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.

Superior branch artery occlusion with retinal edema extending in a wedge-shaped pattern from the artery occluded by the Hollenhorst plaque.

Inferior branch retinal artery occlusion with Hollenhorst plaque and wedge-shaped retinal edema.

Superior branch artery occlusion demonstrating retinal edema.

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

• •
  

  Complete ophthalmic history and eye exam with attention to pupils, noncontact biomicroscopic or contact lens fundus exam, and ophthalmoscopy (retinal vasculature and arteriole bifurcations).

  
  
• •
  

  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.

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.

Central retinal artery occlusion with cherry-red spot in the fovea and surrounding retinal edema.

Central retinal artery occlusion with cherry-red spot.

Cilioretinal artery sparing central retinal artery occlusion with patent cilioretinal artery allowing perfusion (thus no edema) in a small section of the macula.

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

• •
  

  Complete ophthalmic history and eye exam with attention to pupils, noncontact biomicroscopic or contact lens fundus exam, and ophthalmoscopy (retinal vasculature).

  
  
• •
  

  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.

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.

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

• •
  

  Complete ophthalmic history and eye exam with attention to pupils, noncontact biomicroscopic or contact lens fundus exam, and ophthalmoscopy.

  
  
• •
  

  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.

Definition

Occlusion of a branch retinal vein (BRVO). Two types:

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.

Inferior branch retinal vein occlusion demonstrating wedge-shaped area of intraretinal hemorrhages and cotton-wool spots.

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

• •
  

  Complete ophthalmic history and eye exam with attention to pupils, tonometry, gonioscopy, noncontact biomicroscopic or contact lens fundus exam, and ophthalmoscopy.

  
  
• •
  

  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

• •
  

  Good; 50% have ≥ 20/ 40 vision unless foveal ischemia or chronic macular edema is present. Risk of another BRVO in same eye is 3% and in fellow eye is 12%.

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:

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.

Hemiretinal vein occlusion with exudates forming partial macular star.

Fluorescein angiogram of a patient with a retinal vein occlusion demonstrating peripheral capillary nonperfusion.

Central retinal vein occlusion demonstrating hemorrhages in all four quadrants.

Fluorescein angiogram demonstrating no filling of the central retinal vein.

Optociliary shunt vessels in a patient with an old central retinal vein occlusion.

Evaluation

• •
  

  Complete ophthalmic history and eye exam with attention to visual acuity (worse than 20 / 400 likely ischemic), pupils (ischemic likely to have RAPD), Golmann visual fields (ischemic cannot see I4e), tonometry, gonioscopy, noncontact biomicroscopic or contact lens fundus exam, and ophthalmoscopy.

  
  
• •
  

  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.

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

• •
  

  Complete ophthalmic history and eye exam with attention to pupils, tonometry, anterior chamber, gonioscopy, noncontact biomicroscopic or contact lens fundus exam, and ophthalmoscopy. Digital pressure on eye causes arterial pulsation.

  
  
• •
  

  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.

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:

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

• •
  

  Screen all premature infants who weighed < 1500 g at birth or under 30 weeks gestational age at birth, and infants > 1500 g at birth who experienced an unstable postnatal course (AAO guidelines).

  
  
• •
  

  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.

Definition

Retinal vascular complication of diabetes mellitus; classified into nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR).

Epidemiology

Leading cause of blindness in US population aged 20–64 years old.

Symptoms

Asymptomatic, may have decreased or fluctuating vision. Advanced retinopathy can lead to complete blindness.

Signs

Nonproliferative Diabetic Retinopathy

Grading of NPDR (see Box 10-1 ) and risk of progression to PDR depend on the amount and location of hard and soft exudates, intraretinal hemorrhages, microaneurysms (MA), venous beading and loops, and intraretinal microvascular abnormalities (IRMA). Cotton-wool spots, dot and blot hemorrhages, posterior subcapsular cataracts, and induced myopia/hyperopia (from lens swelling due to high blood sugar) are common; may have macular edema, which can be clinically significant (CSME); usually bilateral.

Moderate nonproliferative diabetic retinopathy with intraretinal hemorrhages, microaneurysms, and lipid exudate.

Fluorescein angiogram of same patient as Figure 10-46 demonstrating tiny blocking defects from the intraretinal hemorrhages and spots of hyperfluorescence due to microaneurysms.

Severe nonproliferative diabetic retinopathy with extensive hemorrhages, microaneurysms, and exudates.

Severe nonproliferative diabetic retinopathy with diffuse macular edema and lipid exudate.

Spectral domain OCT of diffuse diabetic macular edema with subretinal fluid, intraretinal fluid, and cystoid macular edema.

Box 10-1

Diabetic Retinopathy Definitions

CLINICALLY SIGNIFICANT MACULAR EDEMA (CSME)

• 
  

  Retinal thickening < 500 μm from center of fovea or

  
  
• 
  

  Hard exudates < 500 μm from center of fovea with adjacent thickening or

  
  
• 
  

  Retinal thickening > 1 disc size in area < 1 disc diameter from center of fovea

HIGH-RISK (HR) CHARACTERISTICS OF PROLIFERATIVE DIABETIC RETINOPATHY (PDR)

• 
  

  Neovascularization of the disc (NVD) > standard photo 10A used in DRS (one-quarter to one-third disc area) or

  
  
• 
  

  Any NVD and vitreous hemorrhage (VH) or preretinal hemorrhage or

  
  
• 
  

  Neovascularization elsewhere (NVE) > standard photo 7 (one-half disc area) and VH or preretinal hemorrhage

SEVERE NONPROLIFERATIVE DIABETIC RETINOPATHY (NPDR) 4 : 2 : 1 RULE

• 
  

  Diffuse intraretinal hemorrhages and microaneurysms in 4 quadrants or

  
  
• 
  

  Venous beading in 2 quadrants or

  
  
• 
  

  Intraretinal microvascular abnormalities (IRMA) in 1 quadrant

Differential Diagnosis

Hypertensive retinopathy, CRVO, BRVO, ocular ischemic syndrome, radiation retinopathy, retinopathy associated with blood disorders, Eales’ disease, hypertensive retinopathy.

Evaluation

• •
  

  Complete ophthalmic history and eye exam with attention to tonometry, gonioscopy (NVG), iris (NVI), lens, noncontact biomicroscopic or contact lens fundus exam, and ophthalmoscopy (retinal vascular abnormalities, optic disc [NVD], and midperiphery [NVE]):

  
  
  
  
  • 
    

    IDDM Type I: Examine 5 years after onset of diabetes mellitus, then annually if no retinopathy is detected.

    
    
  • 
    

    NIDDM Type II: Examine at diagnosis of diabetes mellitus, then annually if no retinopathy is detected.

    
    
  • 
    

    During pregnancy: Examine before pregnancy, each trimester, and 3–6 months post partum.

  
  
  
  
• •
  

  Lab tests: Fasting blood glucose, hemoglobin A1C, blood urea nitrogen (BUN), and creatinine.

  
  
• •
  

  B-scan ultrasonography to rule out tractional retinal detachment in eyes when dense vitreous hemorrhage obscures view of fundus.

  
  
• •
  

  Fluorescein angiogram: Capillary nonperfusion, microaneurysms, macular edema, and disc/retinal neovascularization. Wide-field angiography is helpful to evaluate peripheral nonperfusion and to find early neovascularization.

  
  
• •
  

  Optical coherence tomography: Increased retinal thickness, cysts, and subretinal fluid in cases of macular edema; can highlight the presence of posterior hyaloidal traction and traction macular detachment.

  
  
• •
  

  Medical consultation with attention to blood pressure, cardiovascular system, renal status, weight, and glycemic control.

Proliferative diabetic retinopathy before laser treatment.

Same patient as Figure 10-56 demonstrating quiescent proliferative diabetic retinopathy following pan-retinal photocoagulation. Note absence of neovascularization.

Prognosis

Early treatment allows better control. Good for NPDR without CSME. After adequate treatment, diabetic retinopathy often becomes quiescent for extended periods of time. Focal laser photocoagulation improves vision in 17% of cases (ETDRS conclusion). Complications include cataracts (often posterior subcapsular) and neovascular glaucoma.

Definition

Retinal vascular changes secondary to chronic or acutely (malignant) elevated systemic blood pressure.

Epidemiology

Hypertension defined as blood pressure > 140 / 90 mmHg; 60 million Americans over 18 years of age have hypertension; more prevalent in African Americans.

Symptoms

Asymptomatic; rarely, decreased vision.

Signs

Retinal arteriole narrowing/straightening, copper- or silver-wire arteriole changes (arteriolosclerosis), arteriovenous crossing changes (nicking), cotton-wool spots, microaneurysms, flame hemorrhages, hard exudates (may be in a circinate or macular star pattern), Elschnig spots (yellow [early] or hyperpigmented [late] patches of retinal pigment epithelium overlying infarcted choriocapillaris lobules), Siegrist streaks (linear hyperpigmented areas over choroidal vessels), arterial macroaneurysms, and disc hyperemia or edema with dilated tortuous vessels (in malignant hypertension).

Hypertensive retinopathy with disc edema, macular star, and retinal folds in a patient with acute, malignant hypertension. Inset shows arteriovenous nicking.

Hypertensive retinopathy demonstrating attenuated arterioles, choroidal ischemia, Elschnig spots, and Siegrist streaks.

Fundus findings are graded/classified as follows:

Differential Diagnosis

Diabetic retinopathy, radiation retinopathy, vein occlusion, leukemic retinopathy, retinopathy of anemia, collagen vascular disease, ocular ischemia syndrome, neuroretinitis, anterior ischemic optic neuropathy, papilledema.

Evaluation

• •
  

  Complete ophthalmic history and eye exam with attention to noncontact biomicroscopic or contact lens fundus exam and ophthalmoscopy (retinal vasculature and arteriovenous crossings).

  
  
• •
  

  Check blood pressure.

  
  
• •
  

  Fluorescein angiogram: Retinal arteriole narrowing/straightening, microaneurysms, capillary nonperfusion, and macular edema.

  
  
• •
  

  Medical consultation with attention to cardiovascular and cerebrovascular systems.

Prognosis

Usually good.

Definition

Alteration in retinal vascular permeability after receiving local ionizing radiation usually from external beam radiotherapy or plaque brachytherapy.

Etiology

Endothelial cell DNA damage secondary to the radiation leading to progressive cell death and damage to the retinal blood vessels.

Epidemiology

Usually requires > 30–35 Gy (3000–3500 rads) total radiation dose; appears 0.5–2 years after ionizing radiation; diabetics and patients receiving chemotherapy have a lower threshold.

Symptoms

Often asymptomatic until retinopathy involves macula; decreased vision.

Signs

Microaneurysms, telangiectasia, cotton-wool spots, hard exudates, retinal hemorrhages, macular edema, vascular sheathing, disc edema, retinal/disc/iris neovascularization; may have cataract, dry eye disease, lid abnormalities.

Radiation papillopathy. Note regressed malignant melanoma temporally.

Radiation retinopathy with sclerotic vessels overlying regressed malignant melanoma.

Radiation retinopathy with sclerotic vessels, neovascularization, and preretinal hemorrhage.

Differential Diagnosis

Diabetic retinopathy, sickle cell retinopathy, hypertensive retinopathy, retinal vascular occlusion, retinopathy of anemia/thrombocytopenia, and leukemic retinopathy.

Evaluation

• •
  

  Complete radiation history with attention to radiated field, total dose delivered, and fractionation schedule.

  
  
• •
  

  Complete eye exam with attention to tonometry, gonioscopy, iris, lens, noncontact biomicroscopic or contact lens fundus exam, and ophthalmoscopy.

  
  
• •
  

  Fluorescein angiogram: Capillary nonperfusion, macular edema, and neovascularization may be present.

  
  
• •
  

  Optical coherence tomography: Intraretinal fluid, cstic spaces, and subretinal fluid; can monitor for treatment response.

Prognosis

Fair; complications include cataract, macular edema/ischemia, optic atrophy, vitreous hemorrhage, and neovascular glaucoma. Two-thirds of patients maintain vision better than 20/200.

Definition

Progressive degenerative disease of the retinal pigment epithelium, Bruch’s membrane, and choriocapillaris. Generally classified into two types: (1) nonexudative or “dry” AMD (85%) and (2) exudative or “wet” AMD characterized by CNV and eventually disciform scarring (15%).

Epidemiology

Leading cause of blindness in US population aged > 50 years old, as well as the most common cause of blindness in the Western world; 6.4% of patients 65–74 years old and 19.7% of patients > 75 years old had signs of AMD in the Framingham Eye Study; more prevalent in Caucasians. Risk factors include increasing age (> 75 years old), positive family history, cigarette smoking, hyperopia, light iris color, hypertension, hypercholesterolemia, female gender, and presence of cardiovascular disease; nutritional factors and light toxicity also play a role in pathogenesis. Associated with variants of genes encoding the alternative complement pathway including Y402H single-nucleotide polymorphism (SNP) of complement factor H (CFH) on chromosome 1q31, ARMS2 / HTRA1 on chromosome 10q and LOC387715 on chromosome 10q, tissue inhibitor of metalloproteinase 3 ( TIMP3 ), LIUPC, complement factor B and C2 on chromosome 6p21, complement factor I, and C3. Homozygotes (6 ×) and heterozygotes (2.5 ×) for CFH mutations are more likely to develop AMD. Their risk is even greater if they smoke (odds ratio 34 vs 7.6 in nonsmokers), have elevated ESR, and / or have elevated C-reactive protein.

Symptoms

Initially asymptomatic or may have decreased vision, metamorphopsia early. Advanced atrophic form (see Box 10-2 ) may have central or pericentral scotoma.

Dry, age-related macular degeneration demonstrating drusen and pigmentary changes.

Advanced atrophic, nonexudative, age-related macular degeneration demonstrating subfoveal geographic atrophy.

Fluorescein angiogram of same patient as Figure 10-67 demonstrating well-defined window defect corresponding to the area of geographic atrophy.

Spectral domain OCT of central geographic atrophy. Notice the absence of retinal pigment epithelium in the fovea with increased signal beyond the RPE.

Signs

Normal or decreased visual acuity; abnormal Amsler grid (central/paracentral scotomas or metamorphopsia); small hard drusen, larger soft drusen, geographic atrophy (GA) of the retinal pigment epithelium (RPE), RPE clumping, and blunted foveal reflex.

Differential Diagnosis

Dominant drusen, pattern dystrophy, Best’s disease, Stargardt’s disease, cone dystrophy, and drug toxicity.

Evaluation

• •
  

  Complete ophthalmic history and eye exam with attention to Amsler grid and noncontact biomicroscopic or contact lens fundus exam.

  
  
• •
  

  Fluorescein angiogram: Window defects from GA and punctate hyperfluorescent staining of drusen (no late leakage).

  
  
• •
  

  Fundus autofluoresence: To evaluate areas of geographic atropy that appear dark. Hyperautofluorescent areas on the edges of GA are likely to portend GA enlargement.

  
  
• •
  

  Optical coherence tomography: Areas of drusen and GA can be quantified on OCT. Also useful to rule out wet AMD.

Prognosis

Usually good unless central GA or exudative AMD develops. Severe visual loss (defined as loss of > 6 lines) occurs in 12% of nonexudative cases; presence of large soft drusen and focal RPE hyperpigmentation increases risk of developing exudative form (MPS conclusion). Risk of advanced AMD over 5 years varies depending on category: Category 1 and 2 (1.8%), Category 3 (18%), Category 4 (43%) (AREDS conclusion).

Symptoms

Metamorphopsia, central scotoma, rapid visual loss.

Exudative age-related macular degeneration with large choroidal neovascular membrane and accompanying subretinal hemorrhage and fibrosis as seen on (A) clinical photo, and (B) fluorescein angiogram.

Exudative age-related macular degeneration demonstrating subretinal hemorrhage from choroidal neovascular membrane.

Fluorescein angiogram of same patient as Figure 10-71 demonstrating leakage from the CNV and blocking from the surrounding subretinal blood.

Exudative age-related macular degeneration drusen, pigmentary changes, and an occult choroidal neovascular membrane with associated serous pigment epithelial detachment (arrowheads).

Fluorescein angiogram of same patient as Figure 10-73 demonstrating hyperfluorescent staining of pigmentary changes and drusen, leakage from the CNV and pooling of fluorescein dye within the serous pigment epithelial detachment.

Spectral domain OCT of exudative age-related macular degeneration with subretinal pigment epithelium and subretinal fluid from an occult with no classic choroidal neovascular membrane.

Spectral domain OCT of exudative age-related macular degeneration.

Spectral domain OCT of choroidal neovascular membrane illustrating advanced segmentation algorithms showing the increased retinal thickness and elevated retina on the internal limiting membrane (ILM) map.

Signs

CNV, lipid exudates, subretinal or intraretinal hemorrhage/fluid, pigment epithelial detachment (PED), and retinal pigment epithelial tears; may have late fibrovascular disciform scars.

Differential Diagnosis

Dominant drusen, pattern dystrophy, Best’s disease, central serous retinopathy, Stargardt’s disease, cone dystrophy, drug toxicity, and choroidal neovascularization from other causes, including presumed ocular histoplasmosis syndrome, angioid streaks, myopic degeneration, traumatic choroidal rupture, retinal dystrophies, inflammatory choroidopathies, and optic nerve drusen.

Evaluation

• •
  

  Complete ophthalmic history and eye exam with attention to Amsler grid and noncontact biomicroscopic or contact lens fundus exam.

  
  
• •
  

  Fluorescein angiogram: Two forms of leakage from CNV: (1) classic leakage , defined as lacy, network of bright fluorescence during early choroidal filling views that increases in fluorescence throughout the angiogram and leaks beyond its borders in late views; (2) occult leakage , defined as stippled nonhomogeneous hyperfluorescence at the level of the RPE (best seen on stereoscopic views) that persists through to late views, but the leakage is not as bright as classic lesions (type 1 or fibrovascular PED), or late leakage of undetermined origin (type 2), where the early views show no apparent leakage, but as the angiogram progresses there is hyperfluorescent stippling at the level of the RPE in late views.

  
  
• •
  

  Indocyanine green angiogram: Useful when the CNV is poorly demarcated or obscured by hemorrhage on fluorescein angiogram, or if fibrovascular pigment epithelial detachment is present (to identify areas of focal neovascularization or polypoidal choroidal vasculopathy); focal hotspots likely represent retinal angiomatous proliferation (see below); CNV also appears as plaque of late hyperfluorescence. In general, ICGA should be performed when there is lack of response to anti-VEGF therapy to rule out PCV and other masquerade syndromes.

  
  
• •
  

  Optical coherence tomography: Increased retinal thickness, intraretinal fluid, cystoid spaces, subretinal fluid, pigment epithelial detachment, drusen, drusenoid PED, and/or CNV may all be seen on scans. Also useful to determine whether the CNV is type 1 (below the RPE) or type 2 (above the RPE). Usually thinned choroid on enhanced depth imaging.

Management

• •
  

  Focal laser photocoagulation with argon green/yellow or krypton red laser and a transpupillary delivery system to form confluent (200–500 μm spots) white burns over the entire CNV depending on size, location, and visual acuity based on the results of the Macular Photocoagulation Study (MPS) can be performed in very select extrafoveal lesions (treat entire CNV and 100 μm beyond all boundaries). Note : Only patients with a classic, well-defined CNV met eligibility criteria for the MPS study (see Box 10-3 ).

  
  
  
  

  Box 10-3

  
  

  Macular Photocoagulation Study (MPS) Definitions

  
  

  
  

  
  

  
  
  • 
    

    Extrafoveal: 200–2500 μm from center of foveal avascular zone (FAZ)

    
    
  • 
    

    Juxtafoveal: 1–199 μm from center of FAZ or choroidal neovascular membrane (CNV) 200–2500 μm from center of FAZ with blood or blocked fluorescence within 1–199 μm of FAZ center

    
    
  • 
    

    Subfoveal : Under geometric center of FAZ

  
  

  
  
  
  
• •
  

  Anti-VEGF agents (bevacizumab [Avastin], ranibizumab [Lucentis], and aflibercept [Eylea]) have revolutionized management and prognosis of exudative AMD.

  
  
  
  
  • •
    

    Monthly injections of ranibizumab is effective in patients with either minimally classic or occult with no classic CNV (MARINA study conclusion). Monthly injections of ranibizumab is superior to PDT in patients with predominantly classic CNV (ANCHOR study conclusion).

    
    
  • •
    

    Either monthly or PRN treatment with bevacizumab or ranibizumab is equally effective in treating neovascular AMD at up to 2 years of follow-up (CATT, IVAN, MANTA, and GEFAL study conclusions). However, there are concerns that bevacizumab may have a worse side effect profile owing to its greater systemic bioavailability; PRN dosing was not as efficacious as fixed dosing especially with bevacizumab.

    
    
  • •
    

    Aflibercept injected every 2 months is equivalent to ranibizumab injected monthly after 3 monthly loading doses (VIEW studies conclusion).

  
  
  
  
• •
  

  The ideal treatment paradigm with anti-VEGF agents has not been determined with various retinal specialists using either monthly injections, treat and extend, and / or PRN injections for different patients.

  
  
• •
  

  The phenomenon of tachyphylaxis has been seen in many patients who develop treatment resistance to a particular anti-VEGF agent but show a good response when switched to an alternative anti-VEGF treatment.

  
  
• •
  

  Submacular surgery for removal of CNV or macular translocation has not been promising in regards to vision potential and has largely been abandoned.

  
  
• •
  

  Low-vision aids and registration with blind services for patients who are legally blind (< 20 / 200 best corrected visual acuity or < 20° visual field in better-seeing eye).

  
  
• •
  

  Treatments currently being evaluated in clinical trials include radiation therapy, modulating (feeder) vessel laser photocoagulation, other anti-VEGF agents, long-acting anti-VEGF agents, and combination therapies.

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