Retinal Arterial Occlusions - RETINA AND VITREOUS - Albert & Jakobiec's Principles & Practice of Ophthalmology, 3rd Edition

Albert & Jakobiec's Principles & Practice of Ophthalmology, 3rd Edition

CHAPTER 131 - Retinal Arterial Occlusions

Craig M. Greven,
Wesley H. Adams

Overview

Retinal artery occlusion leads to profound functional deficits in the distribution of the visual field supplied by the affected vessel. These events, although relatively rare, not only have effects on the visual system of the patient, but may be the initial indication of a systemic life-threatening disease.

The average age at presentation of patients with central retinal artery occlusion (CRAO) is the early to mid-60s. However, arterial occlusive disease can occur at any age. Males are affected slightly more commonly than females, and there is no racial predilection.

Numerous mechanisms of retinal arterial occlusion have been documented, but the most common are embolic, thrombotic, vasculitic, and vasospastic. The most common sources of embolic occlusion are atherosclerotic disease of the carotid artery and cardiac disease. Thrombosis is also a major cause of retinal arterial occlusions. Hereditary and acquired conditions, as well as local factors, can promote thrombosis. The number of hereditary conditions associated with retinal arterial occlusive disease continues to grow as our understanding of the coagulation system increases. Vasculitis is another mechanism associated with arterial occlusive disease of the retina. Systemic vasculitic conditions like giant cell arteritis, as well as local areas of vasculitis of the retina, can promote obstruction.

Retinal arterial occlusive disease can be classified as ophthalmic artery, central retinal artery, branch artery, and cilioretinal artery. Ophthalmic and central have the worst visual prognosis, whereas branch and cilioretinal artery occlusions typically have better visual prognosis. The hallmark of arterial occlusive disease of the retina on clinical examination is ischemic retinal whitening, and on fluorescein angiography is delayed perfusion of the affected vessel.

Management of retinal arterial occlusive disease includes attempting to reestablish retinal arterial blood flow, determining the associated systemic disease processes and reason for occlusion, and management of long-term ocular complications. The single most important factor in determining visual outcome in patients with retinal arterial occlusive disease is duration of retinal ischemia. Histopathologic studies have shown that total occlusion of the central retinal artery leads to irreversible visual loss in less than 2h. Aggressive management is indicated in patients who present within 24h of symptoms and the individual management of each patient must be determined on a case-by-case basis.

Systemic workup should include carotid ultrasound to look for atherosclerotic disease, echocardiography, and hematologic workup to rule out a potential thrombotic or vasculitic condition. In age-appropriate patients, a sedimentation (sed) rate and C-reactive protein must be considered when the diagnosis of temporal arteritis is entertained.

INTRODUCTION

Occlusion or obstruction of the ophthalmic, central retinal, branch retinal, or a cilioretinal artery leads to acute loss of vision in the distribution of the affected retina. von Graefe initially described CRAO secondary to emboli related to bacterial endocarditis in the nineteenth century.^[1] Since then our understanding of retinal arterial occlusion has increased dramatically. Although relatively infrequent, these events can profoundly impact not only the visual function of the individual, but also can be the initial indication of life-threatening systemic disease. An understanding of the basic anatomy and pathologic mechanisms of occlusion is essential in determining the appropriate management and evaluation of patients presenting with acute retinal arterial occlusions.

VASCULAR ANATOMY

The ophthalmic artery is the first intracranial branch of the internal carotid artery. After entering the orbit, the ophthalmic artery gives off the central retinal artery, which runs adjacent to the inferior margin of the optic nerve. The central retinal artery penetrates 13 mm posterior to the globe to course through the substance of the nerve to supply the inner retina. Approximately 20 short posterior ciliary arteries arise from the ophthalmic artery and penetrate the sclera in a ring around the optic nerve to supply the choroid and outer retina. Cilioretinal arteries arise from these short posterior ciliary arteries and are present in 30% of eyes and 50% of individuals.^[2,3] In 15% of people a cilioretinal artery supplies some portion of the macular circulation.^[3]

The surface of the optic disk is supplied by branches of the central and branch retinal arteries. The laminar and prelaminar optic nerve is supplied by branches of the posterior ciliary arteries. The deeper optic nerve in supplied by intraneuronal branches from the central retinal artery and recurrent pial branches of the central retinal and ophthalmic artery.

Within the retina, larger branches of the central artery course through the nerve fiber and ganglion cell layers. As the arterial circulation divides and lumen size narrows smaller arterioles and capillaries extend through these layers into the inner nuclear layer.^[4] Central retinal artery circulation does not extend past the boundary of the inner nuclear and inner plexiform layers. The choroidal circulation and choriocapillaris supply the outer retina.

While retinal circulation is generally end arterial in nature, two anastomoses exist in the region of the optic disk between branches of the central retinal artery and short posterior ciliary arteries.^[5] The first occurs in the capillary beds of the optic nerve head. Here superficial capillaries derived from the central retinal artery lie adjacent to those capillaries that penetrate the deeper regions of the prelaminar and lamina cribrosa, that originate from posterior ciliary circulation. The second anastomosis occurs within the dural sheath of the optic nerve. There intraneuronal branches of the central retinal artery communicate with recurrent pial branches.

HISTOPATHOLOGY OF ARTERIAL OCCLUSIONS

The retina has a high oxidative capacity and a high level of glycolytic activity. The decrease or absence of perfusion caused by central retinal artery obstruction leads to decreased delivery of glucose and more importantly oxygen^[6] to the tissues of the retina. Ischemia leads to edema as neuron cellular membranes burst^[4,7] producing the associated funduscopic whitening of the retina caused by opacification of the ganglion cell layer. The opacification is most prominent in the macular region where the multiple layers of ganglion cells reside. Retinal opacification generally decreases toward the periphery as the ganglion cell population diminishes, and is also absent from the avascular zone of the foveola where ganglion cells are absent.^[8] The classic 'cherry red spot' is a result of the visible red reflex of the perfused choroid at this location.

Optical coherence tomography (OCT) of acute CRAO correlates with these histopathologic features and/or characteristics. Findings on OCT demonstrate an increase in inner layer reflectivity and muted outer layer reflectivity around the foveola with normal reflectivity of the retinal pigment epithelium beneath the foveola (Fig. 131.1).^[9] Eventually, cellular debris in the ischemic inner layers of the retina undergoes phagocytosis and gliosis leading to atrophy.



FIGURE 131.1 OCT of CRAO demonstrating increased thickness in the inner retinal layers and muted outer layer/retinal pigment epithelium reflectivity surrounding the foveola. Note that there is normal reflectivity of the retinal pigment epithelium at the foveola.

Animal studies have demonstrated swelling of the organelles that precede axonal and dendritic rupture with decreased neuronal cell count. Mitochondria, the first organelle affected in the ganglion cells,^[6]began to swell as early as 15 min after CRAO in squirrel monkeys.^[7] Microtubules and cisternae of the endoplasmic reticulum are also acutely susceptible to ischemia.^[6] In Kroll's experimental occlusion of the central retinal artery in squirrel monkeys, swelling of the endoplasmic reticulum had occurred by 3.5h.^[7] Müller cells were relatively more resistant to ischemia than the ganglion cells in both species, presumably due to their proximity to retinal capillaries and the choriocapillaris, and a greater ability to metabolize under anaerobic conditions. These changes are similar to those seen in humans.^[7,10,11]

Retinal cellular survival and thus fial visual outcome in humans is related to duration of ischemia and the presence of residual circulation. However, no controlled data are available in humans. In squirrel monkeys, Kroll observed axonal and dendritic lysis by 3.5h and extensive cellular loss by 16h.^[7] Hayreh and associates found that rhesus monkey retinas could tolerate 97-98 min of total occlusion, and that only half of eyes occluded for 102 min recovered vision. However, all eyes occluded 105 min or more suffered irrecoverable ischemia.^[6,12,13]

DEMOGRAPHICS/INCIDENCE/PREVALENCE

Retinal arterial occlusions may occur at any age, but the average age of patients with CRAO in two large series is 62 and 67.^[8,14] Most series demonstrate a slight male predominance.^[8,14,15] There does not appear to be any racial predilection, however. Additionally, the right and left eyes appear to be involved equally. Common systemic risks factors for retinal arterial occlusive disease include hypertension, diabetes, lipid disorders, and cardiac and systemic atherosclerotic disease.

It is difficult to determine the precise incidence and prevalence of arterial occlusive events in the retina. However, Brown and co-authors suggested that 1 in 10000 patient visits to a tertiary-care eye hospital was related to CRAO.^[16] Additionally, he estimated that less than 1 in 50000 outpatient visits to an ophthalmologist will be a patient less than age 30 with retinal arterial occlusive disease.^[16]

MECHANISMS OF OCCLUSION

The principal mechanisms operative in occlusion of the retinal arterial system are embolic, thrombotic, vaso spastic, extravascular compression, and vasculitic. Other mechanisms such as radiation and elevated intraocular pressure occur much less commonly. It is important to note that more than one mechanism may occur at the same time in a patient. An embolism to the retinal arterial circulation can originate as a venous thrombosis reaching the arterial circulation via a right to left cardiac shunt. CRAO secondary to giant cell arteritis is primarily a vasculitic phenomenon, with thrombosis being the ultimate occlusive event.

In general, age is an important factor in determining the mechanism of occlusion. Patients aged 50 and greater are likely to have occlusions associated with embolic disease while younger patients are more likely to have occlusions secondary to thrombosis.

EMBOLISM/ENDOGENOUS

Since retinal arterial occlusive disease is primarily a disease of the elderly, embolic occlusion represents the most common mechanism. Atherosclerosis of the carotid system is the most common source of retinal emboli with 80% being associated with carotid artery disease.^[17,18] A common misconception regarding carotid disease leading to emboli is that the degree of obstruction of the carotid artery is of paramount importance. Although degree of obstruction is important, the presence of an ulcerative plaque, even with minimal stenosis, can be more likely to lead to emboli than an extensively occluded carotid artery. Carotid artery disease can be evaluated by carotid ultrasonography, arteriography, and CT angiography.

The heart and major vessels are another important source of emboli that must be considered when confronted with a patient with embolic retinal arterial occlusions. Valvular abnormalities,^[19-21] tumors, like atrial myxomas,^[22,23] and thrombus formation in the left atrium secondary to conditions like atrial fibrillation, can lead to emboli formation and vascular occlusion. Additionally, right to left shunts, like patent foramen ovale, can allow emboli from venous thrombotic disease to reach the arterial circulation.^[24] Important in evaluating embolic disease originating from the heart is echocardiography. Transthoracic echocardiography is the preferred initial screening technique. In cases where there is a high suspicion of disease that is not detected by transthoracic echocardiography, transesophageal echocardiography can be helpful in identifying a source of emboli.^[25,26] Other rare sources of endogenous emboli include fat emboli from long bone fractures,^[27] amniotic fluid emboli at the time of delivery,^[28,29] and leukoembolization secondary to conditions like pancreatitis.

Emboli/Exogenous Source

Exogenous emboli can reach the retinal circulation leading to arterial occlusive events. Examples include talc emboli associated with intravenous drug abuse^[30] and emboli from injections of steroids in the nasal or periorbital area,^[31,32] or related to blood products like platelet emboli during transfusion. Fragments of catheter tips and artifical heart valves may also cause arterial occlusion.

Retinal Emboli/Types

Although embolic obstruction is presumably the most common cause of retinal arterial occlusions, visible emboli detected ophthalmoscopically are only evident in 20-30% of patients with retinal arterial occlusive disease.^[14] Clinically the most common are cholesterol emboli, platelet fibrin emboli, and calcific emboli (Figs 131.2-131.4).



FIGURE 131.2 Cholesterol emboli at bifurcation of the inferior nasal retinal artery. Note glistening characteristics. No functional deficit was present.



FIGURE 131.3 CRAO with cilioretinal sparring. Note elongated platelet fibrin emboli in retinal arterial tree.



FIGURE 131.4 Inferior hemiretinal artery occlusion in right eye. Note calcific emboli at the inferior margin of the disk causing occlusion.

Cholesterol emboli are small, glistening yellow in color, and typically do not occlude the vessel distal to the emboli. These most commonly arise from atherosclerotic plaques of the carotid artery. Platelet fibrin emboli may appear gray-white, are larger and longer than cholesterol emboli, and may be seen to pass through the retinal vessels.

Calcific emboli are larger, gray-white in color, and associated with more severe local obstructions. Arruga felt that calcific emboli were more likely to arise from cardiac valvular disease.^[15] A comprehensive list of emboli types is provided in Table 131.1.

TABLE 131.1 -- Emboli

I.	Endogenous
A.	Carotid atheroma
B.	Cardiac valvular disease
C.	Cardiac tumor
D.	Fat emboli
E.	Leukoemboli
F.	Amniotic fluid emboli
G.	Septic emboli
II.	Exogenous
A.	Injected steroids
B.	Catheter tips
C.	Talc
D.	Artificial heart valves

THROMBOSIS

Thrombosis is another mechanism causing arterial occlusive disease of the retina. Virchow's classic triad concerning the pathogenesis of thrombosis includes vessel wall abnormalities, stasis of blood flow, and changes in the blood components. While any one of these factors alone may lead to thrombosis, combinations of these factors significantly increase the likelihood of these episodes. While venous thrombosis occurs most commonly, arterial thrombotic disease of the retina also does occur.

Structural abnormalities in a vessel like prepapillary arterial loop can contribute to retinal arterial occlusion by thrombosis. This structural abnormality, which leads to turbulence and stasis of flow, has been reported to cause CRAOs.^[33]

Tremendous advances have occurred during the last two decades in understanding abnormalities of blood components and their relationship to intravascular thrombosis. Both hereditary and acquired abnormalities have been identified. Thrombophilia is the term used to describe conditions that are genetically determined and increase the likelihood of vascular thrombosis (Table 131.2). These abnormalities typically lead to venous thrombosis, but when they interact with other local or systemic hypercoagulable factors like trauma, malignancy, pregnancy, oral contraceptive use, autoimmune disease, and cigarette smoking, they may lead to arterial thrombosis. These hereditary thrombophilic states should be considered in patients with retinal arterial occlusions, particularly with a positive family history of thrombotic events occurring at a young age. While entire textbooks have been devoted to discussing these thrombophilic conditions, a brief explanation of some of the more common of these conditions that have been associated with retinal arterial occlusive events will be useful.

TABLE 131.2 -- Thrombophilias Associated with Retinal Arterial Occlusions

I.	Factor V Leiden
II.	Antithrombin deficiency
III.	Protein C deficiency
IV.	Protein S deficiency
V.	Hyperhomocystinemia
VI.	Anti-phospholipid antibodies
VII.	Lupus anticoagulant
VIII.	Anticardiolipin
IX.	Homozygous C677T polymorphism in methylene tetrahydrofolate reductase
X.	Prothrombin G20210A
XI.	Dysfibrogenemia
XII.	Elevated factor VIII
XIII.	Elevated factor IX

Antithrombin Deficiency

Human antithrombin (AT) is a plasma protein that is a protease inhibitor and prevents the formation of thrombi.^[34] Previously termed AT III deficiency, AT deficiency was the first hereditary deficiency of an anticoagulant protein described. Inherited as an autosomal dominant trait, AT deficiency is associated with a thrombotic tendency typically manifested as venous thromboembolism. However, retinal arterial occlusions secondary to thrombosis have been reported.^[35]

Protein C and S Deficiency

Protein C and protein S are vitamin K dependent plasma glycoproteins synthesized in the liver. Deficiency in these proteins occurs primarily as a hereditary condition inherited as an autosomal dominant trait, but can be an acquired defect associated with advanced severe liver disease. Both protein C and protein S serve as cofactors for the anticoagulant function of activated protein C, a protein that inactivates factors 5A and 8A, and downregulates thrombosis.^[34] Deficiencies of either protein C or protein S leads to a thrombotic tendency, and arterial occlusive disease of the retina has been described with each (Figs 131.5 and 131.6).^[36,37]



FIGURE 131.5 Twenty-four-year-old with diabetes, pregnancy, and protein S deficiency. Note branch macular artery occlusion in left eye.



FIGURE 131.6 Fluorescein angiogram of BRAO secondary to protein S deficiency in left eye.

Activated Protein C Resistance and Factor V Leiden

As mentioned previously, activated protein C inactivates factor V-A and factor VIII-A and downregulates thrombosis. Activated protein C resistance refers to an abnormally reduced anticoagulant response of a subject's plasma to activated protein C in in vitro testing. Although any genetic abnormality of the protein C pathway can cause activated protein C resistance, more than 90% of hereditary activated protein C resistance subjects have the same genetic abnormality termed factor V Leiden. Factor V Leiden is an abnormal factor V associated with a point mutation and a single amino acid change. Factor V Leiden is resistant to the proteolytic action of activated protein C, leading to increased thrombin formation.^[34] The subsequent hypercoagulable state is one of the most common hereditary causes of thrombophilia and has been associated with arterial occlusive disease of the retina.^[38,39]

Hyperhomocystinemia

Homocysteine is an intermediate in the metabolism of the amino acids methionine and cysteine. Hyperhomocystinemia refers to elevated plasma levels of homocysteine and can be caused by numerous factors. The most common genetic cause of hyperhomocystinemia is a mutation in the enzyme methylene tetrahydrofolate reductase (MTHFR) leading to elevated levels of plasma homocysteine. Present in 10-20% of Caucasians, 10% of Asians, and rare in blacks, either alone or in combination with low folate, B6 or B12 levels or other conditions like renal failure, hypothyroidism, smoking, excess caffeine consumption, and inflammatory bowel disease, this defect can be associated with increased levels of plasma homocysteine. The exact mechanism of thrombosis associated with hyperhomocystinemia is poorly understood^[40] but endothelial toxicity and smooth muscle proliferation have been proposed. Arterial thrombotic disease of the retina has been reported.^[41,42]

Antiphospholipid Syndrome

The antiphospholipid syndrome (previously known as antiphospholipid antibody syndrome, anticardiolipin antibodies syndrome, and lupus anticoagulant) is an acquired disorder associated with thrombotic complications. The condition is considered secondary if associated with other diseases like systemic lupus erythematosus, other autoimmune disorders, viral infections, malignancies, or those associated with medications. It is considered primary when it occurs in the absence of any of these conditions. The syndrome is characterized by the presence of antibodies to phospholipid protein complexes (anticardiolipin, antiphosphatidyl serine or anti-? 2 glycoprotein) or by the detection of lupus anticoagulants.^[43] The precise mechanism by which these antiphospholipid antibodies promote thrombosis is poorly understood, but may be related to the inhibition of prostacyclin, a platelet inhibitory prostaglandin. It has also been speculated that it might impair protein C and AT III anticoagulant mechanisms. While venous occlusive disease is most common, arterial occlusive disease of the retina also has been associated with the antiphospholipid syndrome.^[44-50]

VASCULITIS AND GIANT CELL ARTERITIS

The classic vasculitis-related CRAO occurs in giant cell arteritis. As mentioned previously, giant cell arteritis is an example of an arterial occlusion occurring from a combined mechanism, both vasculitis and thrombosis.^[51] Often associated with ocular pain because of the profound ischemia, patients of the appropriate age (greater than 55 years) who present with CRAO should be questioned for associated symptoms like headache, scalp tenderness, jaw claudication, malaise, anorexia, fever, and weight loss, recognizing that 20% of patients with giant cell arteritis are without systemic symptoms. Patients with acute CRAO secondary to giant cell arteritis may have prodromal transient blurring of vision for weeks to months prior to the occlusive event.

The suspected diagnosis is solidified by an elevated erythrocyte sedimentation rate and C-reactive protein and confirmed by temporal artery biopsy. Making an accurate diagnosis and initiation of high-dose steroid therapy is imperative because second eye involvement may occur soon following presentation.

Systemic vasculitis associated with collagen vascular diseases can cause retinal arterial occlusions. Classic examples are rheumatoid vasculitis and systemic lupus erythematosus. Other systemic vasculities like Behçet's disease^[52] may lead to branch retinal arterial occlusions. Localized vasculitis in the retina can occur in other conditions like toxoplasmosis retinitis and Bartonella henselae leading to retinal arterial occlusions (Fig. 131.7).^[53-56]



FIGURE 131.7 BRAO associated with vasculitis secondary to retinitis due to Bartonella henselae.

VASOSPASM

Vasospasm as a primary cause of retinal arterial occlusive disease^[57-62] is felt to be a rare occurrence. Gass has suggested that some degree of reflex spasm may play a role in retinal arterial occlusions from many causes including migraine, collagen vascular disease, and sickle cell hemoglobinopathies.^[63,64]

OTHER MECHANISMS

Local conditions in the eye and orbit may lead to situations predisposing to retinal arterial occlusive events. Examples of conditions associated with retinal arterial occlusion from intrinsic structural anomalies include peripapillary arterial^[33] loop, optic nerve head drusen,^[65] and intraocular foreign body (Figs 131.8 and 131.9).



FIGURE 131.8 BRAO in right eye secondary to prepapillary arterial loop.



FIGURE 131.9 Inferior BRAO secondary to intraocular foreign body imbedded in the retina with distal occlusion of the inferior temporal artery. There is hemorrhage overlying the intraocular foreign body.

Elevated intraocular pressure secondary to angle-closure glaucoma or compression of the globe can lead to CRAO. External compression of the ophthalmic artery or central retinal artery caused by orbital cellulitis, orbital hemorrhage abscess formation, cavernous sinus thrombosis, and neoplastic disease may lead to CRAO.

CLINICAL FINDINGS

AMAUROSIS FUGAX

Amaurosis fugax refers to transient monocular loss of vision, either total or altitudinal, that may serve as a prodromal symptom for retinal arterial occlusion. Visual loss in amaurosis fugax typically lasts 7-30 min with total resolution to normal. Patients with classic symptoms of amaurosis fugax should undergo complete ophthalmic examination, specifically looking for the presence of retinal emboli. In these patients, a systemic workup should be performed for the presence of embolic disease. Specifically, an evaluation of the carotid artery system as well as cardiac evaluation with echocardiography should be performed. Consultation with the patient's internist or neurologist is indicated to determine whether anticoagulants should be initiated.

CLINICAL FINDINGS

AMAUROSIS FUGAX

OPHTHALMIC ARTERY OCCLUSIONS

Ophthalmic artery occlusion causes profound painless unilateral loss of vision. Visual function in these cases is extremely poor as both the retinal and choroidal circulation is interrupted. Visual acuity ranges from counting figers to no light perception. An afferent pupillary defect is present. The classic fundus picture is that of an acutely infarcted retina with extensive retinal whitening (Fig. 131.10). Often there is pallid swelling of the optic disk. Because the choroidal circulation is compromised, a cherry red spot is not visualized. There is often boxcarring or segmentation of the blood column of the retinal vessels. Fluorescein angiography shows no or markedly delayed background choroidal flush and minimal or delayed filling of the retinal vasculature.



FIGURE 131.10 Ophthalmic artery occlusion in left eye secondary to atrial myxoma emboli. Note pallid swelling of the optic nerve. No evidence of cherry red spot. Note segmentation of the blood column in the retinal vessels.

Visual recovery is rare in cases of ophthalmic artery occlusion. Electroretinographic testing can help differentiate ophthalmic artery occlusions from CRAO. In ophthalmic artery occlusions, both the B wave and A wave are absent, while in CRAO with intact choroidal perfusion, the A wave is present.

The chronic picture of ophthalmic artery occlusion is a pale disk with attenuation of the retinal arterials and venules (Fig. 131.11). Often, retinal pigment epithelial abnormalities will occur related to the profound ischemia of the retinal pigment epithelium and choriocapillaris.



FIGURE 131.11 Chronic ophthalmic artery occlusion in right eye. Note pale disk and ischemic retinal arteries and veins.

CENTRAL RETINAL ARTERY OCCLUSIONS

CRAOs also present with painless unilateral profound loss of vision. Visual acuity of less than 20/400 occurs in more than 90% of eyes at the time of presentation. An afferent pupillary defect is present. Visual fields are depressed in the area of the ischemic retina. The retina shows ischemic whitening, and the retinal arterials and veins manifest boxcarring. A cherry red spot is present due to the intact choroidal circulation (Fig. 131.12). The diagnosis may not be obvious in patients presenting within 1-2h of occlusion, prior to the development of an edematous retina. In these cases, fluorescein angiography is useful and will show an intact choroidal flush with absent, incomplete, or delayed filling and a leading edge of dye in the retinal circulation (Fig. 131.13a,b).



FIGURE 131.12 CRAO in left eye. Note cherry red spot with edematous ischemic retina. Note segmentation of blood column.



FIGURE 131.13 Fluorescein angiogram of CRAO left eye at (a) 33 s and (b) 47 s showing a leading edge of dye in the arterial system.

The median fial visual acuity following resolution of edema in CRAOs is counting figers. However, in select cases with intact cilioretinal arteries supplying the fovea, Snellen visual acuity may improve to 20/20 (Figs 131.14 and 131.15). Visual field defects persist in the area of the infarcted retina. Chronic fundus changes in CRAO include optic atrophy, attenuated retinal arterials and venules, and an atrophic-appearing retina.



FIGURE 131.14 Fundus photograph of right eye with CRAO with cilioretinal sparing. Visual acuity improved to 20/20.



FIGURE 131.15 Fluorescein angiogram of right eye showing perfused cilioretinal artery, but CRAO and delayed filling of the retinal arterials.

BRANCH RETINAL ARTERY OCCLUSIONS

Branch retinal artery occlusion (BRAO) presents as an acute painless loss of visual field in the distribution of the occluded artery. Visual acuity may range from 20/20 to 20/400 depending on the degree of foveal involvement. An afferent pupillary defect may be present, depending on the degree of retina involvement. Retinal whitening, along the distribution of the artery is usually present, but may not occur in nasal branch artery occlusions due to the single layer of ganglion cells present there. Emboli are identified in ?30% of cases. Fluorescein angiogram depicts delayed transit of the dye through the affected vessel, and often retrograde filling of the vessel can be observed later in the angiogram (Figs 131.16 and 131.17). Combined branch retinal artery and vein occlusions are relatively rare (Fig. 131.18).



FIGURE 131.16 Inferior BRAO with calcific emboli at inferior margin of the optic disk beneath overlying vein.



FIGURE 131.17 Fluorescein angiogram of inferior BRAO showing delayed perfusion of inferior retina with retrograde filling of inferior retinal veins.



FIGURE 131.18 Combined branch retinal artery and vein occlusion in right eye.

Patients with BRAOs typically retain excellent visual acuity following the acute event, as long as a portion of the foveal vasculature maintains normal perfusion. Visual acuity improves to 20/40 or better in 80% of these eyes, but visual field defects persist.^[66] The fundus appearance may return to near normal weeks to months following the event.

CILIORETINAL ARTERY OCCLUSIONS

Approximately 35% of eyes and 50% of people have cilioretinal arteries. As mentioned previously, cilioretinal arteries are derived from the short ciliary arteries. Typical symptoms of patients with cilioretinal artery occlusions are pericentral scotomas, often subtle, in the distribution of the artery.^[67] As the area supplied by the occlusion is usually small, afferent pupillary defects are often not present. Although any of the previously described mechanisms of occlusion may be operational, cilioretinal artery occlusions may occur in conjunction with central retinal venous occlusive disease and anterior ischemic optic neuropathy (Figs 131.19 and 131.20).^[68]



FIGURE 131.19 Inferior cilioretinal artery occlusion with associated central retinal vein occlusion.



FIGURE 131.20 Cilioretinal artery occlusion in right eye, associated with anterior ischemic optic neuropathy.

Cilioretinal artery occlusions occurring in isolation usually have a prognosis as good as or better than BRAOs, with 90% improving to 20/40 or better visual acuity. When cilioretinal artery occlusions occur concomitant with CRVO, the prognosis varies depending on resolution of complications associated with the central retinal vein occlusion like macular edema, ischemia, and hemorrhage.^[69]

MANAGEMENT

Management of patients with retinal arterial occlusions can be considered in three aspects: (1) management of the acute occlusive event in an attempt to restore visual function; (2) workup of the patient looking for potential systemic conditions requiring treatment; and (3) management of the remote complications and sequelae of the arterial occlusive event. Although the first two are the most important aspects, all are critical for optimal patient management. With regards to visual function, attempts to restore visual function are most critical in central and ophthalmic artery occlusions and many of the methods we will describe are often not utilized in branch or cilioretinal artery occlusions. Patients with BRAO or cilioretinal artery occlusion typically have an excellent prognosis for regaining visual acuity. However, the management of each case much be individualized.

As previously mentioned, the duration of retinal ischemia is the most important factor in determining prognosis. Since it is often difficult to pinpoint the actual initial occlusive event, aggressive management is appropriate, particularly in patients with a duration of occlusion less than 24h. While there are many reports of successful outcomes with various treatments in select cases, unfortunately, there is no proven beneficial treatment for improving visual outcomes in patients with these events.^[70] Therapeutic goals are to restore blood flow as quickly as possible to limit the damage to the cellular constituents of the retina.

Digital ocular massage is a simple, common, noninvasive initial technique utilized to restore retinal circulation. In this technique the figers are used to compress the globe, raising the intraocular pressure with subsequent release of the pressure hoping that the arterial pulse will displace any occlusive emboli into the distal retinal arterioles and restore flow. No statistical benefit of ocular massage has been noted, but as it is a simple treatment with low morbidity, it should be tried in all patients with CRAO.

Reduction of intraocular pressure through ocular antihypertensives and paracentesis which theoretically may also dislodge an embolus have been attempted to improve retinal arterial circulation. Studies have shown no significant difference in fial versus initial visual outcomes in use of topical beta blockers, oral acetazolamide, or paracentesis.^[71,72]

Medical vasodilatation utilizing sublingual nitroglycerin, calcium channel blockers and pentoxifylline have also been used to improve the retinal arterial circulation. While results of one study found that the pentoxifylline group had less neovascularization compared to standard treatment, there was no defiitive improvement in visual outcomes.^[73] To date there are only anecdotes of effectively treating CRAO with nitroglycerin.^[74,75] It has been hypothesized that nifedipine or other calcium channel blockers may reduce the effects of calcium overload in ischemic retina;^[76] however, to date no studies showing an improvement in fial visual outcome have been documented. Carbogen, 95% oxygen and 5% carbon dioxide, is an inhalation treatment that may cause dilation of retinal arterioles,^[77] and has been used to treat CRAO. This modality of treatment has not shown benefit to fial visual outcome and is generally no longer used.^[72]

There are case reports of thrombolytic therapy improving visual recovery even when initiated more than 2h after occlusion. However, less than 16% of CRAO cases are due to platelet-fibrin obstruction.^[15]Given the lack of clinical evidence of improved visual outcome, potential for systemic complications, and inherent difficulty establishing nonembolic etiology, the decision to attempt fibrinolytic therapy using drugs like TPA should be made carefully.^[8,78] More data may justify more widespread future use of local or systemic modalities of treatment.^[71,79-82]

Surgical treatments have been tried with embolic arterial occlusion with occasional/rare efficacy. Laser photo disruption of an embolus has been reported in select patients to cause passage of the embolus through the arterial tree with improvement in outcomes.^[83] Vitrectomy with cannulation of the central retinal artery has also been proposed for management of embolic retinal arterial occlusive disease.^[84] No randomized trial data have confirmed the efficacy of any of these treatments.

Although mentioned previously, in patients with CRAO, if giant cell arteritis is suspected by clinical and laboratory parameters, high-dose steroid therapy should be initiated while awaiting temporal artery biopsy.

The second aspect of management of retinal arterial occlusive disease is systemic workup. This has been covered thoroughly within this chapter, but carotid artery studies including duplex Doppler ultrasound, transthoracic or transesophageal echocardiography,^[85] and hematologic testing to rule out various vasculitic and thrombosis type syndromes must be performed (see Table 131.3).^[86] In general the workup should be tailored to the patient's age^[16,87,88] and co-morbidities. In up to 30% of patients, no systemic associated condition leading to arterial occlusion is documented.

TABLE 131.3 -- Initial Workup

I.	Carotid ultrasound
II.	Echocardiography - transthoracic, transesophageal
III.	ESR, C-reactive protein
IV.	CBC, platelet count
V.	PT, PTT
VI.	Protein C, protein S, activated protein C, factor V Leiden, fasting plasma homocysteine level, anti-phospholipid antibodies

The most devastating long-term ocular complication of retinal arterial occlusive disease is neovascular glaucoma. Neovascular glaucoma has been reported to occur in 2-16% of these eyes.^[89,90] The time from occlusion to development of neovascular glaucoma ranges from one week to years with most events occurring during the first 2 months. While the eye typically has limited vision secondary to the initial occlusion, the preference of a limited vision, comfortable, cosmetically acceptable eye versus a blind painful eye is obvious. Treatment is as with any other form of neovascular glaucoma with laser or cryotherapy to the retina and ciliary body and topical antihypertensive medications.

OCULAR ISCHEMIC SYNDROME

While the ocular ischemic syndrome is not a 'retinal arterial occlusion' it does represent chronic arterial insufficiency to the retina, choroid, and entire globe. The ocular ischemic syndrome can be defied as a syndrome of hypoperfusion to the globe secondary to carotid artery or more rarely ophthalmic artery occlusive disease. Patients with the ocular ischemic syndrome may be asymptomatic initially or may note gradual blurring, often of a transient nature. Patients are typically 50 years old or older and often have significant atherosclerotic disease with other cardiovascular or cerebral vascular symptoms.^[91]

Anterior segment fidings include chronic flare with minimal cellular response and neovascularization of the iris or angle structures. Posterior segment fidings include retinal hemorrhages in all four quadrants, typically present in the midzone. Arterials are narrowed and veins are typically of normal caliber. This is a differentiating feature from central retinal vein occlusion where veins are dilated. Microaneurysms and macular edema may be present and in advanced cases neovascularization of the disk or retina may be present.

On fluorescein angiography there is often delayed asymmetric filling of the choroid, delayed retinal arterial filling,^[92] and prolonged venous transit time.^[93] Additionally, the retinal vessels often stain late in the study indicating chronic retinal ischemia.^[94] Electroretinography typically shows decreased amplitude of the A and B wave secondary to global posterior ischemia (Figs 131.21-131.24).



FIGURE 131.21 Red free photograph of right eye showing fairly normal posterior pole. Neovascularization of the disk is present.



FIGURE 131.22 Fluorescein angiogram shows delayed filling of retinal arterials with asymmetric filling of the choroid.



FIGURE 131.23 Progressive arterial filling with delayed venous filling and prolonged venous transit time and continued asymmetric filling of the choroid.



FIGURE 131.24 Leakage from neovascularization of the disk with late staining of the retinal vessels.

It is critical to make the diagnosis of ocular ischemic syndrome because these patients often develop cerebral vascular accidents. The 5-year mortality in ocular ischemic syndrome is estimated at up to 40%.^[95] Visual prognosis in the ocular ischemic syndrome is poor with the majority of cases progressively losing vision. Panretinal laser photocoagulation may be efficacious in preventing the development of neovascular glaucoma. Focal laser photocoagulation in ocular ischemic syndrome patients with macular edema is another treatment modality where efficacy has not been proven through randomized controlled clinical trials, but may be reasonable. Prompt referral to an internist, neurologist, or vascular surgeon is necessary to address modifiable risk factors and to consider carotid endarterectomy in the appropriate patient. The efficacy of endarterectomy in stroke prevention in symptomatic patients with 70-99% stenosis has been demonstrated in the North American symptomatic carotid endarterectomy trial.^[96]

REFERENCES

1. von Graefe A: Uber embolie der arteria centralis retinae als ursache plötzlicher erblingdung. Arch für Ophthalmology 1859; 5:136-157.

2. Awan KJ: Arterial vascular anomalies of the retina. Arch Ophthalmol 1977; 95:1197-1202.

3. Brown GC, Shields JA: Cilioretinal arteries and retinal arterial occlusion. Arch Ophthalmol 1979; 97:84-92.

4. Wise GN, Dollery CT, Henkind P, et al: The retinal circulation, New York, NY, Harper & Row, 1971.

5. Singh SS, Dass R: The central artery of the retina - II. Distribution and anastomoses. Br J Ophthalmol 1960; 44:280-299.

6. Hayreh SS, Weingeist TA: Experimental occlusion of the central retinal artery of the retina. IV. Retinal tolerance time to acute ischemia. Br J Ophthalmol 1980; 64:896-912.

7. Kroll AJ: Experimental central retinal artery occlusions. Arch Ophthalmol 1968; 79:

8. Hayreh SS, Zimmerman B: Central retinal artery occlusion: visual outcome. Am J Ophthalmol 2005; 140:376-391.

9. Ozdemir H, Karacorlu S, Karacorlu M, et al: Optical coherence tomography -ndings in central retinal artery occlusion. Retina 2006; 26:110-112.

10. Dahrling BE: The histopathology of early central retinal artery occlusion. Arch Ophthalmol 1965; 73:506-510.

11. Ashton N, et al: Focal retinal ischemia, ophthalmoscopic, circulatory and ultrastructural changes. Br J Ophthalmol 1966; 50:285-384.

12. Hayreh SS, Jonas JB: Optic disc and retinal nerve -ber layer damage after transient central retinal artery occlusion: an experimental study in rhesus monkeys. Am J Ophthalmol 2000; 129:786-795.

13. Hayreh SS, Karacorlu S, Karacorlu M, et al: Central retinal artery occlusion and retinal tolerance time. Ophthalmology 1980; 87:75-78.

14. Brown GC, Magargal LE: Central retinal artery obstruction and visual acuity. Ophthalmology 1982; 89:14-19.

15. Arruga J, Sanders MD: Ophthalmologic -ndings in 70 patients with evidence of retinal embolism. Ophthalmology 1982; 89:1336-1347.

16. Brown GC, Magargal LE, Shields JA, et al: Retinal arterial obstruction in children and young adults. Ophthalmology 1981; 88:18-25.

17. Kollarits CR, Lubow M, Hissong SL: Retinal strokes. I. Incidence of carotid atheromata. JAMA 1972; 222:1273-1275.

18. Shah HG, Brown GC, Goldberg RE: Digital subtraction carotid angiography and retinal arterial obstruction. Ophthalmology 1985; 92:68-72.

19. Penner R, Font RL: Retinal embolism from calci-ed vegetations of aortic valve. Spontaneous complication of rheumatic heart disease. Arch Ophthalmol 1969; 81:565-568.

20. Rush JA, Kearns TP, Danielson GK: Cloth-particle retinal emboli from arti-cial cardiac valves. Am J Ophthalmol 1980; 89:845-850.

21. Jampol LM, Wong AS, Albert DM: Atrial myxoma and central retinal artery occlusion. Am J Ophthalmol 1973; 75:242-249.

22. Zamora RL, Adelberg DA, Berger AS, et al: Branch retinal artery occlusion caused by a mitral valve papillary -broelastoma. Am J Ophthalmol 1995; 119:325-329.

23. Zamora RL, Adelberg DA, Berger AS, et al: Branch retinal artery occlusion caused by a mitral valve papillary -broelastoma - correction. Am J Ophthalmol 1995; 120:126.

24. Clifford L, Sievers R, Salmon A, Newsom RS: Central retinal artery occlusion: association with patent foramen ovale. Eye 2005.

25. Kramer M, Goldenberg-Cohen N, Shapira Y, et al: Role of transesophageal echocardiography in the evaluation of patients with retinal artery occlusion. Ophthalmology 2001; 108:1461-1464.

26. Wisotsky BJ, Engel HM: Transesophageal echocardiography in the diagnosis of branch retinal artery obstruction. Am J Ophthalmol 1993; 115:653-656.

27. Chuang EL, Miller 3rd FS, Kalina RE: Retinal lesions following long bone fractures. Ophthalmology 1985; 92:370-374.

28. Chang M, Herbert WN: Retinal arteriolar occlusions following amniotic fluid embolism. Ophthalmology 1984; 91:1634-1637.

29. Kim IT, Choi JB: Occlusions of branch retinal arterioles following amniotic fluid embolism. Ophthalmologica 2000; 214:305-308.

30. AtLee Jr WE: Talc and cornstarch emboli in eyes of drug abusers. JAMA 1972; 219:49-51.

31. Whiteman DW, Rosen DA, Pinkerton RM: Retinal and choroidal microvascular embolism after intranasal corticosteroid injection. Am J Ophthalmol 1980; 89:851-853.

32. Wilkinson WS, Morgan CM, Baruh E, Gitter KA: Retinal and choroidal vascular occlusion secondary to corticosteroid embolisation. Br J Ophthalmol 1989; 73:32-34.

33. Brown GC, Magargal L, Augsburger JJ, Shields JA: Preretinal arterial loops and retinal arterial occlusion. Am J Ophthalmol 1979; 87:646-651.

34. Seligsohn U, Grif-n JH: Hereditary Thrombophilia. In: Lichtman MA, et al ed. Williams Hematology, 7th edn. New York: McGraw-Hill; 2005:1981-1996.

35. Bertram B, Remky A, Arend O, et al: Protein C, protein S, and antithrombin III in acute ocular occlusive diseases. Ger J Ophthalmol 1995; 4:332-335.

36. Greven CM, Weaver RG, Owen J, Slusher MM: Protein S de-ciency and bilateral branch retinal artery occlusion. Ophthalmology 1991; 98:33-34.

37. Greiner K, Hafner G, Dick B, et al: Retinal vascular occlusion and de-ciencies in the protein C pathway. Am J Ophthalmol 1999; 128:69-74.

38. Tayyanipour R, Pulido JS, Postel EA, et al: Arterial vascular occlusion associated with factor V Leiden gene mutation. Retina 1998; 18:376-377.

39. Dhar-Munshi S, Ayliffe WH, Jayne D: Branch retinal arteriolar occlusion associated with familial factor V Leiden polymorphism and positive rheumatoid factor. Arch Ophthalmol 1999; 117:971-973.

40. Weger M, Stanger O, Deutschmann H, et al: The role of hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR) C677T mutation in patients with retinal artery occlusion. Am J Ophthalmol 2002; 134:57-61.

41. Pianka P, Almog Y, Man O, et al: Hyperhomocystinemia in patients with nonarteritic anterior ischemic optic neuropathy, central retinal artery occlusion, and central retinal vein occlusion. Ophthalmology 2000; 107:1588-1592.

42. Wilson RS, Ruiz RS: Bilateral central retinal artery occlusion in homocystinuria. A case report. Arch Ophthalmol 1969; 82:267-268.

43. Rand JH, Senzel L: The Antiphospholipid Syndrome. In: Lichtman MA, et al ed. Williams Hematology, 7th edn. New York: McGraw-Hill; 2005:2009-2027.

44. Dori D, Beiran I, Gelfand Y, et al: Multiple retinal arteriolar occlusions associated with coexisting primary antiphospholipid syndrome and factor V Leiden mutation. Am J Ophthalmol 2000; 129:106-108.

45. Gold D, Feiner L, Henkind P: Retinal arterial occlusive disease in systemic lupus erythematosus. Arch Ophthalmol 1977; 95:1580-1585.

46. Levine SR, Deegan MJ, Futrell N, Welch KM: Cerebrovascular and neurologic disease associated with antiphospholipid antibodies: 48 cases. Neurology 1990; 40:1181-1189.

47. Snyers B, Lambert M, Hardy JP: Retinal and choroidal vaso-occlusive disease in systemic lupus erythematosus associated with antiphospholipid antibodies. Retina 1990; 10:255-260.

48. Singh R, Conway MD, Wilson WA: Antiphospholipid syndrome in a patient with sarcoidosis: a case report. Lupus 2002; 11:756-758.

49. Cobo-Soriano R, Sanchez-Ramon S, Aparicio MJ, et al: Antiphospholipid antibodies and retinal thrombosis in patients without risk factors: a prospective case-control study. Am J Ophthalmol 1999; 128:725-732.

50. Glacet-Bernard A, Bayani N, Chretien P, et al: Antiphospholipid antibodies in retinal vascular occlusions. A prospective study of 75 patients. Arch Ophthalmol 1994; 112:790-795.

51. Fineman MS, Savino PJ, Federman JL, Eagle Jr RC: Branch retinal artery occlusion as the initial sign of giant cell arteritis. Am J Ophthalmol 1996; 122:428-430.

52. Ozdal PC, Ortac S, Taskintuna I, et al: Central retinal artery occlusion associated with ocular Behcet's disease. Eur J Ophthalmol 2002; 12:328-330.

53. Williamson TH, Meyer PA: Branch retinal artery occlusion in toxoplasma retinochoroiditis. Br J Ophthalmol 1991; 75:253.

54. Morgan CM, Gragoudas ES: Branch retinal artery occlusion associated with recurrent toxoplasmic retinochoroiditis. Arch Ophthalmol 1987; 105:130-131.

55. Gray AV, Michels KS, Lauer AK, Samples JR: Bartonella henselae infection associated with neuroretinitis, central retinal artery and vein occlusion, neovascular glaucoma, and severe vision loss. Am J Ophthalmol 2004; 137:187-189.

56. Ormerod LD, Skolnick KA, Menosky MM, et al: Retinal and choroidal manifestations of cat-scratch disease. Ophthalmology 1998; 105:1024-1031.

57. Katz B: Migrainous central retinal artery occlusion. J Clin Neuroophthalmol 1986; 6:69-75.

58. Beversdorf D, Stommel E, Allen C, et al: Recurrent branch retinal infarcts in association with migraine. Headache 1997; 37:396-399.

59. Clarke WN, Vomiero G, Leonard BC: Bilateral simultaneous retinal arteriolar obstruction in a child with hemoglobin SS sickle cell disease. J Aapos 2001; 5:126-128.

60. Al-Abdulla NA, Haddock TA, Kerrison JB, Goldberg MF: Sickle cell disease presenting with extensive peri-macular arteriolar occlusions in a nine-year-old boy. Am J Ophthalmol 2001; 131:275-276.

61. Fine LC, Petrovic VV, Irvine AR, Bhisitkul RB: Correction-spontaneous central retinal artery occlusion in hemoglobin SC disease. Am J Ophthalmol 2000; 130:906-907.

62. Kachmaryk MM, Trimble SN, Gieser RG: Cilioretinal artery occlusion in sickle cell trait and rheumatoid arthritis. Retina 1995; 15:501-504.

63. Gass JD, Tiedeman J, Thomas MA: Idiopathic recurrent branch retinal arterial occlusion. Ophthalmology 1986; 93:1148-1157.

64. Johnson MW, Thomley ML, Huang SS, Gass JD: Idiopathic recurrent branch retinal arterial occlusion. Natural history and laboratory evaluation. Ophthalmology 1994; 101:480-489.

65. Newman NJ, Lessell S, Brandt EM: Bilateral central retinal artery occlusions, disk drusen, and migraine. Am J Ophthalmol 1989; 107:236-240.

66. Ros MA, Magargal LE, Uram M: Branch retinal-artery obstruction: a review of 201 eyes. Ann Ophthalmol 1989; 21:103-107.

67. Leavitt JM: Occlusion of the cilioretinal artery. Arch Ophthalmol 1948; 40:152-156.

68. Brown GC, Moffat K, Cruess A, et al: Cilioretinal artery obstruction. Retina 1983; 3:182-187.

69. Keyser BJ, Duker JS, Brown GC, et al: Combined central retinal vein occlusion and cilioretinal artery occlusion associated with prolonged retinal arterial -lling. Am J Ophthalmol 1994; 117:308-313.

70. Rumelt S, Brown GC: Update on treatment of retinal arterial occlusions. Curr Opin Ophthalmol 2003; 14:139-141.

71. Mueller AJ, Neubauer AS, Schaller U, Kampik A: European Assessment Group for Lysis in the Eye et al: Evaluation of minimally invasive therapies and rational for a prospective randomized trial to evaluateselective intra-arterial lysis for clinically complete central retinal artery occlusion. Arch Ophthalmol 2003; 121:1377-1381.

72. Atebara NH, Brown GC, Cater J, et al: Ef-cacy of anterior chamber paracentesis and carbogen in treating acute nonarteritic central retinal artery occlusion. Ophthalmology 1995; 102:2029-2035.

73. Iwafune Y, Yoshimoto H: Clinical use of pentoxifylline in haemorrhagic disorders of the retina. Pharmatherapeutica 1980; 2:429-438.

74. Kuritzky S: Nitroglycerin to treat acute loss of vision. N Engl J Med 1990; 323:1428.

75. Charness ME, Liu GT: Central retinal artery occlusion in giant cell arteritis: treatment with nitroglycerin. Neurology 1991; 41:1698-1699.

76. Crosson CE, Willis JA, Potter D, et al: Effect of the calcium antagonist, nifedipine, on ischemic retinal dysfunction. J Ocul Pharmacol 1990; 6:293-299.

77. Frayser R, Hickam JB, et al: Retinal vascular response to breathing increased carbon dioxide and oxygen concentrations. Invest Ophthalmol 1964; 3:427-431.

78. Hayreh SS: Retinal artery occlusion with LIF using rTPA. Ophthalmology 1999; 106:1236-1238.

79. Richard G, Lerche RC, Krospe V, et al: Treatment of retinal arterial occlusion with local -brinolysis using recombinant tissue plasminogen activator. Ophthalmology 1999; 106:768-773.

80. Richard G: Retinal artery occlusion with LIF using rTPA. Ophthalmology 1999; 106:1238-1239.

81. Kattah JC, Wang DZ, Reddy C, et al: Intravenous recombinant tissue-type plasminogen activator thrombolysis in treatment of central retinal artery occlusion. Arch Ophthalmol 2002; 120:1234-1236.

82. Beatty S, AuEong AK: Local intra-arterial -brinolysis for acute occlusion of the central retinal artery: a meta-analysis of published data. Br J Ophthalmol 2000; 84:914-916.

83. Ciulla TA, D'Amico DJ, Miller JW: Laser photodisruption of visible retinal artery emboli. Br J Ophthalmol 1995; 79:964-965.

84. Peyman GA: Removal of emboli from the branches of the central retinal artery. Arch Ophthalmol 2001; 119:1224-1225.

85. Sharma S, Sharma SM, Cruess AF, Brown GC: Transthoracic echocardiography in young patients with acute retinal arterial obstruction. RECO Study Group. Retinal Emboli of Cardiac Origin Group. Can J Ophthalmol 1997; 32:38-41.

86. Sharma S: The systemic evaluation of acute retinal artery occlusion. Curr Opin Ophthalmol 1998; 9:1-5.

87. Greven CM: Retinal arterial occlusions in the young. Curr Opin Ophthalmol 1997; 8:3-7.

88. Greven CM, Slusher MM, Weaver RG: Retinal arterial occlusions in young adults. Am J Ophthalmol 1995; 120:776-783.

89. Duker JS, Sivalingam A, Brown GC, Reber R: A prospective study of acute central retinal artery obstruction. The incidence of secondary ocular neovascularization. Arch Ophthalmol 1991; 109:339-342.

90. Hayreh SS, Podhajsky P: Ocular neovascularization with retinal vascular occlusion. II. Occurrence in central and branch retinal artery occlusion. Arch Ophthalmol 1982; 100:1585-1596.

91. Mizener JB, Podhajsky P, Hayreh SS: Ocular ischemic syndrome. Ophthalmology 1997; 104:859-864.

92. Wessing A: Fluorescein angiography of the retina; textbook and atlas, St Louis, MO: Mosby; 1969:xii, 222.

93. Brown GC: The ocular ischemic syndrome. In: Ryan SJ, ed. Retina, St Louis, MO: Mosby; 1989:547-559.

94. Brown GC, Magargal LE: The ocular ischemic syndrome. Int Ophthalmol 1988; 11:239-251.

95. Sivalingam A, Brown GC, Magargal LE, Menduke H: The ocular ischemic syndrome. II. Mortality and systemic morbidity. Int Ophthalmol 1989; 13:187-191.

96. Bene-cial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis : North American symptomatic carotid endarterectomy trial collaborators. N Engl J Med 1991; 325:445-453.

Page

Contents

If you find an error or have any questions, please email us at admin@doctorlib.org. Thank you!