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ADVANCES IN
Ophthalmology
and Optometry
Editor-in-Chief
Myron Yanoff, MD
Chair Emeritus, Department of Ophthalmology, Drexel University,
Adjunct Professor, Department of Ophthalmology,
University of Pennsylvania, Philadelphia, Pennsylvania
ELSEVIER
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ADVANCES IN
Ophthalmology and Optometry
Editor-in-Chief
MYRON YANOFF, MD, Chair Emeritus, Department of Ophthalmology, Drexel Uni-
versity, Adjunct Professor, Department of Ophthalmology, University of Penn-
sylvania, Philadelphia, Pennsylvania
Section Editors
BHAVNA CHAWLA, MD – Ophthalmic Pathology & Ocular Oncology
RP Center for Ophthalmic Sciences, All India Institute of
Medical Sciences, New Delhi, India
DAVID A. CRANDALL, MD – Cataract & Refractive Surgery

Glaucoma Fellowship Director, Henry Ford Health System, Detroit, Michigan
University of Utah, Salt Lake City, Wayne State University, Salt Lake City, Utah
PAUL B. FREEMAN, OD, FAAO, FCOVD – Optometry

Diplomate, Low Vision, Pittsburgh, Pennsylvania, Clinical Professor, Rosenberg
School of Optometry, University of the Incarnate, Word, San Antonio, Texas
MORRIS E. HARTSTEIN, MD, FACS – Oculoplastics

Director, Ophthalmic Plastic and Reconstructive Surgery, Ophthalmology, Shamir
Medical Center, Zerifin, Israel; Tel Aviv University, Sackler School of Medicine,
Tel Aviv, Israel
RUSTUM KARANJIA, MD, PhD, FRCSC, DABO – Neuro-ophthalmology

Department of Ophthalmology, David Geffen School of Medicine at
UCLA, Los Angeles, California; Doheny Eye Institute, Los Angeles,
California, Doheny Eye Institute, Los Angeles, California, Department of Oph-
thalmology, University of Ottawa, Ottawa, Ontario, Canada, Ottawa Hospital
Research Institute, The Ottawa Hospital, Ottawa, Ontario, Canada
RONNI M. LIEBERMAN, MD – Vitreoretinal Disease

Assistant Professor of Ophthalmology, Icahn School of Medicine at Mt. Sinai,
Queens Hospital Center, Jamaica, New York
ANN-MARIE LOBO, MD – Uveitis

Co-Director, Uveitis Service, Assistant Professor, Department of
Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary,
University of Illinois at Chicago, Chicago, Ilinois
vii
SECTION EDITORS continued
STEPHEN ORLIN, MD – Cornea and External Diseases

Associate Professor, Scheie Eye Institute, University of Pennsylvania, Perelman
School of Medicine, Philadelphia, Pennsylvania
JOSEPH M. ORTIZ, MD, FRCOphth – Glaucoma

Consultant in Ophthalmology, Sacred Heart Hospital, Allentown,
Pennsylvania; Consultant in Ophthalmology, Abington Memorial Hospital,
Abington, Pennsylvania; Formerly Assistant Professor of Ophthalmology,
Hahnemann University Hospital, Drexel University School of Medicine,
Philadelphia, Pennsylvania
LEONARD J. PRESS, OD, FAAO, FCOVD – Optometry

Press Consulting, P.C., Lakewood, New Jersey; Adjunct Professor, Southern
College of Optometry, Memphis, Tennessee
APARNA RAMASUBRAMANIAN, MD – Pediatric Ophthalmology

Director of Retinoblasma and Ocular Oncology, Phoenix Children’s Hospital,
Phoenix, Arizona
viii
ADVANCES IN
Ophthalmology And Optometry
CONTRIBUTORS
MARIB AKANDA, MD, Resident, Department of Ophthalmology, Northwell Health,
Great Neck, New York, USA
CESAR ALFARO, MD, The Retina Service, Mount Sinai Hospital, Manhattan, New
York, USA
KARL N. BECKER, MD, Uveitis and Medical Retina Fellow, Illinois Eye and Ear
Infirmary, Chicago, Illinois, USA
DEVIN BETSCH, MD, Resident, Department of Ophthalmology and Visual Sciences,

Dalhousie University, QEII Health Sciences Centre, Halifax, Nova Scotia,
Canada
POOJA V. BHAT, MD, Assistant Professor of Ophthalmology, Co-director of Uveitis

Service, Associate Program Director, Director of Medical Student Education,
Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois,
USA
JYOTIRMAY BISWAS, MS, FMRF, FNAMS, FAICO, FRCS, Uvea Department, Medical
Research Foundation, Senior Consultant, Director of Uveitis and Ocular
Pathology Department, Sankara Nethralaya, Chennai, Tamilnadu, India
DANIEL BRISCOE, MD, Ophthalmology Department, HaEmek Medical Center, Afula,

Israel
JAN RICHARD BRUENECH, PhD, Professor, Biomedical Research Unit, Faculty of

Health and Social Sciences, University of South-Eastern Norway, Campus
Kongsberg, Norway
CAT N. BURKAT, MD, FACS, Professor, Oculoplastic, Orbital, and Facial Cosmetic
Surgery, Department of Ophthalmology and Visual Sciences, University of
Wisconsin-Madison School of Medicine and Public Health, University of
Wisconsin-Madison, Madison, Wisconsin, USA
GREG CALDWELL, OD, FAAO, Optometric Education Consultants, Lilly,

Pennsylvania, USA
JANE W. CHAN, MD, Doheny Eye Institute, Doheny Eye Institute, Los Angeles,
California, USA
ix
CONTRIBUTORS continued
NOEL C.Y. CHAN, MBChB, FRCSEd, Department of Ophthalmology and Visual

Sciences, Prince of Wales Hospital & Alice Ho Miu Ling Nethersole Hospital,
Shatin, HKSAR, China; Department of Ophthalmology and Visual Sciences, The
Chinese University of Hong Kong, HKSAR, China
BHAVNA CHAWLA, MD, Professor of Ophthalmology, Ocular Oncology Service, RP

Center for Ophthalmic Sciences, All India Institute of Medical Sciences, New
Delhi, India
ARIEL CHEN, MD, The Wilmer Eye Institute, Johns Hopkins School of Medicine,
Baltimore, Maryland, USA
KELSEY CHEN, MABS, Medical Student, Midwestern University Arizona College of

Osteopathic Medicine, Glendale, Arizona, USA
DANIEL CHOI, MD, Department of Ophthalmology, Scheie Eye Institute, University of

Pennsylvania, Philadelphia, Pennsylvania, USA
DAVID A. CRANDALL, MD, Glaucoma and Advanced Anterior Segment Fellowship

Director, Department of Ophthalmology, Henry Ford Health System, Detroit,
Michigan, USA; John Moran Eye Center, University of Utah, Salt Lake City,
Utah, USA
DIPANKAR DAS, MS, Department of Pathology, Uveitis and Neurophthalmology, Sri

Sankaradeva Nethralaya, Guwahati, Assam, India
DEEPIKA DHINGRA, MS, DNB, FICO, Advanced Eye Centre, Postgraduate Institute of
Medical Education and Research, Chandigarh, India
ERIN M. DRAPER, OD, FAAO, Attending Optometrist, Neuro-Ophthalmic Disease

Service, Co-Director, Neuro-Ophthalmic Disease Residency Program, The Eye
Institute, Assistant Professor, Pennsylvania College of Optometry at Salus
University, Philadelphia, Pennsylvania, USA
PAUL T. FINGER, MD, Director, New York Eye Cancer Center, New York, New York,
USA
PAUL R. FREUND, MD, MSc, FRCSC, Assistant Professor, Department of

Ophthalmology and Visual Sciences, Dalhousie University, QEII Health Sciences
Centre, Halifax, Nova Scotia, Canada
SAMUEL GELNICK, MD, Resident, Department of Ophthalmology, Northwell Health,

Great Neck, New York, USA
MARK GHASSIBI, MD, Northwell Health Eye Institute, Great Neck, New York, USA
ROBIN GINSBURG, MD, The Retina Service, Mount Sinai Hospital, Manhattan, New
York, USA
x
SNEHA GIRIDHAR, MD, Shri Bhagwan Mahavir Vitreoretinal Services, Sankara

Nethralaya, Chennai, Tamilnadu, India
LUIS F. GONCALVES, MD, Director of Fetal Imaging, Department of Radiology,

Phoenix Children’s Hospital, Departments of Child Health and Radiology,
University of Arizona College of Medicine, Department of Radiology, Mayo
Clinic, Phoenix, Arizona, USA
GIOVANNA GUIDOBONI, PhD, Departments of Electrical Engineering and Computer

Science, and Mathematics, University of Missouri, Columbia, Missouri, USA
PAUL HARASYMOWYCZ, MD, Department of Ophthalmology, University of

Montreal, Montreal Glaucoma Institute and Bellevue Ophthalmology Clinics,
Montreal, Canada
ALON HARRIS, MS, PhD, FARVO, Professor of Ophthalmology, Vice Chair of

International Research and Academic Affairs, Director of the Ophthalmic
Vascular Diagnostic and Research Program at Mount Sinai Hospital, Icahn School
of Medicine at Mount Sinai, New York, New York, USA
IOANA CATALINA IONESCU, MD, PhD, Orbital Center, Department of

Ophthalmology, Amsterdam University Medical Centers, Amsterdam, the
Netherlands
PUNEET JAIN, MD, Consultant, Oculoplasty and Ocular Oncology Department, Eye-
Q Super-Specialty Eye Hospitals, New Delhi, India
RABEA KASSEM, MD, Department of Ophthalmology, University of Montreal,

Montreal, Quebec, Canada
SUSHMITA KAUSHIK, MS, Advanced Eye Centre, Postgraduate Institute of Medical

Education and Research, Chandigarh, India
NUR KHATIB, MD, Orbital Center, Department of Ophthalmology, Amsterdam

University Medical Centers, Amsterdam, the Netherlands
HAYYAM KIRATLI, MD, Ocular Oncology Service, Professor, Department of

Ophthalmology, Hacettepe University School of Medicine, Ankara, Turkey
IREM KOÇ, MD, Ocular Oncology Service, Department of Ophthalmology, Hacettepe

University School of Medicine, Ankara, Turkey
RONNI LIEBERMAN, MD, Assistant Professor, Department of Ophthalmology, Mount

Sinai Medical Center, Ichan School of Medicine at Mount Sinai, New York, New
York, USA
TIANYU LIU, MD, Scheie Eye Institute, University of Pennsylvania, Philadelphia,

Pennsylvania, USA
xi
SUSAN LUO, BS, Department of Ophthalmology and Visual Sciences, University of

Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin,
USA
ILARIA MACCORA, MD, Rheumatology Unit, Meyer Children’s University Hospital,

University of Florence, Florence, Italy
NENITA MAGANTI, MD, Department of Ophthalmology and Visual Sciences,

University of Wisconsin-Madison, Madison, Wisconsin, USA
ASHLEY KAY MAGLIONE, OD, FAAO, Attending Optometrist, Neuro-Ophthalmic

Disease Service, The Eye Institute, Assistant Professor, Pennsylvania College of
Optometry at Salus University, Philadelphia, Pennsylvania, USA
KELLY A. MALLOY, OD, FAAO, Diplomate in Neuro-Ophthalmic Disorders; Chief

Optometrist, Neuro-Ophthalmic Disease Service, Co-Director, Neuro-Ophthalmic
Disease Residency Program, The Eye Institute, Professor, Pennsylvania College
of Optometry at Salus University, Philadelphia, Pennsylvania, USA
ELIZABETH MARUNDE, OD, Neuro-Ophthalmic Disease Resident, The Eye Institute,

Pennsylvania College of Optometry at Salus University, Philadelphia,
Pennsylvania, USA
ARIE Y. NEMET, MD, Department of Ophthalmology, Meir Medical Center, Kfar Saba,
Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
ENNY OYENIRAN, MD, Department of Ophthalmology, Scheie Eye Institute,

University of Pennsylvania, Philadelphia, Pennsylvania, USA
SURINDER S. PANDAV, MS, Advanced Eye Centre, Postgraduate Institute of Medical

Education and Research, Chandigarh, India
CHINTAN A. PATHAK, MD, Department of Ophthalmology and Visual Sciences,

University of Wisconsin-Madison, Madison, Wisconsin, USA
LIRON PE’ER, MD, Department of Ophthalmology, Meir Medical Center, Kfar Saba,
Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
ATHIMALAIPET V. RAMANAN, FRCP, Professor, Department of Paediatric

Rheumatology, Bristol Royal Hospital for Children, Translational Health
Sciences, University of Bristol, Bristol, United Kingdom
APARNA RAMASUBRAMANIAN, MD, Department of Ophthalmology, Phoenix

Children’s Hospital, Department of Radiology, Creighton University, Phoenix,
Arizona, USA
ANGELINE C. RIVKIN, BS, Medical Student, University of Illinois College of Medicine,

Chicago, Illinois, USA
xii
PEEROOZ SAEED, MD, PhD, Orbital Center, Department of Ophthalmology,

Amsterdam University Medical Centers, Amsterdam, the Netherlands
ETHAN S. SEN, MD, PhD, Department of Paediatric Rheumatology, Great North

Children’s Hospital, Faculty of Medical Sciences, Newcastle University, Newcastle
on Tyne, United Kingdom
BRIAN M. SHAFER, MD, Vance Thompson Vision, Sioux Falls, South Dakota, USA
BRENT SIESKY, PhD, Icahn School of Medicine at Mount Sinai, New York, New York,
USA
ETHAN K. SOBOL, MD, The Retina Service, Mount Sinai Hospital, Manhattan, New
York, USA
JOSEPH SOWKA, OD, FAAO, Diplomate, Center for Sight, Sarasota, Florida, USA
JESSICA STEEN, OD, FAAO, Assistant Professor, Nova Southeastern University

College of Optometry, Fort Lauderdale, Florida, USA
MICHAEL E. SULEWSKI Jr, MD, The Wilmer Eye Institute, Johns Hopkins School of
Medicine, Baltimore, Maryland, USA
ZUJAJA TAUQEER, MD, DPhil, Department of Ophthalmology, Scheie Eye Institute,

University of Pennsylvania, Philadelphia, Pennsylvania, USA
VANCE THOMPSON, MD, Director of Refractive Surgery, Vance Thompson Vision,

Sioux Falls, South Dakota, USA
MINH TRINH, MD, Northwell Health Eye Institute, Great Neck, New York, USA
JAMES C. TSAI, MD, Icahn School of Medicine at Mount Sinai, New York, New York,
USA
ALICE C. VERTICCHIO VERCELLIN, MD, PhD, Icahn School of Medicine at Mount

Sinai, New York, New York, USA
MYRON YANOFF, MD, Chair Emeritus, Department of Ophthalmology, Drexel

University, Adjunct Professor, Department of Ophthalmology, University of
Pennsylvania, Philadelphia, Pennsylvania, USA
CANDICE YOUSIF, MD, Glaucoma Fellow, Department of Ophthalmology, Henry

Ford Health System, Detroit, Michigan, USA
TINA ZENG, OD, Neuro-Ophthalmic Disease Resident, The Eye Institute,

Pennsylvania College of Optometry at Salus University, Philadelphia,
Pennsylvania, USA
xiii
ADVANCES IN
Ophthalmology and Optometry
CONTENTS VOLUME 6 2021
Editorial Board vii
Contributors ix
Preface xxvii
Myron Yanoff
In Memoriam xxix
David A. Crandall
Optometry
Optical Coherence Technology in Glaucoma Diagnosis
Joseph Sowka, Jessica Steen, and Greg Caldwell
Introduction 1
Optical coherence tomography retinal nerve fiber layer analysis in
glaucoma diagnosis 2
Optical coherence tomography macular analysis in glaucoma diagnosis 4
Optical coherence tomography angiography in glaucoma diagnosis 7
Clinics care points 10
Disclosure 10
An Update on Neurodegenerative Disease for Eye Care

Providers
Kelly A. Malloy, Erin M. Draper, Ashley Kay Maglione,
Tina Zeng, and Elizabeth Marunde
Introduction: neurodegenerative disease and the eye 13
Neurodegenerative disease definition 13
Varied pathophysiology of neurodegenerative diseases 14
Prevalent visual and ocular associations of neurodegenerative disease 14
Role of eye care providers in neurodegenerative disease 16
Visual and ocular associations of neurodegenerative disease 16
Eyelid function in neurodegenerative disease 16
Anterior segment findings in neurodegenerative disease 20
Posterior segment findings in neurodegenerative disease 21
Afferent visual function in neurodegenerative disease 22
xv
CONTENTS continued
Efferent visual function in neurodegenerative disease 24

Hallucinations in neurodegenerative disease 25
Visual and ocular side effects of neurodegenerative disease treatments 27
Adverse sequela 28
Associated improvement in neurodegenerative disease manifestations 28
Future avenues: neurodegenerative disease, the eye, and the visual system 28
Expected increase in prevalence of neurodegenerative disease 28
Optimal biomarkers involve eyes and vision 31
Summary: neurodegenerative disease, the eye, and the visual system 31
Eye care providers as screeners of neurodegenerative disease 31
Early identification and neurology referral is key 31
Eye care providers help improve quality of life of patients with
neurodegenerative disease 32
Expected surge of research into neurodegenerative disease 34
Disclosure 34
Neuroanatomical Structures in Extraocular Muscles and

Their Potential Implication in the Management of
Strabismus
Jan Richard Bruenech
Introduction 39
Structure and function of human extraocular muscles 40
Sensory receptors in human extraocular muscles 41
Muscle spindles 41
Tendon receptors 41
The role of proprioception in oculomotor control 43
The neural pathway for proprioception 43
The neural substrate for the control of eye movements 44
Binocular vision anomalies 45
Current concepts in the diagnosis and management of strabismus 46
Nonsurgical management of strabismus 46
Optical corrections 46
Neuromuscular stimulation through exercise 47
Surgical management of strabismus 48
Summary and discussion 49
Summary 51
Disclosure 51
Pediatric
Prenatal Diagnosis of Retinoblastoma
Kelsey Chen, Luis F. Goncalves, and
Aparna Ramasubramanian
Introduction 55
Incidence 56
Risk factors 56
xvi
CONTENTS continued
Genetics 56
Tumor staging 57
Treatment 57
Prenatal diagnosis 57
Rationale 57
Prenatal genetic testing 58
Summary 62
Current Management of Pediatric Glaucoma

Sushmita Kaushik, Deepika Dhingra, and Surinder S. Pandav
Introduction 70
Standardized nomenclature 70
Diagnosis 71
Classification 71
Diagnostic techniques 72
Intraocular pressure measurement and current understanding of
its role in pediatric glaucoma 72
Ocular biometry 74
Refractive error 75
Ultrasound biomicroscopy 76
Handheld optical coherence tomography 77
Genetic testing 77
Anesthesia 79
Treatment 79
Medical treatment 79
Surgery 80
Disclosure 83
Systemic Immunomodulatory Therapy in Pediatric

Uveitis
Ilaria Maccora, Ethan S. Sen, and Athimalaipet V. Ramanan
Introduction 87
Significance 89
Current guidelines 89
Recent advances in treatment 89
Disclosure 97
Update on Intravitreal Chemotherapy for

Retinoblastoma
Irem Koç, Hayyam Kiratli, and Bhavna Chawla
Introduction 101
Challenges of endophytic retinoblastoma 102
Treatment of intraocular seeding 102
Safety of intravitreal injections in eyes with retinoblastoma 103
xvii
CONTENTS continued
Classification of seeding 104

Impact of intravitreal injections on patient management 105
Uses of intravitreal chemotherapy other than for vitreous seeds 107
Dosage 107
Pharmacokinetics of intravitreal melphalan 112
Use of intravitreal topotecan 113
Pharmacokinetics of intravitreal topotecan 113
Stability of melphalan and topotecan 114
Future avenues 115
Summary 115
Ophthalmic Pathology & Ocular Oncology
Applications of Plaque Brachytherapy in Posterior

Segment Tumors: A Clinical Review
Puneet Jain, Paul T. Finger, and Bhavna Chawla
Introduction 119
Historical perspective 120
Choroidal hemangioma 121
Management of choroidal hemangioma 122
Management of diffuse choroidal hemangioma 122
Retinal capillary hemangioma 124
Vasoproliferative retinal tumors 125
Retinoblastoma 126
Choroidal melanoma 127
Limitations of plaque brachytherapy 129
Future avenues 129
Methods for dose de-escalation 129
Intraocular Tumors—Advances in Ophthalmic Pathology

Sneha Giridhar, Dipankar Das, and Jyotirmay Biswas
Retinoblastoma 133
Pathology 134
Molecular Pathology 138
Uveal melanoma 138
Pathology 140
Genetics 141
Primary vitreoretinal lymphoma 142
Cytology and immunohistochemistry 142
Molecular features 144
Summary 145
Acknowledgments 145
Disclosure 146
xviii
CONTENTS continued
Adenoid Cystic Carcinoma of the Lacrimal Gland

Nur Khatib, Ioana Catalina Ionescu, Daniel Briscoe, and
Peerooz Saeed
Introduction 147
Significance (in-depth analysis) 148
Signs and symptoms 148
Staging 148
Histopathology 148
Imaging 150
Treatment approach 150
Future avenues 155
Summary 155
Cataract & Refractive Surgery

Micro-Invasive Glaucoma Surgery
David A. Crandall and Candice Yousif
Introduction 159
Significance and current relevance 160
IStent trabecular micro-bypass stent 162
Hydrus microstent 163
Goniotomy-assisted trabeculotomy 165
Trab360 trabeculotomy 166
Trabectome 167
Kahook dual blade 167
Ab interno canaloplasty 168
Visco360 and OMNI 169
XEN gel stent 169
Preserflo 170
Summary 170
Disclosure 172
Vitreoretinal Disease
Artificial Intelligence in Retina

Minh Trinh, Mark Ghassibi, and Ronni Lieberman
Background and introduction 175
Overview of artificial intelligence 176
Evaluating deep learning algorithms 178
Diabetic retinopathy 179
Age-related macular degeneration 181
Future 182
Summary 183
Disclosure 184
xix
CONTENTS continued
Retina in the Age of COVID-19

Samuel Gelnick, Marib Akanda, and Ronni Lieberman
Background 187
Introduction 188
General cleaning and hygiene 188
Personal protective equipment 188
Pandemic restrictions 189
Care in an active pandemic 189
Scheduling visits 189
Precautions for procedures 192
Intravitreal injections 192
Precautions for laser procedures 193
Scheduling follow-up visits 193
Patients with positive screening or testing for COVID-19 194
Care after immediate pandemic restrictions are lifted 195
Continued screening and scheduling precautions 195
Day of appointment precautions 195
Performing elective surgery 196
Operating room precautions 197
Summary 197
Disclosure 198
Diagnostic and Treatment Update on Sickle Cell

Retinopathy
Cesar Alfaro, Ethan K. Sobol, and Robin Ginsburg
Introduction 201
Pathophysiology 202
Epidemiology 202
Ocular manifestations 203
Classification system 205
Diagnosis 206
Optical coherence tomography 207
Optical coherence tomography angiography 207
Ultra-wide fluorescein angiography 209
Management 210
Screening 210
Laser 210
Anti-vascular endothelial growth factor 211
Surgical treatment 212
Summary 212
Glaucoma
Glaucoma Surgery: Which Surgery to Pick for Your

Patient?
Rabea Kassem and Paul Harasymowycz
xx
CONTENTS continued
Introduction 218
Significance 218
Subconjunctival surgery 219
When not to opt for subconjunctival surgery? 219
Nonpenetrating glaucoma surgery 219
Trabeculectomy 222
XEN Gel Implant (Allergan Inc, Irvine, CA, USA) 222
Preserflo Microshunt (Santen Pharmaceutical Co Ltd, Osaka,
Japan) 223
Tube shunts 223
Cyclodestructive procedures 224
Schlemm canal–based procedures 225
Selective laser trabeculoplasty 225
Schlemm canal-based microinvasive glaucoma surgery 226
Suprachoroidal 231
CyPass (Alcon, Fort Worth, TX, USA) 231
Special considerations 231
Patients with very advanced disease 231
Patients with very high intraocular pressure 232
Patients with angle-closure glaucoma 232
Primary angle closure 233
Primary angle-closure glaucoma 233
Patients with neovascular glaucoma 234
Reoperation after failed glaucoma surgery 234
Current relevance and future avenues 236
Summary 239
Disclosure 241
Ocular Blood Flow as It Relates to Race and Disease on

Glaucoma
Brent Siesky, Alon Harris, Alice C. Verticchio Vercellin,
Giovanna Guidoboni, and James C. Tsai
Introduction 245
Significance 246
Racial disparities in glaucoma 248
Mechanisms behind racial disparities in glaucoma 248
Summary 258
Clinical care points 259
Funding 259
Financial disclosures 259
Neuro-ophthalmology
Glaucoma as a Neurodegenerative Disease: A Clinician

Perspective
Noel C.Y. Chan and Jane W. Chan
Introduction 263
xxi
CONTENTS continued
Is glaucoma a neurodegenerative disease? 264

Sick eye comes with a sick brain 264
Common clinical characteristics between glaucoma and
Overlapping pathophysiology between glaucoma and other
Neuroinflammation 267
Oxidative stress and mitochondrial dysfunction 267
Dysregulation of calcium dependent process 268
Alterations of autophagy machinery 268
Misfolding of proteins 268
Activation of glia 269
Glaucoma and cerebrospinal fluid 269
Looking into the future 269
Summary 270
Disclosure 271
Neuro-Ophthalmologic Manifestations of Novel

Coronavirus
Devin Betsch and Paul R. Freund
Introduction 275
Article body 276
Neuro-ophthalmic presentations 276
Management changes 282
Relevance 284
Summary 285
Disclosure 285
Cornea and External Diseases
Advances in Endothelial Keratoplasty Surgery

Ariel Chen, Daniel Choi, and Michael E. Sulewski Jr.
Introduction 289
Significance 290
Lamellar keratoplasty 290
Descemet stripping endothelial keratoplasty 293
Descemet’s membrane endothelial keratoplasty 295
Descemetorhexis without endothelial keratoplasty 298
Relevance and future avenues 298
Summary 301
Disclosure 302
Update in the Management of Keratoconus

Enny Oyeniran and Zujaja Tauqeer
xxii
CONTENTS continued
Introduction 307
Corneal cross-linking 310
Spectacles and contact lenses 313
Scleral contact lenses 315
Intrastromal corneal ring segments 317
Penetrating keratoplasty 319
Deep anterior lamellar keratoplasty 320
Summary 320
Disclosure 321
Update on Refractive Surgery

Tianyu Liu, Brian M. Shafer, and Vance Thompson
Introduction 325
Significance and in-depth analysis of the topic 326
Corneal refractive surgery 326
Intraocular refractive surgery 328
Treatment of presbyopia 330
Current relevance and future avenues to investigate the topic 332
Management of higher-order aberrations: wavefront-optimized,
wavefront-guided, and topography-guided laser ablation 332
Advances in refractive lenticule surgery 333
Accommodative intraocular lens 334
Summary 336
Disclosure 337
Oculoplastics
Xanthelasma Palpebrarum: An Oculoplastic Viewpoint of
Optimal Treatment
Liron Pe’er and Arie Y. Nemet
Introduction 341
Significance (in-depth analysis) 342
Pathophysiology 342
Treatment 343
Surgical or laser treatment 349
Discussion 350
The location 350
Nasal lower eyelid-primary 351
Lesion extending to temporal lower lid 352
Extensive lower lid lesions 352
Nasal bridge 352
Giant xanthelasmas 353
xxiii
CONTENTS continued
Refractive Error Changes Associated with Eyelid Weight

Placement
Cat N. Burkat and Susan Luo
Introduction 358
Significance 359
Efficacy of upper eyelid weight placement 359
Causes of lagophthalmos 360
Operative technique 360
Complications of upper eyelid loading 360
Refractive error changes 360
Transition to platinum 368
Cost of platinum versus gold 368
Future avenues 369
Summary 369
Acknowledgments 371
Disclosure 371
Refractive Change after Upper Eyelid Surgery

Chintan A. Pathak, Nenita Maganti, and Cat N. Burkat
Introduction 373
Preoperative changes 375
Postoperative changes 376
Clinical relevance 377
Acknowledgments 378
Canalicular Stenosis Secondary to Chemotherapeutic

Agents
Nenita Maganti, Chintan A. Pathak, and Cat N. Burkat
Introduction 379
Chemotherapeutic agents known to cause canalicular stenosis 380
5-Fluorouracil 380
Mitomycin-C 381
Docetaxel 381
Significance of epiphora secondary to canalicular abnormality 382
Management of canalicular stenosis 382
Summary 386
Acknowledgments 387
Uveitis
Optical Coherence Tomography Angiography in White Dot

Syndromes
Karl N. Becker, Angeline C. Rivkin, and Pooja V. Bhat
xxiv
CONTENTS continued
Introduction 391
Overview 392
Cross-sectional and en face visualizations of the posterior circulation 393
Birdshot chorioretinopathy 394
Multiple evanescent white dot syndrome 395
Punctate inner choroiditis 396
Serpiginous choroiditis 397
Acute posterior multifocal placoid pigment epitheliopathy 398
Acute zonal occult outer retinopathy 399
Multifocal choroiditis 400
Summary 401
xxv
Advances in Ophthalmology and Optometry 6 (2021) xxvii
ADVANCES IN OPHTHALMOLOGY AND OPTOMETRY
Preface
Myron Yanoff, MD
Editor
I
n Volume 6 of Advances in Ophthalmology and Optometry, we again have asked
experts in each of the pertinent fields to sift through the current literature to
give us insights on the latest developments, such as: Optical Coherence
Technology in Glaucoma Diagnosis; Prenatal Diagnosis of Retinoblastoma;
Systemic Immunomodulatory Therapy in Pediatric Uveitis; Update on Intra-
vitreal Chemotherapy for Retinoblastoma; Microinvasive Glaucoma Surgery;
Artificial Intelligence in Retina; Artificial Intelligence in Neuroophthalmology
Review; Retina in the Age of COVID-19; Neuroophthalmologic Manifesta-
tions of Novel Coronavirus; Advances in Endothelial Keratoplasty Surgery;
Adenoid Cystic Carcinoma of the Lacrimal Gland; Refractive Error Changes
Associated with Eyelid Weight Placement; Optical Coherence Tomography
Angiography in White Dot Syndromes; and much more.
We continue to explore the new ideas, new treatments, and new ways of do-
ing things to give us a fresh frame of reference to sort through the crush of data
and to make sense in a real way of how to proceed.
Myron Yanoff, MD
1915 Foulkeways
Gwynedd, PA 19436, USA
E-mail address: myanoff4@gmail.com
https://doi.org/10.1016/j.yaoo.2021.05.001
2452-1760/21/ª 2021 Published by Elsevier Inc.
Advances in Ophthalmology and Optometry 6 (2021) xxix–xxxi
In Memoriam
IN MEMORY OF DR ALAN CRANDALL
W
e were extremely saddened to hear about the passing of Dr Alan
Crandall, renown ophthalmologist and internationally known hu-
manitarian, this past October. Dr Crandall was a founding member
of Advances in Ophthalmology and Optometry and has served as our Cataracts Sec-
tion Editor for the last five consecutive issues of publication. Dr Crandall’s
boundless expertise and commitment to the publication have, without a doubt,
helped us grow the series into a true and trusted resource for our readers, cli-
nicians around the world. We wanted to acknowledge his passing with some
words of tribute from our Editor-in-Chief, Dr Myron Yanoff, as well as from
Dr Crandall’s son, Dr David A. Crandall.
Even as a resident, Alan stood out as being a very special person. So special that
at the end of his residency, I asked him to stay on staff. He accepted. Whatever
he did, he did it well with a sparkle in his eyes. Whether patient care, surgical
prowess, or my tennis partner, he was a joy to be with. After a few years on
staff, we decided that it was time to perform intraocular lens implantation at the
Scheie Eye Institute (only intracapsular cataract extraction was done by the full-
time staff). We operated together and taught ourselves first to do extracapsular
surgery and then entered into the world of lens implants (all under an air bubble,
as Healon had not yet been invented). Alan was a brilliant surgeon, a gifted
clinician, and a personality that made one wish to work with him. One of my
2452-1760/21/ª 2021 Published by Elsevier Inc.
xxx IN MEMORIAM
saddest days was when Alan decided that it would be best for his family for him
to leave and go back to where he grew up in Salt Lake City.
We remained fast friends until the end. In fact, a year before he left us, he removed
my cataracts (I would have no other cataract surgeon anywhere do the surgery),
of course, with perfect results. Each year at the American Academy of
Ophthalmology meeting, we would have dinner together the night before the
meeting started. I cherished our friendship. I also marveled at his other en-
deavors. He trained hundreds of surgeons around the world and performed
countless free surgeries to restore sight in Utah, on the Navajo Nation, and in
more than 20 countries, including Ghana, Nepal, and South Sudan. Among
many awards, he received the AAO Humanitarian Award, the American So-
ciety of Cataract and Refractive Surgery (ASCRS) Humanitarian Award, and the
inaugural ASCRS Foundation Chang Humanitarian Award.
Alan has left a legacy that few other ophthalmologists even come close to. He left
this world a better place than he found it. He certainly is missed, but his teaching
and training live on. He still lives on in my mind, and always will.
Myron Yanoff, MD
Chair Emeritus
Department of Ophthalmology
Drexel University
Adjunct Professor
Department of Ophthalmology
University of Pennsylvania
Philadelphia, Pennsylvania
E-mail address: myanoff4@gmail.com
Like most children growing up, I did not have a strong sense of my father’s day-to-
day life. I knew that he worked long hours. I knew that he often went in on
weekends to see patients. I knew that he often brought home charts for dicta-
tions, slides to review, and surgical videos. He would have the videos playing
while we worked out in the evening (my siblings and I all knew the steps of
cataract surgery before we had finished high school). As I got older, I came to
appreciate that he did this because he loved what he was doing.
Dad always wanted everyone around him to be happy. For myself and my sib-
lings, he wanted us to find something we enjoyed doing, something that we
would want to do every day, and then strive to be the best at it that we could. He
never made any effort to push me into ophthalmology, or even medicine, except
by the example he provided. The joy he had in his work helped me decide my
path. I’m so thankful this gave me the opportunity to work with him at meetings
and on outreach surgical trips.
He always encouraged me to push myself surgically, always saying, ‘‘oh yeah,
you have the skills to do that,’’ when I would discuss tough cases or new
techniques with him. In him, I had the ultimate phone support for these hard
cases and hard decisions. I knew he would answer any time I called with
questions. Many know that this was not a special benefit I had by being family.
He would do that for anyone who called him at any time.
IN MEMORIAM xxxi
He cast an enormous shadow in ophthalmology, one that I long ago accepted I

would never get out of, but I can continue to do what he wanted, which is to try
to make the world around me better and to be the best I can be. The world (and
my personal world) is poorer for his loss, but rich in the legacy he has left for us.
David A. Crandall, MD
Glaucoma Fellowship Director
Henry Ford Health System
Detroit, Michigan
University of Utah
Salt Lake City, Utah
Wayne State University

Salt Lake City, Utah
Advances in Ophthalmology and Optometry 6 (2021) 1–12
Optical Coherence Technology in

Glaucoma Diagnosis
Joseph Sowka, ODa,*, Jessica Steen, ODb, Greg Caldwell, ODc
a
Center for Sight, 1236 Jacaranda Boulevard, Venice, FL 34292, USA; bNova Southeastern Uni-
versity College of Optometry, 3200 South University Drive, Fort Lauderdale, FL 33328, USA;
c
Optometric Education Consultants, 225 Terrace Drive, Lilly, PA 15938, USA
Keywords
Optical coherence tomography Optical coherence tomography angiography
Glaucoma Optic disc Ganglion cell layer Retinal nerve fiber layer
Parapapillary vasculature
Key points
Optical coherence tomography is a common technology in ophthalmologic and
optometric practice.
Optical coherence tomography can objectively image the peripapillary retinal
nerve fiber layer, ganglion cell and inner plexiform layers, and the peripapillary
retinal vasculature.
Abnormalities in the peripapillary retinal nerve fiber layer, macular region, and
peripapillary vasculature have been shown to occur in glaucoma.
Optical coherence tomography provides an objective, quantifiable assessment of
ocular structure that can be used to assist and enhance glaucoma diagnosis.
INTRODUCTION
Glaucoma is a multifactorial disease consisting of characteristic damage to the
optic disc, retinal nerve fiber layer (RNFL), and visual field, additionally
involving numerous risk factors including race, age, family history, and intra-
ocular pressure at levels incompatible with ocular health of the individual [1,2].
Glaucoma diagnosis has traditionally been accomplished through patient risk
factors assessment, optic disc clinical and photographic analysis, as well as auto-
mated threshold perimetric testing. There exist limitations with this traditional
approach, though. Many risk factors are currently unknown, and those that are
*Corresponding author. E-mail address: jwsowka@gmail.com
2452-1760/21/ª 2021 Elsevier Inc. All rights reserved.
2 SOWKA, STEEN, & CALDWELL
known may be improperly assessed and their impact is not universally agreed
upon. Clinical optic disc assessment is a challenging learned technique not
possessed equally among all clinicians, and there exists no normative database
for comparison. Threshold perimetry has an inherent limitation in that it is a
subjective psychophysical test that depends on patient interaction and re-
sponses and the learned skills of the perimetrist. As an adjunct to clinical exam-
ination, spectral domain optical coherence tomography (SD-OCT) technology
is increasingly being integrated into glaucoma evaluation to provide a more
objective method of assessment that may lead to more accurate and earlier
diagnosis [3].
OPTICAL COHERENCE TOMOGRAPHY RETINAL NERVE FIBER

LAYER ANALYSIS IN GLAUCOMA DIAGNOSIS
Optical coherence tomography is an imaging technique based on interferom-
etry, comparing the coherence between near-infrared light reflected off the
retina and light reflected off a reference mirror. The returning light is compared
with the reference light and allows computer reconstruction of the underlying
tissue with quantitative measurements that can be subsequently compared with
a validated, normative database [3].
Peripapillary RNFL analysis is the SD-OCT parameter most commonly
used for glaucoma diagnosis, drawing from measurements of retinal ganglion
cells (RGC) throughout the retina [4]. An inherent limitation of this parameter
is the high degree of physiologic variability between individuals and the subse-
quent difficulty in universally applying a normative database [4]. Macular
thickness and ganglion cell complex assessment is also used to overcome this
limitation because there is less anatomic variability of RGCs in this area and
pathologic defects are more easily differentiated from anatomic variants. In
addition, OCT angiography also has been investigated as another objective
measure because peripapillary loss of retinal capillaries is being recognized as
an early change in glaucoma [5].
There are several clinically available SD-OCT devices that can measure
RGC tissue and assess this information in a variety of parameters that are sub-
sequently measured against individual proprietary normative databases. Most
devices will assess anatomic quadrants of superior retina, inferior retina, nasal
retina, and temporal retina (in some form) as well as look at overall average
RNFL thickness. There may also be subgroup assessment of individual clock
hours or more defined anatomic areas such as inferior temporal or superior
temporal. The parameters assessed are reflections of the branded technology
and vary by device (any informational inclusion or exclusion of branded tech-
nology throughout this article neither implies superiority nor inferiority of any
device.)
In a pooled meta-analysis, Kansal and associates [2] noted that information
for average, superior, and inferior RNFL parameters were better at differenti-
ating glaucoma from normal populations than for nasal and temporal areas:
this was consistent across glaucoma subgroups.
OPTICAL COHERENCE TECHNOLOGY IN GLAUCOMA DIAGNOSIS 3
Dong and colleagues [6] found that current SD-OCT RNFL thickness pa-
rameters have good diagnostic accuracy and help clinicians in determining
severity stages and differentiating normal from glaucomatous eyes in the early
stages. Their assessment was that average circumpapillary RNFL thickness and
inferior sector RNFL thicknesses were the SD-OCT parameters with the best
diagnostic accuracy, followed by superior quadrant thickness values in terms
of sensitivity [6]. Macular parameters were also seen to have increasing impor-
tance in the management of glaucoma. The investigators also found that eval-
uating optic nerve head (ONH) parameters with SD-OCT was useful in
glaucoma diagnosis. Segmentation of the ONH and identification of Bruch
membrane opening allowed for better measurement of the ONH rim and
RNFL thickness. It was concluded that combined assessment of circumpapil-
lary RNFL and macular and ONH parameters is useful for glaucoma diagnosis
at different levels of severity [6].
Mittal and colleagues [7], in evaluating 2 commonly used SD-OCT devices
(Cirrus, Carl Zeiss, Dublin, CA, USA, and Optovue, Freemont, CA, USA)
found that the average RNFL thickness and superior RNFL thickness of
both the devices and inferior ganglion cell complex (GCC) of RTVue device
best differentiated normal subjects from all-stage glaucomatous eyes. For the
Cirrus device, average RNFL thickness and superior RNFL thickness per-
formed better than other parameters in differentiating early glaucoma from
moderate and advanced disease. For the RTVue device, average, superior,
and inferior RNFL thickness and inferior GCC parameters had the highest
discriminating ability in differentiating advanced from early and moderate
glaucoma. The investigators concluded that average RNFL thickness had the
highest ability to distinguish different stages of the disease. No significant differ-
ence was found between either device in different severity levels [7].
While assessing the diagnostic accuracy of SD-OCT in eyes with preperimet-
ric glaucoma, ocular hypertension, and early glaucoma, Aydo g an and associ-
ates [8] found that average RNFL thickness had the greatest accuracy for
preperimetric glaucoma and eyes with early glaucoma. Average RNFL thick-
ness was a risk factor for both conditions. The diagnostic ability of average
RNFL and average GCC thickness increased along with disease severity [8].
In comparing parameters generated by the Cirrus SD-OCT to red-free
photograph-documented RNFL defects (Fig. 1), it was seen that the thickness
map had the best diagnostic value and was superior to quadrant and clock
hour maps in identifying true RNFL defects [9].
A purported benefit of using OCT technology for glaucoma assessment is
the ability to diagnose the disease earlier when compared with automated peri-
metry. In a study group that included 75 eyes of 75 patients suspected of glau-
coma followed as part of the Diagnostic Innovations in Glaucoma study,
researchers found that significant differences were seen in the RNFL as exam-
ined by SD-OCT up to 8 years before development of visual field defects. In
addition, up to 35% of eyes had abnormal average RNFL thickness 4 years
before development of visual field loss and 19% of eyes had abnormal SD-
OCT results 8 years before field loss. The conclusions were that RNFL thick-
ness assessment with SD-OCT was able to detect glaucomatous damage before
the appearance of visual field defects on standard automated perimetry and
that there were significantly large lead times in many subjects [10].
Optical coherence tomography macular analysis in glaucoma diagnosis

SD-OCT evaluation of macular parameters is complementary to RNFL anal-
ysis in the diagnosis of glaucoma. The macula contains approximately 50%
of the eye’s RGCs arranged in a multilayered pattern, making this area a theo-
retically more sensitive location to determine glaucomatous damage when
compared with evaluation of the smaller diameter RGC axons, which make
up the peripapillary RNFL [11]. SD-OCT evaluation of the macular region
does not directly image RGCs, but instead allows segmentation and thickness
measurement of retinal layers where RGC cell bodies (ganglion cell layer
[GCL]), dendrites (inner plexiform layer), and axons (nerve fiber layer) are
located [12,13].
Instrument proprietary software protocols differ in their segmentation of
retinal layers used for the evaluation of macular parameters in glaucoma and
are therefore not interchangeable between devices. The most common proto-
cols consist of evaluation of the ganglion cell layer and inner plexiform layer
(GCIPL) or the GCC, which is composed of the RNFL, GCL, and inner plex-
iform layer [12].
The Cirrus ganglion cell analysis (Fig. 2) report includes thickness maps (see
Fig. 2A) and deviation maps (see Fig. 2B) of the GCIPL in each eye and hor-
izontal B-scan with superimposed delineation of the outer boundary of the
GCL and IPL (see Fig. 2C). Color-coded sectoral GCIPL thickness (see
Fig. 2D) and summary table (see Fig. 2E), which includes the average and min-
imal GCL and IPL thickness, are provided, which includes comparison with an
age-matched normative database.
Macular parameters are reproducible and have a similar diagnostic ability to
RNFL parameters in the detection of glaucoma [14,15]. Information deter-
mined by each imaging strategy is complementary, as RNFL parameters
more easily detect damage outside of the macular region, where GCIPL or
GCC measurements may be better at detecting glaucomatous damage within
the macular region [16].
Macular damage in glaucoma is typically arcuate in pattern, similar to RNFL
thinning, and is commonly associated with RNFL abnormalities in the same
hemifield [15]. Owing to the anatomic asymmetry of the projection of RGC
axons in the retina toward the optic disc introduced by the horizontal angular
difference between the center of the fovea and the optic disc center, inferior
glaucomatous RNFL thinning has a higher propensity to cause detectible mac-
ular ganglion cell damage when compared with superior RNFL thinning
[12,16].
Macular parameters are less impacted by structural variation between indi-
viduals and may provide an advantage in detection of glaucoma over RNFL
Fig. 1. Cirrus SD-OCT Optic Disc Cube analysis of the optic nerve head and peripapillary
RNFL. Statistically significant departures from the normative database on the RNFL deviation
map, RNFL quadrants, and RNFL clock hours parameters are notated in red and green pixels
and color codes.
evaluation in highly myopic eyes with increased axial length, myopic disc tilt,
vessel deflection, and large peripapillary crescent [17].
In eyes with macular pathology such as epiretinal membrane, diabetic mac-
ulopathy, macular hole, or macular drusen careful evaluation of the GCIPL or
GCC and direct evaluation of the OCT B-scan should be performed for differ-
entiation of glaucomatous from nonglaucomatous damage and potential errors
in automated segmentation [18]. In addition, GCIPL or GCC damage, which
respects the vertical midline, should be suspicious for a postchiasmal event
Fig. 2. Cirrus report of the ganglion cell analysis in primary open-angle glaucoma. (A) Thick-
ness map. (B) Deviation Map. (C) Horizontal B scan. Note abrupt delineation along the hor-
izontal raphe on the thickness map and the statistically significant departure from the
normative database on the OD deviation map and OD sectors parameters.
rather than glaucoma [18]. The utility of evaluation of macular parameters by

OCT in glaucoma may be impacted by retinal and postchiasmal pathology.
When using SD-OCT for either RNFL or macular assessment, one must be
aware of the possibility of obtaining false-positive and false-negative results. In
one study involving Cirrus SD-OCT, 149 eyes from 77 healthy participants
were imaged and it was seen that the false-positive rate was as high as
26.2%. Factors determined to be involved in false-positive assessments included
longer axial length and smaller disc area [19]. Issues such as poor image quality
and lower signal strength can contribute to a false-positive assessment in
normal eyes. The factors that significantly affected the false-positive RNFL co-
lor code results using SD-OCT were axial length and disc area, which may
significantly affect the specificity of SD-OCT. Therefore, axial length and disc
area should be considered during RNFL thickness profile analysis.
Although false-positive SD-OCT results may lead to overdiagnosis and un-
necessary treatment, more concerning would be false-negative results wherein
analysis may indicate an abnormal eye falling into the normative data range
and incorrectly being assessed as normal. Features that may contribute to a
false-negative assessment include acquisition errors and erroneous segmenta-
tion of tissues by the device, allowing the results to fall within the normative
database [20]. When interpreting any global sector analysis, it is imperative
to remember that substantial amounts of anatomic areas are being assessed
to give an overall value. When this happens, a small RNFL defect may be pre-
sent but the area may result in an overall value that falls within a device’s
normative database [21]. In addition, true RNFL defects located at the edge
of inferior and superior temporal zones may occur in areas that are naturally
anatomically thin and fall within a normative database, subsequently being
inappropriately classified as normal [21].
OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN

GLAUCOMA DIAGNOSIS
The contributory role of vascular abnormality to disease development and pro-
gression in glaucoma has received renewed interest with the commercial avail-
ability of optical coherence tomographic angiography (OCTA). OCTA is a
repeatable and reproducible noninvasive imaging technology that can be
applied to evaluate the microvasculature of the peripapillary and macular re-
gion as a complementary tool for the diagnosis and detection of progression
in glaucoma.
OCTA technology uses motion contrast to detect movement of erythrocytes
through the microvasculature of the eye including retinal and small choroidal
vessels to construct multilayered constructs of the vasculature [22,23]. Fluctua-
tions in phase or intensity of sequential OCT B-scans performed in the same
retinal location over very rapid time periods are detected and images are decor-
related to detect movement of red blood cells through retinal and choroidal
vessels [22,23].
Three-dimensional OCTA images are reduced to two-dimensional reports,
which include en face maps of retinal and choroidal microvasculature indicated
by a bright signal. Dark areas on the report represent areas of no detectable
blood flow. Parameters that are included on the report vary, but most
commonly include vessel density (percentage of pixels with perfused vascula-
ture in a measured area) and may include perfusion density (total area of
perfused vasculature in a measured area), flow index (average flow signal in
a measured area), and area measurement of the foveal avascular zone.
Superficial retinal capillaries are branches of the central retinal artery,
whereas the short posterior ciliary arteries supply deeper retinal capillaries,
choroidal vessels, and the prelaminar and laminar regions of the optic nerve
[24]. The anatomic understanding of vascular supply to the RNFL of the
peripapillary region, GCL of the macular region, and the laminar and prelami-
nar regions of the optic nerve make evaluation of both superficial and deep
vascular parameters potentially beneficial in the diagnosis of glaucoma.
The superficial capillary plexus perfuses the RNFL in the peripapillary re-
gion and the GCL in the macula and seems to be preferentially damaged in
glaucomatous eyes as detected by OCTA [24–26]. Localized loss of the chorio-
capillaris in the focal regions of peripapillary atrophy may also be detected in
glaucomatous eyes [24,27]. Clinical application of imaging of deep vasculature
remains limited with commercially available systems owing to susceptibility to
projection artifacts [23,26].
Reduced vessel density detectable by OCTA correlates with level of glau-
comatous damage (Fig. 3) [23,28–30]. Vessel density decreases with advancing
disease [24,25,27,29] and is highly correlated with visual field parameter [23,28]
and OCT RNFL and GCC parameters [27]. Reduced vessel density parame-
ters detected by OCTA have been determined to be an indicator of disease pro-
gression [24,27,29]. However, in the detection of early glaucoma, RNFL, GCC
and GCIPL parameters seem to have improved diagnostic ability when
compared with OCTA parameters alone (Fig. 4) [28,30].
Evaluation of vessel density parameters for detection of structural progres-
sion may be especially useful for eyes with advanced disease or eyes with
high myopia [31,32]. In advanced disease, a measurement floor is reached
when RNFL, GCC, and GCIPL parameters do not change with further disease
progression; however, no detectable floor has been determined for macular
vessel density parameters on OCTA [31].
The complexity of neurovascular coupling where neuronal activity and un-
derlying systemic factors may regulate local blood flow makes it challenging to
evaluate whether microvascular changes cause RGC damage or if reduction in
vessel density is a result of RGC damage owing to lower metabolic demand of
dysfunctional RGCs [25–27,29].
Challenges in the application of OCTA parameters to clinical care include
difficulty interpreting images because of the presence of artifacts [23]. OCTA
is based on the detection of motion, which makes eye tracking software and
image processing algorithms necessary to remove movement artifacts created
by saccades and ocular drift during image acquisition [23]. Projection artifacts,
where the image of vessels in the superficial retina casts a shadow on deeper
retinal layers resulting in duplication of the superficial capillary plexus with
the appearance of detectable flow in outer retinal layers, can limit the utility
of information in the deeper retinal and choroidal microvasculaure [23,26].
Systemic conditions that reduce ocular blood flow including hypertension
and diabetes mellitus also reduce vessel density parameters on OCTA in non-
glaucomatous eyes, and this must be considered during interpretation [33].
The lower and upper thresholds for detection of movement of red blood
cells are parameters that are not adjustable on commercially available systems
but are relevant to understand the limitations in determination of flow on
OCTA. Thresholds for detection of movement are determined with the
Fig. 3. Compromised RNFL and radial peripapillary capillaries (RPC) from early glaucoma in
the right eye. The hemifield and quadrant analysis are showing compromised RNFL inferiorly
with thinner micron measurements (95 vs 73; 118 vs 77). The RNFL thickness maps are
showing RNFL dropout inferiorly (bottom middle). The adjacent vessel density map (measured
in percentage) reveals a wedge defect in the inferior temporal region corresponding to that
seen in the RPC image. The hemifield is intact, and quadrant analysis is showing mild decrease
in RPC percent (right side). (From Caldwell, G. OCT Angiography for Glaucoma. Modern
Optometry. October 2019. Available at: https://modernod.com/articles/2019-oct/oct-angi-
ography-for-glaucoma?c4src¼article:infinite-scroll. Accessed January 2, 2021).
Fig. 4. This is a montage image of the right eye with primary open-angle glaucoma showing
the capillary dropout in the inferior temporal region; it is a classical wedge defect. Notice how
it spares the macula. (From Caldwell, G. OCT angiography for glaucoma. Modern Optometry.
October 2019. Available at: https://modernod.com/articles/2019-oct/oct-angiography-for-
glaucoma?c4src¼article:infinite-scroll. Accessed January 2, 2021).
intention to maximize the utility of the information provided, to limit signal

noise artifacts, and keep image acquisition time similar to that of a typical
SD-OCT scan [22]. As erythrocyte flow may be expected to slow before com-
plete loss of the capillary beds, capillary dropout or reduced vessel density may
be falsely determined by OCTA when in fact erythrocyte movement is present
in vessels, although at a speed that it is less than the minimum threshold for
detection [22].
Early detection and diagnosis of glaucoma requires an assessment of risk fac-
tors, clinical examination including optic disc and RNFL analysis, and func-
tional evaluation with threshold perimetry. SD-OCT analysis of the
peripapillary RNFL, macular GCC and GCIPL, and angiographic assessment
of the optic disc and RNFL blood supply lend an objective and quantifiable
evaluation of anatomic structure that has been shown to be affected by glau-
coma, thus enhancing our clinical ability to detect disease. Potential artifacts
that influence image capture and data interpretation must always be borne in
mind.
CLINICS CARE POINTS
Peripapillary RNFL evaluation is a commonly accepted method of assessing pa-

tients for glaucoma.
Ganglion cell complex and ganglion cell/inner plexiform layer analysis has
been shown to be sensitive to changes occurring from glaucoma due to a
more regular anatomy than that seen in the peripapillary RNFL.
Concurrent maculopathies have the potential to render optical coherence tomo-
graphic measurements of the ganglion cell complex and ganglion cell/inner
plexiform layer inaccurate and must be identified and considered when
applying this information in glaucoma evaluation.
There is increasing evidence to support optical coherence tomographic angiog-
raphy changes in the peripapillary vasculature as valuable diagnostic informa-
tion in glaucoma evaluation.
There exists the potential for false-positive and false-negative assessments from
optical coherence tomography and must be considered when interpreting these
evaluations in glaucoma diagnosis.
Optical coherence tomography is a valuable, objective assessment of structure
that can be used adjunctively with clinical evaluation, functional visual field
testing, and assessment of additional risk factors in glaucoma diagnosis.
Disclosure
J. Sowka: No financial disclosures; J. Steen: No financial disclosures; G. Cald-
well: Advisory Board and Speaker Bureau: Optovue.
References
[1] Quigley HA. Glaucoma. Lancet 2011;377:1367–77.
[2] Kansal V, Armstrong JJ, Pintwala R, et al. Optical coherence tomography for glaucoma diag-
nosis: An evidence based meta-analysis. PLoS One 2018;13(1):e0190621.
[3] Popescu DP, Choo-Smith LP, Flueraru C, et al. Optical coherence tomography: fundamental
principles, instrumental designs and biomedical applications. Biophys Rev 2011;3(3):155.
[4] Bussel II, Wollstein G, Schuman JS. OCT for glaucoma diagnosis, screening and detection
of glaucoma progression. Br J Ophthalmol 2014;98:ii15–9.
[5] Van Melkebeke L, Barbosa-Breda J, Huygens M, et al. Optical coherence tomography angi-
ography in glaucoma: a review. Ophthalmic Res 2018;60(3):139–51.
[6] Dong ZM, Wollstein G, Schuman JS. Clinical utility of optical coherence tomography in
glaucoma. Invest Ophthalmol Vis Sci 2016;57(9):OCT556–7.
[7] Mittal D, Dubey S, Gandhi M, et al. Discriminating ability of cirrus and RTVue optical coher-
ence tomography in different stages of glaucoma. Indian J Ophthalmol 2018;66(5):
675–80.
[8] Aydo gan T, _Ilkay B, Akçay S, et al. Evaluation of spectral domain optical coherence tomog-
raphy parameters in ocular hypertension, preperimetric, and early glaucoma Indian.
J Ophthalmol 2017;65(11):1143–50.
[9] Hwang YH, Kim YY, Kim HK, et al. Ability of cirrus high-definition spectral-domain optical
coherence tomography clock-hour, deviation, and thickness maps in detecting photo-
graphic retinal nerve fiber layer abnormalities. Ophthalmology 2013;120(7):1380–7.
[10] Kuang T, Zhang C, Zangwill LM, et al. Estimating the lead time gained by optical coherence
tomography in detecting glaucoma before development of visual field defects. Ophthal-
mology 2015;122(10):2002–9.
[11] Curcio CA, Allen KA. Topography of ganglion cells in human retina. J Comp Neurol
1990;300:5–25.
[12] Kim KE, Park KH. Macular imaging by optical coherence tomography in the diagnosis and
management of glaucoma. Br J Ophthalmol 2018;102(6):718–24.
[13] Tan O, Li G, Lu AT, et al, Advanced Imaging for Glaucoma Study Group. Mapping of mac-
ular substructures with optical coherence tomography for glaucoma diagnosis. Ophthal-
mology 2008;115:949–56.
[14] Mwanza JC, Oakley JD, Budenz DL, et al. Macular ganglion cell-inner plexiform layer: auto-
mated detection and thickness reproducibility with spectral domain-optical coherence to-
mography in glaucoma. Invest Ophthalmol Vis Sci 2011;52:8323–9.
[15] Oddone F, Lucenteforte E, Michelessi M, et al. Macular versus retinal nerve fiber layer pa-
rameters for diagnosing manifest glaucoma: a systematic review of diagnostic accuracy
studies. Ophthalmology 2016;123:939–49.
[16] Hood DC, Raza AS, de Moraes CG, et al. Glaucomatous damage of the macula. Prog Retin
Eye Res 2013;32:1–21.
[17] Seol BR, Jeoung JW, Park KH. Glaucoma detection ability of macular ganglion cell-inner
plexiform layer thickness in myopic preperimetric glaucoma. Invest Ophthalmol Vis Sci
2015;56:8306–13.
[18] Hwang YH. Patterns of macular ganglion cell abnormalities in various ocular conditions.
Invest Ophthalmol Vis Sci 2014;55:3995–6.
[19] Kim NR, Lim H, Kim JH, et al. Factors associated with false positives in retinal nerve fiber
layer color codes from spectral-domain optical coherence tomography. Ophthalmology
2011;118(9):1774–81.
[20] Hardin JS, Taibbi G, Nelson SC, et al. Factors affecting cirrus-HD OCT optic disc scan qual-
ity: a review with case examples. J Ophthalmol 2015;2015:746150.
[21] Sayed MS, Margolis M, Lee RK. Green disease in optical coherence tomography diagnosis
of glaucoma. Curr Opin Ophthalmol 2017;28(2):139–53.
[22] Wang RK, Jacques SL, Ma Z, et al. Three dimensional optical angiography. Opt Express
2007;15(7):4083–97.
[23] Jia Y, Wei E, Wang X, et al. Optical coherence tomography angiography of optic disc perfu-
sion in glaucoma. Ophthalmology 2014;121:1322–32.
[24] Rao HL, Srinivasan T, Pradhan ZS, et al. Optical coherence tomography angiography and
visual field progression in primary angle closure glaucoma. J Glaucoma 2021;30(3):
e61–7.
[25] Shoji T, Zangwill LM, Akagi T, et al. Progressive macula vessel density loss in primary open-
angle glaucoma: a longitudinal study. Am J Ophthalmol 2017;182:107–17.
[26] Milani P, Bochicchio S, Urbini LE, et al. Diurnal measurements of macular thickness and
vessel density on OCT angiography in healthy eyes and those with ocular hypertension
and glaucoma. J Glaucoma 2020;29:918–25.
[27] Lin S, Cheng H, Zhang S, et al. Parapapillary choroidal microvasculature dropout is asso-
ciated with the decrease in retinal nerve fiber layer thickness: a prospective study. Invest
Ophthalmol Vis Sci 2019;60:838–42.
[28] Liu L, Jia Y, Takusagawa HL, et al. Optical coherence tomography angiography of the peri-
papillary retina in glaucoma. JAMA Ophthalmol 2015;133:1045–52.
[29] Moghimi S, Zangwill LM, Penteado RC, et al. Macular and optic nerve head vessel density and
progressive retinal nerve fiber layer loss in glaucoma. Ophthalmology 2018;125:1720–8.
[30] Rao HL, Pradhan ZS, Weinreb RN, et al. A comparison of the diagnostic ability of vessel den-
sity and structural measurements of optical coherence tomography in primary open angle
glaucoma. PLoS One 2017;12(3):e0173930.
[31] Moghimi S, Bowd C, Zangwill LM, et al. Measurement floors and dynamic ranges of OCT
and OCT angiography in glaucoma. Ophthalmology 2019;126:980–8.
[32] Shin JW, Kwon J, Lee J, et al. Relationship between vessel density and visual field sensitivity
in glaucomatous eyes with high myopia. Br J Ophthalmol 2019;103:585–91.
[33] Rao HL, Pradhan ZS, Weinreb RN, et al. Determinants of peripapillary and macular vessel
densities measured by optical coherence tomography angiography in normal eyes.
J Glaucoma 2017;26(5):491–7.
NEUROANATOMICAL STRUCTURES 53
[23] Lueder GT. Orbital causes of incomitant strabismus. Middle East Afr J Ophthalmol
2015;22(3):286–91.
[24] Paduca A, Arnaut O, Beschieru E, et al. Shared decision making and patients satisfaction
with strabismus care—a pilot study. BMC Med Inform Decis Mak 21, 109 (2021).
[25] Li B, Sharan S. Post-operative analysis of pediatric esotropia associated with high hyperme-
tropia. BMC Ophthalmol 2019;19(1):140.
[26] Bruenech JR & Kjellevold Haugen IB. Neuromuscular principles in the visual system and their
potential role in visual discomfort. In: Dainoff M.J. (eds.). Ergonomics and health aspects of
work with computers. EHAWC 2007. Lecture Notes in Computer Science, vol. 4566.
Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-73333-1_2
[27] Yammouni R, Evans BJ. An investigation of low power convex lenses (adds) for eyestrain in
the digital age (CLEDA). J Optom 2020;13(3):198–209.
[28] Lin TW, Tsai SF, Kuo YM. Physical exercise enhances neuroplasticity and delays Alzheimer’s
disease. Brain Plast 2018;4(1):95–110.
[29] Fischetti F, Cataldi S, Giunto A, et al. Effect of home-based oculomotor exercises on postural
stability in healthy female adults. J Hum Sport Exerc 2020;15(3):653–60.
[30] De Zeeuw CI, Ten Brinke MM. Motor learning and the cerebellum. Cold Spring Harb Per-
spect Biol 2015;7(9):a021683.
[31] Rizzo JR, Fung JK, Hosseini M, et al. Eye control deficits coupled to hand control deficits: eye-
hand incoordination in chronic cerebral injury. Front Neurol 2017;8:330.
[32] Matsuo T, Narita A, Senda M, et al. Body sway increases immediately after strabismus sur-
gery. Acta Med Okayama 2006;60(1):13–24.
[33] Gorman GS, Taylor RW. Mitochondrial DNA abnormalities in ophthalmological disease.
Saudi J Ophthalmol 2011;25(4); https://doi.org/10.1016/j.sjopt.2011.02.002.
[34] Blumer R, Streicher J, Davis-López MA, et al. Palisade endings of extraocular muscles
develop postnatally following different time courses. Invest Ophthalmol Vis Sci
2017;58(12):5105–21.
[35] Paduca A, Bruenech JR, Lundmark P, et al. Can horizontal rectus muscle resection in stra-
bismus surgery affect the proprioception? Black Sea Ophthalmological Society – BSOS Tbi-
lisi International Ophthalmology Conference - TIOC, proceedings December 19 – 20,
2020 Tbilisi, Georgia.
[36] Chen YW, Lin SA, Lin PW, et al. The difference of surgical outcomes between manifest exo-
tropia and esotropia. Int Ophthalmol 2019;39(7):1427–36.
[37] Steinbach MJ, Smith DR. Spatial localization after strabismus surgery: evidence for inflow.
Science 1981;213(4514):1407–9.
Advances in Ophthalmology and Optometry 6 (2021) 13–38
An Update on
Neurodegenerative Disease for
Eye Care Providers
Kelly A. Malloy, OD*, Erin M. Draper, OD,
Ashley Kay Maglione, OD, Tina Zeng, OD,
Elizabeth Marunde, OD
The Eye Institute of the Pennsylvania College of Optometry at Salus Univeristy, 1200 West
Godfrey Avenue, Philadelphia, PA 19141, USA
Keywords
Neurodegenerative disease (NDD) Alzheimer disease (AD)
Parkinson disease (PD) Progressive supranuclear palsy (PSP)
Multiple system atrophy (MSA) Dementia with Lewy bodies (DLB)
Corticobasal degeneration (CBD) Posterior cortical atrophy (PCA)
Key points
Despite varied underlying pathologic conditions, visual and ocular signs/symp-
toms are prevalent in all neurodegenerative diseases (NDD). These ocular find-
ings may help differentiate among neurodegenerative processes.
All NDDs cause retinal thinning, but patterns and severity differ. Alzheimer dis-
ease (AD) and multiple system atrophy affect the more peripheral superior retina,
whereas Parkinson disease (PD) affects the papillomacular bundle. Corre-
sponding visual field defects can occur.
Patients with NDD present with reading difficulty. A common contributing factor
in PD is convergence insufficiency and impaired contrast sensitivity.
Continued
INTRODUCTION: NEURODEGENERATIVE DISEASE AND THE

EYE
Neurodegenerative disease definition
Neurodegenerative diseases (NDD) are conditions in which the cells of the cen-
tral nervous system atrophy or do not function properly. These conditions
tend to progressively worsen, and effective disease-modifying agents are still
*Corresponding author. E-mail address: kmalloy@salus.edu
2452-1760/21/ª 2021 Elsevier Inc. All rights reserved.
14 MALLOY, DRAPER, MAGLIONE, ET AL
Continued
Eye movement disorders are prevalent in NDD. Markedly reduced vertical eye
movements or supranuclear gaze palsy suggests progressive supranuclear palsy.
Visual hallucinations are most common in dementia with Lewy bodies (DLB). Early and
frequent occurrence of hallucinations helps distinguish DLB from AD, both of which
have early cognitive deficits.
elusive [1]. Many diseases that may fall under the umbrella of NDD are asso-
ciated with dementia or advanced age. Other NDDs, such as multiple sclerosis
and glaucoma, do not necessarily have these associations. The focus of this
article is on those NDDs with advanced age and dementia associations, specif-
ically, Alzheimer disease (AD) and the parkinsonian syndromes. Posterior
cortical atrophy (PCA) is also included, which can be a variant of AD [2].
The specific parkinsonian syndromes include the typical Parkinson disease
(PD), and the atypical: progressive supranuclear palsy (PSP), dementia with
Lewy bodies (DLB), multiple system atrophy (MSA), and corticobasal degen-
eration (CBD) [3]. Clinical characteristics of AD and typical PD are listed in
Table 1. Additional distinguishing features of the atypical parkinsonian syn-
dromes are listed in Table 2.
Varied pathophysiology of neurodegenerative diseases

The various NDDs associated with dementia have several different potential
underlying pathologic conditions, but all include abnormal protein deposits
in pathologic brain tissue, which are associated with the disease mechanism.
Interestingly, not all the parkinsonian syndromes share a common underlying
pathologic condition, and some of them actually share an underlying patho-
logic accumulation of tau with AD (Table 3) [3].
Prevalent visual and ocular associations of neurodegenerative disease

Despite varied underlying pathologic conditions and clinical presentations
among the NDD, a commonality is that ophthalmologic signs and symptoms
are prevalent yet often underreported by patients and overlooked by eye
Table 1
Clinical characteristics of Alzheimer disease versus Parkinson disease
Alzheimer disease Parkinson disease
Progressive memory impairment Bradykinesia (slowness of movement)
Impaired executive function Rigidity and/or resting tremor
(decision making and multitasking)
Behavioral changes (irritability and disengagement) Postural instability (later in disease)
Circadian rhythm sleep disturbances Responds to dopaminergic therapy
Olfactory dysfunction Olfactory dysfunction
Data from Refs. [1–3]
UPDATE ON NEURODEGENERATIVE DISEASE
Table 2
Distinguishing systemic features of atypical parkinsonian syndromes
Lewy body dementia Multiple system atrophy Progressive supranuclear palsy Corticobasal degeneration
Dementia with visual Autonomic dysfunction early Impaired vertical gazes Asymmetric limb involvement
hallucinations early Orthostatic hypotension (falls) Postural instability: prone to early in disease
in disease Loss of bladder control backwards falls Impaired cognition early
Fluctuating cognition Cognitive function well preserved Mild executive dysfunction Profound rigidity
REM sleep behavior Rapid progression (shorter life span) Facial dystonia Dysarthria
disorder MSA-P subtype (predominant MSA-C subtype Micrographia Impaired pursuits and saccades
parkinsonism) (predominant Ideomotor apraxia (inability to
cerebellar ataxia) imitate gestures)
Motor dysfunction similar to PD Gait and limb ataxia
Dysarthria
Gaze-evoked nystagmus
Ocular dysmetria
15
16 MALLOY, DRAPER, MAGLIONE, ET AL
care providers (ECPs) [5]. Although the visual and ocular findings associated
with NDD are not always specific for a particular disease, unique clinical find-
ings may help differentiate one neurodegenerative process from another.
Role of eye care providers in neurodegenerative disease
If properly educated on the potential clinical manifestations of NDD, ECPs can
play a vital role in identification and management. Collaboration of ECPs with
neurologists in the diagnosis and management of NDD can vastly improve the
quality of life of patients. The following paragraphs focus on the current liter-
ature regarding the visual and ocular manifestations of AD and parkinsonism
to help ECPs become more familiar with how and why these conditions may
manifest on an eye examination.
VISUAL AND OCULAR ASSOCIATIONS OF

NEURODEGENERATIVE DISEASE
Eyelid function in neurodegenerative disease
Eyelid abnormalities are frequently one of the early signs of an NDD (Table 4).
Possible abnormalities include change in palpebral aperture, blink reflex, and
blink rate.
Eyelid retraction
It is important to examine palpebral apertures in NDD, specifically looking for
eyelid retraction. Visible sclera above the superior limbus, consistent with
eyelid retraction, is prominent in PSP but rare in PD. In PSP, it is this eyelid
abnormality, in addition to ocular motor abnormalities, that are described in
later discussion, which will help to differentiate it from other conditions,
such as PD and MSA [6,7].
Apraxia of eyelid opening
The inability to initiate voluntary opening of the eyelid following a period of
eyelid closure is known as eyelid apraxia and can be seen in some parkinsonian
syndromes, particularly PSP [6]. The apraxia may occur upon awakening from
sleep or a nap and thus may not be evident on clinical examination. Therefore,
it is important for ECPs to inquire about the need for patients to have to manu-
ally lift their eyelids in order to open their eyes. Clinicians should take care to
not mistake ptosis for apraxia of eyelid opening. Although ptosis may be pre-
sent in early-onset PD, it is not a typical presentation of PD or other acquired
NDDs [7].
Blepharospasm and reflex blepharospasm associated with bright stimulus
Blepharospasm, involuntary forceful eyelid closure owing to contraction of the
orbicularis oculi, is often associated with apraxia of eyelid opening in NDD.
Blepharospasm is also more common in atypical PD, particularly PSP and
MSA [7,8]. Reflex blepharospasm, which occurs in response to a strong audi-
tory or visual stimulus, has been suggested as a unique feature of atypical Par-
kinson syndromes, particularly PSP [8]. On clinical examination, a
distinguishing feature of PSP patients may be their response to light stimulus
Table 3
Characteristic micropathology
Alzheimer Parkinsonian syndromes
AD PD DLB MSA PSP CBD
Extracellular amyloid-b Lewy bodies Lewy bodies Glial (oligodendroglia) Tau inclusions Intracellular
(Ab) plaques (intracytoplasmic (intracytoplasmic cytoplasmic inclusions in neurons aggregation
Intracellular neurofibrillary neuronal inclusions made neuronal inclusion may contain ⍺-synuclein (neurofibrillary of tau
tangles (composed of up in large part of made up of and tau tangles) Ballooned
tau) ⍺-synuclein) ⍺-synuclein) Myelin degeneration Tau-positive neurons
Neuritic plaques from Higher percentage of Lewy Found throughout Neuronal loss in putamen, astrocytes Asymmetric
neuronal injury bodies in substantia nigra neocortex, caudate nucleus, SN, (tufted frontoparietal
Can have Lewy bodies (SN) and locus coeruleus brainstem nuclei, locus coeruleus, pontine astrocytes) atrophy
Significant neuronal loss in and limbic nuclei, inferior olivary Neuronal
the SN pars compacta structures nucleus, Purkinje cells of loss of the
and pontine locus Also pathologic cerebellum, anteroposterior
coeruleus condition similar intermediolateral cell midbrain
to AD columns
17
18
Table 4
Visual and ocular associations of neurodegenerative diseases
Alzheimer Parkinsonian syndromes
AD PD DLB MSA PSP CBD
Eyelid Ptosis rare Blepharospasm Eyelid retraction Apraxia of
Apraxia of eyelid opening Apraxia of eyelid Blepharospasm eyelid opening
(later in disease course) opening Apraxia of eyelid
opening (early
in disease
course)
Cornea/ Increased blink Decreased spontaneous Delayed and Very decreased Extremely
dry eye rate early in blink sustained blink spontaneous blink decreased
disease course Increased reflex blink reflex spontaneous
Decrease in corneal Reduced tear volume blink
sensitivity
Reduced tear
MALLOY, DRAPER, MAGLIONE, ET AL

break-up time and
decreased Schirmer
test values
Cataracts Equatorial Increased nuclear sclerotic
supranuclear cataract frequency
cataract More prominent posterior
subcapsular cataract
Retina Ab plaque deposition p-syn deposition in retinal p-syn deposition RNFL thinning RNFL thinning at RNFL thinning
concentrated in ganglion cells in retinal of superior peripapillary superior and
superior quadrant RNFL thinning at ganglion cells quadrant region temporal
RNFL thinning in papillomacular bundle Thinning of ONL; thickening of
superior retina Reduced blood supply of thickening ONL
Reduced blood superficial vascular of OPL
plexus
supply of deep
vascular plexus
Ocular Saccadic intrusions Saccadic intrusions Increased Hypometric Vertical gaze Increased
motility Decreased saccadic Hypometric saccades saccadic saccades paresis saccadic latency
velocity especially vertically latency Abnormal pursuits Saccadic Blinks may be
Hypometric saccades No blink suppression during Ocular misalignment intrusions used to initiate
Increased latency to saccades Nystagmus in MSA-C Large square saccades
initiate saccades Impaired pursuits with cog- Decreased vestibular-ocular wave jerks Impaired smooth
High errors on wheel (jerky) movements reflex Hypometric pursuits
antisaccades Convergence insufficiency suppression saccades
Impaired smooth (early stage)
pursuit Slow saccades,
more so
vertically (later
stage)
19
Another random document with
no related content on Scribd:
The British Minister closes his communication to Lord
Pauncefote as follows: "I request that your excellency will
explain to the Secretary of State the reasons, as set forth in
this dispatch, why His Majesty's government feel unable to
accept the convention in the shape presented to them by the
American Ambassador, and why they prefer, as matters stand at
present, to retain unmodified the provisions of the
Clayton-Bulwer Treaty. His Majesty's government have
throughout these negotiations given evidence of their earnest
desire to meet the views of the United States.
{71}
They would on this occasion have been ready to consider in a
friendly spirit any amendments of the convention not
inconsistent with the principles accepted by both governments
which the government of the United States might have desired
to propose, and they would sincerely regret a failure to come
to an amicable understanding in regard to this important
subject."
CANAL, The Kaiser Wilhelm Ship.
See (in this volume)

GERMANY: A. D. 1895 (JUNE).
CANAL, Manchester Ship.
On the 1st of January, 1894, the ship canal from Liverpool to

Manchester, which had been ten years in course of construction
and cost £15,000,000, was formally opened, by a long
procession of steamers, which traversed it in four and a half
hours.
CANAL: The Rhine-Elbe, the Dortmund-Rhine,

and other Prussian projects.

GERMANY: A. D. 1890 (AUGUST);
and 1901 (JANUARY).
CANDIA: A. D. 1898 (September).

Fresh outbreak.

TURKEY: A. D. 1897-1899.
CANEA: Christian and Moslem conflicts at.

TURKEY: A. D. 1897 (FEBRUARY-MARCH).
CANOVAS DEL CASTILLO, Antonio:

Formation of Spanish Cabinet.

SPAIN: A. D. 1895-1896.
CANOVAS DEL CASTILLO, Antonio:

Assassination.

SPAIN: A. D. 1897 (AUGUST-OCTOBER).
CANTEEN, The Army.

UNITED STATES OF AMERICA:
A. D. 1900 (MAY-NOVEMBER), THE PROHIBITION PARTY;
and 1901 (FEBRUARY).
CANTON: A. D. 1894.
The Bubonic Plague.

PLAGUE.
CANTON: A. D. 1899.
Increasing piracy in the river.

CHINA: A. D. 1899.
CAPE COLONY.

SOUTH AFRICA (CAPE COLONY).
CAPE NOME, Gold discovery at.

ALASKA: A. D. 1898-1899.
CAPE SAN JUAN, Engagement at.

UNITED STATES OF AMERICA:
A. D. 1898 (JULY-AUGUST: PORTO RICO).
CARNEGIE, Andrew: Gifts and offers to public libraries.

LIBRARIES;
and LIBRARY, NEW YORK PUBLIC.
CARNEGIE COMPANY, Sale of the interests of the.

TRUSTS: UNITED STATES.
CAROLINE and MARIANNE ISLANDS:

Their sale by Spain to Germany.
By a treaty concluded in February, 1899, the Caroline Islands,
the Western Carolines or Pelew Islands, and the Marianne or
Ladrone Islands (excepting Guam), were sold by Spain to
Germany for 25,000,000 pesetas—the peseta being equivalent to
a fraction less than twenty cents. Spain reserved the right to
establish and maintain naval and mercantile stations in the
islands, and to retain them in case of war. Spanish trade and
privileges for the Spanish religious orders are guaranteed
against interference.
CARROLL, Henry K.:

Report on Porto Rico.

PORTO RICO: A. D. 1898-1899 (AUGUST-JULY).
CASSATION, The Court of.

The French Court of Appeals.

FRANCE: A. D. 1897-1899.
CASTILLO, Pedro Lopez de:

Letter to the soldiers of the American army.
See UNITED STATES OF AMERICA: A. D. 1898 (AUGUST 21).
CATALOGUE, International, of Scientific Literature.

SCIENCE, RECENT: SCIENTIFIC LITERATURE.
CATALONIA: Independent aspirations in.

SPAIN: A. D. 1900 (OCTOBER-NOVEMBER).
CATASTROPHES, Natural: A. D. 1894.
Late in December, the orange groves of Florida were mostly

destroyed or seriously injured by the severest frost known in
more than half a century.
CATASTROPHES, Natural: 1896.
On January 8, a severe earthquake shock was felt at Meshed,

Kelat and other Persian towns, causing over 1,100 deaths.
In March, the Tigris overflowed its banks, causing

incalculable loss of life and property in Mesopotamia.
A succession of earthquake shocks in March, 1896, did great

damage at Santiago, Valparaiso, and other parts of Chile.
On May 15, a cyclone destroyed part of the town of Sherman, in

Texas, killing more than 120 persons, mostly negroes. The same
day a waterspout burst over the town of Howe in the same state,
killing 8 people.
On May 27, a fierce cyclone swept the city of St. Louis,

Missouri, completely devastating a large part of the city, and
causing great loss of life and property.
A destructive wave swept the Japanese coast in June.

JAPAN: A. D. 1896.
On July 26, a tidal wave, 5 miles in width, inundated the

coast of Kiangsu, in China, destroying many villages and more
than 4,000 inhabitants.
CATASTROPHES, Natural: 1896-1897.
A severe famine prevailed in India from the spring of 1896

until the autumn of 1897.

INDIA: A. D. 1896-1897.
A severe earthquake occurred at the island of Kishm in the

Persian Gulf, in January, causing great loss of life.
In March and April of this year the floods along the

Mississippi river and its tributaries reached the highest
level ever recorded. In extent of area and loss of property
these floods were the most remarkable in the history of the
continent. The total area under water on April 10 was about
15,800 square miles, containing about 39,500 farms, whose
value was close upon $65,000,000. The loss of life was small.
Congress gave relief to the extent of $200,000, besides
appropriating $2,583,300 for the improvement of the
Mississippi.

Extensive floods occurred in Galatz, Moldavia, in June,
rendering 20,000 people homeless.
The islands of Leyte and Samar, in the Visayas group, were

swept by an immense wave caused by a cyclone, in October,
thousands of natives being killed, and much property
destroyed.
{72}
On October 6, the Philippine Islands were swept by a typhoon,

which destroyed several towns. The loss of life was estimated
at 6,000, of whom 400 were Europeans. This was followed on
October 12 by a cyclone which destroyed several villages and
caused further loss of life.
By an eruption of the Mayon volcano in the island of Luzon,

Philippine Islands, four hundred persons were buried in the
lava, and the large town of Libog completely destroyed.
A series of earthquake shocks in Asia Minor during the month

of January occasioned considerable loss of life and property.
In January, Amboyna, in the Molucca Islands, was almost

destroyed by an earthquake, in which about 50 persons were
killed and 200 injured.
On January 11, a tornado wrecked many buildings in Fort Smith,

Ark. The loss of life was reported as 50, with hundreds
injured.
A disastrous blizzard occurred in New England, January 31 and

February 1. Fifty lives were reported as lost, and the damage
in Boston alone amounted to $2,000,000. Many vessels were
driven ashore or foundered, with further loss of life.
Floods on the Ohio river in March and April caused much loss
of life and property. Shawneetown, Illinois on the Ohio river,
was almost entirely destroyed by the flood, more than 60 lives
being lost.
On the night of September 10, the island of Barbados was swept

by a tornado which destroyed 10,000 houses and damaged 5,000
more. Three-fourths of the inhabitants were left homeless, and
about 100 were killed. The islands of St. Vincent and St.
Lucia also suffered great losses of life and property.
A typhoon swept the central provinces of Japan in September,

causing heavy floods, and destroying 100 lives.
Severe floods on the Brazos river, in Texas, occasioned the

death of about 100 people, and property losses to the extent
of $15,000,000.
A destructive tornado in Northern Missouri, in April, did much

damage in the towns of Kirksville and Newtown. Over fifty
persons were killed.
An almost unprecedented failure of crops in eastern Russia

caused famine, disease and awful destruction of life.
A terrific hurricane visited the West Indies August 7 and 8.

Of the several islands affected, Porto Rico suffered most,
three-fourths of the population being left homeless. The total
loss of life in the West Indies was estimated at 5,000.

PORTO RICO: A. D. 1899 (AUGUST).
About 1,500 people lost their lives in an earthquake around

Aidin, Asia Minor, September 2.
The island of Ceram, in the Moluccas, was visited by an

earthquake and tidal wave, November 2. Many towns were
destroyed, and 5,000 people killed.
CATASTROPHES, Natural: 1899-1900.

Recurrence of famine in India.
INDIA A. D. 1899-1900.
The city of Galveston, Texas, was overwhelmed and mostly

destroyed, on the 9th of September, by an unprecedented
hurricane, which drove the waters of the Gulf upon the
low-lying town.

GALVESTON.

Famine in China.

CHINA: A. D. 1901 (JANUARY-FEBRUARY).
CATHOLICS, Roman:
Protest of British peers against the declaration required from
the sovereign.

ENGLAND: A. D. 1901 (FEBRUARY).
CATHOLICS, Roman:
Victory in Belgium.

BELGIUM: A. D. 1894-1895.
See, also, PAPACY.
CEBU: The American occupation of the island.

PHILIPPINE ISLANDS: A. D. 1899 (JANUARY-NOVEMBER).
CENSUS: Of the United States, A. D. 1900.

UNITED STATES OF AMERICA: A. D. 1900 (MAY-OCTOBER).
CENTRAL AFRICA PROTECTORATE, British.

BRITISH CENTRAL AFRICA PROTECTORATE.
CENTRAL AMERICA, A. D. 1821-1898.

Unsuccessful attempts to unite the republics.
"In 1821, after numerous revolutions, Central America

succeeded in throwing off the yoke of Spain. A Congress
assembled at Guatemala in March, 1822, and founded the
Republic of Central America, composed of Guatemala, Salvador,
Honduras, Nicaragua, and Costa Rica. The new Republic had but
a short existence; after numerous civil wars the Union was
dissolved, October 26, 1838, and the five States of the
Republic became so many independent countries. Several
attempts toward a reorganization of the Constitution of the
Republic of Central America remained fruitless and had cost
the lives of certain of their authors, when, through the
influence of Dr. P. Bonilla, President of the Republic of
Honduras, a treaty was concluded between Nicaragua and
Salvador, according to which the three Republics constituted a
federation under the name of the Greater Republic of Central
America. The three Republics became States, and the
sovereignty of the federation was exercised by a Diet composed
of three members, one for each State, and which convened every
year in the capital of the Federal States.
"On the invitation of this Diet, the three States appointed a

delegation which met as a Constituent Assembly at Managua,
Nicaragua, and established a constitution, according to the
terms of which the three States took the name of the United
States of Central America, November 1, 1898. This
Constitution, grand and patriotic, which, in the minds of
those who had elaborated it, meant a complete consolidation of
the three Federal States and a speedy realization of a
reorganization of the Grand Republic of Central America,
dreamed of by Morazan, had a sad ending. The day after the
meeting of the Constituent Assembly a revolutionary movement
hostile to the new federation broke out in Salvador and gave a
new administration to this State. Its first act was to retire
from the Union, and this secession brought about the
dissolution of the United States of Central America; for,
following the example of Salvador, Honduras and Nicaragua took
back their absolute sovereignty."
H. Jalhay,
quoted in Bulletin of American Republics, March, 1899.
{73}
The secession of Salvador was brought about by a revolutionary

movement, which overthrew the constitutional government of
President Gutierrez and placed General Tomas Regolado at the
head of a provisional government, which issued the following
manifesto on the 25th of November, 1898: "Considering—That the
compact of Amapala, celebrated in June, 1895, and all that
proceeds therefrom, has not obtained the legitimate sanction
of the Salvadorean people, and, moreover, has been a violation
of the political constitution of Salvador; That in the
assembled Constituent Assembly of Managua, reunited in June of
the present year, the deputies of Salvador were not directly
elected by the Salvadorean people, and for that reason had no
legal authority to concur to a constituent law that could bind
the Republic; That the union with the Republics of Honduras
and Nicaragua under the contracted terms will seriously injure
the interests of Salvador: Decrees. ART. 1. The Republic of
Salvador is not obliged by the contract of Amapala to
acknowledge any authority in the constitution of Managua of
the 27th August of the current year, and it is released from
the contract of union with the Republics of Honduras and
Nicaragua. ART. 2. The Republic of Salvador assumes in full
its self-government and independence, and will enter the union
with the sister Republics of Central America when same is
convenient to its positive interests and is the express and
free will of the Salvadorean people."
United States, 55th Congress, 3d Session,

Senate Document Number 50.
CENTRAL AMERICA, A. D. 1884-1900.

Interoceanic Canal measures of later years.

CANAL, INTEROCEANIC, with accompanying map.
CENTRAL AMERICA, Nicaragua: A. D. 1894-1895.

Insurrection in the Mosquito Indian Strip.
The Bluefields Incident.
In his Annual Message to Congress, December, 1894, President

Cleveland referred as follows to disturbances which had
occurred during the year at Bluefields, the principal town of
the Mosquito district of Nicaragua, and commonly known as "the
Bluefields Incident:" "By the treaty of 1860 between Great
Britain and Nicaragua, the former Government expressly
recognized the sovereignty of the latter over the strip, and a
limited form of self-government was guaranteed to the Mosquito
Indians, to be exercised according to their customs, for
themselves and other dwellers within its limits. The so-called
native government, which grew to be largely made up of aliens,
for many years disputed the sovereignty of Nicaragua over the
strip and claimed the right to maintain therein a practically
independent municipal government. Early in the past year
efforts of Nicaragua to maintain sovereignty over the Mosquito
territory led to serious disturbances, culminating in the
suppression of the native government and the attempted
substitution of an impracticable composite administration in
which Nicaragua and alien residents were to participate.
Failure was followed by an insurrection, which for a time
subverted Nicaraguan rule, expelling her officers and
restoring the old organization. This in turn gave place to the
existing local government established and upheld by Nicaragua.
Although the alien interests arrayed against Nicaragua in
these transactions have been largely American and the commerce
of that region for some time has been and still is chiefly
controlled by our citizens, we can not for that reason
challenge the rightful sovereignty of Nicaragua over this
important part of her domain."
United States, Message and Documents

(Abridgment, 1894-1895).
In his Message of 1895 the President summarized the later

history of the incident as follows: "In last year's message I
narrated at some length the jurisdictional questions then
freshly arisen in the Mosquito Indian Strip of Nicaragua.
Since that time, by the voluntary act of the Mosquito Nation,
the territory reserved to them has been incorporated with
Nicaragua, the Indians formally subjecting themselves to be
governed by the general laws and regulations of the Republic
instead of by their own customs and regulations, and thus
availing themselves of a privilege secured to them by the
treaty between Nicaragua and Great Britain of January 28,
1860. After this extension of uniform Nicaraguan
administration to the Mosquito Strip, the case of the British
vice-consul, Hatch, and of several of his countrymen who had
been summarily expelled from Nicaragua and treated with
considerable indignity, provoked a claim by Great Britain upon
Nicaragua for pecuniary indemnity, which, upon Nicaragua's
refusal to admit liability, was enforced by Great Britain.
While the sovereignty and jurisdiction of Nicaragua was in no
way questioned by Great Britain, the former's arbitrary
conduct in regard to British subjects furnished the ground for
this proceeding. A British naval force occupied without
resistance the Pacific seaport of Corinto, but was soon after
withdrawn upon the promise that the sum demanded would be
paid. Throughout this incident the kindly offices of the
United States were invoked and were employed in favor of as
peaceful a settlement and as much consideration and indulgence
toward Nicaragua as were consistent with the nature of the
case."
United States,
Message and Documents (Abridgment, 1895-1896).
CENTRAL AMERICA, Guatemala: A. D. 1895.

Mexican boundary dispute.

MEXICO: A. D. 1895.
CENTRAL AMERICA, Nicaragua: A. D. 1896-1898.

Revolutionary conflicts.
Vice President Baca of Nicaragua joined a revolutionary

movement which was set on foot in February, 1896, by the
Clericals, for the overthrow of President Zelaya, and was
declared Provisional President. The rebellion had much support
from exiles and friends in Honduras; but the government of
that State sustained and assisted Zelaya. The insurgents were
defeated in a number of battles, and gave up the contest in
May. During the civil war American and British marines were
landed on occasions at Corinto to protect property there. In
1897, and again in 1898, there were renewed insurrections,
quickly suppressed.
CENTRAL AMERICA, Costa Rica: A. D. 1896-1900.
Boundary dispute with Colombia settled by arbitration.

COLOMBIA: A. D. 1893-1900.
{74}
CENTRAL AMERICA, Nicaragua—Costa Rica: A. D. 1897.
A dispute between Nicaragua and Costa Rica, as to the eastern

extremity of their boundary line, was decided by General
Alexander, a referee accepted by the two republics. The
boundary had not been well defined in a treaty negotiated for
its settlement in 1858. According to the terms of the treaty,
the line was to start from the Atlantic at the mouth of the
San Juan river; but changes of current and accumulation of
river drift, etc., gave ground for dispute as to where the
river actually made its exit. President Cleveland in 1888,
acting as arbitrator at the request of the two countries,
decided that the treaty of 1858 was valid, but was not clear
as to which outlet of the delta was the boundary. Finally, in
1896, an agreement was reached for a final survey and marking
of the boundary line, and President Cleveland, on request,
appointed General Alexander as arbitrator in any case of
disagreement between the surveying commissions. The decision
gives to Nicaragua the territory upon which Greytown is
situated, and practical control of the mouth of the canal.
CENTRAL AMERICA, Guatemala: A. D. 1897-1898.

Dictatorship of President Barrios.
His assassination.
In June, 1897, President José M. Reyna Barrios, whose six

years term in the presidency would expire the next March,
fearing defeat in the approaching election, forcibly dissolved
the National Assembly and proclaimed a dictatorship. Three
months later a revolt was organized by General Prospero
Morales; but Barrios crushed it with merciless energy, and a
veritable reign of terror ensued. In February, 1898, the
career of the Dictator was cut short by an assassin, who shot
him to avenge the death of a wealthy citizen, Don Juan
Aparicio, whom Barrios had executed for expressing sympathy
with the objects of the rebellion of the previous year.
Control of the government was then taken by Dr. Cabrera, who
had been at the head of the party which supported Barrios. A
rising under Morales was again attempted, but failed. Morales,
in a dying condition at the time, was betrayed and captured.
Cabrera, with no more opposition, was elected President for
six years.
CENTRAL AMERICA, Nicaragua—Costa Rica: A. D. 1900.

Agreements with the United States respecting the control of
territory for interoceanic canal.

CANAL, INTEROCEANIC, A. D. 1900 (DECEMBER).
CENTURY, The Nineteenth:

Date of its ending.
Its character and trend.
Comparison with preceding ages.
Its failures.

NINETEENTH CENTURY.
CERVERA, Rear-Admiral,
and the Spanish Squadron at Santiago de Cuba.

UNITED STATES OF AMERICA: A. D. 1898 (APRIL-JUNE);
and (JULY 3).
CHAFFEE, General Adna R.:
At Santiago.

UNITED STATES OF AMERICA: A. D. 1898 (JUNE-JULY).

Commanding American forces in China.

CHINA: A. D. 1900 (JUNE-AUGUST);
(JULY); and (AUGUST).

Report of the allied movement to Peking
and the capture of the city.

CHINA: A. D. 1900 (AUGUST 4-16).
CHAKDARRA, Defense of.

INDIA: A. D. 1897-1898.
CHALDEA, New light on ancient.

ARCHÆOLOGICAL RESEARCH: BABYLONIA.
CHAMBERLAIN, Joseph:
Appointed British Secretary of State for the Colonies.

ENGLAND: A. D. 1894-1895; and 1900 (NOVEMBER-DECEMBER).
Conference with Colonial Premiers.

ENGLAND: A. D. 1897 (JUNE-JULY).
Controversies with the government of
the South African Republic.

SOUTH AFRICA (THE TRANSVAAL): A. D. 1896 (JANUARY-
APRIL);
1896-1897 (MAY-APRIL), and after.
Testimony before British Parliamentary Committee
on the Jameson Raid.
Remarks in Parliament on Mr. Rhodes.

SOUTH AFRICA (THE TRANSVAAL): A. D. 1897 (FEBRUARY-
JULY).
Instructions to the Governor of Jamaica.

JAMAICA: A. D. 1899.
Reassertion of British suzerainty over
the South African Republic.
Refusal to arbitrate questions of disagreement.

SOUTH AFRICA (THE TRANSVAAL): A. D. 1897 (MAY-
OCTOBER);
and 1898-1899.
Declaration of South African policy.

SOUTH AFRICA (THE FIELD OF WAR): A. D. 1901.
CHANG CHIH-TUNG, Viceroy:

Admirable conduct during the Chinese outbreak.

CHINA: A. D. 1900 (JUNE-DECEMBER).
CHEMICAL SCIENCE, Recent advances in.

SCIENCE, RECENT: CHEMISTRY AND PHYSICS.
CHEROKEES, United States agreement with the.

INDIANS, AMERICAN: A. D. 1893-1899.
CHICAGO: A. D. 1894.
Destruction of the Columbian Exposition buildings.
By a succession of fires, January 9, February 14, most of the

buildings of the Exposition, with valuable exhibits not yet
removed, were destroyed.
CHICAGO: A. D. 1896.
Democratic National Convention.

UNITED STATES OF AMERICA: A. D. 1896 (JUNE-NOVEMBER).

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Advances in Ophthalmology and

Optometry, 2021 (Volume 6-1)

PHILADELPHIA LONDON TORONTO MONTREAL SYDNEY TOKYO

Ó 2021 Elsevier Inc. All rights reserved.

DAVID A. CRANDALL, MD – Cataract & Refractive Surgery

PAUL B. FREEMAN, OD, FAAO, FCOVD – Optometry

MORRIS E. HARTSTEIN, MD, FACS – Oculoplastics

RUSTUM KARANJIA, MD, PhD, FRCSC, DABO – Neuro-ophthalmology

RONNI M. LIEBERMAN, MD – Vitreoretinal Disease

ANN-MARIE LOBO, MD – Uveitis

STEPHEN ORLIN, MD – Cornea and External Diseases

JOSEPH M. ORTIZ, MD, FRCOphth – Glaucoma

LEONARD J. PRESS, OD, FAAO, FCOVD – Optometry

APARNA RAMASUBRAMANIAN, MD – Pediatric Ophthalmology

DEVIN BETSCH, MD, Resident, Department of Ophthalmology and Visual Sciences,

POOJA V. BHAT, MD, Assistant Professor of Ophthalmology, Co-director of Uveitis

DANIEL BRISCOE, MD, Ophthalmology Department, HaEmek Medical Center, Afula,

JAN RICHARD BRUENECH, PhD, Professor, Biomedical Research Unit, Faculty of

GREG CALDWELL, OD, FAAO, Optometric Education Consultants, Lilly,

NOEL C.Y. CHAN, MBChB, FRCSEd, Department of Ophthalmology and Visual

BHAVNA CHAWLA, MD, Professor of Ophthalmology, Ocular Oncology Service, RP

KELSEY CHEN, MABS, Medical Student, Midwestern University Arizona College of

DANIEL CHOI, MD, Department of Ophthalmology, Scheie Eye Institute, University of

DAVID A. CRANDALL, MD, Glaucoma and Advanced Anterior Segment Fellowship

DIPANKAR DAS, MS, Department of Pathology, Uveitis and Neurophthalmology, Sri

ERIN M. DRAPER, OD, FAAO, Attending Optometrist, Neuro-Ophthalmic Disease

PAUL R. FREUND, MD, MSc, FRCSC, Assistant Professor, Department of

SAMUEL GELNICK, MD, Resident, Department of Ophthalmology, Northwell Health,

SNEHA GIRIDHAR, MD, Shri Bhagwan Mahavir Vitreoretinal Services, Sankara

LUIS F. GONCALVES, MD, Director of Fetal Imaging, Department of Radiology,

GIOVANNA GUIDOBONI, PhD, Departments of Electrical Engineering and Computer

PAUL HARASYMOWYCZ, MD, Department of Ophthalmology, University of

ALON HARRIS, MS, PhD, FARVO, Professor of Ophthalmology, Vice Chair of

IOANA CATALINA IONESCU, MD, PhD, Orbital Center, Department of

RABEA KASSEM, MD, Department of Ophthalmology, University of Montreal,

SUSHMITA KAUSHIK, MS, Advanced Eye Centre, Postgraduate Institute of Medical

NUR KHATIB, MD, Orbital Center, Department of Ophthalmology, Amsterdam

HAYYAM KIRATLI, MD, Ocular Oncology Service, Professor, Department of

IREM KOÇ, MD, Ocular Oncology Service, Department of Ophthalmology, Hacettepe

RONNI LIEBERMAN, MD, Assistant Professor, Department of Ophthalmology, Mount

TIANYU LIU, MD, Scheie Eye Institute, University of Pennsylvania, Philadelphia,

SUSAN LUO, BS, Department of Ophthalmology and Visual Sciences, University of

ILARIA MACCORA, MD, Rheumatology Unit, Meyer Children’s University Hospital,

NENITA MAGANTI, MD, Department of Ophthalmology and Visual Sciences,

ASHLEY KAY MAGLIONE, OD, FAAO, Attending Optometrist, Neuro-Ophthalmic

KELLY A. MALLOY, OD, FAAO, Diplomate in Neuro-Ophthalmic Disorders; Chief

ELIZABETH MARUNDE, OD, Neuro-Ophthalmic Disease Resident, The Eye Institute,

ENNY OYENIRAN, MD, Department of Ophthalmology, Scheie Eye Institute,

SURINDER S. PANDAV, MS, Advanced Eye Centre, Postgraduate Institute of Medical

CHINTAN A. PATHAK, MD, Department of Ophthalmology and Visual Sciences,

ATHIMALAIPET V. RAMANAN, FRCP, Professor, Department of Paediatric

APARNA RAMASUBRAMANIAN, MD, Department of Ophthalmology, Phoenix

ANGELINE C. RIVKIN, BS, Medical Student, University of Illinois College of Medicine,

PEEROOZ SAEED, MD, PhD, Orbital Center, Department of Ophthalmology,

ETHAN S. SEN, MD, PhD, Department of Paediatric Rheumatology, Great North

JESSICA STEEN, OD, FAAO, Assistant Professor, Nova Southeastern University

ZUJAJA TAUQEER, MD, DPhil, Department of Ophthalmology, Scheie Eye Institute,

VANCE THOMPSON, MD, Director of Refractive Surgery, Vance Thompson Vision,

ALICE C. VERTICCHIO VERCELLIN, MD, PhD, Icahn School of Medicine at Mount

MYRON YANOFF, MD, Chair Emeritus, Department of Ophthalmology, Drexel

CANDICE YOUSIF, MD, Glaucoma Fellow, Department of Ophthalmology, Henry

TINA ZENG, OD, Neuro-Ophthalmic Disease Resident, The Eye Institute,

CONTENTS VOLUME 6  2021

CONTENTS VOLUME 6 2021