HP1 AMERICAN ACADEMY
OF OPHTHALMOLOGY
. .
Protecting Sight Empowering Lives
12 Retina and Vitreous
2023 - 2024
Basic and Clinical
Science Course "
Editorial Committee
Stephen J. Kim, MD, Chair
Amani Fawzi, MD
Jaclyn L. Kovach, MD
Shriji Patel, MD, MBA
Franco M. Recchia, MD
Lucia Sobrin, MD, MPH
Jennifer K. Sun, MD, MPH
Charles C. Wykoff, MD, PhD
,12 Retina and Vitreous
Last major revision 2022–2023
2023–2024
BCSCBasic and Clinical
Science Course™
Funded in part by the Educational Trust
Fund/Retina Research Foundation
Published after collaborative
review with the European Board
of Ophthalmology subcommittee
, The American Academy of Ophthalmology is accredited by the Accreditation Council for Con-
tinuing Medical Education (ACCME) to provide continuing medical education for physicians.
The American Academy of Ophthalmology designates this enduring material for a maximum of
™
15 AMA PRA Category 1 Credits . Physicians should claim only the credit commensurate with
the extent of their participation in the activity.
CME expiration date: June 1, 2025. AMA PRA Category 1 Credits
June 1, 2022, and the expiration date.
™ may be claimed only once between
®
BCSC volumes are designed to increase the physician’s ophthalmic knowledge through study and
review. Users of this activity are encouraged to read the text and then answer the study questions
provided at the back of the book.
™
To claim AMA PRA Category 1 Credits upon completion of this activity, learners must demon-
strate appropriate knowledge and participation in the activity by taking the posttest for Section 12
and achieving a score of 80% or higher. For further details, please see the instructions for requesting
CME credit at the back of the book.
The Academy provides this material for educational purposes only. It is not intended to represent
the only or best method or procedure in every case, nor to replace a physician’s own judgment or
give specific advice for case management. Including all indications, contraindications, side effects,
and alternative agents for each drug or treatment is beyond the scope of this material. All informa-
tion and recommendations should be verified, prior to use, with current information included in the
manufacturers’ package inserts or other independent sources, and considered in light of the patient’s
condition and history. Reference to certain drugs, instruments, and other products in this course is
made for illustrative purposes only and is not intended to constitute an endorsement of such. Some
material may include information on applications that are not considered community standard, that re-
flect indications not included in approved FDA labeling, or that are approved for use only in restricted
research settings. The FDA has stated that it is the responsibility of the physician to determine
the FDA status of each drug or device he or she wishes to use, and to use them with appropriate,
informed patient consent in compliance with applicable law. The Academy specifically disclaims
any and all liability for injury or other damages of any kind, from negligence or otherwise, for any and
all claims that may arise from the use of any recommendations or other information contained herein.
All trademarks, trade names, logos, brand names, and service marks of the American Academy
of Ophthalmology (AAO), whether registered or unregistered, are the property of AAO and are
protected by US and international trademark laws. These trademarks include, but are not limited
to, AAO; AAOE; AMERICAN ACADEMY OF OPHTHALMOLOGY; BASIC AND CLINICAL
SCIENCE COURSE; BCSC; EYENET; EYEWIKI; FOCAL POINTS; FOCUS DESIGN (logo on
cover); IRIS; IRIS REGISTRY; ISRS; OKAP; ONE NETWORK; OPHTHALMOLOGY; OPHTHAL-
MOLOGY GLAUCOMA; OPHTHALMOLOGY RETINA; OPHTHALMOLOGY SCIENCE; OPH-
THALMOLOGY WORLD NEWS; PREFERRED PRACTICE PATTERN; PROTECTING SIGHT.
EMPOWERING LIVES.; THE OPHTHALMIC NEWS AND EDUCATION NETWORK.
Cover image: From BCSC Section 9, Uveitis and Ocular Inflammation. Image courtesy of Sam
S. Dahr, MD, MS.
Copyright © 2023 American Academy of Ophthalmology. All rights reserved. No part of
this publication may be reproduced without written permission.
Printed in South Korea.
,Basic and Clinical Science Course
Christopher J. Rapuano, MD, Philadelphia, Pennsylvania
Senior Secretary for Clinical Education
J. Timothy Stout, MD, PhD, MBA, Houston, Texas
Secretary for Lifelong Learning and Assessment
Colin A. McCannel, MD, Los Angeles, California
BCSC Course Chair
Section 12
Faculty for the Major Revision
Stephen J. Kim, MD
Franco M. Recchia, MD
Chair
Nashville, Tennessee
Nashville, Tennessee
Amani Fawzi, MD Lucia Sobrin, MD, MPH
Chicago, Illinois Boston, Massachusetts
Jaclyn L. Kovach, MD Jennifer K. Sun, MD, MPH
Naples, Florida Boston, Massachusetts
Shriji Patel, MD, MBA Charles C. Wykoff, MD, PhD
Nashville, Tennessee Houston, Texas
,The Academy acknowledges the American Society of Retina Specialists (ASRS), the Macula
Society, and the Retina Society for recommending faculty members to the BCSC Section 12
committee.
The Academy also acknowledges the following committees for review of this edition:
Committee on Aging: Christopher R. Henry, MD, Houston, Texas
Vision Rehabilitation Committee: Linda A. Lam, MD, MBA, Los Angeles, California
BCSC Resident/Fellow Reviewers: Sharon L. Jick, MD, Chair, St Louis, Missouri; Sunil Bel-
lur, MD; Gordon S. Crabtree, MD; Maria Paula Fernandez, MD; Michael J. Heiferman,
MD; Hong-Uyen Hua, MD; Hong-Gam T. Le, MD; Danny Mammo, MD; Archana Nair,
MD; Daniel J. Oh, MD; Ivy Zhu, MD
Practicing Ophthalmologists Advisory Committee for Education: Gaurav K. Shah, MD, Pri-
mary Reviewer, Town and Country, Missouri; Cynthia S. Chiu, MD, Oakland, California;
George S. Ellis Jr, MD, New Orleans, Louisiana; Bradley D. Fouraker, MD, Tampa, Florida;
Philip R. Rizzuto, MD, Providence, Rhode Island; Rosa A. Tang, MD, MPH, MBA, Hous-
ton, Texas; Troy M. Tanji, MD, Waipahu, Hawaii; Michelle S. Ying, MD, Ladson, South
Carolina
In addition, the Academy acknowledges the following committee for assistance in devel-
oping Study Questions and Answers for this BCSC Section:
Resident Self-Assessment Committee: Evan L. Waxman, MD, PhD, Chair, Pittsburgh, Penn-
sylvania; Robert A. Beaulieu, MD, Southfield, Michigan; Benjamin W. Botsford, MD, New
York, New York; Olga M. Ceron, MD, Grafton, Massachusetts; Kevin Halenda, MD, Cleve-
land, Ohio; Amanda D. Henderson, MD, Baltimore, Maryland; Andrew M. Hendrick, MD,
Atlanta, Georgia; Joshua Hendrix, MD, Dalton, Georgia; Matthew B. Kaufman, MD, Port-
land, Oregon; Zachary A. Koretz, MD, MPH, Pittsburgh, Pennsylvania; Kevin E. Lai, MD,
Indianapolis, Indiana; Kenneth C. Lao, MD, Temple, Texas; Yasha S. Modi, MD, New York,
New York; Mark E. Robinson, MD, MPH, Columbia, South Carolina; Jamie B. Rosen-
berg, MD, New York, New York; Tahira M. Scholle, MD, Houston, Texas; Ann Shue, MD,
Sunnyvale, California; Jeong-Hyeon Sohn, MD, Shavano Park, Texas; Misha F. Syed, MD,
League City, Texas; Parisa Taravati, MD, Seattle, Washington; Sarah Van Tassel, MD, New
York, New York; Matthew S. Wieder, MD, Scarsdale, New York; Jules A. Winokur, MD,
Great Neck, New York
European Board of Ophthalmology: Lotte Welinder, MD, Liaison, Aalborg, Denmark; Katja
Christina Schielke, MBBS, Aalborg, Denmark
Financial Disclosures
Academy staff members who contributed to the development of this product state that
within the 24 months prior to their contributions to this CME activity and for the dura-
tion of development, they have had no financial interest in or other relationship with any
entity that produces, markets, resells, or distributes health care goods or services con-
sumed by or used in patients.
,The authors and reviewers state that within the 24 months prior to their contributions
to this CME activity and for the duration of development, they have had the following
financial relationships:*
Dr Fouraker: Addition Technology (C, L), AJL Ophthalmic, SA (C, L), Alcon (C, L),
OASIS Medical (C, L)
Dr Fawzi: Bayer (L), Boehringer Ingelheim (C), Novartis (C), Regeneron Pharmaceuticals
(C), Roche (C)
Dr Henry: Aldeyra Therapeutics (C), Alimera Sciences (C), Castle Biosciences (C), Clear-
side Biomedical (C), Lexitas (C)
Dr Kovach: Novartis (L), Regeneron Pharmaceuticals (L)
Dr Lai: Twenty/Twenty Therapeutics (C)
Dr Lam: Ocutrx (C)
Dr Modi: Alimera Sciences (C), Allergan (C), Carl Zeiss (C), Genentech (C), Novartis (C),
Théa Laboratories (C)
Dr Patel: Alcon (S)
Dr Recchia: Adverum Biotechnologies (S), Astellas Pharma (S), Chengdu Kanghong (S),
Genentech (S), Kodiak Sciences (S), Mylan (S), Novartis (S), Regeneron Pharmaceuticals
(S), REGENXBIO (S)
Dr Robinson: Horizon Therapeutics (O)
Dr Shah: Allergan (C, L, S), Bausch + Lomb (L), DORC Dutch Ophthalmic Research Cen-
ter (International) BV (S), Regeneron Pharmaceuticals (C, L, S)
Dr Sobrin: Novartis (C), Santen (C)
Dr Sun: Adaptive Sensory Technology (S), Boehringer Ingelheim (S), Boston Micro-
machines (S), Genentech (S), JAMA Ophthalmology (C), KalVista Pharmaceuticals (S),
Merck (C), Novartis (C, S), Novo Nordisk (C, S), Optovue (S), Regeneron Pharmaceuti
cals (S), Roche (C, S)
Dr Tang: EMD Serono (L), Horizon Therapeutics (C, S), Immunovant (S), Novartis (S),
Quark Pharmaceuticals (C, S), Regenera Pharma (S), Sanofi (L), ZEISS (L)
Dr Van Tassel: AbbVie (C), Aerie Pharmaceuticals (C), Allergan (C), Bausch + Lomb (C),
Carl Zeiss Meditec (C), Equinox (C), New World Medical (C, L)
Dr Wykoff: AbbVie (C), Acucela (C), Adverum Biotechnologies (C, S), Aerie Pharmaceuti
cals (C, S), Aerpio Pharmaceuticals (C, S), Alcon (C, S), Aldeyra (S), Alimera Sciences (C, S),
Alkahest (S), Allegro Ophthalmics (C, S), Allergan (C, L, S), Apellis (C, S), AsclepiX Thera-
peutics (S), Astellas Pharma (S), Bausch + Lomb (C), Bayer (C, S), Boehringer Ingelheim (S),
* C = consultant fee, paid advisory boards, or fees for attending a meeting; E = employed by or received
a W2 from a commercial company; L = lecture fees or honoraria, travel fees or reimbursements when
speaking at the invitation of a commercial company; O = equity ownership/stock options in publicly or
privately traded firms, excluding mutual funds; P = patents and/or royalties for intellectual property;
S = grant support or other financial support to the investigator from all sources, including research sup-
port from government agencies, foundations, device manufacturers, and/or pharmaceutical companies
,Chengdu Kanghong (C, S), Clearside Biomedical (C, S), EyePoint Pharmaceuticals (C),
Gemini Therapeutics (S), Genentech (C, S), Graybug Vision (S), Gyroscope (C, S), Ionis
Pharmaceuticals (S), Iveric Bio (C, S), Kato Pharmaceuticals (C), Kodiak Sciences (C, S),
Merck (C), Nanoscope (S), Neurotech (S), NGM Biopharmaceuticals (C, S), Notal Vision
(C), Novartis (C, S), OccuRx (C), Ocular Therapeutix (C), OHR Pharmaceuticals (S), ONL
Therapeutics (C), Ophthotech Corporation (S), Opthea (C, S), Outlook Therapeutics (S),
Oxurion (C, S), Palatin (C), PolyPhotonix (C), RecensMedical (C, O, S), Regeneron Phar
maceuticals (C, L, S), RegenxBio (C, S), Roche (C, S), SamChunDang Pharm (S), Samsung
(S), Santen (C, S), SciFluor Life Sciences (S), Senju Pharmaceutical Co, Ltd (S), Takeda (C),
Théa Open Innovation (C), ThromboGenics (S), Tyrogenex (S), Valo Health (C), Visgenx
(O), Vitranu (C), Xbrane Biopharma (S)
All relevant financial relationships have been mitigated.
The other authors and reviewers state that within the 24 months prior to their contribu-
tions to this CME activity and for the duration of development, they have had no financial
interest in or other relationship with any entity that produces, markets, resells, or distrib-
utes health care goods or services consumed by or used in patients.
Recent Past Faculty
Audina M. Berrocal, MD
Graham E. Holder, PhD
Brian C. Leonard, MD
Colin A. McCannel, MD
Richard B. Rosen, MD
Richard F. Spaide, MD
In addition, the Academy gratefully acknowledges the contributions of numerous past
faculty and advisory committee members who have played an important role in the devel-
opment of previous editions of the Basic and Clinical Science Course.
American Academy of Ophthalmology Staff
Dale E. Fajardo, EdD, MBA, Vice President, Education
Beth Wilson, Director, Continuing Professional Development
Denise Evenson, Director, Brand & Creative
Susan Malloy, Acquisitions and Development Manager
Stephanie Tanaka, Publications Manager
Rayna Ungersma, Manager, Curriculum Development
Jasmine Chen, Manager, E-Learning
Sarah Page, Online Education & Licensing Manager
Lana Ip, Senior Designer
Amanda Fernandez, Publications Editor
Beth Collins, Medical Editor
Eric Gerdes, Interactive Designer
Kenny Guay, Publications Specialist
Debra Marchi, Administrative Assistant
American Academy of Ophthalmology
655 Beach Street
Box 7424
San Francisco, CA 94120-7424
,Contents
Introduction to the BCSC . . . . . . . . . . . . . . . . . . . . . . xvii
Introduction to Section 12 . . . . . . . . . . . . . . . . . . . . . . xix
Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PART I Fundamentals and Diagnostic
Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1 Basic Anatomy . . . . . . . . . . . . . . . . . . . . . . . . . 5
Highlights . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Vitreous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Neurosensory Retina . . . . . . . . . . . . . . . . . . . . . . . . . 7
Retinal Topography . . . . . . . . . . . . . . . . . . . . . . . . 7
Retinal Layers and Neurosensory Elements . . . . . . . . . . . . . 9
Retinal Vasculature and Oxygen Supply . . . . . . . . . . . . . . . 13
Retinal Pigment Epithelium . . . . . . . . . . . . . . . . . . . . . 15
Bruch Membrane . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Choroid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Sclera . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
2 Diagnostic Approach to Retinal
and Choroidal Disease . . . . . . . . . . . . . . . . . . . . 21
Highlights . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Ophthalmoscopy . . . . . . . . . . . . . . . . . . . . . . . . . . 22
Examination With the Binocular Indirect Ophthalmoscope . . . . . . 22
Indirect Ophthalmoscopy With the Slit Lamp . . . . . . . . . . . . 22
Imaging Technologies . . . . . . . . . . . . . . . . . . . . . . . . 23
Fundus Camera Imaging . . . . . . . . . . . . . . . . . . . . . 23
Scanning Laser Ophthalmoscopy . . . . . . . . . . . . . . . . . 24
Optical Coherence Tomography . . . . . . . . . . . . . . . . . . 26
Optical Coherence Tomography Angiography . . . . . . . . . . . . 28
Fundus Autofluorescence . . . . . . . . . . . . . . . . . . . . . 29
Adaptive Optics Imaging . . . . . . . . . . . . . . . . . . . . . 32
Retinal Angiographic Techniques . . . . . . . . . . . . . . . . . 32
Ultrasonography . . . . . . . . . . . . . . . . . . . . . . . . . 39
3 Retinal Physiology and Psychophysics . . . . . . . . . . . 43
Highlights . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
Electrophysiologic Testing . . . . . . . . . . . . . . . . . . . . . . 43
vii
,viii ● Contents
Electroretinography . . . . . . . . . . . . . . . . . . . . . . . . . 44
Full-Field (Ganzfeld) Electroretinography . . . . . . . . . . . . . . 45
Multifocal Electroretinography . . . . . . . . . . . . . . . . . . 49
Pattern Electroretinography . . . . . . . . . . . . . . . . . . . . 51
Clinical Considerations . . . . . . . . . . . . . . . . . . . . . . 52
Electro-oculography . . . . . . . . . . . . . . . . . . . . . . . . . 53
Visual Evoked Potentials . . . . . . . . . . . . . . . . . . . . . . . 55
Microperimetry . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
Psychophysical Testing . . . . . . . . . . . . . . . . . . . . . . . . 56
Color Vision . . . . . . . . . . . . . . . . . . . . . . . . . . 57
Contrast Sensitivity . . . . . . . . . . . . . . . . . . . . . . . 59
Dark Adaptometry . . . . . . . . . . . . . . . . . . . . . . . . 61
PART II Diseases of the Retina and Vitreous . . . . . . 63
4 Age-Related Macular Degeneration and
Other Causes of Choroidal Neovascularization . . . . . . 65
Highlights . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
Age-Related Macular Degeneration . . . . . . . . . . . . . . . . . . 66
Genetics and AMD . . . . . . . . . . . . . . . . . . . . . . . 68
Nonneovascular AMD . . . . . . . . . . . . . . . . . . . . . . 69
Neovascular AMD . . . . . . . . . . . . . . . . . . . . . . . . 77
Other C
auses of Choroidal Neovascularization . . . . . . . . . . . . . 93
Ocular Histoplasmosis Syndrome . . . . . . . . . . . . . . . . . 93
Angioid Streaks . . . . . . . . . . . . . . . . . . . . . . . . . 95
Pathologic Myopia . . . . . . . . . . . . . . . . . . . . . . . . 96
Idiopathic CNV and Miscellaneous Causes of CNV . . . . . . . . . 97
5 Diabetic Retinopathy . . . . . . . . . . . . . . . . . . . . . 99
Highlights . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
Terminology and Classification . . . . . . . . . . . . . . . . . . . 100
Diabetes Terminology . . . . . . . . . . . . . . . . . . . . . 100
Diabetic Retinopathy Terminology . . . . . . . . . . . . . . . . 100
Epidemiology of Diabetic Retinopathy . . . . . . . . . . . . . . . . 101
Pathogenesis of Diabetic Retinopathy . . . . . . . . . . . . . . . . . 102
Recommended Diabetes Mellitus–Related
Ophthalmic Examinations . . . . . . . . . . . . . . . . . . . . 103
Systemic Medical Management of Diabetic Retinopathy . . . . . . . . . 104
Nonproliferative Diabetic Retinopathy . . . . . . . . . . . . . . . . 108
Treatment of Nonproliferative Diabetic Retinopathy . . . . . . . . 111
Proliferative Diabetic Retinopathy . . . . . . . . . . . . . . . . . . 111
Management of Proliferative Diabetic Retinopathy
and Its Complications . . . . . . . . . . . . . . . . . . . . 115
Additional Vision-Threatening Complications
of Diabetic Retinopathy . . . . . . . . . . . . . . . . . . . 119
, Contents ● ix
Diabetic Macular Edema . . . . . . . . . . . . . . . . . . . . . . 121
Classification of Diabetic Macular Edema . . . . . . . . . . . . . 122
Management of Diabetic Macular Edema . . . . . . . . . . . . . 123
Cataract Surgery in Patients With Diabetes Mellitus . . . . . . . . . . 128
6 Retinal Vascular Diseases Associated With
Cardiovascular Disease . . . . . . . . . . . . . . . . . . . 131
Highlights . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
Systemic Arterial Hypertension and Associated Ocular
Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
Hypertensive Retinopathy . . . . . . . . . . . . . . . . . . . . 132
Hypertensive Choroidopathy . . . . . . . . . . . . . . . . . . 133
Hypertensive Optic Neuropathy . . . . . . . . . . . . . . . . . 134
Retinal Venous Occlusion . . . . . . . . . . . . . . . . . . . . . . 134
Overview of Retinal Venous Occlusion . . . . . . . . . . . . . . 134
Branch Retin al Vein Occlusion . . . . . . . . . . . . . . . . . . 145
Central Retinal Vein Occlusion . . . . . . . . . . . . . . . . . . 148
Ocular Ischemic Syndrome and Retinopathy
of Carotid Occlusive Disease . . . . . . . . . . . . . . . . . . . 152
Symptoms and Signs of OIS . . . . . . . . . . . . . . . . . . . 152
Etiology and Course of OIS . . . . . . . . . . . . . . . . . . . 153
Treatment of OIS . . . . . . . . . . . . . . . . . . . . . . . . 154
Arterial Occlusive Disease . . . . . . . . . . . . . . . . . . . . . 154
Cotton-Wool Spots . . . . . . . . . . . . . . . . . . . . . . . 154
Branch Retin al Artery Occlusion . . . . . . . . . . . . . . . . . 155
Central Retinal Artery Occlusion . . . . . . . . . . . . . . . . . 158
Cilioretinal Artery Occlusion . . . . . . . . . . . . . . . . . . 162
Ophthalmic Artery Occlusion . . . . . . . . . . . . . . . . . . 162
Paracentral Acute M iddle Maculopathy . . . . . . . . . . . . . . 164
Arterial Macroaneurysms . . . . . . . . . . . . . . . . . . . . . . 165
7 Other Retinal Vascular Diseases . . . . . . . . . . . . . . 167
Highlights . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
Sickle Cell Disease and Retinopathy . . . . . . . . . . . . . . . . . 167
Sickle Cell Disease . . . . . . . . . . . . . . . . . . . . . . . 167
Stages of Sickle Cell Retinopathy . . . . . . . . . . . . . . . . . 168
Nonproliferative Sickle Cell Retinopathy . . . . . . . . . . . . . 168
Proliferative Sickle Cell Retinopathy . . . . . . . . . . . . . . . 168
Other Ocular Abnormalities in Sickle Cell Hemoglobinopathies . . . 171
Management of Sickle Cell Retinopathy and Its Complications . . . . 174
Vasculitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175
Cystoid Macular Edema . . . . . . . . . . . . . . . . . . . . . . 176
Etiologies of CME . . . . . . . . . . . . . . . . . . . . . . . 176
Treatment of CME . . . . . . . . . . . . . . . . . . . . . . . 178
Coats Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . 178
Coats-like Reaction in Other Retinal Conditions . . . . . . . . . . 179
