Retina Atlas

Ophthalmology:
Current and Future Developments

Diagnostic Atlas of Retinal
Diseases
(Volume 1)
Editors
Mitzy E. Torres Soriano
Unidad Oftalmológica “Dr. Torres López”. Centro Médico
Cagua, Aragua, Venezuela
Gerardo García Aguirre

Retina Department,
Asociación para Evitar la Ceguera en Mexico,
Mexico City, Mexico
Co-Editors
Maximiliano Gordon
Centro de la Visión Gordon Manavella,
Rosario, Santa Fe, Argentina
Veronica Kon Graversen

University of North Carolina at Chapel Hill,
Chapel Hill, NC, USA

Ophthalmology: Current and Future Developments

Volume # 1
Diagnostic Atlas of Retinal Diseases
Editors: Mitzy E. Torres Soriano, Gerardo García Aguirre, Maximiliano Gordon & Veronica
Kon Graversen
ISSN (Print): 2468-7162
eISSN (Online): 2468-7170
eISBN (Online): 978-1-68108-357-5
ISBN (Print): 978-1-68108-358-2
©2016, Bentham eBooks imprint.
Published by Bentham Science Publishers – Sharjah, UAE. All Rights Reserved.

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CONTENTS
FOREWORD ................................................................................................................................................................ i
PREFACE .................................................................................................................................................................... ii
ACKNOWLEDGEMENTS ................................................................................................................................. ii
DEDICATION ...................................................................................................................................................... ii
LIST OF CONTRIBUTORS ..................................................................................................................................... iv

CHAPTER 1 NON-PROLIFERATIVE DIABETIC RETINOPATHY .............................................................. 3
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ESSENTIALS OF DIAGNOSIS ......................................................................................................................... 3
Classification ................................................................................................................................................ 12
DIFFERENTIAL DIAGNOSIS ........................................................................................................................ 13
MANAGEMENT ................................................................................................................................................ 15
CONFLICT OF INTEREST ............................................................................................................................. 15
ACKNOWLEDGEMENTS ............................................................................................................................... 15
REFERENCES ................................................................................................................................................... 15
CHAPTER 2 PROLIFERATIVE DIABETIC RETINOPATHY (PDR) ........................................................... 18
0DULD+%HUURFDODQG/XLV$$FDEi
ESSENTIALS OF DIAGNOSIS ....................................................................................................................... 18
MANAGEMENT ................................................................................................................................................ 23
REFERENCES ................................................................................................................................................... 28
CHAPTER 3 DIABETIC MACULAR EDEMA .................................................................................................. 29
0D[LPLOLDQR*RUGRQDQG0LW]\(7RUUHV6RULDQR
MANAGEMENT ................................................................................................................................................ 40
REFERENCES ................................................................................................................................................... 42
CHAPTER 4 CENTRAL RETINAL VEIN OCCLUSION ................................................................................ 44
1HOVRQ6HJRYLD5RGUtJXH]
MANAGEMENT ................................................................................................................................................ 53
REFERENCES ................................................................................................................................................... 55
CHAPTER 5 BRANCH RETINAL VEIN OCCLUSION ................................................................................... 58
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MANAGEMENT ................................................................................................................................................ 64
REFERENCES ................................................................................................................................................... 66
CHAPTER 6 A THREE-DIMENSIONAL LOOK INTO HYPERTENSIVE RETINOPATHY ................... 67
5DIDHO0XFL0HQGR]D
Complications of Hypertensive Retinopathy ............................................................................................... 73
Classification ................................................................................................................................................ 73
MANAGEMENT ................................................................................................................................................ 80
REFERENCES ................................................................................................................................................... 80
CHAPTER 7 CENTRAL RETINAL ARTERY OCCLUSION ......................................................................... 82
6LOYLD0HQGR]D6DQGUD=DPEUDQR'LHJR)HUQDQGR0RMLFDDQG0LW]\(7RUUHV6RULDQR
Symptoms ..................................................................................................................................................... 83
Fundus Findings ........................................................................................................................................... 83
Complementary Exams ................................................................................................................................ 84
MANAGEMENT ................................................................................................................................................ 88
REFERENCES ................................................................................................................................................... 89
CHAPTER 8 BRANCH RETINAL ARTERY OCCLUSION AND CILIORETINAL ARTERY OCCLUSION
....................................................................................................................................................................................... 90
5DXO9HOH]0RQWR\D
MANAGEMENT ................................................................................................................................................ 95
REFERENCES ................................................................................................................................................... 96
CHAPTER 9 RETINAL ARTERIAL MACROANEURYSM ........................................................................... 99
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ESSENTIALS OF DIAGNOSIS ..................................................................................................................... 100
DIFFERENTIAL DIAGNOSIS ...................................................................................................................... 104
MANAGEMENT .............................................................................................................................................. 104
CONFLICT OF INTEREST ........................................................................................................................... 105
ACKNOWLEDGEMENTS ............................................................................................................................. 105
REFERENCES ................................................................................................................................................. 105
CHAPTER 10 MACULAR TELANGIECTASIA ............................................................................................. 107
<RJLQ3DWHODQG0LFKDHO'2EHU
MANAGEMENT .............................................................................................................................................. 114
REFERENCES ................................................................................................................................................. 114
CHAPTER 11 SICKLE CELL RETINOPATHY .............................................................................................. 116
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MANAGEMENT .............................................................................................................................................. 122
REFERENCES ................................................................................................................................................. 123
CHAPTER 12 RADIATION RETINOPATHY ................................................................................................. 125
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MANAGEMENT .............................................................................................................................................. 127
REFERENCES ................................................................................................................................................. 128
CHAPTER 13 OCULAR ISCHEMIC SYNDROME ........................................................................................ 130
(OHRQRUD/DYDTXH
MANAGEMENT .............................................................................................................................................. 134
REFERENCES ................................................................................................................................................. 135
CHAPTER 14 DRY AGE-RELATED MACULAR DEGENERATION ......................................................... 136
$QD'RPtQJXH]<DWHVDQG9LUJLO$OIDUR
MANAGEMENT .............................................................................................................................................. 164
REFERENCES ................................................................................................................................................. 164
CHAPTER 15 WET AGE-RELATED MACULAR DEGENERATION ........................................................ 168
*HUDUGR*DUFtD$JXLUUH
MANAGEMENT .............................................................................................................................................. 182
REFERENCES ................................................................................................................................................. 184
CHAPTER 16 POLYPOIDAL CHOROIDAL VASCULOPATHY ................................................................ 186
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Epidemiology Essentials of PCV ............................................................................................................... 186
Clinical Essentials of PCV ......................................................................................................................... 187
MANAGEMENT .............................................................................................................................................. 190
REFERENCES ................................................................................................................................................. 191
CHAPTER 17 RETINAL ANGIOMATOUS PROLIFERATION (RAP) ...................................................... 193
0D[LPLOLDQR*RUGRQ
MANAGEMENT .............................................................................................................................................. 196
REFERENCES ................................................................................................................................................. 198
CHAPTER 18 CHOROIDAL NEOVASCULAR MEMBRANE IN DEGENERATIVE MYOPIA ............. 201
)HGHULFR)XUQR6ROD
MANAGEMENT .............................................................................................................................................. 206
REFERENCES ................................................................................................................................................. 206
CHAPTER 19 ANGIOID STREAKS .................................................................................................................. 207
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MANAGEMENT .............................................................................................................................................. 216
REFERENCES ................................................................................................................................................. 217
CHAPTER 20 PRESUMED OCULAR HISTOPLASMOSIS SYNDROME ................................................. 219
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MANAGEMENT .............................................................................................................................................. 224
REFERENCES ................................................................................................................................................. 225
CHAPTER 21 EPIRETINAL MEMBRANE ..................................................................................................... 227
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MANAGEMENT .............................................................................................................................................. 232
REFERENCES ................................................................................................................................................. 232
CHAPTER 22 IDIOPHATIC MACULAR HOLE ............................................................................................ 234
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Classification .............................................................................................................................................. 235
MANAGEMENT .............................................................................................................................................. 246
REFERENCES ................................................................................................................................................. 246
CHAPTER 23 MACULAR PSEUDO-HOLE .................................................................................................... 248
-RVH$5RFD+XJR/XJOLRDQG'DQLHOD5RFD
MANAGEMENT .............................................................................................................................................. 252
REFERENCES ................................................................................................................................................. 252
CHAPTER 24 VITREOMACULAR TRACTION ............................................................................................ 254
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MANAGEMENT .............................................................................................................................................. 258
REFERENCES ................................................................................................................................................. 259
CHAPTER 25 PSEUDOPHAKIC CYSTOID MACULAR EDEMA .............................................................. 261
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Pathogenesis ............................................................................................................................................... 261
Incidence and Risk Factors ........................................................................................................................ 264
MANAGEMENT .............................................................................................................................................. 268
REFERENCES ................................................................................................................................................. 272
CHAPTER 26 CENTRAL SEROUS CHORIORETINOPATHY ................................................................... 277
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MANAGEMENT .............................................................................................................................................. 281
REFERENCES ................................................................................................................................................. 283
SUBJECT INDEX .................................................................................................................................................... 286

i
FOREWORD
Drs. Torres, García, Gordon and Kon deliver a very useful and practical work that contains, in
this volume, a collection of images of retinal vascular diseases and macular diseases. The
editors have recruited a vast array of retina specialists from four continents to write the
different chapters that constitute this volume. The chapters are structured in such a way that
the reader may easily find pearls about the diagnosis, differential and treatment, accompanied
by beautiful pictures using different imaging modalities. Our subspecialty has had tremendous
advances in recent years regarding diagnostic imaging, and I’m sure ophthalmologists and
residents will find this compilation really useful and enjoyable.
Dr. Hugo Quiroz-Mercado

Retina Department
Asociación para evitar la Ceguera en Mexico
Mexico City
Mexico
E-mail: hugoquiroz@yahoo.com
ii
PREFACE
We are honored to contribute to the information and education of ophthalmology students

around the world. We have attempted to distill the current knowledge of medical practice and
basic science retina research into a diagnostic atlas of retinal diseases. This is a quick-
reference atlas eBook of the retina, edited by specialists in the field, essential to any
practicing ophthalmologist or resident who has more than a passing interest in diseases and
treatment of the retina.
This e-book includes contributors from Mexico, Venezuela, Argentina, Brazil, United States,
Denmark, Spain, Italy, Costa Rica and Peru. It is divided into three volumes: Volume I,
retinal vascular diseases, choroidal neovascularization related diseases, vitreomacular
interface, and other macular disorders; Volume II, traumatic retinopathies, diseases of
vitreous, peripheral degenerations, retinal detachment, pediatric retinal diseases, and retinal
dystrophies; and Volume III, posterior uveitis, tumors of the retina, and choroid.
This diagnostic atlas eBook of retinal diseases contains full-color, high quality images of the
most frequent retinal pathologies with a brief and comprehensive review of retinal diseases.
Each chapter includes essentials of diagnosis, differential diagnosis and treatment. The format
is concise, well organized, and didactic, without being exhaustive.
We hope and expect that our atlas of retina will facilitate in providing patients with the best
possible care.
ACKNOWLEDGEMENTS
We would like to express our gratitude to Judy Soriano, who provided support with english
composition and edition.
To our friends and colleagues without whose contribution would not have been possible to
realize this project.
We also want to thank the staff of Bentham Science for their help and support and give us the
opportunity to publish this eBook.
DEDICATION
This e-book is specially dedicated to Guillermo Manuel Gordon, MD. He inspired us to

always work hard and try our best. He was a friend and a recognized ophthalmologist of
Rosario-Argentina, who died on May 2nd, 2015.
iii
Dr. Mitzy E. Torres Soriano

Unidad Oftalmológica “Dr. Torres López”,
Centro Médico Cagua,
Aragua,
Venezuela
Dr. Gerardo García Aguirre

Retina Department,
Asociación para Evitar la Ceguera en Mexico,
Mexico City,
Mexico
Dr. Maximiliano Gordon

Centro de la Visión Gordon Manavella,
Rosario, Santa Fe,
Argentina
Dr. Veronica Kon Graversen

University of North Carolina at Chapel Hill,
Chapel Hill, NC,
USA
iv
List of Contributors
Universidad de Buenos Aires-Universidad del Salvador, Retina and
Andrés Bastien
Vitreous, Argentina
Retina Department, Centro Oftalmológico de Valencia (CEOVAL),

Aristides J. Mendoza Valencia, Venezuela
Retina Department, OftalmoSalud, Arequipa, Peru
Ana Domínguez Yates Retina Consultants of Charleston, Charleston, South Carolina, USA
Aziz A. Khanifar Retina Group of Washington, Washington DC, USA
Daniela Roca Ophthalmology Department, Clínica Ricardo Palma, Lima, Peru
Diego Fernando Mojica Centro Oftalmológico de Valencia (CEOVAL), Valencia, Venezuela
Department of Ophthalmology, Henry Ford Health Systems, Detroit, MI,

Daniel D. Kim
USA
Retina Deparmeant, Hospital Oftalmológico Santa Lucia, Buenos Aires,

Eleonora Lavaque
Argentina
Ophthalmology Service, Sanatorio Mapaci, Rosario, Argentina

Federico Furno Sola
Grupo Laser Visión, Rosario, Santa Fe, Argentina
Retina Department, Asociación para Evitar la Ceguera en Mexico, Mexico

Gerardo García Aguirre
City, Mexico
Guillermo Gordon Died
Hugo Luglio Macula D&T, Lima, Peru
Retina Department, Asociación para Evitar la Ceguera en México, IAP,

Jans Fromow Guerra
México City, México
Jose A. Roca Ophthalmology Department, Clínica Ricardo Palma, Lima, Peru
Centro Clínico, de Ojos Maracay, Maracay, Venezuela

Luis Felipe Rivero Centro Oftalmológico Regional Aragua “Filippo Sindoni”, Maracay,
Venezuela
Luis A. Acabá Sidney Kimmel College of Medicine, Philadelphia, PA, USA
Liriany Arrieta Ruiz Unidad Popular de Ojos (UPO), Maracay, Venezuela
Luke B. Lindsell Retina Group of Washington, Washington DC, USA
Uveitis Department, Asociación para Evitar la Ceguera en México. I.A.P,

Luz Elena Concha del Río
Mexico
Retina & Vitreous Service, Clínica Oftalmológica El Viñedo, Valencia,

Luis M. Suarez-Tata
Venezuela
v
Maximiliano Gordon Centro de la Visión Gordon-Manavella, Rosario, Santa Fe, Argentina
Maria H. Berrocal Berrocal & Asociados, San Juan, Puerto Rico
Centro de la Visión Gordon-Manavella, Rosario, Santa Fe, Argentina

Mitzy E. Torres Soriano Unidad Oftalmológica “Dr Torres López”, Centro Médico Cagua, Aragua,
Venezuela
Department of Ophthalmology, Henry Ford Health System, Detroit, MI,

Michael D. Ober USA
Retina Consultants of Michigan, Southfield, MI, USA
Department of Ophthalmology, Glostrup Hospital and Faculty of Health

Michael Larsen
Sciences, University of Copenhagen, Denmark
Department of Ophthalmology, Glostrup Hospital and Faculty of Health

Mette K.G. Andersen
Sciences, University of Copenhagen, Denmark
Department of Medical Sciences, Division of Health Sciences, Universidad

Manuel Garza León
de Monterrey, Monterrey, Nuevo León, México
Uveitis and Ocular Inmunology Department, Instituto de Oftalmología

Miguel Pedroza Seres Conde de Valenciana, México, DF. Clínica de Retina, Guadalajara, Jalisco,
Mexico

Moravia B. Suarez-Tata
Venezuela
Department of Ophthalmology, University of Colorado School of Medi-

Naresh Mandava
cine, Aurora, CO, USA
Retina Department, Grupo de Clínicas IDB, Centro Profesional Arca,

Nelson Segovia Rodríguez
Barquisimeto, Venezuela
Department of Ophthalmology, Henry Ford Health Systems, Detroit, MI,

Paul Baciu
USA
Retina Department, Asociación para Evitar la Ceguera en México, IAP,

Raul Velez-Montoya
Mexico City, Mexico
Universidad Central de Venezuela, Unidad de Neurooftalmología, Hospital

Rafael Muci Mendoza
Vargas de Caracas, Venezuela
Rodrigo Lechuga
Asociación para Evitar la Ceguera en Mexico, Mexico City, Mexico
Perezanta
Vitreoreitnal Disease and Surgery, Department of Ophthalmology,

Richard Hwang
University of Colorado School of Medicine, Aurora, CO, USA

Reinaldo García
Venezuela
Retina Department, Centro Oftalmológico de Valencia (CEOVAL),

Silvia Mendoza
Valencia, Venezuela
vi
Sandra Zambrano Centro Oftalmológico de Valencia (CEOVAL), Valencia, Venezuela
Retina Department, Asociación para Evitar la Ceguera en Mexico, Mexico

Virgilio Morales Cantón
City, Mexico
Veronica Kon Graversen University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Virgil Alfaro Retina Consultants of Charleston, Charleston, South Carolina, USA
Department of Ophthalmology, Henry Ford Health System, Detroit, MI,

Yogin Patel
USA
Ophthalmology: Current and Future Developments, 2016, Vol. 1, 3-17 3
CHAPTER 1
Non-Proliferative Diabetic Retinopathy

Luis Felipe Rivero1,2,* and Maximiliano Gordon3
1
Centro Clínico de Ojos Maracay, Maracay, Venezuela
2
Centro Oftalmológico Regional Aragua “Filippo Sindoni”, Maracay, Venezuela
3
Diabetic retinopathy (DR) is the most frequent ocular complication in patients

with diabetes mellitus. Its early and moderate stages are called non-proliferative
diabetic retinopathy (NPDR). It is characterized clinically by the presence of one
or more of the following signs: microaneurysms, intraretinal hemorrhages,
intraretinal microvascular anomalies (IRMA), cotton-wool spots (CWS), hard
exudates, and venous beading.
ESSENTIALS OF DIAGNOSIS
The hallmark of DR is the development of microaneurysms, which are small

dilations of the capillaries due to weakening of their walls and the loss of
pericytes [1]. They appear clinically as tiny red dots in the retinal stroma,
predominantly in and around the posterior pole. Eventually they may break,
leading to the formation of intraretinal hemorrhages. When the broken
microaneurysms are located in the most superficial layers of the retina, the
hemorrhage will take a flame or splinter-like appearance, oriented along the nerve
fiber layer. When they are located in the deeper layers, the hemorrhage will look
like a red dot or blot. Clinically, microaneurysms and dot hemorrhages are
indistinguishable (Fig. 1), so they are referred to as hemorrhages and/or
microaneurysms (H/Ma). Unless clotted, microaneurysms will show as
hyperfluorescent points in a fluorescein angiogram (FA). They may or may not
*
Corresponding author Luis Felipe Rivero: Centro Clínico de Ojos Maracay, Av. José María Vargas N° 18,
Maracay 2101, Edo. Aragua, Venezuela; Tel: +58(243) 241-8324/5243; E-mail: luife2020@hotmail.com
Mitzy E. Torres Soriano, Gerardo García Aguirre, Maximiliano Gordon & Veronica Kon Graversen (Eds.)
All rights reserved-© 2016 Bentham Science Publishers
4 Ophthalmology: Current and Future Developments, Vol. 1 Rivero and Gordon
leak dye depending on the integrity of their walls (Fig. 2). In an optic coherence
tomography (OCT), they appear as hyperreflective rings usually located in the
middle retinal layers [2] (Fig. 3). The smaller intraretinal hemorrhages will hardly
show in the FA, while the larger ones block the dye (Fig. 4). The largest
intraretinal hemorrhages may be seen in an OCT as moderately hyperreflective
masses located in the inner retinal layers.
Fig. (1). Intraretinal hemorrhages and microaneurysms. Left: Both deep intraretinal hemorrhages and
microaneurysms (H/Ma) appear as small red points and dots. Some of them are pointed with arrows. Right:
Superficial intraretinal hemorrhages have a splinter or flame shape (some of them are pointed with arrows).
Note that superficial hemorrhages as well as CWS follow the striations of the nerve fiber layer.
Capillary wall damage will lead to leakage of fluids and macromolecules. These
will accumulate in the retinal stroma producing macular edema, which can be
observed as areas of thickening of the retina. Lipoproteins diffusing from
microaneurysms or weakened capillaries will be trapped at the outer plexiform
layer forming the so-called hard exudates. They are irregularly shaped yellow-
white spots located slightly deeper in the retina and may coalesce with each other,
forming streaks, clusters or a circinate pattern centered on the leaking structure
(Fig. 5). They may accumulate in the center of the fovea forming a dense plaque,
which carries a very bad visual prognosis [3]. They are not usually seen on a FA,
except when they are extremely dense, causing minimum blockage of the dye. On
the OCT they appear as markedly hyperreflective and irregular interstitial images
with posterior shadowing (Fig. 6).
Non-Proliferative Diabetic Retinopathy Ophthalmology: Current and Future Developments, Vol. 1 5
Fig. (2). Fluorescein angiogram showing microaneurysms. They can be observed as well-defined hyper-
fluorescent (white) dots, appearing in the early phases of the study. Non-leaking microaneurysms will remain
as well-defined dots throughout the angiogram (some are circled in red). Leaking microaneurysms develop a
hazy area around them that increases along the study (some are circled in yellow).
As diabetic retinopathy progresses, there will be further damage to the arterioles

and capillaries, leading to progressive ischemia. Focal ischemia in the inner layers
will result in the arrest of the axoplasmic flow with the subsequent dilation of the
axons, constituting the so-called CWS [4]. Clinically they present as small
superficial grey-white fluffy spots with feathery borders (Fig. 7). They are usually
located near the temporal arcades and near the disc in the nasal retina. They look
hypofluorescent in the FA (Fig. 4). In an OCT they appear as more or less
pronounced focal thickenings of the nerve fiber layer with enhanced
hyperreflectivity (Fig. 8). Over some 6 to 12 months CWS will eventually fade,
leaving almost no signs of their former presence but relative scotomata [5] and
nicks in the inner retinal layers [6].
Fig. (3). OCT showing microaneurysms. Top: a large microaneurysm (white arrow) in the setting of a severe
(center involving) macular edema. Bottom: note that normal vessels (yellow arrows) look very similar to
microaneurysms (white arrows). However, normal vessels are usually found in the inner retinal layers (nerve
fiber layer or ganglion cell layer), while microaneurysms are usually located in the middle retinal layers. In
this case, they are all seen in the inner nuclear layer. The only way to positively differentiate one from the
other is to see where the B scan passes in comparison with the fundus image.
Fig. (4). Fluorescein angiogram of both CWS and flame hemorrhages. Note that both produce blockage of the
dye, although the hemorrhage does so more intensely.
Fig. (5). Hard exudates. Note that they usually form circinate patterns surrounding a group of micro-
aneurysms and that they tend to coalesce.
Fig. 6 contd.....
Fig. (6). a) In an OCT, hard exudates (black arrows) appear as highly hyperreflective and irregular images
with posterior shadowing, usually located by the outer plexiform layer; b) In some cases they form streaks,
especially around the fovea, in what constitutes a macular star (arrow shows one such streak); c) Hard
exudates may migrate and accumulate in the center of the fovea, forming plaques. This case shows early
migration of the lipids; d) These plaques may initiate an inflammatory response, leading to a retinal epithelial
detachment with subjacent fibrosis (red arrow), which carries a very poor visual prognosis.
Fig. (7). Cotton wool spots (arrows). Note their feathery borders and their distribution along the nerve fiber
layer bundle.
Fig. (8). OCT of CWS. Note the severe thickening and reflectivity enhancement of the nerve fiber layer.
Some vessels are seen passing through them. Top: Three adjacent CWS. Bottom: A single large CWS. They
are typically located in the perifoveal area.
In some cases, very small tortuous vessels may develop in the proximity of prior
CWS or in other ischemic areas. These are called IRMA, and are very difficult to
see clinically (Fig. 9). It is not clear what their nature is, but they are probably
intraretinal new vessels or perhaps intraretinal shunts bypassing non perfused
areas [7].
Fig. (9). IRMAs appear clinically as very small, tortuous and hard to see thread-like vessels. This patient has
multiple IRMAs in the inferior and nasal quadrants. Some of them are pointed with arrows.
The last sign of NPDR is venous beading, which is a succession of constrictions

and thickenings of the vein walls and translates significant ischemia (Fig. 10).
This is the feature most strongly associated with progression to proliferative
diabetic retinopathy [8]. As the capillary dropout increases it induces progressive
venous dilatation followed by the appearance of small bumps on the veins, and
finally, strictures will develop. Venous loops and sheathing may also appear.
Fig. (10). Left: Moderate, but significant venous beading. Arrows point to several constrictions. Center:
Severe venous beading with several successive constrictions and dilations of the vein walls. Right: Very
severe venous beading.
Fig. (11). Mild NPDR. Note that only a few microaneurysms can be seen in all four quadrants.
Fig. (12). Moderate NPDR. H/Ma, CWS, venous beading and hard exudates may be present, but do not meet
severity criteria. Note that all four quadrants must be examined to establish the degree of severity.
Classification
A simplified classification, the International Clinical Diabetic Retinopathy

Disease Severity Scale, was published in 2003 to facilitate the staging in the
clinical setting [9]. The part of the scale pertaining NPDR is shown in the
following table (Table 1).
Table 1. International clinical diabetic retinopathy disease severity scale.
Proposed Disease Severity Level Findings Observable with Dilated Ophthalmoscopy

No apparent DR No abnormalities
Mild nonproliferative DR (Fig. 11) Microaneurysms only
Moderate nonproliferative DR (Fig. 12) More than “mild” but less than “severe”
Severe nonproliferative DR (Fig. 13) Any of the following:
20 or more intraretinal hemorrhages in each of the 4 quadrants
Definite venous beading in 2 or more quadrants
Prominent IRMA in 1 or more quadrants and no neovascularization
Proposed by the Global Diabetic Retinopathy Project Group [9].
Fig. (13). Severe NPDR. In this case, more than 20 H/Ma can be counted in each of the four quadrants, along
with several CWS and some hard exudates.
DIFFERENTIAL DIAGNOSIS
Most ischemic diseases may mimic diabetic retinopathy. Especially important are
those pathologies that frequently concur with it, such as vein occlusions [10]
(Fig. 14), hypertensive retinopathy [11], ocular ischemic syndrome [12] and
subretinal neovascular membranes [13].
Fig. (14). Central vein occlusion simulating a severe NPDR in a diabetic patient. Venous tortuosity and
asymmetry with the other eye helped determine the right diagnosis.
Other diseases that should be considered include retinal macro aneurysms,

macular telangiectasias [14], radiation retinopathy [15], autoimmune retinopathies
(such as systemic lupus erythematosus and antiphospholipid syndrome) [16],
neoplasms (leukemia, lymphomas), HIV retinopathy, sickle cell disease [17],
Eales disease and CMV retinitis [18]. Usually the differential diagnosis is
straightforward when the patient is not diabetic or it is based on an examination of
the patient’s past medical history.
MANAGEMENT
The most important measure to prevent the appearance or to slow down the
progression of diabetic retinopathy is to optimize the metabolic control of the
patient [19 - 21]. This includes keeping both fasting and postprandial glycemic
levels within normal limits, hemoglobin A1c below 7%, normal serum lipids, and
a good, though not necessarily strict [22] control of blood pressure. Frequent
exercise, a healthy diet, a normal body mass index and avoiding tobacco may also
aid in maintaining a good metabolic control [23, 24]. Fenofibrate at 200 mg/d has
been shown to slow the progression of DR and should be considered to treat it
[22, 25].
Periodic controls are warranted to assess the evolution of the disease and to
determine the development of macular edema or proliferative retinopathy, which
would require treatment. Mild NPDR should be followed once a year, moderate
every six to 12 months, and severe quarterly [26].
CONFLICT OF INTEREST
The author(s) confirm that this chapter contents have no conflict of interest.
ACKNOWLEDGEMENTS
Declared none.
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simultaneous fluorescein angiography and spectral-domain optical coherence tomography. Am J
Ophthalmol 2012; 153(5): 861-867.e1.
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[3] Fong DS, Segal PP, Myers F, Ferris FL, Hubbard LD, Davis MD. Subretinal fibrosis in diabetic
macular edema. ETDRS report 23. Arch Ophthalmol 1997; 115(7): 873-7.
[http://dx.doi.org/10.1001/archopht.1997.01100160043006] [PMID: 9230827]
[4] McLeod D, Marshall J, Kohner EM, Bird AC. The role of axoplasmic transport in the pathogenesis of
retinal cotton-wool spots. Br J Ophthalmol 1977; 61(3): 177-91.
[http://dx.doi.org/10.1136/bjo.61.3.177] [PMID: 66930]
[5] Kim JS, Maheshwary AS, Bartsch DU, et al. The microperimetry of resolved cotton-wool spots in
eyes of patients with hypertension and diabetes mellitus. Arch Ophthalmol 2011; 129(7): 879-84.
[http://dx.doi.org/10.1001/archophthalmol.2011.51] [PMID: 21746978]
[6] Gomez ML, Mojana F, Bartsch DU, Freeman WR. Imaging of long-term retinal damage after resolved
cotton wool spots. Ophthalmology 2009; 116(12): 2407-14.
[http://dx.doi.org/10.1016/j.ophtha.2009.05.012] [PMID: 19815278]
[7] Campochiaro PA. Ocular neovascularization. J Mol Med 2013; 91(3): 311-21.
[http://dx.doi.org/10.1007/s00109-013-0993-5] [PMID: 23329331]
[8] ETDRS Report Number 12: Fundus photographic risk factors for progression of diabetic retinopathy.
Ophthalmology 1991; 98: 823-33.
[http://dx.doi.org/10.1016/S0161-6420(13)38014-2] [PMID: 2062515]
[9] Wilkinson CP, Ferris FL III, Klein RE, et al. Proposed international clinical diabetic retinopathy and
diabetic macular edema disease severity scales. Ophthalmology 2003; 110(9): 1677-82.
[10] Jaulim A, Ahmed B, Khanam T, Chatziralli IP. Branch retinal vein occlusion: epidemiology,
pathogenesis, risk factors, clinical features, diagnosis, and complications. An update of the literature.
Retina 2013; 33(5): 901-10.
[http://dx.doi.org/10.1097/IAE.0b013e3182870c15] [PMID: 23609064]
[11] Ojaimi E, Nguyen TT, Klein R, et al. Retinopathy signs in people without diabetes: the multi-ethnic
study of atherosclerosis. Ophthalmology 2011; 118(4): 656-62.
[12] Niestrata-Ortiz M, Li JP, Davies N. Rubeosis iridis in patients with diabetes: not forgetting
oculoischaemic syndrome as a differential. BMJ Case Rep 2014.
[http://dx.doi.org/10.1136/bcr-2014-207236]
[13] Hahn P, Acquah K, Cousins SW, Lee PP, Sloan FA. Ten-year incidence of age-related macular
degeneration according to diabetic retinopathy classification among medicare beneficiaries. Retina
2013; 33(5): 911-9.
[http://dx.doi.org/10.1097/IAE.0b013e3182831248] [PMID: 23407352]
[14] Díaz-Rodríguez EJ. Telangiectasias parafoveales idiopáticas tipo 2A. Arch Soc Esp Oftalmol 2005;
80(9): 541-5.
[http://dx.doi.org/10.4321/S0365-66912005000900010] [PMID: 16193439]
[15] Zamber RW, Kinyoun JL. Radiation retinopathy. West J Med 1992; 157(5): 530-3.
[PMID: 1441494]
[16] Sivaraj RR, Durrani OM, Denniston AK, Murray PI, Gordon C. Ocular manifestations of systemic
lupus erythematosus. Rheumatology (Oxford) 2007; 46(12): 1757-62.
[http://dx.doi.org/10.1093/rheumatology/kem173] [PMID: 17681981]
[17] Bonanomi MT, Lavezzo MM. Sickle cell retinopathy: diagnosis and treatment. Arq Bras Oftalmol
2013; 76(5): 320-7.
[18] Takayama K, Ogawa M, Mochizuki M, Takeuchi M. Cytomegalovirus retinitis in a patient with

proliferative diabetes retinopathy. Ocul Immunol Inflamm 2013; 21(3): 225-6.
[http://dx.doi.org/10.3109/09273948.2012.762983] [PMID: 23480605]
[19] The effect of intensive treatment of diabetes on the development and progression of long-term
complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329(14): 977-86.
[http://dx.doi.org/10.1056/NEJM199309303291401] [PMID: 8366922]
[20] Progression of retinopathy with intensive versus conventional treatment in the Diabetes Control and
Complications Trial. Ophthalmology 1995; 102(4): 647-61.
[21] Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment
and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352(9131): 837-
53.
[22] Chew EY, Davis MD, Danis RP, et al. Action to control cardiovascular risk in diabetes. Eye study
research group. The effects of medical management on the progression of diabetic retinopathy in
persons with type 2 diabetes: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye
Study. Ophthalmology 2014; 121(12): 2443-51.
[23] Sumamo E, Ha C, Korownyk C, Vandermeer B, Dryden DM. Lifestyle interventions for four
conditions: type 2 diabetes, metabolic syndrome, breast cancer, and prostate cancer [Internet].Fuente:
Rockville (MD): Agency for Healthcare Research and Quality (US); 2011 May. Report No.:
LFST1209. AHRQ Technology Assessments.
[24] Boretsky A, Gupta P, Tirgan N, et al. Nicotine accelerates diabetes-induced retinal changes. Curr Eye
Res 2015; 40(4): 368-77.
[PMID: 24911405]
[25] Keech AC, Mitchell P, Summanen PA, et al. Effect of fenofibrate on the need for laser treatment for
diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet 2007; 370(9600): 1687-97.
[26] American Academy of Ophthalmology Preferred Practice Patterns Committee. Preferred Practice
Pattern® Guidelines. Comprehensive Adult Medical Eye Evaluation. San Francisco, CA: American
Academy of Ophthalmology; 2014. Available at: www.aao.org/ppp.
18 Ophthalmology: Current and Future Developments, 2016, Vol. 1, 18-28
CHAPTER 2
Proliferative Diabetic Retinopathy (PDR)

Maria H. Berrocal1,* and Luis A. Acabá2
1
Berrocal & Asociados, San Juan, Puerto Rico
2
Sidney Kimmel College of Medicine, Philadelphia, PA, USA
Proliferative diabetic retinopathy (PDR) occurs as a progression of severe diabetic

vascular damage and includes intraretinal capillary closure with resultant ischemia
and the formation of new vessels (Figs. 1-3). Severe non-proliferative diabetic
retinopathy is the precursor of PDR. It includes diffuse intraretinal hemorrhages in
4 quadrants, venous beading in 2 quadrants or more and intra-retinal
microvascular abnormalities (IRMA) in 1 quadrant. The chance of progression to
PDR in 1 year is between 15% and 45% [1, 2].
Severe NPDR can be confused with PDR. Fluorescein angiography is the best
way to differentiate IRMA from neovascularization as the latter shows significant
leakage throughout the study. The evolution of new vessels starts with fine vessels
with minimal fibrosis, then an increase in vessel size and fibrous tissue, and then
the end stage of PDR which includes regressed vessels and significant
fibrovascular proliferation on the posterior hyaloid. Vitreous hemorrhage and sub-
hyaloid hemorrhage can result from PDR.
Differential diagnosis includes NPDR particularly when many IRMAs are present,
other retinovascular diseases like vein occlusions, sickle cell retinopathy,
*
Corresponding author Maria H. Berrocal: 150 Ave De Diego Ste 404, San Juan, 00907, Puerto Rico; Tel: (787)
725-9315; E-mail: mariahberrocal@hotmail.com
Proliferative Diabetic Retinopathy (PDR) Ophthalmology: Current and Future Developments, Vol. 1 19
leukemic retinopathy, hypertensive retinopathy, radiation retinopathy, retinal

vasculitis, sarcoidosis, and ocular ischemic syndrome. Differences in the clinical
picture and fluorescein angiographic appearance are usually sufficient to
discriminate bet-ween these entities.
A
Fig. (1). A. Red-free image of the right eye of a 35 year-old male with prominent neovascularization in the
posterior pole; B. Red-free image of the left eye in the same patient, showing neovascularization and
exudates.
20 Ophthalmology: Current and Future Developments, Vol. 1 Berrocal and Acabá
A B
Fig. (2-I). 66-year-old male with type 1 diabetes mellitus and proliferative diabetic retinopathy. A. Early
fluorescein angiography (FA) of the right eye showing multiple areas of capillary dropout and ischemia,
including the foveal area with enlarged foveal avascular zone. One area of NVE is present in the
superotemporal arcade; B. FA of the nasal retina with severe ischemia and capillary leakage; C. Late FA of
the same eye, showing diffused leakage in the posterior pole; D. OCT of retinal area near neovascularization
showing areas of localized tractional retinal detachment.
E F
Fig. (2-II). E. Image of the left eye, with prominent neovascularization in the disc; F. Early FA showing
intense staining of the neovascularization in the disc; G. FA of the temporal retina, showing severe capillary
dropout throughout the retina with diffused staining and microaneurysms; H. OCT of the fovea showing
macular edema with a large cyst.
Fig. (3). 35-year-old female with type 1 diabetes mellitus. A. Fundus photograph showing very prominent
neovascularization throughout the posterior pole; B. Same eye one week after 1.25 mg intravitreal
bevacizumab, with marked regression of neovascularization.
MANAGEMENT
Medical management includes optimizing diabetic control to prevent progression.

Conditions that can cause worsening of PDR include hypertension, anemia,
pregnancy and renal disease [1 - 4]. The Diabetes Control and Complications trial
(DCCT) showed that intensive glycemic control reduces the progression of PDR
[2].
The mainstay of treatment for high-risk PDR is scatter laser photocoagulation in a

pan retinal distribution (Figs. 4 and 5). This results in regression of neovascular
vessels and prevents progression of the disease [5, 6]. High risk PDR includes any
of these: 1. -mild neovascularization of the disc (NVD) with vitreous hemorrhage
(VH); 2. -moderate to severe NVD with or without hemorrhage; 3. -moderate (1/2
disc area) neovascularization elsewhere (NVE) with VH. Another definition of
high risk includes any three of: 1.-vitreous or pre-retinal hemorrhage; 2.- presence
of new vessels; 3.- new vessels on or near optic nerve (ON); 4.-moderate or severe
neovascularization.
A
Fig. (4A). 40-year-old female with tractional retinal detachment. A. Preoperative image showing
fibrovascular tissue throughout the arcades.
B
Fig. (4B). Postoperative image showing flattened retina, laser photocoagulation scars in the periphery and
residual hemorrhage in the inferior arcade.
A B
C D
Fig. (5). 27 year-old female with type 1 diabetes mellitus. A. Fundus photograph of the right eye showing
neovascularization in the superotemporal arcade, hard exudates and microaneurysms in the posterior pole; B.
FA showing neovascularization with leakage, venous beading and capillary dropout; C. Fundus photograph
of the same eye 8 months later, after panretinal photocoagulation was applied, with some fibrosis in the
superotemporal arcade; D. FA showing increased neovascularization, venous beading and capillary closure.
E F
Fig. (5). E. Fundus photograph of the same eye 11 months after photocoagulation, with a tractional retinal
detachment and massive neovascularization throughout the posterior pole; F. Nasal view of the same eye; G.
Fundus photograph 3 months after vitrectomy with preoperative bevacizumab.
Full PRP is defined as 1,200 or more 500µm spots separated by 1/2 burn width
and 0.1s duration. This can be performed in 1 or 2 sessions.
Surgical management of PDR is performed when there is persistent or severe VH

and or traction retinal detachment threatening the fovea. The Diabetic Retinopathy
Vitrectomy Study (DRVS) results showed a greater benefit of early vitrectomy in
VH eyes in type 1 diabetics, and in very severe PDR (Figs. 4-7) [7].
The advent of VEGF inhibitor therapy for many conditions has made its use
appealing in the treatment of diabetic retinopathy (Fig. 3). Although the benefit of
these agents has been validated for the treatment of diabetic macular edema,
panretinal photocoagulation remains the mainstay of treatment of PDR.
Fig. (6). Tabletop neovascular fibrovascular proliferation in an eye with a tractional retinal detachment.
Fig. (7). 36-year-old with type 1 diabetes mellitus and no prior laser photocoagulation. A. Massive
fibrovascular proliferation causing circumferential traction and a combined rhegmatogenous-tractional retinal
detachment: B. Peripheral view of fibrovascular sheet with very large neovascular vessels.
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1] Davis MD, Fisher MR, Gangnon RE, et al. Risk factors of high-risk proliferative diabetic retinopathy
and severe visual loss: ETDRS Report 18. Invest Ophthalmol Vis Sci 1998; 39: 233-52.
[PMID: 9477980]
[2] Progression of retinopathy with intensive versus conventional treatment in the Diabetes Control and
Complications Trial. Ophthalmology 1995; 102(4): 647-61.
[3] Tight blood pressure control and risk of macrovascular and microvascular complications in type 2
diabetes: UKPDS 38. BMJ 1998; 317(7160): 703-13.
[http://dx.doi.org/10.1136/bmj.317.7160.703] [PMID: 9732337]
[4] Davis MD, Fisher MR, Gangnon RE, et al. Risk factors of high-risk proliferative diabetic retinopathy
and severe visual loss: ETDRS Report 18. Invest Ophthalmol Vis Sci 1998; 39: 233-52.
[PMID: 9477980]
[5] Early photocoagulation for diabetic retinopathy. ETDRS report number 9. Ophthalmology 1991; 98(5)
(Suppl.): 766-85.
[6] Photocoagulation treatment of proliferative diabetic retinopathy. Clinical application of Diabetic
Retinopathy Study (DRS) findings, DRS Report Number 8. Ophthalmology 1981; 88(7): 583-600.
[PMID: 7196564]
[7] Early vitrectomy for severe proliferative diabetic retinopathy in eyes with useful vision: results of a
randomized trial. DRVS report 3. Diabetic Retinopathy Vitrectomy Study Research Group.
CHAPTER 3
Diabetic Macular Edema

Maximiliano Gordon1,2,* and Mitzy E. Torres Soriano1,2,3
1
2
Retina Department, Ophthalmology Service, Hospital Provincial del Centenario, Rosario, Santa
Fe, Argentina
3
Unidad Oftalmológica “Dr Torres López”, Centro Médico Cagua, Aragua, Venezuela
Diabetic macular edema (DME) is the main cause of visual loss in diabetic
patients. It may present at every stage of diabetic retinopathy.
The systemic risk factors identified for DME are hyperglycemia, arterial
hypertension, hyperlipidemia, kidney failure and anemia [1, 2].
Diabetic macular edema is diagnosed with a detailed bio-microscopic examination

with the slit lamp and indirect ophthalmoscopy.
The Early Treatment Diabetic Retinopathy Study (ETDRS) described DME as

retinal thickening or hard exudates (consisting of lipoproteins) within 1 disk
diameter of the center of the macula (Figs. 1, 2, 4a, 5a-b, 6a, 8, 11a).
The term clinically significant macular edema (CSME) indicates the severity of
macular edema and is used for treatment guidelines. CSME is characterized by: 1)
thickening of the retina within 500 µm of the macular center; 2) hard exudates at
the center of the retina or within 500 µm with thickening of adjacent retina; and 3)
one or more disc diameters of retinal thickening, part of which is within one disc
diameter of the center of the macula [3].
*
Corresponding author Maximiliano Gordon: Centro de la Vision Gordon - Manavella, Montevideo 763, CP 2000,
Rosario - Santa Fe, Argentina; Tel: +54 (0341) 4 400 239; E-mail: maximilianogordon19@gmail.com
30 Ophthalmology: Current and Future Developments, Vol. 1 Gordon and Torres Soriano
Fig. (1). Fundus photograph of CSME in both eyes. Microaneurysms, hard exudates and retinal hemorrhages
are shown.
Fig. (2). Fundus photograph of severe and clinically significant diabetic macular edema in both eyes.
In 2002, the American Academy of Ophthalmology proposed an international

classification of DME (Table 1): DME absent: absence of retinal thickening or
hard exudates in the posterior pole. DME present: some retinal thickening or hard
exudates in the posterior pole.
Table 1. International clinical diabetic macular edema (DME) disease severity scale.
Proposed Disease Findings observable on Dilated Ophthalmoscopy

Severity Level
Mild DME Some retinal thickening or hard exudates in posterior pole but far from the
macula center
Moderate DME Retinal thickening or hard exudates that approach the macular center but
without involving it
Severe DME Retinal thickening or hard exudates involving the macula center
Program and abstracts of the American Academy of Ophthalmology 2002 [4].
Diabetic Macular Edema Ophthalmology: Current and Future Developments, Vol. 1 31
Classically, three different types of DME can be observed in fluorescein

angiography (FA): 1) focal leakage: well-defined focal area of leakage from
micro-aneurysms or dilated capillaries (Figs. 3-6); 2) diffuse leakage: wide-
spread leakage from IRMA, retinal capillary bed (Fig. 7); and 3) diffuse cystoid
leakage: diffuse leakage and pooling of dye in the cystic spaces of the macula in
the late phase of the angiogram [5]. However, one of the most important utilities
of the angiography is to roll out macular ischemia (Fig. 7). It has long been
considered that ischemic changes and microvascular pathologies are key in the
development of DME. In diabetic retinopathy, peripheral ischemia leads to an
increased production of vascular endothelial growth factor (VEGF), which can
result in the breakdown of blood-retinal barriers, thus increasing retinal vessel
permeability and causing DME. These areas can be detected using ultra-wide field
fluorescein angiography [6].
a b
c d
Fig. (3). FA of the same patient as shown in Fig. (1). (a-b) Multiple hyperfluorescent points due to
mycroaneurisms with mild leakage in late phases (c-d).
a b
c d
e f
Fig. (4). Fundus photograph (a-b) and FA (c-d) of focal diabetic macular edema. OCT showing focal
increased macular thickness and cystoid macular edema (e-f).
a b
c d
e
f
Fig. (5). (a-b) CSME with abundant and confluent hard exudates involving fovea. (c-d) FA shows multiple
hyperfluorescent points due to microaneurysms with mild leakage in late phases (e-f).
a b
c d
Fig. (6). (a) Fundus photograph of DME in right eye. (b-d) FA shows hyperfluorescent points with mild
leakage in late phases.
a b
c d
Fig. (7). (a) Fundus photograph reveals retinal round hemorrhages and hard exudates in a diabetic female
patient. (b-c) FA shows hypofluorescence from capillary dropout, typical of ischemic diabetic maculopathy
and (d) late hyperfluorescence due to diffuse perivascular leakage.
OCT has shown four important changes in neurosensory retinal structure: cystoid
macular edema (CME) (Figs. 4e-f, 8 and 10), swelling of the retina (Figs. 9 and
10), serous retinal detachment (Fig. 11b), and retinal traction (Fig. 12) [5].
Fig. (8). Cystoid diabetic macular edema with a significant amount of hypereflective foci that correspond to
hard exudates.
Fig. (9). 59 year-old male patient with insulin dependent diabetes mellitus and diabetic retinopathy. Spectral
domain-optical coherence tomography showing (a) focal cystoid diabetic macular edema in his right eye; and
(b) diffuse diabetic macular edema showing retinal swelling and cystoid spaces in his left eye. Visual Acuity:
OD 20/25 OS 20/200.
Fig. (10). Spectral domain-optical coherence tomography showing diffuse diabetic macular edema,
intraretinal dense hard exudates with posterior shadow and hypo-reflective outer retinal layers.
Fig. (11). (a) Fundus photograph of CSME; (b) OCT shows small and medium cystoid intraretinal spaces and
subretinal serous detachment.
Fig. (12). Spectral domain-optical coherence tomography showing diabetic macular edema with vitreoretinal
traction component.
Other causes of macular edema may be hypertensive retinopathy (it can coexist),
vein occlusion (central vein or branch), pseudophakic macular edema, uveitis
(anterior or posterior), radiation retinopathy, and active choroidal neovascu-
larization.
MANAGEMENT
Of the utmost necessity is the strict control of diabetes, hypertension, and

hypercholesterolemia.
Diabetic macular edema is usually a chronic disease. Although sometimes

spontaneous recovery is possible, patients that do not receive treatment will
experience a moderate visual loss (15 or more letters on the ETDRS chart) within
3 years in 24% of CSME cases and in 33% of center-involving CSME cases
[7 - 9].
Laser Photocoagulation: In the ETDRS, grid laser treatment in diffuse macular

edema revealed that treated eyes showed improved visual acuity in 16% of cases,
remained unchanged in 77% of cases, and worsened in 7% of cases, while these
results changed to 11%, 73%, and 16%, respectively, after 2 years of follow-up
[3]. Therefore, these results did not show substantial benefit in treated eyes [10].
However, in patients with focal DME, a focal laser pattern is used for the
treatment of leaking micro-aneurysms revealed by the FA.
Steroids: Some reports suggest the beneficial effects of subtenon or peribulbar

steroid injection therapy for DM [11, 12]. Intravitreal injection of triamcinolone
acetonide is a treatment option for patients with DME who do not respond to laser
photocoagulation. The most frequent ocular adverse effects associated to
corticosteroids are glaucoma and cataract. Actually, some fluocinolone acetonide
implants and dexamethasone long standing delivered intravitreal implants were
approved for DME treatment [5, 10, 13, 14].
Anti-VEGF therapy: Blockage of VEGF has shown to reduce vascular

permeability [5]. Intra-vitreous injection of anti-VEGF agents has been proven to
be a relatively safe treatment option for diabetic edema (Fig. 13) and more
effective than laser photocoagulation of the macula. The most commonly used
VEGF inhibitors are aflibercept (Eylea, Regeneron Pharmaceuticals), ranibizumab
(Lucentis, Genentech) and bevacizumab (Avastin, Genentech) [15]. The first two
are approved for intraocular use by the FDA. Bevacizumab is not approved for
intraocular treatment, but it is used as an off-label therapy.
Fig. (13). 60 year-old male patient with diabetic retinopathy. Spectral domain-optical coherence tomography
showing (a) diabetic macular edema; and (b) resolution after repeated intravitreal bevacizumab in his right
eye. Retinal thickness is significantly decreased.
Micro-pulse laser is a treatment option for DME [16 - 18] that produces multiple
short exposure burns localized to the apical portion of the RPE, with minimal
effects to the surrounding structures [5].
Pars plana vitrectomy may be used to remove vitreomacular traction, which can
reduce the concentration of DME-promoting factors and also improve the fluid
currents and thus the inner retinal oxygenation [5].
The management of DME remains complex, so a combined treatment approach is

often necessary in order to address the persistence of fluid within the macular
region.
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1] Klein R, Klein BE, Moss SE. The epidemiology of ocular problems in diabetes mellitus. In: Feman SS,
Ed. Ocular problems in diabetes mellitus. Boston: Blackwell Scientific Publications 1991; pp. 1-51.
[2] Klein R, Klein BE, Moss SE, Cruickshanks KJ. The Wisconsin epidemiologic study of diabetic
retinopathy. XV. The long-term incidence of macular edema. Ophthalmology 1995; 102(1): 7-16.
[3] Photocoagulation for diabetic macular edema. Early treatment diabetic retinopathy study report
number 1. Early treatment diabetic retinopathy study research group. Arch Ophthalmol 1985; 103(12):
1796-806.
[4] Wilkinson CP. Achieving consensus on an international clinical classification for diabetic retinopathy.
Annual Meeting. October 20-23, 2002; Orlando, Florida.
[5] Bhagat N, Grigorian RA, Tutela A, Zarbin MA. Diabetic macular edema: pathogenesis and treatment.
Surv Ophthalmol 2009; 54(1): 1-32.
[http://dx.doi.org/10.1016/j.survophthal.2008.10.001] [PMID: 19171208]
[6] Wessel MM, Nair N, Aaker GD, Ehrlich JR, D’Amico DJ, Kiss S. Peripheral retinal ischaemia, as
evaluated by ultra-widefield fluorescein angiography, is associated with diabetic macular oedema. Br J
Ophthalmol 2012; 96(5): 694-8.
[http://dx.doi.org/10.1136/bjophthalmol-2011-300774] [PMID: 22423055]
[7] Early treatment diabetic retinopathy study R. photocoag-ulation for diabetic macular edema. Early
treatment diabetic retinopathy study report number 1. Early treatment diabetic retinopathy study
research group. Arch Ophthalmol 1985; 103(12): 1796-806.
[8] Ferris FL, Podgor MJ, Davis MD. Macular edema in diabetic retinopathy study patients. Diabetic
retinopathy study report number 12. Ophthalmology 1987; 94(7): 754-60.
[http://dx.doi.org/10.1016/S0161-6420(87)33526-2]
[9] Ferris FL III, Patz A. Macular edema. A complication of diabetic retinopathy. Surv Ophthalmol 1984;
28 (Suppl.): 452-61.
[http://dx.doi.org/10.1016/0039-6257(84)90227-3] [PMID: 6379946]
[10] Yaseri M, Zeraati H, Mohammad K, et al. Intravitreal bevacizumab injection alone or combined with
triamcinolone versus macular photocoagulation in bilateral diabetic macular edema; application of
bivariate generalized linear mixed model with asymmetric random effects in a subgroup of a clinical
trial. J Ophthalmic Vis Res 2014; 9(4): 453-60.
[http://dx.doi.org/10.4103/2008-322X.150818] [PMID: 25709771]
[11] Bakri SJ, Kaiser PK. Posterior subtenon triamcinolone acetonide for refractory diabetic macular
edema. Am J Ophthalmol 2005; 139(2): 290-4.
[12] Entezari M, Ahmadieh H, Dehghan MH, Ramezani A, Bassirnia N, Anissian A. Posterior sub-tenon
triamcinolone for refractory diabetic macular edema: a randomized clinical trial. Eur J Ophthalmol
2005; 15(6): 746-50.
[PMID: 16329060]
[13] Panozzo G, Gusson E, Panozzo G, Dalla Mura G. Dexamethasone intravitreal implant for diabetic
macular edema: indications for a PRN regimen of treatment. Eur J Ophthalmol 2015; 25(4): 347-51.
[http://dx.doi.org/10.5301/ejo.5000563] [PMID: 25633618]
[14] A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for
diabetic macular edema. Ophthalmology 2008; 115(9): 1447-1449, 1449.e1-1449.e10.
[15] Wells JA, Glassman AR, Ayala AR, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic
macular edema. N Engl J Med 2015; 372(13): 1193-203.
[http://dx.doi.org/10.1056/NEJMoa1414264] [PMID: 25692915]
[16] Friberg TR, Karatza EC. The treatment of macular disease using a micropulsed and continuous wave
810-nm diode laser. Ophthalmology 1997; 104(12): 2030-8.
[http://dx.doi.org/10.1016/S0161-6420(97)30061-X] [PMID: 9400762]
[17] Moorman CM, Hamilton AM. Clinical applications of the MicroPulse diode laser. Eye (Lond) 1999;
13(Pt 2): 145-50.
[http://dx.doi.org/10.1038/eye.1999.41] [PMID: 10450372]
[18] Stanga PE, Reck AC, Hamilton AM. Micropulse laser in the treatment of diabetic macular edema.
Semin Ophthalmol 1999; 14(4): 210-3.
[http://dx.doi.org/10.3109/08820539909069539] [PMID: 10758221]
CHAPTER 4
Central Retinal Vein Occlusion

Nelson Segovia Rodríguez*
Retina Department, Grupo de Clínicas IDB, Centro Profesional Arca, Barquisimeto, Venezuela
Central retinal vein occlusion (CRVO), a member of the group of vascular retinal
diseases, is a sight-threatening condition that needs to be correctly diagnosed and
treated in order to diminish its consequences, which can lead to painful blindness
if neovascular glaucoma (NVG) develops. CRVO occurs predominantly in adults
of 65 years old and over [1]; the prevalence does not differ by gender [2], and it is
predominantly unilateral [3]. Some described systemic risk factors are end-organ
damage from hypertension or diabetes, a hypercoagulable state, and a diagnosis of
stroke or obstructive sleep apnea [4, 5]. The most described ocular risk factor is
glaucoma. Patients with CRVO also show an increased (almost two-fold)
incidence in cerebrovascular accidents compared with age and sex-matched
controls in a US population [6].
Fortunately, this is a relatively easy condition to diagnose based mostly on its

clinical features. CRVO commonly presents as a sudden and painless loss of
vision. Occasionally, the vision loss occurs gradually, mostly happens at night
time in the recumbent position probably by low blood pressure and/or high central
venous pressure. The typical fundoscopic features appear in all the four quadrants
of the fundus: venous tortuosity and dilation, retinal hemorrhages (scattered
superficial and deep), and cotton wool spots (Figs. 1-3). Macular edema and optic
disc swelling are also present. All these features are present in varying degrees
depending on the severity of the occlusion. Long-standing CRVO should be
*
Corresponding author Nelson Segovia Rodríguez: Retina Department, Grupo de Clínicas IDB, Centro Profesional
Arca, Barquisimeto, Venezuela; Tel: +57(315)5929618; Email: nelsegovia@yahoo.com
Central Retinal Vein Occlusion Ophthalmology: Current and Future Developments, Vol. 1 45
suspected if occluded or sheathed retinal veins are observed, or if vascular anas-

tomoses (known as optociliary collaterals) at the optic disc are detected (Fig. 4).
Fig. (1). Central Retinal Vein Occlusion. Fundus photograph shows tortuosity and dilatation of all branches
of the central retinal vein, dot and flame-shaped hemorrhages, macular edema and optic nerve head cupping
is noted. (Courtesy of Mitzy E. Torres Soriano).
Fig. (2). Fundus photograph showing massive intraretinal hemorrhages, venular tortuosity, cotton wool spots
and macular edema, corresponding to an ischemic CRVO.
46 Ophthalmology: Current and Future Developments, Vol. 1 Nelson Segovia Rodríguez
Fig. (3). Red-free photograph shows the typical features of CRVO, corresponding to a non-ischemic CRVO.
Fig. (4). Eye fundus of a patient with long standing CRVO demonstrating optociliary shunts vessels
(optociliary collaterals) in the optic nerve head, and panretinal photocoagulation.
CRVO can be divided into 2 clinical types, ischemic and non-ischemic. Non-
ischemic CRVO (Figs. 3, 5, 6) is the most common type, accounting for about
75% CRVO cases. Non-ischemic CRVO is characterized by mild to moderate loss
of acuity, usually 20/200 or better, and an absent or mild relative afferent
pupillary defect. Conversion to ischemic CRVO occurs in 15% of cases within 4
months and 34% within 3 years. Ischemic CRVO (Figs. 2, 7, 8) is characterized

by severe visual loss (20/200 or worse), a marked afferent pupillary defect,
extensive typical fundoscopic features (Fig. 7), poor perfusion to retina, and
presence of severe electroretinographic changes [7].
In addition to the general clinical assessment made by the patient’s physician,

including a complete blood count, renal function (serum levels of urea and
creatinine), fasting serum lipids and fasting serum levels of glucose and glycated
hemoglobin, a complete evaluation should include:
Fig. (5). Non-ischemic CRVO. Fundoscopy shows tortuosity and dilatation of all branches of the central
retinal vein, dot/blot and flame-shaped hemorrhages, throughout all four quadrants. (Courtesy of Mitzy E.
Torres Soriano).
Fluorescein Angiography (FA): Fluorescein angiography (FA) reveals marked

delay in arteriovenous transit time, which is longer than 20 seconds, masking by
retinal hemorrhages, vessel wall staining, leakage and perfusion status (greater
than 10 disc areas of retinal capillary non-perfusion is the ischemic form) [7, 8]
(Figs. 6, 8-11).
Fig. (6). Fluorescein angiography of (Fig. 5). It reveals delay in arteriovenous transit time, blockage from
retinal hemorrhages, vessel wall staining; in late phases cystoid macular edema (petalloid appearance) and
optic nerve staining. (Courtesy of Mitzy E. Torres Soriano).
Fig. (7). Ischemic CRVO. Fundoscopy showing extensive hemorrhages in the posterior pole and giving the
"blood and thunder appearance". (Courtesy of Mitzy E. Torres Soriano).
Fig. (8). Fluorescein angiography of the eye showing in Fig. (7), showing hypofluorescence due to blockage
from hemorrhages in the retina, capillary non perfusion and areas of capillary leakage. (Courtesy of Mitzy E.
Torres Soriano).
Fig. (9). Fluorescein angiography (FA) image showing optic nerve head swelling, engorged venules,
hypofluorescence by blockage and capillary non-perfusion.
Fig. (10). FA image shows closely the capillary dilation in the optic nerve head and vessel wall staining.
Fig. (11). FA of the mid-periphery showing zones of non-perfusion and capillary abnormalities.
Optical Coherence Tomography (OCT): Optical Coherence Tomography

(OCT) images reveal that the increased retinal thickness is caused mostly by large
cystoid spaces in the inner nerve layer of the foveal region and diffuse intraretinal
edema of the foveal and perifoveal areas [7, 9] (Figs. 12, 13).
Fig. (12). Optical coherence tomography (OCT) of a patient with CRVO and associated macular edema
showing a central field retinal thickness of 794 microns.
Fig. (13). OCT report of the same patient of Fig. (12) shows some clinical features of CRVO like intra retinal
hemorrhages and venous tortuosity. In the OCT image, increased retinal thickness, intra retinal cystoid spaces
of different sizes and neurosensory retina detached from retinal pigment epithelium can be observed (serous
retinal detachment or subretinal fluid).
Electroretinogram (ERG): Electroretinogram (ERG) shows reduced scotopic

and photopic b-wave amplitude in the ischemic form. Another important predictor
of neovascularization is a delayed implicit time in the photopic 30Hz flicker ERG.
Differential diagnosis of CRVO is not a difficult task. Other pathologies such as

diabetic retinopathy, hypertensive retinopathy, and hyperviscosity syndromes
occur bilaterally. If CRVO occurs bilaterally, a careful clinical systemic
examination should be done. Other entities that should be ruled out are anterior
ischemic neuropathy and ocular ischemia with venous stasis retinopathy [10]
caused by severe carotid artery obstructive disease. Most difficulties in the
differential diagnosis are encountered with early, mild non-ischemic CRVO and
late forms and complications that can mimic other conditions.
MANAGEMENT
Treatment of CRVO is mainly focused on macular edema and also on NVG.

Many treatment options have been tried through the years from systemic, local
(ocular medication) to surgical ones. The objective of this chapter is only to name
a few of them, focusing on the actual trends.
Panretinal photocoagulation (PRP) (Fig. 4) is indicated in the case of iris or angle

neovascularization. In the case of optic disc neovascularization or neovascul-
arization elsewhere, PRP also should be performed in order to avoid anterior
segment neovascularization and the consequent NVG. It has been fully
established in the CVOS Study that prophylactic treatment does not prevent iris
and angle neovascularization. Furthermore, regression of iris and angle
neovascularization in response to PRP is more likely to occur in eyes that have not
been treated previously [11]. The main treatments for macular edema are
intravitreal injections of ranibizumab, aflibercept, dexamethasone intravitreal
implant, and off-label use of bevacizumab and triamcinolone. Ranibizumab
showed to be effective, improving the best corrected visual acuity (BCVA) by 15
letters compared to placebo injections at six months [12, 13]. This improvement
was also true with the use of bevacizumab [14]. Aflibercept also showed an
improvement of BCVA, and this result was largely maintained between 6 to 12
months [15]. This evidence, based on randomized clinical trials, shows the
important role of anti-vascular endothelial grow factor (anti-VEGF) in the
treatment of CRVO (Fig. 14). Dexamethasone intravitreal implants improved
Fig. (14). Response to anti-VEGF treatment for macular edema secondary to CRVO. Top: OCT of an eye
with non-ischemic CRVO, showing accumulation of intraretinal fluid and a subfoveal serous retinal
detachment. Visual acuity was 20/40 Bottom: OCT of the same eye, after four doses of 1.25 mg intravitreal
bevacizumab, showing resolution of intra and subretinal fluid. Visual acuity improved to 20/20. (Images
courtesy of Gerardo Garcia-Aguirre, MD).
mean BCVA at 1, 2 and 3 months, but not at six months compared to placebo
[16]. With the use of triamcinolone, the percentage of patients with a gain of
BCVA of 15 letters or more was 26.5%, 25.6% and 6.8% for triamcinolone 1 mg,
4 mg and placebo, respectively. Both triamcinolone concentrations stabilized
visual acuity at month 12 [17]. By comparing the issues of secondary effects
between the use of anti-VEGF drugs and steroids, it has been observed that in the
latter group the rise in intraocular pressure and rate of cataract progression were
higher than in control groups [16, 17]. A study from the European Vitreoretinal
Society also suggests that vitrectomy with internal limiting membrane peeling
may be a good treatment for macular edema due to CRVO. In this study, the
improvement of vision was better than other therapies at every time point in time
[18]. In future, randomized clinical trials are needed to verify these results and
establish a standard of care for the treatment of macular edema secondary to
CRVO.
Follow up: Patients with CRVO should be seen monthly for 6 months to detect
the onset of anterior segment neovascularization and to establish prompt treat-
ment.
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1] Mruthyunjaya P, Fekrat S. Central Retinal Vein Occlusion. In: Stephen J Ryan RETINA. Fourth
Edition. Medical Retina: Elsevier 2006; II: pp. 1339-48.
[http://dx.doi.org/10.1016/B978-0-323-02598-0.50076-8]
[2] Rogers S, McIntosh RL, Cheung N, et al. The prevalence of retinal vein occlusion: pooled data from
population studies from the United States, Europe, Asia, and Australia. Ophthalmology 2010; 117(2):
313-9.e1.
[3] Klein R, Klein BE, Moss SE, Meuer SM. The epidemiology of retinal vein occlusion: the Beaver Dam
Eye Study. Trans Am Ophthalmol Soc 2000; 98: 133-41.
[PMID: 11190017]
[4] Stem MS, Talwar N, Comer GM, Stein JD. A longitudinal analysis of risk factors associated with
central retinal vein occlusion. Ophthalmology 2013; 120(2): 362-70.
[5] Risk factors for central retinal vein occlusion. Arch Ophthalmol 1996; 114(5): 545-54.
[6] Werther W, Chu L, Holekamp N, Do DV, Rubio RG. Myocardial infarction and cerebrovascular
accident in patients with retinal vein occlusion. Arch Ophthalmol 2011; 129(3): 326-31.
[7] Hayreh SS. Classification of central retinal vein occlusion. Ophthalmology 1983; 90(5): 458-74.
[8] Wong T, Scott I. Clinical practice. Retinal-vein occlusion. N Engl J Med 2010; 363(22): 2135-44.
[9] Ko TH, Fujimoto JG, Schuman JS, et al. Comparison of ultrahigh- and standard-resolution optical
coherence tomography for imaging macular pathology. Ophthalmology 2005; 112(11): 1922.e1-
1922.e15.
[10] Kearns TP, Hollenhorst RW. Venous-stasis retinopathy of occlusive disease of the artery. Proc Staff
Meet Mayo Clin 1963; 38: 304-12.
[PMID: 14043286]
[11] A randomized clinical trial of early panretinal photocoagulation for ischemic central vein occlusion.
The central vein occlusion study group N report. Ophthalmology 1995; 102(10): 1434-44.
[12] Brown DM, Campochiaro PA, Singh RP, et al. Ranibizumab for macular edema following central
retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology 2010;
117(6): 1124-1133.e1.
[13] Kinge B, Stordahl PB, Forsaa V, et al. Efficacy of ranibizumab in patients with macular edema
secondary to central retinal vein occlusion: results from the sham-controlled ROCC study. Am J
Ophthalmol 2010; 150(3): 310-4.
[14] Epstein DL, Algvere PV, von Wendt G, Seregard S, Kvanta A. Benefit from bevacizumab for macular
edema in central retinal vein occlusion: twelve-month results of a prospective, randomized study.
Ophthalmology 2012; 119(12): 2587-91.
[15] Brown DM, Heier JS, Clark WL, et al. Intravitreal aflibercept injection for macular edema secondary
to central retinal vein occlusion: 1-year results from the phase 3 COPERNICUS study. Am J
Ophthalmol 2013; 155(3): 429-437.e7.
[16] Haller JA, Bandello F, Belfort R Jr, et al. Randomized, sham-controlled trial of dexamethasone
intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology
2010; 117(6): 1134-1146.e3.
[17] Ip MS, Scott IU, VanVeldhuisen PC, et al. A randomized trial comparing the efficacy and safety of
intravitreal triamcinolone with observation to treat vision loss associated with macular edema
secondary to central retinal vein occlusion: the Standard Care vs Corticosteroid for Retinal Vein
Occlusion (SCORE) study report 5. Arch Ophthalmol 2009; 127(9): 1101-14.
[18] Adelman R, Parnes A, Bopp S, Saad I, Ducournau D. 2015; Strategy for the management of macular
edema in retinal vein occlusion: The European vitreo retinal society macular edema study. Biomed Res
Int 2015; 2015: 870987.
CHAPTER 5
Branch Retinal Vein Occlusion

Liriany Arrieta Ruiz1 and Gerardo García Aguirre2,*
1
Unidad Popular de Ojos (UPO), Maracay, Venezuela
2
Retina Department, Asociación para Evitar la Ceguera en Mexico, Mexico City, Mexico
Branch Retinal Vein Occlusion (BRVO) is a common retinal vascular disease

caused by the occlusion of one of the branches of the central retinal vein, affecting
only a portion, typically a quadrant, of the posterior pole [1]. It is three times more
common than the central retinal vein occlusion, and onset usually occurs in the
elderly. There are some risks factors for its development: hypertension,
cardiovascular disease, obesity and open angle glaucoma.
Patients usually complain of a sudden onset of blurred vision or central visual

field defect.
Upon ophthalmologic examination, typical findings include superficial

hemorrhages, which are usually flame-shaped, retinal edema, and cotton-wool
spots in a sector of retina drained by the affected vein (Figs. 1-3). The horizontal
raphe is respected.
In the chronic stage (Fig. 4), hemorrhages may be absent and macular edema with
telangiectatic vessels can be observed, extending across the horizontal raphe. The
quadrant most commonly affected is the superotemporal (63%) [2].
*
Corresponding author Gerardo García Aguirre: Retina Department, Asociación para Evitar la Ceguera en Mexico,
Vicente García Torres 46, San Lucas Coyoacan, Mexico City 04030, Mexico; Tel: +52 (55) 10841400; Email:
jerry_gar_md@yahoo.com
Branch Retinal Vein Occlusion Ophthalmology: Current and Future Developments, Vol. 1 59
Fig. (1). Flamed-shaped hemorrhages and retinal edema in superior macular area. (Courtesy of Gerardo
Garcia Aguirre (Mexico)).
Fig. (2). Retinal hemorrhages, cotton-wool spots and sclerotic vessels in inferotemporal BRVO. (Courtesy of
Gerardo Garcia Aguirre (Mexico)).
60 Ophthalmology: Current and Future Developments, Vol. 1 Arrieta Ruiz and García Aguirre
Fig. (3). Intraretinal hemorrhages in the superotemporal area and macular edema. (Courtesy of Gerardo
Garcia Aguirre (Mexico)).
Fig. (4). Left eye: Chronic superior temporal branch retinal vein occlusion, sclerotic vessels and neovascul-
arization. Courtesy of Luis Miguel Suarez Tata MD (Venezuela).
BRVO can be subdivided as ischemic or non-ischemic; the non-ischemic type is

associated with a more favorable prognosis. This classification is based on find-
ings observed in a fluorescein angiogram (FA). Non-ischemic BRVO is defined as
the absence of retinal neovascularization and areas of capillary non-perfusion that
amount to less than 5 disc areas. Ischemic BRVO is characterized by 5 or more
disc areas of capillary non-perfusion and/or the presence of retinal
neovascularization. Retinal neovascularization may lead to vitreous hemorrhage.
FA and optical coherence tomography (OCT) are helpful diagnostic tools.

Findings in FA include delayed venous filling, hypofluorescence caused by
hemorrhages and capillary non-perfusion, dilation and tortuosity of veins, leakage
in case of neovascularization and macular edema (Figs. 5-8). OCT is used as a
rapid and noninvasive way of monitoring macular edema (Fig. 9). Eyes may
present cystoid macular edema and serous retinal detachment extending into the
fovea.
Fig. (5). FA shows hypofluorescence caused by hemorrhages and areas of capillary non-perfusion (*Courtesy
by Claudia Arrieta).
Fig. (6). FA shows areas of capillary non-perfusion, dilatation of veins, retinal telangiectasias and
neovascularization. Courtesy of Gerardo Garcia Aguirre (Mexico).
Fig. (7). FA: Ischemic BRVO. Hypoflourescence caused by hemorrhages, capillary non perfusion and
delayed venous filling, dilatation and tortuosity of veins. Areas of non-perfusion exceed 5 disc areas
(*Courtesy by Claudia Arrieta).
Fig. (8). Secondary retinal telangiectasias in an eye with history of inferotemporal BRVO (*Courtesy by
Claudia Arrieta).
Fig. (9). OCT: Cystoid macular edema and serous retinal detachment secondary to BRVO (*Courtesy by
Claudia Arrieta). (*) FA and OCT were performed by Claudia Arrieta MD (Venezuela).
The principal differential diagnoses are diabetic retinopathy and hypertensive

retinopathy.
MANAGEMENT
Management is directed towards the most significant complications of BRVO:

macular edema and retinal neovascularization [3].
Macular edema may be managed expectantly for a short period of time (usually
up to 30 days), since some cases may regress spontaneously. The BVOS study
demonstrated that macular grid laser photocoagulation was helpful for eyes with
vision of 20/40 or worse [4, 5]. The current gold-standard for treatment, however,
is the injection of intravitreal anti-VEGF agents. All three available agents
(ranibizumab [6, 7], aflibercept [8] and bevacizumab [9]) have proven to be safe
and effective for the treatment of macular edema, with significant reduction of
macular thickness and improvement in visual acuity (Fig. 10). Intravitreal steroids
such as triamcinolone [10] or dexamethasone [11] have also proven to reduce
macular edema secondary to BRVO, although results are not as favorable as the
ones obtained with anti-VEGF agents, with the additional concern of side effects
such as cataract or intraocular pressure elevation.
Eyes with retinal neovascularization should be treated with retinal laser

photocoagulation directed toward areas of capillary non-perfusion observed in
FA, to decrease the risk of vitreous hemorrhage and tractional retinal detachment
[5].
Pars-plana vitrectomy should be considered in eyes with persistent vitreous

hemorrhage, tractional retinal detachment or epiretinal membrane.
Fig. (10). Response to anti-VEGF treatment for macular edema secondary to an inferotemporal BRVO. Top:
OCT of an eye with non-ischemic BRVO, showing accumulation of intraretinal fluid and a subfoveal serous
retinal detachment Note the sparing of the superior macula (right side of the image). Visual acuity was 20/60
Bottom: OCT of the same eye, after three doses of 1.25 mg intravitreal aflibercept, showing resolution of
intra and subretinal fluid. Visual acuity improved to 20/20 (Images courtesy of Gerardo Garcia-Aguirre, MD).
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1] Jay SD. Ophthalmology. 3rd ed., Mosby Elsevier 2009.
[2] Rogers S, McIntosh RL, Cheung N, et al. The prevalence of retinal vein occlusion: pooled data from
population studies from the United States, Europe, Asia, and Australia. Ophthalmology 2010; 117(2):
313-9.e1.
[3] Karia N. Retinal vein occlusion: pathophysiology and treatment options. Clin Ophthalmol 2010; 4:
809-16.
[http://dx.doi.org/10.2147/OPTH.S7631] [PMID: 20689798]
[4] Guyer DR, Lampert R, et al. Retina-Vitreous-Macula: Branch Retinal Vein Occlusion. W.B. Saunders
Company 1999; pp. 308-15.
[5] The branch vein occlusion study group. Argon laser photocoagulation for macular edema in branch
vein occlusion. Am J Ophthalmol 1984; 98(3): 271-82.
[6] Campochiaro PA, Heier JS, Feiner L, et al. Ranibizumab for macular edema following branch retinal
vein occlusion: six-month primary end point results of a phase III study. Ophthalmology 2010; 117(6):
1102-1112.e1.
[7] Heier JS, Campochiaro PA, Yau L, et al. Ranibizumab for macular edema due to retinal vein
occlusions: long-term follow-up in the HORIZON trial. Ophthalmology 2012; 119(4): 802-9.
[8] Campochiaro PA, Clark WL, Boyer DS, et al. Intravitreal aflibercept for macular edema following
branch retinal vein occlusion: the 24-week results of the VIBRANT study. Ophthalmology 2015;
122(3): 538-44.
[9] Wu L, Arevalo JF, Roca JA, et al. Comparison of two doses of intravitreal bevacizumab (Avastin) for
treatment of macular edema secondary to branch retinal vein occlusion: results from the Pan-American
Collaborative Retina Study Group at 6 months of follow-up. Retina 2008; 28(2): 212-9.
[http://dx.doi.org/10.1097/IAE.0b013e3181619bee] [PMID: 18301025]
[10] Scott IU, Ip MS, VanVeldhuisen PC, et al. A randomized trial comparing the efficacy and safety of
intravitreal triamcinolone with standard care to treat vision loss associated with macular Edema
secondary to branch retinal vein occlusion: the Standard Care vs Corticosteroid for Retinal Vein
Occlusion (SCORE) study report 6. Arch Ophthalmol 2009; 127(9): 1115-28.
[11] Haller JA, Bandello F, Belfort R Jr, et al. Dexamethasone intravitreal implant in patients with macular
edema related to branch or central retinal vein occlusion twelve-month study results. Ophthalmology
2011; 118(12): 2453-60.
CHAPTER 6
A Three-Dimensional Look into Hypertensive

Retinopathy
Rafael Muci Mendoza*
Universidad Central de Venezuela, Unidad de Neurooftalmología, Hospital Vargas de Caracas,
Venezuela
The amount of arteriolar damage signals the individual prognosis of a

hypertensive subject; therefore, any information about its severity will be
extremely helpful in a practical way. Arteriolosclerosis is the hardening and
narrowing of the arterioles secondary to systemic arterial hypertension [1].
Fundoscopic changes reflect the duration, severity, and the right way to control
hypertension, so monitoring the changes in the retina, the choroid, and the optic
nerve will help the physician determine the best course of care of the hypertensive
patient. “Essential” or “primary” hypertension is a pathological condition
characterized by endothelial dysfunction that affects vessel structure and tone,
thus causing constriction of blood vessels and narrowing of small arteries and
arterioles in the peripheral vascular bed. It is a silent disease and its injurious
effect begins many years before organic damage becomes clinically apparent [2,
3]. Arteriosclerosis follows chronic arterial hypertension like a shadow [4]. The
amount of arteriolar damage is the essential piece of information that signals the
individual prognosis of a hypertensive subject [5, 6]. Retinal arterioles share
similar anatomical, physiological and embryological characteristics with cerebral,
coronary and renal arterioles. Thus, the ocular fundus and the retina are like doors
open to medical curiosity that enable noninvasive, in vivo testing of circulation,
*
Corresponding author Rafael Muci Mendoza: Universidad Central de Venezuela, Unidad de Neurooftalmología,
Hospital Vargas de Caracas, Venezuela; Email: rafalemuci@gmail.com
68 Ophthalmology: Current and Future Developments, Vol. 1 Rafael Muci Mendoza
since a direct fundoscopy allows for easy and bedside observation of the
arterioles. This can lead to extremely important data when the resulting
information is applied to other arterial territories [2].
When considered individually, the fundoscopic technique gains more importance

than a blood pressure check. The reason is that it provides first-hand knowledge to
the trained eye about past and future events in the disease natural history, thus
providing a three dimensional look into hypertensive patients: 1) The acute or
insidious damage to the arteries in the past, since the chronic form causes
progressive arteriolosclerotic changes, unlike recently diagnosed hypertension; 2)
“Here and now”: the current situation of arteriolar and retinal damage, manif-
estation of the process activity, probable diastolic blood pressure readings, and,
especially, which phase of the evolution process the patient is going through:
incorrectly called benign hypertension vs. accelerated-malignant hypertension; 3)
The possibility of differentiating “secondary” forms of hypertension and primary
hypertension, and even the possibility of going deeper into the etiologic diagnosis;
4) Prognosis of the disease in untreated patients; and 5) Objective assessment of
the response to different invasive and noninvasive treatments [4].
We consider the following fundoscopic changes of hypertension, which depend

on diastolic blood pressure readings:
● Arteriolar signs typical of chronic hypertension. 1) Diffuse constriction that is

difficult to observe if it is not in youthful vessels with normal auto regulation
(pregnancy toxemia, acute diffuse glomerulonephritis). It is reversible. 2) Focal
or localized constriction: apparent notches along the arterioles where caliber
narrows and axial reflex is less bright. They are easily visible and constitute
morphological wall changes that cannot be reversed with treatment. A
significant number of them suggest left ventricular hypertrophy (Fig. 1). 3)
Irreversible generalized arteriolosclerosis: This means long-standing hyper-
tension. It manifests as exaggerated axial reflex over arterioles, copper wiring
and silver wiring of arterioles, sheathing of arterioles, and arteriolovenous
crossing changes in its four grades of progressive severity: concealment,
tapering, deflection with depression and compression (Figs. 1-8).
Hypertensive Retinopathy Ophthalmology: Current and Future Developments, Vol. 1 69
Fig. (1). Hypertensive arteriolosclerosis – time function: Arteriolar narrowing and focal narrowing.
Fig. (2). (A) Chronic hypertensive arteriolosclerosis: Copper wiring of arteriole. Abnormal arteriolovenous
crossing of higher grade. Notice that the end that is distal from the crossing is wider than the proximal end,
which denotes compression. A thin layer of collateral vessels can be seen adjacent to the optic disc. (B)
Abnormal crossing (scanning microscopy).
Fig. (3). Chronic arterial hypertension: copper wiring of arterioles and arteriolovenous crossing of higher
grade.
Fig. (4). Chronic arterial hypertension: copper wiring of arterioles and abnormal arteriolovenous crossings;
venous collateral network and deep hemorrhages (manifestation of retinal ischemia); Silver wiring of one
segment of the arteriole.
Fig. (5). Chronic arterial hypertension: copper wiring of arterioles and abnormal arteriolovenous crossings;
Arteriolovenous communication.
Fig. (6). Advanced retinal arteriolosclerosis: Copper wiring, segmental constriction, arteriolovenous crossings
of higher grade; arteriolovenous and venoule-arteriolar –similarity with a Japanese bridge; Systemic
correlation of left ventricular hypertrophy.
Fig. (7). (A) Old occlusion of superior temporal artery –silver wiring of arteriole– with superfluous collateral
vessels; (B) Acute myocardial infarction in evolution; (C) Basilar artery atherosclerosis.
Fig. (8). (A) Chronic hypertensive arteriolosclerosis; (B) Embolic occlusion of the central retinal artery and
its branch arterioles.
● Retinal signs are typical of accelerated-malignant retinopathy. It is associated

with the presence of fibrinoid necrosis in the kidney and includes retinal edema,
cotton wool spots (accumulation of axoplasmic material) that are characteristic
of this acute phase and are an invaluable sign of alarm because it is the way the
retina “complains” when diastolic pressure exceeds 130 mmHg.
Light microscopy reveals the presence of so-called “cytoid bodies” because of its
similarity with cells; hard exudates in the deeper retinal layers. Its pathogenesis
combines alteration of the retinal capillary network and changes in the
choriocapillaris of the choroid. When they are located in the macular area, they
arrange in a star-shaped pattern around the fovea (macular star or stellar

retinopathy); optic disc edema (a manifestation of hypertensive optic neuropathy)
[2] (Figs. 9-18).
Fig. (9). (A) Accelerated-malignant hypertension: cotton wool spots – axoplasmic material accumulations – a
typical sign of alarm that indicates the severity of the disease; (B) Chronic malignant hypertension: hard
exudates in the shape of small dots with waxy appearance.
Complications of Hypertensive Retinopathy
Chronic hypertension, because of concomitant arteriolosclerosis, is responsible for

vascular occlusions, whether arteriolar or venous. Arteriolar obstructions are
associated with thrombotic occlusion or atheromatous embolism. On the other
hand, vein occlusions, central or peripheral branch, the latter related to abnormal
arteriolovenous crossing of higher grade, make it compulsory to carry out an
assessment of the patient’s coronary status. For its part, accelerated-malignant
hypertension can be associated with exudative retinal detachment due to the
presence of fibrinoid necrosis of the choroid (Figs. 19-25).
Classification
We favor Lip and collaborator’s classification system (1994) [5] because it is

simple and it allows the classification of hypertension quickly on different phases
of evolution. Grade I: Non accelerated-malignant; and Grade II: Accelerated-
malignant (Fig. 26).
The differential diagnosis for hypertensive retinopathy with diffuse retinal

hemorrhage, cotton wool spots, and hard exudates includes most notably diabetic
retinopathy. Diabetic retinopathy can be distinguished from hypertensive
retinopathy by evaluation for the individual systemic diseases. Other conditions
with diffuse retinal hemorrhage that can resemble hypertensive retinopathy
include radiation retinopathy, anemia and other blood dyscrasias, ocular ischemic
syndrome, and retinal vein occlusion.
Fig. (10). Chronic secondary accelerated hypertension. (A) 58-year-old male patient; and (B) 60-year-old
male patient. Signs of chronic hypertensive arteriolosclerosis, plus cotton wool spots, which are
manifestations of acceleration-malignancy.
Fig. (11). Accelerated-malignant hypertension. 18-year-old male patient. Rapidly progressive glomerul-
onephritis. (A) Multiple cotton wool spots and macular star. (B) Hyperfluorescence in the optic disc and
around cotton wool spots that put pressure in the retina and capillary closure, and perilesional leakage due to
blood-ocular barrier breakdown. No fluorescence on hard exudates.
Fig. (12). A partial image of the retina showing (A) arteriolosclerotic changes that are typical of long-
standing hypertension: Copper wiring of arteriole with bright axial reflex, irregular caliber and an
arteriolovenous crossing of higher grade; and (B) involutional cotton wool spot and the presence of scattered
hard exudates (a manifestation of acceleration-malignancy).
Fig. (13). Renovascular hypertension in a 59-year-old male patient. (A) Chronic secondary accelerated
hypertension: multiple cotton wool spots; (B) After treatment, retinal signs tend to disappear, leaving hard
exudates in the central area but without modifying arteriolosclerosis (arteriolar wall changes that cannot be
reversed).
Fig. (14). Accelerated-malignant hypertension in a 48-year-old male patient with chronic secondary
malignant hypertension: Macular hard exudates due to retinal edema.
Fig. (15). Accelerated-malignant hypertension in a 62-year-old male patient with atherosclerotic stenosis of
both renal arteries.
Fig. (16). Asymmetric accelerated-malignant hypertension in a 22-year-old female patient with pheoch-
romocytoma.
Fig. (17). (A) Accelerated-malignant hypertension, optic disc edema; fluorescein angiography:
hyperfluorescence in the optic disc and choroidal scars; (B) Left ventricular hypertrophy; (C) Left renal
atrophy.
Fig. (18). Typical condition of accelerated-malignant hypertension: Optic disc congestion, cotton wool spots
– accumulations of axoplasmic material – macular star image in a 20-year-old patient with rapidly
progressive glomerulonephritis.
Fig. (19). Accelerated-malignant hypertension. (A) Bilateral optic disc edema; (B) Subhyaloid hemorrhage.
Fig. (20). (A) Accelerated-malignant hypertension and papilledema. (B) Hypertensive intracerebral
hematoma. Such development of disc edema is unusual.
Fig. (21). (A and B) Eclampsia: 22-year-old patient with bilateral serous retinal detachment and macular
edema; Choroidal infarctions (acute Elschnig spots); (C) Fluorescein angiography: Choroidal
hyperfluorescence in patches and macular edema; (D) Two months later: Scattered hypofluorescent spots:
related to choroidal infarctions (chronic Elschnig spots).
Fig. (22). Chronic arterial hypertension. (A and B) Superior temporal branch vein occlusion: retinography
and fluorescein angiography: Triangular pattern of deep and superficial hemorrhages and cotton wool spots;
(C) Scheme of abnormal arteriolovenous crossings of higher grade.
Fig. (23). (A) Non-arteritic anterior ischemic optic neuropathy; (B) Left disc at risk.
Fig. (24). Examples of venous occlusions in hypertensive patients. (A) Superior temporal branch occlusion;
(B) Hemispheric occlusion; (C) Ischemic occlusion of the central retinal vein.
Fig. (25). Chronic hypertension. (A) Systemic atheromatous embolism (Hollenhorst plaques) at two arteriolar
bifurcations; (B) Histological appearance in posterior capsule of an eye. Visually empty space that was
occupied by cholesterol emboli before tissue dehydration (*). A dreadful clinical sign that anticipates a
vascular catastrophe (myocardial infarction, stroke, aortic dissection or rapidly progressive renal failure).
Hyper retinopathy grading

system (revised)
Lip G et al. J Hypertesion 1995;13:915-924
Grade I (non accelerated-malignant) Grade II (accelerated-malignant)
Retinal changes
Generalized narrowing Hemorrhages, cotton

or tortuosity. Focal wool spots or ± optic
constrictions disc edema
Prnosis
Depends on BP readings, Most untreated

but age and other risk patients✝within 2
factors are important years. Treated ones:
≥12-year average
Fig. (26). Lip’s classification – recommended due to its simplicity.
MANAGEMENT
The treatment for hypertensive retinopathy is primarily focused on reducing blood

pressure.
Antihypertensive medication may reverse hypertensive retinopathy signs, with

clinical case series [6, 7] showing regression of some retinopathy signs (e.g.,
hemorrhages, cotton wool spots) with control of blood pressure.
If complications have occurred, surgery or laser may be required to help heal a

hemorrhage or other resulting condition.
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1] Blandeiner C. Patología cardiovascular adquirida de las principales enfermedades en nuestro medio.
Colección estudios: Universidad central de Venezuel. Consejo de Desarrollo Científico y Humanístico
1998.
[2] Muci-Mendoza R. Retinopatía hipertensiva: Un factor de riesgo Clasificación y valor de la

oftalmoscopia en el tratamiento Clemente-Heimerdinger A, Briceño-Iragorri L, editores Academia
Nacional de Medicina, Venezuela Colección Razetti Volumen VII. Caracas: Editorial Ateproca 2009;
pp. 259-98.
[3] Wong TY, Mitchell P. Hypertensive retinopathy. N Engl J Med 2004; 351(22): 2310-7.
[http://dx.doi.org/10.1056/NEJMra032865] [PMID: 15564546]
[4] Muci-Mendoza R. El fondo del ojo en la hipertensión arterial. el punto de vista del internista. Acta
Cient Venez 1979; 30(5): 429-39.
[PMID: 545973]
[5] Lip GY, Beevers M, Beevers G. The failure of malignant hypertension to decline: a survey of 24
years’ experience in a multiracial population in England. J Hypertens 1994; 12(11): 1297-305.
[http://dx.doi.org/10.1097/00004872-199411000-00013] [PMID: 7868878]
[6] Bock KD. Regression of retinal vascular changes by antihypertensive therapy. Hypertension 1984; 6(6
Pt 2): III158-62.
[PMID: 6519755]
[7] Dahlöf B, Stenkula S, Hansson L. Hypertensive retinal vascular changes: relationship to left
ventricular hypertrophy and arteriolar changes before and after treatment. Blood Press 1992; 1(1): 35-
44.
CHAPTER 7
Central Retinal Artery Occlusion

Silvia Mendoza1, Sandra Zambrano2, Diego Fernando Mojica2 and Mitzy E.
Torres Soriano3,*
1
Retina Department, Centro Oftalmológico de Valencia (CEOVAL), Valencia, Venezuela
2
Centro Oftalmológico de Valencia (CEOVAL), Valencia, Venezuela
3
Centro de la Visión Gordon-Manavella, Rosario-Santa Fe, Argentina
Central retinal artery occlusion is a vaso-occlusive ischemic disease that causes a

sudden painless loss of vision usually irreversible and unilateral. Incidence is 1 to
15 cases per 10,000 it generally occurs in the elderly, and is usually accompanied
by an afferent pupillary defect [1 - 3].
The most frequent causes of obstruction of blood flow are:
1. Atherosclerosis: The deposits of cholesterol and other particles form

atherosclerotic plaques. They slowly thicken towards the artery lumen causing
obliteration or even complete obstruction.
2. Embolism: The ophthalmic artery is the first branch of the internal carotid
artery. When the artery lumen narrows by plaques containing cholesterol or
other particles, some pieces can break off, blocking the flow of the ophthalmic
artery, central retinal artery or one of its branches. The severity of vision loss
depends on the area of obstruction.
3. Collagenosis and coagulopathy [3 - 5].
Risk factors: Hypertension, hypercholesterolemia, blood dyscrasias, vasculitis.
*
Corresponding author Mitzy E. Torres Soriano: Centro de la Visión Gordon-Manavella, Montevideo 763, CP
2000, Rosario - Santa Fe, Argentina; Tel: +54 (0341) 4400239; E-mail: mitzytorres@yahoo.com
Central Retinal Artery Occlusion Ophthalmology: Current and Future Developments, Vol. 1 83
Symptoms
● Sudden painless loss of vision can last for seconds, minutes or be permanent.
● Usually unilateral.
● Loss of the entire visual field if the central retinal artery is affected or partial
loss if a branch is affected.
● Most patients have a history of previous episodes of amaurosis fugax.
Fundus Findings
● Whitish discoloration of the retina, due to edema of the inner retinal layers,
especially at the posterior pole where the nerve fiber layer and ganglion cell
layer are thickest (Figs. 1-4) [1 - 6].
Fig. (1). Central retinal artery occlusion: Note pale retina, narrowed arterioles and “cherry red spot” in
macula.
84 Ophthalmology: Current and Future Developments, Vol. 1 Mendoza et al.
● Cherry-red spot. Visualization of the choroid and retinal pigment epithelium

with xanthophyll pigment in the foveal area, surrounded by edematous retina
(Figs. 1-4) [1 - 5].
● Retinal arterial attenuation [4].
● Optic disc edema and pallor [4].
● At later stages, fundoscopic findings include optic atrophy, retinal arterial
attenuation, cilioretinal collaterals, and macular retinal pigment epithelial
changes [4].
Complementary Exams
● Fluorescein angiography: to assess if the arterial obstruction is complete or
partial and to determine if there is reperfusion (Figs. 2, 4).
A B
C D
Fig. (2). A. Fundus photograph showing retinal pallor and a cherry-red spot. B and C. Early to mid stages of
the fluorescein angiogram showing significant delay in the vascular filling. There is a small area adjacent to
the optic disc that is still perfused by a cilioretinal artery. D. Late Phase of the Angiogram.
● Optical coherence tomography may show increased inner retinal layer thickness
(Fig. 3B) in the acute stage of CRAO, due to retinal edema and optic nerve
swelling [5].
Fig. (3). A. Color photograph of the left fundus showing diffuse retinal whitening with a classic cherry-red
spot. This patient has an area of perfused retina supplied by a cilioretinal artery located just temporal to the
disc. B. Optical coherence tomography shows hyperreflectance of inner retinal layers. (Courtesy of Manuel
Torres MD, Cagua, Venezuela).
A B
C D
E F
Fig. (4). A. Central retinal artery occlusion in a patient with diabetic retinopathy, B. Fundus autofluorescence.
C-F. FA shows non-perfusion of the retinal vasculature from early to late phases. (Courtesy of Manuel Torres
MD, Cagua, Venezuela).
● Visual field: useful for follow-up.

● Electroretinogram: there is a reduction in the b-wave amplitude, due to selective
damage of inner retinal layers (Fig. 5) [5].
Fig. (5). Electroretinogram of the same patient of Fig. (2). There is a reduction in the b-wave amplitude in
cone and rod response of right eye (left side of the image) due to a CRAO.
Although the cherry-red spot is a fairly specific clinical sign, it is not

pathognomonic, since it may also be observed in traumatic commotio retinae, and
in metabolic diseases such as Niemann-Pick disease, Farber disease, Tay-Sach
disease, and Sandhoff disease among others.
MANAGEMENT
Once it ensues, there is no proven treatment for this disease. Retinal tissue can
survive for up to 240 minutes without oxygen before damage is permanent and
irreversible. Therefore the aim of treatment is to restore retinal circulation as soon
as possible.
Treatment strategies include:
● Ocular massage.
● Topic beta-blockers.
● Anterior chamber paracentesis.
● Intravenous or oral acetazolamide.
● Hemodilution.
● Retrobulbar injection of vasodilators such as papaverine.
● Anticoagulation.
● Hyperbaric chamber.
Other therapeutic options are:
● Systemic fibrinolysis: in cases of arterial thrombotic occlusion or fibrin platelet

emboli less than 6 hours of evolution [7 - 13].
● Intra-arterial fibrinolysis: injected into the ophthalmic artery, it may be effective
in the early hours of ischemia. It needs specialized equipment and is not devoid
of complications [7 - 13].
● In cases of ophthalmic artery embolic obstruction, direct removal of the embolus
might be attempted, cutting the affected artery wall with a 20G lancet.
All these therapeutic measures have to be attempted within the first six hours of
the occlusion, and have a very low success rate.
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1] Gil MA, Ortigosa L, Civancos E, Mesa MC, Delgado JL, Abreu P. Mácula rojo cereza: a propósito de
un caso. St Ophthal 1999; 17: 239-41.
[2] Piñero Bustamante A. Aparato ocular. Barcelona: Pharma Consult, S.A; 1992; 41.
[3] Sharma S, Brown M, Brown G. Retinal artery occlusions. Ophthalmol Clin North Am 1998; 11: 591-
600.
[http://dx.doi.org/10.1016/S0896-1549(05)70080-8]
[4] Hayreh SS, Zimmerman MB. Fundus changes in central retinal artery occlusion. Retina 2007; 27(3):
276-89.
[http://dx.doi.org/10.1097/01.iae.0000238095.97104.9b] [PMID: 17460582]
[5] Shinoda K, Yamada K, Matsumoto CS, Kimoto K, Nakatsuka K. Changes in retinal thickness are
correlated with alterations of electroretinogram in eyes with central retinal artery occlusion. Graefes
Arch Clin Exp Ophthalmol 2008; 246(7): 949-54.
[http://dx.doi.org/10.1007/s00417-008-0791-x] [PMID: 18425524]
[6] Conolly BP, Krishnan A, Shah GK, et al. Characteristics of patients presenting with CRAO with and
without giant cell arteritis. Can J Ophthalmol 2000; 35: 379-84.
[7] Schmidt P, Schulte-Mönting J, Schumacher M. Prognosis of CRAO: local intraarterial fibrinolysis
versus conservative treatment. Am J Neurorad 2002; 23: 1301-7.
[8] Beatty S, Au Eong KG. Local intra-arterial fibrinolysis for acute occlusion of the central retinal artery:
a meta-analysis of the published data. Br J Ophthalmol 2000; 84(8): 914-6.
[9] Cilveti Puche A, Lapeira Andraca M, García Campos J. Fibrinolisis sistémica con rTPA en OACR.
Arch Soc Esp Oftalmol 2000; 4: 9.
[10] Neubauer AS, Mueller AJ, Schriever S, Gruterich M, Ulbig M, Kampik A. Minimally invasive therapy
for clinically complete CRAO results and meta-analysis of literature. Klin Mbl Augenheilkd; 217: 30-
36.
[11] Mori E, Yoneda Y, Tabuchi M, Yoshida T, Ohkawas S, Ohsumi Y. Intravenous rTPA in acute carotid
artery territory stroke. Neurology 1992; 42: 976-82.
[http://dx.doi.org/10.1212/WNL.42.5.976] [PMID: 1579252]
[12] Schumacher M, Schmidt D, Wakhloo AK. Intra-arterial fibrinolytic therapy in CRAO. Neuroradiology
1993; 35: 600-5.
[http://dx.doi.org/10.1007/BF00588405] [PMID: 8278042]
[13] Fernández FJ, Guelbenzu S, Barrena C, et al. Fibrinolisis selectiva de arteria oftálmica en la OACR.
Arch Soc Esp Oftalmol 2002; 2: 7.
CHAPTER 8
Branch Retinal Artery Occlusion and Cilioretinal

Artery Occlusion
Raul Velez-Montoya*
Retina Department, Asociación para Evitar la Ceguera en México, IAP. Mexico City, Mexico
Branch retinal artery occlusion (BRAO) is an arterial occlusive disease in which

the obstruction of blood flow is located after the bifurcation of the central retinal
artery in its major branches. The severity of the clinical manifestations will
depend on the exact localization of the obstruction which can be found anywhere
from the emergence of the major temporal or nasal arcades to the small capillary
arterioles [1, 2].
BRAOs are thought to represent 38% of all acute retinal artery obstructions [3]. It
is classified according to its visual outcome in transient and permanent BRAO [2,
4, 5]. Diabetes mellitus, arterial hypertension, ischemic heart disease, and
transient ischemic attacks/cerebrovascular accidents are more prevalent in patients
with BRAO than the matched US population (p<0.001) [2]. Smoking prevalence
in female patients with BRAO is higher; although this association has not been
proven in male patients. When comparing BRAO with central retinal artery
occlusion (CRAO), only diabetes mellitus has a slightly higher prevalence among
patients with CRAO [2].
Embolism is the most common cause of BRAO [5, 7]. There are three main types
or retinal emboli: calcific (10.5%), cholesterol (74%), and platelet-fibrin (15.5%)
[6, 7]. The most common sources of emboli are the carotid artery (plaque) and the
heart (valvular lesions, atrial fibrillation, patent foramen ovale, tumors in left
*
Corresponding author Raul Velez-Montoya: Retina Department, Asociación para Evitar la Ceguera en México,
Vicente García Torres, 46. San Lucas Coyoacán, México DF.04030; México; Tel: +52.55.10841400; Fax:
+52.55.10841404; Email: rvelezmx@yahoo.com
Branch Retinal Artery Occlusion Ophthalmology: Current and Future Developments, Vol. 1 91
atrium and myxoma) [8]. Due to the fact that microemboli are responsible for
most BRAO, and the major source of microemboli is an arterial plaque, the
absence of an abnormal carotid doppler does not rule out the carotid artery as the
source of microemboli [7, 9].
Conversely to CRAO patients, in which visual loss can be severe (light

perception) at presentation, more than 70% of patients with permanent BRAO,
seen within 7 days of onset, will have 20/40 or better at the initial visit especially
if the affected vessel is the inferior temporal artery. Furthermore, 80% of patients
with decreased visual acuity (VA) at presentation (worse than 20/40) will
experience an improvement of VA within 1 week after onset. Final VA of 20/40
or better is seen in 89% of patients, and only 3% of eyes experience a worsening
of VA during follow-up. The most frequently reported visual field defects are a
central scotoma (20%) and inferior central altitudinal defect (13%), which tend to
improve in 47% of the cases within 1 week of onset. In patients with transient
BRAO, VA at presentation of 20/40 or better is seen in more than 90% of cases.
The central and peripheral visual field remains normal. Final VA tends to be
20/40 or better in virtually all cases, regardless of VA at onset (even if it was
worse than 20/40) [1, 5].
During the acute phase of the disease, an area of retinal pallor corresponding to
the area of compromised blood flow and oncotic damage (swelling) can be
identified on fundus examination (Figs. 1, 2) [10 - 12]. However, the initial pallor
is replaced by the normal sheen of the fundus in long-standing cases, making it
more difficult to diagnose [10]. If there is enough ischemia, cotton-wool spots will
develop 6 to 18 hours after onset, especially if the affected vessel is large enough
and close to the posterior pole where the nerve fiber layer is thicker [13, 14]. A
retinal emboli is seen in 47% of cases. However, its absence does not rule out an
embolic case because it may have disintegrated, migrated and disappeared by the
time the eye is examined [15, 16].
92 Ophthalmology: Current and Future Developments, Vol. 1 Raul Velez-Montoya
Fig. (1). BRAO on a diabetic patient after pars plana vitrectomy and silicon oil. A) Color photograph shows
whitening of the posterior pole with normal color of the papillomacular bundle. B) Red-free photograph
shows more clearly the territory supplied by the cilioretinal artery on the same patient.
A B
D
C
Fig. (2). Acute phase of inferotemporal BRAO. A) Fundus photograph shows retinal pallor in inferior
macular area. B and C) FA shows a delay on the vessel filling and transit time. D) Cattle trucking and
staining of the vessels walls (Courtesy of Natalia Pecce MD, Argentina).
Fluorescein angiogram (FA) may show delayed filling, reduced arterial caliber,
“cattle trucking” of the arterial blood column (Figs. 2, 3), and increased transit
time on the affected vessels as well as capillary dropout and collateral vessels
development on the area of the retina affected by compromised blood flow
(Fig. 4) [4, 17, 18]. Optical coherence tomography (OCT) of the ischemic areas
will show marked thickening and hyper-reflectivity of the inner retina during the
acute phase (Fig. 5) [10, 13, 19]. A decrease in retinal thickness may be noticed
after resolution [10, 13]. Fundus autofluorescence of the area supplied by the
occluded retinal artery will show decreased autofluorescence due to blockage of
the normal autofluorescence of the retinal pigment epithelium by the thickened
retina with normal autofluorescence over the rest of the retina [10, 12]. After
resolution, an increase in autofluorescence due to a very thin retina may also be
visualized [10].
Cilioretinal Artery Occlusion (CLRAO): The cilioretinal artery originates from

the short posterior ciliary arteries or from the choroid, and emerges directly from
the optic disc or disc margins, and not from the central retinal artery [5, 16]. It is
usually present in 49.5% of the eyes and supplies the papillomacular bundle [4,
20]. Clinically evident CLRAO is a rare event, since it only comprises between
5.3 to 7.1% of all cases or retinal artery occlusions [16]. It occurs in three clinical
settings: as non-arteritic CLRAO alone; as an arteritic CLRAO associated with
giant cell arteritis; and as CLRAO associated with central/hemicentral retinal vein
occlusions [2, 5]. The clinical presentation at onset will depend on the clinical
setting in which CLRAO occurred. Patients with non-arteritic CLRAO can have
decreased VA (20/40 or worse) and central visual field defects (mostly central and
centrocecal scotomas) which tend to improve during the follow-up [5]. Such
presentations are due to the high variability in size of the cilioretinal artery and the
area it supplies [1]. Translucent, pale gray swelling of the papillomacular bundle
is typically present [21, 22]. The presence of a CLRAO with a white optic disc
edema, posterior ciliary artery occlusion on fluorescein angiography, headache
and jaw claudication in a patient of 50 years of age or older might signify an
association with giant cell arteritis [2, 5]. In this scenario, prompt treatment
should begin to prevent severe bilateral visual loss [22]. When associated with
central or hemicentral retinal vein occlusion, VA at onset as well as VA improve-
ment during follow-up will depend on the type of vein occlusion (ischemic or no
Fig. (3). A) BRAO of the superotemporal arcade on a patient with diabetic retinopathy, previously treated
with panretinal photocoagulation. Color photographs shows a severe decrease in the caliber of the vessels. B)
FA shows a delay on the transit time and a thinner dye column inside the affected vessels.
Fig. (4). A) BRAO of the superotemporal arcade. B to D) FA show a filling defect with extensive capillary
dropout and collateral vessel formations.
ischemic), macular ischemia due to the CLRAO, and the existence of macular
edema [5, 21]. Central visual field defects are usually due to CLRAO [5]. On
fundus examination, CLRAO is accompanied by superficial and intraretinal
hemorrhages [16].
Fig. (5). Spectral domain OCT in a patient with acute BRAO. There is an increase in the thickness of the
inner retinal and increased reflectivity (area between arrow heads).
Although diagnosis of BRAO is mostly clinical and straightforward during the

acute phases, it can prove to be difficult on long-standing cases. Differential must
be done with other entities causing whitening of the retina like commotion retina,
persistence of myelinated nerve fiber layer, central/hemicentral retinal artery
occlusion, and shallow retinal detachment, among others. There are multiple
anecdotal associations of BRAO with various diseases including systemic lupus
erythematosus, polyarteritis nodosa, dengue fever, West Nile virus, AIDS,
toxoplasmosis, herpes zoster, sickle cell disease, Takayasu’s arteritis, post-
smallpox vaccination, Churg-Strauss syndrome, ocular Behçet’s disease, Fabry’s
disease, head injury, and migraine [5].
Susac´s syndrome is a pathology characterized by the clinical triad of

encephalopathy, hearing loss, and BRAO, mostly in young women, and is thought
to be due to microangiopathy [24].
MANAGEMENT
A wise man once said, “A disease without treatment has many treatments.” This is
the case of the arterial occlusive disease [25]. Although most of BRAO cases with
impaired VA or visual field defects will improve regardless of whether it is
transient, permanent, or level of VA at onset, it is nearly impossible to identify

which will improve and which will not, based on purely clinical evidence at
presentation. Current options include the standard non-invasive therapies: the use
of vasodilator to increase blood oxygen content and dilate arteries (sublingual
isosorbide, systemic pentoxifylline, inhalation of carbogen and hyperbaric
oxygen); ocular massage to attempt to dislodge the emboli [4]; lowering of
intraocular pressure to increase retinal artery perfusion pressure (intravenous
acetazolamide and mannitol, anterior chamber paracentesis) [4]; methylpre-
dnisolone [4]; oral acetylsalicylic acid [26]; and the combination of some or all of
the above in a multimodal stepwise approach. None of these therapies has been
shown to be better than a placebo in clinical trials in the treatment of BRAO.
More invasive therapies include isovolemic hemodilution, anticoagulation with
heparin, and local intra-arterial fibrinolysis with tissue plasminogen activator
(tPA). However, the latter has proven to be of doubtful utility since major
randomized clinical trials had found no greater benefit than non-invasive standard
treatments but with higher rate of adverse reactions [26]. There are reports of the
successful destruction of the emboli using an Nd:YAG laser. Nevertheless, there
is still concern about the safety and efficacy of the treatment [27, 28]. In cases of
CLRAO associated with giant cell arteritis, intensive corticosteroid therapy can
prevent further visual loss [23].
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1] Hayreh SS, Podhajsky PA, Zimmerman MB. Branch retinal artery occlusion: natural history of visual
outcome. Ophthalmology 2009; 116(6): 1188-94.
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[2] Hayreh SS, Podhajsky PA, Zimmerman MB. Retinal artery occlusion: associated systemic and
ophthalmic abnormalities. Ophthalmology 2009; 116(10): 1928-36.
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97(1): 84-92.
[4] Varma DD, Cugati S, Lee AW, Chen CS. A review of central retinal artery occlusion: clinical
presentation and management. Eye (Lond) 2013; 27(6): 688-97.
[5] Hayreh SS. Ocular vascular occlusive disorders: natural history of visual outcome. Prog Retin Eye Res
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Ophthalmology 1982; 89(12): 1336-47.
[7] Klein R, Klein BE, Jensen SC, Moss SE, Meuer SM. Retinal emboli and stroke: the Beaver Dam Eye
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[10] Mathew R, Papavasileiou E, Sivaprasad S. Autofluorescence and high-definition optical coherence
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[11] Hafidi Z, Handor H, Laghmari M, Daoudi R. Cilioretinal artery and central retinal vein occlusion after
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[13] Coady PA, Cunningham ET Jr, Vora RA, et al. Spectral domain optical coherence tomography
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[14] McLeod D. Why cotton wool spots should not be regarded as retinal nerve fibre layer infarcts. Br J
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[15] Schmidt D, Schumacher M, Feltgen N. Circadian incidence of non-inflammatory retinal artery
occlusions. Graefes Arch Clin Exp Ophthalmol 2009; 247(4): 491-4.
[http://dx.doi.org/10.1007/s00417-008-0989-y] [PMID: 18989688]
[16] Makino S, Ohkawara Y, Sato Y. A case of cilioretinal artery occlusion resembling hemicentral retinal
artery occlusion. Clin Ophthalmol 2012; 6: 1945-7.
[17] Beatty S, Au Eong KG. Acute occlusion of the retinal arteries: current concepts and recent advances in
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[18] Shinoda K, Yamada K, Matsumoto CS, Kimoto K, Nakatsuka K. Changes in retinal thickness are
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[20] Justice J Jr, Lehmann RP. Cilioretinal arteries. A study based on review of stereo fundus photographs
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CHAPTER 9
Retinal Arterial Macroaneurysm

Rodrigo Lechuga Perezanta1 and Virgilio Morales Cantón2,*
1
Asociación para Evitar la Ceguera en Mexico, Mexico City, Mexico
2
Retina Department, Asociación para Evitar la Ceguera en Mexico, Mexico City, Mexico
The term macroaneurysm was first coined by Robertson, in 1973 making

reference to arterial retinal lesions with saccular or fusiform swelling, localized on
the first three orders of the retinal arterial tree found mainly at arterial bifurcations
[1]. Saccular arterial macroaneurysms are more likely to burst and develop closer
to the optic nerve where perfusion pressure is higher. Retinal arterial macroan-
eurysms are more frequent in women (60 – 80% probably due to hormonal and
hereditary factors) with an average age of 69 years and have a strong association
with systemic diseases such as arterial hypertension, aterosclerotic disease,
hyperlipidemia, polycythemia and cerebrovascular disease. Retinal arterial
macroaneurysms have been described in Leber´s miliary aneurysms, Coats´
disease, branch retinal artery occlusion and Eales´ disease among others [1, 2].
Systemic arterial hypertension causes an increase in hydrostatic pressure and may

lead to hyaline degeneration of the vascular wall, loss of autoregulation tone and
arterial dilatation [2].
Another theory to support that systemic arterial hypertension is a risk factor to the
formation of arterial macroaneurysms is Laplace equation, which states that an
increase in the transmural pressure is directly proportional to the increased tension
of the wall.
Focal embolic damage to the arterial wall is considered to be a part of the

*
Corresponding author Virgilio Morales Cantón: Retina Department, Asociación para Evitar la Ceguera en Mexico,
Vicente García Torres 46, San Lucas Coyoacan, Mexico City, 04030; Mexico; Tel +52 (55) 10841400, Email:
vmoralesc@mac.com
100 Ophthalmology: Current and Future Developments, Vol. 1 Lechuga Perezanta and Morales Cantón
mechanism for lesion formation, which may result in localized ischemia.
Most of these lesions appear on the superotemporal arterial branch (51%),

followed by the inferotemporal branch (28%). Macroaneurysms affecting the
nasal arterial branches may be less frequently diagnosed because patients may not
notice the loss of visual acuity until the macula is affected, which could not
happen, or a vitreous hemorrhage develops. Usually one macroaneurysm is
present, but more lesions have been described affecting the same eye and 10%
may be bilateral.
The main symptom is decreased visual acuity as a consequence of exudation,

edema or hemorrhage. A characteristic finding is the presence of hemorrhage in
different layers including subretinal, intraretinal, sub internal limiting membrane
(Figs. 1A, 2A and 3A) or in the vitreous cavity [1, 3]. Hourglass hemorrhages are
also a typical finding.
These lesions may develop symptoms when acute or chronic decompensation

occurs. Acute decompensation is typically associated with rupture and hemor-
rhage of the macroaneurysm while chronic decompensation is due to abnormal
leakage of plasma constituents across the aneurysmal wall leading to the
accumulation of yellow perianeurysmal intraretinal exudates [4].
When the arterial macroaneurysm is visible during fundus examination, the

correct diagnosis can be achieved without much trouble, but when massive
hemorrhage, exudation or retinal edema are present they suppose a diagnostic
challenge. Fluorescein angiography (Figs. 1B, 2B and 3B) is useful to locate the
lesion when dense hemorrhage is absent so hyperfluorescence is visible.
Macroaneurysm typically shows hyperfluorescence during the early arterial phase
of the angiogram but late phase varies from little staining of the vessel wall to
marked leakage. The absorption and emission spectrum of indocyanine green are
close to infrared range and this allows the dye to be seen through hemorrhage.
This makes indocyanine green a good alternative when diagnostic dilemma is
present due to dense hemorrhage or exudates [5, 6].
Retinal Arterial Macroaneurysm Ophthalmology: Current and Future Developments, Vol. 1 101
Fig. (1). A 74-year-old female patient complains of floaters and photopsia in her left eye from 8 days ago.
Diagnosis of systemic arterial hypertension was made 20 years before. Visual acuity was 20/100, intraocular
pressure 16 mmHg, fundus examination revealed subretinal and intraretinal hemorrhage (A) and fluorescein
angiography showed a hyperfluorescent lesion in the superior temporal arterial vessel in the second branch
(B). No treatment was performed and visual acuity was recovered to 20/60 three months later.
Fig. (2). 70-year-old female with floaters, visual acuity 20/100, intraocular pressure 12 mmHg. Fundus
examination revealed a intraretinal hemorrhage on the superior temporal artery (A) with increased
hyperfluorescence on the same spot (B). No treatment was performed and final visual acuity was 20/40.
Fig. (3). A 77-year-old female with decreased visual acuity from one week before. Visual acuity was
counting fingers, intraocular pressure 18 mmHg, in fundus examination a subretinal and subhyaloid
hemorrhage was found (A). Fluorescein angiography revealed a hyperfluorescent spot that increased in
intensity with time (B). Laser hyaloidotomy was performed and the final visual acuity was 20/800.
Optical Coherence Tomography (OCT) can contribute to achieve a correct

diagnosis. Typical findings include an abnormal saccular dilatation in the internal
layers that characteristically elevates the internal limiting membrane and ganglion
cell layer, modifying the normal architecture of the adjacent retina. The layers
beneath the macroaneurysm are hyporreflective due to a masking effect (Fig. 4).
Fig. (4). OCT image showing a saccular dilatation (arrow) that elevates the retina, with a posterior shadow.
Intraretinal fluid and hyper-reflective foci due to hard exudates may also be observed.
Differential diagnosis includes any cause of hemorrhage and exudates, such as

diabetic retinopathy, venous occlusions, radiation retinopathy, Coats´ disease,
retinal telangiectasis, age-related macular degeneration, retinal capillary angioma,
cavernous hemangioma, malignant melanoma.
MANAGEMENT
There is no established consensus regarding the timing to treat the patient or the
ideal treatment for this lesion but it is generally accepted to treat when there is
exudation involving the fovea with decreased visual acuity [7, 8]. Laser
photocoagulation is the most common treatment, and it can be applied directly or
surrounding the macroaneurysm and using threshold or subthreshold laser [9, 10].
Parodi et al. found the same obliteration of the lesion and visual recovery using
threshold vs subthreshold laser but complications including scar growth, choroidal
neovascularization, subretinal fibrosis, arterial branch occlusion, epiretinal
membranes, increased exudation and retinal traction were avoided using
subthreshold laser. They used a diode infrared laser (810 nm) for the subthreshold
patients and a krypton laser (647 nm) for the threshold group. The selective
damage to the retinal pigment epithelial cells may lead to a better balance of
angiogenic factors and cytokine release [7, 9].
Another alternative is the use of antiangiogenic therapy. In 37 eyes, Pichi et al.

proved that 3 intravitreal injections with bevacizumab (0.05ml/1.25mg) in patients
with complicated macroaneurysms affecting the fovea, are safe and effective to
improve visual acuity from 20/80 to 20/25 and central macular thickness from
520.38 +/- 191.05 to 214.84 +/- 26.86 microns [10].
Pars plana vitrectomy is recommended when persistent vitreous hemorrhage or

preretinal hemorrhage is present. It is also justified when the etiology of the
hemorrhage is undefined.
There is poor visual prognosis when subretinal hemorrhage exists because of

photoreceptor deterioration and controversy exists whether to treat with pneu-
matic displacement versus observation.
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1] Ryan SJ. Retina. Fourth edition 2006. Section 5. Retinal Vascular Diseases. Chapter 81. Acquired
Retinal Macroaneurysm. Mosby: Philadelplia 2006; pp. 1475-1478.
[2] Panton RW, Goldberg MF, Farber MD. Retinal arterial macroaneurysms: risk factors and natural
history. Br J Ophthalmol 1990; 74(10): 595-600.
[3] Goldenberg D, Soiberman U, Loewenstein A, Goldstein M. Heidelberg spectral-domain optical

coherence tomographic findings in retinal artery macroaneurysm. Retina 2012; 32(5): 990-5.
[http://dx.doi.org/10.1097/IAE.0b013e318229b233] [PMID: 22127222]
[4] Abdel-Khalek MN, Richardson J. Retinal macroaneurysm: natural history and guidelines for
treatment. Br J Ophthalmol 1986; 70(1): 2-11.
[5] Townsend-Pico WA, Meyers SM, Lewis H. Indocyanine green angiography in the diagnosis of retinal
arterial macroaneurysms associated with submacular and preretinal hemorrhages: a case series. Am J
Ophthalmol 2000; 129(1): 33-7.
[6] Moradian S, Soheilian M. Periretinal hemorrhage due to retinal arterial macroaneurysm: The role of
ICG angiography in solving a diagnostic dilemma. J Ophthalmic Vis Res 2009; 4(2): 125-6.
[PMID: 23264858]
[7] Battaglia Parodi M, Iacono P, Pierro L, Papayannis A, Kontadakis S, Bandello FM. Subthreshold laser
treatment versus threshold laser treatment for symptomatic retinal arterial macroaneurysm. Invest
Ophthalmol Vis Sci 2012; 53(4): 1783-6.
[http://dx.doi.org/10.1167/iovs.11-8772] [PMID: 22395893]
[8] McCabe CM, Flynn HW Jr, McLean WC, et al. Nonsurgical management of macular hemorrhage
secondary to retinal artery macroaneurysms. Arch Ophthalmol 2000; 118(6): 780-5.
[9] Parodi MB, Iacono P, Ravalico G, Bandello F. Subthreshold laser treatment for retinal arterial
macroaneurysm. Br J Ophthalmol 2011; 95(4): 534-8.
[10] Pichi F, Morara M, et al. Intravitreal bevacizumab for macular complications from retinal arterial
macroaneurysms. Am J Ophthalmol 2013; 129(1): 33-7.
CHAPTER 10
Macular Telangiectasia
Yogin Patel1 and Michael D. Ober1,2,*
1
Department of Ophthalmology, Henry Ford Health System, Detroit, MI, USA
2
Macular telangiectasia (MacTel) was best classified and described by Gass and
Blodi as a form of idiopathic juxtafoveolar retinal telangiectasis [1] and is also
commonly referred to as idiopathic perifoveal telangiectasia. This is a group of
disorders which affects the vasculature of the posterior pole. Numerous
classification schemes have been designed to categorize it, most notably, that of
Gass and Blodi [1] and an update by Yannuzzi et al. [2]. Two major
subclassifications are of greatest importance; MacTel type 1 refers to a unilateral
presentation with prominent microaneurysms that is often grouped within the
spectrum of Coats disease. MacTel type 2 is more often referred to simply as
MacTel, and represents an acquired bilateral retinal vascular disorder. For the
purposes of this review, we will focus on MacTel type 2.
Different studies quote very different numbers for the prevalence of this condition
ranging from as high as 0.1% in the Beaver Dam Eye Study to 0.0045 to 0.022%
in the Melbourne collaborative cohort study [3, 4]. The age at onset is usually in
the late 40s to early 60s. There may be a slight female predominance depending
on the study population quoted.
Patients will often present with a pericentral scotoma or metamorphopsia. Visual

acuity rarely progresses to legal blindness but visual dysfunction is common. The
clinical presentation begins with subtle changes noted in the posterior pole.
*
Corresponding author Michael D. Ober: Retina Consultants of Michigan, 29201 Telegraph Road, Suite 606,
Southfield, MI 48034, USA; Tel: (248) 356-8610; Fax: (248) 356-6473; E-mail: obermike@gmail.com
108 Ophthalmology: Current and Future Developments, Vol. 1 Patel and Ober
Lesions most often begin just temporal to the fovea (Figs. 1A, B). They may then
further evolve to include the larger perifoveal region. The initial presenting
change is often a loss of transparency in the retina temporal to the fovea. With
time the lesion may evolve to include dilation of capillaries and will likewise
spread from their temporal perifoveal origin. Histological studies have
demonstrated that the dilated capillaries are mostly located in the deeper retinal
layers [1]. Although, Yannuzzi and others have observed the involvement of both
the superficial and deep plexus [2]. Later changes include dilated venules, which
are often associated with the abnormal capillaries. These vessels tend to increase
in diameter as they approach the fovea, in contrast to normal vessels. In addition,
these vessels often take characteristic right angle turns, which represent diving of
the vessel toward the deeper retinal layers. Associated changes in the RPE include
crystalline deposits (Figs. 3A, B), pigment migration, and hyperplasia following
these venules [2]. Over the time, secondary atrophy of the pigment epithelium and
neurosensory retina may develop. Some eyes may accumulate vitelliform material
under the central macula. Lamellar thinning of the inner retina within the fovea is
common and manifests with the development of inner lamellar cystic changes
(Fig. 4). On occasion the atrophic changes may progress to a full thickness
macular hole.
Neovascularization is another common later stage development usually preceded

by the appearance of the right angle venules and pigmentary changes. As with any
neovascularization, it may be associated with hard exudate, edema, and
hemorrhage. The neovascularization stems from retinal vessels, but may be
indistinguishable from choroidal neovascularization with chorioretinal anasto-
mosis from other etiologies. Late changes may include the formation of a
disciform scar.
Multimodal imaging is critical in the diagnosis of MacTel. One of the earliest

signs of the disease, even before clinical changes appear, is the loss of the
hypofluorescent center in fundus autofluorescence photos which later progress to
more pronounced hypoautofluorescence corresponding to RPE atrophy with
adjacent granular hyperautofluorescence (Figs. 5A, B). This has been postulated
as a direct result of the depletion in macular pigment [5]. Fluorescein angiography
(FA) findings are often diagnostic and include the characteristic telangiectatic
Macular Telangiectasia Ophthalmology: Current and Future Developments, Vol. 1 109
Fig. (1). (A and B) Color fundus photographs demonstrating the subtle loss of retinal transparency and right
angle vessels most notable temporal to both foveae. Retinal pigment epithelial hyperplasia can be seen
surrounding the right angle vessels (not shown here). Vessels temporal to the fovea are noted to be of
irregular caliber and telangiectatic (Photo Credit: Colin Griffin).
Fig. (2). (A and B) Venous phase fluorescein angiogram showing characteristic dilatation and leakage of
telangiectatic vessels most notably temporal to the foveae (Photo Credit: Colin Griffin).
Fig. (3). (A and B) Color fundus photographs demonstrating loss of retinal transparency, right angle vessels,
and crystalline dots at the vitreoretinal interface (Photo Credit:Matthew Lawrence, CRA)
capillaries temporal to the fovea that leak in later frames (Figs. 2A, B). In the
absence of neovascularization, corresponding optical coherence tomography
(OCT) does not include retinal thickening, subretinal fluid, or pronounced cystic
changes in the region of FA leakage, but rather distortion of the foveal pit with the
temporal side becoming larger and thinner [5]. As the disease progresses there is
often disruption of the normal photoreceptor inner segment and outer segment
layer. This is followed by the formation of atrophic lamellar holes, which do not
demonstrate corresponding leakage on FA.
Fig. (4). Outer retinal cavity formation from photoreceptor disruption. Some abnormality in retinal pigment
migration (Photo Credit: Patricia Streasick, CRA).
Fig. (5). (A and B) Fundus autofluorescence showing moderate increase and decrease in autofluorescence
(Photo Credit: Courtney McClenahay).
The differential diagnosis includes a variety of vascular anomalies of the retina.

Branch retinal vein occlusions may result in abnormal collateral vessels
formation, but emanate from an abnormal arterial-venous crossing point and are
most frequently unilateral or at least highly asymmetric. Radiation can cause
similar telangiectatic vascular changes, but requires relevant history and often
presents with cotton-wool spots and pre-retinal neovascularization. Neovascular
AMD may present with similar appearing neovascularization including
chorioretinal anastomosis, but occurs in the presence of drusen, pigment, and
atrophy without the abnormal retinal capillary vascular telangiectatic changes.
Late stage neovascular scar formation from MacTel may be indistinguishable
from that of other etiologies, but often age and the fellow eye examination is
revealing.
MANAGEMENT
As of yet, there are no accepted methods of treatment for the disorder when it
presents without neovascularization. Laser photocoagulation and PDT appear to
be of no benefit [6]. Anti-vascular endothelial growth factor (VEGF) treatment
has led to debatable anatomic improvement but no visual gain [7, 8]. Intravitreal
steroids have likewise demonstrated no positive effect on disease course [9]. Anti-
VEGF has shown positive results when treating early stages of neovascularization
[10]. Surgical intervention has met with poor outcomes in limited numbers of
patients [11]. The macular holes in MacTel have also had limited success with
surgical correction, mainly thought to be the result of the atrophic rather than
transactional nature of formation [12]. Future efforts are currently focused on a
randomized trial utilizing a ciliary neurotrophic factor emitting implant, but no
data was yet available at the time of writing [13].
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1] Gass JD, Blodi BA. Idiopathic juxtafoveolar retinal telangiectasis. Update of classification and follow-
up study. Ophthalmology 1993; 100(10): 1536-46.
[2] Yannuzzi LA, Bardal AM, Freund KB, Chen KJ, Eandi CM, Blodi B. Idiopathic macular
telangiectasia. Arch Ophthalmol 2006; 124(4): 450-60.
[3] Klein R, Blodi BA, Meuer SM, Myers CE, Chew EY, Klein BE. The prevalence of macular
telangiectasia type 2 in the Beaver Dam eye study. Am J Ophthalmol 2010; 150(1): 55-62.e2.
[4] Aung KZ, Wickremasinghe SS, Makeyeva G, Robman L, Guymer RH. The prevalence estimates of
macular telangiectasia type 2: the Melbourne Collaborative Cohort Study. Retina 2010; 30(3): 473-8.
[http://dx.doi.org/10.1097/IAE.0b013e3181bd2c71] [PMID: 19952995]
[5] Gillies MC, Zhu M, Chew E, et al. Familial asymptomatic macular telangiectasia type 2.
Ophthalmology 2009; 116(12): 2422-9.
[6] De Lahitte GD, Cohen SY, Gaudric A. Lack of apparent short-term benefit of photodynamic therapy
in bilateral, acquired, parafoveal telangiectasis without subretinal neovascularization. Am J
Ophthalmol 2004; 138(5): 892-4.
[7] Gamulescu MA, Walter A, Sachs H, Helbig H. Bevacizumab in the treatment of idiopathic macular
telangiectasia. Graefes Arch Clin Exp Ophthalmol 2008; 246(8): 1189-93.
[8] Charbel Issa P, Finger RP, Kruse K, Baumüller S, Scholl HP, Holz FG. Monthly ranibizumab for
nonproliferative macular telangiectasia type 2: a 12-month prospective study. Am J Ophthalmol 2011;
151(5): 876-886.e1.
[9] Wu L, Evans T, Arévalo JF, et al. Long-term effect of intravitreal triamcinolone in the nonproliferative
stage of type II idiopathic parafoveal telangiectasia. Retina 2008; 28(2): 314-9.
[http://dx.doi.org/10.1097/IAE.0b013e31814cf03e] [PMID: 18301037]
[10] Kovach JL, Rosenfeld PJ. Bevacizumab (avastin) therapy for idiopathic macular telangiectasia type II.
Retina 2009; 29(1): 27-32.
[http://dx.doi.org/10.1097/IAE.0b013e31818ba9de] [PMID: 18936721]
[11] Berger AS, McCuen BW II, Brown GC, Brownlow RL Jr. Surgical removal of subfoveal
neovascularization in idiopathic juxtafoveolar retinal telangiectasis. Retina 1997; 17(2): 94-8.
[12] Gregori N, Flynn HW Jr. Surgery for full-thickness macular hole in patients with idiopathic macular
telangiectasia type 2. Ophthalmic Surg Lasers Imaging 2010; 41 Online: 1-4.
[PMID: 21158375]
[13] Chew EY, Clemons TE, Peto T, et al. Ciliary neurotrophic factor for macular telangiectasia type 2:
Results from a phase 1 safety trial. Am J Ophthalmol 2014. pii: S0002-9394(14)00819-8.
CHAPTER 11
Sickle Cell Retinopathy

Luke B. Lindsell and Aziz A. Khanifar*
Retina Group of Washington, Washington DC, USA
Sickle cell disease is an autosomal recessive condition comprising several

different forms of mutated hemoglobin. Patients who are homozygous for the
hemoglobin S gene (HbS) have the most severe form of sickle cell anemia. Other
genotypes of clinical importance to ophthalmologists include HbSC disease
(double heterozygote for HbS and HbC), HbS/b-thal (double heterozygote for
HbS and beta-thalassemia), and sickle cell trait (one normal Hb allele and one
HbS allele). In general, patients with the more severe genotype of sickle cell
disease have less severe ophthalmic manifestations. For example, HbSS has the
most critical systemic complications, the ocular manifestations are less severe
compared to HbSC disease which has a more moderate systemic course. Although
sickle cell trait is relatively asymptomatic, under hypoxic conditions both
systemic and ophthalmic consequences can occur [1].
Relative hypoxia causes mutated hemoglobin to polymerize, ultimately altering

the morphology of the red blood cell (RBC) to the characteristic sickle shape.
These abnormal RBCs occlude terminal arterioles, leading to ischemia and
possible tissue infarction [2]. Sickle cell retinopathy is one end-organ
manifestation of the disease. Similar to diabetic eye disease, both non-
proliferative and proliferative forms occur, and the proliferative disease is
associated with more significant visual morbidity [3].
*
Corresponding author Aziz A. Khanifar: Retina Group of Washington, Washington DC, USA; Tel: (301) 495-
2357, Fax: (301) 495-2359; E-mail: azizkhanifar@gmail.com
Sickle Cell Retinopathy Ophthalmology: Current and Future Developments, Vol. 1 117
Non-proliferative sickle cell retinopathy is characterized by several possible

findings:
1. Vascular tortuosity – more common in HbSS disease (Fig. 1).

2. Salmon patch hemorrhages – located between the internal limiting membrane
(ILM) and retinal surface (“blowout” of occluded arteriole) [4] (Fig. 2).
3. Intraretinal hemorrhages (Fig. 1).
4. Iridescent spots – small schisis cavity in area of resolved intraretinal
hemorrhage. Hemosiderin-laden macrophages appear as glistening spots [4]
(Fig. 3).
5. Black sunburst – flat areas of hyperpigmentation resulting from intraretinal
hemorrhage infiltrating the subretinal space and damaging the retinal pigment
epithelium (RPE) (Fig. 4).
Fig. (1). Color photo montage. Resolving intraretinal hemorrhage that will become a sunburst or possibly
iridescent spots (black arrow). Faint resolving salmon patch hemorrhage (yellow arrow). Vitreous
hemorrhage (white arrow). Vascular tortuosity is also evident.
118 Ophthalmology: Current and Future Developments, Vol. 1 Lindsell and Khanifar
Fig. (2). Color photo. Large peripheral salmon patch.
Fig. (3). Color photo. Iridescent spots.

Fig. (4). Color photo. Sunburst.
Fig. (5). Multiple imaging modalities. Top: Color photo. Central vitreous hemorrhage. Bottom left: Color
photo. Same eye with the peripheral fibrotic sea fan which was the source of the vitreous hemorrhage. Bottom
right: Fluorescein angiogram. Irregular peripheral vasculature.
Proliferative sickle cell retinopathy (PSR) causes visual loss primarily with
vitreous hemorrhage (Fig. 5) and retinal detachment (tractional or tractional-
rhegmatogenous). Fortunately, however, the incidence of proliferative disease is
low [5]. The hallmark of the disease is neovascularization which initially appears
as tufts at the interface between vascular and avascular retina. This typically
occurs in the temporal quadrant. These tufts can progress to a characteristic “sea
fan” configuration (Figs. 5-7). Fibroglial tissue can proliferate over the surface of
the sea fan and scaffold into the vitreous to potentially initiate a tractional retinal
detachment. Wide field fluorescein angiography (FA) is essential in evaluating the
extent of peripheral non-perfusion [6, 7] (Fig. 8).
Fig. (6). Multiple imaging modalities. Color photo montage: Peripheral sea fan with hemorrhages at
avascular retinal border. Inset fluorescein angiogram: Leakage associated with sea fan.
Fig. (7). Color photo montage. Same patient from Fig. (9), three years after superotemporal scatter laser
photocoagulation. Note regression of the sea fan superotemporally and presence of a newer sea fan nasally.
Fig. (8). Fluorescein angiogram. Peripheral non-perfusion in both eyes. An area of arterio-venous
anastomosis in the right eye (white arrow).
Other retinal findings of importance in sickle cell disease:
1. Angioid streaks – rare finding, usually no significant visual sequelae unless

subfoveal choroidal neovascularization occurs.
2. Maculopathy – an enlarged foveal avascular zone, with no impact on visual
acuity, may be demonstrated with FA [8] (Fig. 9). Spectral domain optical
coherence tomography (SDOCT) can detect 3 different findings: a) enlarged
foveal depression with central thinning [9], b) temporal macular thinning [9]
(Fig. 10), and c) inner retinal atrophy as a consequence of focal infarction [10].
1. Proliferative diabetic retinopathy 9. Eales disease

2. Retinal vein occlusion 10. Other collagen vascular diseases (eg lupus, rheumatoid
3. Familial exudative vitreoretinopathy arthritis)
4. Retinopathy of prematurity 11. Acute retinal necrosis
5. Radiation retinopathy 12. Behçet’s disease
6. Ocular ischemic syndrome 13. Pars planitis
7. Sarcoidosis
8. Talc retinopathy
Fig. (9). Fluorescein angiogram. Enlarged foveal avascular zone.
Fig. (10). Optical coherence tomogram. Neurosensory retinal thinning in the temporal macula of the left eye.
The temporal macula is a watershed region, and relative ischemia in this region can produce this finding
which usually has no visual consequence.
MANAGEMENT
The non-proliferative form of the disease requires serial observation. Vitreous

hemorrhage is the most common proliferative manifestation requiring intervention
although a majority of these will clear spontaneously. Sea fans will frequently
spontaneously regress, and small peripheral lesions without vitreous hemorrhage
can be observed [5, 8]. Scatter photocoagulation is the preferred method for
managing large areas of neovascularization or any neovascularization with
concurrent vitreous hemorrhage [8]. Case reports have shown success with
intravitreal anti-vascular endothelial growth factor for sea fan regression [11].
Small gauge pars plana vitrectomy surgery is indicated for patients with non-
clearing vitreous hemorrhages and tractional retinal detachments. Intraoperatively,
segmentation and localized photocoagulation are recommended [12]. Care should
be taken to minimize intraocular pressure elevation.
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1] Jackson H, Bentley CR, Hingorani M, Atkinson P, Aclimandos WA, Thompson GM. Sickle
retinopathy in patients with sickle trait. Eye (Lond) 1995; 9(Pt 5): 589-93.
[2] Lim JI. Ophthalmic manifestations of sickle cell disease: update of the latest findings. Curr Opin
Ophthalmol 2012; 23(6): 533-6.
[http://dx.doi.org/10.1097/ICU.0b013e328358b921] [PMID: 23047170]
[3] Elagouz M, Jyothi S, Gupta B, Sivaprasad S. Sickle cell disease and the eye: old and new concepts.
Surv Ophthalmol 2010; 55(4): 359-77.
[4] Gagliano DA, Goldberg MF. The evolution of salmon-patch hemorrhages in sickle cell retinopathy.
Arch Ophthalmol 1989; 107(12): 1814-5.
[5] Downes SM, Hambleton IR, Chuang EL, Lois N, Serjeant GR, Bird AC. Incidence and natural history
of proliferative sickle cell retinopathy: observations from a cohort study. Ophthalmology 2005;
112(11): 1869-75.
[6] Patel M, Kiss S. Ultra-wide-field fluorescein angiography in retinal disease. Curr Opin Ophthalmol
2014; 25(3): 213-20.
[http://dx.doi.org/10.1097/ICU.0000000000000042] [PMID: 24614144]
[7] Cho M, Kiss S. Detection and monitoring of sickle cell retinopathy using ultra wide-field color
photography and fluorescein angiography. Retina 2011; 31(4): 738-47.
[http://dx.doi.org/10.1097/IAE.0b013e3181f049ec] [PMID: 21836403]
[8] Bonanomi MT, Lavezzo MM. Sickle cell retinopathy: diagnosis and treatment. Arq Bras Oftalmol
2013; 76(5): 320-7.
[9] Chow CC, Genead MA, Anastasakis A, Chau FY, Fishman GA, Lim JI. Structural and functional
correlation in sickle cell retinopathy using spectral-domain optical coherence tomography and
scanning laser ophthalmoscope microperimetry. American Journal of Ophthalmology 2011; 152(4):
704-11 e2.
[10] Witkin AJ, Rogers AH, Ko TH, Fujimoto JG, Schuman JS, Duker JS. Optical coherence tomography
demonstration of macular infarction in sickle cell retinopathy. Arch Ophthalmol 2006; 124(5): 746-7.
[11] Siqueira RC, Costa RA, Scott IU, Cintra LP, Jorge R. Intravitreal bevacizumab (Avastin) injection
associated with regression of retinal neovascularization caused by sickle cell retinopathy. Acta
Ophthalmol Scand 2006; 84(6): 834-5.
[12] Williamson TH, Rajput R, Laidlaw DA, Mokete B. Vitreoretinal management of the complications of
sickle cell retinopathy by observation or pars plana vitrectomy. Eye (Lond) 2009; 23(6): 1314-20.
CHAPTER 12
Radiation Retinopathy
Veronica Kon Graversen*
University of North Carolina at Chapel Hill, NC, USA
Radiation retinopathy (RR) is the result of ultra-structural impairment of the

vascular endothelial cells and pericytes of the retina and choroid after exposure to
ionizing radiation [1]. Several factors influence the development of retinopathy,
including the type of radiation received (external-beam irradiation versus local
radioactive plaque therapy), total dosage and fraction size schemes used,
concomitant systemic vascular diseases, simultaneous chemotherapy, and
pregnancy [2, 3]. These factors determine the interval to onset and severity of the
disease. The dose required to produce retinopathy is variable, but it is generally
accepted that exposure to 30-35 Gray leads to visual changes [3]. The median
time interval to onset of retinopathy is 27 months but may range from few months
to several years [4].
Photoreceptors are relatively preserved and resistant to the radiation effects.

Therefore, the degree of visual loss depends on the severity of the occlusive
vasculopathy and its sequelae.
Clinical Features: The earliest signs include capillary dilation and

microaneurysm formation. Later in the course of the disease, a nonproliferative
phase may develop. This phase is exudative. Hard exudates, intraretinal
(superficial or deeper) and preretinal hemorrhages, telangiectasia, cotton wool
spots and macular edema are frequently seen (Figs. 1 and 2).
*
Corresponding author Veronica Kon Graversen: Ophthalmology Department, University of North Carolina at
Chapel Hill, NC, USA; Tel: (919)518-6361; Email: veronicakonjara@gmail.com
126 Ophthalmology: Current and Future Developments, Vol. 1 Veronica Kon Graversen
Fig. (1). Fundus photograph of a patient treated with ophthalmic plaque radiation for choroidal melanoma.
The patient developed non-proliferative radiation retinopathy, showing retinal hemorrhages, hard exudates
and telangiectasia.
Extensive retinal ischemia may lead to vascular occlusions, retinal

neovascularization (Fig. 2), vitreous hemorrhage, retinal detachment, and, in some
cases, neovascular glaucoma. These late changes are recognized as the
proliferative phase of the disease [1, 3].
Rarely, choroidal neovascular membranes (CNV), chorioretinal anastomosis and

intravitreal polypoidal neovascularization have been reported [5 - 7].
Imaging. The diagnosis is mainly clinical; however, retinal diagnostic imaging

provides valuable tools monitoring the progression of the disease and treatment
response.
Optical coherence tomography: Ensures early recognition of macular changes.

More severe and chronic cases may reveal outer retinal disruption [8].
Fluorescein angiography: Initial findings include varying degrees of capillary

closure and dilation of microvasculature (Fig. 2). The most affected areas are the
peripapillary region and the macula [9].
Indocyanine green angiography: Detects areas of choriocapillaris perfusion

defects [10].
Radiation Retinopathy Ophthalmology: Current and Future Developments, Vol. 1 127
Fig. (2). Fundus photograph shows microaneurysms, hard exudates and and retinal hemorrhages. Fluorescein
angiography reveals microaneurysms, capillary closure and retinal neovascularization.
1. Diabetic retinopathy.
2. Retinal vascular occlusions.
3. Occlusive retinopathy.
4. Retinal telangiectasia.
5. Human immunodeficiency virus retinopathy.
6. Hypertensive retinopathy.
MANAGEMENT
There are no specific treatment guidelines for radiation retinopathy. Macular

ischemia is usually irreversible and is the most feared complication that results in
blindness. Focal laser treatment can be applied to areas of macular edema [11]. In
recent years, intravitreal or periocular steroids and anti-vascular endothelial
growth factor (VEGF) therapies have been successfully used to treat center-
involving macular edema [11 - 13]. Bevacizumab has been the most studied anti-
VEGF in cases of radiation retinopathy. Nevertheless, similar outcomes have been
reported with other anti-VEGF agents. Refractory cases may benefit from
128 Ophthalmology: Current and Future Developments, Vol. 1 Veronica Kon Graversen
combination therapy with intravitreal triamcinolone and anti-VEGF agents [14].

Anti-VEGF agents have also been combined with micropulse laser with promising
results [15].
Argon laser panretinal photocoagulation is the standard therapy for areas of

capillary nonperfusion with associated neovascularization. An approach similar to
the one published in the ETDRS is applied [11]. Photodynamic therapy has been
proposed for the treatment of severe cases of macular edema or CNV. Hyperbaric
oxygen therapy remains controversial [11, 12]. One case report proposed oral
pentoxifylline as a potential therapy to improve visual acuity [16].
Non-clearing vitreous hemorrhage or retinal detachment is treated with standard

vitrectomy techniques [1].
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1] Spielberg L, de Potter P, Leys A. Radiation retinopathy. In: Ryan SJ. Retina. 5th Ed. vol 2. St Luis.
Mosby 2012; pp. 1083-90.
[2] Kumar B, Palimar P. Accelerated radiation retinopathy in diabetes and pregnancy. Eye (Lond) 2000;
14(Pt 1): 107-8.
[3] Jeganathan VS, Wirth A, MacManus MP. Ocular risks from orbital and periorbital radiation therapy: a
critical review. Int J Radiat Oncol Biol Phys 2011; 79(3): 650-9.
[http://dx.doi.org/10.1016/j.ijrobp.2010.09.056] [PMID: 21281895]
[4] Kaushik M, Pulido JS, Schild SE, Stafford S. Risk of radiation retinopathy in patients with orbital and
ocular lymphoma. Int J Radiat Oncol Biol Phys 2012; 84(5): 1145-50.
[http://dx.doi.org/10.1016/j.ijrobp.2011.12.097] [PMID: 22592046]
[5] Berker N, Aslan O, Batman C, Elgin U, Ozkan SS. Choroidal neovascular membrane in radiation
retinopathy. Clin Experiment Ophthalmol 2006; 34(6): 625-6.
[6] Mendrinos E, Pilly B, Baglivo E, Donati G, Safran AB, Pournaras CJ. Chorioretinal anastomosis as a
rare complication of radiation retinopathy. Acta Ophthalmol 2009; 87(4): 473-5.
Radiation Retinopathy Ophthalmology: Current and Future Developments, Vol. 1 129
[7] Pang CE, Freund KB. Intravitreal polypoidal choroidal vasculopathy in radiation retinopathy.
Ophthalmic Surg Lasers Imaging Retina 2014; 45(6): 585-8.
[8] Raman R, Pal SS, Krishnan T, Laxmi G, Radke N, Sharma T. High-resolution optical coherence
tomography correlates in ischemic radiation retinopathy. Cutan Ocul Toxicol 2010; 29(1): 57-61.
[9] Amoaku WM, Archer DB. Fluorescein angiographic features, natural course and treatment of radiation
retinopathy. Eye (Lond) 1990; 4(Pt 5): 657-67.
[10] Takahashi K, Kishi S, Muraoka K, Tanaka T, Shimizu K. Radiation choroidopathy with remodeling of
the choroidal venous system. Am J Ophthalmol 1998; 125(3): 367-73.
[11] Reichstein D. Current treatments and preventive strategies for radiation retinopathy. Curr Opin
Ophthalmol 2015; 26(3): 157-66.
[http://dx.doi.org/10.1097/ICU.0000000000000141] [PMID: 25730680]
[12] Giuliari GP, Sadaka A, Hinkle DM, Simpson ER. Current treatments for radiation retinopathy. Acta
Oncol 2011; 50(1): 6-13.
[http://dx.doi.org/10.3109/0284186X.2010.500299] [PMID: 20722590]
[13] Finger PT, Chin K. Anti-vascular endothelial growth factor bevacizumab (avastin) for radiation
retinopathy. Arch Ophthalmol 2007; 125(6): 751-6.
[14] Shah NV, Houston SK, Markoe A, Murray TG. Combination therapy with triamcinolone acetonide
and bevacizumab for the treatment of severe radiation maculopathy in patients with posterior uveal
melanoma. Clin Ophthalmol 2013; 7: 1877-82.
[PMID: 24092966]
[15] Murray T. Micropulse laser therapy for the treatment of radiation retinopathy. Retina today 2013; 71-
2.
[16] Gupta P, Meisenberg B, Amin P, Pomeranz HD. Radiation retinopathy: the role of pentoxifylline.
Retina 2001; 21(5): 545-7.
CHAPTER 13
Ocular Ischemic Syndrome

Eleonora Lavaque*
Retina Department, Hospital Oftalmológico Santa Lucia, Buenos Aires, Argentina
Retina Department, Instituto Médico de Ojos, Buenos Aires, Argentina
Ocular ischemic syndrome (OIS) is caused by ocular hypoperfusion. Carotid

stenosis superior to 70% or complete occlusion due to atherosclerosis is the
common cause of this rare condition. In 80% of the cases, OIS is found
unilaterally, on the same side of the carotid stenosis [1, 2]. Occasional causes of
OIS secondary to ophthalmic artery obstruction include Takayasu disease or giant
cell arteritis [3].
Described risk factors are: age between 50-80 years, male gender 2:1, and
vascular diseases such as arterial hypertension (75%), diabetes (56%), coronary
diseases, vascular stroke and hemodialysis [3 - 5].
Ninety percent of the patients present with a history of slowly progressive visual
loss in the affected eye. Dull ischemic pain develops gradually and is relieved
when the patient lies down [4, 5].
Anterior segment ischemic signs include iris or angle neovascularization,

iridocyclitis with flare and cells in 20% of cases, cataract, iris atrophy, sluggish
pupillary reaction to light [1]. Other less common signs of OIS are dilatation of
conjunctival and episcleral vessels, corneal edema, and bullous keratopathy [4, 6].
Posterior segment signs are more frequent than anterior segment signs [4]. Poste-
rior segment ischemic signs include narrow retinal arteries, perifoveal telangi-
*
Corresponding author Eleonora Lavaque: Retina Department, Hospital Oftalmológico Santa Lucia, Buenos Aires,
Argentina; Tel: 00-9-54-56458302; Fax: 00-54-11-48124494; E-mail: eblavaque@hotmail.com
Ocular Ischemic Syndrome Ophthalmology: Current and Future Developments, Vol. 1 131
ectasia, dilated retinal veins, mid-peripheral retinal hemorrhages and micro-

aneurysms. Neovascularization in the optic disc or retina and its complications
(fibrovascular proliferation, cotton-wool spots, vitreous hemorrhage) may be
present but are not frequent (Figs. 1-3) [3, 4].
Fig. (1). Fundus photograph shows round circumscribed hemorrhages at the classical midperipherical loca-
tion.
Fig. (2). 70-year-old Caucasian male patient. Medical background: diabetes, hypertension, coronary bypass,
acute ischemic cerebral stroke, recent left carotid surgery, endarterectomy 2 months before, and indication for
future right carotid endarterectomy because of 79% stenosis. Best-corrected visual acuity was 20/40 in the
right eye, and hand motion in the left eye. Positive biomicroscopy: rubeosis iridis, hyphema in left eye.
Intraocular pressure 15/60 mm hg. Fundus photograph of the right eye: preretinal hyaloid fibrosis, preretinal
hemorrhage at an arteriovenous crossing. Ocular fundus findings in left eye: vitreous hemorrhage.
132 Ophthalmology: Current and Future Developments, Vol. 1 Eleonora Lavaque
Fig. (3). Left eye of the same patient as Fig. (2), after vitrectomy and endophotocoagulation. Round
hemorrhages and photocoagulation scars are present. After vitrectomy, visual acuity improved to 20/100,
intraocular pressure improved to 26 mmHg with topical treatment.
A cherry-red spot, characteristic of macular ischemia, is seen in 12% of eyes, due

to IOP exceeding the perfusion pressure or to a result of embolic occlusion of the
central retinal artery [1, 4].
Eighty percent (80%) of OIS present with very characteristic retinal hemorrhages:
they are round, located in the external retinal layers, and at the mid-periphery
(Fig. 1) [2, 3].
Intraocular pressure is usually normal or low. Although anterior segment

neovascularization is frequent, elevated intraocular pressure is less common than
expected due to flow restriction to the ciliary body. Normal-tension glaucoma can
be present in eyes with normal ocular tension due to hypoperfusion to the optic
disc [1, 2, 4].
In fluorescein angiography, 60% presents prolonged arm-to-choroid and arm-to-

retina circulation time (Fig. 4). The normal retinal filling time is approximately 5
seconds, but in the affected eye it may be 1 minute or longer [4].
Fig. (4). Fluorescein angiogram of an ocular ischemic syndrome. Top: Image 47 seconds after dye injection,
showing only arterial filling. Bottom: Image 1:05 minutes after dye injection, showing delayed vein filling,
and significant capillary nonperfusion (Images courtesy of Gerardo Garcia-Aguirre).
The majority of eyes affected with OIS show staining of the retinal vessels at a
late phase. Endothelial cell damage and increased permeability due to chronic
ischemia are responsible for this sign [2]. Macular edema and hyperfluorescence
134 Ophthalmology: Current and Future Developments, Vol. 1 Eleonora Lavaque
of the optic disc are less common signs [4]. The unilateral nature of all these signs
should alert the physician of the presence of an OIS.
Due to the frequent association with carotid artery stenosis, patients with OIS
must undergo Doppler ultrasound of the carotid arteries to measure the degree of
obstruction, which is usually significant. If carotid Doppler ultrasound yields no
relevant result, Doppler ultrasound of retrobulbar vessels should be performed.
Ocular plethysmography and invasive techniques such as carotid arteriography are
usually performed only previous to carotid surgery [4, 7, 8].
The main differential diagnosis is made with retinal vascular diseases such as
diabetic retinopathy or retinal vein occlusion. In OIS, intraretinal hemorrhages are
less numerous than in diabetic retinopathy, they are round and mostly located in
the mid-periphery (Fig. 1). The presence of hard exudates and fibrovascular
proliferation also suggests diabetic retinopathy. Absence of delayed choroidal and
arterial filling time in a fluorescein angiogram also points to diabetic retinopathy
or vein occlusion [4, 8]. Diabetic retinopathy may coexist with OIS, so marked
asymmetry of retinopathy in a diabetic patient should raise the suspicion of OIS
[3].
MANAGEMENT
Treatment is directed towards reducing retinal and anterior segment ischemia.

Panretinal photocoagulation is indicated in patients with iris and posterior
segment neovascularization to prevent neovascular glaucoma or intraocular
hemorrhages (Fig. 3). However, it is effective in only 35% of eyes since choroidal
ischemia, which is unaffected by laser photocoagulation, plays an important role
in developing neovascularization [3, 4, 6].
Since the most frequent etiology is significant carotid artery obstruction, carotid
artery endarterectomy (CEA) is the surgical method of choice, and has proven to
be effective for the treatment of OIS [9].
Mortality rate for OIS is as high as 40% within 5 years of onset. Patients with
ocular ischemic syndrome should be referred for consultation to the neurologist,
vascular surgeon and cardiologist [5].
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1] Brown GC, Magargal LE. The ocular ischemic syndrome. Clinical, fluorescein angiographic and
carotid angiographic features. Int Ophthalmol 1988; 11(4): 239-51.
[2] Sharma S, Brown GC. In: The Ocular Ischemic Syndrome. Ryan SJ, Hinton DR, Schachat AP, et al.,
editors. Elsevier; 2006. pp. 1491-502.
[3] Mendrinos E, Machinis TG, Pournaras CJ. Ocular ischemic syndrome. Surv Ophthalmol 2010; 55(1):
2-34.
[4] Zemba M, Avram CI, Ochinciuc U, Stamate AC, Camburu RL. Ocular ischemic syndrome--a case
report. Oftalmologia 2013; 57(2): 17-22.
[PMID: 24386788]
[5] Sivalingam A, Brown GC, Magargal LE. The ocular ischemic syndrome. III. Visual prognosis and the
effect of treatment. Int Ophthalmol 1991; 15(1): 15-20.
[6] Kerty E, Eide N. Chronic ocular ischaemia. Acta Ophthalmol (Copenh) 1989; 67(4): 386-92.
[http://dx.doi.org/10.1111/j.1755-3768.1989.tb01620.x] [PMID: 2678884]
[7] Chen CS, Miller NR. Ocular ischemic syndrome: review of clinical presentations, etiology,
investigation, and management. Compr Ophthalmol Update 2007; 8(1): 17-28.
[PMID: 17394756]
[8] Hashimoto M, Ohtsuka K, Ohtsuka H, Nakagawa T. Normal-tension glaucoma with reversed
ophthalmic artery flow. Am J Ophthalmol 2000; 130(5): 670-2.
[9] Dzierwa K, Pieniazek P, Musialek P, et al. Treatment strategies in severe symptomatic carotid and
coronary artery disease. Med Sci Monit 2011; 17(8): RA191-7.
[http://dx.doi.org/10.12659/MSM.881896] [PMID: 21804476]
CHAPTER 14
Dry Age-Related Macular Degeneration

Ana Domínguez Yates and Virgil Alfaro*
Retina Consultants of Charleston, Charleston, South Carolina, USA
Age related macular degeneration (AMD) is a progressive and chronic disorder,

characterized by the onset of degenerative changes in the macular area in people
of 50 years of age or older [1]. Besides age, other risk factors are white race [2],
smoking [3, 4] and female gender [5, 6]. Advanced AMD, is the leading cause of
severe central vision loss in this age group, and geographic atrophy (GA) is
responsible for 25% of cases. The Pathophysiologic mechanism still remains
unclear but it is well known that the Retinal Pigment Epithelium (RPE) plays a
key role [7]. Environmental and genetics factors can alter any given patient’s
susceptibility to the disease [8].
The changes in AMD involve the outer retina, RPE, Bruch’s membrane and
choriocapillaris [9]. Drusen are the hallmark features of AMD. They become
visible on biomicroscopic fundus examination when their diameter exceeds 25
μm. They can be classified [10] by size as small (< 0-63 µm diameter), medium
(64-124 µm diameter) or large (> 0-125 µm diameter) (Fig. 1).
According to their appearance they can be classified as hard or soft. Hard or

crystalline drusen (Fig. 2) appear as small, round yellow-white spots with sharp
borders. They correspond to accumulation or entrapment of hyaline material,
lipids and mucopolysaccharides underneath RPE [11, 12]. Large areas of small
hard drusen increase the risk of soft drusen and RPE atrophy at a relatively young
age [13, 14]. Soft drusen are pale yellow-white spots, more than 63 µm in diame-
*
Corresponding author Virgil Alfaro: Retina Consultants of Charleston, 3531 Mary Ader Ave # D, Charleston, SC
29414, Estados Unidos, USA; Tel: +1 843-763-4466; E-mail: virgil.alfaro@gmail.com
Dry Age-Related Macular Degeneration Ophthalmology: Current and Future Developments, Vol. 1 137
Fig. (1). 60-year-old patient with Dry AMD and visual acuity of 20/20 in both eyes. Small drusen (filled
arrow); medium drusen, with a diameter equal or greater than one half of a large drusen (arrowhead); and
large drusen, diameter greater than or equal to a large vein at the disc margin (unfilled arrow).
Fig. (2). Some small drusen in the superior macula in a 61-year-old patient. Hard drusen appear bright with
sharp and very well defined borders (unfilled arrow).
138 Ophthalmology: Current and Future Developments, Vol. 1 Domínguez Yates and Alfaro
Fig. (3). Soft drusen in a 77-year-old patient. Big and pale yellow–white lesions ill-defined margins (arrow).
ter, with ill-defined boundaries, are preferentially located within the fovea
(Fig. 3). They are a result of RPE dysfunction and derive from basal linear
deposits, between the RPE and the Bruch's membrane [11, 12]. Most of the
molecular constituents of drusen reflex their complex pathogenesis: protein
(immune response modulator; immunoglobulin and complement components;
inflammation molecules), cellular components (RPE blebs, lipofuscin, and
melanin, as well as choroidal dendritic cell), glycoconjugates, neutral lipids and
zinc [15].
On Fluorescein angiography (FA), hard drusen appear as a bright early

hyperfluorescence secondary to a window defects (Fig. 4 a-c). On the other hand,
soft drusen appear as progressively hyperfluorescent spots that persist in late
phases due to staining (Figs. 5 a-d and 6 a-c).
Fig. (4). a) Small hard (unfilled arrow) and medium drusen around and between the temporal arcades, right
eye. b) Early hyperfluorescence due to transmission defect, secondary to attenuation or hypopigmentation of
the RPE cells overlying the drusen. c) Fluorescence fades in late frames.
a b
c d
b c
Fig. (5). a) Soft drusen (unfilled arrow) and RPE defects in a left eye. b) and c) Fluorescein angiogram
showing progressive increase in intensity through arteriovenous phase; d) hyperfluorescence persists in late
stages due to staining.
b c
Fig. (6). Soft drusen (unfilled arrow): Funds photographs: a) funds photographs; (b) early and (c) late FA
frames.
Optical Coherence Tomography (OCT) shows soft drusen as well-defined convex

accumulations of homogenous moderately reflective material, underneath the
highly reflective RPE layer (Fig. 7 a, b) (Figs. 8 and 9) or like multiple
excrescences in succession giving a “sawtooth” configuration (Figs. 7c, 10 and
11). The RPE appears to be clearly defined. Hard drusen are discrete nodules with
moderately and highly reflective material, producing RPE disruptions. In either
case, the hyperreflective junction between the inner and outer photo-receptors
segments is elevated, with overlying compression of the outer retinal layers [16].
Drusen may evolve rapidly and are prone to coalesce and become confluent,
separating the RPE basement membrane from the rest of Bruch´s membrane over
long distances, forming a so-called drusenoid pigment epithelial detachment
(DPED). These lesions are often located in the central macula, appearing as a pale
yellow or white shallow elevation of the RPE (Figs. 12 a and 13 a) [17]. On FA,
they appear as a progressive hyperfluorescence secondary to dye pooling and faint

stain in the late frames (Figs. 12 b-d and 13 b-d). OCT shows areas of elevation
of the RPE, with medium to high homogeneous internal reflectivity. Bruch´s
membrane is seen as a thin moderately reflective line underneath it (Figs. 12 e, 13
e and 14) [18].
Fig. (7). a) Fundus color photograph of soft drusen at the perifoveal area; b) OCT showing elevation of the
highly reflective RPE layer with homogeneous moderately reflective material below it; c) “sawtooth” pattern.
Fig. (8). Soft drusen with moderately reflective material and elevation of the ellipsoid layer.
Fig. (9). Soft drusen underneath a clearly defined RPE layer.

Fig. (10). Multiple excrescences in succession given a “sawtooth” of the RPE.
Fig. (11). Multiple excrescences in succession given a saw toothed of the RPE.
a b
d
c
Fig. (12). a) Fundus Photograph of confluent large drusen conforming a drusenoid PED b) and c) progressive
hyperfluorescence throughout angiogram and d) faint stain in late phases; e) OCT RPE elevation. The
Bruch´membrane is clearly seen as a thin hyperreflective line behind it.
a b
c d
Fig. (13). a) Color photo of drusenoid pigment epithelium detachment b), c) and d) early and late phases of
FA with fluorescein pooling into the space. The margins appear to be well-defined during the frames; e) OCT
shows homogenous reflectivity underneath the RPE layer elevation.
Fig. (14). OCT showing confluent soft drusen (DPED) in the inferior macula.
Depigmentation is an area of RPE atrophy, less weel defined, less regular in

shape, and less severe than Atrofia geográfica. Clumps of gray or black pigment
may be observed in or beneath the retina. FA shows mottled early hyperfluo-
rescence that fades later in the study and hypofluorescence by blockage
respectively (Fig. 15 a-d) [19]. OCT shows clumping of hyperreflective material
at the level of the RPE. Hyperreflective particles in the inner retinal layers
indicate RPE migration [16].
Drusen evolve dynamically overtime, and can fade and disappear. This
spontaneous regression is coupled with hyper and hypopigmentation changes and
calcified drusen (chalky-white or shiny drusen) (Fig. 16) [20]. More frequently,
drusen are able to evolve and progress, and over time increase in volume, height
and area. The presence of large, confluent and extensive soft drusen and RPE
abnormalities are associated with increased risk of progression to advanced AMD
and central visual loss [8, 21, 22]. Furthermore, the presence of DPEDs possesses
an additional high risk of developing geographic atrophy [17].
a b
c d
Fig. (15). a) Drusen and hyper (fill arrow) and hypopigmentation (unfilled arrow) of the RPE in the center of
the macula area; b) and c) FA: low signal intensity due to fluorescein blocking at areas of pigment clumping
(fill arrow) and mottled hyperfluorescence secondary to loss of RPE cells (unfilled arrow) during
arteriovenous frames; d) the window defect fades in the late phase (unfilled arrow) but keeps the same shape
and size.
Most authors use the Age-Related Eye Disease Study severity scale to grade
AMD [23]. It is subdivided in mild, when only a few drusen are present (Fig. 17),
moderate, when several drusen are present (Fig. 18), and advanced, when
neovascular disease and/or geographic atrophy (GA) involving the center of the
macula are present.
Fig. (16). Soft drusen, calcified shiny drusen (unfilled arrow) and hyper and hypopigmentation changes (fill
arrow).
Fig. (17). Mild AMD with extensive small drusen or at least one intermediate size drusen and / or
abnormalities in one or eyes.
Fig. (18). Moderate AMD with extensive intermediate drusen, at least 1 large drusen and /or GA not
involving the center of the macula, either in one or both eyes.
GA is usually a round or oval sharply demarcated patch of partial or complete

RPE loss, with associated atrophy of the overlying retina and underlying
choriocapillaris, typically with exposure of large choroidal blood vessels and
relative color change to the surrounding RPE (Figs. 19-21) [24]. It may involve
the central macula (Fig. 22) or spare it (Fig. 23). GA tends to spare the foveal
center until the later stages of the disease (Fig. 24). In FA, GA appears as a well-
defined hyperfluorescent area at late phases, due to staining of the deep choroid
and sclera (Fig. 25 a-e). OCT shows retinal thinning with attenuation of the outer
retina, hyporeflectivity of the RPE, and loss of the layered structure of the retina,
with prominent choroidal deep vessels (Figs. 26-28) [18].
Fig. (19). Large GA with atrophy of the choriocapillaris and exposure of the underlying choroidal vessels.
RPE alteration in the center of the lesion and surrounding the border.
Fig. (20). Intermediate GA.

Fig. (21). Small GA.
Fig. (22). Round patch of central GA involving the center point of the macula, sharply demarcated, with
large choroidal blood vessels in the back in a patient with advanced AMD.
Fig. (23). Drusen, RPE changes and non-central GA in a 95-year-old patient.
Fig. (24). Large GA sparing the central fovea until late stages.
a b
c d
Fig. (25). a) 71-year-old patient with non-central GA; b) c) d) progressive well-defined hyperfluorescence of
the atrophic area. Hyperfluorescence increases in late phases; e) late phase shows intense hyperfluorescence
because of staining of the underlying choroid and sclera.
Fig. (26). Central GA, with outer retinal thinning (loss of the external limiting membrane -ELM- and inner
/outer segment junction) and atrophy of RPE cells, Bruch´s membrane, and choriocapillaris. Highly reflective
signal from the choroid vessels in the atrophic area.
Accumulation of lipofuscin (LF) granules in RPE cells increases in AMD [25].

Normally, Funds autofluorescence (FAF) is able to visualize lipofuscin yielding a
distinctive pattern (Fig. 29). Variations in the FAF signal reflect modifications in
the density of LF. In early AMD, FAF is able to show more widespread
abnormalities than funds examination and FA. Some hard and soft drusen may
present a ring pattern. Confluent drusen have a mildly increased signal (Fig. 30).
FAF is useful to identify a drusenoid PED (mild, diffuse increased signal
corresponding exactly with the detached area) or an RPE tear. Pigment clumping
are focal changes with an increased FAF signal and RPE atrophy appears as
decreased autofluorescence patch. The borders of an area of GA (junctional zone)
can have five different patterns in FAF, that can predict the rate of progression: no
change, indicating slow progression; focal (Fig. 31), indicating slow progression;
banded (Fig. 32), indicating rapid progression; patchy, indicating slow
progression, or diffuse (Fig. 33), indicating rapid progression [26].
Fig. (27). Central GA with loss of the layered structure of the retina.
Fig. (28). Important retinal thinning due to GA in a patient with advanced AMD.
Fig. (29). Topographic distribution of FAF in a normal right eye. There is a homogeneous background with
very low intensity on the optic disc (no autofluorescent material) and retina vessels (absorption by blood
compounds). A gradual decrease in signal in the inner macula toward the fovea (absorption by luteal
pigment).
Fig. (30). FAF of a patient with moderate AMD. Drusen in a ring pattern (unfilled arrow) with decreased
FAF intensities in the center, within or below the range of the normal background signal, surrounded by an
annulus of increased FAF (may correspond to pigment clumping in fundus photos). Large and confluent soft
drusen (arrow) have an increased signal.
Fig. (31). GA is seen as an area of strong reduction in FAF signal secondary to RPE cell death. Focal pattern
in a left eye: individual hyperautoflorescence spots around the GA margin, not in continuous pattern.
Fig. (32). Banded pattern: continuous hyperautofluorescence around the junction area between the normal
retina and the atrophy. It is related to rapid progression.
Fig. (33). Diffuse pattern: increased FAF intensity at the junctional zone and some spots elsewhere. It is
associated with rapid progression of the atrophy; a) right eye and b) left eye of two different patients.
Sequelae of central serous chorioretinopathy may mimick dry AMD (Fig. 34)
[27]. Pattern dystrophy is a group of macular dystrophies with deposition of
yellow or gray pigment at the RPE. They typically appear in younger patients and
have a characteristic pattern in FA (Fig. 35) [28, 29]. Adult-onset foveomacular
vitelliform dystrophy may also resemble dry AMD (Fig. 36), and can be confused
with DPED (Fig. 37 a, b) or with a solely large subfoveal drusen. In FA, the
vitelliform material blocks the background fluorescence early and stains in late
frames. OCT shows a highly reflective material (Fig. 36 b,c) [30, 31]. Other
differential diagnoses include chloroquine toxicity (Fig. 38 a-d) [32 - 34],
cuticular basal laminar drusen (Fig. 39 a-h) [35], central areolar choroidal [36],
and dominant drusen [37].
a b
c d
e f
Fig. (34). 49-year-old man, visual acuity 20/20 in both eyes and history of previous CSC; a) b) fundus
photos of RPE defects in both eyes. Early and late FA frames showing blockage and transmission defect in
the right eye (c) (d) and the left eye (e) (f).
a b
c d
e f
Fig. (35). 43-year-old woman with asymmetric Butterfly Dystrophy. Visual acuity remains 20/20 in both
eyes. Fundus photos of right (a) and left eye (b). FA in early and late phases in the right eye (c), (d) and left
eye; (e) and (f), showing the typical feature with a hypofluorescence center surrounded by a hyperfluorescent
rim.
b c
Fig. (36). a) Fundus photo of a left eye with Adult- onset foveomacular vitelliform dystrophy. Early FA b)
with central hypofluorescence due to blockage. Late frame shows c) hyperfluorescence due to deposit stains.
Fig. (37). a) Confluent large soft drusen in the left eye of a 71-year-old patient, imitating a round central
yellow vitelliform spot; b) OCT showing a DPED.
Fig. (38). 65-year-old female patient, with a history of hydroxychloroquine treatment and eye toxicity; a)
funds photograph of the right eye, showing no abnormalities; b) fundus photograph of the left eye, showing
pigment changes; c) and d) visual fields with central scotoma in both eyes.
a b
c d
Fig. (39). a) and b) Right and left eyes of a patient with Basal Laminar Drusen. In the color photos there are
some drusen and defects in the RPE in the posterior pole in both eyes. Right eye FA (c) and (d). In FA the
small, round and widely spread drusen are more evident, forming a “stars in the sky” pattern presenting early
hyperfluorescence.
e f
g h
Fig. (39). Left eye FA (e) and (f). At late phases in the right (g) and left eye (h), the hyperfluorescence fades.
MANAGEMENT
There is no adequate therapy for GA in advanced AMD. The AREDS Study was
designed to assess whether active treatment with antioxidants and/or zinc could
reduce the risk of developing advanced AMD or visual acuity loss. The largest
risk reduction was observed in patients with confluent soft drusen or patients with
contralateral advanced AMD. Treatment options for prevention and progress of
GA are limited [38].
ACKNOWLEDGEMENTS
Declared none.
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[http://dx.doi.org/10.1016/S0161-6420(99)90267-1]
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[4] Klein R, Lee KE, Gangnon RE, Klein BE. Relation of smoking, drinking, and physical activity to
changes in vision over a 20-year period: the Beaver Dam Eye Study. Ophthalmology 2014; 121(6):
1220-8.
[5] Klein R, Klein BE, Linton KL. Prevalence of age-related maculopathy. The Beaver Dam Eye Study.
Ophthalmology 1992; 99(6): 933-43.
[6] Friedman DS, O’Colmain BJ, Muñoz B, et al. Prevalence of age-related macular degeneration in the
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degeneration: AREDS Report No. 18. Arch Ophthalmol 2005; 123(11): 1570-4.
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83(3): 358-68.
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[36] Boon CJ, Klevering BJ, Cremers FP, et al. Central areolar choroidal dystrophy. Ophthalmology 2009;
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[38] A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E,
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Arch Ophthalmol 2001; 119(10): 1417-36.
CHAPTER 15
Wet Age-Related Macular Degeneration

Gerardo García-Aguirre*, 1,2
1
Retina Department, Asociaciós para Evitar la Ceguera en Mexico, Mexico City, Mexico
2
Ophthalmology, Escuela de Medicina - Tec de Monterrey, Mexico City, Mexico
Age-related macular degeneration (AMD) is one of the leading causes of legal

blindness in patients over 60 years, especially in developed countries [1]. The
prevalence of the disease varies according to ethnicity [2], and is more common in
smokers [3, 4] and in women [5, 6]. The disease is classified in two stages, known
as dry AMD (which is discussed in another chapter) which is characterized by the
presence of drusen in the posterior pole, and wet AMD, in which the patient
develops neovascularization that stems from the choroid, penetrates Bruch’s
membrane, and by leakage of fluid, hemorrhage and scarring, affecting the center
of the macula.
When a choroidal neovascularization (CNV) develops, patients may complain of

metamorphopsia and a central or paracentral relative scotoma.
Clinical examination usually reveals drusen, and the presence of intraretinal or

subretinal fluid that causes thickening of the retina. Hemorrhage and hard
exudates may also be observed (Figs. 1-6).
*
Corresponding author Gerardo García Aguirre: Retina Department, Asociaciós para Evitar la Ceguera en Mexico,
Vicente García Torres 46, San Lucas Coyoacan, Mexico City 04030, Mexico; Tel: +52 (55) 10841400; E-mail:
jerry_gar_md@yahoo.com
Wet Age-Related Macular Degeneration Ophthalmology: Current and Future Developments, Vol. 1 169
Fig. (1). Fundus photograph of the right eye with subfoveal CNV showing multiple soft and hard drusen in
the macular area. A small subretinal hemorrhage may be observed nasal to the fovea.
Fig. (2). Fundus photograph of the right eye with a subfoveal CNV and large submacular hemorrhage.
170 Ophthalmology: Current and Future Developments, Vol. 1 Gerardo García-Aguirre
Fig. (3). Red-free fundus photograph of the left eye, showing a subfoveal CNV surrounded by hard exudates
and submacular hemorrhage.
Fig. (4). Fundus photograph of the left eye displaying an extrafoveal CNV, just adjacent to the
inferotemporal border of the optic nerve, with associated subretinal hemorrhage.
Fig. (5). Fundus photograph of the left eye, showing a subfoveal CNV with abundant hard exudates and
some subretinal fibrosis.
Fig. (6). Fundus photograph of the left eye showing a massive submacular hemorrhage secondary to CNV.
Fluorescein angiography (FA) is very useful, showing an area of early

hyperfluorescence that increases in intensity and size as the study progresses due
to leakage of fluorescein. Accumulation of dye secondary to a pigment epithelium
detachment (PED) may also be observed (Figs. 7-15).
Optic coherence tomography (OCT) of the macula is an invaluable adjuvant in the

diagnosis and follow-up of patients with CNV secondary to AMD. Different
abnormalities may be observed in any given case, including intraretinal fluid,
subretinal fluid, PED, and/or a hyper-reflective subretinal lesion. Hard exudates
and hemorrhages are also observed as hyper-reflective foci (Figs. 16-19)
Indocyanine green angiography (ICGa) is also useful in some cases, especially

when suspecting a CNV with an arteriolar component (Figs. 20, 21).
If the CNV has not been treated and has been present for several months,
subretinal fibrosis begins to appear, which usually grows into a large disciform
scar that may occupy the entire macular area. The presence of fibrotic tissue has a
very bad visual prognosis (Figs. 22-25).
Fig. (7). Early fluorescein angiogram of the same eye as Fig. (1), showing hyperfluorescence in the
subfoveal area.
Fig. (8). Late fluorescein angiogram of the same eye as in Fig. (7), showing increase of hyperfluorescence in
the foveal area. Hyperfluorescence secondary to drusen is also observed throughout the macula.
Fig. (9). Early fluorescein angiogram of the same eye as in Fig. (2), showing mild hyperfluorescence in the
center of the macula and blockage secondary to hemorrhage.
Fig. (10). Late fluorescein angiogram of the same eye as in Fig. (9), showing leakage of fluorescein
secondary to CNV, surrounded by blockage secondary to hemorrhage.
Fig. (11). Fluorescein angiogram of the same eye as in Fig. (3), showing a large area of hyperfluorescence
that involves the center of the macula, surrounded by blockage secondary to subretinal hemorrhage.
secondary to a large subfoveal CNV.
Fig. (13). Early fluorescein angiogram of the same eye as in Fig. (4), showing hyperfluorescence
surrounding the optic disc.
surrounding the optic nerve.
Fig. (15). Fluorescein angiogram of the same eye as in Fig. (6), showing a large area of blockage secondary
to massive subretinal hemorrhage.
Fig. (16). OCT of the macula showing increased retinal thickness, accumulation of intraretinal fluid and the
presence of a subfoveal hyper-reflective lesion corresponding to a CNV.
Fig. (17). OCT of the macula showing increased retinal thickness, accumulation of intraretinal fluid and the
presence of an extrafoveal hyper-reflective lesion corresponding to a CNV.
Fig. (18). OCT of the macula showing accumulation of subretinal fluid and the presence of a pigment
epithelial detachment.
Fig. (19). OCT of the macula showing accumulation of subretinal fluid and the presence of several pigment
epithelial detachments.
Fig. (20). Combined fluorescein-indocyanine green angiography. The image on the left corresponds to
fluorescein angiography, showing diffuse hyperfluorescence in the macular area. The image on the right
corresponds to indocyanine green angiography, showing thick vessels where the neovascularization
originates. These are called arteriolized CNVs.
Fig. (21). Combined fluorescein-indocyanine green angiography. The image on the left corresponds to
fluorescein angiography, showing diffuse hyperfluorescence in the macular area. The image on the right
corresponds to indocyanine green angiography, showing thick vessels where the neovascularization
originates. These are called arteriolized CNVs.
Fig. (22). Fundus photograph of the right eye showing a large area of subretinal fibrosis. Hard exudates,
intraretinal and subretinal hemorrhage can also be observed.
Fig. (23). Early fluorescein angiogram of the same eye as in Fig. (22) showing mild diffuse
hyperfluorescence in the macular area.
Fig. (24). Late fluorescein angiogram of the same eye as in Fig. (23), showing an area of intense fluorescein
leakage, and some blockage secondary to hemorrhage.
Fig. (25). OCT of a case of disciform scar, showing large quantities of intraretinal fluid, distortion of the
retinal layers, and presence of a large subretinal hyper-reflective lesion corresponding to subretinal fibrosis.
When putting together the age of the patient, the clinical appearance, the presence
of AMD in the contralateral eye, and the findings in FA and OCT, the diagnosis is
usually straightforward. An entity that shares some of the features observed in wet
AMD is central serous chorioretinopathy (CSC). It presents as subretinal fluid
associated to a PED. It usually affects younger patients but may be present at any
age. The presence of drusen in the same or the other eye might facilitate the
differential diagnosis. Also, CSC lacks hemorrhage or hard exudates, which are
relatively common in CNV.
Differential diagnosis should also be made with other causes of CNV, such as
high myopia, presumed ocular histoplasmosis syndrome or idiopathic.
Fig. (26). OCT of the same eye as in Fig. (16) after intravitreal anti-VEGF therapy, showing decreased
retinal thickness, recovery of foveal contour and improvement of intraretinal fluid. Some hyper-reflective
tissue is still observed in the subfoveal area.
MANAGEMENT
The gold standard for the management of CNV secondary to AMD is the injection
of intravitreal anti-VEGF agents. Available agents are aflibercept [7],
bevacizumab [8, 9] and ranibizumab [8 - 10], which are injected on a monthly

basis until intraretinal and/or subretinal fluid disappears. Injection of these agents
usually results in the arrest of disease progression and improved visual acuity
(Figs. 26-28).
Fig. (27). OCT showing loss of foveal depression, increased retinal thickness, presence of intraretinal fluid,
and the presence of a hyper-reflective lesion under the fovea.
Fig. (28). OCT of the same eye as in Fig. (27) after intravitreal anti-VEGF therapy, showing decreased
retinal thickness, recovery of foveal contour and improvement of intraretinal fluid. Some hyper-reflective
tissue is still observed in the subfoveal area. The retina in the foveal area is thinner than normal.
Other treatments include laser photocoagulation, which is reserved for cases in

which the CNV is located outside the macula [11], and photodynamic therapy
with verteporfin, which is sometimes used as an adjuvant to anti-VEGF therapy in
non-responder cases [12].
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
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related maculopathy and age-related macular degeneration. Surv Ophthalmol 1995; 39(5): 367-74.
[2] Friedman DS, Katz J, Bressler NM, Rahmani B, Tielsch JM. Racial differences in the prevalence of
age-related macular degeneration: the Baltimore Eye Survey. Ophthalmology 1999; 106(6): 1049-55.
[3] Thornton J, Edwards R, Mitchell P, Harrison RA, Buchan I, Kelly SP. Smoking and age-related
macular degeneration: a review of association. Eye (Lond) 2005; 19(9): 935-44.
[http://dx.doi.org/10.1038/sj.eye.6701978] [PMID: 16151432]
[4] Klein R, Lee KE, Gangnon RE, Klein BE. Relation of smoking, drinking, and physical activity to
changes in vision over a 20-year period: the Beaver Dam Eye Study. Ophthalmology 2014; 121: 1220-
8.
[5] Klein R, Klein BE, Linton KL. Prevalence of age-related maculopathy. The Beaver Dam Eye Study.
[6] Friedman DS, O'Colmain BJ, Muñoz B, et al. Eye diseases prevalence research group. Prevalence of
age-related macular degeneration in the United States. Arch Ophthalmol 2004; 122: 564-72.
[7] Schmidt-Erfurth U, Kaiser PK, Korobelnik JF, et al. Intravitreal aflibercept injection for neovascular
age-related macular degeneration: ninety-six-week results of the VIEW studies. Ophthalmology 2014;
121(1): 193-201.
[8] Martin DF, Maguire MG, Fine SL, et al. Ranibizumab and bevacizumab for treatment of neovascular
age-related macular degeneration: two-year results. Ophthalmology 2012; 119(7): 1388-98.
[9] Chakravarthy U, Harding SP, Rogers CA, et al. Ranibizumab versus bevacizumab to treat neovascular
age-related macular degeneration: one-year findings from the IVAN randomized trial. Ophthalmology
2012; 119(7): 1399-411.
[10] Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular
degeneration. N Engl J Med 2006; 355(14): 1419-31.
[11] Ladas ID, Chatziralli IP, Kotsolis AI, et al. Intravitreal ranibizumab versus thermal laser
photocoagulation in the treatment of extrafoveal classic choroidal neovascularization secondary to
age-related macular degeneration. Ophthalmologica 2012; 228(2): 93-101.
[12] Tozer K, Roller AB, Chong LP, et al. Combination therapy for neovascular age-related macular
degeneration refractory to anti-vascular endothelial growth factor agents. Ophthalmology 2013;
120(10): 2029-34.
CHAPTER 16
Polypoidal Choroidal Vasculopathy

Jans Fromow Guerra*
Retina Department, Asociación para Evitar la Ceguera en México, IAP, México City, México
Polypoidal choroidal vasculopathy (PCV) is a retinal disorder involving the

choroidal vasculature characterized by the presence of aneurysmal polypoidal
dilations that commonly arise from a network of branching choroidal vessels, that
was described in 1982 by Lawrence Yanuzzi. PCV usually shows a broad
spectrum of manifestations both clinically and epidemiologically. For this reason,
it has been widely debated whether to consider it a subtype of neovascular age-
related macular degeneration (AMD) or a separate clinical entity. Some of the
characteristics of PCV are shared by AMD but some others are radically different.
Epidemiology Essentials of PCV

● PCV predominantly occurs at a mean age of 68.4 years with a range of 21-93
years [1 - 3].
● PCV is more prevalent in non-Caucasians, such as Asians and African-
Americans where it has been reported to be responsible up to 23-54.7% of wet
AMD cases in these populations [4]. However, in Caucasians the prevalence of
this disease has been reported in about 8-13% [5].
● PCV is more prevalent in females than in males in Caucasian (female 52% to
65%) populations and the opposite in Asians (men 63% to 78%) [2].
*
Corresponding author Jans Fromow Guerra: Retina Department, Asociación para Evitar la Ceguera en México,
IAP, Vicente García Torres, 46. San Lucas Coyoacán, México DF. México 04030; Tel: +52.55.10841400; Fax:
+52.55.10841404; E-mail: fromow@me.com
Polypoidal Choroidal Vasculopathy Ophthalmology: Current and Future Developments, Vol. 1 187
Clinical Essentials of PCV

● Localization: PCV can present in different regions: peripapillary, macular or
extramacular. Prevalence of each one of these presentations varies according to
different ethnic groups [6]. Different reports state that unilateral disease can be
found in up to 79.4% to 91.8% of cases [6 - 8].
● Clinical appearance: Clinical examination will reveal orange-reddish colored
vascular dilatations often associated to pigment epithelial detachments (PED),
subretinal hemorrhage, hard exudates and drusen (Fig. 1).
Fig. (1). Clinical appearance of peripapillary PCV.
● Angiographic & OCT Analysis (Figs. 2-6): Indocyanine green angiography

(ICGA) should be considered as the gold standard in PCV diagnosis since
findings in FA can be easily mistaken for wet AMD especially in elderly
patients with drusen and bilateral disease [8, 9]. ICGA will often reveal single or
multiple polyps appearing as vascular aneurysmal dilatations arising from inner
choroidal vessels often seen as a neovascular plaque or a so-called “branching
vascular networks” (BVN). These findings are usually seen within the first 6
minutes after the injection of ICG [10]. However, PCV lesions may not be easily
seen due to minor or extensive hemorrhage. A classification of PCV has been
developed regarding the presence or absence of BVN determined by ICGA:
188 Ophthalmology: Current and Future Developments, Vol. 1 Jans Fromow Guerra
Type I PCV or “Polypoidal CNV” with an apparent BVN and type 2 PCV or
“Typical PCV” with no or faint BVN. These 2 different PCV subtypes have
distinct clinical course, treatment response and genetic background [11 - 13].
OCT shows important diagnostic characteristics (Figs. 2, 3 and 6). In most cases
a sharp elevated PED is observed, that may be associated to a flat, shallower
PED. Polypoidal lesions are usually attached to the back surface of the elevated
PED. In type I PCV the flat shallower PED is associated with the BVN giving a
“double layer sign” [14].
Fig. (2). ICGA and OCT appearance of peripapillary PCV of the same patient as Fig. (1).
Fig. (3). Left: ICG-Macular Type 2 PCV with no or faint branching vascular network. Right. OCT image
where an associated PED can be clearly observed.
Fig. (4). Left: Fluorescein Angiogram, Right: ICG-Angiogram. This comparison clearly shows the advantage
of ICGA in the diagnosis of PCV, that clearly delineates the lesions, which cannot be distinguished in FA.
Macular Type 1 PCV with apparent branching vascular network from which the polyps arise.
Fig. (5). ICGA of peripapillary Type 2 PCV with no apparent BVN.

Fig. (6). Left: ICGA. Macular Type 1 PCV with apparent branching vascular network from which the polyps
arise. Right: OCT showing a polyp PED.
There are two main clinical entities that should be considered first in the
differential diagnosis of PCV: “Regular” wet AMD, especially if there is a
chronic neovascular process with insufficient anti-VEGF treatment response, and
central serous chorioretinopathy (CSC), which in fact shares similar characte-
ristics including increased choroidal thickness. Furthermore, CSC has been
regarded as a risk factor for PCV [14, 15].
MANAGEMENT
There are several trials that show the efficacy of Anti-VEGF treatment for PCV.
Also, since 2002 the efficacy of Photodynamic Therapy with verteporfin for this
entity has been proven, and some others promote a combination approach [8, 16,
17]. To give scientific solution to this question, a multicenter, double-masked trial
known as EVEREST compared these three treatment regimens. The six-month
results revealed that PDT plus ranibizumab therapy and PDT monotherapy were
both superior to ranibizumab monotherapy in achieving complete polyp
regression (77.8 percent and 71.4 percent vs. 28.6 percent, respectively; p < 0.01)
[18]. Ongoing studies are evaluating other Anti-VEGF options such as aflibercept.
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1] Bessho H, Honda S, Imai H, Negi A. Natural course and funduscopic findings of polypoidal choroidal
vasculopathy in a Japanese population over 1 year of follow-up. Retina 2011; 31(8): 1598-602.
[http://dx.doi.org/10.1097/IAE.0b013e31820d3f28] [PMID: 21478804]
[2] Imamura Y, Engelbert M, Iida T, Freund KB, Yannuzzi LA. Polypoidal choroidal vasculopathy: a
review. Surv Ophthalmol 2010; 55(6): 501-15.
[3] Al-Rashaed S. Idiopathic polypoidal choroidal vasculopathy in a young man: case report and literature
review. Middle East Afr J Ophthalmol 2008; 15(2): 90-3.
[http://dx.doi.org/10.4103/0974-9233.52000] [PMID: 21346845]
[4] Sho K, Takahashi K, Yamada H, et al. Polypoidal choroidal vasculopathy: incidence, demographic
features, and clinical characteristics. Arch Ophthalmol 2003; 121(10): 1392-6.
[5] Ciardella AP, Donsoff IM, Huang SJ, Costa DL, Yannuzzi LA. Polypoidal choroidal vasculopathy.
Surv Ophthalmol 2004; 49(1): 25-37.
[6] Hou J, Tao Y, Li XX, Zhao MW. Clinical characteristics of polypoidal choroidal vasculopathy in
Chinese patients. Graefe's archive for clinical and experimental ophthalmology. Albrecht Von Graefes
Arch Klin Exp Ophthalmol 2011; 249(7): 975-9.
[http://dx.doi.org/10.1007/s00417-010-1575-7]
[7] Chang YC, Wu WC. Polypoidal choroidal vasculopathy in Taiwanese patients. Ophthalmic Surg
Lasers Imaging 2009; 40(6): 576-81.
[8] Cho M, Barbazetto IA, Freund KB. Refractory neovascular age-related macular degeneration
secondary to polypoidal choroidal vasculopathy. Am J Ophthalmol 2009; 148(1): 70-8 e1.
[9] Stangos AN, Gandhi JS, Nair-Sahni J, Heimann H, Pournaras CJ, Harding SP. Polypoidal choroidal
vasculopathy masquerading as neovascular age-related macular degeneration refractory to
ranibizumab. Am J Ophthalmol 2010; 150(5): 666-73.
[10] Koh AH, Chen LJ, Chen SJ, et al. Polypoidal choroidal vasculopathy: evidence-based guidelines for
clinical diagnosis and treatment. Retina 2013; 33(4): 686-716.
[http://dx.doi.org/10.1097/IAE.0b013e3182852446] [PMID: 23455233]
[11] Kawamura A, Yuzawa M, Mori R, Haruyama M, Tanaka K. Indocyanine green angiographic and
optical coherence tomographic findings support classification of polypoidal choroidal vasculopathy
into two types. Acta Ophthalmol 2013; 91(6): e474-81.
[http://dx.doi.org/10.1111/aos.12110] [PMID: 23848133]
[12] Tanaka K, Nakayama T, Mori R, et al. Associations of complement factor H (CFH) and age-related
maculopathy susceptibility 2 (ARMS2) genotypes with subtypes of polypoidal choroidal vasculopathy.
Invest Ophthalmol Vis Sci 2011; 52(10): 7441-4.
[13] Miki A, Honda S, Kondo N, Negi A. The association of age-related maculopathy susceptibility 2
(ARMS2) and complement factor H (CFH) variants with two angiographic subtypes of polypoidal
choroidal vasculopathy. Ophthalmic Genet 2013; 34(3): 146-50.
[http://dx.doi.org/10.3109/13816810.2012.749288] [PMID: 23289808]
[14] Yang LH, Jonas JB, Wei WB. Optical coherence tomographic enhanced depth imaging of polypoidal
choroidal vasculopathy. Retina 2013; 33(8): 1584-9.
[http://dx.doi.org/10.1097/IAE.0b013e318285cbb3] [PMID: 23584691]
[15] Kim SW, Oh J, Kwon SS, Yoo J, Huh K. Comparison of choroidal thickness among patients with
healthy eyes, early age-related maculopathy, neovascular age-related macular degeneration, central
serous chorioretinopathy, and polypoidal choroidal vasculopathy. Retina 2011; 31(9): 1904-11.
[16] Shima C, Gomi F, Sawa M, Sakaguchi H, Tsujikawa M, Tano Y. One-year results of combined
photodynamic therapy and intravitreal bevacizumab injection for retinal pigment epithelial detachment
secondary to age-related macular degeneration. Graefe's archive for clinical and experimental
ophthalmology =. Albrecht Von Graefes Arch Klin Exp Ophthalmol 2009; 247(7): 899-906.
[http://dx.doi.org/10.1007/s00417-009-1067-9]
[17] Song JH, Byeon SH, Lee SC, Koh HJ, Kwon OW. Short-term safety and efficacy of a single
intravitreal bevacizumab injection for the management of polypoidal choroidal vasculopathy.
Ophthalmologica 2009; 223(2): 85-92.
[18] Koh A, Lee WK, Chen LJ, et al. EVEREST study: efficacy and safety of verteporfin photodynamic
therapy in combination with ranibizumab or alone versus ranibizumab monotherapy in patients with
symptomatic macular polypoidal choroidal vasculopathy. Retina 2012; 32(8): 1453-64.
[http://dx.doi.org/10.1097/IAE.0b013e31824f91e8] [PMID: 22426346]
CHAPTER 17
Retinal Angiomatous Proliferation (RAP)

Maximiliano Gordon1,2,* and Guillermo Gordon†
1
2
Fe, Argentina
Retinal Angiomatous Proliferation (RAP), or type 3 neovascularization, is a

different form of exudative age-related macular degeneration (AMD) [1]. Its main
characteristic is an abnormal anastomosis between the choroidal and the retinal
vessels. The pathogenesis of this entity remains controversial [2 - 4]. Yannuzzi
et al. believe that the neovascular process originates within the neurosensory
retina. In contrast, Gass proposed that the process begins with choroidal
neovascularization (CNV) [1].
Gass’ classification scheme is based on neovascularization relationship to the

retinal pigment epithelium (RPE). Type 1 neovascularization describes new blood
vessels growing under the RPE, while in Type 2 neovascularization these
proliferate over the RPE. Freund has proposed modifying Gass’ original
classification by adding Type 3 neovascularization, which refers to a type of
neovascularization with preference for the retina [1].
Symptoms are similar to those of AMD. However, patients with RAP tend to be
older. The classical findings include retinal and preretinal hemorrhages, and
pigment epithelial detachments, as well as small and multiple intraretinal blood
[5].
*
Corresponding author Maximiliano Gordon: Centro de la Visión Gordon - Manavella, Montevideo 763, CP 2000,
Rosario - Santa Fe, Argentina; Tel/Fax: +54(341)4400239/4244850; E-mail: maximilianogordon19@gmail.com
†
Died
194 Ophthalmology: Current and Future Developments, Vol. 1 Gordon and Gordon
RAP classification distinguishes three vasogenic stages based on the nature and
progression of the neovascularization process. Stage I involves capillary
proliferation within the retina originating from the deep retinal plexus (intraretinal
neovascularization [IRN]). Stage II is determined by IRN extending into the
subretinal space (subretinal neovascularization [SRN]). Stage III describes
progression to CNV, that can be clearly determined clinically or angiographically.
This stage is sometimes characterized by a vascularized pigment epithelial
detachment and retinal choroidal anastomosis (RCA) [6]. Stage-I RAP lesions
manifest with intraretinal neovascularization with telangiectatic retinal capillaries
and small angiomatous structures perfused by the retinal circulation. Stage-II RAP
lesions extend beyond the photoreceptor layer into the subretinal space resulting
in subretinal neovascularization. A serous PED is often seen. In stage-III RAP, it
is presumed that an RCA is formed. Patients that are not treated for stage-III RAP
lesions can develop large fibrotic scars [7]. In these cases, fluorescein
angiography revealed poorly defined staining that simulates occult CNV (Figs. 1
and 3).
Indocyanine green angiography (Fig. 3) often helps make an accurate diagnosis. It

revealed a focal area of hyperfluorescence corresponding to the neovascu-
larization (“hot spot”). OCT may reveal intraretinal hyperreflectivity, corres-
ponding to angiomatous proliferation associated with intraretinal or subretinal
fluid (Figs. 2 and 4) and/or RPE detachment [6]. Dilated fundus exam showed
hemorrhages and lipid exudates in an area of occult CNV on the basis of
fluorescein angiography and indocyanine green angiography (ICG) revealed the
presence of a hot spot. These findings led to the diagnosis of RAP [6, 7].
Differential diagnosis should include other forms of CNV with ICG hot spots
(occult CNV) and polypoidal choroidal vasculopathy (PCV). This latter disease
presents with normally larger retinal hemorrhages and round reddish-orange
macular lesions in the eye fundus. OCT is also a helpful tool in differentiating
RAP, PCV, and occult membranes. In PCV, polyps appear in OCT as abrupt
neurosensory detachment. Other differential diagnosis is macular telangiectasia.
Retinal Angiomatous Proliferation (RAP) Ophthalmology: Current and Future Developments, Vol. 1 195
a b
c d
e f
Fig. (1). A 73-year-old woman with retinal angiomatous proliferation. Fundus photograph and autofluo-
rescence revealing perifoveal lesion (a and b). Fluorescein angiogram showing hyperfluorescence with
diffuse leakage of dye (c-f) (Courtesy of Alejandro Lavaque, Argentina).
Fig. (2). OCT of the same patient shown in Fig. (1). OCT scans showing subretinal fluid and hyperreflective
subretinal lesion (Courtesy of Alejandro Lavaque, Argentina).
a b
c d
e f
Fig. (3). Fundus photograph (a-b), fluorescein angiography (c-d) and ICG (e-f) of patient with retinal
angiomatous proliferation (Courtesy of Gerardo Garcia Aguirre, Mexico).
The main differences are telangiectasias not associated with serous PED, a
healthier RPE and less frequent choroidal neovascularization associated with
parafoveal telangiectasias [8, 9].
MANAGEMENT
Some treatment options for RAP lesions have been thermal laser photocoa-
gulation, surgical ablation, PDT, intravitreal triamcinolone, intravitreal antiangi-
ogenic drugs and combined treatments.
Fig. (4). OCT of the same patient shown in Fig. (3). OCT scans showing intraretinal fluid and
hyperreflective subretinal lesion. (Courtesy of Gerardo Garcia Aguirre).
Apparently, traditional thermal laser photocoagulation is an effective treatment for

some stage-I and early stage-II RAP lesions outside the fovea. However, when
RAP exists in association with a PED, the effectiveness of most treatments is
deeply affected.
According to short-term results reported on non-randomized studies, RAP lesions

treated with photodynamic therapy (PDT) and intravitreal triamcinolone acetate
(IVTA) [10 - 12] revealed apparently better VA outcomes and/or a reduced
number of treatment sessions in comparison with PDT alone. However, there was
also a high frequency of recurrence [13, 14]. Krebs I. et al. [15] found minimal
differences between the PDT monotherapy group and the combined PDT and
IVTA group regarding progress of distance VA, retinal thickness and lesion size,
and he concluded that new therapeutic strategies might be necessary to address
RAP lesions, probably including therapy with antiangiogenic drugs. As is the case
with classic and occult lesions, intravitreal injection of antiangiogenic agents

seems to be more effective in the treatment of RAP lesions than PDT alone.
Short-term experience with intravitreal injection of anti-vascular endothelial

growth factor (VEGF) in RAP has only been reported in some uncontrolled
studies [16, 17], which showed favorable outcomes; however, frequent intravitreal
injections are expected [18 - 21].
Another treatment option consists of surgical excision of the feeder artery and
vein by means of diathermy technique, if appropriate, for stage-II RAP lesions
with or without serous PED [22]. Future treatments include a combined
therapeutic approach to the management of RAP lesions.
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1] Scott AW, Bressler SB. Retinal angiomatous proliferation or retinal anastomosis to the lesion. Eye
(Lond) 2010; 24(3): 491-6.
[2] Hartnett ME, Weiter JJ, Garsd A, Jalkh AE. Classification of retinal pigment epithelial detachments
associated with drusen. Graefes Arch Clin Exp Ophthalmol 1992; 230(1): 11-9.
[3] Kuhn D, Meunier I, Soubrane G, Coscas G. Imaging of chorioretinal anastomoses in vascularized
retinal pigment epithelium detachments. Arch Ophthalmol 1995; 113(11): 1392-8.
[4] Schneider U, Gelisken F, Kreissig I. Retinal choroidal anastomosis in classic choroidal
neovascularization demonstrated by indocyanine green angiography. Acta Ophthalmol Scand 1995;
73(5): 450-2.
[5] Yannuzzi LA. Retinal angiomatous proliferation in AMD. Review of Ophthalmol. 2003.
[6] Yannuzzi LA, Negrão S, Iida T, et al. Retinal angiomatous proliferation in age-related macular
degeneration. Retina 2001; 21(5): 416-34.
[7] Koreen L, Hollar MW, Cousins SW. Where Do PCV and RAP Fit in the Spectrum of AMD CNV
Subtypes? Determining lesion morphology provides for better diagnosis and treatment. Retinal
Physician, Issue: October 2010.
[8] Gass JD, Oyakawa RT. Idiopathic juxtafoveolar retinal telangiectasis. Arch Ophthalmol 1982; 100(5):
769-80.
[9] Coscas G. Chorioretinal anastomoses 1994. Springer 2009.
[http://dx.doi.org/10.1007/978-3-642-01467-3_11]
[10] Sutter FK, Kurz-Levin MM, Fleischhauer J, Bösch MM, Barthelmes D, Helbig H. Macular atrophy
after combined intravitreal triamcinolone acetonide (IVTA) and photodynamic therapy (PDT) for
retinal angiomatous proliferation (RAP). Klin Monatsbl Augenheilkd 2006; 223(5): 376-8.
[http://dx.doi.org/10.1055/s-2006-926564] [PMID: 16705508]
[11] Mantel I, Ambresin A, Zografos L. Retinal angiomatous proliferation treated with a combination of
intravitreal triamcinolone acetonide and photodynamic therapy with verteporfin. Eur J Ophthalmol
2006; 16(5): 705-10.
[PMID: 17061221]
[12] van de Moere A, Kak R, Sandhu SS, Talks SJ. Anatomical and visual outcome of retinal angiomatous
proliferation treated with photodynamic therapy and intravitreal triamcinolone. Am J Ophthalmol
2007; 143(4): 701-4.
[13] Reche-Frutos J, Calvo-Gonzalez C, Donate-Lopez J, et al. Retinal angiomatous proliferation
reactivation 6 months after high-dose intravitreal acetonide triamcinolone and photodynamic therapy.
Eur J Ophthalmol 2007; 17(6): 979-82.
[PMID: 18050128]
[14] Montero JA, Ruiz-Moreno JM, Sanabria MR, Fernandez-Munoz M. Efficacy of intravitreal and
periocular triamcinolone associated with photodynamic therapy for treatment of retinal angiomatous
proliferation. Br J Ophthalmol 2009; 93(2): 166-70.
[15] Krebs I, Krepler K, Stolba U, Goll A, Binder S. Retinal angiomatous proliferation: combined therapy
of intravitreal triamcinolone acetonide and PDT versus PDT alone. Graefes Arch Clin Exp Ophthalmol
2008; 246(2): 237-43.
[16] Saito M, Shiragami C, Shiraga F, Nagayama D, Iida T. Combined intravitreal bevacizumab and
photodynamic therapy for retinal angiomatous proliferation. Am J Ophthalmol 2008; 146: 935–941.
retinal angiomatous proliferation. Graefes Arch Clin Exp Ophthalmol 2007; 245: 1597-602.
[PMID: 17437123]
[17] Lo Giudice G, Gismondi M, De Belvis V, Cian R, Tavolato M, Galan A. Single-session photodynamic
therapy combined with intravitreal bevacizumab for retinal angiomatous proliferation. Retina 2009;
29(7): 949-55.
[http://dx.doi.org/10.1097/IAE.0b013e3181af106d] [PMID: 19584653]
[18] Meyerle CB, Freund KB, Iturralde D, et al. Intravitreal bevacizumab (Avastin) for retinal angiomatous
proliferation. Retina 2007; 27(4): 451-7.
[http://dx.doi.org/10.1097/IAE.0b013e318030ea80] [PMID: 17420697]
[19] Ghazi NG, Knape RM, Kirk TQ, Tiedeman JS, Conway BP. Intravitreal bevacizumab (avastin)
treatment of retinal angiomatous proliferation. Retina 2008; 28(5): 689-95.
[http://dx.doi.org/10.1097/IAE.0b013e318162d982] [PMID: 18463511]
[20] Joeres S, Heussen FM, Treziak T, Bopp S, Joussen AM. Bevacizumab (Avastin) treatment in patients
with retinal angiomatous proliferation. Graefes Arch Clin Exp Ophthalmol 2007; 245(11): 1597-602.
[http://dx.doi.org/10.1007/s00417-007-0580-y] [PMID: 17437123]
[21] Gharbiya M, Allievi F, Recupero V, Martini D, Mazzeo L, Gabrieli CB. Intravitreal bevacizumab as
primary treatment for retinal angiomatous proliferation: twelve-month results. Retina 2009; 29(6):
740-9.
[http://dx.doi.org/10.1097/IAE.0b013e3181a0be1d] [PMID: 19516116]
[22] Borrillo JL, Sivalingam A, Martidis A, Federman JL. Surgical ablation of retinal angiomatous
proliferation. Arch Ophthalmol 2003; 121(4): 558-61.
CHAPTER 18
Choroidal Neovascular Membrane in Degenerative

Myopia
Federico Furno Sola1,2,*
1
Ophthalmology Service, Sanatorio Mapaci, Rosario, Santa Fe, Argentina
2
Grupo Laser Visión, Rosario, Santa Fe, Argentina
Myopia is a common condition in many countries, particularly in East Asia,

affecting approximately 40% of Chinese adults older than 40 years. The
prevalence of myopia in developed countries is reported to be between 11% and
36%. The overall prevalence of pathologic myopia is approximately 1% to 4% in
the general adult population although there is a wide geographical variation. The
associated prevalence of visual impairment due to pathologic myopia is estimated
to be 0.1% to 1.4%. The definition of pathologic myopia is not standardized, but
is historically classified in clinical trial literature as a myopic refractive error
greater than -6 diopters, or an axial length >26 mm, associated to degenerative
changes involving the sclera, choroid and retina. Choroidal neovascularization
secondary to pathological myopia is a common vision-threatening complication
and often affects adults of working age, and develops in approximately 5% to
10% of patients with pathological myopia. The overall prevalence of choroidal
neovascularization secondary to pathological myopia is therefore estimated to be
approximately 0.04% to 0.05% in the general population [1, 2].
The chorioretinal lesions are viewed as a consequence of excessive axial

elongation. It is believed that progressive distension of the posterior pole stretches
the retina, choroid and sclera, as evidenced by the straightening of the temporal
*
Corresponding author Federico Furno Sola: Grupo Laser Visión, Mariano Moreno 1397, Rosario – Santa Fe,
Argentina; Tel: +54 (0341) 4472122; Email: furnosola@gmail.com
202 Ophthalmology: Current and Future Developments, Vol. 1 Federico Furno Sola
retinal vessels, the appearance of peripapillary atrophy, and the thinning of the
retina and choroid. Various changes may occur in the fundus of a patient with
myopia, related to the presence of myopic conus, staphylomas, retinal pigment
epithelium and choroid disturbances and atrophic areas (Figs. 1-3). Lacquer
cracks are linear or stellate; the lines are fine, irregular in caliber, yellowish-white,
horizontally oriented, single and/or multiple. Lacquer cracks are ruptures of
Bruch´s elastic lamina and carry a guarded visual prognosis because of their
association with focal degenerative lesions and subretinal neovascularization
along their course [1, 2].
It is generally accepted that the pigmented lesion described by Fuchs and the
hemorrhagic lesion reported by Foerster represent different stages of the process
of the development of CNV in myopia (Fig. 2). Neovascularization has been
identified to precede the development of Fuchs spots. The growth of choroidal
new vessels induces a sudden painless reduction in vision usually associated with
metamorphopsia. Biomicroscopically, it is observed as a light-gray, round or
elliptic macular lesion (Fig. 3). The lesion is usually discrete in size and located
next to the fovea [1, 2].
Fig. (1). Numerous areas of pigment epithelium atrophy and choriocapillaris extend to the macular region. A
circular myopic crescent is visible.
Choroidal Neovascular Membrane Ophthalmology: Current and Future Developments, Vol. 1 203
Fig. (2). Numerous areas of pigment epithelium and choriocapillaris atrophy extend into the macular region.
A circular myopic crescent is visible. Hemorrhage occupies the center of the fovea.
Fig. (3). Numerous areas of atrophy of the pigment epithelium and choriocapillaris extend to the macular
region. A circular myopic crescent is visible. Choroidal new vessels with neovascular lesion and macular
edema.
Fluorescein angiography usually shows a lesion that is hyperfluorescent early in

the study (Fig. 4). Later in the study, the hyperfluorescent area grows, although
leakage does not increase significantly (Fig. 5). ICG angiography may detect a
focal hyperfluorescent area that fades with dye washout. On OCT, the CNV
extends above the RPE (Figs. 6 and 7), and generally lacks a significant amount of
subretinal or intraretinal fluid [1, 2].
Fig. (4). Mid phase of fluorescein angiography shows a hyperfluorescent zone located at the foveal avascular
zone.
Fig. (5). Late frame of fluorescein angiography, showing dye leakage.

Choroidal Neovascular Membrane Ophthalmology: Current and Future Developments, Vol. 1 205
Fig. (6). Optical coherence tomography, showing hyperreflective subretinal material with macular edema.
Fig. (7). Optical coherence tomography showing hyperreflective subretinal material.
The differential diagnosis of myopic CNV should include other causes of CNV
such as age-related macular degeneration, idiopathic, angioid streaks, trauma,
tumors, multifocal choroiditis and presumed ocular histoplasmosis syndrome. The
refractive error and the presence of findings compatible with high myopia such as
a posterior staphyloma or the rectification of the temporal arcades should make

the diagnosis relatively straightforward.
MANAGEMENT
The visual prognosis in cases of choroidal new vessels in degenerative myopia

remains controversial. Laser photocoagulation and photodynamic therapy has
fallen by the wayside with the advent of anti-VEGF therapies. The RADIANCE
study is the first controlled trial in patients with myopic CNV to demonstrate that
intravitreal ranibizumab treatment was superior compared with photodynamic
therapy. During the RADIANCE study different dose regimens were assessed,
which showed rapid and similar improvements in mean BCVA from baseline up
to month 3 that were sustained with continued individualized ranibizumab
treatment up to month 12 [1, 2].
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1] Wolf S, Balciuniene VJ, Laganovska G, et al. RADIANCE: a randomized controlled study of
ranibizumab in patients with choroidal neovascularization secondary to pathologic myopia.
Ophthalmology 2014; 121(3): 682-92.e2.
[2] Ryan SJ, Hincon DR, Schachat AP, Wikinson CP (Eds). Retina. 4th ed. Philadelphia: Elsevier 2006;
Vol. 2.
CHAPTER 19
Angioid Streaks
Michael Larsen1,*, Mette K.G. Andersen1, Naresh Mandava2 and Richard
Hwang3
1
Department of Ophthalmology, Glostrup Hospital and Faculty of Health Sciences, University of
Copenhagen, Kobenhave Denmark
2
Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO, USA
3
Vitreoreitnal Disease and Surgery, Department of Ophthalmology, University of Colorado
School of Medicine, Aurora, CO, USA
Angioid streaks is the term used for a characteristic type of posterior segment
lesion consisting of irregular and sometimes branching lines with a red or
brownish appearance that extend from the rim of the optic disc to the periphery of
the fundus (Figs. 1-4, 8A, B, 9A, B) [1]. They were originally described by Doyne
in 1889 [2]. The streaks are caused by breaks in the Bruch’s membrane – retinal
pigment epithelium (RPE) complex [1].
Angioid streaks can be seen in the presence of various extraocular conditions,

most commonly pseudoxanthoma elasticum, a connective tissue disorder caused
by defects in the ABCC6 gene [3]. It gives rise to lax and dimpled skin, mainly on
the flexor side of the neck, elbows and knees (Fig. 6). The inheritance is mostly
autosomal recessive, but autosomal dominant patterns can also be seen. The
precise physiological function of ABCC6 is unknown, but it can be seen to be
involved in transporting intracellular elements to the extracellular space. Defects
in the ABCC6 protein lead to the accumulation of mineralized and fragmented
*
Corresponding author Michael Larsen: Department of Ophthalmology, Glostrup Hospital and Faculty of Health
Sciences, University of Copenhagen, Kobenhave, Denmark; Email: MICLAR01@regionh.dk
208 Ophthalmology: Current and Future Developments, Vol. 1 Larsen et al.
Fig. (1). Angioid streaks (black arrows) of the classic red type that resemble large choroidal blood vessels.
The streaks are found behind the retinal blood vessels at the level of the retinal pigment epithelium. Red
streaks stain early and prominently on fluorescein angiograms. Subfoveal choroidal neovascularization is also
seen in this case (white arrow).
Fig. (2). Brownish and greyish pigmented angioid streaks temporal and superior of the optic disc in a patient
with pseudoxanthoma elasticum. Note also subfoveal hemorrhage and choroidal neovascularization.
Angioid Streaks Ophthalmology: Current and Future Developments, Vol. 1 209
Fig. (3). Parafoveal classic subretinal neovascularization of choroidal origin (black arrows) in a patient with
angioid steaks, one of which can be seen superior to the optic nerve head. Fluorescein angiography (lower
right) shows prominent leakage, which explains the serous detachment of the neurosensory retina (black
arrowheads). The upper right part of the color fundus photograph shows the spotted orange peel (peau
d’orange) appearance of the diffuse outer retinal degeneration.
Fig. (4). Angioid streaks, a mixture of brownish streaks, pale atrophic areas, mainly around the margin of the
optic disc, curved streaks concentric with the disc that are reminiscent of traumatic choroidal rupture lines
and a small active choroidal neovascularization of approximately 250 µm diameter at the inferonasal margin
of the fovea, emanating from the inferior tip of the large pale defect of the retinal pigment epithelium.
Fig. (5). Angioid streaks and diffuse degeneration of the outer retina in a man aged 42 with pseudoxanthoma
elasticum. A peau d’orange pattern is seen most prominently in the temporal fundus. It is highlighted in a
color-stretched section shown in the upper right of the montage. Fundus autofluorescence is absent
corresponding to the streaks and elevated in the scattered dots that are spread over the rest of the macula.
Optical coherence tomography shows varying degrees of photoreceptor outer segment atrophy and pigment
epithelium attenuation in the central macula.
Fig. (6). Hyperkeratotic papules and rugged skin surface in an 18-year-old woman with pseudoxanthoma
elasticum (left) and loose skin that remains elevated after having been pinched on the neck of a 45-year-old
man (right) with the same condition.
elastic fibers in the connective tissue of the skin, vessel walls, and Bruch’s
membrane with consequent weakening of these tissues. Angioid streaks have also
been reported in Paget’s disease, hemolytic conditions such as hereditary
spherocytosis, sickle cell disease and thalassemia and in Ehlers-Danlos syndrome
(type 6), Marfans syndrome, senile elastosis, acromegaly, retinitis pigmentosa,
lead poisoning, and Bassen-Kornzweig syndrome.
Sporadic observations suggest that minor blunt trauma to the eye can lead to the
formation or expansion of angioid streaks and induction of choroidal
neovascularization (CNV). The same mechanism is suspected to be the cause of
subretinal hemorrhage in the absence of CNV. Patients with angioid streaks are
therefore advised to avoid contact sports and to wear protective goggles when
engaging in activities where eye trauma may occur.
Fig. (7). Fibrotic end-stage submacular choroidal neovascularization in an eye with angioid streaks, two of
which are crossing the rim of the image at 12 o’clock and 1 o’clock, respectively.
Clinical diagnosis can usually be made with fundoscopy. Angioid streaks

typically appear as bilateral narrow jagged lines beneath the retina with an
interconnecting pattern radiating out from the peripapillary region (Figs. 1-4, 8A,
B, 9A, B). They are evident a few millimeters from the optic disc and have a
thickness of 50-500 µm [4 - 6]. The streaks develop and spread very slowly over
decades, presumably as a result of mechanical stress in a thickened, calcified and
fragile Bruch’s membrane. The streaks are often bright red and can be mistaken
for large fundus vessels, hence the term angioid (Greek, having the appearance of
a blood vessel). Pale atrophic streaks can also be seen as hyperpigmentation along
the borders of the streaks. Angioid streaks are associated with a high risk of
invasion of the subretinal space by CNV arising from the streaks. Smaller
localized defects in Bruch’s membrane can also give rise to pink patches in the
peripheral fundus called salmon spots. Multiple small semiconfluent yellow dots
are seen in many cases, mostly temporal of the fovea, a characteristic that has
been likened to the skin of an orange and therefore is called peau d’orange (Figs.
3, 5, 8A, B, 9B). Autofluorescence fundus photography shows absence of
autofluorescence corresponding to the streaks and hyperfluorescence in areas with
peau d’orange elements (Figs. 5, 9H-J).
A
Fig. (8). A 24-year-old female with biopsy-proven pseudoxanthoma elasticum, with angioid streaks
emanating from the peripapillary region with a peau d' orange pigmentary pattern of the peripheral retina in
the right (A) and left (B) eyes.
A B
C D
E F
Fig. (9). A 36-year-old female with skin biopsy proven pseudoxanthoma elasticum, with angioid streaks in
the right (A) and left (B) eyes. Note the retinal pigment epithelial changes in the left macula and the peau d'
orange changes in the left temporal macula. Fluorescein angiogram of the right (C) and left (D) eyes defines
the angioid streaks well and shows no evidence of leakage. One year after diagnosis, the patient developed
subfoveal hemorrhage and subretinal fluid in the left eye (E). Fluorescein angiogram demonstrated leakage
from an active choroidal neovascularization (CNV) (F). Her left eye was treated with two bevacizumab
injections without improvement.
During fluorescein angiography, angioid streaks can have a “window defect” due
to RPE atrophy adjacent to them (Figs. 9C, D). Angioid streaks may show up as
irregular hyperfluoresence during early phases and varied degrees of staining in
late phases (Figs. 10B, C, E). Leakage is evident when CNV is present (Figs. 9F,
10C). Angiography can help aid in diagnosis when the clinical appearance on
ophthalmoscopy is unclear [6, 7].
G H
I J
Fig. (9). Four years later, she developed CNV in the right eye, and has been treated with scheduled
bevacizumab in the right eye. Vision remained stable one year after initiating scheduled bevacizumab
treatment. Her right eye shows RPE atrophy and mild cystoid macular edema without hemorrhage (G) and
her left eye shows a disciform scar (I). Fundus autofluorescence clearly defines the areas of RPE atrophy in
both eyes (H,J).
When neither fundoscopy nor fluorescein angiography can confirm the diagnosis,
indocyanine green angiography (ICG) can be a useful tool. Angioid streaks show
up as well defined late phase hyperfluoresence and in some cases are only
detectable by ICG angiography [8].
CNV with foveal involvement is the primary cause of symptomatic visual

dysfunction in eyes with angioid streaks (Figs. 2-4, 9E, F). Neovascularization
arises from streaks that approach or reach the fovea and must be considered a
constant threat that increases with the proximity of the streak to the fovea.
Neovascularization is believed to be promoted by the underlying defect in Bruch’s
membrane. The lesion is commonly a classic (type 2) choroidal neovascu-
larization. Fibrotic involution of streaks after intravitreal VEGF-inhibition therapy
indicates that angioid streaks are composed of vascular tissue that bridges the gap
left by the rupture in Bruch’s membrane [9]. Fibrotic involution is also the natural
end-stage of the spontaneous course of CNV development (Figs. 7, 9I, 10A, D, F,
G).
Fig. (10). A 54 year-old male with angioid streaks, with a disciform scar and crystalline bodies in the right
eye (A). Fluorescein angiography of left eye shows early hyperfluoresence (B) with late leakage (C)
consistent with a choroidal neovascular membrane along the superior arcade. The CNV was treated with laser
and was inactive the following month. Six months after laser, there is a subretinal scar underneath the
superior arcade (D) in the left eye and fluorescein angiography shows late staining but no active leakage (E).
Eight years later, he developed additional scarring in the right (F) and left (G) eyes.
The occasional observation of curvilinear RPE defects that are concentric with the
optic disc in eyes with angioid streaks suggests that these eyes are prone to
traumatic choroidal rupture (Fig. 4). Consequently, patients with lesions typical of
traumatic choroidal rupture should be examined for angioid streaks and systemic
conditions related to angioid streaks. Angioid streaks should be suspected in cases
that may at first glance appear to be age-related macular degeneration with CNV,
idiopathic peripapillary degeneration, peripapillary choroidal neovascularization,
or lacquer-cracks in myopic degeneration.
MANAGEMENT
Patients with angioid streaks are usually asymptomatic and can be monitored.
Because of the brittleness of Bruch’s membrane, patients should be warned of the
potential risk of choroidal rupture from mild trauma. Symptoms arise if the
lesions extend to the foveola, resulting in metamorphopsia, scotomas, and
decreased vision. Complications such as traumatic Bruch’s membrane rupture or
macular CNV can also dramatically impact vision. Untreated CNV has poor
prognosis because of the possible development of a disciform scar (Fig. 9G-J,
10A). Historically, several treatments have been evaluated including laser
photocoagulation, transpupillary thermotherapy, photodynamic therapy, subretinal
CNV extraction, and macular translocation therapy. Most treatments, when
effective, were only able to achieve short term stabilization or a delay of disease
progression, with recurrence being the rule [5]. While certain treatments may be
considered in select cases, treatment with anti-VEGF agents has proven to be the
most effective. Most studies, which have a limited number of patients and use
either bevacizumab [10 - 12] or ranibizumab, have found stabilization or impro-
vement of best corrected visual acuity (BCVA) in a majority of patients after
treatment [13 - 18]. Treatment in earlier disease stages appears to result in
increased BCVA more frequently than treatment in advanced stages, where only
stabilization is achieved [12]. Frequent follow up is still required given the high
rate of recurrence and currently there is no data to support any one particular
treatment regimen e.g. fixed interval vs pro re nata (PRN). Several studies have
investigated combined treatments such as PDT and anti-VEGF [5, 16 - 18] with
encouraging results but further studies will be required to determine whether

combination therapy offers significant advantages over single therapy treatment.
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1] Charbel Issa P, Finger RP, Holz FG, Scholl HP. Multimodal imaging including spectral domain OCT
and confocal near infrared reflectance for characterization of outer retinal pathology in
pseudoxanthoma elasticum. Invest Ophthalmol Vis Sci 2009; 50(12): 5913-8.
[2] Doyne R. Choroidal and retinal changes the result of blows on the eyes. Trans Ophthalmol Soc U K
1889; 9: 128.
[3] Bergen AA, Plomp AS, Hu X, de Jong PT, Gorgels TG. ABCC6 and pseudoxanthoma elasticum.
Pflugers Arch 2007; 453(5): 685-91.
[4] Agarwal A, Ed. Gass`atlas of macular diseases. 5th ed., Edinburgh, UK: Elsevier Saunders 2012.
[5] Gliem M, Finger RP, Fimmers R, Brinkmann CK, Holz FG, Charbel Issa P. Treatment of choroidal
neovascularization due to angioid streaks: a comprehensive review. Retina 2013; 33(7): 1300-14.
[http://dx.doi.org/10.1097/IAE.0b013e3182914d2b] [PMID: 23719398]
[6] Georgalas I, Papaconstantinou D, Koutsandrea C, et al. Angioid streaks, clinical course,
complications, and current therapeutic management. Ther Clin Risk Manag 2009; 5(1): 81-9.
[PMID: 19436620]
[7] Smith JL, Gass JD, Justice J Jr. Fluorescein fundus photography of angioid streaks. Br J Ophthalmol
1964; 48: 517-21.
[8] Dithmar S, Holz FG. Fluorescein angiography in ophthalmology. Springer Science & Business Media
2008.
[9] Bloch SB, Larsen M. Fibrosis of extramacular angioid streaks following ranibizumab treatment of
subfoveal choroidal neovascularization. Acta Ophthalmol 2011; 89(1): e102-4.
[10] Neri P, Salvolini S, Mariotti C, Mercanti L, Celani S, Giovannini A. Long-term control of choroidal
neovascularisation secondary to angioid streaks treated with intravitreal bevacizumab (Avastin). Br J
Ophthalmol 2009; 93(2): 155-8.
[11] Sawa M, Gomi F, Tsujikawa M, Sakaguchi H, Tano Y. Long-term results of intravitreal bevacizumab
injection for choroidal neovascularization secondary to angioid streaks. Am J Ophthalmol 2009;
148(4): 584-590.e2.
[12] Finger RP, Charbel Issa P, Schmitz-Valckenberg S, Holz FG, Scholl HN. Long-term effectiveness of
intravitreal bevacizumab for choroidal neovascularization secondary to angioid streaks in
pseudoxanthoma elasticum. Retina 2011; 31(7): 1268-78.
[http://dx.doi.org/10.1097/IAE.0b013e318207d1dc] [PMID: 21386758]
[13] Vadalà M, Pece A, Cipolla S, et al. Angioid streak-related choroidal neovascularization treated by
intravitreal ranibizumab. Retina 2010; 30(6): 903-7.
[http://dx.doi.org/10.1097/IAE.0b013e3181cafc75] [PMID: 20531143]
[14] Myung JS, Bhatnagar P, Spaide RF, et al. Long-term outcomes of intravitreal antivascular endothelial
growth factor therapy for the management of choroidal neovascularization in pseudoxanthoma
elasticum. Retina 2010; 30(5): 748-55.
[http://dx.doi.org/10.1097/IAE.0b013e3181c596b1] [PMID: 19996818]
[15] El Matri L, Kort F, Bouraoui R, Karim B, Chebil A, Chaker N. Intravitreal bevacizumab for the
treatment of choroidal neovascularization secondary to angioid streaks: one year of follow-up. Acta
Ophthalmol 2011; 89(7): 641-6.
[16] Artunay O, Yuzbasioglu E, Rasier R, Sengul A, Senel A, Bahcecioglu H. Combination treatment with
intravitreal injection of ranibizumab and reduced fluence photodynamic therapy for choroidal
neovascularization secondary to angioid streaks: preliminary clinical results of 12-month follow-up.
Retina 2011; 31(7): 1279-86.
[http://dx.doi.org/10.1097/IAE.0b013e318205b228] [PMID: 21394063]
[17] Donati MC, Virgili G, Bini A, et al. Intravitreal bevacizumab (Avastin) for choroidal
neovascularization in angioid streaks: a case series. Ophthalmologica 2009; 223(1): 24-7.
[18] Prabhu VV, Morris RJ, Shah PK, Narendran V. Combination treatment of low fluence photodynamic
therapy and intravitreal ranibizumab for choroidal neovascular membrane secondary to angioid streaks
in Paget’s disease - 12 month results. Indian J Ophthalmol 2011; 59(4): 306-8.
[http://dx.doi.org/10.4103/0301-4738.82000] [PMID: 21666317]
CHAPTER 20
Presumed Ocular Histoplasmosis Syndrome

Manuel Garza-León1,*, Luz Elena Concha del Río2 and Miguel Pedroza Seres3
1
Department of Medical Sciences, Division of Health Sciences, Universidad de Monterrey,
Monterrey, Nuevo León, México
2
Uveitis Department, Asociación para Evitar la Ceguera en México. I.A.P, Mexico
3
Uveitis and Ocular Inmunology Department, Instituto de Oftalmología Conde de Valenciana,
México, DF. Clínica de Retina, Guadalajara, J., Mexico
Presumed ocular histoplasmosis syndrome (POHS) is an inflammatory eye

disease that has been reported to be associated with systemic fungal infection by
Histoplasma capsulatum [1]. It is restricted mainly to endemic countries and is
mainly seen in the midwest of the United States and where Histoplasma
capsulatum is endemic [2], although there have been reports of a similar disease
from countries that are nonendemic zones for the microorganism [3].
POHS is a posterior uveitis, predominantly diagnosed clinically by the

observation of characteristic fundus lesions in one or both eyes. The ocular triad
of POHS consists in the presence of multiple atrophic choroidal spots (known as
histo spots) (Fig. 1), peripapillary atrophy (PPA) and maculopathy (Figs. 2-5).
Macular lesions are secondary to choroidal neovascularization (CNV) or atrophy
and most of the time display a disciform pattern (Figs. 4, 6). Also, one of the key
manifestations of POHS is the absence of inflammation in the vitreous. The
disease occurs predominately in young adults and linear streaks are described in
5-16% of cases [3, 4]. Initially the disease occurs in one eye, being able to affect
the second eye in 9-22% of cases [5, 6].
*
Corresponding author Manuel Garza-León: Department of Medical Sciences, Division of Health Sciences,
Universidad de Monterrey, Monterrey, Nuevo León, México; Tel: +52 8188824208; Fax: +52 81888242'8; E-mail:
manuel@drgarza.mx
220 Ophthalmology: Current and Future Developments, Vol. 1 Garza-León et al.
Fig. (1). Fundus photographs of a 62-year-old female. Visual acuity was 20/30 in the right eye and 20/25 in
the left eye. The anterior segment had no inflammation, there were no vitreous cells. Several chorioretinal
scars were observed in the posterior pole and periphery.
Fig. (2). Fundus photograph of the same patient as Fig. (1).

Presumed Ocular Histoplasmosis Ophthalmology: Current and Future Developments, Vol. 1 221
Fig. (3). Fluorescein angiogram of the same patient as Figs. (1 and 2). Dye accumulation due to a fibrous
scar is observed adjacent to the optic nerve. Several histo spots may be observed in the periphery.
Fig. (4). OCT of the macula of the same eye as Figs. (1-3). A large area of subretinal fibrosis is observed.
Fig. (5). Color fundus photograph of the posterior pole of a right eye displaying all the components of the
triad: circumferential, pigmented peripapillary atrophy with a subretinal choroidal neovascularization
superotemporal to the fovea, and chorioretinal scars.
Fig. (6). Fluorescein angiogram of the same eye as Fig. (5), showing zones of atrophy of the RPE and
choriocapillaris, and leakage secondary to CNV.
Patients may describe metamorphopsia, reduced vision, or paracentral scotomas

from possible active CNV. Those with PPA and extrafoveal chorioretinal scars do
not manifest visual symptoms. The characteristic ocular presentation was
associated with infection with H. capsulatum through epidemiological studies.
However, only rarely has the H. capsulatum antigen and organism been identified
in an eye with POHS. Diagnosis by histoplasmin skin testing (Fig. 7) has been
abandoned since it was suggested that there was a possibility of flare-up of
maculopathy when performing the test [7].
Fig. (7). Histoplasmin skin testing.
Differential diagnosis includes multifocal choroiditis and panuveitis (MFC),

which belong to the group of conditions called “white dot syndromes” and may
mimic lesions of POHS. A disease similar to MFC but without the vitritis seen in
the active phase is called punctate inner choroidopathy (PIC) [8]. POHS should
also be differentiated from multiple evanescent white-dot syndrome (MEWDS),

acute posterior multifocal placoid pigment epitheliopathy and birdshot retino-
choroidopathy.
Other causes of CNV, like idiopathic CNV, choroidal rupture with CNV, myopic
CNV, and exudative age-related macular degeneration (AMD) are also included
in the differential diagnosis of POHS. Other infectious conditions such as ocular
inflammation secondary to tuberculosis, syphilis, toxoplasmosis, and sarcoidosis
produce granulomatous fundus lesions that may resemble those of POHS. But
these conditions are usually related to other signs of inflammation in any part of
the eye, such as keratic precipitates, anterior uveitis, vitreous cells, and cotton
balls in the vitreous. As mentioned earlier, the absence of these inflammatory
signs and very importantly the presence of a clear vitreous help diagnoses POHS.
MANAGEMENT
Due to the absence of inflammation, treatment of patients with POHS is indicated

only when there is evidence of CNV. In up to 60% of patients who don’t receive
treatment for CNV, visual acuity result is 20/200 or worse, and almost three
quarters of these patients experience reduced visual acuity after initial diagnosis
[9].
Visual prognosis for patients with subfoveal CNV secondary to POHS is poor.
Photodynamic therapy [10], submacular surgery [11], systemic, periocular and
intravitreal steroids [12, 13], and radiation [14] were proposed as therapy options,
but intravitreal anti-vascular endothelial growth factor therapy [15, 16] is the
treatment of choice nowadays.
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1] Woods AC, Wahlen HE. The probable role of benign histoplasmosis in the etiology of granulomatous
uveitis. Trans Am Ophthalmol Soc 1959; 57: 318-43.
[PMID: 16693576]
[2] Asbury T. The status of presumed ocular histoplasmosis: including a report of a survey. Trans Am
Ophthalmol Soc 1966; 64: 371-400.
[PMID: 5964934]
[3] Suttorp-Schulten MS, Bollemeijer JG, Bos PJ, Rothova A. Presumed ocular histoplasmosis in The
Netherlands--an area without histoplasmosis. Br J Ophthalmol 1997; 81(1): 7-11.
[4] Fountain JA, Schlaegel TF Jr. Linear streaks of the equator in the presumed ocular histoplasmosis
syndrome. Arch Ophthalmol 1981; 99(2): 246-8.
[5] Five-year follow-up of fellow eyes of individuals with ocular histoplasmosis and unilateral extrafoveal
or juxtafoveal choroidal neovascularization. Arch Ophthalmol 1996; 114(6): 677-88.
[6] Lewis ML, Schiffman JC. Long-term follow-up of the second eye in ocular histoplasmosis. Int
Ophthalmol Clin 1983; 23(“): 125-35.
[http://dx.doi.org/10.1097/00004397-198302320-00013]
[7] Krause AC, Hopkins WG. Ocular manifestation of histoplasmosis. Am J Ophthalmol 1951; 34(4):
564-6.
[8] Leung TG, Moradi A, Liu D, et al. Clinical features and incidence rate of ocular complications in
punctate inner choroidopathy. Retina 2014; 34(8): 1666-74.
[http://dx.doi.org/10.1097/IAE.0000000000000125] [PMID: 24743642]
[9] Olk RJ, Burgess DB, McCormick PA. Subfoveal and juxtafoveal subretinal neovascularization in the
presumed ocular histoplasmosis syndrome. Visual prognosis. Ophthalmology 1984; 91(12): 1592-602.
[10] Rosenfeld PJ, Saperstein DA, Bressler NM, et al. Verteporfin in Ocular Histoplasmosis Study Group.
Photodynamic therapy with verteporfin in ocular histoplasmosis: uncontrolled, open-label 2-year
study. Ophthalmology 2004; 111(9): 1725-33.
[11] Berger AS, Conway M, Del Priore LV, Walker RS. POllack JS, Kaplan HJ. Submacular surgery for
subfoveal choroidal neovascular membranes in patients with presumed ocular histoplasmosis. Arch
Ophthalmol 1997; 115(8): 991-6.
[12] Martidis A, Miller DG, Ciulla TA, Danis RP, Moorthy RS. Corticosteroids as an antiangiogenic agent
for histoplasmosis-related subfoveal choroidal neovascularization J Ocul Pharmacol Ther 1999; 15(5):
425-8.
[http://dx.doi.org/10.1089/jop.1999.15.425]
[13] Rechtman E, Allen VD, Danis RP, Pratt LM, Harris A, Speicher MA. Intravitreal triamcinolone for
choroidal neovascularization in ocular histoplasmosis syndrome. Am J Ophthalmol 2003; 136(4): 739-
41.
[14] Liem SE, Armbruster FC. Proton-beam irradiation of subfoveal choroidal neovascular membranes in
presumed ocular histoplasmosis syndrome: a case report. J Am Optom Assoc 1998; 69(8): 493-9.
[PMID: 9747044]
[15] Ramaiya KJ, Blinder KJ, Ciulla T, Cooper B, Shah GK. Ranibizumab versus photodynamic therapy
for presumed ocular histoplasmosis syndrome. Ophthalmic Surg Lasers Imaging Retina 2013; 44(1):
17-21.
[16] Cionni DA, Lewis SA, Petersen MR, et al. Analysis of outcomes for intravitreal bevacizumab in the
treatment of choroidal neovascularization secondary to ocular histoplasmosis. Ophthalmology 2012;
119(2): 327-32.
CHAPTER 21
Epiretinal Membrane
Aristides J. Mendoza1,2,*
1
Retina Department, Centro Oftalmológico de Valencia (CEOVAL), Valencia, Venezuela
2
Retina Department, OftalmoSalud, Arequipa, Peru
The epiretinal membrane (ERM) represents the growth of avascular fibrotic tissue
on the surface of the retina in the macular area, which causes loss of vision and
distortion of images when it contracts [1].
ERMs can be caused by a variety of eye problems. They are classified as

idiopathic when not linked to any other eye disease and usually appear after a
posterior vitreous detachment as a result of the formation of retinal tears that
release inflammatory cells and pigment epithelial cells deposited at the posterior
pole. Secondary ERMs are associated with retinal detachment, intraocular
inflammation, trauma and vascular diseases of the retina [2]. There are two types
of ERMs that have different clinical presentations: simple and contractile. Simple
ERMs are membranes with cellophane-like films on the internal limiting
membrane (ILM) with little or no visual symptoms. In general, they are composed
mainly of glial cells. On the contrary, tractional ERMs are thicker with contractile
properties that cause wrinkling of the retina and are usually accompanied by
decreased vision and metamorphopsia. They are composed of glial cells and
contractile cells [3], and are also known as “macular puckers” (Fig. 1).
Epiretinal membranes cause macular structural changes such as retinal folds,

vascular leakage, macular thickening, cystoid macular edema, pseudohole
formation, foveal ectopia, and foveal detachment by tractional forces on the
retinal surface [4].
*
Corresponding author Aristides J. Mendoza: Retina Department, OftalmoSalud, Arequipa, Av Mariscal Benavides
No 307, Urb Selva Alegre, Arequipa, Peru; Tel: +51(054)287373; E-mail ampcff@hotmail.com
228 Ophthalmology: Current and Future Developments, Vol. 1 Aristides J. Mendoza
Fig. (1). Macular pucker secondary to BRVO (Courtesy of Mitzy E. Torres Soriano).
Epiretinal membranes typically affect otherwise healthy elderly individuals and

are unilateral in approximately 90% of cases. Visual symptoms and decreased
visual acuity will depend on the degree of distortion caused in the traction retinal
membrane, which can generate a micro detachment of the posterior pole, as well
as the presence or absence of macular or perimacular edema. Usually, thin
epiretinal membranes don’t cause many symptoms. However, in advanced cases,
there is a reduction in vision, micropsia, metamorphopsia, Amsler grid distortion
and, occasionally, monocular diplopia. Spontaneous separation of an epiretinal
macular membrane, although uncommon, can occur [5, 6].
Slit lamp ophthalmoscopy: brightness or abnormal reflectivity in the macular

region suggests the presence of an ERM (Fig. 2a). More advanced ERMs can
become opaque and thick, and may obscure underlying retinal features (Fig. 1).
ERMs cause changes in the retinal architecture with loss of foveal contour as a
result of contraction.
Epiretinal Membrane Ophthalmology: Current and Future Developments, Vol. 1 229
Fig. (2). (a) Fundus photograph that shows the typical clinical appearance of an ERM. The membrane
adherent to the surface of the retina contracts and the retinal surface appears wrinkled. (b) OCT scan confirms
ERM (Courtesy of Mitzy E. Torres Soriano).
In addition to visual acuity testing, the most common clinical tests involve
fluorescein angiography and optic coherence tomography (OCT). Fluorescein
angiography is moderately helpful, since it can show retinal vascular tortuosity,
straightening, and leakage, as well as cystoid macular edema. OCT is the
diagnostic method of choice, typically demonstrating a hyperreflective line in the
surface of the retina that may be associated to retinal folding, increased macular
thickness, cystoid macular edema, traction macular retinal detachment, and both
lamellar or macular hole formation (Figs. 2b, 3-6). Amsler grid testing may help
quantifying metamorphopsia in eyes with macular distortion [7]. Abnormal
macular function has been shown using the electroretinogram [8, 9].
Fig. (3). (a) and (b) OCT of epiretinal membrane showing marked corrugation of the retinal surface, loss of
foveal depression and diffuse retinal thickening with intraretinal fluid in multiple layers (Courtesy of Centro
de la Visión Gordon-Manavella, Rosario-Argentina).
Fig. (4). Spectral domain optical coherence tomography image showing epiretinal membrane with retinal
folds, and macular thickening (Courtesy of Centro de la Visión Gordon-Manavella, Rosario-Argentina).
Fig. (5). OCT demonstrates ERM and intraretinal fluid (Courtesy of Mitzy E. Torres Soriano).
Fig. (6). OCT scan of the same lesion shown in Fig. (5), demonstrating a thickened ERM with severe
distortion of the retina (Courtesy of Mitzy E. Torres Soriano).
The clinical appearance of an ERM is fairly distinctive. However, macular hole,

parafoveal telangiectasia, vitreomacular traction syndrome, subfoveal neovascular

membrane and macular edema must also be considered. It is a very common
pathology, and therefore may coexist with any of the diagnoses mentioned above.
MANAGEMENT
Most of patients with ERM have symptoms that are mild and either
nonprogressive or slowly progressive, and treatment is rarely indicated. In a few
cases, the membrane may spontaneously release, with a marked decrease in
symptomatology and improvement in visual acuity (VA). For patients with
significant symptoms and substantially reduced VA (usually 20/60 or less), pars
plana vitrectomy (20, 23 or 25 gauge) with epiretinal membrane peeling can
diminish the severity of symptoms and improve VA in 75% of cases or more.
There is no difference in visual outcome between eyes operated with 23 gauge
and 25 gauge [10]. ERM recurrence is observed in approximately 10% of cases
after surgery [11]. The reasons for recurrence are the incomplete removal of the
ERM and the presence of residual ILM after ERM peeling. To enhance the
visualization of these transparent or semi-transparent structures and to overcome
ERM recurrence, various staining methods have been used, including indocyanine
green (ICG), trypan blue (TB), triamcinolone acetonide (TA), and brilliant blue G
(BBG) [12].
The best candidates for surgery are those who have had membranes for a
relatively short time, because the potential for visual recovery decreases as the
duration of preoperative symptoms increases. Integrity of the retinal layers seen
by OCT may be used to predict a good visual outcome [13].
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1] Bu SC, Kuijer R, Li XR, Hooymans JM, Los LI. Idiopathic epiretinal membrane. Retina 2014; 34(12):
2317-35.
[http://dx.doi.org/10.1097/IAE.0000000000000349] [PMID: 25360790]
[2] Joshi M, Agrawal S, Christoforidis JB. Inflammatory mechanisms of idiopathic epiretinal membrane
formation. Mediators Inflamm 2013; 2013: 192582.
[http://dx.doi.org/10.1155/2013/192582]
[3] Kampik A, Green WR, Michels RG, Nase PK. Ultrastructural features of progressive idiopathic
epiretinal membrane removed by vitreous surgery. Am J Ophthalmol 1980; 90(6): 797-809.
[4] Massin P, Allouch C, Haouchine B, et al. Optical coherence tomography of idiopathic macular
epiretinal membranes before and after surgery. Am J Ophthalmol 2000; 130(6): 732-9.
[5] Sumers KD, Jampol LM, Goldberg MF, Huamonte FU. Spontaneous separation of epiretinal
membranes. Arch Ophthalmol 1980; 98(2): 318-20.
[6] Scudder MJ, Eifrhg DE. Spontaneous surface wrinkling retinopathy. Ann Ophthalmol 1982; 94: 44.
[PMID: 1137279]
[7] Bouwens MD, Van Meurs JC. Sine Amsler Charts: a new method for the follow-up of
metamorphopsia in patients undergoing macular pucker surgery. Graefes Arch Clin Exp Ophthalmol
2003; 241(2): 89-93.
[8] Tanikawa A, Horiguchi M, Kondo M, Suzuki S, Terasaki H, Miyake Y. Abnormal focal macular
electroretinograms in eyes with idiopathic epimacular membrane. Am J Ophthalmol 1999; 127(5):
559-64.
[9] Moschos M, Apostolopoulos M, Ladas J, et al. Assessment of macular function by multifocal
electroretinogram before and after epimacular membrane surgery. Retina 2001; 21(6): 590-5.
[10] Kovacević D, Antić IV, Valković A. Comparison of 23 gauge and 25 gauge PPV in the treatment of
epiretinal membranes and macular holes. Coll Antropol 2014; 38(4): 1213-6.
[PMID: 25842761]
[11] Grewing R, Mester U. Results of surgery for epiretinal membranes and their recurrences. Br J
Ophthalmol 1996; 80(4): 323-6.
[12] Kwok AKh, Lai TY, Yuen KS. Epiretinal membrane surgery with or without internal limiting
membrane peeling. Clin Experiment Ophthalmol 2005; 33(4): 379-85.
[13] Inoue M, Morita S, Watanabe Y, et al. Preoperative inner segment/outer segment junction in spectral-
domain optical coherence tomography as a prognostic factor in epiretinal membrane surgery. Retina
2011; 31(7): 1366-72.
CHAPTER 22
Idiophatic Macular Hole

Luis M. Suarez-Tata1,*, Moravia B. Suarez-Tata1 and Reinaldo García1
1
Retina & Vitreous Service, Clínica Oftalmológica El Viñedo, Valencia, Venezuela
Idiopathic macular hole (MH) is an acquired full thickness defect of the retina in
the central macula. Macular holes were first described by Knapp in 1869 [1].
They typically occur in the sixth to eighth decade of life with a 3:1 predominance
in women. The incidence of bilaterally is 5% to 10%. Tangential vitreoretinal
traction (TVT) is the presumed cause of the MH.
Visual acuity, depending on the stage and severity of the MH, may be near normal
or severely reduced to less than 20/400. Amsler grid will often reveal a central
scotoma or metamorphopsia.
Slit-lamp biomicroscopic examination usually shows a round retinal defect that

involves the fovea. Several diagnostic maneuvers may be used to find out if the
lesion observed in examination is indeed a full-thickness defect (vs. a macular
pseudo hole). If a tall, narrow beam is focused on the lesion, the patient may
perceive a break or dent in the beam (the so-called “Watzke-Allen test). This also
may be tested using the aiming beam of a retinal laser photocoagulator.
The gold-standard diagnostic tool is optic coherence tomography (OCT), due to

the fact that it is non-invasive, has a very high resolution, allows careful
evaluation of retinal structures and the vitreomacular interface.
*
Corresponding author Luis M. Suarez Tata: Clínica Oftalmológica El Viñedo, Valencia, Venezuela;
Tel/Fax: +58 (412) 3474188; E-mail: luismiguelsuarez@gmail.com
Idiophatic Macular Hole Ophthalmology: Current and Future Developments, Vol. 1 235
It also enables quantitative information such as minimum hole diameter, base

diameter and retinal edge thickness [2].
Fluorescein angiography may also be used but has fallen into disuse, since
findings are vague (a window defect corresponding to loss of xanthophyll
pigment), and compared to OCT has very little sensitivity and specificity.
Classification
Gass described different stages of development of MH (Table 1) [3, 4].

Nowadays, with OCT and the identification of vitreomacular traction and its
relationship with MH, the International Vitreomacular Traction Study Group has
proposed a new classification based on OCT findings and the status of the
vitreomacular interface (Tables 2-4) [5].
Table 1. Stage of development of idiopathic macular hole.
Normal Layer of vitreous cortex lying on internal limiting membrane of retina (Figs. 1 and 2)
Stage 1A: Early contraction of outer part of vitreous cortex with foveolar detachment (Fig. 3)
Stage 1B: Occult hole. Dehiscense of the retinal photoreceptor layer at the umbo with centrifugal retraction
of the retinal receptors. Further vitreous contraction and condensation of the prefoveal vitreous
cortex with foveal detachment (Figs. 3-5)
Stage 2: Small perifoveal dehiscense. Small (< 400 µm)
(Figs. 6 and 7)
Stage 3: Larger central full-thickness hole usually accompanied by a rim of retina elevation (>400 µm)
(Figs. 8 and 9). The posterior cortical vitreous remains attached. There may be a small
operculum overlying the macular hole.
Stage 4: Macular hole has an associated complete posterior vitreous detachment. These holes are usually
large (> 400 µm) (Figs. 10-13)
Based on Gass JD [3, 4].
There are several diseases that may resemble MH clinically but have distinct
appearances on OCT. Macular pseudohole is an epiretinal membrane that spares
the center of the fovea, causing its borders to elevate, clinically resembling a MH.
The Watzke-Allen test is negative, and on OCT, the outer retinal layers are spared
(Figs. 12-14). Lamellar macular hole is also usually associated to an epiretinal
membrane, and on OCT shows an irregular foveal contour with schisis of the
236 Ophthalmology: Current and Future Developments, Vol. 1 Suarez-Tata et al.
retinal layers in the parafovea, and a preserved photoreceptor layer (Figs. 14-19).
Vitreomacular traction syndrome has also to be considered, and actually is
believed to play an important role in the pathophysiology of MH. Other
differential diagnoses include macular telangiectasia and solar retinopathy [6, 7].
Fig. (1). Fundus photograph showing a normal macula.
Fig. (2). Optical coherence tomography (OCT) image of a normal macula.
Fig. (3). OCT image of a macular hole stage 1-A, showing hyporeflective spaces in the inner and outer retina.
Fig. (4). OCT image of a macular hole stage 1-B, showing hyporeflective space in the inner retina.
Fig. (5). OCT image of a macular hole stage 1-A, showing extensive hyporeflective spaces in the inner retina.
Fig. (6). A 74-year-old patient with a reduction of visual acuity to 20/70. Idiopathic macular hole stage 2.
Appears as a small round defect in the fovea. Fluorescein angiogram shows an area of window defect.
Fig. (7). OCT image of a macular hole stage 2, showing extensive defect in the outer retina.
Fig. (8). OCT image of a stage 3 macular hole with extensive separation of the outer layers.
Fig. (9). OCT image of a stage 3 macular hole, showing separation of the inner and outer retinal layers.
Fig. (10). OCT image of a full thickness macular hole with elevated borders, cystoid macular degeneration
and irregular retinal pigment epithelium.
Fig. (11). OCT image of a full thickness macular hole with a pseudo-operculum.
Fig. (12). Fundus photograph (top) and OCT (bottom) of a chronic macular hole. The photograph shows a
large hole with pigment changes at its bottom. OCT shows a large hole with somewhat flat borders and
irregular retinal pigment epithelium.
Fig. (13). Full thickness macular hole with small dots at the level of the retinal pigment epithelium.
Table 2. Correlation between commonly used clinical macular hole stages and the international
vitreomacular traction study (IVTS) classification system [5].
Full-Thickness Macular Hole Stages in Common Use International Vitreomacular Traction

Classification System Study
Stage 0 Vitreomacular adhesion (VMA)
Stage 1: Impending macular hole (Impending or Occult Vitreomacular traction (VMT)
Hole)
Stage 2: Small hole Small or medium FTMH with VMT
Stage 3: Large hole Medium or large FTMH with VMT
Stage 4: FTMH with PVD Small, Medium, or large FTMH without
VMT
Abbreviations: FTMH full thickness macular hole; PVD posterior vitreous detachment.
Based on International Vitreomacular Traction Study Classification.
Table 3. IVTS classification system for vitreomacular adhesion, traction, and macular hole [5].
Classification Subclassification
Vitreomacular adhesion (VMA) Size: focal (≤1500 µm) or broad (>1500 µm) Isolated or concurrent
Vitreomacular traccion (VMT) Size: focal (≤1500 µm) or broad (>1500 µm) Isolated or concurrent
Full-thickness macular hole Size: small (≤250 µm), medium (>250- ≤400 µm), or large (>400 µm)
Status of vitreous: with or without VMT
Cause: primary or secondary
Table 4. IVTS classification system for macular hole [5].
Full-thickness macular hole (FTMH)

Full-thickness foveal lesion that interrupts all macular layers from the ILM to the RPE
Classification
By Size
(horizontally measured linear width across hole at narrowest point, not ILM)
Small (≤250 µm)
Medium (>250 µm and ≤400 µm)
Large (>400 µm)
By presence or absence of VMT
By Cause
Primary (initiated by VMT)
Secondary (directly due to associated disease or trauma known to cause macular hole in the absence of prior
VMT)
Fig. (14). Macular pseudohole with epiretinal membrane, but no full thickness interruption of all retinal
layers.
Fig. (15). OCT image of a macular pseudohole with epiretinal membrane with cystoid macular edema.
Fig. (16). OCT image of a macular pseudohole with epiretinal membrane that causes an irregular foveal
contour.
Fig. (17). OCT image of an epiretinal membrane causing a lamellar macular hole.
Fig. (18). OCT image showing another case of epiretinal membrane causing a lamellar macular hole. The
foveal contour is irregular and there is some separation of the inner retinal layers.
Fig. (19). OCT image showing another case of epiretinal membrane causing a lamellar macular hole. There is
some fibrous epiretinal proliferation seen as a very thick epiretinal membrane that covers the entire macular
surface.
Pre- and postoperative
B
Fig. 20 contd.....
Fig. (20). A. Fundus photograph of the right eye of a 65 year old female patient showing the pre-operative
appearance of a stage 4 macular hole (yellow dots in the center of the hole at the level of the retinal pigment
epithelium).Visual acuity was 20/200.
B. Fluorescein angiogram showing a window defect in the fovea.
C. OCT image showing a full thickness macular hole.
D.E.F. Fundus photograph, angiogram and OCT of the same eye three months after vitrectomy and ILM
removal. Three months post-operative appearance of full thickness macular hole, now closed and vision
improved to20/50.
Fig. (21). A. Preoperative OCT image of a full-thickness macular hole. B. Postoperative appearance of the
same eye.
Fig. (22). A. OCT image showing a full thickness macular hole with pseudo-operculum. B. Postoperative
OCT image showing some defects in the outer retinal layers.
MANAGEMENT
The standard surgery for the repair of MH was described by Kelly and Wendel [8]
in 1991 and involves a standard three-port pars plana vitrectomy, posterior
hyaloid separation, stripping of epiretinal/internal limiting membranes (ILM) and
gas tamponade. A total air-fluid gas exchange is performed, followed by an air-
gas exchange using a non-expansile concentration of gas (C2F6, C3F8 or SF6).
Although closure of the hole is the rule, the fovea rarely recovers its normal
contour (Figs. 20-22)
Controversial issues in macular hole surgery today involve peeling and staining
the ILM. The most common dyes are Indocyanine green (ICG) [9, 10], Trypan
blue [11], triamcinolone acetonide [12, 13], and Brilliant blue G (BBG) [14].
Staining improves the visibility and the ease of stripping the ILM, but studies
suggest that it may also cause retinal damage.
Different instruments have been used to grasp the ILM creating a surgical plane.
These instruments include the micro-barbed micro-vitreoretinal blade or the
diamond-dusted silicone cannula. After lifting an edge of the membrane, it is
stripped with fine end-gripping tissue forceps.
The success rate for macular hole surgery approaches 80% to 90% with closure of
the macular hole and improvement in visual acuity. However, the most important
predictors of visual outcomes are its size and the time of duration [15].
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1] Knapp. Ueber isolitre Zerreissungen der Aderhaut in Folge von Traumen auf dem Augapfel. Arch
Augenheilk 1869; 1: 6-29.
[2] Desai VN, Hee MR, Puliafito CA. Optical coherence tomography of macular holes. In: Madreperla
SA, McCuen BW, Eds. Macular hole. Boston, Mass: Botterworth-Heinemann 1999; pp. 37-47.
[3] Gass JD. Idiopathic senile macular hole. Its early stages and pathogenesis. Arch Ophthalmol 1988;
106(5): 629-39.
[4] Gass JD. Reappraisal of biomicroscopic classification of stages of development of a macular hole. Am
J Ophthalmol 1995; 119(6): 752-9.
[5] Duker JS, Kaiser PK, Binder S, et al. The international vitreomacular traction study group
classification of vitreomacular adhesion, traction, and macular hole. Ophthalmology 2013; 120(12):
2611-9.
[6] Yun C, Oh J, Hwang SY, Togloom A, Kim SW, Huh K. Morphologic characteristics of chronic
macular hole on optical coherence tomography. Retina 2012; 32(10): 2077-84.
[http://dx.doi.org/10.1097/IAE.0b013e31825620ba] [PMID: 22617832]
[7] Smiddy WE, Gass JD. Masquerades of macular holes. Ophthalmic Surg 1995; 26(1): 16-24.
[PMID: 7746619]
[8] Kelly NE, Wendel RT. Vitreous surgery for idiopathic macular holes. Results of a pilot study. Arch
Ophthalmol 1991; 109(5): 654-9.
[9] Da Mata AP, Burk SE, Riemann CD, et al. Indocyanine green-assisted peeling of the retinal internal
limiting membrane during vitrectomy surgery for macular hole repair. Ophthalmology 2001; 108(7):
1187-92.
[10] Haritoglou C, Gandorfer A, Gass CA, Schaumberger M, Ulbig MW, Kampik A. Indocyanine green-
assisted peeling of the internal limiting membrane in macular hole surgery affects visual outcome: a
clinicopathologic correlation. Am J Ophthalmol 2002; 134(6): 836-41.
[11] Vote BJ, Russell MK, Joondeph BC. Trypan blue-assisted vitrectomy. Retina 2004; 24(5): 736-8.
[12] Kimura H, Kuroda S, Nagata M. Triamcinolone acetonide-assisted peeling of the internal limiting
membrane. Am J Ophthalmol 2004; 137(1): 172-3.
[13] Takasu I, Shiraga F, Otsuki H. Triamcinolone acetonide-assisted internal limiting membrane peeling in
macular hole surgery. Retina 2004; 24(4): 620-2.
[14] Enaida H, Hisatomi T, Hata Y, et al. Brilliant blue G selectively stains the internal limiting
membrane/brilliant blue G-assisted membrane peeling. Retina 2006; 26(6): 631-6.
[PMID: 16829804]
[15] Kusuhara S, Negi A. Predicting visual outcome following surgery for idiopathic macular holes.
Ophthalmologica 2014; 231(3): 125-32.
CHAPTER 23
Macular Pseudo-hole
Jose A. Roca1,*, Hugo Luglio2 and Daniela Roca1
1
Ophthalmology Department, Clínica Ricardo Palma, Lima-Peru, Peru
2
Macula D&T, Lima-Peru, Peru
The term “macular pseudo-hole” (MPH) was coined by Allen and Gass in 1976
[1] to describe any foveal lesion that has a biomicroscopic appearance of a full-
thickness macular hole (FTMH), but is not. It is usually formed by a centrifugal
contraction of an epiretinal tissue (epiretinal membrane) that surrounds but does
not cover the foveolar area, making the borders have a more vertical appearance
[2].
The patient usually has no complaints, and the visual acuity is normal or nearly
normal, ranging from 20/15 to 20/100 (median 20/25) [3]. Because of the good
surgical results of true macular holes, it is important to differentiate between a
true macular hole and a macular pseudo-hole. The appearance of a true macular
hole is different, usually very round, with a halo of marginal detachment
surrounding the hole, tiny yellow deposits in its base (within the hole), a
translucent operculum in front of some holes, and a zone of hyperfluorescence
corresponding to the size of the hole during the early stages of angiography. These
characteristics are not seen in a macular pseudo-hole.
Biomicroscopy of a patient with a macular pseudo-hole usually reveals crinkling

of the inner retinal surface surrounding the hole in the epiretinal membrane and a
punched-out appearance in the area of the hole (Fig. 1) [4]. As the slit beam is
Correspondence: Corresponding author Jose A. Roca: Ophthalmology Department, Clínica Ricardo Palma, Torre B,
piso 10, San Isidro, Lima-Peru; Tel: +51 (1) 2242224; E-mail: jaroca62@gmail.com
Macular Pseudo-hole Ophthalmology: Current and Future Developments, Vol. 1 249
Fig. (1). Fundus photograph of the left eye, showing a macular pseudohole with an epiretinal membrane.
Fig. (2). OCT of the same patient of Fig. (1), showing a macular pseudo-hole with an epiretinal membrane
with a U form fovea and preserved outer retinal layers.
250 Ophthalmology: Current and Future Developments, Vol. 1 Roca et al.
Fig. (3). Autofluorescence of a macular pseudo-hole.
Fig. (4). OCT image of a macular pseudohole showing slight distortion of the foveal contour.
moved across the pseudo-hole, there is usually a light reflex that is evidence of
retinal tissue in the base; the Watzke-Allen sign is negative (positive in FTMH).
The Amsler grid test usually is not decisive in the diagnosis because some patients
who have macular pseudo-holes present scotomas. Fluorescein angiography is
generally normal but may show a very faint zone of hyperfluorescence
corresponding with the pseudo-hole. This zone of hyperfluorescence is typically
much less prominent than the finely granular area of hyperfluorescence seen with
a full-thickness hole [3]. The presence of the semitransparent perifoveolar
epiretinal membrane probably causes the foveolar area to appear faintly
hyperfluorescent in contrast to the perifoveolar area. Autofluorescence imaging
demonstrates bright fluorescence of macular holes with appearance similar to that
obtained by fluorescein angiography. In contrast, macular pseuodoholes show no
such autofluorescence (Fig. 3) [5]. Scanning laser ophthalmoscope (SLO)
microperimetry examination shows no deep scotomas (patients with FTMH have
deep scotomas); this exam has 100% sensitivity and specificity for the differential
diagnosis with FTMH [6]. Optical coherent tomography (OCT) examination
makes the diagnosis of macular pseudo-holes much easier; the OCT
characteristics of a macular pseudo-holes are: thickening of the macula contracted
by an ERM, the U or V shape of the fovea, and no loss of retinal tissue at the
umbo of the fovea (retention of photoreceptors) (Figs. 2 and 4) [7 - 9]. Using
high-resolution OCT, Witkin et al. also described cases combining foveal
thickening due to ERM contraction, with stretching of the foveal edge resulting in
the thinning of the foveal floor. These cases may in fact represent a type of
macular pseudohole induced by both centripetal and centrifugal contraction of the
ERM between several eccentric epicenters [10].
Fish et al. reported that the diagnosis by the initial examining physician was
correct in only 43% of eyes with macular pseudo-holes [11].
Differential diagnosis should be made with a stage 1-A impending hole (foveolar
yellow lesion), solitary drusen, small RPE detachment, small atrophy of the RPE,
choroidal neovascularization, a small focal area of central serous choriore-
tinopathy, foveolar detachment with epiretinal membrane, focal retinal atrophy
252 Ophthalmology: Current and Future Developments, Vol. 1 Roca et al.
associated with bilateral idiopathic juxtafoveolar retinal telangiectasis, pattern

dystrophy, cystoid macular edema, and solar maculopathy [12].
MANAGEMENT
Visual prognosis in these patients is usually good. In a few patients, the additional
contraction of an eccentrically located perifoveal epiretinal membrane may distort
the foveal area. Pars plana vitrectomy to peel the epiretinal membrane may be
indicated in patients with worsening vision. In few of them, the epiretinal
membrane may peel free from the inner retinal surface. Most patients with MPH
will not experience much visual changes.
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1] Allen AW Jr, Gass JD. Contraction of a perifoveal epiretinal membrane simulating a macular hole.
Am J Ophthalmol 1976; 82(5): 684-91.
[2] Gaudric A, Tadayoni R. Macular hole. Ophthalmology 2015.
[http://dx.doi.org/10.1016/B978-1-4557-0737-9.00117-X]
[3] Tsujikawa M, Ohji M, Fujikado T, Saito Y, Motokura M, Ishimoto I. Differentiating full thickness
macular holes from impending macular holes and macular pseudoholes. Tano Br J Ophthalmol 1997;
81: 117-22.
[4] Gass JD. Stereoscopic atlas of macular diseases: diagnosis and treatment. 3rd ed. St Louis: CV Mosby
1987; pp. 684-93.
[5] Ciardella AP, Lee GC, Langton K, Sparrow J, Chang S. Autofluorescence as a novel approach to
diagnosing macular holes. Am J Ophthalmol 2004; 137(5): 956-9.
[6] Tsujikawa M, Ohji M, Fujikado T, et al. Differentiating full thickness macular holes from impending
macular holes and macular pseudoholes. Br J Ophthalmol 1997; 81(2): 117-22.
[7] Haouchine B, Massin P, Tadayoni R, Erginay A, Gaudric A. Diagnosis of macular pseudoholes and
lamellar macular holes by optical coherence tomography. Am J Ophthalmol 2004; 138(5): 732-9.
[8] Chen JC, Lee LR. Clinical spectrum of lamellar macular defects including pseudoholes and
pseudocysts defined by optical coherence tomography. Br J Ophthalmol 2008; 92(10): 1342-6.
[9] Martinez J, Smiddy WE, Kim J, Gass JD. Differentiating macular holes from macular pseudoholes.
Am J Ophthalmol 1994; 117(6): 762-7.
[10] Witkin AJ, Ko TH, Fujimoto JG, et al. Redefining lamellar holes and the vitreomacular interface: an
ultrahigh-resolution optical coherence tomography study. Ophthalmology 2006; 113(3): 388-97.
[11] Fish RH, Anand R, Izbrand DJ. Macular pseudoholes. Clinical features and accuracy of diagnosis.
Ophthalmology 1992; 99(11): 1665-70.
[12] Smiddy WE, Gass JD. Masquerades of macular holes. Ophthalmic Surg 1995; 26(1): 16-24.
[PMID: 7746619]
CHAPTER 24
Vitreomacular Traction
Mitzy E. Torres Soriano1,2,3,* and Maximiliano Gordon2,3
1
Unidad Oftalmológica “Dr. Torres López”, Centro Médico Cagua, Cagua, Venezuela
2
Fe, Argentina
3
Centro de la Visión Gordon-Manavella, Rosario, Argentina
Vitreomacular Traction Syndrome (VMT) occurs as a result of incomplete

posterior vitreous detachment, resulting in persistent vitreous traction on the
posterior retina [1].
The prevalence of VMT syndrome is 22.5 per 100,000 population. The annual
incidence is 0.6 per 100,000 population. The prevalence and incidence of VMT
associated with diabetic retinopathy, diabetic macular edema, age-related macular
degeneration, and other macular diseases (concurrent VMT) are much higher [2].
Patients may be asymptomatic or present the following symptoms: decreased

visual acuity, metamorphopsia, photopsia, and micropsia [1]. Symptoms usually
progress gradually [3].
Optical coherence tomography (OCT) allows visualization of the vitreomacular

interface and confirms vitreomacular adhesion or traction. Intraretinal cystic
changes and foveal detachment can be seen.
Recently, OCT-based anatomic definitions and classifications have been proposed

by the International Vitreomacular Traction Study (IVTS) Group to define these
entities (Table 1) [4].
*
Corresponding author Mitzy E. Torres Soriano: Centro de la Visión Gordon - Manavella, Montevideo 763, CP
2000, Rosario - Santa Fe, Argentina; Tel: +54 (0341) 4400239; E-mail: mitzytorres@yahoo.com
Vitreomacular Traction Ophthalmology: Current and Future Developments, Vol. 1 255
Table 1. IVTS classification system for vitreomacular adhesion and vitreomacular traction.
Vitreomacular Adhesion (VMA): Classification

Evidence of perifoveal vitreous cortex detachment from By size of attachment area:
the retinal surface. Focal <1500 µm (Fig. 1) Broad >1500 µm,
Macular attachment of the vitreous cortex within a 3-mm parallel to RPE and may include areas of
radius of the fovea. dehiscence
No detectable change in foveal contour or underlying (By presence of concurrent retinal
retinal tissues. conditions:)
Isolated
Concurrent
Vitreomacular Traction (VMT): Classification
Evidence of perifoveal vitreous cortex detachment from By size of attachment area:
the retinal surface. Focal <1500 µm (Figs. 2, 3 and 5) Broad >1500
Macular attachment of the vitreous cortex within a 3-mm µm, parallel to RPE and may include areas of
radius of the fovea dehiscence (Fig. 4)
Association of attachment with distortion of the foveal By presence of concurrent retinal conditions:
surface, intraretinal structural changes, and/or elevation of Isolated
the fovea above the RPE, but no full-thickness interruption Concurrent
of all retinal layers.
Fig. (1). Focal vitreomacular adhesion: partial vitreous detachment.

256 Ophthalmology: Current and Future Developments, Vol. 1 Torres Soriano and Gordon
Fig. (2). Focal vitreomacular traction causing distortion of the foveal contour and separation of retinal layers.
Fig. (3). Focal vitreomacular traction in V pattern, epiretinal membrane and significant distortion of the
retinal architecture.
Fig. (4). Spectral domain OCT scan reveals a broad vitreomacular traction and severe distortion of retinal
layers.
Fig. (5). OCT image showing severe vitreomacular traction causing foveal detachment (Courtesy of Francys
Torres MD, Maracay, Venezuela).
Fluorescein angiography can reveal retinal capillary leakage in the macula due to
cystoid macular edema (CME). An associated foveal retinal detachment may be
noted as fluorescein pooling [3, 5].
B-scan ultrasound reveals partial posterior vitreous detachment which is seen as a

thin, smooth, continuous membrane with focal attachment to the retinal surface [3,
6].
The differential diagnosis can include [3]: early full thickness macular hole,
pseudophakic CME, other causes of CME (uveitis, diabetic macular edema,
exudative age related macular degeneration, macular telangiectasia) and ERM,
which could be present as concurrent macular disease (Fig. 3).
MANAGEMENT
Asymptomatic VMA patients are not candidates for surgical therapy [8]. VMA
usually resolves spontaneously as part of the normal process of PVD, although it
may progress to VMT. Periodic monitoring with OCT every 3 months is
necessary. Even in cases that progress to a VMT syndrome, observation still
remains an option, given the possibility of spontaneous resolution (11%) of VMT
(Fig. 6) [7, 9].
(a)
Fig. 6 contd.....
(b)
Fig. (6). (a) Vitreomacular traction causing distortion of the foveal contour. (b) Spontaneous resolution of
vitreomacular traction after 4 months.
Posterior vitrectomy combined with stripping of the posterior hyaloid and ILM
peeling would be the surgical treatment of choice [10, 11].
The medical therapy of VMT consists of pharmacologic vitreolysis. Jetrea®

(ocriplasmin) was approved for the treatment of patients with symptomatic VMA
[12 - 14]. Vitrectomy may still be required in patients failing ocriplasmin therapy
and also in about 20% of the patients successfully treated with ocriplasmin [15,
16].
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1] Hikichi T, Yoshida A, Trempe CL. Course of vitreomacular traction syndrome. Am J Ophthalmol
1995; 119(1): 55-61.
[2] Jackson TL, Nicod E, Simpson A, Angelis A, Grimaccia F, Kanavos P. Symptomatic vitreomacular
adhesion. Retina 2013; 33(8): 1503-11.
[http://dx.doi.org/10.1097/IAE.0b013e31829232fd] [PMID: 23714857]
[3] Bottós J, Elizalde J, Arevalo JF, Rodrigues EB, Maia M. Vitreomacular traction syndrome. J
Ophthalmic Vis Res 2012; 7(2): 148-61.
[PMID: 23275824]
[4] Duker JS, Kaiser PK, Binder S, et al. The international vitreomacular traction study group
classification of vitreomacular adhesion, traction, and macular hole. Ophthalmology 2013; 120(12):
2611-9.
[5] Hermann D, Schubert MD, Binder S, de Smet MD, Gaudric A. Retina and vitreous diseases of the
vitreous and the vitreoretinal interface. Basic Clin Sci Course (BCSC). 2013; pp. 302-4.
[6] Johnson MW. Tractional cystoid macular edema: a subtle variant of the vitreomacular traction
syndrome. Am J Ophthalmol 2005; 140(2): 184-92.
[7] García-Layana A, García-Arumí J, Ruiz-Moreno JM, Arias-Barquet L, Cabrera-López F, Figueroa
MS. A review of current management of vitromacular traction & macular hole. J Ophthalmol 2015;
2015: 809640.
[8] Stalmans P, Duker JS, Kaiser PK, et al. Oct-based interpretation of the vitreomacular interface and
indications for pharmacologic vitreolysis. Retina 2013; 33(10): 2003-11.
[http://dx.doi.org/10.1097/IAE.0b013e3182993ef8] [PMID: 23881226]
[9] Hikichi T, Yoshida A, Trempe CL. Course of vitreomacular traction syndrome. Am J Ophthalmol
1995; 119(1): 55-61.
[10] Yamada N, Kishi S. Tomographic features and surgical outcomes of vitreomacular traction syndrome.
Am J Ophthalmol 2005; 139(1): 112-7.
[11] Witkin AJ, Patron ME, Castro LC, et al. Anatomic and visual outcomes of vitrectomy for
vitreomacular traction syndrome. Ophthalmic Surg Lasers Imaging 2010; 41(4): 425-31.
[12] FDA approves Jetrea for symptomatic vitreomacular adhesion in the eyes. 2012. Available at:
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm324369.htm.
[13] European Medicines Agency. European Medicines Agency - Human Medicines - Jetrea. 2013;
1(January). Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_
opinion_-_Initial_authorisation/human/002381/WC500137451.pdf
[14] Stalmans P, Benz MS, Gandorfer A, et al. Enzymatic vitreolysis with ocriplasmin for vitreomacular
traction and macular holes. N Engl J Med 2012; 367(7): 606-15.
[15] US Food and Drug Administration Center for Drug Evaluation and Research. Medical review(s). 2012.
Available at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/125422Orig1s000MedR.pdf
[16] Syed YY, Dhillon S. Ocriplasmin: a review of its use in patients with symptomatic vitreomacular
adhesion. Drugs 2013; 73(14): 1617-25.
CHAPTER 25
Pseudophakic Cystoid Macular Edema

Andrés Bastien*
Universidad de Buenos Aires-Universidad del Salvador, Retina and Vitreous, Argentina
Pseudophakic cystoid macular edema (CME) was first described in 1953 by A.

Ray Irvine, Jr., in patients with unexplained visual loss following intracapsular
cataract surgery [1]. The cause of the visual loss was identified by Gass and
Norton as marked macular edema with a classic perifoveal petalloid pattern of
staining and late leakage from the optic nerve on intravenous fluorescein
angiography (Figs. 1 - 3) (FA) [2]. The incidence of angiographic CME has
decreased with the transition from intracapsular cataract extraction (60%) to
extracapsular cataract surgery (20%) and with small-incision phacoemulsification
[3, 4]; 20-30% of patients undergoing phacoemulsification have CME on FA [5,
6] and optical coherence tomography (OCT) (Figs. 4 and 5) suggests that it may
be found in up to 40% of patients [7]. The majority of patients do not experience
visual changes [6, 8]. The incidence is lower with current surgical techniques
(0.1% to 2.35%) [9, 10].
Most patients with CME have spontaneous resolution of the edema within 3-4
months [11] One year after surgery, a small minority of patients (<1%) in the
absence of treatment may still have decreased visual acuity from CME [12].
Pathogenesis
Various factors and many presumed mechanisms may be involved in the

pathogenesis of CME, including the release of mediators of inflammation such as
*
Corresponding author Andrés Bastien: Universidad de Buenos Aires-Universidad del Salvador, Retina and
Vitreous, Argentina; Tel/Fax: 00541148114482; E-mail: andresbastien@aol.com
262 Ophthalmology: Current and Future Developments, Vol. 1 Andrés Bastien
prostaglandins, light toxicity, and mechanical irritation [13 - 15]. Inflammatory

mediators disrupt the blood-aqueous barrier (BAB) and blood-retinal barrier
(BRB), leading to increased vascular permeability resulting in macular edema.
Breakdown of the BAB and BRB may be associated with diabetes, glaucoma, and
uveitis [16]. Surgical complication of the anterior segment may lead to the release
of arachidonic acid from cell membranes, with production of either leukotrienes
via the lipooxygenase pathway or prostaglandins via the cyclooxygenase pathway
[13, 14]. These inflammatory biomarkers result in increased retinal vessel
permeability and the development of edema. Contraction of the posterior hyaloid
as a result of inflammation may lead to mechanical traction onto the perifoveal
retinal capillaries and result in CME [15].
Fig. (1). Fluorescein angiography. Perifoveal petalloid staining.

Pseudophakic Cystoid Macular Edema Ophthalmology: Current and Future Developments, Vol. 1 263
Fig. (2). Fluorescein angiography. Perifoveal petalloid staining.
Fig. (3). Fluorescein angiography with macular late leakage.

Fig. (4). OCT. Macular thickening. Cystic spaces in outer plexiform layer.
Fig. (5). OCT. Macular thickening. Cystic spaces in outer plexiform layer and subfoveal fluid.
Incidence and Risk Factors
The most frequent appearance of CME occurs at 6 weeks after surgery. Incidence
increases in patients with high-risk characteristics including diabetes mellitus,
hypertension, history of central retinal vein occlusion, history of uveitis, epiretinal

membrane, or following complicated cataract surgery (Fig. 6) [3, 9]. A recent
large retrospective study showed no increased incidence of clinical CME in
glaucoma patients undergoing uncomplicated cataract extraction [17]. Although
that study found no relationship between the use of prostaglandin analogs for the
treatment of glaucoma and the development of CME, other studies have found
that prostaglandins, synthesized by the uvea and lens epithelial cells, may be one
of the inflammatory mediators associated with CME [18].
Fig. (6). Complicated anterior segment surgeries. Subluxated IOLS, anterior vitreous.
Metabolic disorders: Diabetes, Retinitis pigmentosa, Inherited CME (autosomal-

dominant).
Ischemia: Vein occlusion, Diabetic retinopathy, Hypertensive retinopathy,

Vasculitis, Collagenosis (Fig. 7).
Fig. (7). Cystoid macular edema in telangiectasias.
Hydrostatic forces: Retinal vascular occlusions, Venous occlusion, Arterial

hypertension, Low Intraocular Pression (Fig. 8).
Mechanical forces: Vitreo macular traction (Fig. 9) [21].
Inflammation: Intermediate uveitis, Diabetic Macular Edema, Choroidal

inflammatory diseases (Vogt-Koyanagi Harada, Birdshot).
Pharmacotoxic effects: Latanoprost, Betaxolol [19].

Fig. (8). Differential diagnosis: cystoid macular edema in retinal vein occlusion.
Fig. (9). Macular edema associated with vitreo macular traction, epiretinal membrane and central serous
retinopathy.
Graphic 1. Mechanism of action for Steroids and NSAID in CME.
MANAGEMENT
CME is diagnosed by decreased visual acuity, by FA with the classic appearance

of perifoveal petalloid staining with or without late leakage from the optic disk, or
by OCT. Characteristics of CME on OCT include macular thickening and cystic
spaces in the outer plexiform layer, occasionally with subfoveal fluid [16, 20].
(Figs. 10 - 13).
Fig. (10). Degenerative myopic patients. History of bilateral retinal detachment surgery. Cataract surgery and
pseudophakic macular edema. Treatment with topical non-steroidal anti-inflammatory drugs plus topical
steroids for 3 months. Edema resolution.
Fig. (11-A). Pseudophakic patients with chronic edema.

Fig. (11-B). OCT with cystoid edema and the evolution during 6 months treated with topical steroids plus
topical non-steroidal anti-inflammatory drugs. Edema resolution.
Fig. (12). Pseudophakic macular edema in complicated cataract surgery, with vitreous loss. Resolution after
8 months of topical combination of steroids and non-steroids.
Fig. (13). Pseudophakic macular edema. Resolution after 7 months of treatment with topical combination of
steroids and non-steroids.
Corticosteroids (Graphic 1) [13, 22 - 31].
● Topical
● Intravitreal injection
● Subtenon
Nonsteroidal anti-inflammatory drugs (Graphic 1) [32 - 39].
• Topical.
Anti-vascular endothelial growth factor [40 - 48].
Surgical: pars plana vitrectomy [49 - 53].
ACKNOWLEDGEMENTS
Declared none.
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CHAPTER 26
Central Serous Chorioretinopathy

Daniel D. Kim1, Paul Baciu1 and Michael D. Ober1,2,*
1
Department of Ophthalmology, Henry Ford Health Systems, Detroit, MI, USA
2
Central serous chorioretinopathy (CSC) is an idiopathic disorder characterized by

serous detachment of the neurosensory retina. It has an incidence of roughly
6/100,000 individuals [1 - 3]. Affected patients are usually young to middle age
adults (ages 25-45), male (5-10:1 male:female ratio), and of “Type A” personality
[4 - 6]. The symptoms present unilaterally (60-90% of the time) and patients often
complain of blurred central vision and metamorphopsia with a hyperopic shift [1 -
3, 5, 7]. A history of recent psychosocial stressors, or steroid use is often present.
Disorders causing elevated levels of catecholamines are known to predispose.
Furthermore, pregnancy, phosphodiesterase inhibitors, and illicit drug use have
also less commonly been associated with onset of symptoms [2, 3, 6, 8].
Despite decades of study, the precise etiology and pathophysiology remain

elusive. Much has been learned, however, through multimodal imaging studies
that often yield pathognomonic findings (Fig. 1). Fluorescein angiography (FA) in
acute cases reveals a focal leak at the level of the retinal pigment epithelium
(RPE) appearing as an expanding hyperfluorescent dot (30% have more than one)
sometimes elevating into a smokestack appearance in 10-20% (Figs. 2 and 3).
Ultimately, the subretinal fluid pocket can extend inferiorly due to gravity
creating descending atrophic tracts, which are best seen with fundus
autofluorescence (FAF) [2, 3, 6, 8]. Chronic cases reveal multiple leaks in close
*
Corresponding author Michael D. Ober: Retina Consultants of Michigan, 29201 Telegraph Road, Suite 606,
Southfield, MI 48034, USA; Tel: (248) 356-6473; Fax: (248) 356-6473; E-mail: obermike@gmail.com
278 Ophthalmology: Current and Future Developments, Vol. 1 Kim et al.
proximity with mottled hyper and hypofluorescence of the RPE corresponding to

“sick RPE syndrome” [9, 10]. Indocyanine green angiography (ICGA) demons-
trates hyperfluorescence in mid-frames (not present early or late) often described
as choroidal hyperpermeability (Fig. 4) [2, 3, 6, 8, 11, 12].
As OCT technology has improved, it has become critical for diagnosis. Findings
include subretinal fluid, RPE detachments, and retinal atrophy. Less common
features include cystoid macular edema or cystoid macular degeneration, which is
differentiated by lack of corresponding FA leakage and poor visual potential [2, 5,
8]. While relatively new, visualization of the choroid using enhanced-depth
imaging shows marked thickening of the choroid in CSC (Fig. 5), most prominent
in zones of choroidal permeability with active angiographic leakage [8, 13].
Fig. (1). CSC Fundus photo showing subretinal fluid causing serous retinal detachment (Photo Credit: Henry
Ford Ophthalmic Photography).
Fundus autofluorescence is being used more frequently to image patients with

CSC. Over time, a neurosensory detachment leads to an accumulation of
lipofuscin from shed photoreceptor outer segments yielding patches of speckled
hyperautofluorescence that can become more prominent when subretinal fluid
first resolves. Over time, these areas become hypoautofluorescent as noted around
Central Serous Chorioretinopathy Ophthalmology: Current and Future Developments, Vol. 1 279
old leaks and chronic descending atrophic tracts [2, 8, 14]. Other diagnostic
modalities include multifocal ERG, which shows broad retinal functional
disturbances, and abnormal visual field testing, especially on microperimetry,
indicating that central visual acuity underestimates the amount of visual
impairment [8, 15].
Fig. (2). RPE blowout as imaged by fundus photography (A), early (B) and late (C) fluorescein angiography,
autofluorescence (D) and OCT (E) (Photo Credit: Lorrene Santiego).
Fig. (3). Classic fluorescein angiography findings. Expansile dot, early (A) and late phase (C). Smokestack,
mid (B) and late phase (D) (Photo Credit: A & C – Courtney McClenahan, B & D – Henry Ford Ophthalmic
Photography).
Fig. (4). Mid-phase hyperpermeability on ICGA (Photo Credit: Courtney McClenahay).

Fig. (5). Enhanced Depth OCT imaging showing choroidal thickening and subretinal fluid (Photo Credit:
Logan Jabouri).
Polypoidal choroidal vasculopathy is well known to masquerade as CSC in the

active phase while pattern dystrophy may mimic the late pigmentary changes [16].
Severe variants of CSC are known to occur with multiple large RPE detachments,
dependent exudative retinal detachment and RPE tears all of which can simulate
severe inflammatory disorders such as Vogt-Koyanagi-Harada syndrome or
posterior uveitis. The most common item on the differential, however is age
related macular degeneration with occult choroidal neovascularization, especially
in patients older than 50 years old [2, 3]
MANAGEMENT
Patients who fit a “typical” patient profile for CSC, generally require no further
work-up, but testing for elevated systemic catecholamine levels or sleep apnea
should be considered in the appropriate patient context [2, 3]. CSC is generally
treated conservatively as it most often consists of self-limited episodes that
resolve over weeks to months. However, chronic CSC can lead to permanent
visual impairment [4, 17, 18].
Improving underlying conditions such as eliminating or reducing corticosteroid

use and stress reduction are first line treatments. Most patients are observed
without any further intervention for the first few months, but timing of potential
treatment is individual. Many factors can trigger the need for additional treatment
including failure of spontaneous resolution, monocular status, specific vocational
needs (i.e. pilot or commercial drivers license), recurrent disease, need for
ongoing or increased corticosteroid use, etc.
Verteporfin based photodynamic therapy (PDT) (QLT, Vancouver, CA) has

orphan drug designation for the treatment of CSC and is the current mainstay of
therapy. PDT leads to coagulation of the choroid. The subsequent reperfusion
typically yields a reduction in choroidal thickness, elimination of choroidal
hyperpeability on ICGA and focal leak on FA as well as resolution of subretinal
fluid (Fig. 6). The vast majority of patients treated with PDT have resolution of
fluid and improvement in vision [2 - 4, 8, 10 - 12, 17].
Fig. (6). OCT imaging of PED before (A) and after (B) PDT. (Photo Credit: Courney McClenahay).
Thermal laser photocoagulation will also successfully treat CSC, but is only
indicated for extrafoveal leaks due to the laser induced scotoma and propensity for
secondary choroidal neovascularization [2, 8]. Furthermore, it does not address
the underlying choroidal hyperpermeability and thus may, in theory, carry a
greater risk of recurrence in the first year. Micropulse diode laser is currently
being investigated as a safer alternative to thermal laser photocoagulation [2, 8].
Anti-VEGF agents continue to be investigated with several studies showing

promise; however the self-limiting nature of CSC is a confounding factor in
measuring outcomes. In the authors’ opinion, anti-VEGF does not significantly
alter natural history based upon detailed examination patients showing no change
in choroidal thickness or choroidal hyperpermeability following treatment
(unpublished data) [2, 3, 8, 11, 17]. Numerous systemic medications have also
been investigated with studies looking at anti-glucocorticoid (mifepristone), anti-
mineralocorticoid (eplerenone, finesteride), ketoconazole, rifampin, H pylori
eradication, and high dose anti-oxidants but thus far, evidence has been
inconclusive [1, 6, 7, 19 - 21].
ACKNOWLEDGEMENTS
Declared none.
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[2] Fine HF, Ober MD, Hariprasad SM. Current concepts in managing central serous chorioretinopathy.
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and pathophysiology. Clin Experiment Ophthalmol 2013; 41(2): 201-14.
[4] Chan WM, Lai TY, Lai RY, Liu DT, Lam DS. Half-dose verteporfin photodynamic therapy for acute
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[5] Plateroti AM, Witmer MT, Kiss S, D’Amico DJ. Characteristics of intraretinal deposits in acute
central serous chorioretinopathy. Clin Ophthalmol 2014; 8: 673-6.
[6] Ratanasukon M, Bhurayanontachai P, Jirarattanasopa P. High-dose antioxidants for central serous
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[7] Mateo-Montoya A, Mauget-Faÿse M. Helicobacter pylori as a risk factor for central serous
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chorioretinopathy: review and update. Clin Experiment Ophthalmol 2013; 41(2): 187-200.
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therapy for treatment of chronic central serous chorioretinopathy: a pilot study. Retina 2003; 23(3):
288-98.
[13] Jirarattanasopa P, Ooto S, Tsujikawa A, et al. Assessment of macular choroidal thickness by optical
coherence tomography and angiographic changes in central serous chorioretinopathy. Ophthalmology
2012; 119(8): 1666-78.
[14] von Rückmann A, Fitzke FW, Fan J, Halfyard A, Bird AC. Abnormalities of fundus autofluorescence
in central serous retinopathy. Am J Ophthalmol 2002; 133(6): 780-6.
[15] Kim SW, Oh J, Huh K. Correlations among various functional and morphological tests in resolved
central serous chorioretinopathy. Br J Ophthalmol 2012; 96(3): 350-5.
[16] Yannuzzi LA, Freund KB, Goldbaum M, et al. Polypoidal choroidal vasculopathy masquerading as
central serous chorioretinopathy. Ophthalmology 2000; 107(4): 767-77.
[17] Chung YR, Seo EJ, Lew HM, Lee KH. Lack of positive effect of intravitreal bevacizumab in central
serous chorioretinopathy: meta-analysis and review. Eye (Lond) 2013; 27(12): 1339-46.
[18] Forooghian F, Meleth AD, Cukras C, Chew EY, Wong WT, Meyerle CB. Finasteride for chronic
central serous chorioretinopathy. Retina 2011; 31(4): 766-71.
[http://dx.doi.org/10.1097/IAE.0b013e3181f04a35] [PMID: 21273946]
[19] Meyerle CB, Freund KB, Bhatnagar P, Shah V, Yannuzzi LA. Ketoconazole in the treatment of
chronic idiopathic central serous chorioretinopathy. Retina 2007; 27(7): 943-6.
[http://dx.doi.org/10.1097/IAE.0b013e318050ca69] [PMID: 17891021]
[20] Nielsen JS, Jampol LM. Oral mifepristone for chronic central serous chorioretinopathy. Retina 2011;
31(9): 1928-36.
[http://dx.doi.org/10.1097/IAE.0b013e31821c3ef6] [PMID: 21878843]
[21] Steinle NC, Gupta N, Yuan A, Singh RP. Oral rifampin utilisation for the treatment of chronic
multifocal central serous retinopathy. Br J Ophthalmol 2012; 96(1): 10-3.
[http://dx.doi.org/10.1136/bjophthalmol-2011-300183] [PMID: 22053102]
286 Ophthalmology: Current and Future Developments, 2016, Vol. 1, 2016, 286-291
SUBJECT INDEX
A Choroidal infarctions 78
Choroidal neovascularization 39, 105, 108,
Accelerated-malignant hypertension 68, 73, 168, 193, 201, 208, 211, 213, 214, 219,
74, 76, 77, 78 251
Acceleration-malignancy 74, 75 active 39, 213
Anemia 23, 29, 74 subfoveal 121, 208
Anterior segment neovascularization 53, 55, Choroidal rupture, traumatic 216
132 Choroidal thickness 282, 283
Anti-inflammatory drugs 269, 270, 272 Chronic arterial hypertension 67, 70, 71, 79
Anti-VEGF agents 40, 64, 128, 216, 283 Chronic decompensation 100
Anti-VEGF treatment 54, 65 Chronic hypertensive arteriolosclerosis 69, 72,
Areas, subfoveal 172, 182, 183 74
Arterial attenuation 84 Chronic secondary accelerated hypertension
Arterial hypertension, systemic 67, 99 74, 75
Arterial macroaneurysms 99, 100 Cilioretinal arteries 84, 85, 92, 93
Arterioles, copper wiring of 69, 70, 71, 75 Circular myopic crescent 202, 203
Arteriolized CNVs 179 Clinically significant macular edema (CSME)
Arteriolovenous crossings, abnormal 69, 70, 29, 30, 33, 38
71, 73, 79 CNV 205, 206, 224
Asymptomatic VMA patients 258 myopic 205, 206, 224
Autofluorescence 93, 113, 195, 212, 250, 251, occult 194
279 Color photo montage 117, 120
Combined fluorescein-indocyanine 179
Cotton-wool spots (CWS) 3, 4, 5, 9, 12, 13,
B 58, 59, 91, 114, 131
Cystic spaces 31, 264, 268
Best corrected visual acuity (BCVA) 53, 55, Cystoid macular edema (CME) 32, 35, 227,
206, 216 229, 242, 252, 258, 261, 262, 264, 265,
Blood-aqueous barrier (BAB) 262 266, 267, 268, 278
Blood-retinal barrier (BRB) 31, 262
Blood vessels, large choroidal 149, 151, 208
Brilliant blue G (BBG) 232, 246 D
Bruch’s membrane 138, 168, 207, 210, 212,
214, 215, 216 Decreased visual acuity 91, 100, 103, 104,
B-wave amplitude 87 228, 254, 261, 268
Dexamethasone intravitreal implants 53
Diabetes mellitus 3, 20, 22, 24, 27, 90, 264
C Diabetic retinopathy 3, 5, 13, 15, 18, 26, 29,
31, 36, 41, 64, 74, 86, 94, 127, 134
Capillaries, perifoveal retinal 262 severe non-proliferative 18
Capillary non-perfusion 49, 61, 62, 64 Diabetic retinopathy vitrectomy study (DRVS)
Cataract surgery, complicated 265, 270 26
Cells, glial 227 Diastolic blood pressure readings 68
Centrifugal contraction 248, 251 Differential diagnosis of CRVO 53
Chorioretinal anastomosis 108, 114, 126 Disciform scar 108, 181, 214, 215, 216
Chorioretinal scars 220, 222 Disease, proliferative 116, 119
Soriano et al. (Eds.)
Subject Index Ophthalmology: Current and Future Developments, 2016, Vol. 1 287
Disease progression 183, 216 Flamed-shaped hemorrhages and retinal

Domain-optical coherence tomography 36, 37, edema in superior macular area 59
39, 41 Fluorescein 147, 172, 174, 175, 176
Drusen 137, 138, 139, 140, 159, 163, 169 Fluorescein angiogram 3, 5, 6, 119, 121, 122,
basal laminar 159, 163 133, 134, 139, 174, 176, 189, 213, 221,
hard 137, 138, 140, 169 222
large 137, 149 Fluorescein angiogram (FA) 3, 4, 5, 20, 31,
medium 137, 139 34, 61, 62, 93, 94, 120, 121, 172, 173,
Drusenoid pigment epithelial detachment 174
(DPED) 140, 146, 158, 161 Fluorescein angiography 47, 48, 49, 77, 78,
79, 126, 127, 179, 194, 204, 213, 229,
E 251, 263
Focal vitreomacular traction 256
Eales disease and CMV retinitis 14 Foveal avascular zone, enlarged 20, 121, 122
Early fluorescein angiogram 172, 173, 175, Foveal contour 182, 183, 235, 242
180 irregular 235, 242
Early hyperfluorescence 139, 163, 172 recovery of 182, 183
Early treatment diabetic retinopathy study Foveal depression 183, 230
(ETDRS) 29, 40, 128 Foveal detachment 227, 235, 254, 257
Edema resolution 269, 270 FTMH, large 240
Electroretinogram 52, 87, 229 Full-thickness macular hole (FTMH) 240, 241,
Epiretinal membrane 243, 228, 251, 252, 245, 248, 251
located perifoveal 252 Fundus autofluorescence 86, 93, 113, 210,
semitransparent perifoveolar 251 277, 278
thick 243
thin 228 G
Epiretinal membrane peeling 232
Epithelial detachments 8, 178, 187, 193, 194 Geographic atrophy (GA) 136, 147, 149, 151,
Extrafoveal chorioretinal scars 223 152, 153, 154, 155, 157, 164
Exudates, hemorrhages and hard 34, 168 Giant cell arteritis 93, 96, 130
Eyes 130, 132, 182 Glaucoma 40, 44, 262, 265
affected 130, 132
contralateral 182 H
F Hard exudates and hemorrhages 172
Hemoglobin, mutated 116
Factors, anti-vascular endothelial growth 114, Hemorrhages 23, 45, 47, 74, 100, 105, 125,
123, 128, 198, 272 193, 208, 213
FAF signal 154, 157 dense 100
Faint stain 141, 144 diffuse retinal 74
Features, fundoscopic 44, 47 flame-shaped 45, 47
Female patient 34, 76, 90, 162, 244 preretinal 105, 125, 193
diabetic 34 pre-retinal 23
Female patient complains 101 subfoveal 208, 213
Fibrinoid necrosis 72, 73 Henry ford ophthalmic photography 278, 280
Fibrotic end-stage submacular choroidal Heterozygote, double 116
neovascularization 211 Histoplasma capsulatum 219
288 Ophthalmology: Current and Future Developments, 2016, Vol. 1 Soriano et al.
Hyperfluorescence 74, 77, 100, 133, 139, 141, Intraretinal hemorrhages and microaneurysms
144, 153, 161, 173, 174, 194, 212, 248, 4
251, 278 Intra retinal microvascular abnormalities
progressive 141, 144 (IRMAs) 3, 10, 18, 31
showing 172, 175, 195 Intraretinal neovascularization 194
Hyperfluorescent points, multiple 31, 33 Intravitreal anti-VEGF therapy 182, 183
Hyperreflective 4, 8 Intravitreal injections 40, 53, 105, 198, 271
Hyperreflective subretinal material, showing IVTS classification system for vitreomacular
205 adhesion 241, 255
Hyper-reflective tissue 182, 183
Hypertension 67, 68, 73, 80 L
chronic 68, 73, 80
primary 67, 68 Laser, subthreshold 105
Hypertensive patients 67, 68, 80 Laser photocoagulation 40, 104, 134, 184,
Hypertensive subject 67 196, 206, 216, 283
Hypofluorescence 34, 49, 61, 146, 161, 278 thermal 196, 283
Hyporeflective spaces, showing 236, 237 Late fluorescein angiogram 173, 174, 175,
176, 181
I Leakage 31, 33, 34, 195, 215, 261, 263, 268
diffuse 31, 195
Idiopathic macular hole 234, 235 late 215, 261, 263, 268
Indocyanine 100, 127, 172, 179, 187, 194, mild 31, 33, 34
214, 232, 246, 278 Left ventricular hypertrophy 68, 71, 77
Inferotemporal BRVO 59, 63, 65 Lesions 177, 181, 183, 195, 197
Inner retinal layers 4, 5, 6, 83, 85, 87, 146, 242 Hyper reflective 177, 181, 183
Interface, vitreomacular 234, 235, 254 hyperreflective subretinal 195, 197
Internal limiting membrane (ILM) 55, 100,
104, 117, 227, 235, 241, 246 M
International clinical diabetic retinopathy
disease severity scale 12, 13 Macroaneurysm 100, 104, 105
International vitreomacular traction stud, Macula, normal 236
(IVTS) 240, 254 Macular area 72, 136, 169, 172, 179, 180, 227
International vitreomacular traction study Macular attachment 255
classification 240, 241, 255 Macular edema 39, 45, 53, 54, 55, 58, 60, 61,
Intraocular pressure 55, 96, 101, 102, 103, 64, 65, 78, 125, 128, 133, 203, 205, 269,
131, 132 270, 271
Intraretinal fluid 54, 65, 177, 182, 183 pseudophakic 39, 269, 270, 271
accumulation of 177 Macular hole 235, 241, 242, 243, 245, 248
recovery of foveal contour and improvement full-thickness 241, 245, 248
of 182, 183 lamellar 235, 242, 243
showing accumulation of 54, 65 Macular hole (MH) 114, 232, 234, 235, 236,
Intraretinal hemorrhages 3, 4, 13, 18, 45, 60, 238, 240, 241, 244, 246, 248, 251
95, 101, 102, 117, 134 Macular hole stage 236, 237, 238
diffuse 18 Macular pseudohole 235, 241, 242, 249, 250,
largest 4 251
showing massive 45 Macular retinal pigment 84
Macular thickening 227, 230, 264, 268
Maculopathy 121, 219, 223 Permanent BRAO 90, 91

Membrane 100, 104, 117, 227, 228, 235 Photodynamic therapy 128, 184, 190, 197,
epiretinal macular 228 206, 216, 224
internal limiting 100, 104, 117, 227, 235 Pigment epithelium 108, 203, 238, 239
Metamorphopsia 107, 168, 202, 216, 223, 227, irregular retinal 238, 239
228, 234, 254, 277 Pigment epithelium detachment (PED) 172,
Microaneurysms 3, 4, 6, 11, 13, 21, 24, 30, 33, 182, 187, 197, 282
107, 127 Plexiform layer, outer 4, 8, 264, 268
Microemboli 91 Posterior hyaloid 18, 259, 262
Multiple evanescent white-dot syndrome PPA and extrafoveal chorioretinal scars 223
(MEWDS) 224 Progressive glomerulonephritis 74, 77
Multiple imaging modalities 119, 120 Pro re nata (PRN) 216
Myopia 201 Prostaglandins 262, 265
pathologic 201 Pseudoxanthoma elasticum 207, 208, 210, 213
pathological 201 Punctate inner choroidopathy (PIC) 223
N R
Neovascularization 53, 114, 130 Radiance study 206
angle 53, 130 Ranibizumab 40, 53, 64, 183, 216
pre-retinal 114 Rapid progression 154, 157, 158
Nerve fiber layer 3, 4, 5, 6, 9, 83, 91 indicating 154
Network, vascular 188, 189 RAP lesions 196, 197, 198
Non-clearing vitreous hemorrhage 123, 128 Red blood cell (RBC) 116
Non-ischemic CRVO 46, 47, 54 Reflective material 140, 141, 142, 159
Normal autofluorescence 93 Reflective RPE layer 140, 141
Regions, peripapillary 126, 211, 212
O Resolving intraretinal hemorrhage 117
Retina , adjacent 29, 104
OCT image 52, 104, 188, 236, 237, 238, 239, Retina 52, 108, 136, 149, 193, 209, 210, 236,
242, 243, 244, 245, 250, 257 238, 277
OCT of epiretinal membrane 230 neurosensory 52, 108, 193, 209, 277
OCT scans 195, 197, 229, 231 outer 136, 149, 210, 236, 238
Ophthalmic arteries 82, 88 Retinal angiomatous proliferation 193, 195,
Optical coherence tomography 51, 61, 85, 93, 196, 197
104, 126, 140, 205, 210, 236, 254, 261 Retinal architecture 228, 256
Optic coherence tomography (OCT) 4, 51, 54, Retinal artery 72, 82, 83, 90, 93, 132
61, 63, 141, 146, 177, 178, 182, 183, Retinal artery occlusion 82, 86, 93
194, 229, 234, 235 Retinal choroidal anastomosis (RCA) 194
Retinal damage 68, 246
P Retinal detachment 23, 25, 26, 35, 52, 54, 61,
63, 64, 65, 119, 120, 123, 126, 128, 227,
Panretinal photocoagulation 24, 26, 46, 53, 94, 229, 258, 278
134 associated foveal 258
Papillomacular bundle 92, 93 serous 35, 52, 54, 61, 63, 65, 278
Perifoveal vitreous cortex detachment 255 tractional 23, 25, 26, 64, 120, 123
Peripapillary PCV 187, 188 traction macular 229
290 Ophthalmology: Current and Future Developments, 2016, Vol. 1 Soriano et al.
Retinal edema 58, 59, 72, 76, 85, 100 S

Retinal emboli 90, 91
Retinal folds 227, 230 Scanning laser ophthalmoscope (SLO) 251
Retinal hemorrhages 30, 44, 47, 48, 52, 59, Scotomas 91, 162, 216, 234, 251
132, 127, 131, 194 Serous chorioretinopathy 182, 251, 277
characteristic 132 Serous PED 194, 196, 198
intra 52 Showing epiretinal membrane 230
mid-peripheral 131 Showing retinal hemorrhages 126
Retinal layers 4, 6, 72, 108, 140, 181, 232, Showing subretinal fluid 195, 278
235, 236, 238, 241, 245, 255, 256, 257 Sickle cell disease 14, 95, 116, 121, 210
deeper 72, 108 Sickle cell trait 116
middle 4, 6 Skin, histoplasmin 223
outer 140, 235, 238, 245 Small drusen 137
Retinal neovascularization 61, 64, 126, 127 Soft drusen 136, 138, 139, 140, 141, 142, 148,
Retinal pallor 91, 92 154, 156, 164
Retinal pigment 105, 109, 213 confluent 156, 164
Retinal pigment epithelium (RPE) 117, 136, Spectral domain optical coherence
140, 141, 143, 146, 147, 193, 207, 208, tomography (SDOCT) 121, 230
209, 240, 241, 255, 277 Spots 3, 58, 59, 91, 114, 117, 118, 131
Retinal signs 72, 75 cotton-wool 3, 58, 59, 91, 114, 131
Retinal stroma 3, 4 iridescent 117, 118
Retinal surface 117, 227, 229, 230, 255, 258 Stage-II RAP lesions 194, 198
inner 248, 252 Staining 47, 48, 50, 262, 263, 268
Retinal telangiectasia 62, 127 perifoveal petalloid 262, 263, 268
Retinal thickening 29, 30, 112 vessel wall 47, 48, 50
Retinal thickness 41, 51, 52, 93, 177, 182, Stenosis, carotid 130
183, 197 Subfoveal CNV 169, 170, 171, 224
increased 51, 52, 183 Subfoveal fluid 264, 268
showing decreased 182, 183 Subhyaloid hemorrhage 18, 78, 103
showing increased 177 Submacular hemorrhage 169, 170, 171
Retinal tissue 88, 251 large 169
Retinal traction 35, 105 massive 171
Retinal transparency 109, 111 Subretinal fibrosis 105, 171, 172, 180, 181,
Retinal vein 45, 47, 58, 80 221
Retinal vein occlusion 44, 58, 74, 121, 134, Subretinal fluid 52, 54, 65, 112, 168, 172, 178,
267 182, 183, 194, 213, 278, 281, 282
Retinal vessels 108, 133, 193, 202 Subretinal hemorrhage 105, 169, 170, 174,
Retinitis pigmentosa 210, 265 176, 180, 187, 211
Retinopathy 121, 125, 134 associated 170
Retinovascular diseases 18 massive 176
Right eye 19, 20, 24, 34, 36, 131, 158, 159, small 169
160, 162, 169, 214, 215, 220, 222 Subretinal neovascularization 194, 202, 209
RPE atrophy 108, 136, 146, 154, 213, 214 classic 209
RPE cells 139, 147, 154
Subretinal space 117, 194, 212 Vein occlusions 13, 14, 18, 39, 73, 93, 134,
Superotemporal, subretinal choroidal 265
neovascularization 222 Venous beading 3, 10, 11, 12, 18, 24
Superotemporal arcade 20, 24, 94 severe 11
Vessels 6, 59, 60, 91, 93, 94, 108, 109, 111,
T 179
affected 91, 93, 94
Tangential vitreoretinal traction (TVT) 234 normal 6, 108
Telangiectasias 125, 126, 196, 232, 266 right angle 109, 111
parafoveal 196, 232 sclerotic 59, 60
Temporal macula 122 showing thick 179
Thickness macular hole 108, 238, 239, 240, VH eyes 26
244, 245, 258 Visual acuity 54, 64, 65, 100, 101, 102, 103,
Topical combination 270, 271 105, 107, 159, 160, 232, 234, 244, 246
Topical non-steroidal 269, 270 Visual field defects 58, 93, 95, 96
Tortuosity, vascular 117, 229 Visual fields 83, 87, 162
Traction, vitreo macular 266, 267 Visual loss 29, 91, 96, 119, 125, 146, 261
Transit time, arteriovenous 47, 48 Vitrectomy 25, 55, 132, 244, 259
Treatment of CRVO 53 Vitreomacular Adhesion (VMA) 240, 241,
Triamcinolone 53, 55, 64 254, 255, 258
Trypan blue (TB) 232, 246 Vitreomacular traction syndrome 232, 236,
254
V Vitreous cells 220, 224
Vitreous cortex 235, 255
Vascular diseases 58, 121, 130, 134, 227 Vitreous hemorrhage (VH) 23, 61, 64, 117,
Vascular endothelial growth factor (VEGF) 119, 122, 126, 131
31, 40, 114, 123, 128, 198, 224, 272 W
Vascular occlusions 73, 126, 127, 266
Vascular retinal diseases 44 Watzke-Allen test 234, 235
Wool spots, multiple cotton 74, 75

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Ophthalmology:

Current and Future Developments

Gerardo García Aguirre

Veronica Kon Graversen

Ophthalmology: Current and Future Developments

Diagnostic Atlas of Retinal Diseases

ISSN (Print): 2468-7162

eISSN (Online): 2468-7170

eISBN (Online): 978-1-68108-357-5

ISBN (Print): 978-1-68108-358-2

©2016, Bentham eBooks imprint.

Published by Bentham Science Publishers – Sharjah, UAE. All Rights Reserved.

Bentham Science Publishers Ltd.

LIST OF CONTRIBUTORS ..................................................................................................................................... iv

SUBJECT INDEX .................................................................................................................................................... 286

Dr. Hugo Quiroz-Mercado

We are honored to contribute to the information and education of ophthalmology students

This e-book is specially dedicated to Guillermo Manuel Gordon, MD. He inspired us to

Dr. Mitzy E. Torres Soriano

Dr. Gerardo García Aguirre

Dr. Maximiliano Gordon

Dr. Veronica Kon Graversen

Retina Department, Centro Oftalmológico de Valencia (CEOVAL),

Aziz A. Khanifar Retina Group of Washington, Washington DC, USA

Daniela Roca Ophthalmology Department, Clínica Ricardo Palma, Lima, Peru

Diego Fernando Mojica Centro Oftalmológico de Valencia (CEOVAL), Valencia, Venezuela

Department of Ophthalmology, Henry Ford Health Systems, Detroit, MI,

Retina Deparmeant, Hospital Oftalmológico Santa Lucia, Buenos Aires,

Ophthalmology Service, Sanatorio Mapaci, Rosario, Argentina

Retina Department, Asociación para Evitar la Ceguera en Mexico, Mexico

Guillermo Gordon Died

Hugo Luglio Macula D&T, Lima, Peru

Retina Department, Asociación para Evitar la Ceguera en México, IAP,

Jose A. Roca Ophthalmology Department, Clínica Ricardo Palma, Lima, Peru

Centro Clínico, de Ojos Maracay, Maracay, Venezuela

Luis A. Acabá Sidney Kimmel College of Medicine, Philadelphia, PA, USA

Liriany Arrieta Ruiz Unidad Popular de Ojos (UPO), Maracay, Venezuela

Luke B. Lindsell Retina Group of Washington, Washington DC, USA

Uveitis Department, Asociación para Evitar la Ceguera en México. I.A.P,

Retina & Vitreous Service, Clínica Oftalmológica El Viñedo, Valencia,

Maximiliano Gordon Centro de la Visión Gordon-Manavella, Rosario, Santa Fe, Argentina

Maria H. Berrocal Berrocal & Asociados, San Juan, Puerto Rico

Centro de la Visión Gordon-Manavella, Rosario, Santa Fe, Argentina

Department of Ophthalmology, Henry Ford Health System, Detroit, MI,

Department of Ophthalmology, Glostrup Hospital and Faculty of Health

Department of Ophthalmology, Glostrup Hospital and Faculty of Health

Department of Medical Sciences, Division of Health Sciences, Universidad

Uveitis and Ocular Inmunology Department, Instituto de Oftalmología

Retina & Vitreous Service, Clínica Oftalmológica El Viñedo, Valencia,

Department of Ophthalmology, University of Colorado School of Medi-

Retina Department, Grupo de Clínicas IDB, Centro Profesional Arca,

Department of Ophthalmology, Henry Ford Health Systems, Detroit, MI,

Retina Department, Asociación para Evitar la Ceguera en México, IAP,

Universidad Central de Venezuela, Unidad de Neurooftalmología, Hospital

Vitreoreitnal Disease and Surgery, Department of Ophthalmology,

Retina & Vitreous Service, Clínica Oftalmológica El Viñedo, Valencia,

Hyper retinopathy grading