:875.
41. Ellison AC. The limulus lysate test: A rapid test for diagnosis
of pseudomonas keratitis or endophthalmitis. Arch Ophthal-
mol 1978;96:1268.
42. McBeath I, Forester RK, Rebell G. Diagnostic limulus lysate
assay for endophthalmitis and keratitis. Arch Ophthalmol
1978;96:1265.
43. Rao NA. A laboratory approach to rapid diagnosis of ocular
infections and prospects for the future. Am J Ophthalmol
1989;107:283.
44. Egerer I, Stary A. Erosive ulcerative herpes simplex blepharitis.
Arch Ophthalmol 1980;98:1760.
45. Darougar S, Walpita P, Thaker U et al. Rapid culture test for
adenovirus isolation. Br J Ophthalmol 1984;68:405.
46. Repose JS, Nestor MS, Holland GN et al. Analysis of retinal
cotton wool spots and cytomagalovirus retinitis in the acquired
immunodeficiency syndrome. Am J Ophthalmol 1983;95:118.
47. Pepose JS, Holland GN, Nestor MS et al. Acquired immuno-
deficiency syndrome: Pathogenic mechanism of ocular disease.
Ophthalmol 1985;92:472.
48. Vastine DW, Schwartz HB, Yamashroya HM et al. Cytologic
diagnosis of epidemic keratoconjunctivitis by direct immuno-
fluorescence. Invest Ophthalmol Vis Sci 1977;10:195.
 Chapter 151

Neoplasms of Conjunctiva
and Cornea
Anita Panda

INTRODUCTION Reticuloses
A. Lymphoma
The neoplasms of conjunctiva and cornea are
B. Lymphosarcoma
inseparable entities. The corneal epithelium consists
C. Mycosis fungoides.
of nonkeratinized squamous epithelial cells which are
interspersed with spare Langerhan’s cells and Vascular tumors
dendritic melanocytes at the limbus. It differs from A. Benign
its conjunctival counterpart, in that the conjunctival • Hemangioma
epithelium has more nonsquamous cells and mucin- • Lymphangioma
producing goblet cells. The corneal epithelium rests B. Malignant
on the relatively avascular Bowman’s layer, whereas • Angiosarcoma
the conjunctival epithelium rests on its underlying • Kaposi’s sarcoma.
substantia propria with lymphatics and blood vessels
Pigmented tumors
which form the main source of a wide range of
A. Benign: Nevus
mesenchymal tissue tumors besides epithelial tumors.
• Epithelial
CLASSIFICATION OF TUMORS OF • Subepithelial
CONJUNCTIVA AND CORNEA (DUKE ELDER)1 B. Malignant
• Malignant melanoma
Epithelial tumors • Intraepithelial melanoma.
A. Surface epithelium
1. Benign keratoacanthoma Peripheral nerve tumors
2. Benign precancerous A. Benign
• Dyskeratosis (leukoplakia) • Neurofibroma
• Intraepithelial epithelioma • Neurilemmoma
3. Malignant epithelioma. B. Malignant
B. Glandular tumors • Malignant schwannomas.
1. Benign: Adenoma papillary cystadenoma, Corneal and conjunctival neoplasms can also be
lymphomatous oncocytoma subdivided into primary and secondary neoplasms.2
2. Malignant: Pleomorphic adenoma. The latter being a rarer entity, primarily arising due
to involvement of cornea from the tumors of neighbo-
Mesoblastic tumors ring ocular tissues.2
A. Inflammatory granuloma Primary corneal neoplasms are those that originate
B. Benign: Fibroma, myxoma, osteoma from the squamous cells of the corneal epithelium or
C. Malignant: Sarcoma. proliferations of intraepithelial dendritic melanocytes.
1202 Section 9: Miscellaneous Topics

Again these neoplasms can be described to be benign

or malignant depending on their histopathologic
nature.

Benign
A common benign variety being the choristomas.
These are tumor-like growth of elements not normally
indigenous to the site in which they are found. Proto-
typical choristomas are the solid dermoid and
dermolipomas (Figs 151.1A and B).

Dermoid and Dermolipoma

Dermoids are composed of dermis like collagen with
structures of ectodermal origin like sweat glands,
sebaceous glands, hairs and fat lobules (Figs 151.1A Fig. 151.1A: Clinical photography R/E showing a solid dermoid
and B). A dermolipoma is one in which the fat is at temporal limbus with two other isolated corneal opacities
predominant over the other cutaneous adnexal
structures. Association of these epibulbar choristoma
with other ocular and systemic disorders is a well-
known entity. Another commonly described tumor is
lacrimal choristoma which can be simple or complex
depending on whether it contains only lacrimal or
other ectodermal structures also.
Other rarer epibulbar choristomas being osseous
and neuroglial in which cornea generally remains
uninvolved. These lesions remain stationary in
contrast to the former ones which generally tend to
increase in size along with the growth of the globe.

Mesenchymal Tumors
Fibrous Histiocytoma
Fibrous histiocytomas consisting of fibrocytes and
lipidized histiocytes commonly arise at the limbus
with secondary corneal involvement. The bicellular
composition and their cartwheel configuration are
characteristics of these tumors.
Squamous Epithelial Neoplasms
of Cornea and Conjunctiva2,3
The active mitotic zone at the limbus, the region of
transition of the conjunctival into corneal epithelium,
remains the site of origin of squamous epithelial
dysplasia and carcinomas with gradual spread over
to the corneal or conjunctival surface.
Benign Squamous Neoplasia
Dyskeratosis Typical lesions occur at limbus or over the
peripheral cornea and adjacent conjunctiva as
Fig. 151.1B: Clinical photograph L/E showing a upper temporal
dermolipoma with a solid dermoid extending from 3 to 6 o’clock
limbus
translucent white keratinized plaques; surrounding
conjunctiva may be vascularized.
Foreign body sensation is a common complaint of
this benign lesion inherited as autosomal dominant
trait and occurring in the 1st decade of life. Histolo-
gically, areas of acantholysis with dyskeratosis are
seen. These tumors commonly recur after excision, but
they have no potential for malignancy.
Squamous papillomas These are sessile or pedunculated
lesions showing papillomatous appearance with
central fibrovascular core surrounded by non-
keratinizing squamous epithelial cells, usually of the
exophytic type. They arise from any part of the
conjunctiva, limbal region and may show corneal
 Chapter 151: Neoplasms of Conjunctiva and Cornea 1203
involvement. These lesions appear with areas of ulcers are associated with inflammatory component,
keratinizations and pigmentation. These do not show it triggers rapid proliferation of the mass. The older
any potential to turn malignant. A rare endophytic terminology of Bowen’s disease is not recommended
variant reported in literature in which the cornea and intraepithelial neoplasia is a much more accepted
remains involved. term as it accurately refers to the pathological nature
of the lesions (Fig. 151.2). Whether the squamous
Pseudoepitheliomatous hyperplasia (Keratoacanthoma) This
epithelial neoplasia is intraepithelial or invasive is a
benign lesion is a reactive hyperplasia of the squamous
histopathological diagnosis. Clinically, these lesions
epithelial cells of the conjunctiva. It may show corneal
appear as slightly raised, variable shaped translucent
involvement if originating from limbus. Clinically, it
or gelatinous, demarcated from the surrounding
starts as a rapid progressing elevated white lesion with
region. They commonly appear at the interpalpebral
occasional hyperkeratotic surface. Central umblication
region, temporarily or nasally, with marked vascula-
may be seen. Histopathological evaluation may be
rization depending on which, they may appear gray
required for differentiation from squamous dysplasia.
or reddish. Plaques of keratinization (leukoplakia)
Histologically, these lesions show masses of
might occur. Two other types have also been des-
squamous epithelium filled up with acanthosis which
cribed:
gradually merges into the surrounding normal
a. Nodular form which is rapidly growing and has
epithelium. This differentiates it from squamous
tendency for lymphatic metastasis (Fig. 151.2).
dysplasia where there is a demarcation between
b. Diffuse type which is rare (Fig. 151.3).
abnormal and normal epithelium. In keratoacanthoma
there is a central core of keratin surrounded by
acantholytic lobules of hyperplastic squamous
epithelium.

Premalignant and Malignant Lesions

Primary Corneal Epithelial Dysplasia
This is a very rare entity which shows involvement of
the corneal epithelium only or disproportionate
corneal epithelial involvement from a small limbal
lesion. Clinically, it appears as a wide area of frosted
corneal epithelium or individual islands of opalescent
epithelium. Histologically, it shows severe dysplastic
changes in the corneal epithelium. The Bowman’s Fig. 151.2: Clinical photograph showing a nodular lesion
layer restrains further spread into the underlying over conjunctiva extending to cornea (neoplasm)
layer. The importance of primary corneal dysplasia is
its tendency to recur either due to following inade-
quate excision leaving behind some basal cells or
residual abnormal limbal cells.

Precancerous Lesions
These are the potentially malignant lesions which
usually arise at the limbus and spread to other areas.
Histologically, the conjunctiva shows gelatinous
thickening and varying degrees of leukoplakia.

Intraepithelial Neoplasia
The active mitotic zone at the limbus forms the site of
origin for majority of squamous dysplasias. These Fig. 151.3: Clinical photograph showing a diffuse growth
lesions generally show an indolent growth. If the over the conjunctiva and cornea (neoplasm)
1204 Section 9: Miscellaneous Topics

These lesions commonly cause, foreign body sensa-

tion, irritation or redness and diminished vision.
Histologically, the lesion shows abnormally pro-
liferating epithelial cells showing atypical mitosis and
hyperchromatism and nuclear pleomorphism, which
differentiates it from the earlier benign lesions.
Depending on the thickness of the epithelium
involved, intraepithelial neoplasia has been classified
into the following:
a. Dysplasia:
i. Mild—less than one-third occupied by abnormal
cells.
ii. Moderate—three quarters occupied by atypical
cells. Fig. 151.4: Microphotograph of intraepithelial neoplasm
showing intact Bowman’s membrane
iii. Severe—near total involvement.
b. Carcinoma in situ: This shows total involvement
of the epithelium with loss of normal surface layer
without the break of the basement membrane
(Fig. 151.4).

Invasive Squamous Cell Carcinoma

Squamous dysplasia or carcinoma in situ in due course
of time can break the underlying basement membrane
and invade the substantia propria of the conjunctiva,
and Bowman’s layer of the cornea. Once there is
invasion into the underlying Bowman’s membrane, it
becomes an invasive carcinoma (Fig. 151.5). This is
more common at the conjunctival side of the lesion as
the Bowman’s offers resistance to deep penetration of
the tumor cells. However, these locally invasive
lesions do not show any regional lymphatic spread.
Depending on the histological appearance of the
cells, they are further subdivided into five types:
a. Epidermoid/squamous cell/large cell/prickle
cell
b. Spindle cell/small cell/basal cell
c. Clear cell type
d. Mucoepidermoid/goblet cell type4,5
e. Fragmented type.
Spindle cells are the most common type, while
epidermoid cells are less and others are rarer. Occa-
sionally, mixed cell types may be found. Variants of
spindle cell and mucoepidermoid type are very
aggressive.
Mucoepidermoid Carcinoma
These are malignant tumors characteristically
composed of mucus-secreting cells intermixed with
cells showing epidermoid features in variable
Fig. 151.5: Microphotograph of invasive
squamous cell carcinoma
proportions. Sometimes, a third type of cell, called
intermediate or basal cell, has also been described in
this tumor. This is a rare tumor but more aggressive
than squamous cell carcinoma.
Melanocytic Tumors
Melanosis
These are diffuse flat melanotic lesions of the
conjunctiva. They may be congenital or acquired. The
acquired lesions are slow growing and may show
malignant transformation which can be judged by its
nodular appearance (Fig. 151.6).
Benign epithelial melanosis Commonly seen in Black
patients—streaks of melanin are seen in the peripheral
corneal epithelium presenting as flat lesion with no
malignant potential. This represents a benign state of
metabolic hyperactivity of the normal melanocytes
scattered in the conjunctiva and cornea.
 Chapter 151: Neoplasms of Conjunctiva and Cornea
Fig. 151.6: Clinical photograph of L/E showing conjunctival
melanosis over upper bulbar conjunctiva
Benign melanocytic nevi This is the most common
proliferative lesion of the conjunctival melanocytes.
It represents the proliferation of abnormal (modified)
but non-neoplastic melanocytes which aggregate in
the epithelial layer. They occur usually within the first
two decades of life. Depending on the location of the
functional nests, they are classified as subepithelial,
or compound nevi. Conjunctival form can occur
commonly at any site; but with increased predilection
to the limbus, and rare at the basal conjunctiva. Limbal
lesion might involve the peripheral cornea. About
20 percent of conjunctival melanomas arise from pre-
existing nevi. Abnormal proliferative melanocytes
aggregation at the junction of basal epithelium in adult
is called primary acquired melanosis. It may be a
precursor of invasive malignant melanoma.
Invasive Malignant Melanoma
This presents as a raised fragmented or nonfrag-
mented lesion appearing in adult life. They arise from
primary acquired melanosis (60-40%); pre-existing
nevi (20%) and previous unfragmented lesions (10%).
It can occur at any point of the conjunctiva. Lesions of
the limbus and epibulbar surface have better prognosis
than that of fornices or palpebral conjunctiva. Those
measuring 1.5 mm do not metastasize and those above
2 mm have regional lymph glands and distant
metastasis.
Pagetoid Sebaceous Cell Carcinoma
Sebaceous cell carcinoma usually starts in the
meibomian gland, Zeiss’ gland or sebaceous gland of
caruncle and these cells show pagetoid pattern of
1205
involvement along the epithelial surface and thus
corneal epithelial involvement.
INCIDENCE
Though uncommon an average incidence of 0.13/
100,000 has been reported. However, it is less common
than oculo-orbital squamous cell carcinoma.3
AGE AND SEX DISTRIBUTION
It predominantly occurs in older individual. The
average age of occurrence is 56 years. Males are more
affected than females.3
Predominance in Caucasians is reported. Further,
Caucasian population at latitudes closer to the equator
than 30° are at particular ocular risk.3
ETIOLOGY
Stem Cell Theory3
These cells are located at the limbal region. Charac-
teristically, the cells are long lived and have great
potential for clonagenic cell division. Thus, they have
the tendency for corneal epithelial replacement.
Ultraviolet B Light
Exposure to excess ultraviolet B light (UV-B) is
identified as a risk factor.
Human Papilloma Virus
Human papilloma virus (HPV) type 16 has been
considered as an etiological factor.
Related Diseases
Cases of pterygium, pinguecula, climatic droplet
keratopathy, cataract and corneal degeneration are at
particular risk due to common factor of UV-B light
exposure. Chronic lymphocytic leukemia and
Hodgkin’s lymphoma are at particular risk. Xero-
derma pigmentosum is identified as an associated
factor in children. Further, its association with human
immunodeficiency virus (HIV) is reported.
MANAGEMENT
Investigations
Exfoliative Cytology6
This is a procedure by which the specimen is taken
from one or more appropriate areas of the lesion by a
1206 Section 9: Miscellaneous Topics
sterile platinum spatula, fixed with 95 percent alcohol
and stained with Papanicolaou technique.
Advantages
a. Diagnosis of conjunctival and corneal tumors.
b. Exclusion of the diagnosis of cancer in persistent
unilateral epibulbar inflammation.
c. An alternative to biopsy when the patient refuses
to get it done so.
d. Detection of recurrence.
e. It can differentiate between dysplasia, carcinoma
in situ and invasive lesion.
Limitations
a. It is a difficult technique to practice.
b. It is uncomfortable for the patient.
c. It requires an experienced pathologist for interpre-
tation.
d. It does not localize the lesion.
e. It does not indicate the degree of invasion.
Impression Cytology7
It can be performed by placing a cellulose acetate filter
paper sheet over the surface of the lesion. After
removing the paper which contains the most super-
ficial epithelial cells can be fixed and stained with
Papanicolaou technique.
Advantages
a. It is simple, noninvasive and can be repeated.
b. It enables more precise localization of the area.
c. It can assess cell-to-cell relationship.
d. It can differentiate between dysplasia, carcinoma
in situ and invasive lesions.
Limitations
It cannot predict the deeper involvement.
Immunohistology
By using bromodeoxyuridine, a thymidine analogue,
the conjunctival epithelial cell cycling can be judged.
It has been used to demonstrate an increased
proliferation of basal epithelial cells and suprabasal
cell DNA synthesis.
Nucleolar organizer regions which are composed
of genes coding for RNA can be detected by this
technique.
Advantages
a. It distinguishes dysplasia from neoplasia.
b. The degree of malignant potential can be judged.
Limitations
It is time-consuming.
Frozen Section Guided Excision8-10
This procedure, though considered as a diagnostic and
therapeutic modality; it cannot provide a proper
diagnosis.
Histopathology1-4
This is the final method of examination of the total
specimen. This can be performed after cutting the
specimens and staining with H and E stain.
Advantages
a. It can detect the degree of dysplasia.
b. It can differentiate between dysplasia, carcinoma
in situ and invasive squamous cell carcinoma.
c. It can also identify the nature of the malignant cells,
thus differentiating between types of invasive
squamous cell carcinoma.
Limitations
Though it provides exact final diagnosis, it does not
ascertain the total eradication.
Electron Microscopy
This procedure can be beneficial to diagnose a case of
ocular surface squamous neoplasia by identifying
excessive number of organelles including mito-
chondria, endoplasmic reticulum, tonofilaments,
reduced number of desmosomes alteration in base-
ment membrane and deposition of fibrillogranular
material between the basement membrane and
Bowman’s layer.
Treatment
Surgery
Wide excision It is the most accepted method of therapy.
While doing, care should be taken to dissect all
abnormal tissue within the wide surgical margin of
2 to 3 mm normal tissue.1-3
a. Rose bengal staining may help in delineation of
extent of abnormal tissue after excision.
b. Frozen section of the lesion can be used to assess
the adequacy of excision margins. It can accurately
delineate horizontal tumor spread.8,9
c. Microscopic tumor margin surveillance by Moh’s
micrographic technique. The method involves
removal of graft mass of tumor with a lateral
resection margin of 2 mm.
 Chapter 151: Neoplasms of Conjunctiva and Cornea
Specimen is carefully oriented and processed by
permanent section within 24 hours; if contains tumor
cells, patients returned for a second stage excision
within 3 to 4 days with additional excision of 2 mm of
tissue.
Excision with lamellar keratoplasty Removal of deep
corneal invasion can be managed by lamellar kerato-
plasty.
Excision with limbal cell transplant Excessive removal
of limbal tissue during tumor excision can be managed
by additional limbal allograft or autografy.
Enucleation and Exenteration Though not performed
routinely, these are indicated in aggressive cases.
Partially removed tumor commonly has a tendency
to recur with more aggressive behavior due to
disruption of the integrity of Bowman’s membrane.
Excimer The use of 193 mm argon fluoride excimer
laser for recurrent cases provides a better alternative.
Radiotherapy
Use of strontium 90, is proved to be beneficial. It
delivers a 100 percent in most superficial layers of
tumor location.
Dose Lesion less than 1 mm or postoperative 1 × 60
Gy or 3 × 20 Gy, lesion more than 1 mm 4-7 × 20 Gy at
weeks intervals.
Cryotherapy
This is recommended after wide excision of tumor. A
nitrous oxide cryoprobe is used to form an ice ball
extending 2 mm for the conjunctiva, 1 mm for the
episcleral tissue and limbus and 0.5 mm on the cornea.
After end-to-end closure of the conjunctiva, the
procedure is repeated. If the dissection is inadequate,
the freezing is recommended three times. The time of
application of probe each time should not be more
than 3 seconds.
It acts by destroying cells initially by its freezing
effect and later by obliteration of the microcirculation.
It may also activate an immunological response to
1207
liberate tumor antigens. The most important area to
freeze is the limbus.
Immunotherapy and Chemotherapy
Mitomycin C Topical mitomycin C 0.02 percent 4 times
a day for about 3 weeks has been advocated for corneal
intraepithelial neoplasia without excision.10 Following
excision, a single application of the drug over
conjunctiva and episclera provides good result.
5-FU This is another cytotoxic drug that can be used
as an alternative to MMC.
Recurrence
It is always dependent on the status of surgical margin.
The rate of recurrence as reported in literature varied
from 17 to 52 percent.
Metastasis
Intraocular invasion and metastases are very very rare.
REFERENCES
1. Sir Stewart Duke Elder (Ed). Disease of Outer Eye. London:
Henri Kimpton, 1977;1137-39.
2. Frederick AJ. Corneal tumors. In HE Kaufman (Ed): The
Cornea. New York: Churchill Livingstone 1988.
3. Lee Graham A, Lawrence WH. Ocular surface squamous
neoplasia. Survey of Ophthalmology 39:429-49.
4. Rao NA, Font R. Mucoepidermoid carcinoma of the
conjunctiva. Cancer 1976;38:1699-1709.
5. Gamel JW, Richard AE, Gulbor Pierre. Mucoepidermoid
carcinoma. Arch Ophthalmol 1984;102:730-31.
6. Gelender H, Forster RK. Papanicolaou cytology in the
diagnosis and management of external ocular tumors. Arch
Ophthalmol 1980;98:909-12.
7. Mahoney MC, Burne WS, Majerovics A et al. The epidemio-
logy of ophthalmic malignancies in New York. Ophthal-
mology 1990;97:1143-47.
8. Panda A, Sharma N. Lamellolamellar sclerokeratoplasty for
squamous cell carcinoma of conjunctiva and cornea.
Ophthalmic News International 1996;7:42.
9. Panda A, Sharma N, Sen S et al. Squamous of conjunctiva
and cornea. Ophthalmology Today 1996;278-79.
10. Wilson MW, John LH, George SM et al. Topical mitomycin C
for conjunctival epithelial dysplasia and neoplasia. Am J
Ophthalmol 1997;124:303-11.
 Chapter 152
Management of Corneal
Epithelial Defects
Anita Panda, Neelam Pushker
MICROANATOMY OF CORNEAL EPITHELIUM
Epithelium of the cornea and conjunctiva forms the
outermost layer of the anterior part of eyeball and its
adnexa, derived from surface ectoderm. The corneal
epithelium is a stratified, squamous, nonkeratinized
epithelium, composed of approximately five to seven
layers of cells. Outermost layer of flat surface cells, is
followed by polygonal wing cells and columnar basal
cells. Epithelial cells are closely attached to each other
with regular intermembranous spacing of 200 Å. All
the layers contain numerous desmosomal attachments
(maculae occludens), which form permeability barrier.
Array of tonofilaments within the cells maintain the
shape. Surface cells are two layers deep with
innumerable microplicae and microvilli of the anterior
plasma membrane which augments free surface
area for tear film retention and stability. The wing
cells consist of three layers. Columnar basal cell is
composed of single layer of mitotically dividing cells
with actin filaments in it, which play a role in cell
migration. Hemidesmosomes and anchoring fibrils
help in tight adherence of basal cells to the basement
membrane. Branches from the trigeminal nerve pierce
the Bowman’s layer and terminate as unmyelinated
nerve ending among the basal epithelial cells. Energy
source is stored as glycogen in the cells which depletes
during epithelial wound healing.1
The surface renewal cells for the corneal epithelium
are located in the limbal zone called stem cells. These
cells are primitive cells with low mitotic activity. Each
stem cell divides into transient amplifying cells (TAC)
and stem cells. The TAC matures into approximately
1000 terminally differentiated cells which does not
divide further.2 Stem cells extend approximately 0.5
mm on the cornea and 1 mm on the conjunctival
surface.3
FUNCTIONS OF THE CORNEAL EPITHELIUM
• Corneal epithelium provides a very smooth
refracting surface. Any kind of epithelial irregu-
larities (defect, edema, drying) leads to profound
effect on the vision because of light scattering.
• It maintains clarity of the cornea by modulating
fluid transport out of the stroma.
• It forms a functional barrier between tears and
intraocular environment, by maintaining relative
impermeability to water-soluble agents and tear-
borne pathogens.
• The epithelial cells have elaborate reticulation
which holds the tear film and contributes to the
tear film stability.
Any insult to the epithelium, direct or indirect due
to an abnormal endothelial pump function may give
rise to epithelial defect (Table 152.1).
EXAMINATION
The corneal surface is very smooth, lustrous and
transparent. Epithelial defect makes the corneal
surface irregular. Though an accurate assessment of
the corneal surface may be made by Placido kerato-
scopic disk, its approximate area and rarely a small
epithelial defect may not be detected. A slit lamp
examination after staining the cornea with vital stains
 Chapter 152: Management of Corneal Epithelial Defects
Table 152.1: Causes of epithelial defect
1. Ocular disorders
• Traumatic
— Chemical/thermal burns
— Radiation injury
— Fingernail/paper cuts
— Corneal foreign body
— Postsurgical (keratoplasty, radial
keratotomy, photorefractive, keratectomy,
phototherapeutic keratectomy)
• Inflammatory
— Uveitis
— Marginal keratitis
• Degeneration and dystrophy
— Meesman’s dystrophy
— Reis Buckler dystrophy
— Stromal dystrophy
— Fuchs’ dystrophy
• Neurogenic
— Herpes simplex keratitis
— Herpes zoster keratitis
• Nutritional
— Vitamin A deficiency
• Iatrogenic
— Drug induced
— Contact lens induced
• Miscellaneous
— Filamentary keratitis
— Dry eye
— Raised intraocular pressure
2. Systemic disorders
— Diabetes
— Epidermolysis bullosa
is essential for the minute examination and assessment
of the size of the defect size. Fluorescein dye (1%) is
usually employed for delineating areas of epithelial
loss. It stains the denuded area brilliant green. Rose
bengal dye one percent is used for staining superficial
punctate keratitis because this dye can detect diseased
and devitalized cells.
For monitoring healing rate, it is essential to
calculate defect size which can be determined either
by using Haag-Streit 900 slit lamp or planimetry.
Slit Lamp Examination
After instilling one percent fluorescein dye or applying
moistened fluorescein sodium ophthalmic strip in
lower cul de sac, maximum and minimum dimensions
of the epithelial defect is measured by slit lamp.
Approximate area is calculated in sq mm.4
1209
Planimetry
Cornea is stained with fluorescein dye and photo-
graphed using a fundus/anterior segment camera
with a blue filter. The photograph is photocopied on
a graph paper. The area of the defect and the cornea is
calculated and size is expressed as a percentage of the
total corneal area.5 The rate of epithelial defect healing
is determined by calculating the percentage area of
the defect on successive days. The mean values for
each day are plotted on the graph.5
NORMAL CORNEAL EPITHELIAL HEALING
Most of the experimental studies on the surface
characteristics of the corneal epithelial cells have been
done using scanning electron microscope.6-8 These
studies show consistent pattern of epithelial wound
healing but controversies regarding several facts, still
exist. Following insult to the corneal epithelium, the
process of cellular and subcellular organization and
multiplication of the epithelial cells start. The funda-
mental healing process is divided into two phases
(biphasic process), i.e. latent phase and linear healing
phase.9
Latent phase is the time when remaining viable
cells are transformed into motile cells. Immediate
response to cell trauma is loss of surface microvilli,
and retraction of wound edges. The damaged cells and
cellular debris slough off in a few minutes. Poly-
morphonuclear leukocytes appear at the site of defect
in approximately 8 to 24 hr from tears and conjunctival
capillaries. It further helps in removing cellular
remnants. At the end of this phase, hemidesmosomes
break and leading cells in the defect send pseudo-
podia.
Linear healing phase is the time required for
complete restoration of epithelial thickness and
continuity. The first step toward this phase is flattening
and migration of the cells in amebic fashion toward
the denuded surface called ‘epithelial slide’.10 This is
an active process which requires detachment from
underlying fibronectin and presence of actin filaments
for its movement. Fibrin and fibronectin stimulate
epithelial cells to release plasminogen activator which
converts plasminogen to plasmin. Plasmin, a proteo-
lytic enzyme, breaks adhesion of epithelial cells to the
fibrin and fibronectin, and helps in migration of these
cells.1
Further, fibronectin and fibrin are deposited on the
denuded surface but reabsorbed after restoration of
1210 Section 9: Miscellaneous Topics

epithelial integrity. Sliding continues at a constant rate,

till cells encounter each other which leads to contact
inhibition of migrating cells. At the end of migration,
the defect takes a ‘V’ shape. The cells which cover the
defect begin to reveal characteristics of basal cells, i.e.
cells become columnar. Epithelization is taken over
by these basal cells, i.e. mitosis starts, with peak at
24 hours. Contact by cytoplasmic processes forms the
tight cell-to-cell and cell-to-basement membrane junc-
tions. Till the interconnections are loosen, the disrup-
tion of epithelial continuity is possible at any stage.
Irregularities of the epithelial surface leads to poor
adherence of precorneal tear film. If the epithelial base-
ment is not damaged, the sliding cells form hemides-
mosomes and anchoring fibrils by two days. Basement Fig. 152.1: Process of normal corneal
membrane, if destroyed, takes a long time to reform. epithelial wound healing
New basement membrane complexes comprise of
short discontinuous segments of basement membrane
material. If severely damaged, it takes 6 to 8 weeks
for complete basement reconstruction (Fig. 152.1).

CLINICAL PATTERNS OF HEALING PROCESS

Nonuniform reduction in the area of epithelial defect
has been noted in most of the studies.5 Along the
circumference of the epithelial defect, migrating
epithelial sheets develop three to six leading convex
fronts which advance toward the center (Fig. 152.2).
These fronts are apparent in 12 to 36 hours after
trauma. Depending on the number of convex fronts,
different geometric shapes, i.e. pentagon, hexagon,
triangle, etc. are formed. Finally, these sheets meet Fig. 152.2: Diagrammatic representation of clinical pattern.
each other to form a contact line shaped ‘Y’ or two (1) Corneal epithelial defect, (2) Convex leading fronts,
‘Y’s placed with their long axes end to end. The contact (3) Geometric shapes, (4,5) Contact lines
line may be fragmented and is generally formed in
hydration and oxygenation, prevents infection and
the center of the original defect. Finally, punctate
gives immediate symptomatic relief. Traditionally, the
staining is left which gradually disappears with
medical management of acute corneal epithelial defect
complete restoration of epithelial continuity. In defects
consists of instillation of topical cycloplegics, antibiotic
involving the corneoscleral limbus, no cell fronts
ointment, and pad and bandage. Persistent epithelial
develop from the limbal segment. From the surround-
defect requires both medical and surgical treatment.
ing area, the epithelial sheets develop and fill the
Rationale of different modalities should be known
defects.5
before deciding the treatment plan.
MANAGEMENT OF ACUTE EPITHELIAL DEFECT
Medical
Corneal epithelial defect represents a substantial
Topical Medications
proportion of the ocular morbidity presenting to the
eye casualty department. Till date, none of the Prevention of infection by instillation of topical
treatment modalities could show better efficacy over antibiotics is essential in the treatment of corneal
the other. Ideal treatment modality is one which epithelial defect. Ointment is preferred to drops, since
provides faster epithelial healing, adequate corneal it provides longer contact time and acts as a lubricant
 Chapter 152: Management of Corneal Epithelial Defects
between the epithelial defect and lid, hence topical
fibrinectin prevents desiccation and frictional damage
to migrating epithelial sheet by the lid movements.
Thus, it alleviates the pain and accelerates epithelial
healing. There is no place for steroid preparation in
the management of corneal epithelial defect. Use of
only topical medications in first instance, has shown
good results.13 Use of topical cycloplegics provides
symptomatic relief by reducing ocular pain and
inflammation by alleviating ciliary spasm.11,12
Double Eye Pads and Bandage
(with Antibiotic Ointment, with/without
Cycloplegics)
Controversial aspects of occlusive patching use, still
exists. Presumed benefits of patching are that it
provides stable corneal environment for epithelial
healing, immobilizes eyelids which lessen trauma to
the migrating epithelial sheets and immediate
symptomatic relief. Although a few studies have
shown increase in discomfort with padding, which
may be either because of pressure of a firm eye pad
on the abraded surface or eye pad becoming loose
which allows lid opening beneath it.4,14 Potential
disadvantages of patching include decrease corneal
oxygenation which slows epithelial migration and
proliferation, and increases corneal temperature and
decreases natural irrigation by tears which risk the
eye to infection, especially if defect is produced by
contact lens use.15 Besides this, it leads to temporary
monocularity which has adverse effect on depth
perception and visual field. In children, it may
endanger visual development.
For small epithelial defects, role of padding is negli-
gible, as it tends to heal quickly. Candidates for patch-
ing include patients with very large corneal abrasion
and those producing significant photophobia.
Contact Lens/Capping
Soft Bandage Contact Lens (BCL)
with Topical Antibiotic Drops
Soft bandage contact lens with topical antibiotic is
usually not13 preferred at the first instance for treating
epithelial defect. Its main advantages are provision
of useful vision during healing period without any
cosmetic blemish. Specific indications for its use are,
a very symptomatic patient or a patient with history
of recurrent erosions,16 large corneal abrasion17 or
because of professional reasons. Complications of
1211
contact lens use are corneal edema, vascularization
and infection. Most important disadvantage being cost
factor, as most of the epithelial defects take 5 to 7 days
to heal and the cornea cannot be fully examined with
a contact lens in place.
Collagen Shield
Collagen shield is another alternative to hydrophilic
bandage contact lens (BCL).18 It has several theoretical
advantages over BCL, it conforms to the corneal
contour and eliminates fitting problems, it biode-
grades with time and hence increases oxygen
transmission. It speeds re-epithelialization, provides
useful vision and is more comfortable than padding.18
Thus, it is preferred in patients with only one seeing
eye, or those who cannot tolerate a patch for cosmetic
reasons, and in contact lens wearers where prophy-
lactic administration of topical antibiotics is essential.
Main disadvantages with its use are excessive
movement of the shield or its dislodgement into the
superior or inferior fornix.18 Cost factor is also one of
the limitations of its use.
Collagen shield is fabricated from porcine scleral
tissue containing collagen, mostly type I with type III.
Molds of shield in the form of contact lens is available
which is hydrated and placed in the eye where it takes
the shape of the cornea. The shield is of 14.5 mm
diameter, a 9.0 mm radius of curvature and approxi-
mately 0.1 mm thickness. Depending on the number
of cross-linkages in the collagen matrix, the shield
dissolves over a period of 12 to 72 hr and requires
replacement.19
Surgical
Various surgical procedures for persistent epithelial
defects include the following:
a. Tissue adhesive
b. Conjunctival graft
c. Lamellar keratoplasty, and more recently limbal
transplantation and amniotic membrane graft.
When there is poor visual potential, treatment with
conjunctival flaps or tarsorrhaphy is contemplated.
Tissue Adhesive
Cyanoacrylate is a tissue adhesive which was first used
on a human eye by Webster et al in 1968.20 Since that
time, various studies have been made using different
cyanoacrylate adhesives, i.e. n-heptyl, octyl, isobutyl,
methyl-2, etc. Recently, tissue adhesive used are alkyl
1212 Section 9: Miscellaneous Topics
derivatives isobutyl (histacryl-n-blue B-Braun,
Germany) and n-butyl-nexacryl (Tri Point Medical LP
Raliegh, NC),21 cyanoacrylate. None of these tissue
adhesives has received FDA approval. These are
stored at 4 to 8°C in a plastic container with an
installation spout for several months. This method of
storage helps in preventing contamination and
polymerization. It is applied after anesthetizing the
cornea with topical xylocaine 4 percent, under slit
lamp. Use of speculum, helps in exposing the area
properly. After drying and debriding the area of
application, a small drop of tissue adhesive is placed
on the thinnest area with dried cotton tip applicator
or 27 G needle. The area is covered properly.
Polymerization takes 2 to 3 minutes to occur after
which bandage soft contact lens is applied. Prophy-
lactic topical antibiotic drop is started and patient is
examined daily. Adhesive can be kept in place till
complete healing occurs or till it sloughs off spon-
taneously. It is reported to stay in place for average
2 to 3 months.21 Complications reported with its use
are corneal infiltration, endophthalmitis, uveitis, glau-
coma, scarring of conjunctiva and symblepharon
formation.21,22
Conjunctival Graft
Conjunctival graft has been advocated for persistent
epithelial defect. Zeiske23 produced a monoclonal
antibody for 50k keratin which is specific for stem cells
and reported stem cells in 1 mm of perilimbal
conjunctiva. Procedure includes resection of abnormal
conjunctiva approximately 5 mm posterior to the
limbus for 360 degrees, combined with total superficial
keratectomy to remove the vascularized and scar
tissue. From fellow eye pieces of 3 mm in diameter
conjunctiva are taken, which are sutured on the
periphery of the cornea with 10 ‘0’ monofilament
nylon sutures.24 This procedure depends upon the
transformation of conjunctival epithelium into corneal
epithelium.
Conjunctival Flap
The indications of conjunctival flap are patients with
persistent epithelial defects with (usually herpetic or
neurotropic keratitis, keratoconjunctivis sicca) poor
visual prognosis. Gundersen flap,25 which includes
360° peritomy and covering of the cornea with
conjunctiva which is sutured inferiorly to inferior
limbal conjunctival edge and superiorly to episclera.
The superior conjunctiva is left bare which covers by
rapid re-epithelialization.
Limbal Allograft Stem Cell Transplantation
Limbal transplantation26 is based on the concept that
the limbal epithelium contains the stem cell population
for corneal epithelial cell proliferation and differen-
tiation and has been advocated for a number of ocular
surface disorders including epithelial abnormalities.
The concept of stem cell though not new, most of
us are not used to the terminology. By definition, these
cells are present in all self-renewing tissues. These are
long-living cells have greater potential for clonagenic
cell division and are ultimately responsible for cell
replacement. Anatomically, there are ridges in the
perilimbal conjunctiva perpendicular to the cornea
and these perilimbal arrays are the source of stem cells.
The stem cell population is broadest in the upper and
lower limbal poles. Following the healing of an
eccentric epithelial defect, there is appearance of
pigmented migration lines from the limbal region.
This suggests that for the replacement of corneal
cellular loss, the centripetal movement of limbal cells
are responsible. Further, such healing is accomplished
by cellular proliferation and migration of adjacent
cells. It is also known that a large eccentric epithelial
defect heals much quicker than small central defect.
This is because the peripheral corneal epithelium has
a higher proliferative rate.
Following corneal grafting, the host central
epithelium is replaced by the centripetal movement
of the surrounding host corneal cell. Persistent
epithelial defect in a corneal graft indicates decrease
in the epithelial stem cell population. Therefore,
replacement of these lost or damaged cells by limbal
cell transplantation offers a source for new cells which
subsequently will be responsible for the maintenance
of a smooth ocular surface.
Surgical Procedure
A 360° peritomy is performed in the recipient eye and
the conjunctiva is recessed 3 mm beyond the limbus
followed by a superficial keratectomy and peeling off
abnormal epithelium.
The graft is either obtained from a moist chamber
stored eyeball or in situ removal from the cadaver
cornea.
The size varies from 5 to 10 mm long (approxi-
mately 2 to 4 clock hours) 2 to 3 mm width and 0.5 to
 Chapter 152: Management of Corneal Epithelial Defects
1 mm thick for the superior and inferior limbus. The
harvested tissues are fixed to the opposite limbus in a
fashion that 0.5 to 1 mm extends into the clear cornea
and 2 mm beyond the surgical limbus, with 10-0
monofilament nylon suture at 2 ends. Additional one
suture is applied at scleral end. A large therapeutic
high water content soft lens (16.5 mm diameter, 9.5
mm base curve, DK 75) is placed at the end of the
surgery. Subconjunctival antibiotics and cortico-
steroids complete the surgery. Postoperatively, it is
required to use preservative free topical antibiotics
and corticosteroids along with high dose of systemic
corticosteroid or preferably cyclosporin A.
Tarsorrhaphy
Tarsorrhaphy helps in keeping ocular surface
hydrated and hence prevents damage to the sliding
epithelial cells by desiccation. Unlike occlusive
patching, it does not hamper corneal oxygenation and
natural irrigation by tears. Added benefit of lateral
tarsorrhaphy is, it prevents monocularity and adverse
effects related to it. Cosmetic blemish is its major
disadvantage.
Amniotic Membrane Transplantation
More recently, use of preserved amniotic membrane
to manage persistent corneal epithelial defect
effectively has been advocated. 27 This procedure
should be tried in refractory cases before considering
treatment by conjunctival flap or tarsorrhaphy.
Amniotic membrane can be easily harvested, but it
requires storage at –80°C in a sterile container
containing the media. The membrane can be preserved
up to 70 days.
The amniotic membrane contains a thick basement
membrane and an avascular stromal matrix. These
features are crucial to successful transplantations. The
basement membrane facilitates migration of epithelial
cells and promotes epithelial differentiation. The
basement membrane is also important in preventing
epithelial apoptosis. Besides this, it also reduces
inflammation, scarring and vascularization and helps
in reconstructing perilimbal stroma. Amniotic
membrane does not express usual major histo-
compatibility antigens, such as HLA A, B or DR and
does not require therapy with immunosuppressants.
These actions collectively are responsible for
promoting rapid epithelialization. In the initial stage
the membrane becomes opaque. However, it is
1213
dissolved subsequently providing a clear healthy
corneal epithelium.
In conclusion though the corneal epithelial stability
is altered due to a variety of causes, if diagnosed early
and treated effectively, a normal corneal surface is
maintained. Further, considering the updated
knowledge regarding the therapy of the persistent
epithelial defect, the prospective randomized
comparative study with longer follow-up is required
to establish an ideal procedure.
REFERENCES
1. Arffa RC. Anatomy. In Craven L, Cox KJ, Loonstyn SK (Eds):
Grayson’s Diseases of the Cornea. St. Louis: Mosby-year book,
Inc, 1997;7-8.
2. Cairme AB, Lala PK, Osmond DG (Eds). Stem Cells of
Renewing Cell Populations. New York:Academic Press, 1976.
3. Zeiske JD, Bukersogla G. Characterization of potential marker
of corneal epithelial stem cells. Invest Ophthalmol Vis Sci
1992;33(1):143-52.
4. Kirkpatrick JNP, Hoh HB, Cook SD. No eye pad for corneal
abrasion. Eye 1993;7: 468-71.
5. Dua HS, Forrester JV. Clinical pattern of corneal epithelial
wound healing. Am J Ophthalmol 1987;104:481-89.
6. Brewitt H. Sliding of epithelium in experimental corneal
wounds: A scanning electron macroscopic studies. Acta
Ophthalmol 1979;57:945-57.
7. Haik BG, Zimny ML. Scanning electron microscopy of corneal
wound healing in the rabbit. Invest Ophthalmol Vis Sci
1977;16:787-96.
8. Kuwabara T, Perkins DG, Cogan DG. Sliding of the
epithelium in experimental corneal wounds. Inv Ophthalmol
Vis Sci 1976;15:4-14.
9. Crosson CE, Klyce SD, Beuerman RW. Epithelial wound
closure in the rabbit cornea. Inv Ophthalmol Vis Sci
1986;27:464-73.
10. Buck RC. Cell migration in repair of mouse corneal
epithelium. Invest Ophthalmol Vis Sci 1979;18:767.
11. Knox KA, McIntee J. Nurse management of corneal abrasion.
Br J Nurs 1995;4:440-60.
12. Duke-Elder S. Textbook of Ophthalmology. London: Henry
Kimpton, 1954;6:5993-98.
13. Sabri K, Pandit JC, Thalller VT et al. National survey of corneal
abrasion treatment. Eye 1998;12:278-81.
14. Cintron C, Kublin CL, Covington H. Quantitative studies of
corneal epithelial wound healing in rabbits. Curr Eye Res
1981-82;1:507.
15. Patternson J, Fetzer D, Krvall J et al. Eye patch treatment for
the pain of corneal abrasion. Southern Medical Journal
1994;89:227-29.
16. Williams R, Buckley RJ. Pathogensis and treatment of
recurrent erosions. Br J Ophthalmol 1985;69:435-37.
17. Acheson JF, Joseph J, Spalton DJ. Use of soft contact lenses in
an eye casualty department of the primary treatment of
traumatic corneal abrasion. Br J Ophthalmol 1987;71:285-89.
18. Wedge CI, Roothman DS. Collagen shields: Efficacy, safety
and comfort in the treatment of human traumatic corneal
1214 Section 9: Miscellaneous Topics
abrasion and effect on viscous in healthy eyes. Can J
Ophthalmol 1992;27:295-98.
19. Frantz JM, Dupuy BM, Kaufman HE et al. The effect of
collagen shields on epithelial wound healing in rabbits. Am J
Ophthalmol 1989;108:524-28.
20. Webster RG, Slansky HH, Refojo MF et al. The use of adhesive
for the closure of corneal perforation: Reports of two cases.
Arch Ophthalmol 1968;80:705-09.
21. Leahey AB, Gottsch JD, Stark WJ. Clinical experience with n-
butyl cyanoacrylate (nexacryl) tissue adhesive. Ophthal-
mology 1993;100:173-80.
22. Weiss JL, Lindstrom RL, Doughman DJ. The use of tissue
adhesive in corneal perforations. Ophthalmology 1983;90:6.
23. Zeiske JD, Bukusogla G. Characterization of potential marker
of corneal epithelial stem cells. Invest Ophthalmol Vis Sci
1992;33(1):143-52.
24. Thoft RA. Conjunctival transplantation. Arch Ophthalmol
1977;95:1425.
25. Gundersen T. Conjunctival flaps in the treatment of corneal
disease with reference to a new technique of application. Arch
Ophthalmol 1958;60:880.
26. Donald TH, Linda T, Ficker A et al. Limbal transplantation.
Ophthalmology 1994;101:29-36.
27. Lee SH, Tseng Scheffer CG. Amniotic membrane trans-
plantation for persistent epithelial defect. Am J Ophthalmol
1997;121:303-12.
 Chapter 153

Ocular Manifestations
in Tropical Diseases
R Mukherji

Worldwide there are 1 to 2 billion persons affected by Tuberculoid Type

tuberculosis and more than 6 billion persons are dually
In this type, hypopigmented anesthetic patches appear
infected by tuberculosis and AIDS. Though any
on the skin, commonly of the face, lateral aspects of
disease of humans can occur anywhere in the world
the arms and legs, buttocks and scapular region.
with the same clinical features, some diseases are more
Thickened nerves and loss of hair of the skin are
common and at times are endemic in certain areas.
common manifestations; white patches in the skin of
The hot and humid climate of the tropical region plays
the eyelids and loss of hair of the eyebrows and lids
an important role in the multiplication and survival
(madarosis) are characteristic ocular signs. The
of the organisms. With the improvement of the socio-
common ocular complication in this type is due to
economic conditions and implementation of proper
lagophthalmos from 7th nerve palsy and consequent
preventive measures, many of the tropical diseases
exposure keratitis. Secondary infection leading to
are on the decrease. Thus, though tuberculosis is a
sloughing corneal ulcer, iris prolapse and panoph-
global problem, its incidence is high in India.
thalmitis lead to blindness.
According to the WHO estimates, 14 million people
are suffering from tuberculosis in India and it takes a
Lepromatous Type
toll of 0.5 million every year.1,2
The incidence and pattern of diseases vary in In this type, the eye is actually invaded by Lepra bacilli.
different regions of the tropics.3 Onchocerciasis is Small episcleral nodules may appear. The chalky
common in tropical Africa and epidemic dropsy is white punctate superficial infiltration of cornea is
known to occur only in India. Following is an account pathognomonic of the disease. Leprotic interstitial
of some of the diseases common in tropical countries. keratitis is also common. Cornea is usually anesthetic.
Minute round yellowish white nodules are formed
Leprosy over the surface of the iris (iris pearls). These pearls
contain the Lepra bacilli.4 Blindness in leprosy can be
Leprosy, a chronic infective disease caused by
prevented by early institution of treatment with
Mycobacterium leprae, is common in tropics and
diaminodiphenyl sulphone and its derivatives along
subtropics. India is believed to have the largest
with energetic treatment of iritis with steroids.
number of nearly one-third of the estimated 4 million
leprosy cases in the world. About 25 percent of leprosy
Bacillary Dysentery
cases have ocular involvement. Clinically and
pathologically, there are two types of leprosy— Acute infection of the mucous membrane of the large
(a) tuberculoid type and (b) lepromatous type. intestine due to bacilli of the genus Shigella is a
1216 Section 9: Miscellaneous Topics
common gastrointestinal disorder. Catarrhal con-
junctivitis has been reported in the early stages of the
disease. Some patients might develop uveitis.
Cholera
Infection by Vibrio cholerae following ingestion of
infected water, milk, cut-fruit, uncovered food, etc. is
still a problem of the tropical third world countries.
The characteristic profuse watery stool and severe
vomiting make the patient acutely dehydrated which
may lead to coma. Ocular involvement is due to half
open eyes of the patient during the comatose stage.
The lower half of the cornea is exposed and becomes
dry. Lack of lacrimal secretion during the stage of
acute dehydration leads to ulceration of lower half of
the cornea. The severe dehydration also alters the fluid
constituents of the lens which may lead to cataract
formation.
Amebiasis
The infection by Entamoeba histolytica is quite frequent
in tropical countries. It is estimated that about
20 percent of rural population are the victims of this
parasitic intestinal disease causing dysentery, hepatitis
and liver abscess.
Ocular Involvement of Amebiasis
a. Anterior and posterior uveitis
b. Recurrent vitreous hemorrhage
c. Retinal periphlebitis.5
In none of the affected cases, however, Entamoeba
histolytica could be isolated from the eye. The
presumptive diagnosis was based on coexistent
disease process and definite improvement of the eye
condition after antiamebic treatment.
Giardiasis
Infection by Giardia lamblia is a common intestinal
infection in the Indian subcontinent. Keratitis, uveitis,
extensive chorioretinitis and retinal hemorrhages in
patients with giardiasis have been reported.6 All the
reported cases responded well to the treatment of
giardiasis.
Malaria
Annually, there are about 300 million cases of malaria
worldwide and 30 million persons from non-endemic
countries visit malaria endemic countries; thus, there
is a significant possibility of traveler’s malaria. The
parasite responsible for malaria in humans belongs
to Plasmodium family—P. vivax (tertian malaria),
P. malariae (quartan malaria), P. falciparum (subtertian
malaria) and P. ovale. Ocular complications are more
common in P. falciparum infection. Almost all the
structures of the eye may be involved in malaria.7
Conjunctival hyperemia, subconjunctival hemor-
rhage, conjunctival pigmentation, dendritic ulcer,
interstitial keratitis, uveitis, vitreous hemorrhage,
retinal hemorrhage, retinal detachment, optic neuritis,
paralysis of extraocular muscles and orbital cellulitis
have been reported.2 Retinal hemorrhage is considered
to be due to rheologic complications—the parasitized
erythrocytes tend to clump along the vessel wall
leading to occlusion.12
Leishmaniasis
Leishmaniasis is widespread in Central Asia, Africa,
few countries in Europe and in the Far East. The
disease is caused by the protozoan Leishmania which
is transmitted to man by sandfly (Phlebotomus). Three
distinct types have been recognized:
i. Visceral leishmaniasis caused by Leishmania
donovani—responsible for kala-azar.
ii. Cutaneous leishmaniasis caused by Leishmania
tropica—manifested as granulomatous sores in the
exposed parts of the body, known as oriental sore.
iii. Nasopharyngeal leishmaniasis (espundia) caused
by Leishmania braziliensis and is mostly prevalent
in South America.
In kala-azar, persistent irregular fever for a long
period, enormous enlargement of spleen, moderate
enlargement of liver and marked degree of anemia
are characteristic features. The diagnosis is made by
identifying L donovani in smears from spleen and bone
marrow puncture.
Ocular Manifestation
Retinal hemorrhages occur perhaps due to severe
anemia. Thrombosis of central retinal vein also may
occur. Ocular involvements of postkala-azar dermal
leishmaniasis include episcleral nodules which may
lead to deep corneal vascularization.8 Post kala-azar
uveitis also has been reported.9
In oriental sore, tiny ulcerating papules may be
found in the eyelids at the site of the bite by the sand-
fly. It may be associated with conjunctivities. In
espundia, the ulcer is limited to face and mucous
 Chapter 153: Ocular Manifestations in Tropical Diseases
membrane of the anterior third of the nasal septum.
In severe cases, ulcer may destroy the nose and the
eyelids.
Trypanosomiasis (Sleeping Sickness)
The disease is caused by a protozoa Trypanosoma gam-
biense, transmitted by bites of tsetse flies (Glossina). It
is widespread in Africa and is characterized by chronic
irregular fever, skin eruptions, local edema, adenitis
with physical and mental lethargy.
Ocular lesions include lid edema, interstitial
keratitis, uveitis and optic neuritis.
Chagas’ disease is a variant of trypanosomiasis
found in Central and South America caused by
Trypanosoma cruzi. It is transmitted by triatome bugs.
Unilateral edema of the eyelid is a characteristic ocular
lesion in this disease.
Ocular Helminthiasis
Ocular involvement in patients having worms or
larvae in the body is quite frequent. In such cases, man
is the true or definitive host where the parasite passes
through its adult and reproductive stages. The mobile
worm infects the eye or ocular adnexal tissue.
Following are the common parasitic diseases affecting
the eye.
Onchocerciasis
It is caused by the filarial worm Onchocerca volvulus
or Onchocerca caecutiens. The disease is widely endemic
in tropical Africa and parts of the tropical America.
The disease is spread by the black (biting) fly
(Simulium) which freely breeds in the rivers. The
blindness caused by onchocerciasis is known as
riverine blindness. About half a million people in the
world are blind or partially blind due to oncho-
cerciasis. Systemic manifestations consist of skin
nodules, lymphadenopathy. Ocular manifestations are
very common and include swelling of eyelids,
proptosis, thicknening of the conjunctiva and
nummular keratitis. It is not rare to see microfilaria
wandering in the anterior chamber and vitreous
cavity. Uveoretinal inflammation is most important
pathology of onchocerciasis so far as visual loss is
concerned. The toxins liberated from the dead worms
induce the uveal pathology. Plastic iritis associated
with edema of iris stroma produces the spongy pumice
stone appearance of the iris. Light brown exudative
deposits in the lower part of the anterior chamber
1217
produces an inverted pear-shaped appearance of the
pupil which is considered a characteristic ocular sign
of the disease.
Chorioretinal inflammation leading to atrophy of
the neural tissue with consecutive optic atrophy is the
ultimate cause of blindness. Ophthalmoscopic
examination of the fundus shows clumping of retinal
pigment, atrophy of choriocapillaries and subretinal
fibrosis. Glaucoma and cataract may be complications
of uveoretinal inflammation. The effective treatment
of onchocerciasis is with diethylcarbamazine
(Hetrazan) and suramin (Antrypol).
Loiasis
Loiasis, found in the equatorial rainy forests of Central
and West Africa, is caused by the filarial worm Loa
loa. The intermediate host is a biting fly of the genus
Chrysops. The microfilaria transformed into adult
worm in the body moves freely in the subcutaneous
connective tissue. Unlike onchocerciasis, the symp-
toms in loiasis are produced by the adult worms and
not by the microfilaria.
Common ocular manifestation is transient painful
localized inflammatory edema of the eyelids—known
as ‘Calabar swellings’. This is a benign disease so far
as vision is concerned. Loiasis is often associated with
onchocerciasis, treatment is also the same in both the
conditions.
Schistosomiasis
Schistosomiasis (bilharziasis) is a chronic infection
with trematode worms of the genus Schistosoma. The
parasites inhabit in the veins of the pelvis or abdomen
and manifest as genitourinary schistosomiasis or
intestinal schistosomiasis. Ocular involvement is rare.
Urticaria and edema of the lids may be seen.
Gnathostomiasis
This is due to a parasite known as Gnathostome,
ingested by men by eating semicooked fish usually
found in dirty shallow drains. Cases of gnathostomias
had been reported from the eastern region of
undivided India including present Bangladesh.10 The
worm roams in the eye causing retinal hemorrhage
and subsequent chorioretinitis. Surgical removal of the
live worm may be done while it is visible in the
anterior chamber.
1218 Section 9: Miscellaneous Topics
Toxocara Infection (Toxocariasis)
It is common in puppies and cats and is caused by
T. canis or T. feline. It can affect the eyes of children
playing with them. Dogs can be infected trans-
placentally and puppies shed more eggs than the adult
dog. Eggs are deposited in the soil and after about
two weeks, enter into humans. Eggs hatch after they
are ingested by humans and the larvae migrate
through the intestinal wall to enter into portal
circulation. Exudative or hemorrhagic retinitis leading
to retinal detachment and extensive granulomatous
inflammation of the choroid may be found.
Toxocariasis should be considered as differential
diagnosis of retinoblastoma.
Cysticercosis
This is a common parasitic cyst found in the eye and
brain caused by the pork tapeworm—Taenia solium.
Here, man is the intermediate host harboring the
bladder worm stage known as cysticercus cellulose.
The cysts are oval translucent of 6 to 18 mm diameter.
The cysts are formed in the orbital cavity and should
be considered in differential diagnosis of proptosis.
Intraocular cysts may be subretinal, causing retinal
detachments or may be in vitreous. The head of the
larval worm called scolex may be seen with
ophthalmoscope as moving white spots. Such cysts
can be removed from the vitreous. If punctured during
removal, it may cause severe inflammation in the eye.
The old cysts may become calcified.
Hydatid Disease: Hydatid Cyst: Echinococcus Cyst
Echinococcus granulosus, the most common species of
Echinococcus and the smallest of the tapeworm family,
is about 0.3 cm long. Its common definitive host is the
dog. The eggs pass from the dog’s intestine in feces,
and the grazing animals, like sheeps, goats, cows and
pigs, swallow the eggs along with contaminated grass.
These animals are intermediate hosts and human
infestation begins when the tissues of animals
containing Echinococcus cysts with scolices are
ingested; thus humans also become intermediate
hosts. Sometimes, men may ingest the scolex directly
by contaminating their hands with the dog’s excreta
while fondling them. The Echinococcus embryos pass
through the blood vessels and form hydatid cyst in
the orbit. As the cyst grows, painless progressive
proptosis occurs with some associated edema of the
eyelids. The larvae prefer to form the cyst inside the
muscle cone; and, therefore, the proptosis is very often
axial. Sometimes, active inflammatory reaction with
discomfort and pain sets in.
The cyst is surrounded by a pseudocapsule formed
from condensation of the fibrous tissue and the
germinal layer inside this pseudocapsule produces
numerous daughter and grand-daughter cysts which
give the cysts a multilocular character.
Ophthalmomyasis
This is a condition where the eye or adnexa are
invaded by maggots (larvae). Cattle, sheep, horse, deer
and man are the known hosts and eggs are deposited
by the flies in the lid margins or on the conjunctiva
producing local inflammatory changes (ophthalm-
omyasis externa). In ophthalmomyiasis interna, larvae
pass through their second stage and can penetrate the
eye and orbit causing tissue damage.
Yaws
Yaws is a contagious disease due to Treponema pertenue
and is found in equatorial Africa, Asia, Central and
South America, the Pacific Islands and Australia. Eyes
are involved in the later stage of the disease where
there may be ulceration of the eyelids, interstitial
keratitis and iritis.
Trachoma
Trachoma is a major cause of blindness world over. It
is estimated that about 500 million people suffer from
this disease. Of these, at least 2 million people are
blind, and many are visually handicapped due to
corneal scarring.11
The causative organism is Chlamydia trachomatis,
which is in between bacteria and virus. Like bacteria,
they multiply by binary fission and like viruses they
produce inclusion bodies; they are sensitive to
sulphonamides and tetracyclines. C trachomatis is
found in the conjunctival and corneal epithelium and
also in the mucous membrane of the genital tract; the
latter causes inclusion blennorrhea of the newborn.
Hence, the organism is sometimes grouped under
‘TRIC’ (trachoma inclusion conjunctivitis agent). The
main carriers of the infection are children and
the disease spreads from child to child through
conjunctival discharge in overcrowded unhygienic
surroundings. The disease initially starts as a mild
conjunctivitis which soon becomes chronic with an
irritable eye. The eyelid edema, discomfort and
 Chapter 153: Ocular Manifestations in Tropical Diseases
photophobia ensue with corneal involvement. For the
purpose of treatment, trachoma has been classified
initially by McCallum and later by WHO (Table 153.1).
Since reinfection is common in trachoma, long
continued treatment with tetracyclines and sulfona-
mides along with treatment of corneal ulcer is
necessary. The sequelae of trachoma, particularly
trichiasis and entropion should be treated imme-
diately.
Epidemic Dropsy
Epidemic dropsy is due to toxic effect of adulterated
mustard which is used as cooking medium. The
Table 153.1: Classifications of trachoma
McCallum Classification
Stage I: Conjunctival hyperemia, papilae and follicle
formation—mostly in the upper palpebral
conjunctiva.
Stage II: Corneal ulceration and pannus formation—
sometimes secondary infection is responsible
for sloughing of cornea at this stage.
Stage III: After a few weeks of active inflammation,
healing starts with cicatrization. The scarring
of the follicles forms pits known as ‘Herbert’s
pits’.
Stage IV: This is the stage of sequelae where lids
thickened with excessive scar tissue leads to
ptosis, entropion and trichiasis. Stricture of the
ducts of lacrimal glands in the superior fornix
and loss of function of the accessory lacrimal
glands and globlet cells gives rise to xerosis and
keratinization of the conjunctiva.
WHO Classification
Stage I: Active trachoma with follicles (TF)—represents
active moderate infection. At least, five follicles
and some papillae are detected in the upper
tarsal conjunctiva; the conjunctival blood
vessels can still be seen.
Stage II: Active trachoma intense (TI)—represents
severe infection; numerous follicles and
papillae in the tarsal conjunctiva obscure the
blood vessels.
Stage III: Trachomatous scarring (TS)—scars on the
upper tarsal plate is indicative of previous
trachoma infection.
Stage IV: Trachomatous trichiasis (TT)—some eyelashes
are seen rubbing against cornea which need
immediate treatment.
Stage V: Corneal opacities (CO)—complete opacification
of the cornea with gross visual loss.
1219
adulteration is by oil from the seeds of the Mexican
poppy, Argemone mexicana, which has close resem-
blance with mustard oil seeds. The first outbreak of
the epidemic was recorded in 1877 in Kolkata. The
toxic substance is “sanguinarine”, the toxic effect of
which is dilatation and engorgement of the capillaries
in the deeper layer of the skin and fatty tissues, heart
and skeletal muscles, pulmonary avleoli, submucous
tissues of the intestines, liver, kidney, ovaries, uterus,
thyroid, pia-arachnoid membranes of the brain and
nerve fibers.5 The onset of the disease is insidious.
There may be loose motions occasionally with blood.
Irregular fever, dyspnea, palpitation, edema of the legs
and ecchymotic patches in the skin are essential
features of the disease. Death is usually due to heart
failure from toxic myocarditis.
About 10 percent of cases present as primary open
angle glaucoma. Classically, there is markedly high
tension which may be up to 70 to 80 mm Hg (Schiotz)
in a white eye without any pain. Afterward, typical
glaucomatous cupping and field defects set in
engorgement of retinal veins or retinal hemorrhage
may be present. The treatment aims at immediate
lowering of tension with Timolol and Acetazolamide
to be followed by standard modalities of treatment
for open angle glaucoma.
REFERENCES
1. Manson-Barh PEC, Bell DR. Manson’s Tropical Diseases, 19th
edn, London: Balliere, Tindall and Cox, 1987.
2. Sanford-Smith J. Eye Diseases in Hot Climates, 2nd edn,
London: Wright, 1990.
3. Sorsby A. Modern Ophthalmology, Vol. II, 2nd edn, London:
Butterworths, 1972.
4. McDougall AC, Yawalkar SJ. Leprosy: Basic information and
management. Cibia-Giegy Ltd: Basle, 1987.
5. Bhaduri BN. Eye complications in the protozoal parasitic
diseases of the tropics. XIX Concilium Ophthalmologicum
Acta 1962;1:79.
6. Carrol ME, Anast BP, Birch CL. Giardiasis and uveitis. Arch
Ophthalmol 1961;65:775.
7. Samaviego JMV. Ocular manifestations of some tropical
diseases. Am J Ophthalmol 1951;34:1574.
8. Somerset EJ. Ophthalmology in the Tropics. London: Bailliere
Tindall and Cox, 1962.
9. De-Chant W, Rees PH, Kager PA. Post-kala-azar uveitis. Br J
Ophthalmol. 1980;64,650.
10. Sen K, Ghosh N. Ocular gnathostomiasis. Br J Ophthalmol
1945;29:618.
11. WHO. Guide to Trachoma Control, WHO Geneva, 1981.
12. Biswas J, Fogla R, Srinivason P et al. Ocular malaria. Ophthal-
mology 1996;103:1471.
 Chapter 154
Eye in Connective Tissue
Disorders
Jyoti S Padalay
Connective tissue consists of fibers which are as
follows:
1. Collagenous
2. Reticular
3. Elastic, and
4. Ground substance polysaccharide matrix which
contains fibroblasts lymphocytes, plasma cells,
macrophages and mast cells.
Collagen
It is highly polymerized in its most soluble form in
the vitreous. The cells found in the cornea and sclera
are the fibroblasts and in the vitreous is mast cell
which is responsible for the production of heparin
and hyaluronic acid.
Reticulin Fiber
These are most abundant around vessels and muscle
fibers; in the eye most commonly found in vitreous
and uvea.
They are similar to collagen structurally but having
high concentration of fatty acids attached to them
which gives them characteristic staining properties.
Elastin
Unlike collagen and reticulin, elastin cannot be
regenerated during life.
Ground Substance
In certain tissue such as vitreous the ground substance
is more abundant than the collagen component,
whereas in other structures like sclera, reverse is true.
In addition to the presence of cell, an enzyme called
as collagenase regulates the amount of collagen tissue;
the amount of ground substance is under hormonal
control. Corticosteroids suppress the formation of
granulation tissue by interfering with production of
both hyaluronic acid and collagen.
Fibrinoid Necrosis
The basic pathology of connective tissue disorder is
fibrinoid necrosis and granuloma formation in the
effected tissue. The term fibrinoid necrosis is derived
from its staining character with eosin. It is, however,
distinct from fibrin and collagen and is almost always
result of immunologically induced changes within the
tissue.
Fibrinoid necrosis in disseminated lupus erythro-
matosis and scleroderma appears to be the result of
metabolic disturbance in DNA and in protein
chemistry while that seen in rheumatic fever and
polyarteritis is related to a hypersensitivity reaction
to a variety of agents. In rheumatoid arthritis and
disseminated lupus erythromatosis there is an
increased concentration of gamma globulins similar
to that found in the Arthus reaction and in thrombo-
cytopenic purpura there is high concentration of
fibrinogen and fibrin characteristic of Schwartzman
reaction. Thus, similar morphological changes do not
imply common pathogenesis.
According to the current theory some agents like
viral infection or even trauma alter somebody
component which turns it into autoantigen. This
 Chapter 154: Eye in Connective Tissue Disorders
antigen in its turn incites the production of immuno-
globulins which is present in the diseased connective
tissue. This antibody causes precipitation of the
mucopolysaccharide of the ground substance and
damages the protective coat of the collagen fibers
resulting in edema of the ground substance and
disintegration of the collagen fibrils. The edema is
probably due to the altered mucopolysaccharide
which can imbibe more water. As the edema
increases, the collagen fibers become separated,
thinned and fragmented producing the histological
appearance of fibrinoid necrosis. Associated with this
reaction, lymphocytic infiltration with macrophages
and multinucleated giant cells aggregate around the
site of the lesion producing an Aschoff nodule or a
Klinger’s microgranuloma. Depending upon the type
of the disease, vascular changes also occur consisting
of vasculitis, endothelial proliferation and fibrinoid
degeneration of vessel wall which may lead to
thrombosis and infarction of the tissue supplied by
this vessel.
The tissue destruction is probably the result of
release of lysosomal enzymes from the breakdown
of leukocytes.
Rheumatoid Factors
The serum of 85 percent of patients with rheumatoid
arthritis contains, an antibody known as rheumatoid
factor. This is antibody in the IgM class and react
specifically with altered IgG of the patient. This forms
the basis of the rose water sheep’s cell agglutination
test and the latex fixation test; sheep’s cells or latex
particles are coated with human or animal IgG which
is then placed in contact with the patient’s serum and
if the rheumatoid factor Ig is present then aggluti-
nation will occur.
Rheumatoid factor can be found in other connec-
tive tissue disease also but in low titer.
Rheumatoid factor present in rheumatoid arthritis
implicates the seriousness of the disease like subcuta-
neous nodules, arthritis, scleritis and peripheral
neuropathy.
Lupus Erythematous (LE) Cell
The LE cell can be found in serum of systemic lupus
erythematosus. Antinuclear antibody enters the
neutrophil leukocytes. The nucleus then swells, loses
its chromatin network and is extruded from the cell.
1221
LE cell is the result of antibody antigen reaction
within the nucleus of the leukocyte. The same
antinuclear (anti-DNA) antibodies, several types of
which have now been identified, form the basis of
the antinuclear factor tests which are usually
performed by immunofluorescence.
LE cells are also found in rheumatoid arthrittis,
discoid lupus erythematosus, lupoid hepatitis and
some drug reactions. Antinuclear factors in rheuma-
toid arthritis and Sjögren’s syndrome are of the IgM
type, whereas those found in systemic lupus erythe-
matosus (SLE) are of the IgG type.
VARIOUS TYPES OF CONNECTIVE
TISSUE DISORDERS
1. Acquired generalized disorders of connective
tissue affecting the eye.
A. Usually associated with joint disease
• Rheumatoid arthritis
• Juvenile chronic polyarthritis (Still’s disease)
• Ankylosing spondylitis
• Reiter’s disease
• Behcet’s syndrome
• Systemic lupus erythematosus
• Dermatomyositis and polymyositis
• Progressive systemic sclerosis (sclero-
derma).
B. Occasionally Associated with Joint Disease
a. Necrotizing angiitis:
• Polyarteritis nodosa and hypersensitivity
angiitis
• Temporal arteritis and polymyalgia
rheumatica
• Takayasu disease
• Cogan’s syndrome.
b. Allergic granulomatous angiitis:
• Wegener’s granulomatosis.
c. Rarely associated with joint disease:
• Relapsing polychondritis
• Sarcoidosis
• Amyloidosis
• Erythema nodosum
• Ulcerative colitis
• Crohn’s disease
• Sjögren’s syndrome.
There are no specific eye changes in rheumatic
fever except that the patients who have had this
condition are more prone to develop episcleritis later
in life. The antimyocardial antibody does not appear
to have any effect on ocular tissue.
1222 Section 9: Miscellaneous Topics

2. Acquired generalized metabolic disorders Other changes in cornea are acute stromal keratitis
affecting connective tissue and the eye: producing diffuse opacities throughout the cornea
• Gout. and sclerokeratitis ‘A’ which looks like sugar crystals
3. Hereditary generalized disorder of connective in the deeper stroma. Mooren’s ulcer is a classical
tissue affecting eye. example of corneal manifestation of connective tissue
a. Defects in metabolism of collagen: disorder.
• Marfan’s syndrome
• Homocystinuria Anterior Uveitis
• Ehlers-Danlos syndrome
It is an unusual complication rheumatoid arthritis
• Osteogenesis imperfecta.
though rheumatoid factor has been found only in 20
b. Defect in metabolism of elastin and collagen:
percent of patients with uveitis.
• Pseudoxanthoma elasticum.
c. Defect in the metabolism of the mucopolysac-
Keratoconjunctivitis Sicca
charides:
• Hurler’s syndrome MPS-I Sicca
• Hunter’s syndrome MPS-II
It is present in 30 to 40 percent cases of rheumatoid
• Sanfilippo syndrome MPS-III
arthritis. It is a part of Gougerot-Sjögren syndrome;
• Marquio syndrome MPS-IV
with decreased secretion of lacrimal, salivary and
• Scheie’s syndrome MPS-V
mucosal glands of upper respiratory tract. Enlarge-
• Maroteauz Lamy syndrome MPS-VI.
ment of the gland with hypofunction is present. This
(There are various degrees of cloudiness of the
results in reduction of watery content of tears and
cornea).
production of abnormal mucus secretion. Lysozyme
in the tear is reduced and the IgG level in the serum
OCULAR MANIFESTATIONS
is increased early in the disease. Sjögren’s syndrome
OF CONNECTIVE TISSUE
is also found in systemic lupus erythematosus, pro-
Scleritis and Episcleritis gressive systemic sclerosis, polymyositis and poly-
arteritis nodosa.
a. Episcleritis—episcleral tissue is involved. Eye is
Keratoconjunctivitis sicca is associated with
red and sore, it may or may not be painful.
dryness of eyes, pain, discomfort and fever.
b. Scleritis—usually anterior which can be diffuse,
Abnormal epithelium can be stained with a drop of 1
nodular or necrotizing scleritis. Pain in scleritis is
percent rose bengal. The tear break-up time is
usually severe.
reduced; this can be tested by examining with slit
Nodular scleritis represents rheumatoid nodule
lamp biomicroscope after instillation a drop of 2
but the biopsy of nodule is difficult as it may cause
percent fluorescein over the cornea. In the early stage
perforation of globe; the condition heals by formation
of keratoconjunctivitis sicca the tear break-up time
of fibrous tissue.
and Schirmer’s test may be normal. Corneal
Necrotizing scleritis is of two types: (i) associated
complications include filamentary keratitis and central
with serious inflammation and diffuse anterior
corneal laceration. Treatment is by replacing the tears
scleritis, (ii) without inflammation known as sclero-
with alkaline methyl cellulose drops or occasionally
malacia-perforans.
occluding lacrimal puncta. For abnormal mucus acetyl
Complications like glaucoma and cataract do not
cystine drops may be prescribed.
develop until inflammation has progressed all 360°
of the globe.
Juvenile Chronic Polyarteritis (Still’s disease)
Systemic manifestations are morning stiffness of
Cornea
joints. It is common in young girls (usually below 16
Destructive changes in the corneal periphery are due years), movements of wrists and cervical spine are
to antigen-antibody reaction leading to collagen affected. Low grade fever, generalized
destruction. Marginal ulceration appear which may lymphadenopathy, hepatosplenomegaly and
need keratoplasty. occasional skin rash are common accompaniments. It
 Chapter 154: Eye in Connective Tissue Disorders
may be associated with pericarditis and anemia, ESR
is raised with leukocytosis.
Ocular Involvement
Uveitis is present in about 10 percent of children with
Still’s disease. Joint symptoms may precede eye
findings of the usual triad of band shaped
keratopathy, iriodocyclitis and complicated cataract.
Ankylosing Spondylitis
It is a chronic progressive arthritis occurring in males
before the age of thirty affecting the sacroiliac and
cervical vertebral joints.
Ocular Manifestations
Uveitis is most common; severity of uveitis being
unrelated to the severity of the arthritis. Iritis usually
clears up without any residual damage to the eye,
although many attacks may occur over the period of
years.
Reiter’s Disease
Reiter’s syndrome consists of urethritis, polyarthritis,
and conjunctivitis. Young adult males are commonly
affected.
Arthritis is usually of sudden onset and symme-
trical, involving knees, ankles and metatarso-
phalangeal joints.
Ocular Involvements
Conjunctivitis Bilateral mucopurulent conjunctivitis
develops within four weeks of onset of the disease
in one-third of cases.
Discharge is yellowish, copious and transient.
Treatment with antibiotics has no effect on conjunc-
tivitis.
Keratitis Punctate epithelial erosions may occasionally
coalesce into frank ulceration.
Scleritis Scleral and episcleral involvement is rare but
occurs in young men having evidence of sacroiliac
arthritis and genital infection.
Uveitis It may be severe, with much exudate in the
anterior chamber, dense synechia and fine keratic
precipitates. It responds to steroids but tendency for
recurrence is common. Secondary glaucoma may
develop.
1223
Other changes Optic neuritis, retinitis, posterior uveitis
have been recorded in Reiter’s syndrome.
Behcet’s Syndrome
It is characterized by ulcers of the mouth and
genitalia of young adults with uveitis and hypopyon.
Joint involvement occurs in 2 percent of the patients;
knee and ankle joints are frequently affected.
Neurological disorders include cranial nerve palsies,
meningoencephalitis, organic mental syndromes,
pseudobulbar palsy, hemiplegia and paraplegia. In
males genital ulcers occur in the scrotum and shaft of
the penis; in females ulceration develops all over the
genitalia.
Ocular Involvements
Ocular manifestations consist of bilateral anterior
uveitis with hypopyon, posterior uveitis, retinitis,
vasculitis and disseminated chorioretinitis. Sponta-
neous regression of ocular lesions is common. Corneal
involvement is limited to keratouveitis only.
Systemic Lupus Erythematosus (SLE)
The SLE is common in female in the ratio of 4:1.
Though the disease may take a benign and chronic
course, fulminating and fatal termination may result
due to involvement of renal, cardiorespiratory and
central nervous system.
Butterfly rash on face and alopecia may occur in
50 percent of adults and 70 to 80 percent of children
may have renal involvement.
Ocular Manifestations
Keratoconjunctivitis sicca occurs in about 25 percent
of patients.
Conjunctiva Intense hyperemia with velvety appear-
ance of conjunctiva leaving depressed scar after
healing or cicatrization of conjunctiva.
Cornea Punctate epithelial corneal erosions later
coalesce to form deep ulcers forming disciform
keratitis or marginal keratitis with cloudy cornea.
Sclera Necrotizing anterior scleritis is common.
Uveal and retinal changes Uveitis occurs in 1 percent of
patients of SLE; gray, white or yellow miliary type
of lesion in iris and choroid are common.
1224 Section 9: Miscellaneous Topics
Retinal changes show hemorrhages and cotton-
wool spots with disk edema.
Dermatomyositis and Polymyositis
These are rare inflammatory conditions of the muscles
and skin giving rise to weakness and eventual atrophy
of the muscles of the limb girdles, neck and pharynx.
Eye changes show cotton-wool exudates in fundus
specially at posterior pole with vasculitis.
Scleroderma Progressiva Systemica
Sclerosis It is a disease involving skin of face, neck
and hands; the skin becomes edematous and fibrotic.
It also involves alimentary tract, esophagus and heart.
Ocular Involvements
These include phimosis of the lids and reduction in
tear secretion due to involvement of lacrimal and
accessory lacrimal glands. Ocular involvement is the
same as occurs in polyarteritis nodosa. Uveitis is rare.
Polyarteritis Nodosa
This usually affects the bifurcations of vessels.
Aneurysm formation and even occlusion of vessels
may occur. Central nervous system, heart, kidneys
and gastrointestinal tracts are usually involved.
Histologically vascular lesions in angiitis start in the
intima and subendothelial region of small vessels. It
can be due to adverse drug reaction.
Ocular Involvements
Eye changes occur in 20 percent of patients with poly-
arteritis nodosa.
Scleral and corneal changes In episcleritis and polyarte-
ritis nodosa sclerokeratitis are common. Destructive
process starts at the limbus resulting in painful
marginal ulceration. Other changes are choroiditis,
vasculitis subhyaloid hemorrhage, papilledema and
central retinal artery occlusion.
Temporal Arteritis (Cranial Arteritis, Giant Cell
Arteritis and Polymyalgia Rheumatica)
This affects elderly people. The pathology is in the
media and adventitia of medium or large sized
arteries but clinical picture may be seen in the
temporal arteries only. In cranial arteries the patient
frequently complains of difficulty in chewing, pain
in the face or scalp and inability to comb his hair or
lie on a pillow because of thickened tender arteries.
Loss of weight and general malaise with high ESR
are common systemic manifestations.
Ocular Manifestations
Controversy exists as to whether polymyalgia and
temporal arteritis are different manifestation of the
same diseased process. Visual loss is common in both
the conditions. Unilateral blindness occurs in 50
percent of cases and bilateral in 25 percent. Biopsy of
affected portion of the artery is a confirmatory method
of diagnosis.
Central retinal-artery occlusion with sudden loss
of vision is a common manifestation. Retina is pale
with cherry red spot at macula and peripapillary
edema. Anterior ischemic optic atrophy is the most
common legacy of giant cell arteritis.
Treatment
Corticosteroids therapy is urgent and obligatory. The
dose and duration of treatment is monitored by
assessment of ESR at frequent intervals.
Takayasu Disease
(Pulseless Disease, Aortic Arch Aortitis)
The pathology is similar to that of giant cell arteritis.
The aortic arch is common site of pathology resulting
in reduced blood flow to limbs and cephalic region.
Ocular symptom is transient amaurosis due to
poor blood supply to posterior pole of the brain;
sometimes vascular occlusion develops. It is a bilateral
condition though one eye is affected first; if left
untreated the second eye is affected within 5 to 6
days. The condition may remain unnoticed; it may
be detected only when blood pressure cannot be
recorded with BP instrument applied to the arms but
can be recorded when applied to lower limbs.
Cogan’s Syndrome
This consists of interstitial keratitis, deafness, vertigo
and tinnitus. Scleritis and uveitis may also be seen. It
is due to involvement of small vessels of inner ear
and eye.
Allergic Granulomatous Angiitis:
Wegener’s Granulomatosis
This is a variation of hypersensitivity angiitis. The
eye may be directly involved due to necrotizing
angiitis or may be secondarily involved due to
 Chapter 154: Eye in Connective Tissue Disorders
pressure by the granulomatous extraocular lesion.
Persons of 4th to 5th decades of life are affected.
Proptosis may be a common presentation due to
orbital or paranasal granulomas.
Ocular Complication
Forty-three percent of patients have eye involvement.
Proptosis, limitation of ocular movement, visual loss,
exudative retinal detachment, posterior scleritis,
midstromal keratitis, massive necrotizing scleritis,
cotton-wool spots in the fundus with normal blood
pressure are probable ocular features.
The condition responds to steroid but may have
fatal termination due to renal involvement.
ACQUIRED GENERALIZED DISORDERS
OF CONNECTIVE TISSUE SOMETIMES
ASSOCIATED WITH JOINT DISEASE
Relapsing Polychondritis
It is a rare relapsing condition in which cartilaginous
structures of joints, ears, nose, larynx, trachea and
epiglottis are affected, with malaise, fever and anemia.
Ocular complications occur in 60 percent of cases.
Scleritis and uveitis with retinal detachment due to
posterior diffuse scleritis.
Sarcoidosis
Sarcoid is a granulomatous disease involving every
tissue of the body.
Its etiology is unknown. Diagnosis is confirmed
by Kveim antigen (salins suspension of lymph node
taken from infected patient) given intradermally. The
nodule which forms at the site of injection is excised
and examined histologically after 6 weeks; it shows
noncaseating tubercle in all sarcoid patients.
Ocular Involvement
It is present in 30 to 40 percent of patients. In 8 to 10
percent patients lacrimal and salivary glands are
involved.
It may cause reduction of tear secretion resulting
in keratoconjunctivitis sicca. If salivary glands
involved at the same time it is called as Mikulitz’s
syndrome and if in addition nervous system (seventh
nerve) is involved then it is known as Heerfordt’s
syndrome. Lesions of conjunctiva, cornea and sclera
are rare. There may be sarcoid nodules of conjunctiva.
1225
Anterior uveitis is a common manifestation of
sarcoid. About 30 percent of cases present with
anterior uveitis.
Amyloidosis
Amyloid is an intracellular filamentous glycoprotein.
Deposition of amyloid usually results from chronic
infection or inflammation which can occur in healthy
young adults affecting heart, spleen and kidney.
Ocular Manifestations
Conjunctiva Tumor like masses found in the fornices
later involve bulbar conjunctiva as well. Treatment
is excision and mucous membrane grafting.
Cornea Band shaped keratopathy and Salzmann’s
nodular dystrophy may develop. Amyloid change
also follows chronic iridocyclitis.
Erythema Nodosum
This condition is characterized by formation of
nodule, over the shoulder and extensor surface of
the legs and arms. Nodules may be painful. The size
of the nodule varies between 1 and 7 mm.
Ocular complications are nodular episcleritis,
scleritis and anterior uveitis.
ACQUIRED SYSTEMIC METABOLIC DISORDER
AFFECTING CONNECTIVE TISSUE AND THE EYE
Gout
Main pathology of gout is deposition of crystals of
monosodium urates in the tissues. Uric acid is the
end product of purine metabolism and a high tissue
uric acid concentration may result either from over-
production of uric acid or its diminished excretion.
Ocular Manifestations
Conjunctivitis is the only ocular manifestation of acute
gout. Like gout arthritis, conjunctivitis may also be
painful due to irritation of the tissue cells by the urate
crystals.
Chronic Gout
It is characterized by presence of tophi, which
contains monosodium citrate and may occur
elsewhere in the body.
1226 Section 9: Miscellaneous Topics
Ocular Manifestations
Ocular manifestations of chronic gout are anterior
uveitis and scleritis.
HEREDITARY GENERALIZED DISORDER
OF CONNECTIVE TISSUE WHICH ALSO
AFFECTS THE EYE
Marfan’s Syndrome
This syndrome is characterized by long limbs with
thin bones. Arachnodactyly due to excessive prolife-
ration of epiphyseal cartilage, muscular hypoplasia
with deficiency of cutaneous fat and cardiac lesions
occur in some 36 percent of Marfan’s syndrome.
Ectopia Lentis
This is bilateral symmetrical displacement of the lens.
Displacement is typically upward and temporally.
Secondary glaucoma is a common complication.
Marchesani Syndrome
The features of this syndrome are short stature, wide
spade like hands and feet, and abundance of subcuta-
neous fat. Ocular abnormality is sphero or micro-
phakia causing a marked lenticular myopia, secondary
glaucoma and subluxation of lens.
Homocystinuria
In this condition due to inborn metabolic error the
suspensory ligaments of the lens are not strong
enough to keep the lens in position. The lens is
subluxated downward. Diagnosis is confirmed by
detection or homocystine in urine.
Osteogenesis Imperfecta
This condition is associated with blue sclera, brittle
bone, and deafness. Basically there is hypoplasia of
the mesoderm which causes thinning of sclera and
uveal tissue shines through it. Hypermotility of the
joints and poorly developed musculature are common
associations. Other accompanying features are
repeated spontaneous fracture of bones and deafness
due to otosclerosis.
Ehlers-Danlos Syndrome
Joints characterized by loss of collagen tissue in the
dermis and subcutaneous tissue and articular
ligaments giving rise to hyperelasticity and hyper-
extensibility of the skin which may be limited to one
part of the body.
Ocular abnormalities are thinning of sclera, kerato-
conus, microcornea and subluxation of lens due to
laxity of zonules. Angiod streaks and other retinal
changes are due to degeneration of Bruch’s
membrane.
Pseudoxanthoma Elasticum
This is a rare form of atrophy in early life with
appearance of yellow striae on the neck, axillae, and
abdomen and sometimes on the elbow and knees.
Pathologically the streaks consist of degeneration
of elastic tissue of peripheral blood vessels. Angioid
streaks in the eye are due to splits in Bruch’s
membrane.
REFERENCES
1. Watson PG. Connective tissue disorders and the eye. In PP
Trevor-Roper (Ed): Recent Advances in Ophthalmology.
Churchill Livingstone 1975;214-27.
 Chapter 155
Oxidative Stress and
Antioxidants in Ophthalmology
Souvik Banerjee
In early 1940s, it was reported that premature infants
were suffering from an abrupt increase in the
incidence of eye damage leading to occasional
complete blindness. In subsequent years it was
realized that a retinopathy developed in premature
infants which was associated with high oxygen
content in the incubators, they were placed in. Careful
monitoring of the oxygen level and administration
of alpha tocopherol could decrease the incidence. As
for the survival of premature infants high oxygen
level is required sometimes, the problem remained.1
Though oxygen was known as a probable direct
inhibitor of some key enzymes in earlier days, it was
postulated afterwards that the oxygen toxicity could
be due to the formation of oxygen radicals.2 This
hypothesis was gradually converted into superoxide
theory of oxygen toxicity when superoxide
dismutase, an antioxidant enzyme, was discovered.
This enzyme specifically removes the excess
superoxide free radicals responsible for toxic effect
of oxygen.3
FREE RADICALS
A free radical is any species capable of independent
existence that contains one or more unpaired electrons
in an orbital. The situation is energetically unstable,
making such species often highly reactive and short
lived. Stability is achieved by the removal of electrons
from the surrounding molecules to produce an
electron pair. However, the remainder of the attached
molecule then possesses an unpaired electron and
becomes a free radical. Thus it may lead to propa-
gation of a free radical chain reaction. Antioxidants
decrease this reactivity and the chain is broken.4
The most important free radicals in biological
systems are radical derivatives of oxygen. While
transfer of a single electron to oxygen produces free
radical superoxide anions, a two electron reduction
of oxygen would yield hydrogen peroxide. Two
superoxide molecules can react together to form
hydrogen peroxide and oxygen. In the presence of
transition metal ions, hydrogen peroxide produces
most reactive and damaging of the oxygen free
radicals, the hydroxyl radical. The superoxide acts
probably as a source of hydrogen peroxide mainly
and as a reductant of transition metal ions, e.g. iron
and copper. On the other hand hydrogen peroxide
acts as a source of hydroxyl radicals in the presence
of reactive transition metal ions. Thus in the absence
of metal catalyst, superoxides and hydrogen
peroxides are readily removed and are harmless to a
great extent in biological system. The hydroxyl
radical, on the other hand is capable of a greater
damage within a small radius of its site of production.
Other free radicals of importance are singlet oxygen,
carbon centered radicals arising out of reaction with
lipids, nucleic acids, carbohydrate and proteins;
peroxyl radicals, alkoxyl radicals and thiyl radicals.5,6
Cell membranes rich in polyunsaturated fatty acid
are often attacked by oxidising radicals causing lipid
peroxidation which proceeds as a self perpetuating
chain reaction producing lipid hydroperoxides and
a wide range of aldehydes, lipid peroxyl and
1228 Section 9: Miscellaneous Topics
lipid alkoxyl radicals. Lipid peroxidation has been
implicated in a wide range of tissue injuries and
diseases including vascular diseases. Oxidative
damage to proteins, lens crystallin, has long been
suggested to be involved in cataract.7,8
DEFENCE AGAINST FREE RADICALS
There are some in-built defensive mechanism to
combat free radicals. Their role is to prevent the
generation of free radicals or to intercept any that
are generated. They can be enzymes, e.g. superoxide
dismutase (copper and zinc containing cytosolic
enzyme or manganese containing mitochondrial
enzyme), catalases and peroxidases or they can be
non-enzyme, e.g. reduced glutathione, alpha-
tocopherol, carotenoids and ascorbic acid. As the
production of reactive oxygen species and antioxidant
defenses are approximately balanced, a tilting of
balance in favor of the reactive oxygen species can
create a state of oxidative stress. It can result from a
depletion of dietary antioxidants caused by
malnutrition or undernutrition or excessive
production of superoxides and hydrogen peroxide
produced by elevated oxygen level, metabolism of
xenobiotics, e.g. drugs and toxins, chronic
inflammatory diseases and diabetes mellitus.4,9 The
direct implication of free radicals in ophthalmological
disorders was probably evidenced by an animal
experiment which was performed to produce
intracellular free radicals by intravitreal injection of
xanthine-xanthine oxidase. It produced a strong
inflammatory response with vitreous infiltrates and
epiretinal membrane formation inconstantly
associated with retinal detachment.
Electroretinogram showed a decrease of the a, b and
c waves beginning within a few hours after injection.
An intravitreal and epiretinal infiltration by
leucocytes and epithelial derived cells, dense
vitreoretinal membranes and retinal detachments
with occasional neovascularization was confirmed
histologically. This demonstrated directly the close
relationship between free radicals, inflammatory
pathways and vitreoretinal proliferative disorders.
These changes could be reversed by antioxidants and
free radicals scavengers.10
Oxidative stress is greatly increased in diabetes
because of prolonged exposure to hyperglycemia.
Glucose combines with serum protein and lipo-
proteins in a nonenzymatic glycation reaction and
may be auto-oxidised in situ generating free radicals
and causing local oxidative damage leading to
atherosclerosis and microvascular complications,
e.g. retinopathy and nephropathy. Antioxidants,
ascorbate and tocopherol, inhibit glucose auto-
oxidation and reduce the covalent linking of glucose
to serum protein in vitro and also inhibit the glycation
of serum proteins in vivo.11-17 Since diabetic retino-
pathy is a highly specific microvascular complication
of diabetes mellitus and retinal metabolism is
intimately related with the pathophysiology of age
related macular degeneration, role of antioxidants
drew the attention of the basic scientists as well as of
the ophthalmologists. Their role in cataract formation
also could not be ignored due to their possible role
in the inhibition of lens protein glycation.18,19
PATHOPHYSIOLOGY
Fovea, the central depression in the retina, has
maximum density of cone photoreceptors along with
yellow pigments mainly the dihydroxycarotenoids,
lutein and zeaxanthin. Due to this pigmentation, fovea
and its immediate surrounding regions are called
macula lutea or yellow spot. Clinically macula
includes the central retina surrounding the fovea for
a radius of 3 to 4 mm extending approximately to the
optic disk. Age-related macular degeneration (AMD)
is a degeneration of the retina and the retinal pigment
epithelium in the macular region. Occurring late in
life, it is the leading cause of new cases of legal
blindness and hardly any treatment is available for
most patients. Fortunately there are clinical evidences
that antioxidant nutrients protect the retina and its
pigment epithelium from damage and reduce the risk
of developing AMD. It seems that the relation
between the photoreceptors and nourishing tissues
beneath the retina is disturbed in AMD. Near the
foveal crest and slightly more eccentric, the retina
and its pigment epithelium appear to be especially
vulnerable to age related degeneration.20 This is the
area where the greatest percentage of rod
photoreceptors is lost during normal aging21 and a
maximum of lipofuscin occurs here locally in the
retinal pigment epithelium.22 One of the reasons for
this local vulnerability may be due to low antioxidant
protection of foveal crest. Vitamin E concentration
goes through a local minimum in this region and
retinal carotenoid concentration are much lower than
at the foveal center.23,24
Three known risk factors for AMD are probably
related to oxidative processes: cigarette smoking,
 Chapter 155: Oxidative Stress and Antioxidants in Ophthalmology
sunlight exposure and low concentration of ocular
melanin. Erythrocytes of smokers are more
susceptible to lipid peroxidation in vitro, perhaps
because of reduced activity of protective enzymes
against large quantities of pro-oxidants.25 Vitamin E
concentration has been found to be least affected by
smoking, whereas carotenoids are substantially
reduced.26 An inverse relationship between smoking
and plasma concentration of vitamin C has also been
observed.27 Many mechanisms may be involved in
light damage to the retina; one of them is thought to
be the peroxidation of polyunsaturated membrane
lipids. The photoreceptors are rich source of fatty
acids that can be oxidised.28 Rod outer segments have
some of the highest concentration of polyunsaturated
fatty acids of any known membrane systems.29 It has
been shown that n-3 fatty acids deficiency causes
acuity deficits in monkeys implying that these poly-
unsaturates contribute to cone as well as rod
function. 30 Evidence has been accumulating that
oxygen and its radical participate in the damage from
blue light. Primate retinas have the lowest damage
threshold for blue light. 31 Damage from short
exposure of light at high intensity is greatest in retinal
pigment epithelium and photoreceptors are also
involved.32 This high damage potential of blue light
is probably conferred in part by endogenous
photosensitizers, e.g. cytochrome, flavins and
hemoproteins in the tissue, all of which are excited
by blue light and are readily damaged by exposure
to blue light.33 The retinal carotenoids are well suited
to inhibit blue light damage.
Carotenoids and Tocopherol
Carotenoids are abundantly found in fruits,
vegetables and green plants. Out of 600 carotenoid
only 20 are found in human system of which lutein
and zeaxanthin have been found to be associated with
macula and lens. Probably, due to their more polar
character, others, e.g. beta carotene, alpha carotene,
lycopenes and beta-cryptoxanthin were much
preferred earlier by the nutritionists for their role as
a provitamin A. They act as an antioxidant and
prevent macula from damaging near-to-UV blue light.
It is proposed that the carotenoids inactivate singlet
oxygen by physical or chemical quenching; the
intensity depends on the number of double bonds,
type of end groups and other chemical properties.
The association of dietary lutein and zeaxanthin and
AMD risk has been indicated in the several
1229
epidemiological studies. An intake of around 6 mg/
day had been shown to significantly lower the AMD
risk compared with those having lower intake. The
same intake has also been found to cause a reduced
risk of cataracts. Lower macular pigment density has
been found to be well-correlated with higher lens
optical density among older adults though the
mechanism of this effect is still unclear. These
carotenoids are found in the lens though at a much
lower concentration than in the macula. Carotenoids
are 40 carbon atom long chain molecules having
centrally located series of double bonds which confer
its color and free radical quenching properties. Though
the chemical structure and the number of double
bonds are the same in lutein and zeaxanthin, the
position of a double bond makes some differences.
In lutein the position of this double bond confers a
more chemically reactive allylic hydroxyl end group.
While an extra conjugated double bond in
zeaxanthine takes part in quenching the singlet
oxygen. This could be the reason for zeaxanthine’s
better antioxidant properties. Both these carotenoids
span the plasma membrane with their hydrocarbon
chain buried in the lipid bilayers with their
hydrophilic hydroxyl groups oriented on either side
of the membrane. This orientation not only stabilizes
the membrane but also maximizes their contact with
the highly oxidizable membrane lipids. The outer
segment of rod cells is the most vulnerable to
oxidative stress because of its rich polyunsatured
fatty acids content which are readily oxidizable.
Leutin and zeaxanthine are present mostly in this
segment to combat the oxidative stress. Visible blue
light wavelengths are the highest energy and
potentially most damaging wavelength of light which
reaches the retina. It has to pass through the yellow
carotenoids before reaching the sensitive rod and
cone cells.
Epidemiological studies on the role of carotenoids
on AMD risk are conflicting. The Eye Disease Case
Control study (EDCC) reported that AMD risk was
significantly lower with increasing serum concen-
trations of lutein and zeaxanthin. An intake of 5.8
mg per day had a significantly lower AMD risk
compared to those with an intake of 1.3 mg per day.
In contrast, the Beaver Dam Eye Study found no
significant difference in AMD risk between the daily
intake of 0.87 mg/1000 kcal and 0.16 mg/1000 kcal.
As in the EDCC study, only 5.8 mg daily intake could
be found to be statistically significant correlation with
1230 Section 9: Miscellaneous Topics
AMD; the Beaver Dam population might not have
sufficient daily intake to reduce the risk
significantly.34-38
Due to carotenoids, the macular region of the
retinal pigment epithelium and the retina as a whole
are less vulnerable to blue light damage than are other
regions. Antioxidant nutrients are important in
preventing light damage to other ocular tissues also.
There is a striking correlation between the chemistry
of these protective agents and the profile of oxygen
tension in the retinal layers. Photoreceptors are
metabolically more active in the dark consuming more
energy and more oxygen. Due to high consumption
of oxygen, the oxygen tension in retina is lower in
the dark than in the light. Enzymes of anaerobic
glycolysis are most active near the oxygen minimum.
The overall laminar pattern places the highest
densities of retinal carotenoids in the layers with
lowest oxygen tension and the highest concentration
of vitamin E in the layer with the highest oxygen
tension. Thus, vitamin E is more concentrated in rod
outer segments than in the inner retina, whereas the
macular carotenoids are denser in the rod-sparse area
of the foveal avascular zone and in the fiber layers of
the inner retina.35 Relative to alpha-tocopherol, beta-
carotene and other retinal carotenoids become
progressively more effective as an antioxidant as the
oxygen tension decreases. At low oxygen tension
near 4 mm Hg, it can inhibit lipid peroxidation more
effectively than can alpha-tocopherol. Because
carotenoids can be destroyed relatively rapidly at
high oxygen tensions, the low oxygen tension in the
inner retina coupled with protection by the substantial
amount of vitamin E in the foveal center may facilitate
the accumulation of high carotenoid densities.36 The
retinas of monkeys fed carotenoid deficient diet for
more than three years are devoid of macular pigment;
abnormal retina with defects in the cones also
developed. Retina was fragile and prone to split in
the region of photoreceptor axons where the
carotenoids were depleted. Retinal pigment
epithelium cells were reduced in number engorged
with a large amount of lipofuscin.39 Monkeys fed
diets deficient in vitamin E for two years developed
degenerative changes in the macular region of the
retina involving the photoreceptor outer segment.
Retinal pigment epithelium showed accumulated
lipofuscin. Vitamin E concentration in plasma was less
than 2.3 micromole/L.40 Experiments on animals have
shown that retinal ascorbate is oxidized during
exposure to damaging light regimes and that supple-
mental ascorbate could protect against light damage.
Thus, ascorbate was found to provide some
protection against oxidative injury in the retina,41 and
could be related to AMD.
Ascorbic Acid
An antioxidant role of ascorbic acid in vivo has been
suggested by experimental studies in guinea pigs or
genetically scorbutic rats (Osteogenic Disorder
Shionogi or ODS) which like humans are unable to
synthesize ascorbic acid. Guinea pigs fed a diet
marginally deficient in ascorbic acid, showed a
significantly higher concentrations of endogenous
malondialdehyde than the animals fed diets contain-
ing 20 to 40 times the amount of ascorbic acid required
to avoid scurvy.42 Genetically, scorbutic ODS rats fed
a scorbutic diet showed higher concentration of
plasma and liver thiobarbituric acid reactive sub-
stances (TBARS) and lipid peroxides than do rats fed
ascorbic acid supplemented diets.43 However, supple-
mentation of ODS rats with ascorbic acid, in contrast
with vitamin E, did not protect against the
endogenous formation of TBARS.44 Ascorbic acid has
an in vitro protective role in isolated LDL from
oxidation by various radicals and oxidants, probably,
by scavenging most aqueous reactive oxygen and
nitrogen species before they can interact with and
oxidize other substrates including lipids.45
Adhesions of leukocytes to the endothelium is an
important initiating step in atherosclerosis.45 Smokers
have lower plasma vitamin C concentrations than
non-smokers46 and monocytes isolated from smokers
exhibit increased adhesive propensity to the endo-
thelial cells. Supplementation of smokers with 2000
mg vitamin C/day for ten days elevated plasma
vitamin C concentration from 48 to 83 μmol/L and
significantly reduced monocyte adhesion to endo-
thelial cells.47
Healthy individuals given an oral dose of 1000
mg of vitamin C in combination with 800 IU vitamin
E had increased vasodilatation several hours after a
single high-fat meal. Several mechanisms are possible
for these positive effects of vitamin C on
vasodilatation and are likely related to vitamin C’s
antioxidant activity. Endothelium-derived relaxing
factor or NO plays an important role in vasodilatation
 Chapter 155: Oxidative Stress and Antioxidants in Ophthalmology
and also inhibit platelet aggregation and leukocyte
adhesion.45 Supplementation with 7 gm of L-arginine,
the physiologic substrate for nitric oxide (NO)
synthase, could reduce significantly monocyte and
endothelial cell adhesion. The NO is rapidly
inactivated by reactions with superoxide radicals and
release of NO from endothelial cells can be inhibited
by oxidized LDL.48 Therefore, vitamin C may spare
NO by scavenging superoxide radicals or preventing
the formation of oxidized LDL. High concentrations
of vitamin C are required to scavenge superoxide
radicals in competition with NO because of the large
difference in rate constants. Vitamin C also maintains
intracellular concentrations of glutathione by a sparing
effect on regeneration of thiols from thiyl radicals
which may enhance the synthesis of NO or increase
the stabilization of NO through formation of
s-nitrosothiol species. 48 Like vitamin C,
administration of a cysteine delivery agent known
to increase intracellular glutathione concentrations
enhances vasodilatation in patients with coronary
artery disease.49 The totality of evidence from the
human studies strongly suggest that higher intakes
of vitamin C, and possibly supplementation, is needed
to lower morbidity and/or mortality from
cardiovascular disease, cancer and cataract or to
combat oxidative damages. A long time 500 mg/day
dose or acute 1 to 3 gm doses of vitamin C
significantly improve vasoreactivity, an important
consideration for the clinical expression of cardio-
vascular and cerebrovascular diseases. It has been
suggested also that an updated prudent diet should
more specifically aim at daily intake of 250 to 450 mg
ascorbate. Ascorbate is an important antioxidant both
in cells and plasma.50 When alpha-tocopherol acting
as an antioxidant transfers a phenolic hydrogen to
ROO 0 of PUFA, it is converted to tocopheroxyl
radical, which is reconverted to tocopherol by
ascorbate. The resulting ascorbate radical is reduced
to ascorbate by glutathione.48 Ascorbate is the only
cellular reducing agent which can replace superoxide
in metal catalyzed Haber-Weiss reaction under
physiological conditions. As a free radical scavenger,
it can directly react with O20, OH0 and HOCl0 and
other ROOH. Bioflavonoids potentially protect
ascorbate, and in turn ascorbate protects oxygen
radical sensitive folate.51
Glutathione
Mammalian lens contains an unusually high concen-
tration of glutathione which depletes in most form
1231
of cataract. Glutathione (γ-glutamyl cysteinylglycine)
is a water-soluble tripeptide mainly found in the cell
cytosol and other aqueous compartments of living
system. It exists in a reduced form (GSH) and the
oxidized form (GSSG). The GSSG/GSH ratio has been
emphasized as a true indicator of oxidative stress.
The high negative redox potential of this ratio (E’o =
0.33 v) makes it an ideal pair in oxidation reduction
system. Being an efficient electron donor, its effective
reducing power is utilized in free radical scavenging
and other metabolic activities. Its cellular status is
maintained by its synthesis and its utilization by
peroxidases, transferases, transhydrogenases and
transpeptidases as well as by its recycling from GSSH.
The glutathione peroxidases use GSH to detoxify
peroxides generated in the plasma membrane and
other cellular fractions. During the antioxidant
activities of ascorbic acid, dehydroascorbic acid is
produced. GSH transhydrogenase use GSH to
reconvert dehydroascorbate to ascorbate. It takes part
in various reactions where the integrity of SH groups
is to be maintained. Thus, recycling of GSSG to GSH
by NADPH-dependent glutathione reductase is an
essential prerequisite for glutathione action. Probably,
the lipid phase antioxidants, e.g. alpha-tocopherol and
the carotenoids may also be conserved with the help
of glutathione.
The deficiency of GSH causes a marked increase
in membrane permeability in lens making it suscep-
tible to oxidative damage. This results in inactivation
of Na+ / K+ pump leading to ionic change and cataract
development. Recent studies indicated an important
hydroxyl radical scavenging function for GSH in lens
epithelial cells, independent of the cells ability to
detoxify H2O2. The relatively low ratio of GSH to
protein SH in the nucleus of the lens, combined with
diminished activity of GSSG/GSH cycle makes the
nucleus vulnerable to oxidative insult. During the
early phase of age-related macular degeneration
(AMD), retinal pigment epithelium (RPF) undergoes
apoptosis due to oxidative stress in the mitochondria.
GSH and its amino acid precursors can protect RPF
cells from oxidant-induced apoptosis. Glutathione
peroxidase is a selenoenzyme. Selenium thus helps
in removing H2O2, lipid and phospholipid hydro-
peroxide.52-57
The Last Word
From the different observational epidemiological
studies around the world, the following positive
observations emerged till date:58-63
1. There is no conclusive evidence that multivitamins
1232 Section 9: Miscellaneous Topics
are protective. Getting the nutrients we need from
foods is preferable.
2. Multivitamins use for more than ten years lowers
the risk for nuclear and cortical cataract but not
for posterior subcapsular cataract.
3. Overall cataract risk is lower in people taking
retinol, beta carotene carotenoids, vitamin E and
C supplements.
4. Out of all vegetables only spinach has the strongest
association with nuclear cataract.
5. A combination containing vitamin E 500 mg,
vitamin E 400 IU, betacarotene 15 mg, zinc oxide
80 mg and copper 2 mg has most positive response
in high-risk category for macular degeneration
progression which was 25% less. Risk of vision
loss caused by advanced AMD is found to be
reduced by 19% in the same high-risk group.
6. A significant but modest inverse relation was
observed between intakes of betacarotene and
vitamin E and the incidence of large drusen and
between zinc and the incidence of pigmentary
abnormalities.
7. Dietary antioxidants and zinc are not associated
in anyway with overall early AMD.
The evidence of oxidative damage to the retinal
pigment epithelium, the choriocapillaries and lens
leading to AMD, diabetic retinopathy and cataract
are light and oxygen dependent. The role of
antioxidants to ameliorate these disorders also has
been somewhat established. But still the specificity
is lacking. The dosage of antioxidants either alone or
in combination will, probably, depend on the lifestyle
and dietary habit of an individual, other associated
complications, geo-socio-economical consideration,
age, sex and duration of the disease. Antioxidants
are potential drugs and it is pertinent to address
safety issues before recommending megadose
supplementation with them.
REFERENCES
1. Ehrenkranz RA. Vitamin E and retinopathy of prematurity:
Still controversial. J Paediatr 1989;114:801.
2. Gerschman K. Gilbert DL, Nye SW et al. Oxygen poisoning
and X-irradiation: A mechanism in common. Science 1954;
119:623.
3. Fridovich I. Superoxide dismutases. Methods Enzymol 1986;
58:61.
4. Halliwell B, Gutteridge JMC. Free Radicals in Biology and
Medicine (2nd edn), London:Clarendon Press, 1989.
5. Halliwell B, Gutteridge JMC. Role of free radicals and catalytic
metal ions in human disease: An overview. Methods Enzymol
1986;186:1.
6. Cheeseman KH, Slater TF. An introduction to free radical
biochemistry. Brit Med Bull 1993;49:481.
7. Esterbauer H, Zollner H, Schaur RJ. Aldehydes formed by
lipid peroxidation: Mechanism of formation, occurrence and
determination. In C Vigo-Pelfrey (Ed): Membrane lipid
Oxidation Boca Raton: CRC 1990;239.
8. Spector A. Aspects of the biochemistry of cataract. In H Haisel
(Ed): The Ocular Lens. New York: Marcel Dekker 1985;405.
9. Halliwell B, Free radicals and antioxidants: A personal view.
Nutr Rev 1994;52:253.
10. Baudouin C, Pisella PJ, Ettaiche M, Goldschild M, Becquet F,
Gastand P, Droy-Lefaix MT. Effects of EGb 761 and superoxide
dismutase in an experimental model of retinopathy generated
by intravitreal production of superoxide anion radical. Graefes
Arch Clin Exp Ophthalmol 1999;237:58.
11. Barnett AH. Pathogenesis of diabetic microangiopathy: An
overview. Am J Med 1991;90:67.
12. Hunt JV, Dean RP, Wolff SP. Hydroxyl radical production
and autooxidative glycosylation: Glucose autooxidation as
the cause of protein damage in the experimental glycation
model of diabetes mellitus and aging. Biochem J 1988;256:205.
13. Hunt JV, Wolff SP. Oxidative glycation and free radical
production: A causal mechanism of diabetic complications.
Free Radic Res Commun 1991;115:12-13.
14. Sinclair AS, Girling AJ, Gray L et al. Disturbed handling of
ascorbic acid in diabetic patients with and without diabetic
microangiopathy using high dose of ascorbate supple-
mentation. Gerontology 1992;38:268.
15. Ceriallo A, Gingliano D, Quatraro A et al. Vitamin E reduction
of protein glycosylation in diabetes: New prospects for preve-
ntion of diabetic complications? Diabetic Care 1991; 14:68.
16. Ceriallo A, Quatraro A, Gingliano D. New insights on
nonenzymatic glycosylation may lead to therapeutic
approaches for the prevention of diabetic complications. Diabet
Med 1992;9:297.
17. Stalba P, Hatle K, Kmakova K et al. Effect of ascorbic acid on
nonenzymatic glycation of serum proteins in vitro and in vivo.
(Abstract) Diabetologia 1987;30:529.
18. Varma S. Scientific basis for the medical therapy of cataracts
by antioxidants. Am J Clin Nutr 1991;53:335S.
19. Richer SP. Is there a prevention and treatment strategy for
macular degeneration? J Am Optom Assc 1993;64:838.
20. Sarks SH, Sarks JP. Age related macular degeneration: Atropic
form. In SJ Ryan, AP Schachat, RM Murphy (Eds): Retina,
Medical Retina St. Louis:Mosby 1994;2:1071.
21. Curcio CA, Millican CL, Allen KA, Kalina RE. Aging of the
human photoreceptor mosaic: Evidence for selective vulner-
ability of rods in central retina. Invest Ophthalmol Vis Sci
1993;34:3278.
22. Dorey CK, Stauranghi G, Delori FC. Lipofuscin in aged and
AMD eyes. In JG Hollyfield, TMM LaVail, RE Anderson (Eds):
Retinal Degeneration. New York: Plenum Press, 1993;3-14.
23. Crabtree DV, Adler AJ, Snodderly DM. A local minimum of
vitamin E in macaque retina is automatically coincident with a
common locus of atrophy in human retina. Invest Ophthalmol
Vis Sci 1994;35:1392 (Abstract).
24. Snodderly DM, Handelman GJ, Adler AJ. Distribution of
 Chapter 155: Oxidative Stress and Antioxidants in Ophthalmology
individual macular pigment carotenoids in central retina of
macaque and squirrel monkeys. Invest Ophthalmol Vis Sci
1991;268.
25. Allard JP, Royall D, Kurein R, Muggli R, Jeejeebhoy KN. Effect
of beta-carotene supplementation on lipid peroxidation in
humans. Am J Clin Nutr 1994;59:884.
26. Rimm E, Colditz G. Smoking, alcohol and plasma lipids of
carotenes and vitamin E. Ann NY Acad Sci 1993;68(6):323.
27. Schectman G, Byrd JC, Gruchow HW. The influence of smoking
on vitamin C status in adults. Am J Pub Health 1989;79:158.
28. Anderson RE, Rapp LM, Wiegand RD. Lipid peroxidation and
retinal degeneration. Curr Eye Res 1984;3:223.
29. Fliesler SJ, Anderson RE. Chemistry and metabolism of lipids
in the vertebrate retina. Prog Lipid Res 1983;22:79.
30. Neuringer M, Connor WE, Lin DS, Barstad L, Luck S.
Biochemical and functional effects of prenatal and postnatal
Omega-3 fatty acid deficiency on retina and brain in rhesus
monkeys. Proc Natl Acad Sc USA 1986;83:4021.
31. Ham WT Jr, Mueller HA, Ruffolo JJ Jr, Guerry D, Guerry RK.
Action spectrum for retinal injury from near-ultraviolet radia-
tion in the aphakic monkey. Am J Ophthalmol 1982;93:299.
32. Ruffolo JJ Jr, Ham WT Jr, Mueller HA, Mille JE. Photochemical
lesions in the primate retina under conditions of elevated blood
oxygen. Invest Ophthalmol Vis Sci 1984;25:893.
33. Spikes JD. Photosensitization. In KC Smith (Ed): The science
of photobiology. New York:Plenum Press1977;87.
34. Lim BP, Nagao A, Terao J, Tanaka K, Suzuki T, Takama K.
Antioxidant activity of xanthophylls on peroxyl radical-
mediated phospholipid peroxidation. Biochem Biophys Acta
1992;112(6):178.
35. Snodderly DM, Auran JD, Delori FC. The macular pigment II.
Spatial distribution in primate retinas. Invest Ophthal Vis Sci
1984;25:674.
36. Burton GW, Ingold KU. Beta-carotene: An unusual type of
lipid antioxidant. Science 1984;224:569.
37. Snodderly DM. Evidence for protection against age-related
macular degeneration by carotenoids and antioxidant vitamins.
Am J Clin Nutr 1995;62 (Suppl):1448S.
38. Rapp LM, Maple SS, Choi JJ. Lutein and zeaxanthin concentra-
tions in rod outer segment membranes from perifoveal and
peripheral human retina. Invest Ophthalmol Vis Sc 2000;
41:1200.
39. Feeney-Burns L, Neuringer M, Gao CL. Molecular pathology in
monkeys fed semipurified diets. Prog Clin Biol Res
1989;314:601.
40. Hayes KC. Retinal degeneration in monkeys induced by defi-
ciencies of vitamin E or A. Invest Ophthalmol Vis Sci
1974;13:499.
41. Tso MOM. Pathogenetic factors of aging macular degeneration.
Ophthalmology 1985;92:628.
42. Barja G, Lopes-torres M, Perez-Campo R et al. Dietary
vitamin C decreased endogeneous protein oxidative damage,
malondialdehyde and lipid peroxidation and maintains fatty
acid unsaturation in the guinea pig liver. Free Radic Biol Med
1994;17:105.
43. Kimura H, Yamada Y, Morita Y, Ikeda H, Matsuo T. Dietary
ascorbic acid depresses plasma and low density lipoprotein
lipid peroxidation in genetically scorbutic rats. J Nutr
1992;122:1904.
1233
44. Cadens S, Lertsiri S, Otsuka M, Barga G, Miyazawa T.
Phospholipid hydroperoxides and lipid peroxidation in liver
and plasma of ODS rats supplemented with alpha-tocopherol
and ascorbic acid. Free Radic Res 1996;24:485.
45. Frei B. Vitamin C as an antiatherogen: Mechanism of action. In
L Packer, J Fuchs (Eds): Vitamin C in Health and Disease.
New York:Marcel Dekker Inc.1997;163.
46. Cross CE, Halliwell B. Nutrition and human disease: How
much extra vitamin C might smokers need? Lancet 341:1091,
1993.
47. Weber C, Wolfgang E, Weber K, Weber PC. Increased adhe-
siveness of isolated monocytes to endothelium is prevented by
vitamin C intake in smokers. Circulation 1996; 93:1488.
48. Levine GL, Frei B, Koulouris SN, Gerhard MD, Keaney H, Vita
JA. Ascorbic acid reverses endothelial vasomotor dysfunction
in patients with coronary artery disease. Circulation
1996;93:1107.
49. Vita FJA Frei, B Holbrook, M Gokce, N Leaf, C Keaney JF.
L-2-Oxothiazolidine-4-Carboxylic acid reverses endothelial
dysfunction in patients with coronary artery disease. J Clin
Invest 1998;101:1408.
50. Singer M, Webb AR. Oxford handbook of critical care. New
York: Oxford Univ Press 1998;71.
51. Gaby S, Bendich A et al. Vitamin intake and health: A scientific
review. New York: Dekker 1991.
52. Glutathione reduced (GSH). Technical monograph. Alternative
Medicine Review 2001;6(6).
53. Reddy VN. Glutathione and its function in the lens—an
overview. Exp Eye Res 1990;50(6):77.
54. Bando M, Obazawa H. H2O2 dependent NADH oxidation
activity in senile cataractous human lens: Its relation to
glutathione redox cycle. Jpn J Ophthalmol 1990;34(2),188-95.
55. Cai J, Nelson KC, Wu M, Sternberg P Jr, Jones DP. Oxidative
damage and protection of the RPE. Prog Retin Eye Res 2000;
19(2):205.
56. Giblin FJ. Glutathione: A vital lens antioxidant. J Ocul
Pharmacol Ther 2000;16(2):121.
57. Kidd PM. Glutathione: Systemic protectant against oxidative
and free radical damage. Alt Med Rev 2000;2(3):155.
58. The Age-Related Eye Disease Study (AREDS). Design impli-
cations, AREDS Report No. 1. The Age-Related Eye Disease
Study Research Group. Control Clin Trials 2000;20:573.
59. The Age-Related Eye Disease Study. A Clinical Trial of Zinc
and Antioxidants. Age-Related Eye Disease Study Report No.
2. J Nutr 2000;130(5S Suppl):1516S.
60. Lyle BJ, Mares-Perlman JA. et al. Antioxidant intake and risk
of incident age-related nuclear cataracts in the Beaver Dam
Eye Study. Am J Epidemiol 1999;149:801.
61. Smith W, Mitchell P, Webb K et al. Dietary antioxidants and
age-related maculopathy: The Blue Mountains Eye Study.
Ophthalmology: 1999;106:761.
62. Vandenlangenberg GM, Mares-Perlman JA, Klein R et al.
Association between antioxidant and zinc intake and the 5 year
incidence of early age-related maculopathy in the Beaver Dam
Eye Study. Am J Epidemiol 1998;148:204.
63. Kuzniarz M, Mitchell P, Gumming RC, Flood VM. Use of
vitamin supplements and cataract: The Blue Mountain Eye
Study. Am J Ophthalmol 2001;132:19.
 Chapter 156

Contact Lenses
RP Bhatia, LC Dutta

BRIEF HISTORY combined together becomes 1.40. Basically contact

lenses are of two types—scleral contact lens and
Tracing back the history of contact lenses takes us way
corneal contact lens. Now corneal contact lenses are
back to the year 1508. Leonardo de Vinci of Italy
more commonly used.
designed a large bowl half filled with water and
The contact lens with the posterior curvature
suggested that a person could improve his vision by
approximating that of the anterior surface of the
immersing his head up to ears, face down in it. Then
cornea and the anterior surface with a radius of
after a series of changes Dr Thomos Young (1801) who
curvature shorter than that of the cornea increases the
came up with the first most significant idea in the
refractive power of the eye. Similarly an anterior
history of contact lenses by designing a tube 1/4 inch
contact lens surface with a greater radius of curvature
long with a lens of 20 mm focal length fixed at its distal
than that of the cornea decreases the refractive power.
end and closely applied to the eye after filling it with
The high surface tension of tear fluid is a strong
water. This eliminated optical defects of corneal
determining factor in the positioning of the contact
curvature and later substituted it for a regularly
lens on the eye. Peripheral part of the cornea is flatter
ground lens. In his own words “On application the
than the central zone which is the central optical zone.
eye suddenly became farsighted”. Then in 1888 when
The area of maximum curvature of the cornea is the
three scientists: A Fick of Zurich, K Kalt of Paris and
corneal apex which is approximately 4 mm in
August Mullar-Gladback of Kiel, working indepen-
diameter. This may or may not coincide with the center
dently attempted to adopt the human eye to contact
through which the line of vision or the optical axis
lenses for different purposes.
passes.
Thereafter the pace of development was accele-
The tear fluid in between the contact lens and the
rated, ground and molded lenses replaced blown
cornea contains dissolved oxygen which is required
types. Materials changed gradually from glass to
by the corneal epithelium for aerobic metabolism. If
plastic. Corneal contact lenses replaced scleral ones.
inadequate tear exchange occurs between the contact
Designs, materials and techniques are undergoing
lens and the cornea, this metabolism may be reduced
continuous advancement for better patient’s satisfac-
resulting in deficiency of corneal glycogen stores
tion and comfort.
leading to epithelial and stromal edema. The refractive
index of the cornea may increase due to the edema
OPTICAL PRINCIPLES OF CONTACT LENS
hence, there may be some amount of induced myopia
The optical principle of contact lens is that the on lens removal. This causes the spectacle blur.
refraction at corneal surface is eliminated; the film of Hydrogel lens and gas permeable semisoft lenses are
tear fluid between the contact lens and cornea on either ideal for extended wear. First generation hydrogel
side, the three together acts as one refracting unit. contact lenses were made from hydroxyethyl-
Here, the refractive index of the three media, viz. methylacrylate (HEMA). When polyvinyl-pyrolidone
PMMA, tear fluid and the cornea (refractive index of (PVP) is added to HEMA, the water content is
PMMA = 1.496, tear fluid = 1.338; cornea = 1.376) increased and the lenses made from this material is
 Chapter 156: Contact Lenses
second generation soft contact lens. Third generation
contact lens is made of a hydrogel substrate obtained
by polymerization of hydrophilic monomer with a
cross-linking agent. This hydrogel substance leaves
two compartments; one permanent solid compartment
which consists of the polymer network and a variable
aqueous compartment which consists of random
orientation of spaces between the polymer chains.
Hydrogel lenses adhere closely to the corneal surface
requiring only a tear film of capillary thickness
between the lens and the cornea.
MATERIALS USED FOR CONTACT LENSES
Today the contact lens practitioner must not only keep
up-to-date with changes in lens construction materials
and fitting techniques but also learn to evaluate the
new materials, which are being introduced. Numerous
properties have got to be satisfied in an ideal contact
lens material, important among which are as follows:
1. Safety
2. Optical properties
a. Refractive index
b. Transparency.
3. Physical properties:
a. Specific gravity/density
b. Properties of elongation and recovery
c. Tear resistance
d. Hardness
e. Scratch resistance
f. Thermal conductivity
g. Hydration
h. Wettability
i. Porosity and permeability
4. Resistance to chemical agents
5. Electrical properties.
The first contact lenses were made of glass. So upto
1930s nothing much was done due to obvious limi-
tation. Then came the era of synthetic plastics with
the introduction of polymethyl methacrylate (PMMA)
which led to wide advancements in the field of contact
lens. In 1961 the ‘soft hydrogels’ were introduced.
Since then considerable research has been going on
for newer materials with better properties.
Polymethyl Methacrylate (PMMA)
The PMMA has been the all time popular contact lens
material till date. It is an amorphous, thermoplastic, a
polymer of methylmethacrylate. It is safe with
hundred percent transparency and a refractive index
of 1.496. Pigments for color tints and antibacterial
1235
substances for such effects can be added to it. Its
physical properties are good and it is resistant to most
chemical except for a few like ketones, esters and
aromatic hydrocarbons. It is not malleable, hence, it
is a hard or rigid contact lens
The disadvantage is that it does not possess very
good wettability; though this can be overcome with
use of wetting solution. Surface coating of lenses with
silicon oxide has been tried. To improve refractivity
of the material it can be co-polymerized with styrene,
a liquid hydrocarbon.
Other Materials
• Polymethylpentine
• Diethyl glycol
• Polycarbomate (high refractive index-1.586)
• Polystyrine
• Cellulose acetate butyrate
• Lonomers-Monomers held together byelectrostatic
bonds.
Soft Hydrophilic Materials
First reported in 1960, they have gained popularity
over the years. They have 50 to 90 percent water
though 30 to 60 percent water content is most suitable.
The available materials are:
HEMA Cross-linked with EGDMA
These are the most widely used hydrogels. These are
made up of 2-hydroxyethyl methacrylate cross-linked
by an agent ethylene glycoldimethacrylate (EGDMA).
The water content varies with pH and temperature.
Polar/ionic materials in bathing solution, when placed
in eye it varies until it has equilibriated with the
lacrimal fluid. At this point the water content is 38 to
39 percent and refractive index is 1.43.
These are soft, transparent, flexible when hydrated,
permeability to O2, glucose and water is low; similar
to PMMA. Though in porosity it is better and fluo-
rescein permeates through. These have been proven
nontoxic.
HEMA-PVP (Polyvinyl pyrrolidine) hydrogel This is
HEMA cross-linked with PVP through the agent
EGDMA and is very widely used.
Glyceryl Methacrylate (GMA) Polymers
Glyceryl is a transparent hydrogel polymer which can
be cross-linked with tetraethylene glycol dime-
thacrylate to form a thermo setting plastic.
1236 Section 9: Miscellaneous Topics
By varying the diluation of monomer, before
initiating polymerization; and also amount of cross-
linking agents the water content can be set between
60 and 90 percent.
The refractive index of GMA varies in linear
fashion with water content. With 95 percent water
index is about 1.34 and with 75 percent about 1.37.
HEMA-PGMA Copolymers
Copolymers can be formulated of HEMA and PGMA.
Water content of copolymers can be varied between
40 percent in case of HEMA and 50 percent if solely
PGMA. A combination gives water content inter-
mediate between the two homopolymers.
Others
Polyelectrolyte complexes In this the polymers are
held together in three-dimensional network by ionic
charges between two oppositely charged polymers.
Complexes of poly (Vinyl benzyl-trimethyl ammo-
nium chloride—VBTAC) and poly (styrine sulfonate—
NaSS) when placed in a solution, they ionize forming
two polymers with many ionized units along them;
they go together like a zipper so that opposite charges
are opposing forming an insoluble plastic.
The VBTASS polysalt formed is homogeneous,
amorphous and transparent.
It is extremely hard, when dry and leathery, when
hydrated. Relative Index varies with water content
from about 1.52 with 30 percent water to 1.38 with
75 percent water.
The material is permeable to water, electrolytes and
other small water soluble molecules. It is insoluble in
most common solvents. It has an advantage of being
permeable to gases but its heat stability is questio-
nable.
Newer materials These are still under evaluation.
Principle among these are:
• Elastomers/Rubbers These have very good stretching
and recovery properties and are good potential
contact lens materials.
• Silicone These are hydrocarbon substituted poly-
siloxane rubbers to which silica fillers up to 40
percent can be added to vary the physical
properties. The soft type is used for lens material.
It is transparent with refractive index of 1.439,
flexible and with very good gas and solute
permeability which is a distinct advantage over
other materials.
Disadvantages are its poor hydration and low wett-
ability. The latter can be overcome by surface
treatment and use of wetting solutions by patients.
Combinations of rubbers and polymers For example,
styrine-betadeinci when has properties intermediate
between the ones of its components.
Collagen Collagen reconstituted from porcine source
has been used to manufacture therapeutic contact
lenses which gradually dissolve in the tear film and
additionally serve to increase the contact time of drops
concurrently used for therapeutic purposes. When
fully hydrated, these lenses have a high water content
and moderate oxygen transmissibility. However,
collagen has not yet been used for manufacture of
cosmetic lenses.
INDICATIONS FOR CONTACT LENS
The indications of contact lens wear can be broadly
divided into: (1) Optical (2) Therapeutic (3) Cosmetic
(4) For drug delivery (5) Occupational (6) As low
vision device
Optical
Myopia Better than glasses because there is little
marginal aberration, better transmission, perception
and larger field.
Hypermetropia Such patients have to exert less accom-
modation and convergence with contact lens. Contact
lenses provide larger field, better transmission and
little interference.
Astigmatism In patients with irregular corneal surface,
due to any previous ocular disease, corneal lens
provides regular surface and so astigmatism may
decrease to some extent. If there is coarse corneal
irregularity, one can use piggy back system with a
hard lens fitted over the soft lens which gives good
acuity and protects corneal epithelium.
 Chapter 156: Contact Lenses
Presbyopia Presbyopic correction in a hypermetrope
can be delayed by few years by use of contact lenses.
Aphakia Contact lens provides wider and brighter
field, smaller magnification, lesser convergence and
marginal aberration. But foremost is better chances of
binocularity compared to correction by spectacles.
Contact lenses for infant aphakics Intraocular lens
implantation in infants are being practised by many
surgeons; but the difficulty in obtaining adequate
parameter for infants, the subsequent growth of the
eye after implantation and the number of compli-
cations make them unacceptable in most cases.
Epikeratophakia is a promising solution but it is not
popular due to obvious reasons. In most of the
countries, this procedure should be reserved as an
alternative in some older patients who are intolerant
to contact lenses. Contact lens correction of infant
aphakia is an acceptable method of optical correction
and has got high quality of optical correction with low
complication rate. Daily wear high water content soft
lens affords good result.1,2
Anisometropia and aniseikonia Contact lenses in such
cases help by bringing the size of image of defective
eye nearer to the emmetropic eye which helps in
binocular vision of the patient.
Due to absence of aberration they also provide
larger field, bright and clear image.
Keratoconus and irregular astigmatism It provides
regular corneal surface but as such has no effect on
basic course of the disease. Excellent vision is usually
achieved long after spectacle correction has failed and
long before corneal scarring has indicated that surgery
should be considered.
Albinism Contact lenses help by correcting the
associated myopic astigmatism. They are also better
for the same reasons as in high myopia and astig-
matism. Photophobia may be retarded through a
darker contact lens. Lenses with opaque scleral part
and lenses with multiple holes in optical area are a
better aid.
Nystagmus Contact lenses decrease amplitude of
nystagmus. They also improve performance by better
correction of associated refractive anomaly.
Therapeutic
Different materials are used for preparation of
therapeutic contact lenses.
1237
Soft and Silicone Lens
Soft lenses in plano power varying from low to high
water content have been used for many years as
therapeutic lenses, particularly to reduce pain or
facilitate healing. Silicon rubber lens is more
comfortable than other soft lenses. The hydrophobic
nature of silicone material allows it to retain its
physical properties on dry eyes. Due to its defined
shape it can be useful in perforated cornea to postpone
surgery. Silicone lens can also be used as extended
wear and daily wear lens in infantile and elderly
aphakic eyes.
Hard Gas Permeable Lens
Hard gas permeable lens have got some advantages.
These can be used after radial keratotomy where
PMMA lens may cause vascularization.
Scleral Lens
Scleral lenses are prepared from gas permeable
materials. Patients can tolerate hard gas permeable
scleral lenses more comfortably than PMMA lenses.
Soft lenses and flush fitting shells are useful in the
following ocular diseases:
Dry eye Success has been less predictable. Large
amount of mucus collects under the lens causing
blurring of vision and secondary infection in few cases.
In ocular pemphigoid soft lens may protect and
moisten corneal epithelium but conjunctival shrinkage
and symblephron formation may cause lens buckling
and loss.
Corneal edema Lenses reduce it probably through
massage like action.
Corneal grafts Protect graft epithelium and permit
healing of epithelial defects.
Corneal Burns/Indolent Ulcers
Bullous keratopathy and exposure keratitis Contact lenses
are used to relieve pain by protection of exposed
corneal nerve endings and occasionally to improve
visual acuity.
Recurrent corneal erosions and corneal epithelial defects In
cases where epithelial healing fails to occur in a
reasonable time with conservative therapy, these help
by protecting fragile epithelium from trauma of the
eyelids.
1238 Section 9: Miscellaneous Topics
These also allow sufficient time for formation of
hemidesmosomal attachments to epithelial basement
membrane.
Symblephron After cutting adhesions a scleral shell is
given.
Keratoconjunctivitis sicca Artificial tears are used with
soft lenses for a week or two.
Chemical Burns
Healing of epithelial defects which takes weeks to
months.
Perforation and wound leak Lens closes the leak suffi-
ciently to allow reformation of shallowed anterior
chamber.
Cosmetic
Cosmetic Lenses
Soft lenses can be used to cover unsightly opaque
cornea. However, rigid cosmetic shell also can serve
this purpose. The lens may be tinted to match the color
of the opposite eye. Pupil can be painted black.
Opaque contact lens can be used a temporary measure
to prevent diplopia of recent origin due to muscle
palsy. Occlusion therapy of strabismus in children or
adolescents also can be tried with contact lens.3
A deformed eye with useful vision is corrected by
painted lens with clear pupil which bears the optical
correction.
Colored contact lenses for cosmetic purpose in
ocular albinism. The central 4-5 mm and the most
peripheral part covering the limbus and the adjoining
rim of sclera is not colored. Oculocutaneous albinism
is associated with nystagmus and for correction of
refractive error with nystagmus, contact lenses work
better. Also these are used to change color of iris by
actresses.
Occupational
In sports, contact lenses have an advantage because
of fewer hazards of serious injury, better optics and
wider field.
Fogging of spectacles in temperature variation can
be avoided by using contact lenses as they are at body
temperature.
Contact Lenses as a Low Vision Aid
A high power minus lens over the cornea and high
power eye glass (spectacle) as the principle of Galilean
telescope can be used as a low vision device.
Diagnostic
In fundoscopy A high minus central lens neutralizes the
cornea as a result fundus can be viewed directly.
In gonioscopy To visualize angle, and to operate on the
angle in infantile glaucoma.
CONTRAINDICATIONS
First and foremost point to be kept in mind is that
contact lenses should never be used till any ocular
pathology, if present, is properly treated and taken
care of.
Besides they should not be worn during respiratory
disorders, e.g. cold and cough, as there are chances of
displacement and corneal irritation due to constant
watering of eyes in such conditions.
Contraindications are best divided into several
heading as:
Disease of lids For example, stye, chalazion, trichiasis,
entropion, ectropion, squamous and ulcerative blepha-
ritis.
Disease of conjunctiva Conjunctivitis such as viral
bacterial, fungal, allergic and vernal.
In cases of chronic hyperemia and pterygium
(contact lens may irritate the pterygium head and even
the regressed one may become vascularized).
Diseases of cornea For example, epithelial dystrophies,
pannus formation, corneal ulcer. Contact lens in such
cases may flare up the disease and may lead to further
deterioration.
Vth nerve paralysis Due to decreased corneal sensation
any trauma due to contact lens wear may lead to
corneal ulceration.
Exophthalmos Lens is not picked up by the lid as the
upper lid does not reach the limbus.
Other ocular contraindications are scleritis, episcleritis,
anterior uveitis, choroiditis and postglaucomatous
surgery with bleb.
Nonmedical and systemic causes Though mentioned in
the end but still these factors play a very important
role in failure of contact lenses. Without proper and
apt motivation patient will not accept contact lenses
readily and will not take proper care if the examining
doctor leaves any lacunae on his part in convincing
the patient.
Failures are more common in male patients having
low myopia with larger pupils.
 Chapter 156: Contact Lenses
Patients with poor general health and old patients
may face difficulty in handling and manipulation of
contact lenses.
Endocrine disorders are contraindications for
contact lenses, e.g. diabetes and patient going through
menopause. As this may change quality and quantity
of tear film, making tolerance uncomfortable.
Initial fitting of contact lenses should be avoided
in pregnant women as change in endocrine balance
may cause corneal edema, discomfort and adaption
problems.
FITTING OF CONTACT LENS
History
Before going to actual examination, history plays a
very important role as it helps eliminate some
contraindications as well as to know the cause for
wearing contact lens. Patient’s general history must
be taken, specially regarding systemic diseases like
diabetes or hyperthyroidism. History of medication
like diuretics, birth control pills, antihistaminics, alpha
and beta blockers for glaucoma interfere in tolerance
of contact lenses by causing problems like water
logging, conjunctival dryness, allergic manifestations,
etc.
A complete ocular history, viz. any previous ocular
trauma or disease, is very important. Patients with
special correction, binocular vision anomalies or
previous orthoptic training should be thoroughly
investigated and understood.
History of patient’s hobbies, occupation and
particular visual requirement should also be elicited.
Motivation and reasons for wanting contact lenses are
always relevant.
External Examination
A careful and proper examination of lid, conjunctiva,
cornea, anterior chamber and other related structures
should be done without fail before putting a lens on
to the eye. Any abnormality should be carefully noted
so that any change produced by wearing of contact
lenses can be easily differentiated.
Gross examination can be done by torchlight, loupe
and ophthalmoscope. Detailed slit lamp examination
is necessary for detecting any defect in integrity of
corneal epithelium, stroma and endothelium. Dry
spots, epithelial bullae, etc. must be excluded.
1239
Visual Function
Visual acuity and refraction should be assessed prior
to any further investigation.
In cases of unilateral aphakia, high refractive error
and in pre-presbyopic period assessment of binocular
vision is very important.
Keratometry
To measure the radius of curvature of the central area
of the cornea. The instrument should be caliberated
every week with an average of three readings taken.
Peripheral Keratometry
To obtain a better clinical picture of the corneal topo-
graphy, different procedures for recording readings
at various points across the cornea have been used.
This is done by an instrument known as topogometer
which records keratometry at known distance from
visual center.
Corneal and Pupillary Diameter
These are measured by a transparent scale in
millimeters. Pupillary diameter can also be measured
by pupillometer. Palpebral aperture is measured by a
transparent scale with patient looking forward.
Additional Tests
a. Assessment of lid tension by lifting upper lid.
b. Corneal sensation.
c. Schirmer’s test to find out the quality and quantity
of tear fluid.
d. Blinking rate—normally 12 to 15 times per minute.
Patient Consultation
It is of utmost importance to discuss with patient what
is involved in both fitting and wearing of contact
lenses before doing contact lens evaluation.
The procedure related to initial investigation,
examination and follow-up care should be explained
in terms of approximate number of visits and total
financial implications.
All the fears of patient like ‘contact lenses cause
permanent ocular damage’ or ‘being lost’ should be
allayed with patience and understanding.
Following initial examination and fitting proce-
dures a clinician should spare some time to explain to
1240 Section 9: Miscellaneous Topics

patient the type of lens fitted, its advantage for the

patient and the reason for which it was selected.
Once the patient is satisfied, insertion and removal
should be taught; care of lens and wearing schedule
should be explained.
Approximate Life of Lens
Hard (GP) lens : 4 years
Soft lens : 2 years
Structure of a Corneal Contact Lens
Figure 156.1 depicts the structure of a corneal contact
lens and other basic measurements and values.

Fitting Procedures
The ideal contact lens should have a good physical
and optical fat, so that patient can wear the lenses
without discomfort and the lens should not produce
any harmful effect on the eye. The vision should be
without any distortion and at least equal to or better
than the spectacles. The movement of lens on the eye
should be smooth without jerk or friction. That the
person is wearing lenses should not be noticeable to
the other fellows to give the best cosmetic result. It
means that an ideal and comfortable contact lens wear
should not change the blink rate, should not give any
watering from the eye, should not produce any
congestion in the eye and should not produce any
corneal damage, e.g. corneal abrasion, corneal edema
even after long wear.
The flatter meridian of the keratometry reading
known as ‘K’. For example if
HA = 7.50 mm (45 D)
VA = 7.00 mm (48 D)
Then 7.50 mm or 45 D would be ‘K’. A lens having
curvature more than ‘K’ will be called as flatter than
‘K’ and steeper than ‘K’ if lens curvature is less than
‘K’; example: 7.70 is flatter than ‘K’ and 7.30 is steeper
than ‘K’.
Fitting of Hard and Gas Permeable Contact Lenses
There are various methods of fitting these lenses and
one may adopt depending upon what is best suited
in the circumstances.
Methods
1. By keratometry alone
2. By trial lenses
3. Combination of keratometry and trial lenses.
Initially the accurate refraction of the patient is
done and then any of the methods can be followed.
Fig. 156.1: Parts of a corneal contact lens
The effective spectacle power is derived by taking into
consideration the vertex distance at zero and
transforming the cylinder into a minus cylinder.
For example : –5.25 D Sph/+1.00D Cyl 90°
Changed to : –4.25 D Sph/–1.00D Cyl 180°
Correction for
vertex distance : –4.00 D Sph/–1.00D Cyl 180°
By keratometry alone This method is not so accurate and
reliable. Average keratometry, i.e. mean of the two
readings is taken as back central optic radius.
In this method patients’ central and peripheral
corneal curvatures and the width of the palpebral
aperture are helpful in determing lens design but, as
already mentioned, unless behavior of trial lens on
the eye is judged the accurate prescription cannot be
given by keratometry alone.
By trial lenses In this method the various trial lenses
are used and the fitting is judged by fluorescein
pattern. But this method is also unsatisfactory because
many trial lenses are used to find an appropriate lens.
This method is time-consuming and may be harmful
to the cornea if there is wide variation in trial and ideal
lenses specially in steeper lens.
Combination of keratometry and trial lenses This is the
best method. Though keratometry forms the main
basis for corneal lens fitting, the behavior of trial lenses
on the basis of keratometry is of utmost importance
and gives the best lens fit.
 Chapter 156: Contact Lenses
The trial lenses usually available for practice
include the following:
a. Low myopic set (–3D)
b. High myopic set (–12D)
c. Set for keratoconus
d. Set for aphakia (+ 12D)
Keratometry is done in two principal meridians
and if there is an astigmatism less than 0.50 D fitting
is done on ‘K’, i.e. on flatter meridian. If there is
astigmatism between 0.50 and 1.00 D then 0.25 D is
added to the flatter reading of keratometry. In cases
with more than 2.0 D of astigmatism 1/3 to 1/2 of the
difference is added to flatter meridian of the
keratometry reading. This decides the power of the
first trial lens to be put on to the eye.
Example
1. HA = 45.00D (7.50 mm)
VA = 45.50D (7.42 mm)
The fitting will be done on ‘K’ i.e. 45.00D
2. HA = 45.00D (7.50 mm)
VA = 46.00D (7.34 mm)
The fitting will be done on 45.25
3. HA = 45.00D (7.50 mm)
VA = 48.00D (7.03 mm).
The fitting will be done on 46.00D to 46.50D.
Note: It should be kept in mind that the dioptric power
of the cornea changes inversely to the curvature of
cornea.
After washing the hands with soap and water first
trial lens is put on to the eye. The trial lens should be
chosen from appropriate trial set. This not only helps
judge the behavior of the lens better but also needs
less overhead correction. For example if a patient has
refractive error –9.00D it will be wise to choose a lens
from high myopic set (–12D) while in case of –4.5D
myopia a lens from low myopic set (–3D) will be more
appropriate.
Note: Some people use local anesthetic agent before
putting trial lens but most people do without it.
Before judging the fit of the lens, it is important to
allow sufficient time (15 to 20 minutes) to the patient
after putting first trial lens. But if the patient is
extremely uncomfortable with trial lens it should be
removed immediately and a review of the keratometry
and resultant change in the appropriate trial lens, if
any, is advisable.
Next, sterile fluorescein 1 percent drops or strips
are used to judge the fitting of the contact lens. This is
done by blue light under magnification with ultra-
1241
violet lamp or by slit lamp. In a good fitting, thin film
of fluorescein should be present in the center as well
as at all the periphery with a very thin intermediate
zone 0.50 to 1.00 mm wide. If there is collection of
fluorescein pool at the center it shows a steep fit. While
no fluorescein at the center depicts central touch or a
flat fit. So the next change in the trial lens should be
done accordingly (Figs 156.2A and B).
In addition, a well-fitted lens should nearly be
centrally placed and should move smoothly with
blinking and with the movements of the eye. During
blinking the lens moves slightly downward and then
rises up with the movement of upper lid and
ultimately comes down to the central position. If the
lens sags down then one must assume it to be a flat fit
or this may occur in high hypermetropic lens and in
aphakia. In moving the eye side to side the lens moves
in opposite direction but on looking straight again it
should center well on the cornea. If the lens tries to
dislodge on the conjunctiva or falls down from the
eye frequently it shows a very flat fit, too small a lens
or tight lids. This may also occur in high power lenses.
In a toric cornea the pool of fluorescein shows a
band in one meridian depending upon the toricity of
the cornea.
In keratoconus the fluorescein pool never depicts
ideal pattern; in the satisfactory fitting there is a small
central touch with a moderately uniform pool of
fluorescein at center and periphery. The overall size
of contact lens should be such that the movement of
the lens should be minimal. If a larger lens is required
suitable peripheral curves should be ordered.
Figs 156.2A and B: Showing the fluorescein
lists for proper fitting
1242 Section 9: Miscellaneous Topics
After the satisfactory fitting of contact lens over-
head refraction should be done and the final power of
lens should be calculated by taking account of the
vertex distance.
Insertion and Removal of Lens
There are many methods described but here most
simple and practical method is described. The patient
must be clearly explained about the hygiene in inser-
tion, removal and storage of the lenses. The hands
must be washed thoroughly with soap and water
specially the finger tips and palm, every time patient
touches the lenses. After washing the hands these
should not be dried by towel and one should not touch
skin, cosmetics, hair or comb, etc. to avoid any grease
or chemical coming into contact which may spoil the
lens.
Always right lens should be inserted and removed
first in right handed people to avoid interchange. The
lens must be cleaned by appropriate cleaning solution
and rinsed well with soaking solution or normal saline.
Insertion The cleaned lens is taken on right index finger
with its concavity facing up. The right upper lid is
held up by the fingers of other hand and the lower lid
is pulled down by the middle and ring fingers of the
right hand. While looking in the mirror the lens is
gently placed on the cornea. Now fingers are released
from the lids and gentle blinking is done. Insertion in
the other eye is done by the same method. Some
people advocate change of hand but the authors
consider it to be unnecessary.
Removal While looking in the mirror eyes are kept wide
open. The right index finger fixes the lower lid at lower
limbus and left index finger first pulls upper lid up
and then gently slides it down and laterally pushing
the upper edge of the lens and thus the lens drops
out.
Some prefer to use index and middle fingers of
same hand to widen the palpebral fissure and then
pulling the lids laterally in a scissor fashion to push
the lens out.
Wearing Schedule
It is always advisable for a new patient to gradually
increase the daily wearing time of the contact lenses.
This helps to adopt the cornea to the lens better.
Following schedule is followed in our patients:
1st day — 1 hour
2nd day — 2 hours
3rd day — 4 hours.
If there is no discomfort, the patient is advised to
wear the lenses for 8 hours from the next day. It is
emphasized not to wear the lenses for more than 8
hours continuously. If the patient wishes to put on
the lenses for more than 8 hours, it is recommended
that it may only be done after a minimum gap of 2
hours. The patient is strictly instructed to remove
lenses before going to sleep.
Bifocal Lenses
The use of bifocal contact lenses is still not very
popular. The reason being that these lenses must have
very little movement and good centration to have
consistent vision for distance and near. Hence, these
lenses have to be tight fitted and prism blasted or
truncated to minimize rotation. In the commonly used
bifocal lenses, the near segment is in the lower part of
the lens. In another type, the near segment is
peripheral while central portion is used for seeing at
the distance.
Soft Contact Lenses
Soft lens is chemically hydroxy ethylmethacrylate
(HEMA) which is cross-linked with EDMA (ethyldi-
methylacrylate) or PVP (polyvinyl pyrrolidine) and
ethylene glycol dimethacrylate. The water content
varies between 25 and 85 percent in the commercially
used lenses.
Advantages
The advantages of these gel lenses include:
1. Comfortable wear
2. Practically no displacement
3. Patients’ adaptation is quicker and more comfor-
table.
4. Minimal blur, glare and photophobia.
Disadvantages
1. Less visual acuity specially in high cylindrical
errors, i.e. more than 2D.
2. Replacement of the lens is required sooner than
Hard/GP lens due to splitting, tearing, deposits,
etc.
3. Proper cleaning, sterilization and enzyme treat-
ment for deposits is very essential.
4. Verification of dioptric power of lens is very
difficult.
5. The fit of the lens is difficult to evaluate since
fluorescein cannot be used as it stains lens perma-
nently. Flurexon may be used to evaluate fit.
 Chapter 156: Contact Lenses
Methods of Fitting
Detailed and careful examination of eye including slit
lamp and applanation tonometry is done. The
horizontal visible iris diameter (HVID) is measured
by transparent scale.
1. By measurement only: (No trial lens)
a. Keratometry, keratotopography and kerato-
photopography
b. Corneal diameter
c. Palpebral fissure
d. Refraction.
The usual lens diameter is 12 to 16 mm and at least
0.75 to 1.00 mm bigger than corneal diameter. The
accuracy of such a lens prescribed by measurement
alone is limited.
2. By trial lenses:
a. Initial base curve should be 0.50 to 1.00 mm
flatter than ‘K’. This flattening is in direct
proportion to hydration of the lens.
b. The lens should be 1.50 to 2.00 mm larger than
HVID.
c. The power of the lens is similarly calculated as
described in GP lens.
Evaluation of the Fit
a. The lens should center well on the eye and the
margin of the lens should extend evenly in all
directions of gaze.
b. With blinking the lens movement should not be
more than 1.00 mm. If it is more, then the lens is
loose or flat. If the movement is less than 0.50 mm
it is a tight fit lens.
c. Any compression of scleral vessels by the lens
denotes a tight fit.
d. Visual acuity and overhead refraction is done. The
retinoscopic reflex should be clearly crisp both
before and after blinking. If the vision or the
retinoscopic reflex clears on blinking it is a steep
fit. On the contrary, if the reflex becomes hazy or
vision diminishes it signifies a flat fit.
Note Thicker lenses are fitted larger and steeper
than thinner lenses. Rigid lenses are fitted steeper.
Oxygen Permeability through Contact Lens
It is measured in laboratory conditions as:
Dk/L
where,
Dk = Oxygen permeability of the lens measured in
cm2 × ml of oxygen/seconds × ml × mm Hg
1243
L = Thickness of lens in mm.
D = diffusion
K = solubility
If the eye is open, the Dk/L value must be 20 or
more and if the eye is closed the Dk/L value must be
75 or more to avoid hypoxia to the cornea (Posle, KA,
1979).
Oxygen permeability is inversely proportionate to
the thickness of the lens. In hydrogel lens the major
oxygen transmission is done through the contact lens
itself as there is very little tear exchange under these
lenses. We have choice of two major group of hydrogel
materials:
a. Highly hydrated lens which are made thick (as on
making them thin they become fragile), e.g.,
Permalens and Softcon.
b. Low water content lens which can be made as thin
membrane, e.g., Hydrocurve.
Rigid Gas Permeable Scleral Contact Lenses
High Dk contact lens polymer is used for hyper oxygen
transmissible contact lens to provide sufficient
oxygenation of the cornea specially in extended wear
contact lens to avoid hypoxia. Hyperoxygen trans-
missible contact lens for long time extended wear upto
30 days are reported to be safe in a controlled case
study.30,31
Care of Worn Lenses
It is mandatory to clean the lens with proper cleaning
solution once before wearing it in the morning and
once after removing it to keep in the lens storage box
before going to bed at night. It is unsafe to rinse or
store any type of contact lens in tap water because of
risk of infection by organisms like acanthameba which
causes keratitis. Gas permeable lens and hard lens
wearers may also have acanthameba keratitis, but soft
lens wearers get it more commonly.5 Contact lens wear
is an important predisposing factor for infectious
keratitis. Extended wear contact lens has a 10 to
15-fold higher risk for infectious keratitis as matched
with daily wear lens (Table 156.1). Bacteria bound with
the deposits which develops on the surface of the
contact lens within first few days of wear.6,7 In the
recent past lens cleaning solutions with preservatives
like benzalkonium chloride, chlorhexidine, sorbic acid
and thiomersal were used; as these chemicals cause
some deleterious effects on the cornea, these are not
used now.

Classification Disorders
Metabolic Acute epithelial necrosis
(Hypoxic) (Over wear syndrome)
Epithelial
Tight lens syndrome2
Microcystic epithelialiopathy3,4
Epithelial edema5 (Sattler’s
veil) or central corneal
clouding
Stromal Stromal edema (striate
keratopathy)
Neovascularization superficial
and deep3
Deep stromal opacity6
Endothelial Endothelial polymegathism12-15
Traumatic Corneal abrasion1
Toxic and Toxic keratopathy7
Allergic
Thiomersal keratopathy8
Giant papillary conjunctivitis
(contact lens related papillary
conjunctivitis)
Contact lens intolerance7
Table 156.1: Disorders caused by contact lens wear
Causes Symptoms
Epithelial cell necrosis Blurred vision before of
and separation of cells3 necrosis due to corneal
edema
Lens tightening Vision is affected. Starts
precipitated by hypoxia during or after overnight
and reduced pH wear
Impaired epiretinal Discomfort or asympto-
metabolic activity matic
Hypoxia and tear Blurred vision after few
hypotonicity11 hours of wearing. May
recover on lens removal
or progress to acute
epithelial necrosis
Stromal lactate Blurring of vision
accumulation causing occasionally
corneal swelling
Hypoxia and release of None unless lipid
vasogenic mediators keratopathy results from
deep vessels causing
loss of vision. May be
asymtomatic.
Prolonged hypoxia and None
hypocapnia
Trauma during lens Sudden onset of pain/ Linear or sharply circum-
handling or trapped epiphora. Ressolves in hours scribed epithelial defects.
foreign bodies behind
the lens, deposits on lens
or poor lens fitting
Exposure to compounds Pain arising soon after
adsorbed by lens inserting a lens soaked in
proteolytic enzyme, chemi-
cally preserved soaking
solution
Preservatives act as Irritation and redness soon
hapters causing a after inserting, vision
delayed hypersensitive affected in severe cases
response
Multifactorial etiology. Increased discharge. Itching
Immune response to on lens removal. Irritation
antigenic proteins on
lens, mechanical effect
of lens edge
Due to lens spoilation Chronic redness, discomfort
and loss of tolerance, vision
may be blurred
1244
Corneal Signs Conjunctival signs Types of lens worn
Corneal punctate Ciliary injection PMMA-HCL,
epithelial erosions which SCI
may coalesce to form ulcer.
Ulcer is larger in SCL wearers
Stromal edema and epithelial Ciliary injection EWCL
defects common and limbal
indentation from tight lens
Few erosions. Clear or opaque None All types of lens
epithelial cysts and punctate
keratitis
Dull corneal reflex from None All types of lens
central corneal edema
Deep stromal folds from None except Usually EWCL
corneal edema occurring in when associated
severe acute epithelial edema with acute epithelial necrosis
Superficial or deep stromal None Common with SCL
vessels. Lipid keratopathy Rare with HCL
associated with deep vessels.
Pre-Descemet’s central
corneal opacity12,15
Endothelial polymega- None All types
thism13,14
Hyperemia Common with HCL
Wide spread punctate lesions Ciliary injection SCL
Section 9: Miscellaneous Topics
Superior limbic injection, Intense SCL rare in HCL
neovascularization, keratopathy hyperemia when
affecting superior quadrants the lens is in the
eye some follicular changes
after lens removal
None Upper tarsal SCL
hyperemia,
mucus and fine
papillary
response. Giant Papillae
Punctate stain common Hyperemia All lenses
papillae and
follicles common
Contd...
 Chapter 156: Contact Lenses 1245
The deposits are more common in soft lenses.

Most common with

Initially the deposits consist of lipid materials,
Common with SCL
Types of lens worn

precipitated protein and some inorganic materials.

EWCL, rare in

PMMA-HCL
Later on remnants of shredded epithelial cells along
HCL with dead or living organisms constitute a part of the

HCL
HCL
SCL
deposits. Use of protein removal tablets help to
dissolve these deposits. The active ingredients of the
tablets are papain, pancreatin or proteins with lipase
and pronase.
Conjunctival signs

Care of Lens Cases

Inferior limbal
Interpalpebral

Devonshire et al reported that microbial contamination

Hyperemia

depression
congestion

hyperemia

hyperemia

affects 53 percent of lens cases; 41 percent of them were

Ciliary

None

None

contaminated with amebial species and all of them

showed concomitant bacterial conjunctivitis. This
underlying stromal infiltrate.

opacity. Inferior interpalpeb-

indicates that lens case hygiene is probably as

Pseudomonas, Staphylococcus,
Acanthamoeba associated21-24

Irregular astigmatism—good Irregular keratometry and

marginal keratitis with or

3 and 9 o’clock positions.

important as lens hygiene if new or disinfected lenses

Punctate keratopathy at
Appearance similar to

Fluorescein poding in

are not. Disinfected lenses will be recontaminated if

Rapid onset and progression Epithelial ulcer with

Rarely vascularized
without ulceration

ral punctate stain

they are stored in dirty or contaminated lens case.8

epithelial vision
Corneal Signs

vision with contact lens and topography

Care of Trial Lenses

Trial contact lenses, if not regularly disinfected after
use in each patient, is a common source of cross
infection. Though, as yet contact lenses have not been
poor vision with spectacles
Inferior limbal redness and

Asymtomatic or blurred
Discomfort redness and

proven to transmit HIV from one individual to

of pain, hyperemia and

Interpalpebral redness

another, this potential still exists, because HIV has

Rarely discomfort

been isolated in tear fluid.8 All current methods of

disinfection kill the HIV organisms but heat disinfec-
discomfort
Symptoms

discharge

discharge

tion is the most reliable. However, if heat is normally

used, one will have to change the trial lenses very
Static air bubble under lens.

frequently.
ocular susceptibility and

lens edge and abnormal

Multifactorial including
Inflammatory response

exposure to pathogens

surface adjacent to the

Drying of the corneal

Undesirable Effects of Contact Lens Wear

Incomplete blinking
without infecting

metabolic factors
Mechanical and

It is natural that after putting the contact lens in the

eye the patient is conscious of some foreign body
sensation for a variable period of time. If the fitting is
agents
Causes

blink

faultless then the awareness will gradually disappear.

If the awareness persists and on the top of it, burning,
itching and stinging sensation does develop, some-
times with acute pain, then it suggests that there is
anomaly in fitting. Ruben et al after a study of 151
Sterile corneal infiltrate

Microbial keratitis16,17

Inferior corneal stain

3 and 9 o’clock stain

patients wearing soft contact lens for one year revealed

Corneal warpage11

EWCL—extended wear contact lens

PMMA—polymethyl methacrylate

no gross irreversible lesions with loss of vision except

Dimple’s veil10

superficial punctate corneal stains and chronic corneal

(Modified from Dart, 199329)
Disorders

edema which was not statistically significant. 9

HCL—hard contact lens
Dellen

SCL—soft contact lens

Nevertheless, some relative risk of contact lens wear

does exist specially when proper lens care is not taken
by the lens wearer and proper lens fit is not attained.
Classification

Tear Surface

Distortion
Microbial

The causes of such risks include metabolic, abrasive,

Disorder
infection
Keratitis

Corneal
Contd...

Sterile

toxic and hypersensitive response, infections and

sterile corneal infiltrate (Table 156.1). The most serious
1246 Section 9: Miscellaneous Topics
long-term effect of PMMA lens wear is corneal
hypoxia which results in reduction of corneal
sensitivity. Epithelial changes resulting from chronic
hypoxia which may lead to decreased metabolism
include epithelial thinning and epithelial edema with
microcyst formation.10 For similar reasons, stromal
changes may occur. Hypoxia precipitates a shift from
aerobic metabolism to a less efficient anaerobic
metabolism leading to accumulation of lactic acid
thereby causing acidification of the stromal environ-
ment. Some of the changes include stromal edema,
stromal distortion, stromal thinning, vascularization11
and stromal opacity at the pre-Descemet’s level.12
Morphological changes also have been detected in the
endothelium on specular microscopy. These changes
include transient endothelial blebs, increased
polymegathism13,14 and cyan mottled opacification at
the level of the Descemet’s membrane in the peripheral
cornea.15 It is possible that the opacity at the level of
Descemet’s membrane is related to the long-standing
corneal hypoxia induced by contact lens wear.
A major sight threatening complication of contact
lens wear is microbial keratitis, particularly Pseudo-
monas.16,17 Pseudomonas organisms survive well in the
moist environment offered by contact lens and
solutions. The process of insertion and removal of the
contact lens provide ample chance for damage to the
corneal epithelium from trauma and hypoxia. In
extended wear contact lens the incidence of microbial
ulcer is more than in daily wear lens. Long-standing
hypoxia is considered to be the main cause of this high
incidence.18 Using a contact lens or a solution conta-
minated with Pseudomonas provides a potent combi-
nation of source and point of entry into the cornea.
The relative risk of extended wear vs daily wear
contact lenses in respect of corneal infection is
uncertain. Theoretically the less frequent handling
required in extended wear contact lens has a less
chance of surface contamination and hence, fewer
corneal infection than occurs with more frequently
manipulated daily wear lenses. Alternatively, the long
periods of sterilization of extended wear contact lenses
could increase the risk of infectious keratitis should a
lens become contaminated.
Pathogenesis of Ulcer Formation
Abrasion of the corneal epithelial cells is the first stage
of the formation of corneal ulcer in patients wearing
contact lens. The initial stage is loss of corneal
sensitivity and hypoxia. Relative hypoxia is un-
avoidable in any type of contact lens. Gas permeable
materials also are not cent percent gas permeable.
Therefore, corneal epithelial stress due to relative
hypoxia cannot be avoided. Hence, there is loss of
continuity of the epithelial surface clinically detected
by slit lamp biomicroscopy after staining with
fluorescein. Further, during contact lens fitting there
is possibility of epithelial abrasions and micro-
organisms can multiply to cause corneal ulcer.
Pseudomonas is the most common pathogen in contact
lens related corneal ulcers, followed by Staphylococcus.
In addition to bacterial ulcer, acanthameba also have
been isolated in contact lens caused corneal ulcer even
in wearers of disposable lens.19
Acanthameba Keratitis
Acanthameba, a ubiquitous free living, freshwater
parasite, was first recognized in 1973. Acanthamebic
keratitis is a rare complication of contact lens wear
but may occur in patients not wearing contact lens.
Eighty-three percent of acanthameba keratitis occur
in patients of contact lens wear both hard and soft
lenses.20,21 Contact lens wear with use of homemade
saline solution is an important risk factor associated
with acanthameba keratitis. Both hard or rigid gas
permeable contact lens and soft contact lens may
develop acanthameba keratitis. Any type of contact
lens which involves rinsing with tap water or drinking
water may cause acanthameba keratitis. 22,23 But
acanthameba may be a cause of keratitis in patients
who do not wear contact lens indicating that
acanthameba infection may develop from environ-
mental source.24 Acanthameba keratitis does not
develop in disposable contact lens wearer provided
the lens is discarded after being worn continuously
for one week. The main point of disposable character
of the lens is that it should not get any chance of being
contaminated by rinsing or cleaning solution any by
the lens storage box.
Giant Papillary Conjunctivitis
This is a common complication of prolonged use of
soft contact lens. Common symptoms are irritation,
watering and mucoid discharge. Treatment consists
of discontinuation of the lens till the symptoms
disappear.
 Chapter 156: Contact Lenses
Disposable Contact Lens
During the current decade, disposable contact lenses
(DCL) have become available.25 The disposable contact
lens was introduced because it was thought that
frequent replacement would minimize or eliminate
corneal infections and other complications of soft
contact lens wear. Standard disposable contact lenses
are recommended to be used for one or two weeks
only. But considering the annual cost for the lens most
of the wearers prefer to use them for longer periods
and its disposable character is lost. Due to this, chances
of bacterial and acanthamebal keratitis in disposable
contact lens wearers are more than what is expected.
On the other hand the possibility of developing
hypoxic stress to the cornea with disposable contact
lens is the same as with other reusable hydrogel
contact lens of similar composition and water
content.26 Therefore, as regards to corneal stress
secondary to contact lens wear, disposable contact
lenses are not better than conventional lenses of similar
composition and hydration and can lead to compli-
cations secondary to hypoxic stress, similar to those
associated with conventional soft contact lenses.27 Of
course, perhaps due to inexpensive manufacturing
technology, the disposable contact lenses are cheaper
than regular daily wear or extended wear lenses.
However, the concept of disposability may give
patients and practitioners a false sense of safety
regarding extended wear and that the increased cost
of disposable contact lenses may encourage patients
to wear them longer than recommended.28 Disposable
contact lens should be discarded after being worn for
the recommended period.
Advantages of disposable contact lenses are as
follows:
a. No risk of contamination from storage, cleaning
or wetting solutions.
b. Elimination of toxic and allergic reactions to
various preservatives in cleaning and wetting
solutions.
c. Less risk of surface deposits and lens aging.
Extended Wear Lenses
The lenses for extended wear approved by FDA are
hydrocurve II 55 and permalens which have 55 percent
and 70 percent hydration, respectively. The wearing
time is variable from days to months.30,31 In spite of
all the claims, the extended wear lenses do cause
various corneal damages if worn during sleep,
1247
e.g. corneal edema, superficial punctate keratitis
epithelial microcysts, neovascularization, corneal
ulcers and even infection. Moreover, protein, lipid and
calcium deposits over the lenses cause giant papillary
conjunctivitis. Other problems include repeated
breakage, warpage, loss and thus, costly replacement
of the lenses.
REFERENCES
1. Amaya LG, Speedwell L, Taylor D. Contact lens for infant
aphakia. Br J Ophthalmol 1990;74:150.
2. Nelson LB, Cutler SI, Calhoun JH et al. Silsoft extended wear
contact lenses in paediatric aphakia. Ophthalmology
1985;92:1529.
3. Buckley T, Marris F. Contact lens practice. In Davidson SI,
Jay B (Eds): Recent Advances in Ophthalmology. Edinburgh,
New York, London, Melbourne, Tokyo: Churchill Livingstone
1992;19-34.
4. Tolarmo, JH, Larkin DS. Bilateral acanthameba keratitis and
gas permeable contact lens. Am J Ophthalmol 1993;116:651.
5. Aswad MI, Baum J, Auza M. The effect of cleaning and
disinfection of soft contact lens on corneal infectivity in an
animal model. Am J Ophthalmol 1995;119:738.
6. Fowler SA, Allansmith MR. Evolution of soft contact lens
coatings. Arch Ophthalmol 1980;98:95.
7. Devonshire P, Munro FA, Abernitly C et al. Minimal conta-
mination of contact lens cases in West of Scotland. Br J
Ophthalmol 1993;77:41.
8. Fujikawa LS, Salahuddin SZ, Abhasi D. HTLV III in the tears
of AIDS patient. Ophthalmology 1986;93:1479.
9. Ruben N, Brown D, Lobasker J et al. Clinical manifestations
secondary to soft contact lens wear. Br J Ophthalmol 1976;
60:520.
10. Humphrey JA, Larke JR, parrish ST. Microepithelial cysts
observed in extended wear contact lens wearing subjects. Br
J Ophthalmol 1980;64:88.
11. Remeiju L, van Rij G, Beckhuis WH et al. Deep corneal stromal
opacity in long-term contact lens wear. Ophthalmology
1990;97:281.
12. Hirst LW, Aua C, Cohn J et al. Specular microscopy of hard
contact lens wearer. Ophthalmology 1984;91:1147.
13. Matsuda M, Masamara I, Suda T et al. Corneal endothelial
changes associated with aphakic extended wear contact lens.
Arch Ophthalmol 1988;106:70.
14. Holland EJ, Lee RM, Bucci FA et al. Mottled cyan opacification
of the posterior cornea in contact lens wearer. Am J
Ophthalmol 1995;119:620.
15. MacRay SM, Matsuda M, Shetlans S et al. The effect of long-
term hard and soft contact lens wear on the corneal endo-
thelium. Am J Ophthalmol 1985;102:50.
16. Dart JKG. Predisposing factors in microbial keratitis: The
significance of contact lens wear. Br J Ophthalmol 1988;72:926.
17. Alfonso E, Mandelbaum S, Fox MJ et al. Ulcerative keratitis
associated with contact lens wear. Am J Ophthalmol
1986;101:429.
18. Mandino BJ, Weissman BA, Farb M. Corneal ulcers associated
with daily wear and extended wear contact lenses. Am J
Ophthalmol 1986;102:58.
1248 Section 9: Miscellaneous Topics
19. Ormeroa LD, Smith RE. Contact lens associated microbial
keratitis. Arch Ophthalmol 1986;104:79.
20. Jones BD. Acanthameba—the ultimate opportunist. Am J
Ophthalmol 1986;102:527.
21. Stethr-Green JK, Bailey TM, Visvesvara GS. Epidemiology of
acanthameba keratitis in the United States. Am J Ophthalmol
1989;107:331.
22. Larkin DPF, Kilvinton S, Easty DL. Contamination of contact
lens storage cases by Acanthameba and bacteria. Br J
Ophthalmol 1990;74:133.
23. Chyne EW, Lopas MA, Pavan-Langston D. Acanthemeba
keratitis, contact lens and non-contact lens characteristics.
Ophthalmology 1995;102:1369.
24. Seal D, Stapleton F, Dart J. Possible environmental sources
of Acanthameba Spp in contact lens wear. Br J Ophthalmol
1992;76:422.
25. Driebe WT. Disposable soft contact lenses. Sur Ophthalmol
1989;34:44.
26. Weissman BA, Schwartz SD, Gottschalk-Katsev N. Oxygen
permeability of disposable soft contact lenses. Am J
Ophthalmol 1990;110:269.
27. John T. How safe are disposable contact lenses. Am J
Ophthalmol 1991;111:766.
28. Dunn JP, Mondino BJ, Weissman BA et al. Corneal ulcers
associated with disposable contact lenses. Am J Ophthalmol
1989;108:113.
29. Dart CKG. Disease and risks associated with contact lenses.
Br J Ophthalmol 1993;77:49.
30. Yamamoto K, Ladage PM. Affective effects of 30 –night wear
Hpper-O2 transmissible contact lens on bacterial binding and
corneal epithelium. A I year clinical trial. Ophthalmology
2002;109,27.
31. Schein OD, Rosenthal P, Ducharme C. A gas-permeable
scleral contact lens for visual rehabilition. Am J Ophthalmol
1990;108,318.
 Index
A laboratory tests 1328 treatment of dry AMD 1525
systemic findings 1326 AREDS findings 1526
A and V syndrome 901
treatment 1328 laser photocoagulation 1526
clinical features and diagnosis 903
medical therapy 1328 nutritional supplements 1525
etiology 902
Acute zonal occult outer retinopathy 1300 treatment of exudative AMD 1528
anomalies of muscle insertion 903
Adamantiades-Behcet’s disease 1320 alternative treatments 1529
combined patterns 903
Adenocarcinoma of lacrimal gland 656 feeder vessel photocoagulation 1530
horizontal school of urist 902
Adenoma 963 low vision aids 1531
vertical school 902
Adenoma sebaceum 661 pharmacologic intervention 1530
treatment 903
Adie’s syndrome 954 photodynamic therapy 1528
A mass in the orbit 675
Adnexal and anterior segment lesions in radiation therapy 1529
Abducens palsy of childhood 984
AIDS 1136 retinal translocation 1530
Aberrant regeneration 981
Adrenergic agonists 569 surgical removal of CNV 1530
Abnormal/anomalous retinal
nonselective alpha-adrenergic thermal laser treatment 1528
correspondence 880
agonists 569 transpupillary thermotherapy 1529
detection 881
dipivefrin hydrochloride 570 Albinism 819
harmonious 880
epinephrine 569 causes 819
treatment 882
selective alpha-adrenergic agonists 570 clinical classification 819
unharmonious 881
apraclonidine 571 heredity 820
AC/A ratio 876, 886
brimoniline 571 management 820
Acanthameba keratitis 165, 168, 169, 176,
clonidine 570 Alkaptonuria 821
1246
Adrenergic blocking agents 571 Allergic conjunctivitis 90
Accessioning system 181
beta-blockers 572 seasonal allergic 91
Accessory lacrimal glands 62
intrinsic sympathomimetic activity 572 clinical features 91
Accommodation 959
betaxolol 573 management 91
Accommodative esotropia 889
carteolol 573 Allergic granulomatous angitis 1224
acquired nonaccommodative 895
levobunolol 573 Alloplastic refractive keratoplasty 277
essential infantile 893
timolol 572 Alport’s syndrome 778
hypoaccommodative 891
Affinity membrane test 86 Alzheimer’s syndrome 978
nonrefractive accommodative 890
After image test 876 Amacrine cells 1439
partial accommodative 892
Age-related macular degeneration 1151, Amblyopia 744
refractive accommodative 889
1477, 1491, 1517, 1521, 1761 fixation pattern 745
Accommodative intraocular lenses 342
aging changes in RPE and Bruch’s pathogenesis 746
Acidophil adenoma 963
membrane 1522 straight eye 744
Acquired immunodeficiency syndrome
(ICG) and (FFA) 1524 treatment 747
1127, 1337
classic CNV 1524 CAM 749
Acquired retinoschisis 1562
classification 1523 occlusion 747
Acral lentigo maligna 53
clinical features 1523 visual acuity 746
Actinic keratosis 49
occult CNV 1524 with squint 745
Acute chemical burns 1175
animal models 1534 Amblyopia 803, 882
Acute disseminated encephalomyelitis
future directions 1532 CAM treatment 885
977
gene therapy 1532 fixation pattern 884
Acute epidemic hemorrhagic
photoreceptor cell transplantation squint 883
conjunctivitis 74
1532 straight-eye amblyopia 883
Acute posterior multifocal placoid
RPE transplantation 1532 Amblyoscope 875
pigment epitheliopathy 1298
genetic basis 1534 Amebiasis 1216
Acute retinal necrosis syndrome
microelectronic visual implants 1533 Amniotic membrane 1169
1130, 1292, 1325
cortical implants 1533 embryology, anatomy, physiology
clinical features 1325
epiretinal implants 1533 and histopathology 1169
complication 1326
subretinal implants 1522 functions 1170
differential diagnosis 1327
molecular basis 1534 tissue harvesting and use 1170
etiology 1327
prevalence 1521 transplantation 1171
histopathology 1328
risk factors 1522 clinical uses 1171
investigations for diagnosis 1327
1806 Modern Ophthalmology
glue application 1173 Argyll robertson pupil 955, 960 Benign 730
identification of epithelial surface Arteriosclerosis 1599 Benign mixed tumor 730
1172 Artificial drainage devices 618 Berger’s space 316
indications and surgical procedures classification 618 Bezold-Burcke effect 1144
1172 Ahmed glaucoma valve 621 Bifocals 920
limbal autograft transplantation Baerveldt implant 621 Bimatoprost 584
1173 Joseph-Hitchings valve implant 621 Biometry 522
persistent epithelial defect 1173, Krupin-Denver valve implant 621 Biostatistics 1092
1175 Molteno implant 619 analysis of variance 1099
preparation and preservation 1171 posterior tube shunt implants 618 arithmetic mean or average 1093
repair of leaking filtering bleb 1174 Schocket procedure 621 central tendency 1093
surgical technique 1172 complications 622 clinical significance 1097
Amniotic membrane transplantation indications for use 622 coefficient of variation 1094
1213, 1182 Ascorbic acid 1230 computer programs 1099
surgical procedure 1183 Asepsis or antisepsis 1121 correlation 1094
Amyloidosis 1225 Ash leaf spots 661 correlation coefficient 1095
Anesthesia for cataract surgery 361 Associated with ocular anomalies 761 dispersion 1094
regional 361 Associated with systemic anomalies 761 estimation 1096
Aneurysms 697, 698, 1004 differential diagnosis 761 hypothesis 1096
circle of willis 1005 treatment 762 inferential statistics 1096
internal carotid artery 1005 Astigmatic keratotomy 159 large sample tests 1098
ophthalmic artery 1005 clinical features 166 median 1093
Angiomatosis retinae 664 Astrocytes 1440 mode 1094
clinical picture 664 Astrocytic hamartomas 662 multiple regression analysis 1096
pathology 665 Asymptomatic narrow angles 534 non-parametric tests 1099
systemic features 665 Ataxia-telangiectasia 670 null hypothesis 1097
treatment 666 Atypical dry eye syndromes 106 paired ‘t’ test 1098
Angiosarcoma 55 Augmented surgical formula 892 regression analysis 1095
Angle of deviation and face turn 869 Automated perimetry 515 sampling distribution 1096
Angle of the anterior chamber 468 instrumentation 515 scale of measurement 1093
Aniridia 325, 477, 537, 765, 811 interpretation of results 516 scatter diagram 1095
clinical findings 766 recent advances 519 small sample tests 1098
management 766 testing strategies 515 standard deviation 1094
Anisocoria 961 Axenfeld syndrome 478 statistical methods 1099
Ankyloblepharon 6 Axenfeld-Rieger syndrome 766 statistical significance 1097
Ankylosing spondylitis 1223, 1269, 1372 extraocular features 767 student’s ‘t’-test 1098
Anomaloscope 1147 histopathological features 767 tests of significance 1097
Anophthalmos/microphthalmos 1033 management 768 variables 1092
Anterior chamber 333 ocular features 767 X2-test 1098
Anterior chamber paracentesis 1386 Birdshot retinochoroidopathy 1296
Anterior optic neuritis 973 B Bitot’s spot 753
Anterior segment ischemia 1735 Bacillary dysentery 1215 Bleb failure 599
Anterior staphyloma 134 Bacterial keratitis 165 Bleb-related problems 608
Anterior stromal infiltrates 209 Bacterial keratitis 166 encapsulated 613
Anterior uveitis 543, 584, 1138, 1222, 1268, Bacterial keratitis 173 management 614
1313, 1321, 1372 Bag sulcus fixation 358 failing bleb 611
management 1374 Bagolini lens 873 early 612
Antiglaucoma drugs 566 Balanced salt solution/saline 1756 late 613
Antimetabolites 597 Balloon catheter dilatation 714 prevention and management 612
Antimicrobial susceptibility testing 188 Balloon catheter dilatation 723 infection 615
Antiretroviral therapy 1140 Band shaped keratopathy 1175 clinical features 615
Antithyroid antibodies 703 Bandage contact lens 1211 management 615
Aqueous TAP 1422 Bangerter pleoptophore 746 prevention 616
Arcuate scotoma 969 Barraquer tonometer 296 leakage 610
Arcus senills 220 Basal cell clinical findings 610
Argemon mexicana 536 carcinoma 49 management 610
Argon laser closure of cyclodialysis cleft nevus syndrome 669 overfiltration 609
594 Basophil adenoma 963 clinical features 609
Argon laser trabeculoplasty 565, 588 Behcet’s disease 1377 management 609
Argon-laser suturelysis 593 Behcet’s syndrome 1223 symptomatic 614
 Index 1807
management 614 Burkitt’s lymphoma 648 small incision 336
Blepharitis 17 ultra-small incision 338
classification 17 C Cavernous hemangiomas 55
anterior 18 Calcification in a phthisical eye 638 Cavernous sinus 985
clinical features 19 CAM visual stimultor 923 Cavernous sinus syndrome 967
differential diagnosis 20 Canalicular laceration 715, 716, 718 Cecocentral scotoma 969
management 20 Canalicular obstruction 718 Central corneal thickness 481
pathogenesis 18 Canaliculitis 184 Central retinal artery occlusion 1579
Blepharitis 32, 183 Canaliculodacryocystorhinostomy associated diseases 1581
Blepharochalasis 57 717, 722 management 1581
Blepharoconjunctivitis 106 Candidriasis 1296 ocular investigations 1580
Blepharophimosis 5 Capillary hemangioma 54 pathophysiologic mechanisms 1581
Blood supply of the visual pathways 946 Capillary hemangioma 830 signs 1579
Blood-retinal barrier 1440 Capsid 1324 Central retinal vein occlusion 1584
Blue cone monochromatism 1115 Capsular bag distension syndrome clinical characteristics 1585
Bony orbit 625 359, 460 electroretinography (ERG) 1586
apex 627 Capsular bag opacification 799 fundus fluorescein angiography
base 627 Capsular bag syndrome 410 (FFA) 1586
size, shape, and relations 625 Capsular block syndrome 460 newer techniques 1587
walls 626 Capsular contracture syndrome 359 ocular neovascularization 1587
inferior orbital 626 Capsular tension ring 398, 814 ophthalmoscopy 1586
lateral wall 626 Capsulopalpebral fascia 928 perimetry 1586
medial 626 Capsulorhexis 599 relative afferent pupillary defect
roof 627 Capsulotomy 380 1586
Bony orbits 629, 1024 Carbonic anhydrase inhibitor 574 visual acuity 1585
apertures at the base 630 oral 574 demographic characteristics 1584
fat and reticular tissue 630 topical 575 management 1589
globe 1025 Carotenoids and tocopherol 1229 laser photocoagulation 1590
retrobulbar space 1025 Caroticocavernous fistula 1007 medical therapies 1589
surgical spaces 629 Carotid artery imaging 1785 natural course and complications 1588
central 629 Carotid artery insufficiency 543 pathogenesis 1584
peripheral orbital 629 Carotid cavernous fistula 1050 systemic diseases 1589
sub tenon’s 629 Caruncle 64 Central retinal vein occlusion 1760
subperiosteal 629 Catalytic RNA 1106 Central scotoma 969
Botulinum toxin 922 Cataract 327 Central serous chorioretinitis 1358
Bourneville disease 660 biochemical changes 330 Central serous chorioretinopathy 1493
Boutonneuse (marseilles) fever 1341 classification 327 Central serous chorioretinopathy 1772
Bowen’s disease 111 cuneiform opacities 327 associated fundus finding 1775
Bowen’s disease 124 cupuliform 328 differential diagnosis 1776
Bowen’s disease perinuclear variety 328 general types 1772
(intraepithelial epithelioma) 49 definition 327 pathogenesis 1776
Bowman’s membrane 132 etiopathogenesis 329 treatment 1777
Brain stem 985 environmental factors 329 Central serous retinopathy 1761
Branch retinal artery occlusion 1582 other factors 330 Cephaloceles 825, 1036
Branch retinal vein occlusion 1591, 1761 personal factors 329 Chalazion (meibomian cyst) 30
associations 1594 formation 327 Chediak Higashi syndrome 820
clinical features 1591 medical therapy 330 Chemical trauma 231
complications 1593 aldose reductase inhibitors 331 evolution of tissue injury 234
management 1595 antioxidants 330 pathomechanism 233
laser photocoagulation 1595 Cataract 776, 861 treatment 236
medical 1595 anterior polar 77 surgical 238
ophthalmoscopic features and blue dot 776 Chemosis 68
fluoriscein angiography 1592 congenital 776 Chicken eyes 752
Brown syndrome 914 coronary 777 Chickenpox 1333
clinical features posterior polar 777 Chlamydia trachomatis 76
differential diagnosis 915 virus induced 778 Cholera 1216
management 915 zonular 777 Cholinergic drugs 567
Bruch’s membrane 1251 Cataract in post-trabeculectomy eyes 399 anticholinesterases 568
Bullous central serous chorioretinopathy Cataract surgery 336 demecarium bromide 569
1773 large incision 336
1808 Modern Ophthalmology
echothiophate effect of scarring 78 Collagen 1220
(phospholine iodide) 568 McCallans 77 Collagen shield 1211
isoflurophate 569 treatment 79 Collection of samples 182
physostigmine (eserine) 569 Clinical features 24 Collector channels 471
parasympathomimetics 567 Clinical pathology 525 Coloboma 1032, 775
carbachol 568 clinical types and features 529 Coloboma of lid 5
pilocarpine 567 acute 530 Color vision 1144
Chorioretinal biopsy 1427 chronic 530 anatomy 1146
external approach 1427 creeping 530 factors affecting 1144
internal/endoretinal approach 1428 intermittent 529 retinal distribution 1144
Chorioretinal inflammation 1559 subacute 530 testing 1146
Choroid 1251 epidemiology 526 theories 1145
Choroidal coloboma 1564 management 531 Communications with the orbit 1011
Choroidal detachment 1352, 1735 long-term 533 Compensatory head posture 864
anatomy 1352 medical 531 Compressive optic neuropathy 1003
clinical features 1353 physical 532 Computerized tomography 1020, 1028
etiology 1353 supportive 532 Computerized tomography scanning 639
investigations 1354 special methods of examination 527 Concussion injury 548
treatment 1355 gonioscopy 528 Condensing lenses 1445, 1554
Choroidal effusion 552 peripheral ac depth 527 Confocal laser scanning 510
Choroidal hemangioma 667, 1034, 1414, primary angle closure laser ophthalmoscopy 487
1763 (glaucoma) suspect 527 Congenital aphakia 775
circumscribed 1414 provocative tests 528 Congenital stationary 1113
clinical features 1414 clinical use of 1089 Conjugation 203
diagnosis 1415 cataract surgery 1089 Conjunctiva 61, 1013
differential diagnosis 1416 ECCE 1089 anatomy 61
management 1416 extraocular surgery 1090 arteries 63
photocoagulation 1416 glaucoma 1089 epithelium 63
diffuse 1416 ICCE 1089 lymphatics 64
clinical features 1417 keratoplasty nerve supply 64
diagnosis 1417 membrane surgery 1090 veins 64
management 1417 postoperative period 1090 wound healing and inflammation 63
pathology 1417 retinal surgery 1090 Conjunctiva-tenonplasty 239
Choroidal hemorrhage 1410, 1751 trauma 1090 Conjunctival diseases 66
Choroidal melanoma 1764 vitreous loss 1090 acquired pigmentation 70
Choroidal neovascular membrane 1777 Clivus ridge syndrome 1007 angular conjunctivitis 68
Choroidal neovascularization 1153 CMV retinitis 1294, 1668 chronic 75
classic 1153 clinical features 1668 concretions 68
combined 1154 management 1669 discharge 66
occult 1153 treatment 1669 edema 68
polypoidal 1154 anti CMV therapy 1671 follicles 67
recurrent 1156 immune reconstitution therapy follicular 71
classic 1157 1672 acute 71
occult 1157 prophylaxis 1672 chronic 74
Choroidal nevi 1410 toxic effects of anti CMV therapy hyperemia 67
Choroideremia 1114 1672 lymphadenopathy 69
Chromophobe adenoma 963 Coats’ disease 835, 853, 1031, 1653, 1763, membrane formations 67
Chronic chiasmal arachnoiditis 962 1681 nodule at limbus 68
Cicatrization 842 clinical presentation 1682 papilla 67
Cilia 2 demographics 1681 phlyctenular keratoconjunctitivis 68
Ciliary body 1250 diagnosis and ancillary testing 1684 pigmentations 69
Ciliary body band 475, 478 differential diagnosis 1684 subconjunctival hemorrhage 69
Ciliary muscles 1251 etiology 1681 ulcers 68
Cilioretinal artery occlusion 1582, 1588 histopathology 1683 Conjunctival flap 1212
Cinematography 728 management 1684 Conjunctival flap 597
City university color vision test 1147 pathophysiology 1681 Conjunctival glands 62
Classification 76 prognosis 1686 Conjunctival graft 1212
clinical picture 77 systemic association 1684 Conjunctival hyperemia 584
diagnosis 78 Cogan’s syndrome 1224, 987 Conjunctival impression cytology 103

Conjunctival impression cytology 1083
Conjunctival limbal autograft 1183
Conjunctival scraping 103
Conjunctival squamous cell carcinoma
1137
Conjunctivitis 71, 80, 183
acute catarrhal 80
acute purulent 80
chronic catarrhal 80
membranous and pseudomembranous
81
phlyctenular kerato 81
clinical manifestations 81
differential diagnosis 82
signs 81
symptoms 81
Conjunctivodacryocystorhinostomy 722
Connective tissue 1220
Connective tissue disorders 1221
acquired generalized disorders 1225
acquired systemic metabolic disorder
1225
hereditary generalized disorder 1226
ocular manifestations 1222
Conradi syndrome 811
Constriction of pupil 406
Contact hypersensitivity 97
Contact lens 287
Contact lens fitting 156, 157
Contact lenses 1234
contraindications 1238
fitting of lens 1239
evaluation of fit 1243
external examination 1239
fitting procedures 1240
insertion and removal of lens 1242
wearing schedule 1242
indications 1236
cosmetic 1238
diagnostic 1238
occupational 1238
optical 1236
therapeutic 1237
materials used 1235
glyceryl methacrylate
(GMA) polymers 1235
HEMA cross-linked with EGDMA
1235
HEMA-PGMA copolymers 1236
polyelectrolyte complexes 1236
polymethyl methacrylate 1235
soft hydrophilic materials 1235
optical principles 1234
types 1242
bifocal 1242
disposible 1247
extended wear 1247
oxygen permeability 1243
rigid gas permeable scleral 1243
soft 1242
Index
undesirable effects 1245
Contents of orbit 1011
Continuous curvilinear capsulorhexis 370
Contrast orbitography 643
Contrast sensitivity 426
Contrast sensitivity and glare 333
Conventional extracapsular
cataract surgery 407
Core biposy 644
Cornea 1222, 333
Cornea and ocular surface disorders 1063
Cornea farinata 219
Cornea plana 134
Corneal clouding 1735
Corneal degenerations
endothelial dystrophies 217
corneal guttata 217
Fuchs’ dystrophy 217
keratoglobus 218
posterior polymorphous dystrophy
218
epithelial and Bowman’s 213
locational 219
central 219
peripheral 220
membrane dystrophies 213
anterior crocodile shagreen or
anterior mosaic dystrophy of vogt 215
band-shaped corneal opacity 214
dystrophic recurrent erosion 215
epithelial and Bowman’s 213
membrane dystrophies 213
reis-buckler’s dystrophy 215
stromal dystrophies 215
central crystalline dystrophy
(schnelder’s crystalline
dystrophy) 216
fleck dystrophy speckeled
dystrophy of francois
and neetens) 217
gelatinous drop like dystrophy 216
granular dystrophy-groenouw’s
type I: (Bread-crumb dystrophy)
215
lattice dystrophy
(biber-haab-dimmer) 216
macular dystrophy (groenouw II)
216
Corneal diseases 156
Corneal dystrophies 254
Corneal edema 798, 1751, 1789
Corneal endothelium 150
Corneal epithelial dysplasia 1203
Corneal epithelial stem cells 1180
Corneal epithelium 1179, 1208
examination 1208
planimetry 1209
slit lamp examination 1209
functions 1208
healing 1209
1809
clinical patterns 1210
management of acute epithelial defect
1210
contact lens/capping 1211
medical 1210
surgical 1211
microanatomy 1208
Corneal esthesiometry 144
Corneal grafting 128
congenital abnormalities 133
cornea 131
development 132
methods of examination 137
role of vital dyes 141
microanatomy 132
Bowman’s membrane 132
endothelium 132, 133
posterior elastic membrane 132
substantia propria 132
pigmentation 134
copper 135
gold 135
iron 134
melanin 135
silver 135
Corneal mucous plaques 209
Corneal opacity 861
Corneal opacity leucoma 134
Corneal scrapings 169
Corneal sensitivity 144, 956
Corneal stem cell diseases 299
possible stem cells diseases 300
probable stem cell diseases 300
treatment 301
autogenous stem cell
transplantation 301
bulbar conjunctival transplantation
301
corneal stem cell
autotransplantation 301
corneal stem cell
homotransplantation 301
transplantation of cultured corneal
Limbal stem cells 302
unequivocal corneal stem cell loss 299
Corneal suction ring 296
Corneal topography 154, 288
Corneal transplantation 1188
complications 1189
immunosuppression 1188
Corneal ulcer 161
diagnosis 169
interpretation of cultures 171
interpretation of smears 170
techniques 172
etiologic factors 163
fungi 164
infective 163
protozoa 164
viruses 164
1810 Modern Ophthalmology
pathogenesis 161 Cytomegalovirus (CMV) retinitis 1129 nephropathy 1606
histopathology and stages 161 retinal detachment 1130 pregnancy 1606
mechanisms 162 systemic hypertension 1606
risk factors 165 D Diabetic retinopathy 1759
treatment 173 Dacryoadenitis 105 Diagnostic vitrectomy 1424
medical 173 Dacryoadenitis 731 Diffractive multifocal lenses 424
surgical 178 Dacryocystectomy 724 Diffuse congenital hemangiomatosis 669
types 162 Dacryocystitis 184, 718 Diffuse large B cell lymphomas 648
acanthameba 163 Dacryocystography 712, 726 Diffuse subretinal fibrosis 1297
bacterial 162 radiography in operated cases of Diplopia 633, 684, 685, 879, 940, 949, 1736
fungal 163 sac 728 Direct goniotomy 763
herpes simplex ocular 162 techniques 727 Disciform keratitis 209
Corneal ulceration/keratomalacia 753 types 726 Dislocated nucleus 1788
Corneal xerosis 753, 754 Dacryocystorhinostomy 719 incidence 1788
Cortical cleaving 371 Dacryops or ductal cyst 730 laser tissue interactions 1793
Corticosteroids 94, 282 Dacryoscintigraphy 728 light absorption 1794
Cotton-wool spots 1583 Dalen-Fuchs nodules 1316, 1380 problems of retained lens matter 1788
Cover test 952 Decentration of an iol 801 risk factors 1788
Craniopharyngioma 964 Decompensation 466 role of the primary surgeon 1789
criteria for selection of material 1086 Degenerative myopia 1656 thermal effects 1794
Crouzon’s syndrome 811 histopathology 1656 chorioretinal photocoagulation
Cryotherapy 7 ocular manifestations 1656 1795
Cryptococcosis 657 pathogenesis 1656 grading of photocoagulation burns
Cryptophthalmos 6 treatment 1662 1795
Crystalline lens 1703 Dehiscence of orbital bones 638 photodynamic therapy (PDT) 1796
Crystalline lens 774 Demyelinating diseases 974 vascular photocoagulation 1796
congenital abnormalities 775 Depth of focus 426 timing of pars plana vitrectomy 1790
structure 774 Dermal eruption 211 complications of pars 1791
Cultivated limbal 1187 Dermatitis 33 Dislocations 465
Cultivated limbal transplant rejection Dermatome 1334 Disorders of visual integration 991
1190 Dermatomyositis 1224 Displacement of lens 324
Culture methods 186 Dermoid cyst 731 Displacement of lens 539, 949
anaerobic 187 Dermoid/epidermoid 1035 Distichiasis 7
bacterial 186 Dermoid/epidermoid cyst 824 Diurnal variation of IOP 483
fungal 186 Dermoids 123 DNA testing 1101
mycobacterial 187 Descemet’s membrane 132 Dominant behr optic neuropathy 1002
viral 187 Descemet’s membrane detachment 357 Donor cornea 255
Cutaneous horn 49 Diabetes mellitus 481 Donor corneal rims 184
Cyclic oculomotor palsy 982 Diabetic retinopathy 1605 Double elevator palsy 906
Cyclocryotherapy 301 clinical features 1607 classification 906
Cyclophotocoagulation 590 nonproliferative 1607 clinical characteristics 906
Cycloplegic refraction 877 proliferative 1609 differential diagnosis 907
Cyclosporine 94 genetic factors 1607 Double eye pads and bandage 1211
Cystic swellings 640 management 1612 Driving ability 428
Cystic tumors 824 antiplatelet therapy 1613 Dry eye 102, 299
differential diagnosis 825 focal photocoagulation 1616 Dry eye syndromes 105
Cysticercosis 1218 laser photocoagulation 1613 Duane’s retraction syndrome 984
Cystinosis 820 laser treatment 1617 Duane’s retraction syndrome (Stilling-
Cystoid macular edema 467, 584, 803, lipid reduction 1613 Turk-Duane’s syndrome) 912
1735, 1789 medical treatment 1612 treatment 914
Cytology 113 panretinal photocoagulation 1614 Ductions and versions 867
Cytomegalovirus 1329 peripheral retinal cryoablation 1617 Dysplastic nevus syndrome 53
clinical features 1330 vitrectomy 1618 Dystrophies 265
differential diagnosis 1330 risk factors 1605
histopathology 1331 age 1605 E
laboratory investigations 1331 control of blood glucose levels 1605 Eales’ disease 1653, 1675, 1761
route of transmission 1329 duration of diabetes 1605 clinical features 1675
treatment 1331 promptness of referral 1606 etiopathogenesis 1677
ganciclovir 1332 systemic factors 1606 immunological studies 1677
 Index 1811
pathology 1678 bleb-associated 1539 clinical features 1689
management 1678 chronic 1539 complications 1691
anterior retinal cryotherapy 1678 traumatic 1540 etiology 1689
corticosteroids 1678 clinical diagnosis 1540 management 1690
photocoagulation 1678 complications 446 pathology 1690
vitrectomy 1679 endogenous 1306 surgical technique 1690
signs 1675 fungal 1306 Epiretinal membrane 1476, 1559, 1594,
inflammation 1675 fungal 1309 1779
macular changes 1676 late 464 treatment 1780
neovascularization 1676 management 1543 types and causes 1779
nonperfusion 1675 antibiotics 1544 Episcleral osseous choristoma 123
Ectopia lentis 1226 corticosteroids 1545 Episcleritis 307, 1222
Ectopia lentis 808 intravitreal drug injection 1545 Epitarsus 65
Ectopia lentis et pupillae 775 vitrectomy 1546 Epithelial cysts 63
Ectopia lenus et pupillae 323 medical treatment 443 Epithelial tumors 123
Ectropion 12 antibiotics 445 Epitheliopathy 102
Ehler-Danlos syndrome 136, 324, 811, 823, corticosteroids 445 Epithelium transplantation 1187
1226 microbiological diagnosis 1540 cultivation of epithelia 1188
Elastin 1220 antimicrobial susceptibility testing current status 1188
Electro-nystagmography (ENG) 861 1543 immunosuppression 1188
Electrolysis 7 culture 1542 transplantation 1188
Electron microscopy 88, 186, 1199, 1206 microscopy 1540 Epstein-Barr virus 1336
Electrooculogram 1455 molecular diagnosis 1543 Erythema multiforme 300
clinical measurement 1456 vitreous biopsy 1542 Erythema multiforme major (Stevens-
clinical uses 1456 postoperative management 445 Johnson syndrome) 83
fast oscillations of EOG 1457 surgical treatment 444 Erythema nodosum 1225
limitations of EOG recording 1457 treatment 1549 Esodeviations 889
Electroretinogram 1457 vitrectomy study 446, 1548 Esophoria 887
clinical protocol 1459 Endoscopic biopsy 644 Esotropia 984
clinical uses 1461 Endoscopic nasal lacrimal surgery 723 Essential blepharospasm 57
ERG measurements and recording Endothelial cell density 151 Euryblepharon 5
1460 Endothelitis 202 Ewing’s tumor 829
flash stimulus characteristics 1458 Enophthalmos 674, 684, 685 Excision biopsy 1428
ground electrodes 1458 Entropion 8 anterior segment tumors 1428
origin of 5 basic ERG waveforms 1460 cicatricial 10 external approach 1428
pediatric ERG recording 1460 cicatricial 14 internal approach 1429
recording electrodes 1457 congenital 8, 12 posterior segment tumors 1429
reference electrodes 1458 mechanical 16 external approach 1429
Electroretinography 1147, 1785 paralytic 14 internal approach 1429
Embryology of eyeball 1019 senile (involutional/atonic) 8 Excisional biopsy 644
Embryotoxon 134 senile or involutional 12 Exfoliative cytology 1205
Emphysema 684 spastic 8 Exodeviation 898
Empty Sella syndrome 964 Entropion surgery 1174 classification 898
Encephalitis periaxialis diffusa 977 Enucleation 1432 definition 898
Encephalofacial angiomatosis 667 Enzymatic vitrectomy 1630 etiology 898
clinical features 667 Enzyme-linked immunoabsorbent assay Exophoria 887
cutaneous involvement 668 203, 1385 Exophthalmometers 636
ocular involvement 667 Eosinophilic granuloma 651 Exophthalmometry (proptometry) 635
visceral involvement 668 Epiblepharon 4 Exophthalmos 702
treatment 668 Epicanthal folds 4 Exposure keratitis 58
Endocapsular ring 398 Epicapsular star 775 Exposure keratopathy 209
Endogenous fungal endophthalmitis 1296 Epidemic dropsy 1219 External examination of the eye 950
Endolaser 1710 Epidemic dropsy glaucoma 536 Extracapsular cataract extraction 367
Endophthalmitis 183, 359, 412, 442, 464, Epidemic keratoconjunctivitis 72 cortex removal 372
600, 799, 833, 1291, 1305, 1539, 1703, Epidemic typhus 1341 nucleus removal 372
1751 Epikeratophakia 276 preoperative evaluation 367
acute bacterial 1308 Epikeratophakia 784 fundus evaluation 368
chronic bacterial 1309 Epikeratoplasty 272 IOL power calculation 368
classification 1539 Epilation 7 refraction and visual acuity 368
acute postoperative 1539 Epimacular proliferation 1689
1812 Modern Ophthalmology
slit-lamp biomicroscope clinical features 1651 Fluorescence microscopy 185
examination 368 stage 1 1651 Fluorescent treponemal antibody-
special tests 368 stage 2 1651 absorption 1386
tonometry 368 stage 3 1653 Fluorophotometry 143
surgical techniques 369 diagnosis 1653 Flying spot 291
anesthesia 369 etiology 1650 Focal macular ERG 1471
anterior capsulotomy 369 histopathology 1650 Foldable IOLs 352
corneoscleral incision 369 inheritance 1651 accommodating intraocular 355
hydroprocedure 371 management 1654 aniridia 356
incision 369 platelet abnormalities 1651 blue light-filtering 357
Extraocular lesions 1035 Familial exudative vitreoretinopathy 835 collamer 353
congenital and developmental Familial exudative vitreoretinopathy 852 laser adjustable 355
conditions 1035 Familial exudative vitreoretinopathy multifocal intraocular 354
inflammatory conditions 1037 (FEVR) 1565 diffractive 354
neoplasms 1041 Farnsworth 100-hue test 1147 refractive 354
Exudative retinal detachment 1564 Farnsworth D-15 1147 negative spherical 357
Eye and adnexa 332 Fascia lata 1730 phakic 352
Eye bank 242 Fassanella servat operation 40 piggyback intraocular 355
cornea preservation 248 Fassanella servat surgery 41 smart lens 352
tissue media preservation 249 Fellucid marginal degeneration 220 suture-free 353
equipment 243 Ferry’s line 135 thinoptx rollable 356
organization 242 Fibrinoid necrosis 1220 toric intraocular 355
regulatory laws 243 Fibrous histiocytom 1202 with endocapsular ring design 353
strategies to enhance eye collection 243 Field changes 963 Foldable lenses 336
grief counseling 243 Field utilization device 1167 Follicles 67
legal improvement 243 Filtering bleb 465 Folliculosis 71
operational efficiency 243 Filtering blebs 608 Forced duction test 877, 926
publicity 243 Fine needle aspiration biopsy 1424 Foreign bodies 1053
structure and function 242 clear corneal approach 1426 Formation of retinal breaks 1558
tissue retrieval 244 limbal approach 1426 Foster kennedy syndrome 967
collection of blood 245 pars plana approach 1425 Freckle (ephelis) 52
donor cornea viability 246 transscleral approach 1426 Free radicals 1227
enucleation 245 Fine needle aspiration biopsy 643 defence against 1228
evaluation methods 246 Fine needle aspiration biopsy 653 pathophysiology 1228
in situ corneoscleral excision 246 complications 657 Friend test 950
preliminary procedures 244 cytological interpretation 655 Frontal gaze palsy 987
Eye bank specular microscopy 150 indications 655 Frontalis sling surgery 44
Eye tracking 290 limitations 658 Frosted branch angiitis 1132
Eyelid tumor 48 technique 653 Fuch’s heterochromic iridocyclitis 1272
epithelial 48 guidelines 654 Fuchs’ heterochromic uveitis 1362
benign 48 Fine-needle aspiration 1080 clinical features 1362
malignant 49 Flap closure 599 differential diagnosis 1363
melanocytic 52 Fleischer ring 135 etiology 1362
benign 52 Floppy eyelid syndrome 1192 HLA association 1363
glandular 53 management 1193 immunopathology 1364
malignant 53 pathology 1192 investigative procedures 1363
neurogenic 55 Floppy eyelid syndrome 58 electron microscopy 1364
vascular 54 management 59 light microscopy 1363
Eyelids 1 pathology 59 management 1364
blood supply 3 Flow cytometry 1079 ocular features 1363
development 1 Fluence test 289 pathology 1362
lymphatics 3 Fluid (vitreous, aqueous or other fluids) role of genetics 1362
nerve supply 3 cytology 1082 Functional vision 1160
structure 1 Fluid-gas exchange 1710 Functional visual loss 950
Fluorescein angiography 1359 Fundoscopy 288
F Fluorescein conjugated lectin 86, 1197 Fundus drawing 1508
Facial nerve paralysis 106 Fluorescein dye disappearance test 712 Fundus evaluation 877
Familial exudative vitreoretinopathy 1650 Fluorescein fundus angiography 1773, Fundus fluorescein angiography
attempts at grading 1651 1785 1315, 1319, 1480

angiographic characteristics 1482
characteristics and uses 1480
characteristics of optic disk 1484
conclusion and applications 1488
fluorescein angiographic sequence
1481
fluorescein solution 1481
injecting the fluorescein 1481
interpretation of fluorescein
angiography 1484
autofluorescence 1484
blocked fluorescence 1486
filling defects 1486
hyperfluorescence 1486
hypofluorescence 1486
leakage 1485
pseudofluorescence 1484
retrofluorescence 1486
staining 1485
transmission or window defect
1484
monochromatic fundus photography
1481
normal fluorescein angiogram 1481
stereoscopic fundus photography 1481
technique 1480
Fundus fluorescein angiography 1683
Fundus fluorescein angiography (FFA)
1367
Fungal infection 1136
Fungal keratitis 165, 166, 175
Fungus identification 1197
Fungus identification 86
G Graft infection 264
Gaint retinal tears 1705
Galactosemia 818
treatment 819
Ganglion cells 1439
Gaze palsy 951
Gaze paresis 988
Gene therapy 1647
Genetic information 1103
genetic counseling 1103
genetic testing 1104
Genetics 1100
Genetics and cell biology 1648
Genital ulcers 1321
Giant cell arteritis 696
Giant papillary conjunctivitis 1193
management 1194
pathology 1193
Giant papillary conjunctivitis 1246
Giant retinal tears 1564, 1702, 1708
clinical evaluation 1708
fellow eyes of GRT 1713
surgical management 1708
Giardiasis 1216
Gillespie’s syndrome 765
Index 1813
Glands of krause 62 cavernous 1419
Glare 359 ocular features 1419
Glare control devices 1165 racemose 1420
Glaucoma 263, 493, 802, 1063, 1190, 1735, Hemangiomata 125
1788 Hemicentral retinal vein occlusion 1596
Glaucoma after cataract 545 Hemolytic glaucoma 548
Glaucoma filtration surgery 603 Hemorrhagic retinopathy 803
5-fluorouracil 604 Herbert’s follicles 77
events in wound healing 603 Herpes simplex 199
antimetabolites in glaucoma 604 Herpes simplex infection 167
mitomycin-C 605 Herpes simplex keratitis 265
Glaucoma in children 759 Herpes simplex virus 1332
clinical types 760 investigations 1333
examination techniques 759 ocular manifestation 1332
symptoms and signs 759 aquired 1333
Glaucoma in phakomatosis 769 congenital 1332
Glaucoma scope 513 treatment 1333
Glaucoma surgery 1176 Herpes virus hominis 73
Glaucomatocyclitis crisis 1275 Herpes zoster 1274
Glaucomatous optic nerve damage 485 Herpes zoster 33
Glioma of the optic nerve and chiasm 965 Herpes zoster keratitis 207
Glomus tumor 55 Herpes zoster ophthalmicus 208, 1137,
Glutathione 1231 1334
Gnathostomiasis 1217 Herpes zoster ophthalmous (HZO) 175
Goblet cells 62 Herpes zoster virus 1333
Goldmann posterior fundus contact lens Herpetic iridocyclitis 1273
1449 Hess chart 874
Goldmann three mirror examination 1510 Heterophoria 886
Goldmann three-mirror lens 1448 classification 887
Gonioscopy 528 etiology 886
Goniosynechia 476 examination of phoria 887
Gout 1225 management 888
Gradenigo’s syndrome 696 symptoms 887
Graft failure 266 High plus reading glasses 1165
Highly active antiretroviral therapy 1139
Graft rejection 264 Hirschberg’s light reflex test 869
Granulocytic sarcoma 649 Histiocytoses 650
Granuloma 833, 834 Histiocytosis X 655
Granulomatous uveitis 1381 Histocompatibility antigens 1607
Graves’ disease 700, 1039 Histopathology 1071
Graves’ ophthalmopathy 641 exenterated specimen 1074
Grid photocoagulation 1760 grossing 1072
Ground substance 1220 corneal button 1072
grossing an eye 1072
H lid biopsy 1072
Hamartias 660 immunologic and molecular
Hamartomas 660 techniques 1077
Hand-Schuller-Christian disease 651 molecular diagnostic tools 1079
Heidelberg retina tomograph 510 staining 1075
Hemangioma 1048 electron microscopy 1075
capillary 1049 special stains 1075
cavernous 1049 tissue embedding and cutting 1075
Hemangioma of the retina 1418 tissue fixation 1071
capillary 1418 tissue processing 1074
clinical findings 1418 Histopathology 114
diagnosis 1418 treatment 115
differential diagnosis 1418 chemotherapy 118
systemic features 1419 cryotherapy 118
treatment 1419 immunotherapy 118
1814
radiotherapy 118
surgical excision 117
HLA-B27 associated diseases 1372
Hodgkin’s lymphoma 650
Holladay formula 349
sources of error in iol power
calculation 349
a-constant error 350
error in determination of axial
length of the eye 350
error in keratometry 350
Home tonometry 484
Homocystinuria 1226
Homocystinuria 323, 776, 810, 821
biochemical tests 822
Hordeolum internum (acute meibomitis)
31
HSV keratouveitis 1273
Hudson-St hli’s line 135
Human crystalline lens 315
dislocation or luxation 322
etiology 322
ocular diseases causing
displacement 325
traumatic displacement 325
growth 316
epithelial cells 318
lens capsule 316
substance (cortex and nucleus) 319
management 325
cataractous lens 326
dislocated lens 326
subluxated crystalline lens 325
subluxation 322
Human immunodeficiency virus 1337
laboratory test 1339
precaution against transmission 1339
treatment 1339
Human immunodeficiency viruses 1127
Human leukocyte antigens 1385
Human T lymphotropic virus 1340
Humphrey field analyzer 517
Hutchinson’s freckle) 53
Hutchinson’s pupil 955
Hyaline degeneration 219
Hyaluronidase 361
Hydatid disease 1218
Hydrodelineation 371
Hydrodissection 371
Hyperemia 67
Hyperlysinemia 810
Hypermature cataract 539
Hyperosmotic glaucoma 539
Hyperosmotic intravenous agents 576
Hyperphoria 887
Hypertensive choroidopathy 1600
pathophysiology 1600
Hypertensive optic neuropathy 1603
Hypertensive retinopathy 1601
complications of sclerotic phase 1602
Modern Ophthalmology
exudative phase 1602 decontamination of OR surfaces 1124
sclerotic phase 1601 gowning and gloving 1125
vasoconstrictive phase 1601 handwashing 1121
Hypervitaminosis A 757 personnel of the OR 1124
Hyphema 548 record keeping 1126
Hypotonic maculopathy 609 surgical scrub and skin preparation
Hypotony 1430 1125
Hypotony maculopathy 599 the OR environment 112
Hypovitaminosis A 106 universal body substance precautions
HZV retinitis 1335 1122
Infectious epithelial keratitis 200
I sequelae 200
Iatrogenic retinal tears 1751 Infectious keratitis 1137
Idiopathic anterior uveitis 1268 Inferior orbital fissure 1012
Idiopathic central serous Infiltrative optic neuropathy 1002
choroidoretinopathy 1477 Inflammatory bowel disease 1270
Idiopathic intracranial hypertension 997 Inflammatory bowel disease 1374
circulation of CSF 997 Inflammatory pseudotumor 731
diagnosis 998 Infraorbital canal 1012
etiology 997 Inhibitors of collagen organization 606
pathology 998 Injurious chemicals 231
symptoms 998 acids 232
treatment 998 acetic 233
surgical 999 chromic 233
Idiopathic juxtafoveolar retinal hydrochloric 233
telangiectasis 1763 hydrofluoric 232
Idiopathic polypoidal choroidal inflammation 233
vasculopathy 1493 nitric 233
Idiopathic uveal effusion syndrome 1565 ocular surface damage 233
Imaging evaluation of the intracranial sulphuric 232
visual pathway 1056 alkalis 231
Immune recovery uveitis 1139 ammonia and ammonium
Immunofluorescence/fluorescent hydroxide 231
antibody test 203 calcium hydroxide 232
Immunofluorescent staining 1199 magnesium hydroxide 232
Immunological rejection 1189 sodium hydroxide 232
Immunosuppressive drugs 705 Interlenticular opacification 418
Implantable miniaturized telescope 356 Intermediate uveitis 1280
Inborn error of metabolism 818 anatomy 1280
Incisional biopsy 643 cataract extraction 1287
Incontinentia pigmenti 1654 clinical features 1281
Indocyanine green angiography 1151 differential diagnosis 1283
additional consideration 1156 ancillary tests 1283
ICG guided laser photocoagulation electrophysiological 1284
1157 laboratory investigations 1284
imaging 1152 systemic association 1283
properties of 1151 ultrasonography 1284
when to use 1158 heredity 1285
Indocyanine green angiography 1367 immunology 1284
Indocyanine green angiography 1489 natural course, complication 1282
clinical applications 1491 nomenclature 1280
clinical interpretation 1490 pathogenesis 1285
dosage 1490 pathology 1284
physical and pharmacologic properties treatment 1285
1489 step 1 1285
Indocyanine green angiography 1773 step 2 1286
Infection 1190 step 3 1286
Infection control practices 1121 step 4 1286
care of instruments/sterile supplies/ Intermittent corneal touch 465
drugs 1122 Intermuscular septum 927
 Index 1815
Internal retinochoroidotomy 1430 optics 347 management 224
Internal tamponade 1714 second generation 344 Keratoepithelioplasty 239
clinical application 1715 third generation 344 Keratolimbal allograft 1185
fluid-air exchange and internal Iridectomy 532, 533, 1428 Keratomalacia 754
drainage 1715 Iridocorneal endothelial syndrome 477 Keratometry 143
gas mixtures 1716 Iridocycletomy 1428 automated 143
Internuclear ophthalmoplegia 988 Iridocyclitis 1268 manual 143
Interstitial keratitis 209 Iridoplasty 532 Keratomileusis 278
Intraepithelial neoplasia 1203 Iris 1249 Keratomycosis 191
Intraocular biopsy techniques 1422 Iris chaffing 465 aetiology 192
Intraocular gases 1753 Iris nodules 1411 clinical features 192
characteristics 1754 Iris processes 475 filamentous fungus 192
complications 1754 Iris processes and synechia 478 yeast infection 192
contraindications 1754 Iris prolapse 406 common fungi responsible 191
indications 1754 Iris sun-tan syndrome 576 filamentous 191
postoperative care 1754 Iritis 584 yeast 191
Intraocular inflammation 1788 ISNT rule 484 incidence 191
Intraocular lens implantation 367, 374, 375 Isolated ectopia lentis 811 laboratory diagnosis 194
configuration 376 Isoniazid skin test 1358 corneal biopsy 195
looped design 376 culture 194
implantation site 375 J methods 195
asymmetric fixation 376 Jones’ dye tests 711 scraping and debridement 194
ciliary sulcus fixation 375 Juvenile arthritis 1374 smear 194
in the bag fixation 376 Juvenile chronic polyarteritis technique of scraping 194
IOL material 377 (Still’s disease) 1222 management 195
foldable 377 Juvenile rheumatoid arthritis 1270, 1375 adjunct therapy 196
PMMA 377 characteristics 1375 drugs 195
Intraocular lens implantation 464, 784, 794 management 1376 medical 195
complications of 464 management of complications 1376 surgical 196
intraoperative 464 Juxtacanallcular tissue 469 pathogenesis 192
postoperative 464 Keratophakia 277
Intraocular lymphomas 1301 K Keratoplasty 252
Intraocular metastatic tumor 1403 Keratoprosthesis 108
Kaposi’s sarcoma 126
clinical features 1405 Keratoses 124
Karichkoff lens 1450
anterior uvea 1405 Keratouveitis/endothelitis 209
Karyotyping 1079
ciliary body 1406 Kestenbaum formula 1162
Keratinizing metaplasia 751
iris 1406 Kissing nevus 51, 52
Keratitis 183
optic nerve head 1407 Klippel-Trenaunay-Weber syndrome 669
Keratoacanthoma 48
retinal 1408 Klippel-Trenaunay-Weber syndrome 771
Keratoconjunctivitis sicca 1137
diagnosis 1408 Krukenberg’s spindle 135
Keratoconjunctivitis sicca 1222
ophthalmoscopic examination 1408 Kveim test 1385
Keratoconus 134, 155, 222
pathogenesis 1405
etiology 22 L
sites 1404
connective tissue abnormality
time of metastasis 1404 Laboratory data management 182
theory 222
Intraocular pressure 480, 482 Laboratory tests 85
enzyme theory 222
Intraoperative 296 culture and isolation test 85
eye rubbing 223
Intraretinal hemorrhages 1607 cytological 85
genetic theory 222
Intraretinal microvascular abnormalities direct detection 85
hormonal theory 222
1608 serological tests 86
associations 223
Intraretinal neovascularization 1608 Lacrimal fistula 714
clinical features 223
Intravitreal hemorrhage 1625 Lacrimal gland 708, 729
diagnosis 223
Invasive squamous cell carcinoma 1204 anatomy 729
keratometry 223
Inverted follicular keratosis 49 tumors 730
keratoscopy 224
IOL development 344 Lacrimal gland pathology 1054
ophthalmoscopy 223
fifth generation 347 lesions of the lacrimal sac and duct
pachymetry 224
first generation 344 1055
retinoscopy 223
fourth generation 347 Lacrimal passage 726
slit lamp examination findings 223
IOL design features 348 Lacrimal passages 712
differential diagnosis 224
materials 347 Lacrimal system 708
histopathology 224
haptics 347
1816
anatomy 708
lacrimal apparatus 710
lacrimal gland 708
nasolacrimal duct 709
nerve supply 708
diseases 713
acquired disorders 715
benign lymphoepithelial lesion 713
congenital anomalies 713
infection 713
non-infective chronic inflammations
713
investigation 711
tests of lacrimal excretion 711
tests of lacrimal secretion 711
physiology 710
drainage of tears 710
secretion of tears 710
symptoms of dysfunction 711
Lactoferrin radial immunodiffusion assay
103
Lamellar grafting 11
Lamellar keratoplasty 268
advantages 268
indications 269
methods of lamellar dissection 269
problems 268
surgical steps 270
conventional 270
donor tissue preparation and
fixation 273
inlay modified segmental L K 270
onlay lamellar keratoplasty 272
onlay limbal transplantation 272
Lamp delivery system 1759
Langerhans’ cell histiocytoses 650
Lantern tests 1146
Laser assisted in-situ keratomileusis 286
clinical examination 287
complications 296
contraindications 286
preoperative evaluation 286
Laser cycloablation 543
Laser delivery system 290
Laser goniophotocoagulation 594
Laser gonioplasty 593
Laser goniopuncture 594
Laser interferometry 333
Laser iridectomy 534
Laser iridotomy 565
Laser lenses 1449
Laser peripheral iridotomy/iridectomy
589
argon laser iridotomy 590
Nd:YAG irodotomy 590
Laser revision of failing blebs 594
Laser treatment of bleb for hypotony 594
Laser-tissue interaction 288
Laser-tissue interactions 1757
Lasers in retinal diseases 1797
Modern Ophthalmology
delivery systems 1799 Louis-Bar syndrome 670
laser media 1798 Low vision 1160
laser output modes 1798 causes 1161
principles 1797 devices 1162
Late uveitis 466 computer systems 1167
Lateral geniculate body 945 non-optical 1166
Lattice degneration 1557 optical 1162
Learning curve 492 video magnifiers 1167
Leber’s hereditary 1115 enhancing impaired vision 1161
Leber’s hereditary optic atrophy 977 impact of ocular disease 1161
Leiomyoma of iris 1411 Low vision aids 1531
Leishmaniasis 1216 Lowe’s oculocerebral syndrome 778
Lens 1066 Lowe’s syndrome
Lens capsule 316 (oculocerebrorenal syndrome) 772
Lens dislocation 358 Lumbar puncture 999, 1319
Lens implantation 333 Lumbar-peritoneal shunt 1000
Lens induced glaucoma 538 Lupus erythematous (LE) cell 1221
Lens subluxation 808 Lyme disease 1313, 1387
acquired 812 Lymphadenopathy 69
et pupillae 812 Lymphangioma 55, 125, 830, 1049
heritable 809 Lymphoid tumors 646
management 813 classification 646
surgical 814 leukemic lesions 649
traumatic 812 lymphocytic lesions 647
Lens swelling (phacomorphic) 538 Lymphomas 125, 731, 1138
Lens-induced uveitis 1310 Lymphoproliferative disease 1041
Lens-particle glaucoma 539
Lens: associated uveitis 1276 M
Lensectomy 845, 1709 Macrodacryocystography 728
Lenticonus 775 Macrophthalmos/buphthalmos 1033
Leprosy 1215 Macular edema 1476, 1588, 1595, 1608,
Lesions of the bony orbit 1055 1609
Letterer-SIWE disease 651 Macular heterotopia 1611
Leukemia 649, 829, 836, 854 Macular hole 1474, 1691
Leukoplakia 111, 124 basic surgical technique 1693
Levator aponeurosis 2 classification 1691
Lid edema 633 clinical examination 1692
Lid edema or fullness 702 complications 1694
Lid infections 1137 indications 1693
Lid retraction 46, 704, 701 management 1692
Lid swelling 675 pathogenesis and pathology 1691
Ligament of lockwood 928 use of adjuvants 1693
Light microscopy 184 Macular holes 1564
Limbal allograft stem cell transplantation Macular pucker 1736
1212 Maddox Rod test 873, 887
Limbal stem cells deficiency 1181 Magnetic resonance imaging 642, 1022
classification and etiology 1181 basics 1022
clinical features 1181 MR protocols for orbits 1024
diagnosis 1182 Magnifiers 1163
management 1182 Mainster lens 1449
preparation of the bed 1182 Malaria 1216
surgical techniques 1182 Malignant 731
Limbus test 868 management 732
Limulus amebocyte lysate assay 1197 Malignant glaucoma 551
Limulus amebocyte lysate assay 87 clinical features 555
Lipid degeneration 219 clinical picture 552
Live related direct conjunctival limbal conditions of development 551
allograft 1185 course of the disease 557
Loiasis 1217 differential diagnosis 552, 558
Lost lens syndrome 465 management 553
 Index 1817
laser therapy 553 Measurement of vergence 868 basic concepts 1108
medical 553 Mechanism of phacoemulsification 387 techniques 1108
surgery 553 Medulloepithelioma 853, 1032 chromosome walking and jumping
management 558 Megalocornea (anterior megalophthalmos) 1112
surgical 559 134 linkage 1110
trabeculectomy 559 Meibomian gland 21 polymerase chain reaction 1112
pathogenesis 552 anatomy and physiology 22 preparation of probes 1110
pathogenesis 557 pathogenesis 23 probes 1109
Malignant histiocytosis 651 treatment 26 pulsed field gel electrophoresis
Malignant melanoma 1397 Meibomian gland dysfunction 25 1111
clinical presentation 1397 Meibomitis 21 southern blotting 1109
diagnosis 1398 Melanocytoma 1411 X chromosome and the eye 1112
clinical appearance 1398 Melanoses 124 Molluscum contagiosum 34, 1137
fundus fluorescein angiography Melanosis 1204 Monoclonal antibody 88, 1198
1398 Mendelian inheritance 1102 Monocular telescope 1166
invasive technique 1399 Metastasis 1207 Monocular vs binocular vision 867
new diagnostic tests 1399 Metastatic lesions 1042 Mooren’s ulcer 227, 303
transillumination 1399 Metastatic tumor 676 clinical features 304
ultrasonography 1398 behavior of different tumors 676 diagnosis 305
pathology 1399 factors facilitating metastasis 677 epidemiological features 303
growth pattern 1399 presentation 677 etiology 303
histologic characteristic 1400 diagnostic modalities 677 management 306
pigmentation 1399 biopsy 679 pathogenesis 305
systemic evaluation 1402 computerized tomography 678 pathology 303
treatment modalities 1401 laboratory examination 678 Moorfields regression analysis 487
chemotherapy and immunotherapy magnetic resonance imaging 679 Mosaicism 1106
1402 physical examination 677 Mucin secretors 62
enucleation 1401 ultrasonography 678 Mucoceles 672, 1048
exenteration 1402 primary sites 676 Mucoepidermoid carcinoma 124, 1204
local resection 1401 treatment 679 Mucous membrane grafting 108
photocoagulation 1401 chemotherapy 680 Mšller’s cells 1439
Malignant melanoma of the choroid 1431 hormonal therapy 680 Muller’s muscle 2
current management 1431 radiotherapy 680 Multifocal choroiditis with panuveitis
enucleation 1432 surgery 680 1297
internal resection 1432 Metastatic tumors 829 Multifocal iols 421
brachytherapy 1433 Microaneurysms 1607 biometric considerations 422
photochemotherapy 1433 Microcornea 772 multifocal iol styles 423
photocoagulation 1432 Microcornea patient selection 422
radiotherapy 1433 (anterior microphthalmos) 133 postoperative outcome analysis 423
local resection 1432 Microglia 1440 principle of multifocality 421
periodic observation 1432 Microkeratome 291 Multifocal VEP multifocal ERG 1471
Malignant melanoma/melanocytoma Microphthalmos 772 Multiple evanescent white dot syndrome
1410 Microphthalmos 825 1298
Malignant uveal melanoma 1033 Microspectrophotometry 1148 Multiple myeloma 650
Management of amblyopia 922 anomalies 1148 Multiple sclerosis 975
Mandibulofacial dysostosis 811 disorders 1148 Multipuncture capsulotomy 369
Marchesani syndrome 1226 drugs causing deficiency 1149 Munson’s sign 223
Marcus gunn pupillary sign 956 systemic disorders causing deficiency Murine typhus 1341
Marfan’s syndrome 323, 775, 809, 822, 1149 Muscle force generation test 877
1226 Microspherophakia 323 Myasthenia gravis 916
Marginal keratitis 227 Microtropia 896 diagnosis 917
Marginal myotomy 931 Miosis 1735 Mycobacterial infection 1135
Masquerade syndromes 836, 1277, 1300 Miotics 531 Mydriasis 598
malignant diseases 836 Miotics 921 Myopia 481, 1559, 1653, 1656
nonmalignant diseases 837 Mitochondrial inheritance 1103 Myopia
Mass lesions of anterior segment 1067 Mitomycin C 598 Myotonic dystrophy 779
Massive subretinal hemorrhage 1704 Mixed adenoma 963
Mast cell stabilizers 93 Mobius’ syndrome 984 N
Maxillary hypoplasia 767 Modes of inheritance 1103 Nanophthalmos 1565
Mean height contour graph 487 Molecular genetics 1108 Nanophthalmos 538
1818
Narrow angle glaucoma 475
Nasolacrimal duct 709
Nasolacrimal duct (NLD) block 713
Nasopharyngeal tumors 695
Natural history 899
Negative lens 1447
Neodymium 796
Neonatal conjunctivitis 733
clinical features 734
chemical conjunctivitis 735
chlamydial neonatal conjunctivitis
735
gonococcal neonatal conjunctivitis
735
herpes simplex neonatal
conjunctivitis 736
laboratory diagnosis 736
etiopathogenesis 733
prevention 739
treatment 738
Neoplasms 1138
Neoplasms of conjunctiva and cornea
1201
age and sex distribution 1205
classification of 1201
benign 1202
invasive malignant melanoma 1205
invasive squamous cell carcinoma
1204
melanocytic tumors 1204
mesenchymal tumors 1202
mucoepidermoid carcinoma 1204
pagetoid sebaceous cell carcinoma
1205
premalignant and malignant 1203
etiology 1205 incidence 1205
management 1205
investigations 1205
treatment 1206
cryotherapy 1207
immunotherapy and chemotherapy
1207
radiotherapy 1207
surgery 1206
Neoplasms of the optic nerve 1045
Neovascular glaucoma 540
management 543
pathogenesis 540
pathologic process 540
Neovascularization 1594
Neovascularization of the iris and angle
478
Nephritis and uveitis 1276
Neuroblastoma 829
Neurocutaneous syndromes 1037
Neurofibromatosis 55, 662
clinical features 663
eyelid and orbital lesions 663
glaucoma 663
ocular involvement 663
Modern Ophthalmology
retinal and optic nerve lesions 663 phacosandwich and phacosection
systemic manifestations 663 techniques 384
uveal tract 663 phacosandwich technique 382
pathology 664 sclerocorneal pocket tunnel incision
treatment 664 379
Neurofibromatosis 770 wound closure 386
Neuromyelitis optica (devic’s disease) 977 Noninfectious corneal ulceration 176
Neuroophthalmic lesions 1138 Noninfectious inflammation 799
Neuroprotective agents 576 Nonpigmented ciliary epithelium 1250
Neurotrophic keratopathy 201, 209 Nonsteroidal anti-inflammatory agents
Nevoid basal cell carcinoma syndrome 51 284
Nevus cell tumors 52 Nonsteroidal anti-inflammatory drugs 94
Nevus flammeus 55 Normal chamber angle 474
Nevus of ota 670 Normal tension glaucoma 502
Nevus of ota clinical picture 502
(oculodermal melanocytosis) 52 definition 502
New accommodating lens 425 differential diagnosis 505
visual outcomes 425 epidemiology 505
New plant breeding 758 pathogenesis 506
newer 1088 treatment 506
Newer laser procedures for glaucoma 594 Norrie’s disease 852, 1114, 1653
Night blindness 752, 1113, 1641 Nucelic acid hybridization reactions
Night vision devices 1168 88, 1198, 1002
Nitrogen mustard 300 Nystagmus 860
Nodular melanoma 53 atypical congenital idiopathic 862
Non-infectious retinopathy 1128 latent 862
Non-infectious uveitis 1388 management 863
degree of inflammation 1389 manifest congenital 863
duration of inflammation 1389 neurological 862
history of previous uveitis 1389 see-saw 862
management 1390 sensory defect 861
ancillary treatment 1394 typical congenital idiopathic 862
cytotoxic and immunosuppressive Nystagmus 989
chemotherapy 1394 acquired forms 990
intravitreal steroids 1391 congenital motor 989
newer topical steroid 1391 monocular forms 989
nonsteroidal anti-inflammatory physiologic 989
drugs 1393 Nystagmus surgery 864
pars plana vitrectomy 1394
periocular drugs 1391 O
peripheral retinal cryopexy 1393 O’Brien’s block 362
steroids 1390 Oblique dysfunction 868
systemic steroids 1392 Obstruction of canaliculus 722
response to initial treatment 1389 Occlusion 747, 748
risk of structural damage 1389 Occlusion test 899
uveitis active or inactive 1389 Occlusion-induced amblyopia 922
Non-phaco small incision cataract surgery Octopus single field printout 491
378 Ocular appendages 1012
anesthesia 378 choroid 1016
capsulotomy 380 ciliary body 1016
completing the tunnel 380 eyeball 1014
fish hook technique 384 size 1014
hydroprocedures 380 structure 1014
IOL implantation 385 eyelids 1012
microvectis technique 382 gross structure 1013
nuclear delivery 381 margins 1012
nucleus prolapse 381 lacrimal apparatus 1014
phacofracture/phacosection technique multislice (multidetector) 1021
383 outer tunic 1015

cornea 1015
sclera 1015
uveal tract 1015
retina 1016
structure 1017
scanning protocols 1021
spiral CT 1020
the lens 1018
vitreous humor 1018
Ocular cicatricial pemphigoid
82, 300, 1195
differential diagnosis 83
pathology 83
Ocular cysticercosis 1292
Ocular detachment 1033
Ocular disease 1321
Ocular electrophysiology tests 1455
Ocular helminthiasis 1217
Ocular hypertension 493
Ocular infections 189
Ocular infective organisms 1196
Ocular ischemic syndrome 1577, 1783
ancillary studies 1785
clinical features 1783
differential diagnosis 1578, 1786
etiology 1783
investigations 1577
carotid angiography 1578
electroretinography 1578
fundus fluorescein angiography
(FFA) 1577
management 1786
pathogenesis 1783
signs 1577
symptoms 1577, 1784
systemic associations 1578
treatment 1578
Ocular ischemic syndrome 1783
Ocular lesions 1028
adult 1033
children 1028
Ocular motility 951
Ocular motor dysmetria 987
Ocular motor palsies 980
abducens (sixth cranial) nerve 983
cavernous sinus and orbit 984
fasciculus 983
nerve (petrous) 984
peripheral nerve (subarachnoid)
983
isolated oculomotor palsy 982
oculomotor nerve 980
fasciculus 980
nucleus 980
peripheral nerve 981
intracavernous space 981
orbital space 981
subarachnoid space 981
special syndromes 981
Index 1819
trochlear (fourth cranial) nerve 982 Optic nerve 969
fasciculus 982 Optic nerve cupping 481
peripheral 982 Optic nerve drusen 1001
trochlear nerve 983 Optic nerve dysplasia 1001
Ocular motor paralysis 976 aplasia 1001
Ocular neovascularization 1588 coloboma 1002
Ocular surface 1179 hypoplasia 1002
Ocular surface disorders 1174 morning glory disk 1002
Ocular surface squamous neoplasia 110 pit 1002
Ocular syphilis 1135 Optic nerve glioma 1003
Ocular toxocariasis 853, 1031, 1135 Optic nerve head 973
Oculocardiac reflex 940 Optic nerve meningioma 1003
Oculodermal melanocytosis 670, 771 Optic nerve sheath decompression 999
Oculomotor apraxia 987 Optic nerve trauma 1002
Olivopontocerebellar atrophy 988 Optic nerve tumors 826
Onchocerciasis 1217 differential diagnosis 826
One and a half syndrome 988 treatment 827
Open angle glaucoma 475 Optic neuritis 675, 1040, 1115
Ophthalmia neonatorum 733 Optic neuropathy 486
Ophthalmic artery obstruction 1581 Optic tract 971
Ophthalmic Kaposi’s sarcoma 1138 Optical coherence tomography
Ophthalmic photography 1083 513, 1367, 1474
Ophthalmic viscosurgical devices 448 Ora pear’s 1557
characteristics and advantages 452 Oral acyclovir 207, 211
viscoadaptive ovd-HEALON-5A Oral aphthous ulcers 1320
452 Orbicularis bracing 10
classification 448 Orbicularis ocult 2
high viscous-cohesive 449 Orbital and periorbital cellulitis 1047
higher viscosity-cohesive 450 Orbital apex syndrome 968
low viscosity dispersive 451 Orbital blow-out fractures 682
lower viscosity-dispersive 449 classifications 683
super viscous-cohesive 449 clinical features 684
soft shell technique 452 incidence 682
surgical application of 453 management 685
use 453 surgical 686
capsular bag filling and IOL management 687
implantation 453 mechanism 683
capsulorhexis 453 medial blow-out fractures 687
cataract surgery 453 clinical features 687
cleavage of lens structure 453 imaging studies 687
glaucoma surgery 455 medical therapy 688
irrigation and aspiration 453 surgical therapy 688
nuclear emulsification 453 roentgen examination 685
Ophthalmomyasis 1218 Orbital cellulitis 184, 689
Ophthalmoplegic 38 clinical features 691
Ophthalmoplegic migraine 697, 982 complications 691
Ophthalmoscopy 957 differential diagnosis 691
Opportunistic infections 1128 etiopathogenesis 689
Opsocionus 987 predisposing factors 689
Optic atrophy 975 routes of infection 689
classification 978 laboratory and imaging studies 692
pathology 978 management 692
treatment 978 antibiotics 692
Optic chiasm 970 surgical 693
Optic disk area 484 microbiology 690
Optic disk drusen 1035 bacteria 690
Optic disk vasculitis fungi 690
(papillophlebitis) 1002 parasites 691
Optic foraman 1012 pathophysiology 690
1820 Modern Ophthalmology
Orbital cellulitis and abscess 671 Pars plana cysts 1505, 1557 intermediate 264
Orbital cysticercosis 1048 Pars plana surgery 1737 late 265
Orbital decompression 704 accessory instrumentation 1740 donor corneal preservation 255
Orbital fascia 628 complications 1750 intermediate-term storage 257
bulbi 628 full function system 1739 long-term storage 258
expansions 628 indications 1737 short-term storage 257
intermuscular septa/membrane 629 instrumentation 1738 indications 252
sheaths 628 cutting 1739 surgical techniques 259
Orbital fractures 1052 illumination 1738 anesthesia 259
Orbital infections 1138 infusion 1738 chamber entry and corneal button
Orbital lesions 631 suction 1739 removal 260
adulthood 632 principles 1737 eye exposure, fixation, and scleral
childhood 631 types 1737 support 259
Orbital meningioma 632 Pars plana vitrectomy 1790 field preparation and draping 259
Orbital neuralgia 675 Pars planitis 835, 1280 graft placement and chamber
Orbital pseudotumor 830, 1037 Pars plicata 1249, 1250 maintenance 261
Orbital radiation 705 Patellar fossa 316 iol insertion 260
Orbital septum 9 Pattern electroretinogram 1467 management of the lens 260
Orbital trauma 1051 clinical uses 1468 management of vitreous 260
Orbital varix 830 recordings and measurements 1468 suturing the corneal button 261
Orbitocranial diseases 995 Pediatric cataracts 397 trephination of donor material 260
Orthoptics 922 subluxated or dislocated cataract 397 trephining of recipient button 259
Oscillopsia 949 Pediatric cataracts 780 Penetrating keratoplasty 253, 547
Osteogenesis imperfecta 1226 anterior capsule management 789 Perfluorocarbon 1709
Osteomyelitis 675 bipolar radiofrequency Perfluorocarbon liquids 1701
capsulotomy 792 applications 1701
P can-opener anterior capsulotomy complications 1704
Pachometry 288 790 Perfluorocarbon liquids 1755
Pachometry (pachymetry) 142 curvilinear capsulorhexis 789 complications 1755
Pagetoid 53 fugo plasma bladeTM anterior uses 1755
Panfundoscopic lens 1449 capsulotomy 793 Perfluorocarbon liquids 1790
Pannus 78 intraocular lens implantation 794 Periorbita 628
Panretinal photocoagulation 1614, 1615, lens substance removal 794 Periosteitis 675
1760 manual continuous 789 Peripheral corneal ulces 226
Panuveitis 1303 vitrector-cut anterior capsulectomy clinical features 226
fungal 1305 790 etiological factors 226
infectious causes 1303 diagnosis 780 Peripheral granuloma 1291
Papilledema 992 dye-enhanced pediatric cataract Peripheral iridotony 559
differential diagnosis 995 surgery 797 Peripheral retina 1496, 1497
fluorescein angiography 994 indications for treatment 780 applied anatomy 1497
ophthalmoscopic appearance 993 IOL implantation 785 degenerative lesions 1498
pathogenesis 992 power selection 785 degenerative peripheral cystoid
pathology 993 size 785 degneration 1499
symptomatology 993 optical rehabilitation 782 full thickness retina tear 1501
Papillitis 973 aphakic glasses 783 lattice 1498
Papilloma 123 contact lenses 783 partial thickness retina tear 1501
Paralysis of upgaze 988 epikeratophakia 784 pavingstone 1503
Paralytic squint 938 intraocular lens implantation 784 retinal hole 1502
Paralytic strabismus 935 perioperative and postoperative retinal tuft 1500
Paranasal sinus diseases 671 medications 797 snail track 1499
Parasellar syndrome 697 posterior capsule management 795 white with pressure and white
Paravasalsinuses 689 postoperative complications and without pressure 1500
Parinaud’s Dorsal midbrain syndrome management 797 developmental anatomy
960 surgical techniques 786 lesions 1497
Pars plana 1249, 1250, 1505 anesthesia 788 microanatomy 1497
applied anatomy 1505 wound construction 788 Peripheral retinal cryopexy 1393
developmental anatomy 1505 Penalization therapy 923 Peritomy 301
lesions 1505 Penetrating corneal transplantation 252 Persistent corneal edema 466
microanatomy 1505 complications 262 Persistent hyaloid system 775
surgical anatomy 1505 early 262

Persistent hyperplastic primary vitreous
1030
Persistent hyperplastic primary vitreous
772
Peter’s anomaly 768
clinical features 768
management 769
mechanism of glaucoma 769
ocular abnormalities 768
pathogenesis 769
Peyman vitreophage 1739
PFCL-silicone oil exchange 1711
Phaco in colobomatous eyes 398
Phacoanaphylactic glaucoma 539
Phacoanesthesia 335
Phacoemulsification 402
problems faced by a surgeon 402
mental block 402
phaco machine specification 403
problem of coordination 402
role of phaco skill transfer courses
403
selection of eye 403
selection of initial patients 403
surgeons ability 402
understanding phaco setting for
403
use of operating microscope 403
transition and their management 404
continuous curvilinear
capsulorhexis 404
hydrodissection and
hydrodelineation 404
phaco incisions 404
phacoemulsification techniques 405
Phacoemulsification 409
complications 409
anterior capsulotomy 410
chamber collapse 410
corneal 410
general 409
glaucoma due to viscoelastic 412
related to hydro procedures 410
related to incision 410
retained lens matter 411
retinal 412
Phacoemulsification 599
Phacoemulsification in a vitrectomized
eye 398
Phacoemulsification in different type of
cataracts 395
hard nucleus 396
intumescent cataract 396
posterior polar cataract 395
white cataract 395
Phacoemulsification in patients with
pseudoexfliation 400
Phacoemulsification in postsurgical eyes
398
Index
Phacoemulsification in uveitic eyes 401
Phacoemulsification with small pupil 400
Phacolytic glaucoma 539
Phacomachine 387
aspiration pump 388
diaphragmatic pump 389
foot pedal 389
irrigation aspiration handpiece 388
peristaltic pumps 388
phaco tips/needles 388
ultrasonic handpiece 387
venturi pump 389
Phacotrabeculectomy 597, 600
Phagocytic inflammatory cells 1381
Phakic intraocular lens 224
Phakomatosis 660
Pharmacologic mydriasis 960
Pharyngoconjunctival 72
Phlyctenular keratoconjunctitivis 68, 81
Phlyctenulosis 82
Photocoagulation 1432
Photorefractive keratectomy 159
Photorefractive keratectomy 279
medical treatment 282
corticosteroids 282
nonsteroidal anti-inflammatory
agents 284
wound healing modulators 285
preoperative evaluation 279
prk for astigmatism 281
cylindrical ablation 282
elliptic ablation 282
surgical technique 280
Photostress test 949
Phthisis bulbi 754
Physiology 524
Pierre-Robin syndrome 772, 811
Piggy-back foldable intraocular lenses
430, 803
complications 432
depth of focus using a piggy back
system 432
image quality 432
power calculation 431
primary implantations 431
secondary implantation 432
primary 430
high hyperopes 430
minus power piggyback lenses 431
multifocal piggyback iol 431
toric piggyback iols 431
secondary 431
Pigment dispersion glaucoma 556
Pigment dispersion syndrome 477
Pigment dispersion syndrome 544
Pigmentary degeneration depositions 219
Pigmented ciliary epithelium 1251
Pigments over the anterior lens capsule
775
1821
Pinguecula 127
Pituitary apoplexy 697
Pituitary tumor 962
Plasma cell tumors 649
Plasmacytoma 655
Plasmapheresis 705
Plateau iris 534
Pleomorphic adenoma 656, 730
Pleoptics 748
Pleoptics 923
Plexiform neurofibroma 56
Plica semilunaris 65
Pneumatosinus dilatans 673
Pneumocystis carinii choroidopathy 1136
Polyarteritis nodosa 1224
Polyarteritis nodosa 229
Polymerase chain reaction 204, 1079, 1107,
1112
Polymorphisms 1101
Polymyositis 1224
Positive aspheric lenses 1447
Posner-schlossman syndrome 544
Post-PK astigmatism 157
Posterior capsular rupture 358, 406
Posterior capsular tear 411
Posterior capsule opacification 341, 412,
414
barrier effect of iol optic 417
evaluation techniques 416
immunological inhibitors 418
management 418
pathogenesis 415
pharmacological techniques 418
prevention 416
biocompatibility of iol 417
capsulorhexis edge on the IOL
surface 417
hydrodissection-enhanced cortical
clean-up 416
in-the-bag fixation of iol 417
maximum iol optic posterior
capsule contact 417
why to eliminate 415
Posterior capsule scraping 374
Posterior capsulorhexis 795
Posterior capsulotomy 547
Posterior nucleus dislocation 406
Posterior pole granuloma 1291
Posterior scleritis 1319
Posterior segment lesions 1128
Posterior uveitis 833, 1289, 1313, 1492
differential diagnosis 1289
infectious 1289
non-infectious 1289
Posterior vitreous detachment 1259
Posterior-uveitis in acquired
immunodeficiency syndrome 1294
Posteriorly dislocated 1703
Postkeratoplasty astigmatism 266
1822
Postoperative 297
lasik procedure 291
Postoperative glaucoma 545
Postsurgical uveitis 1308
Postvitrectomy glaucoma 1751
Potential acuity meter 332
Power calculation 349
calculating iol power by biometry 349
empirical 349
Precancerous lesions 49
Preoperative 296
preparations 1087
cellugel 1088
chondroitin sulfate 1088
collagen 1088
hydroxy propyl methyl cellulose
1088
ocugel 1088
sodium hyaluronate 1087
Presumed ocular tuberculosis 1356
diagnosis 1357
Pretectal afferent pupillary defects 960
Prevalence 899
Primary 760
Primary angle closure glaucoma 522
anatomical features 522
Primary open angle glaucoma 479
diagnosis 482
management 493
pathogenesis 481
optic nerve damage 482
raised IOP 481
risk factors 480
the problem 479
treatment 494
laser 495
medical 494
surgical 495
Primary pigmentary dispersion syndrome
555
Primary posterior capsulotomy 795
Primary posterior capsulotomy 796
Prism bar cover test 870
Progressive hepatolenticular disease
(Wilson’s disease) 821
Progressive iris atrophy 477
Progressive outer retinal necrosis 1131
Progressive outer retinal necrosis 1293
Progressive outer retinal necrosis 1336
Progressive supranuclear palsy 988
Proliferative diabetic retinopathy 1702
Proliferative diabetic retinopathy 1705
Proliferative vitreoretinopathy 1633
classification 1633
clinical features 1635
investigations 1637
management 1637
adjuvant therapy 1638
prophylaxis 1637
surgical 1638
Modern Ophthalmology
pathogenesis 1633 evaluation 38
risk factors 1635 Beli’s phenomenon 39
Proliferative vitreoretinopathy (PVR) 1705 phenylephrine test 40
Proptosis 632 surgical treatment 40
Proptosis 672 aponeurotic repan 45
Prostaglandins 575 fassanella servat operation 40
Prostaglandins 583 frontalis sling surgery 44
latanoprost 583 levator resection 41
Prostigmin 37 other surgical procedures 45
Protein energy malnutrition 752 Pulsed field gel electrophoresis 1111
Provocative tests 528 Punctal atresia 715
Pseudo-anterior uveitis 462 Punctal ectropion 715
Pseudo-Duane’s syndrome Punctal stenosis 715
(acquired retraction syndrome) 913 Punctate inner choroidopathy 1298
Pseudocarcinomatous hyperplasia 48 Punctiform opacity 776
Pseudodendrites 208 Pupil in Horner’s syndrome 956
Pseudoexfoliation syndrome 476 Pupil size 288
Pseudoexfoliation syndrome 561 Pupillary block glaucoma 552
clinical picture 562 Pupillary capture 800
anterior chamber and angle 562 Pupillary dilator pathway 953
blood-aqueous barrier 563 Pupillary pathways 958
conjunctiva and cornea 562 afferent 958
intraocular pressure 563 afferent 959
iris and pupil 562 parasympathetic 958
lens, zonules, and ciliary body 562 parasympathetic 960
definition 561 sympathetic 958
diagnosis 564 sympathetic 960
epidemiology 561 Pupilloconstrictor pathway 954
heredity 562 Pupils and pupillary reactions 952
incidence with glaucoma 562 Pyridostigmin (mestinon) 37
incidence without glaucoma 561
systemic associations 562 Q
etiopathogenesis 563 Q fever 1341
history 561
management 565 R
mechanism of glaucoma 564
Radial keratotomy 158, 277
pathophysiology 563
Radiation dermatosis 49
Pseudoexfoliative syndrome 537
Radiation keratopathy 300
Pseudohypopyon 836
Radiopaque dyes 726
Pseudoisochromatic color plates 1147
Raeder’s paratrigeminal syndrome 696
Pseudomelanoma 1398
Raised intraocular pressure 458
Pseudophakic bullous keratopathy 1175
Rapid antigen detection 203
Pseudopterygium 128
Raster stereography 512
Pseudotumor
Rathke’s pouch cyst 964
(inflammatory orbital disease) 656
Reactive lymphoid hyperplasia 647
Pseudotumor cerebri 997
Recombinant DNA technology 1107
Pseudoxanthoma elasticum 1226
Reflection image 487
Psoriatic arthritis 1269
Refraction 287
Psoriatic arthritis 1374
Refraction errors 886
Pterygium 127
Refractive 423
Pterygium surgery 1175
Refractive correction 920
Ptosis (blepharoptosis) 35
Refsum’s syndrome 811
classification 35
Reiter’s disease 1223
aponeurotic 37
Reiter’s syndrome 1269, 1373
mechanical 38
Relapsing polychondritis 230, 312, 1225
myogenic 35
Removal of subincisional cortex 391
neurogenic 37
extension of the incision 391
pseudoptosis 38
mobilization cortex 392
synkinetic 38
mobilization of the cortex 392
complication 45

system using two separate cannulas 392
advantages of bimanual technique
394
incisions for two cannulas 393
principles for use of two cannulas
393
technical features of the two
cannulas 392
technique 393
technique of using viscoelastic 392
technique with a curved coaxial
cannula 392
verticalization of the coaxial tip 391
Reporting system 181
Residual refractive error 803
Reticulin fiber 1220
Retina 1435
anatomy 1436
central retina 1436
peripheral fundus 1437
blood supply 1440
embryology 1435
structure 1438
amacrine cells 1439
bipolar cells 1439
ganglion cells 1439
horizontal cells 1439
photoreceotors 1438
retinal pigment epithelium 1438
supporting structure of retina 1439
Retina sparing internal resection 1430
Retinal angiomatous proliferation 1154
Retinal arterial macroaneurysms 1763
Retinal astrocytomas 853
Retinal breaks 1764
Retinal capillary hemangioma 1763
Retinal chip research 1647
Retinal detachment
characteristics of the types 1563
clinical features 1560
signs 1561
symptoms 1560
differential diagnosis 1562
pathogenesis 1558
precipitating factors 1559
predisposing factors 1560
Retinal detachment 1594, 1703, 1706
Retinal detachment 802
Retinal detachment surgery 1552
examination of the patient 1552
indirect ophthalmoscopy 1553
instrumentation 1554
method 1554
principle 1553
normal retinal periphery and
peripheral lesions 1555
Retinal detachment surgery 1568
alternative techniques 1574
DACE technique 1575
Index 1823
orbital/episcleral (Lincoff) balloon field of view 1444
1574 fundus examination documentation
pneumatic retinopexy 1574 1446
primary vitrectomy 1575 magnification 1444
suprachoroidal implantation 1575 non-contact system 1453
anesthesia for scleral buckling 1569 BIOM 1453
closure of retinal breaks 1571 optical principle of wide-angle lens
buckling materials 1571 1453
configuration of buckle 1571 SDI 1453
episcleral exoplants 1572 optics of indirect ophthalmoscopy
intrascleral implants 1572 1443
intraoperative complications 1574 surgical lenses 1450
drainage complications 1574 Retinectomy 1710, 1720
localization of retinal breaks 1570 Retinitis pigmentosa 1641
management of subretinal fluid 1572 evaluation and investigations 1642
drainage technique 1573 management 1646
nondrainage technique 1572 molecular genetics 1646
preparation of the operative field 1569 current state of research 1647
rationale and goals 1569 signs 1642
surgical exposure 1569 symptoms 1641
treatment of retinal breaks 1571 variants 1645
Retinal detachments 1704 Retinoblastoma 537, 831, 835, 836, 849,
Retinal dialysis 1559, 1564, 1750 1028, 1116, 1764
Retinal disease 1321 age at diagnosis 849
Retinal disorder 556 clinical features 850
Retinal dysplasia 852 developmental abnormalities 852
Retinal edema 1563 differential diagnosis 851
Retinal hemorrhages 1216 genetics 849
Retinal hole 1502 hereditary conditions 852
Retinal holes 1558 inflammatory conditions 853
Retinal incarceration 1703 management 854
Retinal neovascularization 1596 chemotherapy 857
Retinal pigment epithelium 1438 cryotherapy 855
Retinal tamponade 1712 enucleation 856
Retinal tear and detachment 1789 external beam radiotherapy 856
Retinal tears 1558 laser photocoagulation 855
Retinal telangiectasis 1511 orbital exenteration 857
group 1 1511 plaque brachytherapy 855
differential diagnosis 1512 thermotherapy 855
group 2 1512 pathogenesis 849
differential diagnosis 1516 pathology 851
natural course 1515 tumors 853
pathogenesis 1517 Retinoblastoma 851
treatment 1518 Retinocytoma 850
group 3 1518 Retinopathy of prematurity 537, 773, 835,
Retinal tuft 1501 838, 1031, 1653, 1704
Retinal venous macroaneurysms 1763 classification 839
Retinal viewing system 1442 location of the disease 840
binocular indirect ophthalmoscopy plus disease 840
1443 regressed ROP 840
biomicroscopy of the retina 1446 stages of the disease 840
contact lenses 1447 threshold ROP 840
noncontact lenses 1447 examination 842
compensation for refractive error 1444 prevention and treatment 843
contact system 1450 recent advances 847
conventional lenses 1450 risk factors 841
optical principle 1451 birthweight and gestational age 841
wide-angle system 1452 delicate balance 841
direct ophthalmoscopy 1442 multiple gestation 842
examination technique 1445
1824 Modern Ophthalmology
prolonged intubation 842 Sample collection devices 182 indications 438
treatment 843 methods 183 recent advances 441
cryotherapy 843 sample collection devices 182 Scleritis 308, 1222
laser photocoagulation 844 bard parker blade numbers 15 182 associated systemic diseases 312
multicentric cryotherapy 844 calcium aigiate swab 182 etiology 311
vitreoretinal surgery 844 cotton swabs 182 infection of the sclera 313
vasculogenesis in 838 glass slides 183 infections 313
Retinoschisis 852, 1500, 1653, 1767 kimura platinum spatula 182 therapeutic regimes 313
basic types 1767 needle and syringe 182 episcleritis therapy 314
degenerative or senile 1767 Sarcoidosis 731, 1225, 1311, 1337 surgery 314
x-linked or juvenile 1767 causes of poor vision 1312 types 308
clinical features 1769 clinical features 1311 anterior 309
treatment 1769 diagnosis 1312 diffuse anterior 309
Retinotomy 1719 differential diagnosis 1313 necrotizing 310
Retrobulbar block 362 etiology 1311 nodular 310
comfortable regional 363 investigations 1313 posterior 310
general 365 ocular manifestations 1311 Sclerocornea 134
local 364 pathology 1312 Scleroderma progressiva systemica 1224
peribulbar (periocular) injection 363 posterior segment findings 1312 Sclerokeratitis 209
subtenon anesthesia 363 sarcoidosis in children 1312 Scleromalacia perforans 310
topical 363 SBK formula 349 Sclerotic scatter 139
Retrobulbar neuritis 974 Scanning laser polarimetry 511 Scrub typhus 1341
Retrogeniculate lesions 971 Schirmer test 711 Sealed capsule irrigation 341
Retroillumination 140 Schirmer’s test 102 Sebaceous gland tumors 53
Retrolental plate 845 Schistosomiasis 1217 Seborrheic keratosis 48
Rhabdomyosarcoma 827 Schlemm’s canal 470 Secondary corneal edema 209
diagnosis 828 Schwalbe’s line 471, 474 Secondary glaucoma 465, 536
differential diagnosis 828 Sclera 135 Secondary intraocular lens
pathology 827 blood supply 135 implantation 434
treatment 828 congenital anomalies 136 associated surgical procedures 435
Rhegmatogenous retinal detachment 1777 Scleral 1735 complications 437
Rhegmatogenous retinal detachment 542 Scleral bucking 846, 1708, 1713, 1730 contraindications 434
Rhegmatogenous retinal detachment 853 alternative techniques 1732 indication 434, 436
Rheumatoid arthritis 106, 228 alternatives 1734 IOL exchange 435
Rheumatoid arthritis 311 complications 1734 preoperative preparation 435
Rheumatoid factor 1385 intraoperative 1735 types 436
Rickettsial uveitis 1324 postoperative 1735 Secondary membrane formation 799
Rickettsial uveitis 1341 fate 1734 Secretomotor fibers 708
“Ridge” or “mesenchymal” shunt 842 length 1731 See-saw nystagmus 990
Rieger’s syndrome 324 life of the buckling effect 1731 Seidel test 141
Rift valley fever retinitis 1340 material of the buckle 1730 Sensory disturbances 949
Rigid lenses 336 currently used 1730 Sensory tests 871
Riley-day syndrome 106 newer materials 1731 Serologic test 204
Rodenstock optic nerve head analyzer 509 used in the past 1730 Serpiginous choroiditis 1299, 1366
Rollable lenses 338 orientation 1731 ancillary investigations 1367
Rose bengal 141 placement 1731 clinical features 1366
Rose Bengal stain 102 shape 1731 manifestation 1367
Round cell tumor (retinoblastoma) 657 techniques 1732 signs 1366
Rubella 1335 types and classifications symptoms 1366
Rubeosis iridis 1752 Scleral depression 1445, 1507, 1555 complications 1367
Rubinstein-taybi syndrome documentation 1508 differential diagnosis 1369
(broad thumb syndrome) 772 technique 1507 pathogenesis 1369
Rush disease 842 Scleral perforation 940 treatment 1371
Scleral spur 471, 475 Serpiginous ulceration 209
S Scleral tunnel design 598 Serum angiotensin converting enzyme
Saccharin test 711 Scleral-fixated PCIOL 438 1385
Salivary gland dysfunction 106 ab-externo approach 439 Seventh nerve block 362
Salzmann’s nodular degeneration 219 ab-interno approach 438 Short wave automated perimetry 520
Sampaolesi’s line 478 complications 439 Siderosis 134

Silicone oil 1704, 1716, 1754
adherence 358
applications of 1705
complications 1706
chemical properties 1754
complications 1755
indications 1755
injection technique 1717
mode of action 1754
Sjögren’s syndrome 1377
Sjögren’s syndrome 229
Skew deviation 989
Skin grafting 15
Slit lamp biomicroscopy 102, 137, 1262
forms of illumination 138
diffuse 141
direct 138
indirect 138
modern clinical 137
Slit lamp examination 1510
Slit lamp indirect ophthalmoscopy 1510
Small B cell lymphomas 647
Sodium fluorescein 141, 1480
Sodium hyaluronate 1756
Soft tissue injuries 1053
Solid tumors 640
Southern blotting 1109
Spasmus nutans 863
Spectacle devices 1162
Spectacle use and patient satisfaction 428
Specular microscopy 147
clinical 148
narrow slit of light 148
wide slit of light 148
clinical applications 155
evolution 154
factors affecting image quality 149
indications 149
instrumentation 150
limitations 160
methods of evaluation 150
qualitative assessment 151
quantitative assessment 151
normal 155
optical principles 147
reading and interpretation 159
techniques 149
types 148
Specular microscopy 255
Sphenoidal ridge syndrome 966
Squamous cell carcinoma 51, 124
Squamous cell papilloma 48, 1202
Squash or imprint cytology 1081
Stem cell 1179
characteristics 1180
Stem cell deficiency 1176
Stem cell transplant 272
Stem cells 298, 1647
Stereometric analysis 487
Stereophotogrammetry 509
Index
Stereoscopic indirect ophthalmoscope 1506
Sterilization 334, 348
chemical 348
gas 348
radiation 349
Steroid glaucoma 545
Steroids 205
Stickler’s syndrome 822
Stiles-crawford effect 1145
Stoker’s lize
Stoker-busaca line 135
Strabismus 867
diplopia tests 872
facultative inhibition 880
haploscopic test 874
obligatory inhibition 880
stereoacuity estimation 871
Strabismus surgery 924
aims 924
amount of operation 936
closure of the wound 939
cyclovertical deviations 937
horizontal deviations 937
paralytic squint 938
postoperative care 939
special forms of strabismus 938
suturing the muscle to the sclera 939
anatomical considerations 926
capsulopalpebral fascia 928
check ligaments 928
extraocular muscles 926
fascial coverings 927
intermuscular septum 927
ligament of lockwood 928
muscle capsule 928
orbital fat 928
tenon’s capsule 927
complications 939
postoperative 940
preoperative 939
indications 924
patient evaluation 925
surgical procedures 929
adjustable sutures 934
anteroplacement of obliques 936
botulinum toxin to weaken the
action of a muscle 932
correction of A/V patterns 935
marginal myotomy 931
muscle transposition operations 934
paralytic strabismus 935
posterior fixation suture 932
recession 930
resection operation 933
strengthening operations 933
tenotomy or myectomy 931
use of plastic materials 936
weakening operations 929
weakening-strengthening
operations 934
1825
surgical techniques 928
anesthesia 928
exposure of the muscle 929
Stroma 1251
Stromal diskiform keratitis 175
Stromal keratitis 201, 207, 211
necrotizing 202
stromal immune 202
Stromal ulceration 234
Sturge-Weber syndrome 667, 764, 770, 811
Subarachnoid space 985
Subconjunctival hemorrhage 69
Subdural hematoma 1007
Subfoveal choroidal neovascularization
1721
management 1721
adjuncts to surgery 1724
case selection 1722
complications 1724
feasibility of surgical excision 1725
instrumentation 1722
postoperative management 1724
retinotomy and foveal translocation
1725
surgical technique 1722
Submacular cysticercosis 1698
Submacular hemorrhage 1694
alternative techniques 1696
indications for surgical intervention
1695
Submacular hemorrhage 1726
complications 1727
management 1726
surgical technique 1726
Subretinal membrane 1703
Subretinal neovascularization 1697
indications 1697
surgical technique 1698
Subretinal strands in proliferative
vitreoretinopathy 1727
Substantia propria 132
Subvitreal hemorrhage 1625
Sulfite oxidase deficiency 811
Superior oblique muscle sheath syndrome
914
Superior oblique myokymia 983
Superior orbital fissure 638, 1011
Superior orbital fissure syndrome 675,
966, 968
Suppression 879
Suprachoroid 1251
Suprachoroidal hemorrhage 552, 1704
Supranuclear disorders 986
affecting the calibration of saccadic eye
movements
affecting the conjugacy of gaze 988
affecting the size and velocity of
saccades 988
clinical disorders 987
affecting the initiation of eye
1826
movements 987
vertical eye movements 988
Surface tension 1714
Surgical lenses 1450
Swedish interactive thresholding
algorithm 489
Sympathetic adrenergic receptors 579
alpha receptor agonist 580
apraclonidine 581
brimonidine tartrate 581
dipivefrin 581
epinephrine 580
beta blockers 579
betaxolol 580
levobunolol (betagan) 580
timolol 579
Sympathetic fibers 709
Sympathetic ophthalmia 1314
clinical features 1314
diagnosis
differential diagnosis 1316
histopathology 1316
treatment 1316
corticosteroids 1317
enucleation 1316
immunomodulators 1317
Sympathetic ophthalmia 1319
Sympathizing eye 1378
clinical features 1378
immunopathology 1380
incidence 1378
laboratory investigations 1382
management 1382
ocular complications 1383
pathogenesis 1380
pathology 1380
time of onset 1378
Syphilis 1274, 1303
clinical features 1303
HIV 1304
uveitis in syphilis 1303
Systemic amyloidosis 537
Systemic lupus erythematosis 106, 229,
1223
Syte (hordeolum externum) 30
T Thyroid myopathy 702
T cell lymphomas 648
Takayasu disease 1224
Tarsal wedge resection 10
Tarsitis 31
Tarsorrhaphy 1213
Tear break-up time 711
Tear film break up time 102
Tear lysozyme assay 103, 711
Tear osmolarity 103
Tears 99
associated conditions 106
clinical features 102
examination 102
Modern Ophthalmology
investigations 102
natural course of disease 105
staining procedure 104
technique 104
clinical features 111
diagnosis 113
differential diagnosis 105
etiology 110
fear film layer 99
aqueous 100
lipid 99
mucin 100
fluids of tear film 100
management 106
anti-inflammatory therapy 107
contact lenses 107
decreasing tear viscosity 108
estrogen 108
keratoprosthesis 108
mucous membrane grafting 108
surgical measures 108
tear conservation 107
tear stimulants 107
tear substitutes 106
topical vitamin A 108
physiology 99
tear film abnormalities 101
aqueous deficiency 101
epitheliopathy 102
lipid abnormality 101
mucin deficiency 101
Telangiectasia 125
Telecanthus 4
Telescopes 1164
Temporal arteritis 1224
Tendency oriented perimetry 489
Tenon’s capsule 628
Tenon’s capsule 927
Teratoma 825
Terrien’s degeneration 220
Testing of visual function 949
Theoretical formulae 349
Thermokeratoplasty 276
Third nerve palsy 960
Thyroid function tests 637, 703
Thyroid hormone 699
Thyroid myopathy 704
Tilted optic disk 1001
Tissue adhesive 178, 1211
Tissue culture 1079
Tissue retrieval 244
Tolosa-Hunt syndrome 695
Tonometry 635
Tonotomy or myectomy 931
Topical carbonic anhydrase inhibitor 581
brinzolamide 582
dorzolamide 581
Topical medications 1210
Torticollis 865
Total limbal stem cell deficiency 1176
Toxocara canis 833
Toxocara infection (toxocariasis) 1218
Toxocariasis 833, 1291, 1653
atypical presentations 834
clinical presentation 833
differential diagnosis 835
laboratory tests 835
cytology 835
elisa test 835
pathology 835
treatment 836
Toxoplasma gondii 1344
definitive hosts 1345
intermediate hosts 1345
life cycle 1344
Toxoplasmosis 1289, 1344, 1345, 1386
additional therapeutic approaches
1350
cryotherapy 1350
photocoagulation 1350
vitrectomy and lensectomy 1350
AIDS 1348
clinical features 1345
complications 1348
diagnostic tests 1348
treatment 1348
Trabecular aspiration 559, 565
Trabecular meshwork 468
filtering part 469
nonfiltering part 469
Trabecular meshwork 474
Trabecular spaces 470
Trabeculectomy 565, 599, 1174
Trabeculotomy ab externo 762
Trachoma 599, 1218
“Train-track” sign 668
Traction retinal detachment 1566, 1611
Transfixation 128
Transpupillary thermotherapy 1762
Trauma 1702, 1705
Traumatic iridocyclitis 1276
Traumatic mydriasis 960
Travoprost 585
Treatment 899
indications for surgery 900
Treatment of viral retinitis 1132
acyclovir 1133
catheter-less therapy 1133
ganciclovir intraocular implant
1134
intravenous cidofovir 1133
intravitreal medications 1134
oral ganciclovir 1133
foscarnet 1132
ganciclovir 1132
Trichiasis 7
Trigeminal nerve paralysis 106
Trypanosomiasis (sleeping sickness) 1217
 Index 1827
Tuberculin skin test 1357 etiology 1260 Visual loss 633
Tuberculm (Mantoux test) 1385 examination 1257 Visual sensory system 943
Tuberculosis 1275, 1290, 1313, 1356 general 1259 blood supply of the visual pathways
Tuberous sclerosis 660, 771 local 1257 946
clinical features 661 history-taking 1256 lateral geniculate body 945
Tubular interstitial 1276 incidence 1260 occipital cortex 946
Tumors 478 sample uveitis questionnaire 1265 optic chiasm 944
Tumors of cerebellopontine angle 1008 family history 1265 optic disk 943
Tumors of illrd ventricle and internal medical history 1266 optic nerve 944
hydrocephalus 1008 signs 1255 optic radiations 946
Tumors of neural origin 1043 optic tracts 945
Tumors of pineal body and midbrain 1009 V retina 943
Turner’s syndrome 779 Variable penetrance and expressivity 1105 Visual symptoms 427
Types of lasers 1758 Varicella zoster virus 1333 Vitamin A deficiency 751
Types of variation in DNA 1100 disease 1130 assessment 755
Vascular lesions 1048 categories 751
U Vascular tumors 125 disorders cycle 752
UGH (Ellingson’s) syndrome 466 Vascular tumors of the retina 1418 treatment 755
UGH and PUGH syndrome 546 Vasculorhexis 1626 fortification of dietary items 757
Ulcer formation 1246 Vasoproliferative tumor of the retina 1420 periodic supplementation 757
Ultrasonography 639 Venous varix 1050 vitamin A prophylaxis 756
Ultrasound biomicroscopy 1062 Vergence system 990 Vitamin A prophylaxis 756
clinical applications 1063 Vernal conjunctivitis 1194 Vitelliform foveomacular dystrophy 1516
instrumentation 106 Vernal keratoconjunctivitis 91, 227 Vitrectomy 444, 1546, 1550, 1709, 1737,
principle 1062 atopic kerato 94 1742
technique 1062 management 95 indications 1742
Ultrasound biomicroscopy 145 giant papillary 95 management 1744
Unoprostone 584 differential diagnosis 96 anterior segment disorders 1749
Uvea 1066 management 96 diabetic retinopathy 1745
Uveal effusion syndrome 1319 pathomechanism of formation of Eales’ disease 1745
Uveal effusion syndrome 1354 papillae 96 endophthalmitis 1748
Uveal inflammation 543 vernal kerato 91 epiretinal membranes 1744
Uveal tract 1249 clinical features 91 giant retinal breaks 1747
congenital and developmental defects pathogenesis 92 intraocular foreign bodies 1748
1252 treatment 93 macular holes 1749
coloboma of choroid 1252 Vertical strabismus 908 ocular trauma 174
cysts of iris and ciliary body cysts dissociated vertical deviation 909 proliferative vitreoretinopathy 1747
1253 noncomitant vertical deviations 910 retinal detachment 1746
heterochromia iridis 1252 strabismus sursoadductorious 909 submacular surgery 1749
hypoplasia of iris 1252 Video indirect ophthalmoscopy 1510 vitreous hemorrhage 1744
persistent pupillary membrane Videokeratography 155,157,158 Vitrectorlexis 790
1252 Videokeratography 158 Vitreomacular traction syndrome 1477,
persistent tunica vasculosa lentis Viral keratitis 165, 167, 171, 173, 199 1691
1252 Viscocanalostomy 455 Vitreoretinal 1067
gross and microanatomy 1249 complications of use 458 Vitreous 1440
choroid 1251 topical ophthalmic anesthesia 457 embryology 1436
ciliary body 1250 Viscoelastic substances 448, 1086 optical anatomy 1440
iris 1249 Viscoelastic substances 789 Vitreous aspiration/biopsy 1386
Uveitis 211, 798, 1254, 1334 Visual acuity 425 Vitreous base 1506
basic mechanism 1255 Visual acuity estimation 867 Vitreous hemorrhage 1559, 1588, 1594,
classification 1254 Visual cycle and vitamin A 756 1611, 1624, 1789
according to type of inflammation Visual deficit 948 causes 1626
1255 Visual evoked potential 1468 complications 1630
anatomical 1254 clinical uses 1469 diagnosis and investigations 1627
etiological 1254 normal waveforms 1469 diagnostic ultrasound 1628
clinical approach to a patient 1261 recording and measurement 1468 MRI 1629
examination of patients 1262 Visual field defects 969 etiopathology 1626
history taking 1261 altitudinal 969 vitreous barriers 1626
laboratory evaluations 1264 Visual field examination 489 fate 1627
slit lamp biomicroscopy 1262 Visual field loss 1641 in vitrectomized eyes 1630
1828
treatment 1629
Vitreous substitutes 1741
Vitreous TAP 1423
Vitreous tap 1550
Vogt-koyanagi-harada (VKH)
syndrome 1317
ancillary investigations 1319
clinical features 1317
acute uveitic stage 1317
chronic or convalescent phase 1318
chronic recurrent phase 1318
prodromal stage 1317
differential diagnosis 1319
etiology 1319
extraocular signs 1318
treatment 1320
Modern Ophthalmology
Von Hippel-Lindau disease 664 Wildervanck syndrome 811
Von Hippel-Lindau syndrome 771 Wilms’ tumor 829
Von Recklinghausen’s disease 55, 662 Wilson’s disease 220
Wound dehiscence 265, 465
W Wyburn-Mason syndrome 669
Warts (verruca vulgaris) 34
Wegener’s granulomatosis 229, 1224 X
Wegener’s granulomatosis and X-linked retinitis pigmentosa 1112
polyarteritis nodosa 312 Xanthelasma 57
Weil-Marchesani syndrome 324, 776, 810 Xanthogranulomas 651
Weiss procedure 11 Xeroderma pigmentosum 49
Wernicke’s hemianopic pupil 956 Xerophthalmia 751, 752, 755
Whipple’s disease 1377
White limbal girdle of vogt 220 Y
Whitnall’s ligament 2 Yag laser posterior capsulotomy 796
Yaws 1218