10
Retina and Choroid
Branch Retinal Artery Occlusion
Central Retinal Artery Occlusion
Central / Hemiretinal Vein Occlusion
Coats’ Disease / Leber’s Miliary Aneurysms
Familial Exudative Vitreoretinopathy and Norrie’s Disease
Retinopathies Associated with Blood Abnormalities
Acquired Retinal Arterial Macroaneurysm
Age-Related Macular Degeneration
Retinal Angiomatous Proliferation
Polypoidal Choroidal Vasculopathy
Myopic Degeneration / Pathologic Myopia
Central Serous Chorioretinopathy
Vitreomacular Adhesion and Traction
Epiretinal Membrane / Macular Pucker
Peripheral Retinal Degenerations
Proliferative Vitreoretinopathy
Intermediate Uveitis / Pars Planitis
Posterior Uveitis: White Dot Syndromes
Posterior Uveitis: Other Inflammatory Disorders
Posterior Uveitis: Evaluation / Management
Hereditary Chorioretinal Dystrophies
Hereditary Macular Dystrophies
Trauma
Choroidal Rupture
Tear in choroid, Bruch’s membrane, and retinal pigment epithelium (RPE) is usually seen after blunt trauma. Acutely, the rupture site may be obscured by hemorrhage; scars form over 3–4 weeks with RPE hyperplasia at the margin of the rupture site. Anterior ruptures are usually parallel to the ora serrata; posterior ruptures are usually crescent-shaped and concentric to the optic nerve. Patients may have decreased vision if commotio retinae or subretinal hemorrhage is present, or if the rupture is located in the macula; increased risk of developing a choroidal neovascular membrane (CNV) during the healing process (months to years after trauma). Good prognosis if the macula is not involved, but poor if the fovea is involved.
• No treatment recommended, unless CNV occurs.
• Laser photocoagulation of juxtafoveal and extrafoveal CNV; consider anti-VEGF agent for subfoveal CNV (experimental).
• Monitor for CNV with Amsler grid.
Commotio Retinae (Berlin’s Edema)
Gray-white discoloration of the outer retina due to photoreceptor outer segment disruption following blunt eye trauma; can affect any area of the retina and may be accompanied by hemorrhages or choroidal rupture. There is no intercellular edema; whitening is due to intracellular edema and disorganization of outer retinal layers. It is termed Berlin’s edema if involving the macula, and commotion retinae in all other areas. Can cause acute decrease in vision if located within the macula, which resolves as the retinal discoloration disappears; may cause permanent loss of vision if the fovea is damaged, but usually resolves without sequelae. Visual acuity does not always correlate with the degree of retinal whitening seen on exam. Occasionally, a macular hole can form in the area of commotio with variable prognosis.
• Fluorescein angiogram: Early blocked fluorescence in the areas of commotio retinae.
• No treatment recommended.
Purtscher’s Retinopathy
Multiple patches of retinal whitening, large cotton-wool spots, and hemorrhages that surround the optic disc following multiple long-bone fractures with fat emboli or severe compressive injuries to the chest or head. May have optic disc edema and a relative afferent pupillary defect (RAPD). Usually resolves over weeks to months.
In the absence of trauma, a Purtscher’s-like retinopathy may be associated with acute pancreatitis, collagen–vascular disease, leukemia, dermatomyositis, and amniotic fluid embolus.
Figure 10-4 Multiple patches of retinal whitening, cotton-wool spots, and intraretinal hemorrhages secondary to Purtscher’s retinopathy.
• Fluorescein angiogram: Leakage from retinal vasculature with late venous staining.
• No treatment recommended.
Traumatic Retinal Holes
Full-thickness tear in the retina, often horseshoe shaped; usually occurs along the vitreous base, posterior border of lattice degeneration, or at cystic retinal tufts (areas with strong vitreoretinal adhesions). As most patients are young, the formed vitreous tamponades the tear and prevents a retinal detachment. Associated with pigmented vitreous cells (“tobacco-dust”, also known as Schaffer’s sign), vitreous hemorrhages, operculum (often located over the retinal hole), and posterior vitreous detachment. Patients usually report photopsias and floaters that shift with eye movement. Liquefied vitreous can pass through the tear into the subretinal space, causing retinal detachment even months to years after the tear forms; chronic tears have a ring of pigment around the retinal hole.
Giant Retinal Tear
Traumatic retinal hole measuring > 90° in circumferential extent or > 3 clock hours.
Avulsion of Vitreous Base
Separation of vitreous base from ora serrata that is pathognomonic for trauma.
Oral Tear
Tear at the ora serrata due to split of vitreous that has a fish-mouth appearance.
Preoral Tear
Tear at anterior border of vitreous base most often occurs superotemporally.
Retinal Dialysis
Most common form after trauma; circumferential separation of the retina at the ora serrata, usually in superotemporal (22%) or inferotemporal (31%) quadrant. Risk of retinal detachment increases over time with 10% at initial examination and 80% by 2 years.
• Retinal surgery required if rhegmatogenous retinal detachment, retinal dialysis, avulsion of the vitreous base, or giant retinal tear exists; should be performed by a retina specialist.
Chorioretinitis Sclopeteria
Trauma to retina and choroid caused by transmitted shock waves from high-velocity projectile that causes choroidal rupture, retinal hemorrhages, and commotio retinae. Vitreous hemorrhage is common. Lesions heal with white fibrous scar and RPE changes. Low risk of retinal detachment in young patients with a formed vitreous; however, the appearance can simulate retinal detachment in these patients.
Figure 10-7 Chorioretinitis sclopeteria with subretinal hemorrhage and commotio retinae (same patient as Figure 1-6).
Hemorrhages
Preretinal Hemorrhage
Hemorrhage located between the retina and posterior vitreous face (subhyaloid) or under the internal limiting membrane of the retina (sub-ILM). Often amorphous or boat-shaped, with flat upper border and curved lower border, which obscures the underlying retina. Caused by trauma, retinal neovascularization (diabetic retinopathy, radiation retinopathy, breakthrough bleeding from a choroidal neovascular membrane), hypertensive retinopathy, Valsalva retinopathy, retinal artery macroaneurysm, posterior vitreous detachment, shaken-baby syndrome, or retinal breaks, and less frequently by vascular occlusion, retinopathy of blood disorders, or leukemia.
Intraretinal Hemorrhage
Bilateral intraretinal hemorrhages are associated with systemic disorders (e.g., diabetes mellitus and hypertension); unilateral intraretinal hemorrhages generally occur in venous occlusive diseases or ocular ischemic syndrome.
Flame-Shaped Hemorrhage
Located in the superficial retina oriented with the nerve fiber layer; feathery borders. Usually occurs in hypertensive retinopathy and vein occlusion; may be peripapillary in glaucoma, especially in normal-tension glaucoma (splinter hemorrhage) and disc edema.
Dot / Blot Hemorrhage
Located in the outer plexiform layer, confined by the anteroposterior orientation of the photoreceptor, bipolar, and Müller’s cells; round dots or larger blots. Usually occurs in diabetic retinopathy.
Roth Spot
Hemorrhage with white center that represents an embolus with lymphocytic infiltration. Classically associated with subacute bacterial endocarditis (occurs in 1–5% of such patients); also occurs in leukemia, severe anemia, sickle cell disease, collagen vascular diseases, diabetes mellitus, multiple myeloma, and acquired immunodeficiency syndrome (AIDS) (see Figures 10-40, 10-43).
Subretinal Hemorrhage
Amorphous hemorrhage located under the neurosensory retina or RPE; appears dark and is deep to the retinal vessels. Associated with trauma, subretinal and choroidal neovascular membranes, and macroaneurysms (see Figure 10-71).
All three types of hemorrhages may occur together in several disorders including age-related macular degeneration (AMD), acquired retinal arterial macroaneurysm, Eales’ disease, and capillary hemangioma.
Cotton-Wool Spot
Asymptomatic, yellow-white, fluffy lesions in the superficial retina (see Figure 10-4). Nonspecific finding due to multiple etiologies including: retinal ischemia (retinal vascular occlusions, severe anemia, ocular ischemic syndrome), emboli (Purtcher’s retinopathy [white blood cell emboli], intravenous drug abuse [talc], cardiac/carotid emboli, deep venous emboli), infections (acquired immunodeficiency syndrome, Rocky Mountain spotted fever, cat-scratch fever [Bartonella henselae], leptospirosis, onchocerciasis, bacteremia, fungemia), collagen vascular diseases (systemic lupus erythematosus, dermatomyositis, polyarteritis nordosa, scleroderma, giant cell arteritis), drugs (interferon, chemotherapeutic agents), neoplasms (lymphoma, leukemia, metastatic carcinoma, multiple myeloma), retinal traction (epiretinal membrane), trauma (nerve fiber layer laceration, long-bone fractures, severe chest compression [white blood cell emboli]), systemic diseases (acute pancreatitis, hypertension, diabetes mellitus, high-altitude retinopathy), and radiation. Appears as thickening of the nerve fiber layer on OCT. Thought to develop secondary to obstruction of a retinal arteriole with resultant ischemia leading to blockage of axoplasmic flow within the nerve fiber layer.
• Treat underlying etiology (identified in 95% of cases).
Branch Retinal Artery Occlusion
Definition
Disruption of the vascular perfusion in a branch of the central retinal artery, leading to focal retinal ischemia.
Etiology
Mainly due to embolism from cholesterol (Hollenhorst’s plaques), calcifications (heart valves), platelet–fibrin plugs (ulcerated atheromatous plaques due to arteriosclerosis); rarely due to leukoemboli (vasculitis, Purtcher’s retinopathy), fat emboli (long-bone fractures), amniotic fluid emboli, tumor emboli (atrial myxoma), or septic emboli (heart valve vegetations in bacterial endocarditis or IV drug abuse). The site of the obstruction is usually at the bifurcation of retinal arteries. May result from vasospasm (migraine), compression, or coagulopathies.
Epidemiology
Usually occurs in elderly patients (seventh decade); associated with hypertension (67%), carotid occlusive disease (25%), diabetes mellitus (33%), and cardiac valvular disease (25%). CRAO is more common (57%) than BRAO (38%) or cilioretinal artery occlusion (5%) (in 32% of eyes, a cilioretinal artery is present).
Symptoms
Sudden, unilateral, painless, partial loss of vision, with a visual field defect corresponding to the location of the occlusion. May have history of amaurosis fugax (fleeting episodes of visual loss), prior cerebrovascular accident (CVA), or transient ischemic attacks (TIAs).
Signs
Visual field defect with normal or decreased visual acuity; focal, wedge-shaped area of retinal whitening within the distribution of a branch arteriole; 90% involve temporal retinal vessels; emboli (visible in 62% of cases) or Hollenhorst’s plaques may be visible at retinal vessel bifurcations. Retinal whitening resolves over several weeks and visual acuity can improve. In chronic stages, arterial attenuation with sector nerve fiber layer loss may be seen; artery-to-artery collaterals may form and are pathognomonic.
Figure 10-13 Superior branch artery occlusion demonstrating retinal edema.
Figure 10-14 Fluorescein angiogram of same patient as Figure 10-13 demonstrating no filling of superior retinal vessels and delayed filling of affected veins.
Differential Diagnosis
Commotio retinae, branch retinal vein occlusion, CRAO with cilioretinal artery sparing, combined artery and vein occlusion.
Evaluation
• Check blood pressure.
• Lab tests: Fasting blood glucose (FBS), glycosylated hemoglobin, and complete blood count (CBC) with differential. Consider platelets, prothrombin time/partial thromboplastin time (PT / PTT), protein C, protein S, factor V Leiden mutation, antithrombin III, homocysteine level, antinuclear antibody (ANA), rheumatoid factor (RF), sickle cell disease, antiphospholipid antibody, serum protein electrophoresis, hemoglobin electrophoresis, Venereal Disease Research Laboratory (VDRL) test, and fluorescent treponemal antibody absorption (FTA-ABS) test in patients < 50 years of age. In patients > 50 years old, check erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to rule out arteritic ischemic optic neuropathy due to giant cell arteritis. If positive and / or if the patient’s history and exam are consistent, start giant cell arteritis treatment immediately (see Chapter 11). If the BRAO is accompanied by optic nerve edema and / or retinitis, consider serologic testing for infectious etiologies such as Bartonella, Lyme, and toxoplasmosis.
• Fluorescein angiogram: Delayed or absent retinal arterial filling in a branch of the central retinal artery; delayed arteriovenous transit time; capillary nonperfusion in wedge-shaped area supplied by the branch artery; staining of occlusion site and vessel wall in late views. When occlusion dissolutes, retinal blood flow is usually restored.
• Optical coherence tomography (OCT): Thickened and hyperreflective inner retinal layers during acute occlusion that corresponds to intracellular edema. Reflectivity of outer retina is blocked. Later, the retina is thinned with atrophy of the inner retina.
• Consider B-scan ultrasonography or orbital computed tomography (CT) scan to rule out a compressive lesion if the history suggests this etiology.
• Medical consultation for complete cardiovascular evaluation including baseline electrocardiogram, echocardiogram (may require transesophageal echocardiogram to rule out valvular disease), and carotid Doppler ultrasonography.
• In patients < 50 years of age, a hypercoagulability evaluation should be considered.
Prognosis
Retinal pallor fades and circulation is restored over several weeks. Good if fovea is spared; 80% have ≥ 20 / 40 vision, but most have some degree of permanent visual field loss; 10% risk in fellow eye.
Central Retinal Artery Occlusion
Definition
Disruption of the vascular perfusion in the central retinal artery (CRAO) leading to global retinal ischemia.
Etiology
Due to emboli (only visible in 20–40% of cases) or thrombus at the level of the lamina cribosa; other etiologies are the same as for BRAO including temporal arteritis, leukoemboli in collagen vascular diseases, fat emboli, trauma (through compression, spasm, or direct vessel damage), hypercoagulation disorders, syphilis, sickle cell disease, amniotic fluid emboli, mitral valve prolapse, particles (talc) from IV drug abuse, and compressive lesions; associated with optic disc drusen, papilledema, prepapillary arterial loops, and primary open-angle glaucoma.
Epidemiology
Usually occurs in elderly patients; associated with hypertension (67%), carotid occlusive disease (25%), diabetes mellitus (33%), and cardiac valvular disease (25%). CRAO is more common (57%) than BRAO (38%) or cilioretinal artery occlusion (5%) (in 32% of eyes, a cilioretinal artery is present); rarely bilateral.
Symptoms
Sudden, unilateral, painless, profound loss of vision; may have history of amaurosis fugax (fleeting episodes of visual loss), prior CVA, or TIAs.
Signs
Decreased visual acuity in the count fingers (CF) to light perception (LP) range; RAPD may be present; diffuse retinal whitening and arteriole constriction with segmentation (boxcaring) of blood flow; visible emboli (20–40%) rarely occur in central retinal artery; cherry-red spot in the macula (thin fovea allows visualization of the underlying choroidal circulation). In ciliary retinal artery sparing CRAO (25%), a small wedge-shaped area of perfused retina may be present temporal to the optic disc (10% spare the foveola, in which case visual acuity improves to 20 / 50 or better in 80%). Note: Ophthalmic artery obstruction usually does not produce a cherry-red spot owing to underlying choroidal ischemia.
Figure 10-17 Cilioretinal artery sparing central retinal artery occlusion with patent cilioretinal artery allowing perfusion (thus no edema) in a small section of the macula.
Figure 10-18 Fluorescein angiogram of same patient in Figure 10-17 demonstrating no filling of retinal vessels except in cilioretinal artery and surrounding branches.
Differential Diagnosis
Ophthalmic artery occlusion, commotio retinae, cherry-red spot due to inherited metabolic or lysosomal storage diseases, methanol toxicity.
Evaluation
• Check blood pressure.
• Lab tests: Fasting blood glucose (FBS), glycosylated hemoglobin, and complete blood count (CBC) with differential. Consider platelets, prothrombin time/partial thromboplastin time (PT / PTT), protein C, Protein S, factor V Leiden mutation, antithrombin III, homocysteine level, antinuclear antibody (ANA), rheumatoid factor (RF), sickle cell disease, antiphospholipid antibody, serum protein electrophoresis, hemoglobin electrophoresis, Venereal Disease Research Laboratory (VDRL) test, and fluorescent treponemal antibody absorption (FTA-ABS) test in patients < 50 years of age. In patients > 50 years old, check erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to rule out arteritic ischemic optic neuropathy due to giant cell arteritis. If positive and /or if the patient’s history and exam are consistent, start giant cell arteritis treatment immediately (see Chapter 11). If the CRAO is accompanied by optic nerve edema and /or retinitis consider serologic testing for infectious etiologies such as Bartonella, Lyme disease, and toxoplasmosis.
• Fluorescein angiogram: Delayed retinal arterial filling and arteriovenous transit time with normal choroidal filling and perfusion of optic nerve from ciliary branches; prolonged arteriovenous circulation times; extensive capillary nonperfusion.
• Optical coherence tomography: Thickened and hyperreflective inner retinal layers during acute occlusion that corresponds to intracellular edema. Reflectivity of outer retina is blocked. Later, the retina is thinned with atrophy of the inner retina.
• Electrophysiologic testing: ERG (reduced b-wave amplitude, normal a-wave).
• Consider B-scan ultrasonography or orbital CT scan to rule out compressive lesion if history suggests compression.
• Medical consultation for complete cardiovascular evaluation including electrocardiogram, echocardiogram (may require transesophageal echocardiogram to rule out valvular disease), and carotid Doppler ultrasound.
Management
• Treat immediately before starting workup (if patient presents within 24 hours of visual loss), but best hope is to treat within 90 minutes.
• Digital ocular massage to try to dislodge emboli.
• Systemic acetazolamide (Diamox 500 mg IV or po).
• Topical ocular hypotensive drops: β-blocker (timolol 0.5% 1 gtt q15min × 2, repeat as necessary).
• Anterior chamber paracentesis (immediately lowers IOP to 0 mmHg): This procedure is easily performed at the slit lamp after prepping the eye with topical anesthetic, broad-spectrum antibiotic, and povidone-iodine. A lid speculum is placed, the eye is grasped with forceps at the nasal limbus to prevent movement and provide counter-traction, and either a disposable microsurgical knife (15° or MVR blade) or else a 30-gauge 
inch (13 mm) needle on a 1 mL syringe without the plunger, is inserted parallel to the iris through the peripheral cornea at the temporal limbus. If necessary, gentle pressure can be applied to the posterior lip of the paracentesis site so that aqueous can be released in a controlled fashion. Treat with a topical broad-spectrum antibiotic (gatifloxacin [Zymaxid] or moxifloxacin [Vigamox] qid for 3 days).
• Consider admission to hospital for carbogen treatment (95% oxygen–5% carbon dioxide for 10 minutes q2h for 24–48 hours) to attempt to increase oxygenation and induce vasodilation.
• Unproven treatments include hyperbaric oxygen, antifibrinolytic drugs, retrobulbar vasodilators, sublingual nitroglycerine, and Nd : YAG laser to dislodge the emboli.
• If arteritic anterior ischemic optic neuropathy (see Chapter 11) is suspected: Systemic steroids (methylprednisolone 1 g IV qd in divided doses for 3 days, then prednisone at least 1 mg / kg po qd for at least a month with a very slow taper; decrease by no more than 2.5 mg /wk). Most patients will require a year of high-dose steroid treatment.
Prognosis
Retinal pallor fades and circulation is restored over several weeks. Poor prognosis; most have persistent severe visual loss with constricted retinal arterioles and optic atrophy. Rubeosis (20%) and disc /retinal neovascularization (2–3%) can rarely occur. Presence of visible embolus associated with increased mortality; most common cause of mortality is myocardial infarction.
Ophthalmic Artery Occlusion
Definition
Obstruction at the level of the ophthalmic artery that affects both the retinal and choroidal circulation leading to ischemia more severe than CRAO.
Etiology
Usually due to emboli or thrombus, but can be caused by any of the etiologies listed for CRAO.
Epidemiology
Usually occurs in elderly patients; associated with hypertension (67%), carotid occlusive disease (25%), diabetes mellitus (33%), and cardiac valvular disease (25%).
Symptoms
Sudden, unilateral, painless, profound loss of vision up to the level of light perception or even no light perception.
Signs
Marked constriction of the retinal vessels, marked retinal edema often without a cherry red spot (although it may be present); may have RAPD; later, optic atrophy, retinal vascular sclerosis, and diffuse pigmentary changes.
Differential Diagnosis
Central retinal artery occlusion, commotio retinae, cherry-red spot due to inherited metabolic or lysosomal storage diseases, methanol toxicity.
Evaluation
• Check blood pressure.
• Lab tests: Fasting blood glucose (FBS), glycosylated hemoglobin, and complete blood count (CBC) with differential. Consider platelets, prothrombin time/partial thromboplastin time (PT / PTT), protein C, Protein S, factor V Leiden mutation, antithrombin III, homocysteine level, antinuclear antibody (ANA), rheumatoid factor (RF), sickle cell disease, antiphospholipid antibody, serum protein electrophoresis, hemoglobin electrophoresis, Venereal Disease Research Laboratory (VDRL) test, and fluorescent treponemal antibody absorption (FTA-ABS) test in patients < 50 years of age. In patients > 50 years old, check erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to rule out arteritic ischemic optic neuropathy due to giant cell arteritis. If positive and / or if the patient’s history and exam are consistent, start giant cell arteritis treatment immediately (see Chapter 11).
• Fluorescein angiogram: Delayed or absent choroidal and retinal vascular filling, extensive capillary nonperfusion.
• Electrophysiologic testing: ERG (reduced or absent a and b wave amplitudes).
• Medical consultation for complete cardiovascular evaluation including electrocardiogram, echocardiogram (may require transthoracic echocardiogram to rule out valvular disease), and carotid Doppler ultrasound.
Prognosis
Severe visual loss is usually permanent.
Branch Retinal Vein Occlusion
Definition
Occlusion of a branch retinal vein (BRVO). Two types:
Nonischemic (64%)
< 5 disc areas of capillary nonperfusion on fluorescein angiogram.
Ischemic
≥ 5 disc areas of capillary nonperfusion on fluorescein angiogram.
Etiology
Usually caused by a thrombus at arteriovenous crossings where a thickened artery compresses the underlying venous wall due to a common vascular sheath; associated with hypertension, coronary artery disease, diabetes mellitus, and peripheral vascular disease; rarely associated with hypercoagulable states (e.g., macroglobulinemia, cryoglobulinemia), hyperviscosity states (polycythemia vera, Waldenström’s macroglobulinemia), systemic lupus erythematosus, syphilis, sarcoid, homocystinuria, malignancies (e.g., multiple myeloma, polycythemia vera, leukemia), optic nerve drusen, and external compression. In younger patients, associated with oral contraceptive pills, collagen vascular disease, AIDS, protein S /protein C /antithrombin III deficiency, factor XII (Hageman factor) deficiency, antiphospholipid antibody syndrome, or activated protein-C resistance (factor V Leiden PCR assay).
Epidemiology
Usually occurs in elderly patients, 60–70 years old; associated with hypertension (50–70%), cardiovascular disease, diabetes mellitus, increased body mass index, and open-angle glaucoma; slight male and hyperopic predilection. Second most common vascular disease after diabetic retinopathy.
Symptoms
Sudden, unilateral, painless, visual field loss. Patients may have normal vision, especially when macula is not involved.
Signs
Quadrantic visual field defect; dilated, tortuous retinal veins with superficial, retinal hemorrhages, and cotton-wool spots in a wedge-shaped area radiating from an arteriovenous crossing (usually arterial over-crossing where an arteriole and venule share a common vascular sheath). More common superotemporally (60%) than inferotemporally (40%; rare nasally since usually asymptomatic). The closer the obstruction is to the optic disc, the greater the area of retina involved and the more serious the complications. Microaneurysms or macroaneurysms, macular edema (50%), epiretinal membranes (20%), retinal and /or iris /angle neovascularization (very rare), and vitreous hemorrhage may develop; neovascular glaucoma is rare.
Figure 10-19 Inferior branch retinal vein occlusion demonstrating wedge-shaped area of intraretinal hemorrhages and cotton-wool spots.
Figure 10-20 Fluorescein angiogram of same patient as Figure 10-19 demonstrating lack of perfusion in inferior retinal vein with blocking defects from the intraretinal hemorrhages. Site of occlusion is shown with an arrowhead.
Differential Diagnosis
Venous stasis retinopathy, ocular ischemic syndrome, hypertensive retinopathy, leukemic retinopathy, retinopathy of anemia, diabetic retinopathy, papilledema, papillophlebitis (in young patients).
Evaluation
• Check visual fields.
• Check blood pressure.
• Lab tests: Fasting blood glucose, glycosylated hemoglobin; consider CBC with differential, platelets, PT / PTT, ANA, RF, angiotensin converting enzyme (ACE), ESR, serum protein electrophoresis, lipid profile, hemoglobin electrophoresis (in African Americans), VDRL, and FTA-ABS depending on clinical situation. In a patient < 40 years old and in whom a hypercoagulable state is being considered: check human immunodeficiency virus (HIV) status, functional protein S assay, functional protein C assay, functional antithrombin III assay (type II heparin-binding mutation), antiphospholipid antibody titer, lupus anticoagulant, anticardiolipin antibody titer (IgG and IgM), homocysteine level (if elevated test for folate, B12, and creatinine), factor XII (Hageman factor) levels, and activated protein C resistance (factor V Leiden mutation PCR assay); if these tests are normal and clinical suspicion for a hypercoagulable state still exists: add plasminogen antigen assay, heparin cofactor II assay, thrombin time, reptilase time, and fibrinogen functional assay.
• Fluorescein angiogram: Delayed retinal venous filling in a branch of the central retinal vein, increased transit time in affected venous distribution, blocked fluorescence in areas of retinal hemorrhages, and capillary nonperfusion (ischemic defined as ≥ 5 disc areas of capillary nonperfusion) in the area supplied by the involved retinal vein. Retinal edema with cystic changes is not present acutely, but appears later. Wide-field angiography is being used increasingly to visualize peripheral nonperfusion.
• Optical coherence tomography: Monitor for cystic macular edema and intraretinal swelling. Useful to monitor treatment response.
• Medical consultation for complete cardiovascular evaluation.
Prognosis
Central / Hemiretinal Vein Occlusion
Definition
Occlusion of the central retinal vein (CRVO); hemiretinal occlusion (HRVO) occurs when the superior and inferior retinal drainage does not merge into a central retinal vein (20%) and is occluded (more like CRVO than BRVO). Two types:
Nonischemic / Perfused (67%)
< 10 disc areas of capillary nonperfusion on fluorescein angiogram.
Ischemic / Nonperfused
≥ 10 disc areas of capillary nonperfusion on fluorescein angiogram.
Etiology
Usually caused by a thrombus in the area of the lamina cribosa; associated with hypertension (60%), coronary artery disease, diabetes mellitus, peripheral vascular disease, and primary open-angle glaucoma (40%); rarely associated with hypercoagulable states (e.g., macroglobulinemia, cryoglobulinemia), hyperviscosity states especially in bilateral cases (polycythemia vera, Waldenström’s macroglobulinemia), systemic lupus erythematosus, syphilis, sarcoid, homocystinuria, malignancies (e.g., multiple myeloma, polycythemia vera, leukemia), optic nerve drusen, and external compression. In younger patients, associated with oral contraceptive pills, collagen vascular disease, acquired immunodeficiency syndrome (AIDS), protein S /protein C /antithrombin III deficiency, factor XII (Hageman factor) deficiency, antiphospholipid antibody syndrome, or activated protein C resistance (factor V Leiden polymerase chain reaction [PCR] assay).
Epidemiology
Usually occurs in elderly patients (90% are > 50 years old); slight male predilection. Ischemic disease is more common in older patients and those with cardiovascular disease. Younger patients can get inflammatory condition termed papillophlebitis or benign retinal vasculitis with benign clinical course.
Symptoms
Sudden, unilateral, loss of vision or less frequently history of transient obscuration of vision with complete recovery. Some report pain and present initially with neovascularization of the iris and neovascular glaucoma following a loss of vision 3 months earlier (“90-day glaucoma”). Patients may have normal vision if perfused, especially when the macula is not involved.
Signs
Decreased visual acuity ranging from 20 / 20 to hand motion (HM) with most worse than 20 / 200 (vision worse in ischemic type; usually > 20/ 200 in nonischemic); dilated, tortuous retinal veins with superficial, retinal hemorrhages, and cotton-wool spots in all four quadrants extending to periphery; optic disc hyperemia, disc edema, and macular edema common; RAPD (degree of defect correlates with amount of ischemia). Nonischemic disease rarely produces neovascularization; ischemic disease can produce rubeosis (20% in CRVO, rare in BRVO), disc/retinal neovascularization (border of perfused/nonperfused retina), neovascular glaucoma, and vitreous hemorrhages. Collateral optociliary shunt vessels between retinal and ciliary circulations (50%) occur late. Impending CRVO may have absence of spontaneous venous pulsations (but this can also occur in normal individuals). Transient patchy ischemic retinal whitening may occur early in nonischemic CRVO.
Differential Diagnosis
Venous stasis retinopathy, ocular ischemic syndrome, hypertensive retinopathy, leukemic retinopathy, retinopathy of anemia, diabetic retinopathy, radiation retinopathy, and papilledema.
Evaluation
• Check blood pressure.
• Lab tests: Fasting blood glucose, glycosylated hemoglobin; consider CBC with differential, platelets, PT / PTT, ANA, RF, ACE, ESR, serum protein electrophoresis, lipid profile, hemoglobin electrophoresis (in African American), VDRL, and FTA-ABS depending on clinical situation. In a patient < 40 years old and in whom a hypercoagulable state is being considered: check human immunodeficiency virus (HIV) status, functional protein S assay, functional protein C assay, functional antithrombin III assay (type II heparin-binding mutation), antiphospholipid antibody titer, lupus anticoagulant, anticardiolipin antibody titer (IgG and IgM), homocysteine level (if elevated test for folate, B12, and creatinine), factor XII (Hageman factor) levels, and activated protein C resistance (factor V Leiden mutation PCR assay); if these tests are normal and clinical suspicion for a hypercoagulable state still exists: add plasminogen antigen assay, heparin cofactor II assay, thrombin time, reptilase time, and fibrinogen functional assay.
• Fluorescein angiogram: Delayed retinal venous filling, increased transit time (> 20 seconds increases risk of rubeosis), extensive capillary nonperfusion (ischemic defined in CVOS as ≥ 10 disc areas of capillary nonperfusion), staining of vascular walls, and blocking defects due to retinal hemorrhages. Retinal edema with cystic changes that are not present acutely, but appear later. Wide-field angiography is being used increasingly to visualize peripheral nonperfusion.
• Optical coherence tomography: monitor for cystic macular edema and intraretinal swelling. Useful to monitor treatment response.
• Electrophysiologic testing: ERG (reduced b wave amplitude [< 60% of normal more likely ischemic], reduced b : a-wave ratio [< 1 associated with increased risk of ischemia and neovascularization], prolonged b-wave implicit time).
• Medical consultation for complete cardiovascular evaluation.
Prognosis
Clinical course is variable; evaluate monthly for first 6 months. Nonischemic type has better prognosis (10% will completely resolve). Risk of neovascularization depends on amount of ischemia (CVOS conclusion); 16% of nonischemic patients progress to ischemic disease; 60% of ischemic patients develop neovascularization and 33% develop neovascular glaucoma.
Venous Stasis Retinopathy
Milder form of nonischemic central retinal vein occlusion (CRVO) representing patients with better perfusion. Dot/blot/flame hemorrhages, dilated/tortuous vasculature, and microaneurysms occur, usually bilateral; more benign course. Associated with hyperviscosity syndromes including polycythemia vera, multiple myeloma, and Waldenström’s macroglobulinemia.
Ocular Ischemic Syndrome
Definition
Widespread ischemia of both the anterior and posterior segments of one eye due to ipsilateral carotid occlusive disease (less frequently obstruction of the ipsilateral ophthalmic artery), carotid dissection, or arteritis (rare).
Etiology
Due to a 90% or greater occlusion of the ipsilateral carotid artery or rarely ophthalmic artery.
Epidemiology
Usually occurs in patients aged 50–70 years old (mean = 65 years); 80% unilateral; male predilection (2 : 1). Associated with atherosclerosis, ischemic heart disease (50%), hypertension (67%), diabetes mellitus (50%), previous stroke (25%), and peripheral arterial disease (20%); rarely due to inflammatory conditions including giant cell arteritis. Blood flow to the eye is relatively unaffected until carotid obstruction exceeds 70%; ocular ischemic syndrome usually does not occur until it reaches 90% (decreasing CRA perfusion by 50%); 50% of patients have complete ipsilateral carotid artery obstruction.
Symptoms
Gradual loss of vision (90%) over days to weeks with accompanying dull eye pain/headache (40%) or “ocular angina”; patients may also report amaurosis fugax (10%) or a delayed recovery of vision after exposure to bright light due to impaired photoreceptor regeneration. May occur suddenly in 12% of cases where a cherry-red spot is also present.
Signs
Gradual or sudden decreased visual acuity ranging from 20 / 20 to NLP; retinal arterial narrowing and venous dilatation without tortuousity, retinal hemorrhages (80% midperipheral), microaneurysms, macular edema, cotton-wool spots, disc/retinal neovascularization (37%), and spontaneous pulsations of the retinal arteries; anterior segment signs including episcleral injection, corneal edema, anterior chamber cells and flare (keratic precipitates are absent and flare is often disproportionate to the amount of cell present), iris atrophy, chronic conjunctivitis, and rubeosis (66%) are common. Intraocular pressure may be elevated, but may also be normal even with 360° synechia. Light digital pressure on the globe through the eyelid often produces arterial pulsations (does not occur in other diseases in differential) and can shut down perfusion of the central retinal artery.
Differential Diagnosis
Nonischemic CRVO, venous stasis retinopathy, diabetic retinopathy, hypertensive retinopathy, aortic arch disease, parafoveal telangiectasis, radiation retinopathy, Takayasu’s disease.
Evaluation
• Check blood pressure.
• Fluorescein angiogram: Delayed arteriovenous transit time (> 11 seconds) in 95%; delayed or patchy choroidal filling (> 5 seconds) in 60%, arterial vascular staining in 85%.
• Electrophysiologic testing: ERG (reduced or absent a-wave and b-wave amplitudes).
• Medical consultation for complete cardiovascular evaluation including duplex and carotid Doppler ultrasound scans (≥ 90% obstruction of the ipsilateral internal or common carotid arteries). Carotid angiography is usually not needed except in cases where ultrasound is equivocal.
Prognosis
Poor prognosis; 5-year mortality rate is 40% mainly owing to cardiovascular disease. Sixty percent of patients have count fingers or worse vision at 1 year follow-up; only 25% have better than 20 / 50 vision. When rubeosis is present, 90% will be count fingers or worse within 1 year. One-third of patients have improved vision after carotid endarterectomy, one-third remain unchanged, and one-third worsen despite surgery.
Retinopathy of Prematurity
Definition
Abnormal retinal vasculature development in premature infants, especially after supplemental oxygen therapy.
Epidemiology
Usually bilateral; associated risk factors include premature birth (< 32 weeks’ gestation), low birth weight (< 750 g: 90% develop ROP and 16% develop threshold disease; 1000–1250 g: 45% develop ROP and 2% develop threshold disease), supplemental oxygen therapy (> 50 days), and a complicated hospital course.
Symptoms
Asymptomatic; later may have decreased vision.
Signs
Shallow anterior chamber, corneal edema, iris atrophy, poor pupillary dilation, posterior synechiae, ectropion uveae, leukocoria, vitreous hemorrhage, retinal detachment, and retrolental fibroplasia; may have strabismus.
International classification of ROP describes the retinal changes in five stages:
Stage 1
Thin, circumferential, flat, white, demarcation line develops between posterior vascularized and peripheral avascular retina (beyond line).
Stage 2
Demarcation line becomes elevated and organized into a pink-white ridge, no fibrovascular growth visible.
Stage 3
Extraretinal fibrovascular proliferation from surface of the ridge.
Stage 4
Dragging of vessels, and subtotal traction retinal detachment (4A is macula attached, 4B involves the macula).
Stage 5
Total retinal detachment (almost always funnel detachment).
International classification of ROP also describes the extent of retina involved by number of clock hours and location by zone (centered on optic disc, not the fovea because retinal vessels emanate from disc):
Zone 1
Inner zone (posterior pole) corresponding to the area enclosed by a circle around the optic disc with radius equal to twice the distance from the disc to the macula (diameter of 60°).
Zone 2
The area between zone 1 and a circle centered on the optic disc and tangent to the nasal ora serrata.
Zone 3
Remaining temporal crescent of retina (last area to become vascularized).
Finally, international classification of ROP defines “plus” disease:
“Plus” Disease
At least two quadrants (usually 6 or more clock hours) of shunted blood causing vascular engorgement in the posterior pole with tortuous arteries, dilated veins, pupillary rigidity due to iris vascular engorgement, and vitreous haze.
Differential Diagnosis
Coats’ disease, Eales’ disease, familial exudative vitreoretinopathy, sickle cell retinopathy, juvenile retinoschisis, persistent hyperplastic primary vitreous, incontinentia pigmenti (Bloch–Sulzberger syndrome), and other causes of leukocoria (see Chapter 7).
Evaluation
• The first exam should be either prior to discharge from the hospital, 4 weeks chronological age, or by 31 weeks postgestational age, whichever is later.
• Complete ophthalmic history with attention to birth history and birth weight.
• Complete eye exam with attention to iris, lens, and ophthalmoscopy (retinal vasculature and retinal periphery with scleral depression).
• Cycloplegic refraction as many develop refractive errors especially myopia.
• Pediatric consultation.
Prognosis
Depends on the amount and stage of ROP; 80–90% will spontaneously regress; may develop amblyopia, macular dragging, strabismus; stage 5 disease carries a poor prognosis (functional success in only 3%); may develop high myopia, glaucoma, cataracts, keratoconus, band keratopathy, and retinal detachment.
Coats’ Disease / Leber’s Miliary Aneurysms
Unilateral (80–95%), idiopathic, progressive, developmental retinal vascular abnormality (telangiectatic and aneurysmal vessels with a predilection for the macula); usually occurs in young males (10 : 1) < 20 years old (two-thirds present before age 10). Retinal microaneurysms, retinal telangiectasia, lipid exudation, “light-bulb” vascular dilatations, capillary nonperfusion and occasionally neovascularization, exudative retinal detachments, and subretinal cholesterol crystals occur primarily in the temporal quadrants, especially on fluorescein angiogram where microaneurysm leakage is common. May present with poor vision, strabismus, or leukocoria. Spectrum of disease from milder form in older patients with equal sex predilection and often bilateral (Leber’s miliary aneurysms) to severe form with localized exudative retinal detachments and yellowish subretinal masses, and is included in the differential diagnosis of leukocoria (Coats’ disease). Clinical course varies but generally progressive. Rarely associated with systemic disorders including Alport’s disease, fascioscapulohumeral dystrophy, muscular dystrophy, tuberous sclerosis, Turner’s syndrome, and Senior–Loken syndrome. On histopathologic examination there is loss of vascular endothelium and pericytes with subsequent mural disorganization. Classified into five stages:
Stage 1
Telangectasia only
Stage 2
Exudation (a = extrafoveal, b = subfoveal)
Stage 3
Exudative retinal detachment (a = subtotal, b = total)
Stage 4
RD with glaucoma
Stage 5
End-stage disease
Figure 10-32 Leber’s miliary aneurysms demonstrating dilated arterioles with terminal “light-bulbs.”
Figure 10-33 Fluorescein angiogram of same patient as Figure 10-32 demonstrating capillary nonperfusion, microaneurysms, and “light-bulb” vascular dilations.
• Treatment: Scatter laser photocoagulation to posterior or cryotherapy to anterior areas of abnormal vasculature, telangiectasia, and areas of nonperfusion when symptomatic. May require multiple treatment sessions. Goal is to ablate areas of vascular leakage and to allow resorption of exudate.
Familial Exudative Vitreoretinopathy and Norrie’s Disease (X-Linked Recessive)
(See Hereditary Vitreoretinal Degenerations section below.)
Incontinentia Pigmenti (X-Linked Dominant)
Ocular, CNS, dermatologic, and dental findings including skin blisters, retinal neovascularization, vitreous hemorrhage, and traction retinal detachment. Associated with mutation in the NEMO gene located on chromosome Xq28.
• Fluorescein angiogram: Shows perpheral nonperfusion; wide-angle angiography is especially useful.
• Treatment: Scatter laser photocoagulation to ischemic retina when neovascularization develops. Consider vitrectomy when traction retinal detachment or nonclearing vitreous hemorrhage is present should be performed by a retina specialist.
Eales’ Disease
Bilateral, idiopathic, peripheral obliterative vasculopathy that occurs in healthy, young adults aged 20–30 years old, with male predilection. Patients usually notice floaters and decreased vision and have areas of perivascular sheathing, vitreous cells, peripheral retinal nonperfusion, microaneurysms, intraretinal hemorrhages, white sclerotic ghost vessels, disc/iris/retinal neovascularization, and vitreous hemorrhages. Fibrovascular proliferation may lead to tractional retinal detachments. May have signs of ocular inflammation with keratic precipitates, anterior chamber cells and flare, and cystoid macular edema; variable prognosis. Eales’ disease is a diagnosis of exclusion; must rule out other causes of inflammation or neovascularization including BRVO, diabetic retinopathy, sickle cell retinopathy, multiple sclerosis, sarcoidosis, tuberculosis, SLE, and other collagen–vascular diseases.
• Treatment: Scatter laser photocoagulation to nonperfused retina when neovascularization develops. If vitreous hemorrhage obscures view of retina, peripheral cryotherapy can be applied to ablate peripheral avascular retina.
• Consider periocular or systemic steroids for inflammatory component.
Macular Telangiectasia (Idiopathic Juxtafoveal / Perifoveal Telangiectasia)
Group of retinal vascular disorders with abnormal perifoveal capillaries confined to the juxtafoveal region (1–199 μm from center of fovea). Several forms:
Type 1A (Unilateral Congenital Parafoveal Telangiectasia)
Occurs in men in the fourth to fifth decades. Yellow exudate at outer edge of telangiectasis usually temporal to the fovea and 1–2 disc diameters in area; decreased vision ranging from 20 / 25 to 20 / 40 from macular edema and exudate. May represent mild presentation of Coats’ disease in an adult.
• Optical coherence tomography: Characteristic outer retinal hyporeflective cavities that do not correspond to leakage on FA. May eventually lead to atrophy.
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