• Ocular ischemic syndrome (OIS) refers to anterior and posterior segment signs and symptoms related to chronic ocular hypoperfusion.
• Most common cause is severe carotid occlusive disease.
• The most common symptoms are monocular visual loss and ocular/orbital pain.
• Patients are also at increased risk for cerebral and myocardial infarction.
• Relatively uncommon but probably underdiagnosed
• Estimated at 7.5 cases per million per year
• Males > females 2:1 (atherosclerotic disease)
• Older age: mean 65 years, range 50–80 years
• No racial predilection
• Bilateral involvement in up to 22% of cases
• Decreased vascular perfusion in the presence of poor collateral circulation leads to hypoperfusion of ocular tissues.
• Ischemia and subsequent neovascularization produce ocular signs and symptoms.
• Reduced blood flow to the eye/orbit
– Most common is severe atherosclerotic disease of carotid vascular system (generally ≥90% stenosis), with internal > common > external carotid.
– 5% lifetime risk for patients with internal carotid artery (ICA) stenosis to develop OIS
– Less common: ophthalmic artery disease, systemic vasculitis (giant cell arteritis [GCA]), vaso-occlusive disease (i.e., aortic arch syndrome), Takayasu arteritis
COMMONLY ASSOCIATED CONDITIONS
• Systemic vascular disease
– Systemic arterial hypertension (HTN)
– Diabetes mellitus (DM)
– Coronary artery disease (CAD)
– Previous cerebrovascular accident or transient ischemic attack
– Peripheral vascular disease
• Loss of vision
– Most frequent symptom; present in 70% or above at presentation, absent in less than or equal to 10%
– Variable in severity and onset—more than 2/3 are less than 20/60 at presentation; most experience vision loss over weeks to months, although some have abrupt vision loss
• Pain—40% present with pain due to increased intraocular pressure (IOP) or ischemia (“ocular angina”—dull, constant ache over the brow)
• Transient vision loss/amaurosis fugax
– Present in 10–15% of patients
• Afterimages or prolonged recovery of vision after light exposure
• Anterior segment
– Conjunctival and episcleral injection
– Corneal edema and/or Descemet’s folds
– Iris atrophy and neovascularization (66%)
– Anterior and posterior synechiae
– Fixed and semidilated pupil or afferent pupil defect (APD)
– Mild iritis in 20% (flare > cell)
– Neovascular glaucoma in 1/3 of patients
– IOP may be low/normal second to decreased ciliary body perfusion.
– Hypotony can further exacerbate corneal decompensation, cataract, and maculopathy.
• Posterior segment (more frequent)
– Narrowed retinal arteries
– Veins dilated but not tortuous
– Retinal hemorrhages in 80% of patients, mostly dot-blot and in midperipheral retina
– Microaneurysms common in midperipheral retina; more visible on fluorescein angiogram
– Spontaneous retinal arterial pulsations
– Cherry-red spot (12%) from embolic or increased IOP induced occlusion of central retinal artery
– Cotton–wool spots (6%)
– Choroidal ischemia and peripheral wedge-shaped chorioretinal atrophy
– Neovascularization of disc (NVD) in 35%, neovascularization elsewhere (NVE) in 10%
• Orbital infarction syndrome
– Ischemia of intraocular and intraorbital contents
– Corneal hypoesthesia, intraocular inflammation, hypotony, ophthalmoplegia, ptosis, proptosis, orbital pain
• Systemic exam
– Pulses, carotid and cardiac auscultation
DIAGNOSTIC TESTS & INTERPRETATION
Initial lab tests
• Fluorescein angiography (FA)
– Delayed or patchy choroidal filling in 60% of patients; most specific FA sign
– Prolonged arteriovenous transit time in up to 95% of patients; most sensitive
– Staining of retinal vessels in 85%; arterial more than venous staining
– Leading edge of arterial dye
– 15% with macular edema (noncystoid pattern), often with disc leakage
– Retinal capillary nonperfusion
• Consider ESR or C-reactive protein (CRP) if suspected GCA
Follow-up & special considerations
• Indocyanine green angiography (ICG)
– Prolonged arm–choroid time; slow intrachoroidal filling time; and watershed zone filling
• Carotid Doppler ultrasound
– Most commonly used noninvasive test shows anatomy and hemodynamics.
– Reduced peak systolic velocity and increased vascular resistance of end arteries
– May be limited by complex anatomy, large plaque, calcific shadows, or tortuous vessels
– Operator and machine dependent
Follow-up & special considerations
• Retrobulbar vessel Doppler
– May show reversal of ophthalmic artery flow, a highly specific indicator of high-grade ICA stenosis or occlusion
• Magnetic resonance angiography
– Noninvasive; evaluates anatomy of intracranial vessels and very accurate
– Limits include claustrophobia, pacemaker, metallic stents, and obesity.
• Carotid angiography
– Gold standard for imaging cerebrovascular system, but expensive and invasive (risk for cerebral infarction)
– Perform if surgery a consideration
• Electroretinography (ERG)
– Ischemia of outer and inner retina with decreased amplitude of a and b waves
• Visual-evoked potentials (VEP)
– Increased latency, decreased amplitude
– Decreased ophthalmic and central retinal artery pressure
Loss of endothelial cells and pericytes in peripheral retinal vessels can lead to vessel leakage.
• Central retinal vein occlusion (CRVO)
– Dilated and tortuous retinal veins (due to outflow obstruction in CRVO vs. decreased inflow in OIS)
– Flame-shaped (more superficial) hemorrhages in all 4 quadrants
– Swollen optic nerve
– Macular edema is common.
• Diabetic retinopathy
– Always bilateral, usually symmetric
– Microaneurysms and dot-blot hemorrhages common in posterior pole as well as midperipheral retina
– Hard exudates common
– Rare diabetic papillopathy
Goal is to treat the underlying problem (ocular hypoperfusion) and associated ocular complications.
• Topical treatment (1)[B]
– Steroids—reduce inflammation
– Cycloplegia—stabilize blood–aqueous border
– IOP-lowering agents that reduce aqueous outflow (beta-blockers, alpha-agonists, or carbonic anhydrase inhibitors)
– Avoid pilocarpine and prostaglandins (may increase inflammation)
• Intravitreal injections (2)[C]
– Anti–vascular endothelial growth factor (VEGF) and steroids can be considered to treat macular edema.
– Anti-VEGF may help with neovascularization.
• Panretinal photocoagulation can cause regression of NVD, neovascularization of the iris (NVI), and NVE in 1/3 of cases and can reduce risk of neovascular glaucoma (NVG).
• NVG is often refractory to medical treatment and may require surgery with trabeculectomy, tube shunt, or cycloablation if poor visual prognosis.
• Systemic disease must be treated as patients have high risk of vascular death.
– Treatment of systemic disease: HTN, DM, dyslipidemia, CAD
– Antiplatelet therapy
– Lifestyle modification: smoking cessation, healthy diet, weight loss
Issues for Referral
• All patients with OIS should have medical workup by primary care physician.
• Consider consultations from cardiology and neurosurgery.
Thrombolytic therapy can be considered in appropriate patients
• Carotid endarterectomy (CEA) (3)[A]
– CEA and aspirin superior to aspirin alone in preventing stroke in patients with symptomatic/asymptomatic carotid stenosis
– CEA for symptomatic stenosis of 50–99% if risk of stroke/death is less than 6%
– CEA for asymptomatic stenosis of 60–99% if risk of stroke/death is less than 3%
– Effect on visual outcome inconclusive: more beneficial if CEA performed before development of NVG
• Carotid artery stenting
– Alternative in patients with difficult anatomy or medical conditions that preclude CEA
• Extraintracranial bypass surgery
– Consider if complete occlusion of ICA or common carotid artery (CCA)
Low-fat, low-salt, low-sugar diet given other systemic conditions
• Overall visual prognosis is poor.
– Visual acuity at presentation is an important predictor of final outcomes.
– Iris neovascularization at presentation associated with poor visual outcome—97% of these eyes have final visual acuity (VA) less than finger counting
• Systemic outcomes
– Mortality rate 40% at 5 years
– Cardiovascular disease (myocardial infarction [MI]) accounts of 2/3 for deaths.
– Cerebral infarcts cause 19% of deaths.
– Cancer is the 3rd leading cause.
– Mortality rate is 11% in age- and sex-matched controls.
1. Mendrinos E, Machinis TG, Pournaras CJ. Ocular ischemic syndrome. Surv Ophthalmol 2010;55(1):2–34.
2. Hazin R, Daoud YJ, Khan F. Ocular ischemic syndrome: Recent trends in medical management. Curr Opin Ophthalmol 2009;20(6):430–433.
3. Goldstein LB, Adams R, Alberts MJ, et al. Primary prevention of ischemic stroke: A guideline from the American Heart Association/American Stroke Association Stroke Council: Cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation 2006;113(24):873–923.