RETINAL REVIEW
From the Comprehensive Ophthalmology Review Course, presented by the Jules Stein Eye Institute and the Doheny
Eye Institute
David Sarraf, MD, Assistant Clinical Professor of Ophthalmology, Jules Stein Eye Institute, The David Geffen
School of Medicine at the University of California, Los Angeles
 | Grade 1: arterial narrowing
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| Grade 2: arterial sclerosis (arteriovenous [AV] nicking or changes in direction)
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| Grade 3: retinopathy (severe sclerosis, “silver wiring” or severe AV nicking, “dot-and-blot” hemorrhages, exudates, and
featureless fundus)
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| Grade 4: disc edema and macular star (hypertensive optic neuropathy or choroidopathy with serous detachment; signs include
small lesions with pigmented center surrounded by atrophy [Elschnig spots], or sclerotic choroidal vessels [Siegrist
streaks]; often associated with malignant hypertension)
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| Complications: retinal vascular occlusion; macular aneurysms
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| Cotton wool spots: always investigate; focal infarcts of nerve fiber layer, causing axoplasmic stasis; differential diagnosis
includes diabetes, hypertension, embolic events of carotid or cardiac origin, autoimmune diseases (lupus), vasculitides
(eg, sarcoid), iatrogenic conditions (eg, interferon toxicity)
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| Branch retinal artery occlusion: key feature sectorial ischemic whitening without congestion (congestion hallmark of
venous occlusion), possible emboli; markedly delayed AV transit time; retrograde perfusion on fluorescein angiography
essential feature; therapy requires systemic work-up; for central retinal artery occlusion (CRAO), consider distillation
maneuvers (eg, anterior chamber paracentesis, within first 24 hr)
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| Central retinal artery occlusion: characterized by cherry red spots as well as cotton wool spots; widespread delay in retinal
arterial perfusion, with perfusion remaining in ciliary portion of disc; “boxcar” arteries another sign; Purtscher’s-like retinopathy
(rosette of cotton wool spots in macula); selective B-wave loss on electroretinography confirms presence of
CRAO; in elderly, consider giant cell arteritis (GCA; measure erythrocyte sedimentation rate and C-reactive protein, and
ask patient about signs and symptoms of GCA)
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| Ophthalmic artery occlusion: vision loss more severe than with other forms of CRAO; finger counting, hand motion, and
light perception especially affected; no cherry red spot, due to involvement of choroidal perfusion, leading to choroidal
as well as inner retinal ischemia; fluorescein angiography shows widespread delay in ciliary choroidal and disc perfusion,
as well as slower AV transit time
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| Venous occlusion: hypertension primary risk factor
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| Branch retinal vein occlusion (BRVO): may be major supratemporal or macular (affects tributary of major retinal vein);
usually occurs in supratemporal region of fundus; early signs sectorial pattern of congestion with hemorrhage and cotton
wool spots, possibly exudates; this clears over time, leaving microvascular remodeling and collateralization; glaucoma
another risk factor, although risk for central vein occlusion greater
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| Management: focal macular laser (FML) with angiographic guidance effective as long as macula still intact; for those patients,
laser panretinal photocoagulation (PRP) applied in quadrantic pattern helpful, but only after neovascularization
has developed; according to Branch Vein Occlusion Study Group, FML decreases risk for vision loss 25% to 50% and
increases chances of achieving 20/40 vision by 50%; quadrantic PRP decreases risk for vitreous hemorrhage by >50%
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| Central retinal vein occlusion (CRVO): no benefit found for FML or prophylactic PRP in preventing neovascularization
of iris (NVI); can wait until NVI develops, as long as patient complies with regimen of monthly examinations; NVI
more common with CRVO than with BRVO or hemiretinal vein occlusion
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| Clinical signs of ischemic CRVO: severe vision loss, afferent pupillary defect, dense confluent hemorrhage, and severe
venous tortuosity
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| Nonischemic CRVO: severe venous tortuosity, engorgement, and delayed arteriovenous transit time; consider in differential
diagnosis for cystoid macular edema; systemic bevacizumab (Avastin) sometimes used as treatment, but
may cause transient ischemic attack
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| Disc collaterals: risk in longstanding CRVO; differentiate from congenital prepapillary loops, that extend into vitreous
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| Other retinal vascular diseases
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| Macroaneurysm: natural history includes autosclerosis, regression, and fibrosis, with spontaneous improvement of macular
edema; saccular dilatations of large-caliber arterioles; include in differential diagnosis of conditions that produce
hemorrhage at pre-, intra-, and subretinal levels; use light touch with focal treatment (longer duration, lower energy
setting, and larger spot size than usual)
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| Coats’ disease: peripheral telangiectasia; usually unilateral in men, sometimes bilateral in women; longstanding macular
edema may produce fibrotic scars; “lightbulb” aneurysms and profuse lipid exudation in subretinal space may occur
in young men; lipid deposits and large exudative detachments also possible; fluid removal recommended (even if
eye blind) to prevent painful disease progression; laser treatment of aneurysms appropriate in earlier stages; leukocoria
may occur in pediatric patients
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| Leber’s miliary aneurysms (milder form of Coats’ disease): unilateral retinal vasculopathy in men with few other signs of retinal
vascular disease; circinate patterns of exudation and lightbulb aneurysms present, but no subretinal exudation
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| Type 1 idiopathic juxtafoveal retinal telangiectasis (IJT): mildest form of Coats’ disease; occurs unilaterally, in men ≈30
yr of age; in temporal region; large, plump microaneurysms with circinate pattern of exudation; easily treated with laser;
type 2 IJT very different (variant in diabetes; occurs in older people of both sexes; aneurysms difficult to see, with
no circinate pattern; resists laser treatment; subretinal neovascular membranes common complication)
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| Peripheral neovascularization: various causes, including diabetes, venous occlusive disease, salmon-patch hemorrhage,
and sickle cell disease
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| Sickle cell retinopathy: may occur in homozygous (SS) or hemoglobin-C (SC) form; SS more debilitating systemically,
but SC more likely to affect the retina; proliferative—arteriovenous anastomotic occlusion, neovascularization,
hemorrhage, and detachment; nonproliferative—iridescent spots, salmon-patch hemorrhage, and black
sunburst sign
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| Retinopathy of prematurity (ROP): histopathology similar to that of sickle cell disease
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| Stage 0: no demarcation (no retinopathy)
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| Stage 1: line of demarcation flat
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| Stage 2: line has height, width, and depth (ridge)
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| Stage 3: elevated ridge, with fibrovascular fronds and preretinal hemorrhage
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| Stage 4: partial retinal detachment
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| Stage 5: total retinal detachment
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| Other considerations: rule out plus disease (venous tortuosity and dilatation; posterior form more significant than peripheral);
structurally unfavorable outcomes include retinal detachment, macular folds, and retrolental fibroplasia; cryotherapy
can reduce risk for structural outcomes by 25% to 50% at 10 yr (does not increase chances of optimal
outcome); risk for retinal detachment persists as patients age
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| Familial exudative vitreoretinopathy (FEVR): can mimic ROP; consists of disc dragging, temporal vessel dragging, nonperfusion
with temporal fibrovascular proliferation in patient with no history of prematurity; autosomal dominant condition;
patients develop bilateral picture resembling ROP, with risk for exudation and vitreous hemorrhage
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| Incontinentia pigmenti: abnormalities resembling those from FEVR or ROP, but with no history of prematurity; other
signs include skin and systemic abnormalities
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| Hypercoagulable states: can cause bilateral CRVO or venous occlusion, or peripheral neovascularization
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| Age-related macular degeneration (ARMD): chief cause of blindness in elderly; affects 10 million people, including 1 to
2 million with wet or atrophic form; most patients develop choroidal neovascularization (CNV)
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| Stages identified in Age-Related Eye Disease Study (AREDS)
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| Stages 1 and 2: dry form of ARMD; low risk for vision loss; 5-yr risk for CNV 1%; small drusen <3000 µ from fovea
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| Stage 3: high-risk dry ARMD; treat with vitamins; CNV risk 17% to 18% in same eye
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| Stage 4: 40% risk for CNV in contralateral eye; AREDS showed that antioxidant vitamins and zinc in doses 10 to 100
times recommended daily allowance can decrease risk for CNV and vision loss at stages 3 and 4; note—high doses
of vitamin A may increase risk for lung cancer in smokers, and high doses of vitamin E may increase risk for heart
disease in some people; use caution when recommending supplements
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| CHOROIDAL NEOVASCULARIZATION
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| Background: goal to treat as early as possible; occult type develops under retinal pigment epithelium (RPE); classic type
develops under macula; symptoms include central scotoma, micropsia, macropsia, and metamorphopsia; patients in
stages 3 and 4 should have Amsler grid test; angiography recommended for symptomatic patients to determine location
of CNV (extrafoveal or subfoveal)
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| Macular photocoagulation study: argon laser ablation improved vision in patients with extrafoveal and juxtafoveal membranes
associated with ARMD, idiopathic CNV, or histoplasmosis; membrane must be >200 µ from fovea; 2-yr risk for
recurrence 50% in patients with extrafoveal membranes, leading to decline in vision despite treatment; recurrence rate
70% in patients with juxtafoveal membranes, making laser treatment impractical
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| Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Trial: actively dividing endothelial cells
take up injected benzoporphyrin-derivative dye (verteporfin); photodynamic laser selectively ablates CNV membrane; trial
demonstrated marginal but statistically significant prevention of moderate and severe vision loss; however, works mainly on
classic membranes (lesion >50% of complex), and treatment must be repeated because vessels grow back
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| Occult subfoveal membranes: most often associated with wet ARMD; no macular edema seen with serous pigmented epithelial
detachment (PED), but seen with fibrous PED, which carries worse prognosis (however, may be more amenable
to treatment than serous PED); with photodynamic therapy (PDT), vision declines more quickly with occult than classic
membranes, probably function of membrane size; in Verteporfin in Photodynamic Therapy (VIP) study, PDT effective
on occult membranes <4 disc areas in size, but loses efficacy thereafter
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| Intravitreal therapies: pegaptanib (Macugen) inhibits angiogenesis; binds directly to VEGF-165 isomer in eye; administered
in series of injections; approved by Food and Drug Administration in December 2005; slows vision loss, but
<10% of patients experience significant visual improvement; associated with vision decline; membranes continue to
grow in size and leakage area, although more slowly than without drug (addition of antibody-based therapies may
stabilize or even improve vision)
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| Other causes of CNV membranes
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| Presumed ocular histoplasmosis
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| Myopia: membrane may regress spontaneously, leaving Fuch’s spot; pathologic myopia sometimes associated with
nummular atrophy; VIP-Pathological Myopia (VIP-PM) trial showed benefit of PDT in preventing vision loss and
improving vision
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| Angioid streaks: main cause pseuodoxanthoma elasticum, with calcified RPE prone to hemorrhaging and scarring;
treatment difficult due to high propensity for recurrence; other causes include Ehlers-Danlos syndrome, Paget’s disease,
and sickle cell disease; many cases idiopathic; temporoposterior peau d’orange skin classic sign
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| Subretinal fluid: sometimes associated with CNV membranes
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| Central serous retinopathy (CSR): large volume of subretinal fluid; angiography shows inkblot (90% of cases) and
smokestack leaks (10% of cases); large neurosensory detachment not uncommon; fibrin sometimes associated with
leaks in pregnant patients or people taking steroids
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| Risk factors: type A personality, hypertension, pregnancy, and steroid use
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| Chronic changes: diffuse leak-associated RPE mottling; gravitational troughs from fluid accumulation when patient supine;
indocyanine green dye can reveal choroidal leakage; tomography also helpful; treatment should involve removing
fluid and drying area
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| Older patients: CSR may resemble CNV membrane; CNV usually contains heme and has lacy irregular appearance vs
homogeneous inkblot or smokestack look of CSR
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| Other causes: idiopathic polyploidal choroidal vasculopathy (IPCV; saccular choroidal aneurysms usually seen in nasal
macula; bleed easily); degenerative CNV membranes; inflammatory diseases (Vogt-Koyanagi-Harada syndrome); toxemia
of pregnancy (hemolysis, elevated liver enzymes, and low platelet count [HELLP syndrome]); congenital disc
anomalies (pit or coloboma); choroidal mass lesions from tumor metastases; retinal vascular disease (signals RPE-
Brooks choriocapillaris disturbance; occurs in 20% of diabetics with macular edema)
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Educational Objectives
| The goal of this program is to review the causes and treatment of retinal disorders. After hearing and assimilating this program,
the listener will be able to
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| 1. Name the stages of hypertensive retinopathy.
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| 2. Describe the major forms of retinal arterial occlusion.
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| 3. Identify the major cause and characteristics of retinal venous occlusion.
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| 4. List other common retinal vascular diseases.
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| 5. Explain the findings of the Age-Related Eye Disease (ARED), Treatment of Age-Related Macular Degeneration
with Photodynamic Therapy (TAP), Verteporfin in Photodynamic Therapy (VIP), and VIP-Pathological Myopia
(VIP-PM) trials.
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Discussed on this Program
Acetazolamide [Dazamide, Diamox, Diamox Sequels]
Bevacizumab [Avastin]
Interferon alpha [Veldona Lozenge]
Interferon beta-1a (recombinant) [Avonex, Rebif]
Interferon beta-1b [Betaseron]
Pegaptanib sodium [Macugen]
Ranibizumab (RhuFab V2) [Lucentis]
Triamcinolone acetonide [several preparations and trade names]
Verteporfin [Visudyne]
Suggested Reading
No authors listed: Vitamin E gets an F. Research linking high doses of vitamin E to heart failure is causing new worries
about the AREDS vitamins for macular degeneration. Harv Health Lett 30:6, 2005; Arnold JJ et al: Acute severe visual
acuity decrease after photodynamic therapy with verteporfin: case reports from randomized clinical trials-TAP and VIP report
no. 3. Am J Ophthalmol 137:683, 2004; Branch Vein Occlusion Study Group: Argon laser photocoagulation for
macular edema in branch vein occlusion. Am J Ophthalmol 98:271, 1984; Dhalla MS et al: Combined photodynamic therapy
in subfoveal and juxtafoveal idiopathic and postinflammatory choroidal neovascularization. Retina 26:988, 2006; Erdinc
A, Ozdek SC: Intravitreal triamcinolone compared with macular laser grid photocoagulation for the treatment of
cystoid macular edema. Am J Ophthalmol 142:197, 2006; Evans JR: Antioxidant vitamin and mineral supplements for
slowing the progression of age-related macular degeneration. Cochrane Database Syst Rev 19: CD000254, 2006; Harding
S: Photodynamic therapy in the treatment of subfoveal choroidal neovascularization. Eye 15:407, 2001; Kaiser PK,
Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP) Study Group: Verteporfin therapy
of subfoveal choroidal neovascularization in age-related macular degeneration: 5-year results of two randomized clinical
trials with an open-label extension: TAP Report No. 8. Graefes Arch Clin Exp Ophthalmol 244:1132, 2006; Karacorlu
SA et al: Optical coherence tomography after photodynamic therapy for patients with pathological myopia. Retina 26:752,
2006; Mandell MA, Sharma S: Ophthaproblem. Central retinal vein obstruction. Can Fam Physician 51:1627, 2005; Pece
A et al: Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization secondary to pathologic myopia:
long-term study. Retina 26:746, 2006; Ruiz-Moreno JM et al: Photodynamic therapy in subfoveal and juxtafoveal idiopathic
and postinflammatory choroidal neovascularization. Acta Ophthalmol Scand 84:743, 2006; Schmidt-Erfurth U: Indocyanine
green angiography and retinal sensitivity after photodynamic therapy of subfoveal choroidal neovascularization.
Semin Ophthalmol 14:35, 1999; Schwartz SG et al: Bilateral CRAO and CRVO from thrombotic thrombocytopenic purpura:
OCT findings and treatment with triamcinolone acetonide and bevacizumab. Ophthalmic Surg Lasers Imaging
37:420, 2006; Zumbro DS et al: Diagnostic and therapeutic challenges. Retina 26:571, 2006.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. For this issue, the following
has been disclosed: Dr. Sarraf has been a one-time consultant for Eyetech Pharmaceuticals and Novartis.
Dr. Sarraf spoke at the Comprehensive Ophthalmology Review Course, held March 10-12, 2006, in Los Angeles, CA, and
sponsored by the Jules Stein Eye Institute, David Geffen School of Medicine at the University of California, Los Angeles, and
the Doheny Eye Institute, Keck School of Medicine at the University of Southern California. The Audio-Digest Foundation
thanks Dr. Sarraf and the sponsors for their cooperation in the production of this program.
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